key: cord-0010240-gaxz88lk authors: nan title: Abstracts for the Annual Scientific Meeting of the Thoracic Society of Australia & New Zealand ‘Maintaining Lung Health from Cradle to Grave’ 7–12 April 2000, Melbourne, Australia date: 2017-07-24 journal: Respirology DOI: 10.1111/resp.2000.5.s1.a1 sha: f60cc2627d2f9036b00a98fea3733e6253b012eb doc_id: 10240 cord_uid: gaxz88lk nan GD3/mm2 GD8/mm2 GD4/mm2 LGNmm2 "p<0.05. CD8 positive cells were increased in the LTR compared to controls, no other significant differences were detected. No significant differences in any of the cell markers were found after 3 months treatment with FP compared to baseline and placebo. Conclusions: In stable LTR on triple immunosuppression the addition of inhaled FP does not affect the degree of airway inflammation. CD8 positive cells are increased in stable LTR, but neutrophil numbers in the subepithelium are not different from controls. This contrasts with the increased numbers of neutrophils in established BOS. This group of patients is being followed over Aims: Asthma continues to be a major burden for its sufferers, their families and society in general. We wished to obtain a better understanding of our local population, to see how this compared with other published work and to see if there were areas in which we were deficient or could improve. Methods: A 3 part "PAQART' (paediatric asthma quality assurance review team) questionnaire was administered to all asthma admissions (or their parents/guardians) from 01/04/98 until 30/06/98. This consisted of parental information on background and current asthma status, as well as an admission and a discharge part filled in by medical staff. Results: There were 103 admissions with asthma over this time to 98 patients and forms were completed on 79 of them (76.9). Firstly we compared patients without forms (by medical record review) with those who had data and found no significant differences in: age, sex, length of stay, first diagnosis, prior oral steroid use, prior antibiotic use, "PAQART' admission score, other medical problems and those who received specialist medical follow up. 37 of the 68 known asthma patients had a written asthma plan, which was followed by14. When these groups were compared there was a significant decrease in the length of stay in those patients who had an asthma plan versus with those without, which was further decreased, though not significantly, if the plan was followed. There was no difference in their age, admission score, background disease as measured by days off school and courses of steroids in the past year, and frequency of wheezing. They had a non-significant increase in pre-hospital oral steroids (25% Vs. 12.5% P=0.21 ), and a tendency to be girls (59.5% Vs. 38.8% P=0.09) Discussion: Our study further advances the benefits of having an asthma plan, while raising the question of why in our population boys seem to be less likely than girls to actually possess one. It is recognised that inhaled corticosteroids have systemiCj effects on the hypothalamic-pituitary-adrenal (HPA) axis and bone metapolism. Fluticasone propionate (FP) is a high potency corticosteroid with moderate accumulation after multiple dose therapy. The prevalence of HPA axis suppression and low bone mineral density in children treated with high dose fluticasone propionate is investigated in this cross-sectional study. ~ 45 children and adolescents aged 4 -20 years attending asthma clinics at Monash Medical Centre were enrolled. Criteria for inclusion into the study were subjects treated with FP at a dose ~ 500 mcg for at least 6 months using a puffer and spacer or Accuhaler® with mouth rinsing. Subjects were excluded if they had received oral or systemic steroids in the previous two weeks or had another chronic illness. Early morning serum cortisol levels were obtained and those subjects with a cortisol level less than 400nmoVL underwent a modified Synacthen test (tetracosactrin 250 mcg IM) and dual energy X-ray absorptiometry (DEXA scan) of the lumbar spine and total body. Results: The subjects of mean age 12.8 years (range 4 -20 years) had been treated with mean daily dose FP 979.6 mcglm2/day (range 333 -2985 mcglm2/day) for a mean duration of 2.3 years (range 6 -48 months). 68% of subjects had serum cortisol levels less than 400 nmoVL. Of these subjects, 25% demonstrated an inadequate cortisol response to tetracosactrin stimulation, defined as a less than twofold increase in serum cortisol from baseline and a peak cortisol level !> 550 nmoVL at !> 60 minutes post tetracosactrin administration. None of the subjects in the study demonstrated low bone mineral density for bone age(< -1.5 SD from mean) when compared to healthy sex and age matched controls. There was a significant negative correlation (correlation coefficient -0.31, p < 0.05) between the dose of FP I body surface area and morning serum cortisol levels. Conclusion: These results indicate that use of high dose inhaled fluticasone propionate may be associated with significant adrenocortical suppression in a dose dependent manner. There was no associated reduction in bone mineral density in this study group. Background: AAAD are known to have lower levels of lung function than adult Australians of European descent. Our previous studies of crosssectional design have been unable to determine if this results from reduced lung growth during childhood, earlier cessation of lung growth or a greater decline in lung function with increasing age, which may all be due to environmental factors. Aim: To measure the rate of decline in lung function in AAAD and its relation to respiratory symptoms and smokirlg. Methods: Surveys of respiratory function were carried out in a community of AAAD in the northwest of Western Australia in 1993 Australia in , 1995 Australia in and 1999 to provide data for longitudinal analysis. Subjects answered a modified BMRC questionnaire on cough, sputum, dyspnoea and smoking. FEV1 was measured with a dry bellows spirometer. Generalised estimating equations were used to estimate the effect of calendar time on the rate of decline in FEV 1 where people were assumed to be random effects with repeated measures. Fixed effects for age, height and smoking were included using the STATA v5.0 software. Results: In the 1999 survey, the prevalence of cigarette smoking was 54.4% in males and 29.6% in females. Levels of lung function measured cross-sectionally were similar to those in our previous studies and comparable with those of other studies of AAAD. After adjustment for height and smoking, the average rate of decline in FEV 1 in adults was estimated to be 31 mis/yr (SE=3 mis/yr) in males and 23 mis/yr (SE=2 mis/yr) in females. The presence of doctor diagnosed asthma was associated with an increased decline of 9 mis/yr (SE=3 mls/ys) (P=0.008), self-reported wheeze with an increased decline of 5 mis/yr (SE=2 mls/ys) (P=0.05) and current cigarette smoking with an increased decline of 9 mis/yr (SE=3 mls/ys) (P=0.002). The presence of cough, sputum, or dyspnoea was not associated with a significant increase in the rate of decline of FEV 1 . Conclusions: Cigarette smoking, a history of asthma and the presence of wheeze are associated with greater rates of decline of lung function. This provides further evidence that environmental factors may be important in determining the level of impairment of lung function in AAAD. There were statistically significant linear trends in all four outcomes measured (P<0.001 ). We conclude that this classification differentiates groups of children who have different prognoses. Furthermore, seventeen years after original classification, adults who were classified as having current asthma during childhood are much more likely to have 'asthma that matters'. Support: CHATA, Allen + Hanburys, NHMRC, Asthma NSW. AstraZeneca Smoking cessation is difficult to achieve and best outcomes are seen using nicotine replacement therapy. We have previously presented outcome data from the Smoking Cessation Program at our hospital1. Our data indicated that the 12 month abstinence rate was higher in smokers of less than 30 cigarettes/day (20.4%) than those who smoked 30 per day (16.4%). Aim: to assess the effect of nicotine gum used in combination to a standard course of nicotine patches in heavy smokers. Methods: patients smoking 30 cigarettes/day presenting to the program were offered the opportunity to participate. In addition to standard interventions of counselling and nicotine patches, participants were provided with 4 mg nicotine gum to use as required. At 3 months, all participants were contacted by telephone or letter and asked their current smoking status. Continued abstainers were asked to attend the clinic for measurement of breath carbon monoxide concentrations. Outcomes were compared with historical controls studied 18 months previously. Results: 107 participants were recruited over 4 months for the combination group. Their mean age was 45.0 {12.2 (SD)) years and 62.9% were female, similar to the control group of 116 whose mean age was 42.4 (11.8(SD)) years and 62.3% were female. Smoking uptake occurred at a similar age in the combination group and controls (15.5 (4.6(SD)) vs 16.0 (5.8(SD)) (p=0.48). However, there was a significant difference in the average number of cigarettes smoked per day [41.7 (12.6(SD)) vs 38.2 (11.1 (SD)) (p=0.36)] and the Fagerstrom score of nicotine addiction [8.2 (1.5(SD)) vs 7.5 (1.9(SD)) (p=0.0025)]. At 3 months after entry into the program only 18.9% of the combination group were abstinent compared to 31% of historical controls. Breath carbon monoxide confirmed abstinence in the non-smokers, with a mean concentration of 2.5 (2.2(SD)) ppm. Conclusion: The addition of nicotine gum to topical replacement did not improve 3 month abstinence rates in heavy smokers. This may reflect greater nicotine addiction in the experimental group when compared to historical controls. 1 The prevalence of cigarette smoking and smoking cessation rates in a hospital population. Richard Wood-Baker. TSANZ Annual Scientific Meeting, Adelaide, 1998 Introduction: Mucociliary clearance (MCC) removes inhaled particulate matter, microorganisms, excess secretions and cellular debris from the respiratory tract. MCC is impaired in many respiratory conditions including chronic airflow limitation (CAL) and may vary over time, during acute exacerbations and with pharmacological intervention. Current methods of measuring MCC are limited by long acquisition time, radiation dose, difficulty of aerosol generation and deposition, signal attenuation and the need for patient cooperation. Aims: (i) To develop a rapid, simple, direct measurement of TMV for assessment of MCC suitable for clinical and research use; (ii) To compare TMV in normal subjects with that of CAL patients. Methods: A 0.1 ml droplet of macroaggregated albumin labelled with eemTc (2-5 MBq) was injected, after cutaneous application of local anaesthetic, through the cricothyroid membrane into the trachea of a seated subject. For data acquisition the subject lay supine for 15 min under a GE 400 gamma camera interfaced to an Icon workstation (Siemens). All data were stored in Icon Interfile format and analysed by CiliaC©, a program written in IDL specifically for the project. TMV was measured in 14 normal subjects and 17 patients with CAL. Results~ The test was well tolerated and no adverse events were reported. TMV (mean±SEM) in normal subjects was 8.0 ± 0.8 mm/min. TMV (mean±SEM) for patients with CAL was 0.6 ± 0.8 mm/min. TMV was significantly different in CAL patients than normal subjects (p< 0.001, Student's I-test). Conclusions: We have developed a rapid, safe, direct measure of TMV that gives values similar to those reported elsewhere. Using this technique we have shown that TMV is significantly slower in patients with CAL than in normal subjects. Supported by the ALF/ Boehringer lngelheim CAL Fellowship Key words: mucociliary clearance, scintigraphic, CAL The ai_m of this s~u~y ~as to determine whether the surviyal of patients with Chrome Airflow l1m1tat1on (CAL) on home oxygen therapy (HOT) seen in routine clinical practice was less than that of the original Randomized Controlled Trials (RCTs) and to investigate factors influencing survival. Methods: A list of recipients prescribed HOT for CAL at Flinders Medical Centre from 1 January 1977 to 31 March 1999 was generated retrospectively. Survival data were compared with that reported for the two original RCTs and recent overseas studies. Factors influencing survival were studied. Results: Survival data were collected for 505 CAL patients on HOT (male:female 249:256) mean age (males, females) 69.9, 71.0 years. Survival was less than that of the original RCTs but comparable to that reported for Belgian and Swedish CAL patients. Overall crude survival was 75% at 1 year, 51% at 2 years, 19% at 5 years and 1% at 10 years. Median survival was 21.9 months for males and 28.2 months for females with a significant survival advantage for female sex (log rank test p = 0.016). Cox's Proportional Hazard modelling showed a lower body mass index (BMI) was significantly associated with reduced survival for males while for females age, co-morbidity, BMI, and FEV 1 , at baseline were related to survival. CAL patients using more than 19 hours per day on their oxygen concentrator had improved survival over those using less than 19 hours per day. Conclusions: Survival for CAL patients on HOT, where the tighter selection criteria of the original RCTs do not always apply, is less than that of the original RCTs but comparable to that recently reported overseas. Gender differences are apparent. The Australia and New Zealand (ANZ) LVRS Database was established in 1997 to provide clinicians in Australia with information that leads to the best possible outcomes for people who undergo LVRS. At October 1999, the database contained individual patient data from 235 cases from 10 centres. The data have been entered and verified in Access 97 and analysed in SPSS version 9. Univariate and multivariate analysis was undertaken to examine the effect of pre-operative medical and peri-operative surgical factors on morbidity and 3 month mortality post surgery. 129 (55%) cases were male. Mean age at surgery was 62. Post-operative physiological (FEV1) and functional (6 min walk) parameters improve to 12 months. Pre-operative functional status and surgical factors have the greatest effect on morbidity and 3 month mortality post-operatively. The 6MWT and ISWT are commonly used measures of exercise capacity in patients referred for pulmonary rehabilitation. Previous research has shown lower heart rate (HR) and dyspnoea levels with the 6MWT1, indicating that it may only submaximally stress the cardiorespiratory system. Aim: To compare the cardiorespiratory responses associated with the 6MWT and ISWT in patients with COPD. Methods: 15 patients (12 male), mean (SD) age 62.6 (7.7) years and FEV 1 0.91 (0.47)1, 31.4 (13) %predicted were studied. ISWT and 6MWT were conducted using standard protocols with strong encouragement to maximise performance. HR (Polar monitor) and dyspnoea (Borg 0-1 O scale) were measured at one minute intervals during both tests. Oxygen saturation (Sp0 2 ) was measured preand immediately post-exercise. Results: There were no significant differences in maximum HR, dyspnoea or the magnitude of desaturation with the two tests (Table) . Mean(SD) distance walked in the ISWT and 6MWT was 397(136) and 507(108)m respectively. Sp0 2 (%) Dyspnoea Pre-ex. Max-ex. Pre-ex. Post-ex. Pre-ex. Max-ex. ISWT 89.6(12) 125. 1(18) 95.5(1.5) 86.3(6.3) 0.6(0.8) 6.0(2.2) 6MWT 91.9(13) 126.9(15) 94.9(1.6) 86.8(5.6) 0.6(0.8) 5.9(2.1) With strong encouragement the 6MWT and ISWT can provide equivalent degrees of cardiorespiratory stress. However, unlike the 6MWT, the external pacing and standard increments in workload of the ISWT enables comparison between patients at equivalent workloads and the prescription of a walking program based on workload. Contraction of the human diaphragm contributes to the response of the trunk muscles that stabilises the spine during rapid limb movements. This postural function must be coordinated with the respiratory activity of the diaphragm. During repetitive limb movement there is usually phasic modula,tion of diaphragm electromyographic activity (EMG) with respiration, as well as tonic activity and phasic modulation with each limb movement. Aim: To determine whether this pattern of activity occurs in subjects with increased respiratory demand. Methods: Two groups were tested: (i) six subjects with severe chronic airflow limitation (CAL) who were awaiting lung volume reduction surgery; and (ii) nine subjects with no history of respiratory disease who breathed with an increased dead space for 4 minutes. EMG recordings of the right costal diaphragm were made with intra-muscular electrodes inserted into the 7th or 8th intercostal space. Movement of the left arm was recorded with a potentiometer. Patients with CAL performed rapid repetitive shoulder movements (30') for 10-20 s while standing or sitting. The normal subjects moved their left arm for the first 1 Os of each minute of dead-space breathing. The contribution of the diaphragm to respiration and postural control was assessed by evaluation of the frequencies of phasic modulation of EMG amplitude. This was quantified by analysis of the distribution of power in the power spectral densities. Results: Unlike normal subjects, the CAL subjects had no or minimal modulation of diaphragm EMG at the frequency of limb movement. In the trials in which normal subjects breathed with increased dead space the power of the EMG data at the movement frequency was significantly reduced by the second minute. These results indicate that in situations of increased respiratory demand the contribution of the diaphragm to postural control is reduced. Supported by the NHMRC and the Australian Lung Foundation. SOCS (suppressor of cytokine signalling)-1 is one of a family of eight proteins containing an SH2 domain and C-terminal SOCS Box mottt. To explore the physiological roles of the SOCS proteins, we are generating mice in which these genes are replaced by B-galactosidase. SOCS-1-/-mice were born but exhibited stunted growth and died before weaning with fatty degeneration of the liver and monocytic infiltration of several organs. B-galactosidase activity in SOCS-1 +/-mice was detected in most cells within the thymus, as well as in splenocytes and bone marrow cells, particularly in B-lymphoid populations. Consistent with this expression profile, the thymus in diseased SOCS-1-/-mice was significantly reduced in size, the animals were lymphopenic and their haemopoietic organs exhibited deficiencies in B-lymphocytes. These data suggest that mice lacking SOCS-1 are unable to properly control responses to cytokines that have cytotoxic side-effects. As neonatal exposure to interferongamma is known to cause liver damage and lymphopenia, we investigated the role of this cytokine in the pathology of SOCS-1-15 % from baseline) following challenge with wine containing 300 ppm sulfite, but did not respond to wines containing 20, 75 or 150 ppm sulfite. Asthmatic responses were maximal at 5 min, with an average decline in FEV 1 of 28.7 ± 13 %, and took between 15 and 60 min to return to baseline levels. In the cumulative dose-response study, the responsiveness of 12 asthmatics providing a history suggesting a sensitivity to the sulfite additives in wine was compared with the response of 6 asthmatics reporting no sensitivities to these drinks. No signtticant difference was observed in any of the lung function parameters measured (FEV 1 , PEF, FEF 2 s-75 ) in these 2 groups. Conclusions: These results suggest that only a small number of wine-sensitive asthmatics respond to a single dose challenge with sulfitedwine under laboratory conditions and that cofactors may be playing a role in the sensitivity of many asthmatics to wine. A cumulative dose challenge protocol did not increase the sensitivity of our test for reactivity to the sulfites in wine. R. Siebers, J. Lane, M. Sakaguchi*, P. Fitzharris, J. Crane. Wellington Asthma Research Group, Wellington School of Medicine, Wellington, New Zealand· and National Institute of Health~. Tokyo Japan Mite occlusive bedding covers are recommended to reduce house dust mite (HDM) allergen exposure for HDM sensitised individuals with allergic disease. As inhaled HDM allergen is more relevant than HDM allergen levels in settled dust, we have studied whether occlusive bedding covering reduces the airborne HDM allergen, Der p 1 in bedrooms. We obtained dust samples by vacuuming (1 m2/min) from pillows, duvets, and mattresses of 12 subjects. Additionally, air was sampled for 8 hr/night for 7 nights with a personal sampler (Sibata, Japan) at 1 Umin. Pillows, duvets, and mattresses were then covered with occlusive covers (Alprotec, UK) for 7 days, and during this time air was sampled as described above. After the 7 days, dust samples were obtained as described above directly from the surface of the bedding covers. Week o rho = 0.23 (p=0.0057); Week 8 rho = 0.27 (p=0.0008) Petri dish with rate of change in total allergen: rho= 0.10 (p=0.2286) Conclusions: The bed intervention did not result in a lower rate of Der p 1 allergen settling in Petri dishes kept adjacent to beds despite intervention beds having less total allergen and a lower concentration of allergen in dust. Petri dish Der p 1 allergen levels showed a weak but signtticant correlation with bed reservoir levels but not the rate of total allergen change in beds. The allergen content of settling airborne dust may be affected by sources other than the bed. ( We have previously found that young adults perceive food intolerance and allergies as common, however lgE mediated food allergy is deemed to be uncommon. Aim: To determine how much of perceived food allergy/intolerance was due to lgE mediated food allergy, as defined by skin prick tests (SPT). Methods: In 1998, 457 young adults {26-50 years) underwent SPT to five common food allergens (cow's milk, peanut mix, egg white, shrimp and wheat) and were asked whether they had ever suffered any food "illness/trouble", and if so to list such food(s). A positive SPT was defined as wheal formation of <: 3mm diameter. Cohen's kappa {K) was used to assess the agreement between SPT and self-reported reactions to food(s) which contain the allergen of interest. Results: 62 participants had a positive SPT to at least one food allergen. The Introduction: iPEEP may contribute to chronic respiratory failure in COPD, constituting an inspiratory threshold load {ITL) on muscles already at a severe mechanical disadvantage. Extrinsic PEEP has been advocated to relieve the ITL caused by iPEEP. We sought to document the effect of incrementally increasing extrinsic PEEP (as CPAP) on ITL during wakefulness. Methods: Nine patients with severe stable COPD (mean FEV 1 30.7% pred) were studied. CPAP was increased in 1cmH 2 0 increments to a maximum of 1 OcmH 2 0. At each pressure we measured: i) iPEEP as the change in oesophageal pressure (t.Poes) from the onset of inspiratory effort to the start of flow ii)Change in transdiaphragmatic pressure (t.Pdi) over the same interval. iii) Pressure-time product {PTP) for the respiratory muscles. iv) End-expiratory lung volume (EELV). Results: In 8 subjects, t.Pdi closely matched t.Poes, indicating minimal contribution of abdominal expiratory muscles to measured iPEEP. In these 8, mean (± SEM) baseline iPEEP was 2.86 (0.61) cmH 2 0. CPAP significantly reduced but did not abolish measured ITL. Mean minimum ITL was 0.96(0.15) cmH 2 0 (p<0.05). PTP per litre ventilation reduced from 5.84(1.03) to 2.8J (0.42) cmH 2 0/L without a change in minute ventilation, but at the expense of progressively increasing lung volume, to a maximum of 0.58(0.11) L above baseline.Conclusions: In severe stable COPD it is not possible to abolish the ITL due to iPEEP using CPAP. lnspiratory muscle pressure output is reduced but there is progressive hyperinflation. Possible reasons include i) iPEEP is not due to dynamic airway compression, but rather fixed airflow obstruction ii) marked inhomogeneity in severity of dynamic airway compression prevents complete counterbalancing of iPEEP. The root mean square of the diaphragm EMG signal (RMSdi) during inspiration has been used to quantify activation of the diaphragm during tidal breathing (Sinderby et al JAP 1998; 85:2146-58) . To examine the RMSdi response to hypelcapneic ventilatory stimulation, its repeatability, and methods of normalisation, we measured breath-by-breath RMSdi, tidal volume, duration of respiratory cycle (Ttot), and end-tidal PC0 2 in four healthy subjects (age [mean ± SD] 44.8 ± 13.5 yrs, BMI 2! §.1 ± 1.0 kg/m2) on two occasions during steady-state ventilation at seven levels of FiC0 2 between O and 0.08 presented in random order. RMSdi was measured using a multi-electrode oesophageal catheter and controlled for signal contamination and diaphragm position. We also measured RMSdi obtained during a slow inspiration from FRC to TLC (RMSdimax), electrocardiogram R wave amplitude at the oesophageal electrode pair closest to the diaphragm and thickness of the costal diaphragm by ultrasound. We found that (a) the coefficient of variation of RMSdi over 1 O breaths at peak ventilatory stimulation (FiC0 2 0.08) ranged from 0.07 to 0.15, and this coefficient improved only minimally when a greater number of breaths were analysed, (b) RMSdi increased progressively with FiC0 2 in all subjects, (c) the repeatability of RMSdi improved after normalisation with either RMSdimax or R wave amplitude, {d) differences in RMSdi between the subjects were eliminated after normalising with RMSdimax and Ttot (p = 0.10, ANOVA) and (e) RMSdi was not proportional to thickness of the costal diaphragm. We conclude that neural drive to the diaphragm in healthy individuals can be measured using the mean RMSdi over 10 breaths during steady state ventilation, and can be normalised by dividing it by the RMSdi during a breath from FRC to TLC and the duration of the respiratory cycle. , but the severity of this and how it is related to daytime function is unclear. Aim To assess the incidence of SDB and neurobehavioural function in asymptomatic subjects. Methods As part of a study looking at neurobehavioural function in patients with obstructive sleep apnoea, 23 subjects were recruited as normal centrals. A standard script was used to eliminate those who had any symptoms of SDB, including snoring and breathing problems while asleep, and those who had any psychiatric or other medical problems. These subjects then underwent overnight polysomnography, a Maintenance of Wakefulness Test (MWT) and neurobehavioural assessment. Results The 18 males and 5 females had a mean ( which had a reduced score in 10 subjects (43.5% Airway infection, inflammation and respiratory symptoms may occur in infants with cystic fibrosis (CF) from the first few months of life. To explore the relationship between airway infection, lung function and respiratory symptoms, we conducted a cross-sectional study in 41 children with CF (median age 17 mo) who had bronchial lavage and lung function measurement under general anaesthesia. Forced expiratory volume in half a second (FEV 0 _ 5 ) was determined by the raised volume rapid thoracic compression technique. A colony count 2'.105 CFU/ml bronchial lavage fluid and/or a dlf!erential neutrophil count >50% was considered positive for airway infection/ inflammation. A healthy control group (n=8, aged 5-32 mo) had lung function testing prior to elective surgery. Results: 18/41 (44%) children had airway infection, 56% of whom were asymptomatic. Conversely, 7/23 (30%) infants without airway infection were symptomatic. Mean FEV 0 . 5 (95%CI) adjusted by analysis of covariance for height for those with and without infection was 215ml (187, 243) and 244ml (219, 269) respectively. Mean FEVo.5 for the control group was 280ml (95%CI 239,321). The difference between the groups was significant (p=0.04). No correlation was found between FEV 0 _ 5 and markers of inflammation. Symptomatic children had lower lung function, regardless of the presence of infection (P=0.004). Concluslon: Airway infection in infants with CF is associated with lower lung function but the presence of respiratory symptoms is more predictive of lower lung function than infection status. The primary defect in CF or other factors affecting airway calibre may lead to impairment of lung function and respiratory symptoms in the absence of infection. G. Nixon is supported by the Grand Lodge of New Zealand Freemasons. Key words: Cystic fibrosis, infant, lung function, infection, cough. Reid DW, Wrthers NJ, Francis L, Wils9n JW, Kotsimbos TC. Cystic Fibrosis Service, Department of Respiratory Medicine and Monash University Medical School, Alfred Hospital, Melbourne, Victoria. Introduction; Iron deficiency (ID) is common in cystic fibrosis (CF) and is normally attributed to gastrointestinal factors and chronic inflammation secondary to sine-pulmonary sepsis. Hypothesis; Pseudomonas aeruginosa (PA) requires iron for proliferation and we hy~othesise that ID in CF might be directly related to PA infection and severity of lung disease. Methods; We measured iron status and several systemic markers of inflammation in 31 CF patients (median age 27 years, range 21-36 years) and assessed the relationship to FEV1%predicted, daily sputum volume and degree of pancreatic enzyme supplementation. Additionally, we measured the sputum concentrations of total iron and ferritin in an unselected subgroup of 13 subjects. Results; Seventy percent of subjects studied were ID (serum iron,.:; 7µmol/L &/or transferrin%sat. ,.:;16%). Significant relationships existed between serum iron, transferrin%sato., C-reactive protein (CRP) & ferritin:CRP ratio and FEVl%pred. (r=0.5, r=0.4, r=-0.7, r=0.7 respectively, p<0.05). The volume of sputum expectorated daily was strongly associated with FEV1 %predicted, transferrin%sato., and serum ferritin:CRP ratio (p<0.05). No relationship existed between ID and pancreatic supplementation. Sputum concentrations of total iron (median 63µmol/L, range 17-134 µmol/L) and ferritin (median 5038 µg/L, range 894-6982 µg/L) exceeded normal plasma levels and negatively correlated with FEV1%predicted (r=-0.6, r=-0.5 respectively, p<0.05). Conclusions; ID in CF patients appears to be directly related to the severity of suppurative lung disease. Iron loss into the airway may facilitate PA infection and contribute to iron deficiency. Both long-acting J3-agonists and inhaled corticosteroids (ICS) are effective add-on therapy in persistent asthma. Clinicians usually make empiric choices between these 2 different classes of drugs. Induced sputum identifies a group with persistent asthma but suppressed inflammation (noneosinophilic) asthma in whom we hypothesised that Salmeterol (S) may provide better asthma control than ICS. 78 adults with stable symptomatic asthma were recruited and those with suppressed eosinophils (E<5%, n=33) entered a 1 week run-in period followed by concealed random allocation to add-on therapy with fluticasone 500µg/day (F) or S 50µg/day with doubleblind evaluation of the treatment effect after 1 month. Baseline airway responsiveness (AR) was moderately increased, mean PD 20 5.75ml, and improved 2-fold to 11.5ml with S (p<0.05), whereas F led to no change in AR (7.51ml, p>0.05). Sputum eosinophil cationic protein (ECP) was high at baseline {2519ng/ml) and was not suppressed by therapy (S=3673, F=2258) . Sputum E at baseline was 1.3%, and remained unchanged after S, but fell to 0.6% after F (p<0.05). Peak flow improved by 28Umin with S (p<0.01 ), but was not altered by F (1. The concentration of nitric oxide in exhaled air (eNO) is associated with atopy and may also be a measure of airway inflammation. Individuals allergic to pollens and fungi have been reported to have more symptoms during seasons when the levels of the aeroallergens in ambient air are high. Aim: To determine if the association between eNO levels and sensitisation to specific allergens is the same in summer and winter. Methods: Skin prick test results for five allergens in 286 atopic children from Wagga and Moree were related to concentration of eNO in winter and summer 1998. At the skin prick test, a wheal size >3 mm was defined as being sensitised. Expired air was collected in a 3L wine cask bag and the NO content measured by chemiluminescent analyser Results: The proportion of children sensitised to house-dust mite was 64.3%, to Alternaria was 43.4%, to rye grass pollen was 53.5%, to C/adosporium was 23.4% and to cat was 18.5%. House dust mite and Cladosporium were significant predictors of eNO in both summer (p<0.001) and winter (p<0.001 ). Between winter and summer eNO increased in Moree (p<0.001) and decreased in Wagga (p<0.001). Sensitisation to house dust mite, C/adosporium, Alternaria, ryegrass or cat were not significant predictors of change in eNO in either town, although a negative association between Alternaria sensitisation and change in eNO in Wagga was of borderline significance (p=0.03). Conclusion: In this sample of atopic children, eNO was related to sensitisation to house dust mite and C/adosporium. The direction of seasonal changes in eNO differed in the two towns, but were probably unrelated to allergic sensitisation. The factors which determine seasonal change in eNO remain unclear. Asthmatics can be classified as good or poor perceivers of airway function either in the laboratory or in the community. In a study done in 1988 -90, good perceivers were identified as having a significant negative correlation of visual analogue score (VAS) against coded PEF. Only ten of 300 patients were recording daily PEF using a Mini-Wright meter. We report a case of a good perceiver who has maintained a PEF and treatment diary card from first assessment in 1989 to re-assessment in 1999. Methods: The male patient, aged 66 in 1989, had known asthma. Perception of asthma was assessed in 1989 and 1999 using a 100 mm VAS with O mm being "No Asthma" and 100 mm being "Worst Ever Asthma". PEF were recorded using turbine PEF meter up to 4 times daily for 14 days. The readings of PEF were not visible to the patient. The diary card, kept by the patient, showed twicedaily PEF. The variability of PEF and the effects of stated treatment for each day were analysed. Results: In 1989, PEF ranged from 30% to 107% predicted and VASmax was 93mm. VAS and PEF were significantly correlated (r = -0.85), with a slope of-1.03 mm%-1. In 1999, PEF ranged from 87% to 120% predicted and VASmax was 23mm. VAS and PEF were significantly correlated (r = -0.33), with a slope of-0.21 mm%-1. Variation in PEF was up to 70% prior to March 1990, with PEF ranging from 180 to 460 l.min-1, with inhaled 13 2 -agonists being the primary treatment. In March 1990 Becloforte improved PEF from a mean of 308 ± 53 l.min-1 to 425 ± 31 l.min-1. Subsequently the variation in PEF was maintained to about ± 20%, with PEF ranging from 405 to 520 l.min-1. Seven major reductions in PEF were observed (t.PEF > 75 l.min-1), some requiring medical intervention. The changes observed in perception demonstrate the probable effects of inhaled corticosteroids on perception of asthma, with a reduced slope compared to that in 1989. The control of asthma is clearly improved, with marked reduction in PEF variability_ The diary card has provided a unique insight into the variation of PEF and the requirements for treatment over 1 O years in this patient. Serial measurements of airway calibre are used in the diagnosis and management of asthma. Traditionally PEF is used to calculate Bronchial Lability (BL) as: [highest daily PEF -lowest daily PEF]/highest daily PEF. FEV 1 is less effort dependent and more reliable than PEF, and has been shown to reflect flow in both large and small airways. Portable data storage spirometers now makes serial FEV 1 measurements possible. Aim: Determine the measurement of airway calibre (FEV 1 or PEF) and calculation of BL that best separates normal subjects from those with asthma. Method: On the basis of asthma questionnaire, spirometry and methacholine challenge, 25 well-defined asthma and 25 normal subjects were identified. All subjects then performed serial spirometry, recorded 7 times per day for 4-7 days using an electronic data storage spirometer (Micromedical DiaryCard, UK). Only sessions where spirometric data met ATS acceptability and reproducibility criteria were used in subsequent analysis. BL indices of overall variability, within-day variability, between day variability and circadian variability for FEV 1 and PEF were calculated, and the upper limit of the normal range (95•h percentile for normal subjects) determined for each index. Results: The traditional method of determining BL using daily amplitude in PEF had an upper limit of normal of 18.2% and correctly identified only 50% of subjects with asthma. By contrast the coefficient of variation of FEV 1 from all sessions (CovFEV 1 ) best separated the asthma from the normal group. In the normal group CovFEV 1 had an upper limit of normal of 4.5%. Values in excess of this level were strongly suggestive of asthma (sensitivity= 92%). For all indices of BL, FEV 1 proved a significantly better measure than PEF (p<0.01). Where the quality of spirometric data can be assured, FEV 1 proved more sensitive than PEF in separating the asthma and normal groups for all indices of BL. The index of BL providing the greatest sensitivity in the detection of asthma was CovFEV 1 . Air ionisers employ the generation of potential differences in the kilovolt range to produce negatively charged particles. The particles they emit are hydrated, mobile and highly reactive. Air ionisation has been associated with altered serotonin metabolism in human and animal experiments. II is an effective means of precipitating airborne particles including particulate, airborne allergens and microorganisms, however, the effect of the use of these devices upon the clinical condition of asthmatics is the subject of controversy. This study aimed to assess the effect of nightly negative air ionisation (estimated 250 000 negative ions/ml at 1 metre from emitters) upon measures of asthma in 53 adult subjects (28 active, 25 placebo). Methods: A double-blind, placebo-controlled, study design with two parallel groups was utilised. Following a 1 week run in, subjects used active ionisers or sham devices for 9 weeks. Lung function (pre and post bronchodilator FEY,, FVC, FEF 2 s-rs"kl and Asthma Quality of Life were assessed in interviews at 5 week intervals. Subjects recorded peak flows, medication usage and symptoms twice-daily. Total plasma serotonin concentrations were also measured. Results: There was a signtticant difference found between groups in the Social Disruption subscale. The active group showed less of an increase (1.68, p=0.040) after sex adjusted analysis, suggesting a detrimental effect of air ionisation upon Quality of Ltte. Short acting bronchodilator usage increased more in the active group (1.82 doses per day, p=0.19) between weeks 5 and 6 than in the placebo group. Lung function scores were not significantly different between groups, although there was a trend for decreased FEV1 and increased response to bronchodilator in the active group. Plasma 5-HT was increased in the active group by 101.5 nmol/L (p=0.43) after 9 weeks of treatment. These results suggest that there may be a detrimental effect of the nightly use of air ionisers in asthma treatment. II is essential that further investigation of these effects be undertaken in well controlled patients lo establish if the negative air ioniser usage is truly a risk factor for asthma exacerbations in the community. Longacting beta 2 agonists now have an established role as an adjunct to inhaled corticosteroids in asthma management. Eformoterol Is available in two dry powder devices, Foradile Aerolizer® and Oxis Turbuhaler®. There has been no comparative study of their clinical effect. We compared the bronchodilator response, time to onset of response and time to maximum bronchodilator response following 12 µg eformoterol delivered by these devices. Nineteen nonsmoking asthmatic patients with a documented bronchodilator response were enrolled in the randomised, single-blinded, crossover trial. The severity of baseline airflow limitation ranged from mild (FEV 1 >70% predicted) to moderately severe (FEV 1 50-59% predicted). The patients were assessed on two separate study days at least one week apart. FEY, was measured for a total of 6 hours after a single dosage of eformoterol. Side effects were also recorded. Statistical analyses were performed using SPSS. The area under the FEV 1 -time curve (AUC) was calculated for each device and evaluated by paired I-test. There was no significant difference in AUC, time to onset or time to peak effect. One third of patients experienced side effects with each device which resolved within the study period. These included tremor, nausea and headache. We conclude that there is no significant clinical difference between 12 µg of eformoterol delivered by either device. Methods:ln a prospective, multicentre, randomized, doubleblind, parallel group study we compared the effectiveness of (A) adding formoterol (Foradile®)(FORM) dry powder inhalation 12mcg bd to beclomethasone (BDP) 500mcg bd with (B) doubling the BDP dose to 1000mcg bd in asthma patients on BDP 1000mcg a day or equivalent. Subjects: All had 2 of the following on 2 of the last 7 days of a 4 week run-in: daytime(DT) symptoms limiting activity; any nocturnal(NT) symptoms; use of at least 4 puffs of rescue bronchodilator(BD); diurnal variation in PEF of> 15%. There were no differences between groups in baseline characteristics, symptoms, PEF and 2 hour post waking urinary cortisol/creatinine ratios (UCCR) as a measure of adrenal Hyperventilation syndrome may be due to many causes, but gastrooesophageal reflux disease (GORD) has not been aetiologically linked to date. 21 cases have been identified. Three are reported here. Each was diagnosed with GQRD and each was cured with appropriate treatment. Case 1 (SE) A 25 year old Lebanese born female presented in May 1998 with a four year history of "as if I have not taken a full breath". She was sighing regularly. Lung function tests & CXR were normal. ylinical examination was normal apart from an indented tongue and obesity. Gastroscopy showed one small area of reflux oesophagilis and biopsy showed H.pylori colonisation. She was treated with triple antibiotic therapy (Helicopack) for fourteen days. Her symptoms resolved and she remains symptom free after 18 months follow up. Case 2 fJP) A 40-year-old male East Timorese refugee presented with a four-month history of "I can't breathe properly'' especially when going upstairs. At night he woke with shortness of breath "as if I have not taken a full breath" and obtained some relief by drinking water. He also had a dry cough. Clinical examination revealed no abnormality except for repeated sighing. Lung function tests, CT scan and serum iron were normal. Gastroscopy showed a deep oesophageal ulcer (grade 3) at the lower end of the oesophagus. He was treated with Losee HP7 followed by Omeprazole 20 mgs bd for 6 months and 16 months later he was "very well". Case 3 fSEl A 22-year-old Australian born male of Lebanese extraction presented in September 1996 complaining of "as if I have not taken a full breath" and sighing many times each day for 4-5 years. His wife feared that "my husband does not like me". Spirometry and CXR were normal. Gastroscopy showed severe ulcerative oesophagitis (grade 4). He was treated with omeprazole 20 mgs bd for 6 months and at last follow up on 9/11/99 he said, "I am very well thank you. You cured me long ago". GORD can cause the above mentioned symptom which is curable and physicians should be aware of ii and treat accordingly. Objectives: To determine if short-term or long-term outcomes in subjects with poorly controlled asthma can be improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines. Methods: Parallel-group study of 61 subjects with poorly controlled asthma, randomised to receive 32aaµg or 16aaµg budesonide daily by Turbuhaler® for B wks (double-blind), then 16aaµg/day for B wks (single-blind), followed by 14 months of open-label budesonide dose titration using a simple clinical algorithm. Study design incorporated a written asthma crisis plan based on electronic PEF monitoring. Primary outcome variable for Wks 1-16 was change in airway hyperresponsiveness (AHR), and for the open-label phase, mean daily budesonide dose. Results: During Wks 1-16, subjects starting wtth 32aaµglday were 3.B times more likely to achieve remission of AHR (PD 20 FEV 1 2:3.92µmol) than those starting with 16aaµg/day, but other outcome measures did not differ significantly (e.g. increase in morning peak expiratory flow + 134 cf. + 127Umin, p=a.B). Subjects achieving remission were less likely to experience an exacerbation (2113 cf. 27/48, p=a.a2). During budesonide dose reduction, there was no significant difference in mean budesonide dose (1327µg/day cf. 1325 µglday, p>a.3). By completion/withdrawal, there was no significant difference in overall improvement in AHR (+3.9 cf. +4.2 doubling doses, p>a.6) or in asthma control (median symptoms a.a cf. a.a days/wk, ~2-agonist use a.a cf. a.1 occasions/day, p>a.B). Median compliance with electronic monitoring was 89% over the whole study. Conclusions: A high starting dose of budesonide in subjects with poorly controlled asthma caused more rapid remission of AHR, but tight control of asthma was achieved with both starting doses. Supported by AstraZeneca Sweden, AstraZeneca Australia, and NHMRC Key words: asthma, inhaled corticosteroids, airway hyperresponsiveness Alyson Roberts and Cheryl Salome Institute of Respiratory Medicine University of Sydney NSW 2aa6 Symptoms of wheeze or chest tightness, reported in questionnaires, form part of the definition of asthma in epidemiological studies, but these words may have different subjective meanings. Aim: To determine if the appropriateness of the terms used to describe methacholine induced airway narrowing differs between asthmatics and non-asthmatics, or, in a community sample, between subjects with reported wheeze and those who have not wheezed. Methods: 23 non-asthmatic and 19 asthmatic subjects underwent methacholine challenge (a.a4-2aa µmoles), to cause respiratory discomfort. They then marked a visual analogue scale (VAS) to rate the appropriateness of each of 9 terms to best describe the sensations induced by the methacholine. The distance of the mark from the left-hand end of the VAS labelled 'not at all appropriate' was recorded as the % of the total VAS length. This protocol was repeated in subjects selected from a population sample, with (n=32) and without (n=2a) reported recent wheeze. Results: The asthmatics (23.5 ± 6.3%) had a slightly greater % fall in FEV1 than the non-asthmatic subjects (16.2 ± 4.6%)(p=a.a6). Asthmatics rated 'I feel wheezy' {68.2 ± 13.1 %)(p«a.aa1 ), 'My chest feels tight' (68.9 ± 13.B%)(p< 30 to be a good predictor of the StGQ score after adjusting for number of comorbidities and history of smoking (p < 0.001). On average, people with a RSQ score> 30 will have a StGQ score 13.4 points higher {95%CI: 8.7, 18.2) than those with score .;; 30. This is a clinically significant difference. Conclusion: The RSQ, used as a measure of severity, is a good predictor of clinically significant differences in Qol in adult asthmatics, and is sufficiently brief to be useful in general practice, and also as an alternative to lengthy Qol measures in some research settings. The AMAQ {Asthma Medication Adherence Questionnaire) has been developed to estimate adherence to asthma preventer medication based on patients' attitudes and behaviours. Methods: Literature review and patient interviews were used to identify items that could measure traits and behaviours relevant to adherence, along with questions to record reported adherence. Items were trialled to assess appropriateness, clarity, and comprehensiveness, modified through several draft versions, and then presented to patients by a non-clinician, emphasising that non-adherence was known to be common, honesty was desired, and responses were confidential. Results were analysed using Factor Analysis to refine item clusters representing each domain {eg. perceived stigma, asthma severity), and Cronbach Alpha was used to reduce the number of items in each cluster and enhance reliability. Multiple regression was then applied to select and weight items to form a scoring method predictive of nonadherence. Results: Analyses were based on 26 subjects under 50 years of age (all patients over age 50 reported full adherence). Seven item clusters were selected to be predictive of non-adherence, eg. 'perceived stigma', 'subjective estimate of asthma seriousness', 'locus of control'. The model predicted preventer non-adherence with multiple A= .90; R2= .81; Adjusted R2= .69, F(8, 13)=6.88, p<.001. Conclusions: The AMAQ offers a survey instrument that estimates non-adherence based on reported attitudes to asthma medication. It also provides a systematic and comprehensive assessment of attitude factors and behaviours associated with nonadherence, and could be used to allocate subjects a priori to treatment groups in clinical trials to control for non-adherence effects. There is little understanding about what most influences decision-making around smoking in young people wtth asthma. We aimed to examine the perceptions, attttudes and behaviours of adolescents with asthma, focussing on understanding the experiences and practices of smoking and tts impact on asthma and medication use. Method: 90 young people (10-24 years) were recruited from 3 tertiary asthma clinics and participated in an in-depth interview that was recorded and transcribed. Content and thematic analyses were undertaken, with data management assisted by NUD.IST. Results: 57 participants reported to be non-smokers, 11 classified themselves as smokers, 4 as former smokers and 7 as marijuana smokers. Smoking status was not detailed in 11. Across all age groups participants knew that smoking was bad for their health. However, nearly all smokers in the sample mentioned initial peer pressure, via constructions of "being cool", as contributing to their smoking. This was frequently despite acknowledging that smoking made their asthma worse. The smokers chose to premedicate with reliever medications prior to social events where they knew that they and/or others would be smoking. This behaviour was paralleled among the non-smokers who premedicated prior to participating in social events where they expected to be exposed to passive smoke. Both groups viewed this as a reasonable means of participating in social activities wtthout overly compromising short term health outcomes. These findings indicate that smoking (passive and active) is commonly experienced as an asthma trigger, but that in smoking adolescents, this knowledge is more influential in informing use of reliever medication than in stopping smoking. This suggests that smoking cessation strategies must be attuned to both social as well as health contexts. The extent of poor adherence with preventative medications for asthma is increasingly recognised. Adolescents are widely believed to be less adherent than other populations although there is little evidence to support this belief. The rellabillty of adolescent self report (AR) versus parent report (PR) of adolescent medication taking is unknown. We aimed to measure adherence with preventative asthma medications in adolescents and compare AR and PR of adherence with objective measures of adherence. Method: 30 consecutive adolescents were enrolled following routine review at a tertiary adolescent asthma clinic. An electronic Doser was attached to all metered-dose inhalers (MDI) for one month. Telephone follow up with adolescents and parents (separately) identified AR and PR for the last 7 days and the total study period, using clinical approaches to optimise self report. Results: Mean adherence rates for preventative medication were 71 % (last 7 days) and 78% (study period). However, adolescents were fully adherent on only 40.6% (last 7 days) and 53.4% (study period) of days. Extra dosing was identified throughout the study period, rather than rapid MDI emptying or 'dumping'. There was moderate association but weak agreement with AR over the last 7 days of monitoring only (ICC = 0.25). PR showed poor agreement with objective monitoring over both time periods. PR agreed better with AR. Concluslons: Mean adherence in this selected population of adolescents is as high as has been previously reported in any population with asthma. However, adolescents were fully adherent on less than half of all days studied. Adolescents reported medication use more reliably than parents over the last 7 days of monitoring. guidelines, yet teaching about asthma In medical school is seldom assessed. We studied asthma knowledge, confidence in asthma management, and effectiveness of an asthma education workshop. Methods: Interactive teaching sessions on management of asthma and a practical session using asthma devices. Theoretical knowledge was assessed by a 20 item questionnaire, completed before the workshop at 2 wks. Practical knowledge was assessed by confidence scores in use of asthma devices (0-5 : not confidentvery confident) before, immediately after the workshop, and at 2 weeks. Results: Mean (SE) knowledge scores increased significantly from 64.4 (6.1)% to 74.2 (5.6)% (p<0.05, paired I-test) at 2 weeks. Students scored poorly in questions on: predictors of asthma mortality, nebuliser and TurbohalerR use, asthma management plans, side effects of inhaled glucocorticosteroids, and physical signs in acute asthma. Confidence scores rose significantly for all practical aspects of asthma management (p<0.01; Wilcoxon matched pairs test), and declined at 2 weeks, but still remained significantly higher than baseline. Discussing asthma 3.3 (0.8) 4.4 (0.6).. 4.1 (0.7)** Use of PF meter 4.0 (0.9) 4.6 (0.6)** 4.4 (0.7)* Use of MDI 3.8 (0.2) 4.7 (0.5)** 4.3 (0.7)* Use of spacer 3.5 (0.9) 4.7 (0.5)** 4.3 (0.6)* Use of turbohaler 3.3 (0.9) 4.7 (0.5)** 4.1 (0.9)* Use of nebuliser 3.1 (1) 4.6 (0.8)** 4.0 (0.8)** Conclusions: Medical student knowledge about several important features of asthma care was poor. Our workshop increased knowledge and confidence in management of asthma. Key words: Asthma, education, asthma devices PEER-LED ASTHMA EDUCATION IMPROVES QUALITY OF LIFE IN ADOLESCENTS S Shah J Peat G Cantwell H Wang P Sindusake R Henrv. P Gibson Asthma is a major health problem in adolescents. The Adolescent Asthma Action (Triple A) Program is the first peer-led asthma education program, which empowers young people to take control and improves knowledge and attitudes about asthma in the school community. Aim: To establish the effect of the Triple A Program on quality of ltte (QoL) in a randomized controlled trial. Methods: Students were from six high schools in rural Australia. The schools were randomly allocated to either the intervention or control group. 1379 students from Years 7 {12.5yrs) and 1 O {15.5yrs) completed the ISMC video questionnaire to measure asthma prevalence. Students who reported wheezing in the last year (n=272, 86% R.R) completed the Paediatric Asthma Quality of Life Questionnaire and performed spirometry. Following the implementation of the program in the 3 intervention schools, these variables were re-assessed. Results: Prevalence of recent wheeze was 25%. At baseline, most students with recent wheeze reported mild to moderate impairment of QoL due to asthma. FEV 1 was 103% predicted and the FVCNC ratio was 89%. Total QoL scores after adjusting for year and gender significantly improved in the intervention group when compared to the control group (p=0.03) with 25% of students with asthma achieving a clinically relevant improvement, compared to 12% in the control group (p=0.01). This effect was greatest in Year 10 students and in females. Significant improvements occurred in the activities domain (41% vs 28%, p=0.03) and some improvement in the symptoms domain (26% vs 18%) and the emotions domain (27% vs 20%), however these failed to reach statistical significance except for males in the emotions domain (39% vs HI%, p=0.02). Lung function improved significantly in both the control and interven~on groups. FEV 1 NC ratio remained stable over time. Conclusion: The Triple A Program leads to a clinically and statistically important improvement in QoL, but not in lung function, in students with asthma. The challenge in the new millennium is dissemination and sustainability of the program. Asthma is a very common, chronic disease in both children and adults. The respiratory epithelium is important in asthma as it is the first tissue to contact inhaled allergens and contributes to the inflammatory response due to its ability to synthesise a range of pro-inflammatory products under the Influence of a variety of stimuli. In this regard, we have shown that allergenic house dust mite proteases are potent inducers. What Is not clear from our studies, however, is how the mite protease induced effects are mediated at the cell4lar level. Recent identification of a novel family of G-protein coupled cell surface receptors which activate a variety of cellular functions, once cleaved by proteases, has been of particular significance in this study. Thus far, four PAR have been identttied and differentiated on the basis of their activation by dttferent proteases; PAR 1,3 and 4 are activated by thrombin whereas PAR-2 and 4 is activated by trypsin. We have for the first time shown the presence of PAR in airway epithelial cell lines BEAS-28, A549, NCl-H332 and cultured human lung cells using specific antibodies. Further we have confirmed the presence of mRNA for these receptors. We used ELISA to determine the effect of the small peptides consisting of six amino acid residues, corresponding to the cleaved nascent Nterminus portion of the receptor of PAR-1 to -4 in activating the receptors on the release of the pro-inflammatory cytokines IL-8, IL-£, and GMCSF from the lung epithelial cell lines. These results demonstrate that activation of PARS present on human airway epithelial cells will lead to the production of proinftammatory cytokines. Further, we have also shown that thrombin and trypsin are also capable of cleaving this protease-activated receptor. Thus, this study takes us a step closer to understanding the mechanism of action of the dust mite proteases and allergens on the lung epithelium. Supported by the NHMRC & Asthma foundation WA. Key words: Protease activated receptor, Cytokines, Allergy. The majority of proteins making up the house dust mite (HDM) are not allergenic. Immune responses to these proteins may alter responses to HDM allergens by changing the cytokine milieu around antigen presenting cells. Alms: To isolate and characterise HDM non-allergens, and to study the immune responses to recombinant non-allergens in allergic and non-allergic subjects. Methods: A Dermatophagoides pteronyssinus t..gt11 library was screened with rabbit anti-HDM serum and antigenic clones screened for absence of lgE binding. A suitable clone was sequenced and expressed as a recombinant fusion protein. Immune responses to this protein were studied in allergic and non-allergic volunteers by immunoglobulin binding, peripheral blood mononuclear cell (PBMC) proliferative responses, and cytokine production. Results: A cDNA clone coding for ferritin, probably heavy chain, was isolated and a recombinant protein expressed using the pET vector. No lgE binding to the recombinant protein was seen from a battery of allergic sera. The protein induced significant PBMC proliferative responses (Mean proliferation (SE) 8811(1050) cpm vs control 1265(149) cpm (n=15, p<0.0001 ). There was no difference between allergic and non-allergic groups in proliferative responses. Stimulated PBMC produced significant IL-5 (Mean IL-5 106 (20) pg/ml) and interferon-y (Mean IFN-y 2077 (751) pg/ml). There was no difference between allergic and non-allergic groups for either cytokine. Conclusions: House dust mite ferritin has been cloned, sequenced and expressed as a recombinant protein, which has the immunoglobulin binding characteristics of a non-allergen. Significant T-helper 2 type cytokine production is observed with PBMC stimulation. The classification of proteins as allergens or non-allergens may require more than just the ability to bind lgE. Support: NH&MRC Key words: House dust mite, allergy, recombinant, ferritin, non-allergen Nominations for awards: Nil Purpose of study: To report the 10-year cumulative experience at the Attred Hospital with a rush venom immunotherapy protocol used on patients who have presented with anaphylaxis after insect venom stings. Methods: Patients were referred to the allergy untt after a history suggestive of anaphylaxis following insect venom sting. Skin tests and RAST levels confirmed causative insect. Patients were treated over a 5-day period in a hospital providing full emergency resuscitation facilities. The schedule consisted of: Day 1 (0.1-0.4-1-2-4-8 µg of venom), Day 2 (10-20-30-40 µg), Day 3 (50-50 µg), Day 4 (100 µg), Day 5 (100 µg). Results: 68 venom-allergic patients received a total of 73 courses of rush immunotherapy. 65 were treated with honey bee venom, 7 wtth yellow jacket venom (vespula sp.) and 1 with paper wasp venom (polistes sp.) The mean age was 38.02 years wtth a range 13-71 years. The severity of the initial sting was graded according to Mueller's scale: grade I (2.94%), grade II (16.18%), grade Ill (27.94%), and grade IV (52.94%). Of the 68 patients 24 were atopic and 1 O were asthmatic. Of the 73 courses of VIT, complications occurred in 27 courses, of which 25 were hypersensttivity reactions. One patient was inttially inadvertently given the incorrect venom (polistes instead of vespula wasp venom), and 2 patients developed gramnegative sepsis presumably, from infected intravenous sites. During induction 13 patients (17.8%) developed severe generalised reactions. In all 949 injections were administered during the induction phase, and adrenaline was administered on 14 occasions (1.48%). During the maintenance phase severe hypersensitivity reactions necessitating the use of adrenaline occurred in 4 patients. As a consequence of repeated severe generalised reactions during maintenance, One patient was advised to discontinue immunotherapy. Conclusions: The experience gained over 10 years of using a rush protocol during the induction phase of VIT suggests that this should continue to be performed in an in-patient setting with appropriate resuscitation measures. Of those patients receiving VIT, 89% were bee-allergic. This figure is different to that seen in Europe and the United States, where most patients are waspallergic. Respirology (2000) 5, (Suppl.) Young children spend most of their time indoors (80%-90%) and exposure to indoor air pollutants has been associated with increased acute respiratory disease morbidity, increased prevalence and incidence of respiratory symptoms and aggravation of asthma. In a case-control study carried out in Perth, indoor environmental factors were studied in relation to respiratory illness in 192 children, aged between 6 months and 3 years old. Cases (n=88) were children who attended the Accident and Emergency Department at Princess Margaret Hospital and were diagnosed with acute asthma. Controls (n=104) were healthy children and identified from birth records through the Health Department. Information about respiratory conditions experienced by the child and characteristics of the home was collected in a self-administered questionnaire, completed by the child's parents/guardians. Formaldehyde, nitrogen dioxide, VOCs, house dust mites, temperature and humidity were monitored in each household. Skin prick tests were performed on all children. The unconditional logistic regression model showed that VOCs exposure was a statistically significant independent risk factor for asthma with OR= BACKGROUND: Aspirin sensitive asthma is a distinct syndrome affecting about 10% of asthma patients. Rhinosinusitis is a significant co-morbidity in these patients with rhinorrhoea, anosmia and recurrent nasal polyposis. Aspirin desensitisation has been found to improve nasal symptoms as well as reduce steroid requirements, reduce need for repeated nasal polypectomies, and fewer emergency presentations for asthma. However, currently published desensitisation protocols are time and labour intensive. AIM: To develop a protocol of outpatient clinic desensitisation for aspirin sensitive asthmarhinosinusitis suitable for a hospital or specialist ambulatory clinic. METHODS: Patients with asthma-rhinosinusitis with a history or suspicion of aspirin sensitivity were recruited from the Allergy Clinic of the Attred Hospital. Baseline lung function was obtained and patients were included if FEV1 was greater than 70% predicted. Patients were challenged in the clinic commencing with oral aspirin 50 mg (half a Cardiprin™ tablet) and observed for 2 hours with hatt hourly peak flow and symptom records, and FEV1 at the end of challenge. If the challenge was negative, the patient returned at weekly intervals, and challenged wtth 100, 200 and 300 mg until a positive challenge. If the challenge was positive, then the patient was maintained at that threshold dose of aspirin daily until the next visit when they would be challenged at the next higher dose. A validated rhinoconjunctivitis quality of life (RQOL) questionnaire was obtained before and after desensitisation RESULTS: 9 patients (5M,4F) with mean age of 43±12 years and mean baseline FEV1 92±16 (%predicted) of were challenged. The threshold dose of a positive challenge was 50 mg for 3 patients, 100 mg for 4 patients and 200 mg for 1 patient, and 300 mg for 1 patient. The mean maximal fall in FEV1 was 12±9% with the lowest FEV1 reached being 66% predicted. One patient developed persistent urticaria after reaching 200 mg and was withdrawn. The RQOL score fell from a median of 74 (range 26-131) predesensitisation to 30 (range 9-136) post-desensitisation. Patients were maintained on aspirin ranging from 100 mg daily to 600 mg bd. CONCLUSION: Gradual aspirin desensitisation is safe and feasible within an ambulatory hospital or specialist clinic setting, with the use of daily maintenance aspirin between visits to maintain the threshold. Recent reports suggest that bacterial endotoxin may be associated with asthma severity. Little is known about housing characteristics that influence the distribution of endotoxins in domestic dust. Endotoxin levels in dust were measured from a selection of houses with carpets in Wellington, New Zealand (n=74). Using standard methods, we sampled dust from the whole living-room floor. Endotoxin levels were measured using a LAL assay. Questionnaires were used to collect information on home characteristics. The geometric mean level of endotoxin on the whole floor was 28,352 endotoxin units per gram of dust (EU/g), (Geometric sd= 3.4). Alter adjusting for confounders, houses without insulation had significantly (p=0.008) higher endotoxin levels (39,064 EU/g, sd=4.0) than houses with insulation or a room or garage below the living room (18,672 EU/g, sd=2.3). Endotoxin levels were also independently higher (p=0.04) in houses situated on sloping ground (35,603 EU/g, sd=3.7), compared with houses situated on flat ground (20,252 EU/g, sd=2.7), and in carpets which had been steamcleaned or shampooed in the last year (52,351 EU/g, sd=3.4), compared to carpets not steam-cleaned or shampooed (25,348 EU/g, sd= 3.3), (p=0.05). Houses without insulation or situated on sloping ground may have higher levels of endotoxins because they are likely to be damp or have poor underfloor ventilation. These are characteristics of many Wellington homes and it is in these homes that endotoxin levels may affect respiratory health. The higher levels of endotoxins in carpets which have been steam-cleaned or shampooed may also be due to an increase in moisture within these carpets alter cleaning. Gibson PG, Mitchell C, Bauman A, Henry R, Camino E, Robertson C, Laudau L, Ruffin R. National Asthma Campaign (NAG), South Melbourne, Australia. The NAG conducted a third epidemiological study of primary school aged children and their parents in late 1998 to assess changes in asthma management. Methods: Three surveys were conducted in six major centres, with samples of 13086 parents in 1990, 13991 In 1993 and 16844 in 1998. Response rates were 84%, 84% and 64%. Parents reported their asthma symptoms, diagnosis, medication and management. Results: Parents were aged 37-38 years (mean) across surveys. Rates of 12 month wheeze were similar across surveys, at 19. 1 % in 1990 , 18.1 % In 1993 and 20.2% In 1998 , whilst diagnosed asthma rates were 7.1%, 7.2% and 8.8%. In those with diagnosed asthma, use of any reliever medication declined over time (89.7%, 89.5%, 83.1%) as did theophylllne use (20.5%, 3.9%, 0.9%). preventer use declined in 1998 {36.8%, 44.5%, 40.6%). There was a decline in the proportion with asthma who reported having any lung function test in the previous year (40.2%, 44.4%, 32.5%), and having a peak flow meter (18.7%, 29.9%, 16.8%), but the proportion with a written action plan increased (14.0%, 19.9%, 25.6%). Smoking rates of those with asthma (22.2%) were similar to those without asthma (23.9%). However, of those with asthma and frequent symptoms 30% currently smoked, compared to 18.3% of those with less frequent symptoms. There were signttlcant trends in asthma medication use and management across levels of educational attainment. Conclusions: Use of written action plans has increased but use of PFM and having Jung function assessed has decreased from 1993. Regular bronchodilator use declined, with higher levels of preventer use maintained. These results were remarkably similar to trends in asthma management among primary school children. Acknowledgments: National Asthma Campaign and participating centre research assistants. Sao Cheng, Neil Pearce, on behalf of the ISAAC Steering Committee and the European Community Respiratory Health Survey Wellington Asthma Research Group Wellington School of Medicine PO. Box 7343 Wellington, New Zealand International and regional prevalence comparisons are required to test and generate hypotheses about the causes of increasing asthma prevalence worldwide. The International Study of Asthma and Allergies in Childhood {ISAAC) is the first such study in children and the European Community Respiratory Health Survey (ECRHS) is the first such study in adults. We have therefore conducted a comparison of the findings from these two surveys, for the 17 countries in which both surveys were undertaken. There was a strong correlation between the ISAAC and ECRHS prevalence data, with 64% of the variation at the country level, and 74% of the variation at the centre level, in the prevalence of "wheeze in the last 12 months" in the ECRHS Phase I data being explained by the variation in the ISAAC Phase I data. There was also generally good agreement in the international patterns observed in the two surveys for self-reported asthma (74% of country level and 36% of centre level variation explained), self-reported asthma before age 14 years (64% and 26%), hay fever (61% and 73%), and eczema (41% and 50%). These findings therefore add support to the validity of the two studies which provide a new picture of global patterns of asthma prevalence, and identify some of the key phenomena which future research must address. In 1964, 295 wheezy children and 106 controls were recruited at age 7 years, to determine the outcome of childhood asthma. A further 83 children with severe asthma were included in 1967 at age 10. The subjects have been reevaluated e<1ch 7 years with clinical history, lung function measurements, BHR and atopy status. In this report, we present the results at age 42. To date, clinical history is available for 328 subjects and lung function for 238. At recruitment, children were classified as: q, controls; MWB, mild wheezy bronchitis (<5 episodes of wheezing with. RTI); WB, wheezy bronchitis {>5 episodes of wheezing with RT!); A, asthma (wheezing unassociated with RTI); SA, severe asthma (persistent symptoms) At 42, the subjects were reclassified as: W-no wheeze in the last 3 years; X-no wheeze in the last 3 months; Y-wheezing in past 3 months, once per week. Data in the table represent the outcome at age 42 for each of the groups at age 7 I 10. These results show a good clinical outcome for childhood asthma into adult years with relative preservation of lung function. Only those with severe asthma in childhood have a modest reduction in lung function in adulthood. Overall, there has been little change in clinical status in the last 7 years and no further deterioration in lung function. Asthma is considered a contributory factor in SCUBA-diving related mortality and is present in up to 9% of deaths. Current asthma is regarded as a medical contra-indication to diving. Although routine screening aims to exclude asthmatics from dive training, some asthmatics are known to dive. The prevalence of asthma amongst divers, and in relation to diving mortality, is unknown. We aimed to determine the prevalence of asthma in a cohort of Western Australian recreational SCUBA divers. We sought to characterise their general health, to identify any diving related problems and to determine the beliefs of divers regarding the implication of asthma on dive safety. Methods: Questionnaires were mailed to 982 divers who had either recently completed a PADI diving course, or who were members of the University of WA dive club. Results: In the 540 (55%) respondents, the prevalence of current asthma was 9.7% (95% Cl 7.1-12.3%). This not significantly different from the prevalence of 11.6% in Australian adults. Past asthma was present in 5.6% and a further 15.3% had symptoms suggestive of asthma. Most asthmatic divers reported only symptoms of mild airways disease. There were no significant differences in the general health of asthmatic and non-asthmatic divers. Asthmatics had not experienced any increase in diving related technical or health problems. Although most asthmatics identified asthma related diving risks, many continued to dive despite active disease. Conclusions: The prevalence of current asthma in divers does not support the contention that asthmatics are over represented in diving deaths. Current screening is ineffective at identifying asthma and precludes education of asthmatics in the potential risks of diving. In recent decades, a number of authors have argued that allergen exposure is the major primary cause of asthma, and that the global increases in asthma prevalence are due to increases in exposure to aeroallergens. We have assessed the epidemiological evidence in support of this hypothesis. No longitudinal studies were identified in which allergen exposure during infancy in a random population sample has been related to asthma risk after age six years. Two studies have been conducted in selected populations chosen on the basis of a family history of asthma or allergy; one study found a non-statistically significant association whereas the other study found no association. Many of the identified prevalence studies in children showed negative associations between allergen exposure and current asthma, and the weighted averages of the population attributable risks in children were 4% for Der p 1, 11% for Feld 1, -4% for Bia g II, and 6% for Can f 1. There was little change in these estimates in studies in which children whose parents had adopted allergen avoidance measures were excluded. Furthermore, evidence from population studies is equivocal and provides little consistent evidence that allergen exposure is associated with the prevalence of asthma at the population level. Population-based cohort studies are clearly required, but currently available evidence suggests that allergen exposure is at most a minor risk factor for the primary causation of asthma in children. In a previous analysis we found an association between infant size at birth and the development of asthma and atopy in childhood. We have further analyzed the data to investigate factors influencing infant size at birth, and how they relate to asthma and atopy in later childhood. Methods: A longitudinal birth cohort of 1037 children born in Dunedin, New Zealand in 1972-1973 who were enrolled at age 3 years and were subsequently assessed every 2-3 years. Results: At age 13 years, data were available on 735 subjects (71% of the original cohort). Those infants with a placental weight of less than 460 gm (10"' centile) had an adjusted odds ratio for reported asthma of 0.2 (95% Cl 0.1-0.9) at age 13 years. Placental weight was not associated with bronchial hyperresponsiveness or skin prick test positivity at 13 years, or serum total lgE at 11 years. The placental weight to birth weight ratio was not associated with reported asthma or any of the markers for atopy. Conclusions: Reduced placental growth is independently associated with a reduced prevalence of asthma at age 13 years. The placenta plays a crucial role in fetal nutrition and development and the factors influencing placental growth may also be "programming" the fetal immune or respiratory systems. Whilst the true role of diet in asthma remains unknown, it has been hypothesised that diet may be a risk factor for asthma. Current interest is focused on the protective effect of fresh oily fish (specifically, long chain omega 3 fatty acids) and Vitamin E intake and the possible deleterious effect of dietary sodium. Methods: 638 young adults participated in a communitybased cohort study of dietary risk factors for asthma. Participants completed a detailed respiratory questionnaire and a subset (n=419) also completed a semi-quantitative food frequency questionnaire and underwent methacholine challenge to measure bronchial hyper-reactivity (BHR). Predictive models were developed with multivariate logistic and linear regression. Results: 81 participants (38.9 (SD 6.3) years, 49% male) were defined as having current asthma on the basis of self-reported wheeze in the past 12 months and BHR. They had a BMI of 26.6(6.0) kglm2 and 19% were current smokers. These characteristics did not differ significantly from those participants without current asthma (n=338 Background/Methods: As part of the populationbased ISAAC (International Study of Asthma and Allergy in Childhood) study conducted in Upper Austria we analysed breastfeeding habits and the influence on the development of asthma, allergic rhinitis and eczema in children up to the age of 6 -9 years. ResuHs: 74.6% of the parents reported breastfeeding their 'infants: 25.9% were exclusively breastfed for less than 2 months, 25.9% for 2 to 4 months, 13.2% for 5 -6 months (the recommended duration of exclusive breastfeeding) and 10.4% of the children were exclusively breastfed for more than 6 months. Smoking during pregnancy and low educational level were inversely related to breastfeeding and duration of exclusive breastfeeding. In comparison to children without family history of atopic diseases, risk and high riskchildren were exclusively breastfed more often and for a longer period of time. No significant reduction in the prevalence of lttetime diagnosis of asthma was found etther for breastfed infants in comparison to those not breastfed (OR: 0.92; Cl: 0.82-1.04), nor did the length of exclusive breastfeeding have any significant influence on asthma prevalence; breastfeeding reduced the risk of allergic rhinitis (OR: 0.83; Cl: 0.74-0.94). For atopic eczema, breastfeeding and length of exclusive breastfeeding was associated with an increase in risk (OR: 1.23; Cl 1.13-1.34). Conclusion: A protective effect of breastfeeding was found only for allergic rhinitis. We found no significant effect of breastfeeding on asthma prevalence and even a negative influence on atopic eczema. Despite the otherwise undoubted advantages of breastfeeding for child nutrition, the importance of the recommended length of exclusive breastfeeding for allergy prevention should not be overemphasised. Atopic disorders are characterized by elevated serum immunoglobulin E (lgE) levels and are dependent on the specific triggering of lgE-sensitized mast cells by allergen. Mast cell chymase (MCC) has an imp~rtant role in allergic inflammation within the respiratory tract and dermis. A previous study identified a polymorphism in the MCC gene (14q11.2), which can be detected by BstX1 enzyme restriction, and reported an association between this polymorphism and eczema. The aim of this study was to identify whether there was an association between genetic variants in the MCC gene and atopic outcomes in two unselected paediatric populations. Population 1: 77 six year old subjects from a cohort of infants recruited from an Australian hospital antenatal clinic. Population 2: 135 children (mean age 9 years) from Venezuela. Phenotypic parameters included skin prick testing, serum total & specttic lgE titres, blood eosinophil measurements and a questionnaire was administered to ascertain family history and environmental exposures in both populations. In addition, spirometry and histamine challenge were conducted on population 1. In the Australian population, an association was found between the BstX1 polymorphism and specific lgE to mixed grass (p = 0.039). However, there was no association between this polymorphism and asthma, eczema or other atopic outcomes. In the Venezuelan population, the BstX1 polymorphism was associated with a physician diagnosis of asthma (p = 0.005). but not associated with elevated serum lgE levels or skin prick reactivity. These findings suggest that variants in the mast cell chymase gene are important in the genetics of atopy. (1 l Department of Paediatrics, University of Western Australia (2) Genetic Services Princess Margaret Hospital for Children, WA, 6008. The A38G polymorphism in the 5' non-coding region of axon 1 of the Clara cell secretory protein (CC16) gene has previously been associated with an increased risk of developing asthma and reduced levels of circulating CC16 protein. Aim: To screen the promoter region of the CC16 gene to identify other polymorphisms that may alter CC16 gene function. Methods: Sixty four children were selected for asthma from a tertiary hospital respiratory clinic and 44 controls were recruited from a suburban general hospital. DNA from each subject was used in PCR to amplify the 550bp CC16 promoter region. Two PCR products, 287 and 273bp in length, encompassing the CC16 promoter region were screened for mutations using single stranded conformational polymorphism (SSCP) analysis and heteroduplex analysis. DNA sequencing on a 10% random sample was used to confirm these results. Results: No polymorphisms were identified in the CC16 promoter region. Concluslons: The association between the A38G polymorphism, asthma and reduced plasma CC16 levels is most likely due to altered CC16 gene function caused by the A38G polymorphism and not another linked polymorphism in the CC16 promoter region. Supported by the NH&MRC The II:! adrenoceptor (~R) has key functions in asthmatic airways, and exhibits desensitisation and down-regulation with prolonged 11:!-agonist exposure in asthmatics. Functionally relevant ~R polymorphisms have recently been characterised. lle-164 reduces ~R affinity for 11:!-agonists. Codon 16/27 polymorphisms enhance down-regulation, reduce bronchodilatation and increase nocturnal asthma. 5' leader cistron polymorphism reduces receptor density and expression. We hypothesised that these ~R polymorphisms modify asthma severity. Aim: To examine ~R polymorphisms as disease-modifying genes in asthma. Methods: We recruited 53 adults with life-threatening asthma (admission to ICU due to asthma), 127 mild asthmatics (no ICU admission) and 177 healthy anonymous blood donors. ~R genotypes were determined using PCR. Results: Patients with lifethreatening asthma had mean (SD) age 42 (18) years and 55% were female. The lle-164 variant was associated with an odds ratio of 6.9 (95% Cl 1.2-38.2) for life-threatening asthma (see Table) . There was no association of codon 16/27 or 5'1eader cistron polymorphisms with life-threatening asthma. The lle-164 polymorphism in the coding region of the ll:!AR gene was infrequent but increased the risk of life-threatening asthma. Correlation of ~R genotype to asthma phenotype has implications for understanding the pathogenesis of severe asthma, predicting prognosis and individualising asthma management. The genes for Clara cell secretory protein (CC16) and CD14 both contain common polymorphisms (A38G and C-159T respectively) that have been associated with asthma-related phenotypes and altered serum levels of CC16 and CD14 respectively. Aim: To investigate the relationship between CC16 A38G and CD14 C-159T and the atopic phenotype in an unselected cohort. Method: 276 eight year olds were recruited from an unselected Australian population and followed-up at age 25. Assessment included questionnaire, spirometry, histamine challenge and skin prick test. Blood was taken at age 25 for DNA and total serum lgE. Genotypes were determined using restriction enzyme digestion. Independent association analyses were done relating genotype to phenotype at age 8 and 25. Results: CC16: 14% were 38AA, 50% 38AG and 36% 38GG. There was no association between CC16 genotype and asthma-related parameters (asthma diagnosis, symptoms, bronchial hyper-responsiveness (BHR), wheeze + BHR) in subjects analyzed at age 8 and 25. CD14: 28% were -159CC, 49% -159CT and 23% -159TT. At age 8 there was a 2.5 fold lower risk of one l!:3mm skin prick test in -159TT subjects compared with -159CC and -159CT subjects (95%Cl=1.04-5.88, p=0.039). There were no associations between CD14 genotype and other atopic parameters. At age 25 there was no association between CD14 genotype and atopic parameters. Conclusion: A reduced risk of a positive skin prick test was found in 8 year old children with the CD14 -159TT genotype, but the association was of marginal statistical significance. No other associations were found between CC16 A38G or CD14 C-159T and asthma or atopic parameters in subjects age 8 or 25 years. These data suggest that these two polymorphisms do not have a significant role in inherited susceptibility to atopy or asthma in this population. Eformoterol fumarate dihydrate is a long acting beta-2 agonist for bronchodilation in asthmatic treatment. To date, Foradile® Aerolizer® and Oxis® Turbuhaler® are the only dry powder inhalers available for the delivery of eformoterol. The two products differ in the formulation, the aerosol production mechanism and the device resistance to air flow. Our aim was to compare the in vitro performance of these two inhalers in producing the eformoterol aerosols. The particle size distributions of the two inhalers was assessed by a four-stage liquid impinger (plus filter) with a glass throat, at flows of 30 -120 Umin. Eformoterol collected from the impinger was assayed by high performance liquid chromatography using UV detection at 240 nm. Fine particles are those ,.:; 4.4 -6.8 µm in the aerosols, depending on the air flow. At high air flows, 90 and 120 Umin, both inhalers produced similar amounts (4 µg) of fine particles in the aerosol per dose discharged. This fine particle mass is about 30% of the label claim. As the flow was decreased to 30 and 60 Umin, both inhalers produced significantly less fine particles (p < 0.05), with the Oxis® Turbuhaler® producing lesser amounts than the Foradile® Aerolizer®. At a ·comfortable' inspiratory effort of 40 cmH 2 0, the Foradile® Aerolizer® would produce a significantly higher fine particle mass in the aerosols. We conclude that the in vitro performance of the two inhalers for eformoterol was equivalent at high but not at low air flows. Theophylline is still widely used in the treatment of asthma. There is increasing evidence that theophylline has anti-inflammatory effects. Theophylline decreases the production of pro-inflammatory cy1okines such as tumor necrosis factor-alpha (TNF-a) and increases the production of the anti-inflammatory cy1okine IL-10. We investigated the production of IL-10, TNF-a and GM-CSF from alveolar macrophages (AM) and whole blood, in a double blind placebo controlled crossover trial to assess the antiinflammatory activity of low dose theophylline in 15 patients with mild asthma (mean age: 30.5 ± 2.1, FEV1% predicted: 87.9 ± 8.1 % PC 20 methacholine: 0.85 ± 0.34 mg/ml exhaled NO: 21.0 ± 2.9 ppb). AM were obtained by fiberoptic bronchoscopy and bronchoalveolar lavage (BAL). Following treatment there was no significant increase in the production of IL-10 either constitutively or following stimulation (LPS 10µg/ml, IL-1~ 10ng/ml), nor an attenuation of TNF-a or GM-CSF production in AM. There was a significant reduction of BAL and sputum eosinophils following theophylline (3.S ± 0.6 to 1.8 ± 0.2S %, p<0.05 in BAL and 11.3 ± 1.6 to 7.9 ± 1.1 %, P10-fold higher levels of IL-4 and IL-5 (>100pg/mV2x1Q5 cells, p<0.01 ), but not IFN-y, ultrapurified CD4+ T cells did not express Jyn. However, lyn was highly expressed in the rare NK1. 1 + natural killer (NK) cell population. Depletion of NK cells with monoclonal antibodies, but not inactivation by gene targetting of their principle effector molecule, perforin, prevented development of the multi-trait asthma phenotype. These data represent the first example of a single molecular defect causing an asthma-like syndrome involving multiple, diverse and seemingly unrelated disease loci simultaneously. We propose that lyn links these diverse loci by a fundamentally important, undiscovered, biochemical mechanism governing asthma severity and progression, acting principally on the NK1 . Interleukin (IL)-13 appears to be capable of inducing the entire allergic asthma phenotype. Goblet cell hyperplasia, mucus hyperproduction and subepithelial fibrosis have been demonstrated in response to IL-13 in murine models of allergic bronchoconstriction. However, there are no studies of the distribution of IL-13 receptor in human airways. We studied the localisation of the IL-13 receptor-a1(1L-13Ra1) in the airways of a cohort of normals and asthmatics that have been followed prospectively with reassessment every 7 years since the age of 7 (H Oswald et al, BMJ 1994; 309: 95-6) and have recently returned for extensive review (age 42 years) including basic lung function tests and bronchoscopy. Endobronchial biopsies were analysed immunohistochemically for JL-13Ra1from10 asthmatics of varying severity and 6 nonasthmatic controls. Fibroblasts were isolated from separate biopsies taken at the same time and cultured in DMEM (20% FCS and bFGF 3nM) for up to 5 weeks to produce an explant culture. Second passage cells were immuno-stained for IL-13Ra1. IL-13Ra1 was detected in basal epithelial cells, eosinophils, mononuclear cells and fibroblasts within the biopsies. IL-13Ra1 was also identified in fibroblasts cultured from biopsy specimens. We conclude that the expression of the IL-13Ra1 on cells associated with key asthma pathology is consistent with emerging evidence of IL-13 in a role for perpetuating the inflammatory response in asthma. This work was funded by NH&MRC Australia, Glaxo-Welcome UK. AL James, G Pearce-Pinto, J Elliot, N Carroll. Department of Pulmonary Physiology, Sir Charles Gairdner Hospital. Nedlands 6009, Western Australia. Airway remodelling in asthma includes increased wall thickness, areas of smooth muscle and mucous glands and deposition of extracellular matrix proteins and results in altered airway function. It is thought to be due to airway inflammation and responds to therapy with inhaled corticosteroids. Measuring airway inflammation and remodelling may be necessary to optimise therapy. Airway dimensions can only be measured on whole transverse sections. Aim: To determine if the sub-basement membrane thickness (BM!), which can be measured on a bronchial biopsy, reflects changes in dimensions across the entire airway wall. Methods: Transverse sections of large airways (> 10 mm internal perimeter) from cases of fatal asthma (FA, clinically severe), nonfatal asthma (NF, mild) and control (C) cases (n=5 each) were examined. BMt was measured at X400 and related to the area of the inner airway wall (WAi), outer wall (WAo), total wall (WAt), smooth muscle (ASM), mucous glands (Agl), cartilage (Acart) and numbers of eosinophils (Eos). Results: The mean value for BMt was stable after 15 measurements, taken randomly round the airway perimeter at intervals of 0.1 mm. Mean BM! was 5 µmin C and increased in NF (7 µm) and FA (9 µm) cases. BM! correlated positively with WAi (as % of total cross-sectional area, p<0.05), ASM (p<0.001), Agl (p<0.001) and Eos in the inner (p<0.05) and outer (0.001) airway wall for all cases grouped and, for the FA group alone, with ASM (p<0.05) and Agl (p<0.05). BMt was not related to BM length, muscle shortening, Acart, WAo or WAt. These findings suggest that BM! is a marker of airway remodelling in asthma, particularly in severe cases and that changes in BM! may be useful to monitor asthma treatment. Support: NHMRC Key words: Sub-basement membrane, airway remodelling, asthma. Awards: nil Greg King. Barbara Moore and Peter Pare. Institute of Respiratory Medicine. Sydney Australia and UBC Pulmonary Research Laboratory. Vancouver ~ Introduction: Inhibition of DI during repeated methacholine inhalation increases airway narrowing in normals reaching a plateau at 10 minutes (G. King et al, Am J Resp Grit Care Med 1999). Since the bronchodilator response to DI is impaired in asthmatics, we hypothesised that inhibition of DI would have less of an effect on airway narrowing during methacholine inhalation in asthmatics compared with normals. Methods: We studied 4 male and 3 female asthmatics (age range 27-53 years) who received 5 x PC15 doses of methacholine given 5 minutes apart and measured FEV1 after each dose. On 4 separate days, they were given 2, 3, 4 or 5 doses in random order, but FEV1 was measured only at baseline and after the last dose. Dis were inhibited between times. Results: Geometric mean PC15 was 2 µmol. When Dis were allowed, the maximum decrease in FEV1 occurred after 3 doses and was 22 ± 5.7% of baseline. When Dis were inhibited, % decrease in FEV1 was enhanced which became greater as the duration of inhibition of DI increased. The % decrease after the last dose was 39 ± 6.8% when Dis were inhibited compared with 19 ± 2.5% when Dis were allowed. Conclusion: Inhibition of DI during methacholine inhalation in asthmatics increases airway narrowing by a similar degree in asthmatics and normals. It has been suggested that bronchodilatation after deep inspiration (DI) is reduced in asthmatics. The relationship between the magnitude of narrowing and amount of reversal has not been determined. We hypothesized that in normals, DI induced bronchodilatation is greater as narrowing increases whereas in asthmatics, the bronchodilatation fails to increase with greater narrowing. METHODS: 16 normals and 1 B asthmatics (airway hyperresponsiveness and wheeze) inhaled doubling doses of methacholine up to a maximum dose of B µmol. The difference between flow at 40% VC on complete (V40c) and partial (V40p) expressed as the % baseline V40p (V40DI) was measured, as was the decrease in V40p as percent baseline (iW40p). The relationships between V40DI and 1W40p were examined using a mixed effects linear regression model. The mean ±SEM % decrease in t.V40p was 49 ± 4% in normals and 70 ± 3% in asthmatics (p<0.01) and for FE;V1 was B ± 1% and 21 ± 2% respectively (p<0.01 ). The linear regression slopes of V40DI vs 1W40p were 0.58 (p<0.01) in normals and 0.06 (p>0.05) in asthmatics. The reversal of bronchodilatation due to DI increases to match increasing airway narrowing in normals but does not similarly increase in asthmatics. This difference could be due to mechanical differences of the airway walls or functional differences in airway smooth muscle. RESULTS: Based on enzymatic activity by gelatine zymography, the inactive pre-cursor of MMP-2 was highly expressed in asthmatic serum samples, while it could not be detected in controls. Similar, high amounts of active MMP-2 were present in asthmatic serum samples, while only a low expression of active MMP-2 was observed in controls.The MMP-9 pre-cursor was more often expressed in sera obtained from asthma patients, while only few controls expressed low amounts of the MMP-9 pre-cursor. Active MMP-9 was not detectable in any serum sample. Interestingly, the active forms of both MMP were highly expressed in bronchoalveolar fluid samples of asthmatics. We observed a distinct expression of MMP-2 and MMP-9 in the serum and BAL of asthmatic patients. It is yet unclear whether the enhanced expression of these MMP contributes to disease progression or if it represents a remodelling process of the lung to reconstitute the structure of its ECM. There are little data regarding the potential effects of anti asthma treatment on indices of airway remodelling such as airway vascularity in asthma patients. Methods: We studied 45 symptomatic asthmatic subjects who were receiving treatment with low dose inhaled corticosteroids and 28 non asthmatic normal subjects as a control population. Subjects underwent bronchoscopy with airway biopsy and asthmatic subjects were then randomised to receive supplementary inhaled salmeterol 50µg bd, fluticasone propionate 1 OOµg bd or placebo for 3 months. Biopsy ol the airway was then repeated. The biopsies were analysed for vascular structures in the sub-epithelial lamina propria. Results: Sufficient biopsy material was available for analysis of vascularity in 34 of the asthmatic and 25 of the normal subjects. We confirmed that asthmatic airways had a significant increase in the number of vessels/mm2 of lamina propria compared to normal airways (524±137 vessels/mm2, n=34 vs 425±130 vessels/mm2, n=25; p=0.004). As previously described decrease in vascular area with low dose ICS at baseline was evident (Orsida et al. Thorax 1999; 54: 289-295) . There was a decrease in the density of vessels of lamina propria after supplementary treatment only in the salmeterol group compared to baseline (before, 535 ±153 vessels/mm2 vs after, 400±142 vessels/mm2; n=l 2; p=0.04). There was no significant change in the fluticasone (n=l 1) or placebo (n=l 1) treatment groups. PLA 2 represents a large group of enzymes that share as a common characteristic the capacity to hydrolyse fatty acids from the sn-2 position of glycerophospholipids. Hydrolysis of phospholipids by PLA 2 provides the precursors for eicosanoid synthesis that is important in lung inflammation and asthma. We have determined secreted PLA 2 activity levels in plasma of a cohort of 64 stable asthmatics (43 mild and 21 severe) as well as in 23 control subjects. Correlation between plasma PLA 2 activity values and gender, age, atopy, % of predicted PEF (%PEF) and vitamin C levels was analysed. Variables were compared by either unpaired, two-tailed I-test or by linear regression analysis. PLA 2 levels were significantly higher in males compared to females (p= 0.0287). Levels of PLA 2 negatively correlated with plasma vitamin C concentrations (p= 0.0080). Furthermore, negative correlation with vitamin C levels and asthma status was also significant (p=0.0066). Positive correlation between %PEF and PLA 2 was observed in control and mild asthmatics (p=0.0420 and 0.0389 respectively) but no such correlation was observed in severe asthmatics (p=0.2378). In male subjects PLA 2 levels correlated significantly with age (p=0.0253) and atopic status (p=0.0481) while in females no significant correlation among these parameters was observed. Preliminary results of this study suggest that effects of dietary anti-Oxidants and plasma PLA 2 on lung inflammatory processes might be gender-dependent. Further studies are needed to characterize the relationship between vitamin C and PLA 2 levels as well as the effect of gender on these measurements. Pathol 1997; 10:1043 -1046 suggested that antigenicity levels for cell markers decreased alarmingly over time in bronchial biopsy specimens that were embedded in glycolmethacrylate (GMA), which has taken on 'gold standard' status in recent years. This raised the question of whether the same would occur when looking at indices of airway wall remodelling such as collagen Ill (scar tissue) and collagen IV (vessels) staining. This prospective study was undertaken to see what changes occurred to levels of these collagens over time, as a prelude to a long term study of airway remodelling in asthma. Nasal polyps were collected from 8 patients and embedded in GMA after appropriate processing. Sections were stained for collagen Ill and IV (after etching in acetone for 15 minutes and then digesting in 0.001 % trypsin to improve staining) and then scored using computerised image analysis where collagen IV yielded a score of vessel number expressed per mm of basement membrane and collagen Ill was expressed as percentage positive area. Survey sections were measured to 100µm below the basement membrane. Sectioning, staining and scoring were carried out at baseline (base;1 day post polypectomy) and subsequently at 1 month (TP1), 2 months (TP2) and 3 months (TP3) Establishment of primary human cell lines from the lung provides a unique basis to study pathogenetic mechanisms of lung diseases on a cellular level. To our knowledge no data are published on primary bronchial smooth muscle cells cultured from asthmatics. To investigate cell proliferation, BSMC from three patients with asthma were cultured and compared with BSMCs from non-asthmatic non-sensitised controls. Cells were grown under sterile conditions in RPMI supplemented with 10% fetal calf serum (FCS), 8 mM Lglutamine and antibiotics. Cells were seeded onto 24 well plates (1xl04 cells/cm2) and grown until reaching a logarithmic growth phase. Cell cultures were kept in FCS free medium for 48 hours. Following serum deprivation cells were restimulated with 10% human serum (obtained from atopic patients with asthma or non-sensitised healthy controls). Cell counts were performed daily for the following 4 days. In addition, proliferation was assessed by 3H-thymidin incorporation. Asthmatic cells grew more rapidly compared with controls. Cell growth increased by a mean of 87.3% if sensitised serum was used compared with an increase of a mean of 48.6% under non-sensitised conditions. Asthmatic cell lines exhibited a greater increase in cell proliferation under sensitised conditions compared with control cells. Summary: In this study we found evidence that bronchial smooth muscle cells of patients with asthma grow faster compared with controls. This effect was more apparent if cells were grown under sensitised conditions. Increased cell proliferation might contribute to airway thickening and altered contractility, which is observed in asthma. (1)Department of Thoracic Medicine Royal Adelaide Hospital. (2)Division of Human Immunology Institute of Medical and Veterinary Science Adelaide Introduction: A reliable disease marker for acute exacerbations (AE) of ABPA is not available. Currently the diagnosis is made clinically based on symptoms, radiology, total lgE and eosinophil counts. IL-5 plays an important role in eosinophil accumulation in the airways of patients with ABPA. Then chain of the IL-5 R exists as membrane bound and soluble isoforms. Hypothesis: Changes in the ratio of membrane to soluble nll-5R (M/S nll-5R) correlate with disease activity. Aims: To compare the usefulness of M/S nll-5R with other markers to predict AE of ABPA. We developed an assay to measure the isoforms of nll-5 R RNA in peripheral blood leukocytes. Patients were followed prospectively for 6 months. AE were diagnosed clinically and were managed by the treating physician. We serially measured total eosinophil count, total lgE, Aspergillus specific lgE and eosinophil cationic protein (ECP). RNA for the isoforms of the nll-5R was measured in peripheral blood using RT-PCR with real time PCR technology (Taqman). Results: 9 AE were observed in 10 patients. All AE were treated with prednisolone. There was a significant correlation between eosinophil counts and disease activity (P<0.01 ). An increase in ECP with exacerbations was also observed, but was not significant (P=0.09). lgE was a poor marker of disease activity. While, as a group, there was no significant change in mean M/S nll-5R ratios with AE, in one patient the ratio varied inversely with eosinophil count. Conclusion: Eosinophil counts, but not total lgE, were a reliable marker for AE in ABPA. We intend to carry out further studies on M/S nll-5R in a larger group, including the ettects of corticosteroids on this ratio. Salivary contamination confounds the accurate interpretation of induced sputum cell counts in asthma. The acceptable levels of contamination and its ettect on measurements are not well established. The aim of this study was to examine the effects of salivary contamination on cell counts and to establish quality markers that could be used to determine the adequacy of sputum samples. Healthy adults(n=6) provided samples of blood and saliva. Granulocytes were isolated using percoll gradient centrifugation and ammonium chloride lysis of red cells. Aliquots of saliva were added to the granulocyte suspension in the following concentrations (v %): 0%, 10%, 30%, 50%, 70%, 80% and 100%. A total cell count and viability were performed on the saliva-granulocyte suspension with cytospin slides prepared for ditterential cell counts and supernatant assayed for ECP. Saliva contained between 25 and 128 x 104/ml cells per ml, of which 25 -44% were viable. The cellular differential of saliva contained 65 to 86% squamous cells, with the remainder being neutrophils. No eosinophils or lymphocytes were seen in saliva samples. The concentration of ECP in saliva ranged from 5 to 60ng/ml. The addition of increasing volumes of saliva to the granulocyte suspension had no significant effect on total and differential counts up to 50vol%. Salivary contamination at 70vol% was associated with a squamous cell count of >50%. There was si9nificantly reduced cell viability from 98.9% to 59% (p<0.01), eosinophil percentage from 15% to 7% (p=0.01), lymphocyte percentage from 1% to 0% (p=0.01) and ECP from 241 ng/ml to 37ng/ml (p<0.01 ). There was a non-significant trend for neutrophils to increase with the addition of saliva (p=0.08). In conclusion, salivary contamination has little effect on the cellular differential until there are >50% squamous cells present. There are significant effects on fluid phase markers at all levels ot contamination. We propose quality criteria for sputum samples of >90% viability and <50% squamous cells in order to minimise the confounding effects of salivary contamination. More research is required to control for the effects of salivary contamination on fluid phase markers. Supported by NHMRC Increased exhaled nitric oxide is associated with inflammatory changes in the lung and airway, and likewise elevated exhaled carbon monoxide is also associated with asthmatic inflammation in non-smokers. Volatile anaesthetic agents and intubation are known irritants of 1he major airways. These agents might therefore be expected to affect the regulation of nitric oxide synthases in the upper airway. We therefore studied subjects who were undergoing abdominal surgery, principally gynaecological, to assess the changes in exhaled nitric oxide before and after surgery and a general anaesthetic. 36 subjects agreed to participate, 2 had asthma, 11 were current smokers. All had exhaled nitric oxide measured using a gas impermeable bag and a flow restriction to increase oral pressure to approximately 5cm of water, thus avoiding nasal contamination of the sample. Sampling was repeated 24-30 hours later as soon as the subject felt able to provide a specimen. The role of eosinophilic airway inflammation in the variant asthma syndromes of cough and chest colds is not well defined. We tested the hypothesis that children with persistent cough and chest colds have increased sputum eosinophils, similar to those with wheeze, The parents of 390 primary school children completed a symptoms questionnaire. Children with wheeze (n=25), cough (n=12), recurrent chest colds (n=17) and no symptoms (controls, n=24) consented to allergy skin prick tests, spirometry, combined hypertonic saline inhalation challenge with sputum induction, peak expiratory flow (PEF) and symptom diary over a 2 month period. Children with wheeze had significantly reduced PEF (p=0.001) and higher sputum eosinophils when compared to the cough, chest cold and control groups (Medians: 3.1% vs 0.5%, 0%, 0%, p=0.03). The prevalence of eosinophilic bronchitis (sputum eosinophils >2.5%) was 45% in the wheeze group which was significantly higher than the control group (9.35%, p=0.04). Eosinophilic bronchitis was present in two children with cough (17%) and two with chest colds (12%, p>0.05 vs control). In these groups eosinophilic bronchitis was not associated with AHR (p>0.05) but tended to be associated with rhinitis. Children with cough and chest colds reported greater exposure to environmental tobacco smoke. In conclusion, this community-based survey of children with chronic respiratory symptoms has shown that wheeze is a good discriminator for the presence of eosinophilic bronchitis: persistent cough and recurrent chest colds without wheeze should not be considered variants of asthma. Sputum neutrophils and total cell counts were similar between the groups (P> 0.05). In conclusion, asthma with Chlamydia pneumoniae infection and CP-G seropositivity is characterised by an increase in the severity of IL-5 mediated eosinophil inflammation and eosinophil degranulation. An lgA response in association with lgG seropositivity to CP appears to protect against some of the inflammatory changes in asthma. Persistent CP infection may increase the severity of eosinophi\ic airway inflammation in asthma. Supported by Hoechst Marion Roussel Chlamydia Pneumoniae (CP) causes acute respiratory tract infections and persistence of the agent is seen in chronic severe asthma. Aims: To determine the prevalence of acute or reactivating infection with CP in acute asthma and it characterises the effect on airway inflammation. Methods: Adults (n=54) presenting to the emergency room with acute exacerbations of asthma had a clinical assessment, spirometry and sputum induction, acutely and four weeks later. Paired serum samples were taken for chlamydia pneumoniae (CP) lgG and lgA and tested using ELISA. Results: Initial serum demonstrated a prevalence CP lgG of 41% (n=22) and CP lgA of 31% (n=17). Ten (18.5%) showed an increase in \gG and 21(38.5%) showed an increase in lgA consistent with either acute infection or reactivating infection. Those with rising CP lgA had more intense airway inflammation in sputum (median total cell count x 106; 11.4), compared to those with negative or stable CP lgA (2.4, p<0.01 ). In addition there was an increase in levels of eosinophilic cationic protein (median 7071.1vs1016.7 ng/mL, p=0.02) in sputum supernatant. An increase in serum \gG did not significantly influence airway inflammation (median total cell count 4.6 vs 2.8, p=0.3) and eosinophilic cationic protein (median 2087.9 vs 1269.1, p=0.6) though there was a trend similar to that seen in those with an increase in serum lgA. Conclusion: In acute severe asthma, serological evidence of acute or reactivating infection with CP was seen in 18% (rise in lgG) and 39% (rise in \gA antibodies) of subjects. Acute asthma exacerbations accompanied by a rise in GP lgA had more intense airway inflammation with marked eosinophil degradation. • Refer to page A 18 for G Respirology (2000) 5, (Suppl.) Research & University of WA Department of Paediatrics Perth WA 6008 Alms: To determine the influence of infective inflammation on response to allergen we have administered nebulised lipopolysaccharide (LPS) a) during the primary sensiUsation phase, b) during allergen challenge or c) between the acute and late phase of the allergen response using an in vivo animal model. During the primary sensitisation of PVG rats to ovalbumin (OA), a single aerosol challenge of LPS (50µg/ml) given day -1 or up to day 4 after sensitisation, completely abolished allergic sensitisation, resulting in no increase in lgE or response to OA challenge. Presence of LPS (0.5, 5 or 50µg/ml) with OA in the same nebuliser during allergen challenge resulted in an immediate decrease in lung function (time-to-peak decreased from 10.0±0.9(SEM) to 2.5±0.2 minutes (n=6, P<0.001) but abolished tephase hyper-responsiveness, cellular influx and vascular leakage (assessed by Evans Blue dye) in a dose-dependent manner (n=5, P<0.01 ). Exposure of sensitised animals to LPS, 18 hours post allergen challenge also inhibited the late-phase hyper-responsiveness when measured at 24 hours (n=5, P<0.05) but further exacerbated the QA-induced neutrophil influx and Evans Blue leakage (n=5, P<0.01). In the later group of animals, aminoguanidine (iNOSselective: 1 OOmg/kg sc) was effective in reducing the cellular influx and vascular leakage (n=5, P<0.001) whilst L-NAME (cNOS-selective: 100mg/kg sc) potentiated the allergen-induced hyper-responsiveness (n=5, P<0.01). These results suggest that the modification of allergic response by LPS is dependent on the dose and timing of exposure. Whilst LPS exposure prior to sensitisation inhibits lgE production and hence the development of allergic inflammation, exposure post allergen challenge further exacerbates the QA-induced cellular inflammation in rats. In this model, nitric oxide production by iNOS plays a major role in the migration of inflammatory cells and vascular permeability following allergen challenge while that produced by cNOS limits bronchial hyper-responsiveness. Animal models have shown that \L-13, produced by activated CD4+ TH 2 cells, plays a key role in the pathophysiological features of allergic asthma. The function of \L-13 in human cultured airway smooth muscle cells (HASM) has been elucidated by investigating the presence of the receptor for IL-13 (IL-13Ra1). its regulation at a transcriptional level and the effect of IL-13 on cell proliferation. HASM were grown to confluence in standard culture flasks and 8 chamber slides, and then serum-deprived for 24hr before a 30 minute pretreatment with either fluticasone propionate (FP 1 nM) or 2-methoxyestradio\ (2-Meo 10µM) prior to incubation in cytokine mix (TNFa 0.03nM + \L-1 a 0.1 ng/ml) or medium alone. lmmunoperoxidase staining was used to determine the presence and location of the IL-13 Ra1 (n=3). The expression levels of 2 mRNA transcripts for the IL-13 Ra1 (4.2kb and 2kb) were assessed by northern Blotting (n=6). DNA synthesis was assessed by incorporation of 3H-thymidine to determine growth potential of \L-13 in the presence and absence of 5% FCS (n=6). \L-13Ra1 was detected in cultured HASM by immunohistochemistry. The increased staining intensity for IL-13Ra1 following addition of the cytokine mix was accompanied by redistribution of immunoreactive \L-13Ra1 from cytoplasm to a distinctly perinuclear location. The intensity and redistribution of \L-13Ra1 were reduced by pretreatment with either FP or 2-Meo. The level of the 2kb mRNA transcript was increased by the cytokine mix and decreased upon the addition of either FP or 2-Meo (69.8±5.0 & 60.2±12% of the cytomix level, respectively), IL-13Ra1 concentration-dependently stimulated DNA synthesis with additive effects with 5% FCS. These data are compatible with a functional influence of IL-13 on HASM. This work was funded by NH&MRC (Australia) Department of Pharmacology: University of Melbourne, Victoria 3010 Changes in extracellular matrix (ECM) and airway wall rigidity are integral aspects of asthmatic airway wall pathology. The ECM in the subepithelial space of the asthmatic airway is characterised by excessive collagen deposition, which together with airway smooth muscle (ASM) stiffness, increase airway wall rigidity. Reduced distensibility of asthmatic airways limits stretch of ASM cells beyond resting state, reducing airway strain. Alm: We have investigated whether two important pathological features of asthma, increased amounts of ECM collagen type I, and reduced strain, affect ASM proliferation and its regulation by the glucocorticoid, dexamethasone. Methods: Bovine and human ASM were seeded in Flexcell™ plates containing a flexible silastic membrane coated with collagen I or laminin. A 72 h period of 4% stretch of the silastic membrane was applied at a frequency of 15 per minute, to mimic the strain expected in situ (AJRCCM 158, S176, 1998). Cell numbers were determined by haemocytometry. Results: Neither matrix type nor level of strain significantly affected bovine ASM proliferation. However, following 72 h incubation with bFGF (300 pM), cells subjected to reduced strain and seeded on collagen were significantly more responsive to bFGF-induced mitogenesis (Laminin/strain 100; Laminin/no strain 129±9; Collagen/strain 142±20; Collagen/no strain 157±20, P<0.05, n=6-7). Similar effects were seen with human ASM cells. In cells seeded onto collagen and subjected to reduced strain, dexamethasone significantly inhibited bFGFinduced proliferation in bovine ASM cells ( Asthma and COPD are characterised by persistent airway inflammation. We hypothesised that this results from persistent immune stimulation by activated cells in situ in smokers who develop COPD and in asthmatics. Lymphoid aggregates (LA) have been described in asthma and COPD. We hypothesised that these structures, if present, may represent a local site within the airway for antigen presentation and T-cell stimulation to occur. We counted the number of cases of COPD and asthma of varying severity with defined lymphoid aggregates and whether they expressed HLA-DR or not. Transverse sections of 3 or 4 large airways from controls (CO), smokers with normal lung function (SC), mild (FEV1 <80%) and severe (FEV1<20%) COPD and mild (nonfatal -NFA) and severe (fatal -FA) asthma; n=8 in each group, were stained with HAM56 (macrophages) and anti-HLA-DR monoclonal antibodies. HAM56 was used to determine if HLA-DR + cells within lymphoid aggregates were macrophages or not. The combination of a long acting ~2-agonist with inhaled steroid appears to be more effective in treatment of asthma than increasing the dose of steroid. It is possible that, inter alia, long acting !3:z-agonists have moderate antiinflammatory effects in airway disease that are complementary to or synergise with those of anti-asthma steroids. Alm: We tested the hypothesis that cytokine (IL-8 and SCF) levels in media of cultured ASM cells would be more sensitive to inhibition by the combination of ~2-agonist and steroid than either agent alone. Methods: ASM cells were grown to confluence, then serum-deprived for 24h before treatment. Cytokine levels in smooth muscle supernatants were measured by ELISA after o, 24, and 48h incubation with IL-1a (1 ng/ml). Anti-asthma drugs were added 30 min prior to IL-1a addition. Results: IL-8 levels increased time-dependently in culture (t=Oh, 5.9±1.1 ng/mg protein, t=48h, 24.4±10.9 ng/mg protein, n~). IL-1a (1ng/ml) increased ASM IL-8 levels over 48 h (control 100%, IL-1a 563±37%). Neither budesonide (100 nM) nor formoterol (10 nM) affected basal IL-8 levels. Budesonide (1-100 nM) concentration-dependently reduced IL-1a-stimulated IL-8 release (IL-1a 100%; IL-1a/bud 1 nM 57±8%; IL-1a/ bud 100 nM 49±8%). However, formoterol (10 nM) had no inhibitory effect, either alone or when co-incubated with budesonide. SCF levels also increased time-dependently in culture (!=Oh, 113±38 pg/mg protein; t=48h 448±142 pg/mg protein). In contrast to the stimulatory effect of IL-a on IL-8 levels, IL-1a reduced SCF levels over 48 h (control 100%; IL-1a 72±10%). Budesonide further reduced SCF release (53±5% control), while formoterol produced no further inhibitory effect, alone or in combination with budesonide. Conclusions: These results suggest that ASM levels of IL-8 and SCF were reduced by budesonide alone and this action was not influenced by the long-acting ~2-agonist formoterol. Key words: Airway smooth muscle, formoterol, budesonide, IL-8, stem cell factor Lien Ho1. Richard Ruffin and Peter Zalewski. Department of Medicine, The University of Adelaide, The Queen Elizabeth Hospital. Woodville Rd Woodville SA, 5011 The human respiratory tract is rich in mast cells, especially beneath the bronchial epithelium and these play an important role in airway inflammation. Zinc is known to be anti-inflammatory and one of our interests is to determine whether mast cells are rich in Zn, which is released during degranulation. We are also interested in whether Zn has an antiinflammatory effect through the suppression of NF-KB transcription factor. The distribution of intracellular labile Zn was visualised in cord blood and HMC-1 mast cells using a Zn-specific fluorophore, Zinquin and image analysis. High levels of Zinquin fluorescence indicated the cells were rich in Zn. Mast cells were degranulated with lgE/anti-lgE, PMA, and Ca ionophore A23187 and compound 48/80 for 4hr at 37°C. Zinquin fluorescence was decreased in HMC-1 treated with lgE/anti-lgE from 101.5 ± 2.6 to 59.3 ± 3.7 pixels (p<0.001 ). NF-KB was activated in NCl-H292 bronchial epithelial cells with 20ng/ml TNF-a for 4hr at 37°C. It was detected by immunofluorescent labelling using a primary antibody specific to the p65 subunit of NF-KB. Zn supplementation by 25µM ZnS0 4 +1µM pyrithione resulted in suppression of NF-KB. Differences in levels of fluorescence were seen in untreated cells (51.6 ± 1.5), TNF-a treated (111.1 ± 2.1) and Zn+ TNF-a treated cells (57. 7 ± 1.3) pixels (p<0.001 ). These results indicate that Zn is likely to be released from mast cells and have a role in the suppression of NF-KB in airway epithelial cells, with possible implications for asthma. Key words: Mast cells, zinc, degranulation, inflammation and NF-KB. Interest is growing in the regulation of gene expression in human cultured airway smooth muscle (HASM) in relation to cell cycle, phenotype and cytokine production. The normalization of gene expression by housekeeping genes uses the assumption that these housekeeping genes, such as tubulin or 23 kD Highly Basic Protein (23 kD HBP), or more commonly, ~-actin or glyceraldehyde 3-phosphate dehydrogenase (GAPDH), are expressed at constant levels. Alm: Our aim was to identify the gene which best meets the criteria for housekeeping: namely, that its level of expression be unaffected by different treatment regimens and that the variance of both its absolute levels and the variance of the normalized product of interest are minimised. Methods: We have used cDNA arrays (Atlas™ array) and northern analysis to pattern gene expression in mitogen-stimulated HASM in the presence and absence of anti-asthma agents. Results: The presence of multiple housekeeping genes in the array revealed that different mitogenic and drug treatments altered expression of certain housekeeping genes. These observations were confirmed by northern Analysis, a more quantitatively reliable method than the array methodology. ~-Actin was up regulated by thrombin (150% compared to control), conversely tubulin was down regulated by 2-methoxyestradiol (50% compared to control). Given that there was a significant difference in variance of the absolute levels of these two housekeeping genes across the different treatment regimens, these genes were not further evaluated. Although there was no significant difference in the variance of the absolute levels of either GAPDH or 23 kD HBP, the 23 kD HBP housekeeping gene had a significantly higher coefficient of variation (paired t-test, p < 0.0001) when used to normalized either cyclin D1 or p21c1P1 genes. The characterisation of cellular infiltrates in bronchial lavage (BAL) is important in the diagnosis of a variety of lung disorders (Jeffery, 1998). In chronic bronchitis, the predominant cell infiltrate in BAL is macrophages and T cells. In chronic obstructive pulmonary disease (COPD), macrophages, neutrophils and CD8 positive T cells are present. Asthma Is characterised by a marked eosinophil infiltrate and CD4 positive T cells. We describe a rapid multiparameter flow cytometric assay using fluorescently conjugated monoclonal antibodies to characterise cellular subtypes in BAL. The use of standard control beads allows simultaneous analysis of absolute numbers of cells using a single platform assay, without the need for manual cell counts. There was good agreement between this automated counting method (counting 100,000 cells) and standard manual counting methods (counting 200 cells) to quantify absolute cell numbers. We conclude that the speed and accuracy of defining cell populations in BAL using flow cytometric techniques may aid in the differential diagnosis of lung disease. This technique would also be amenable to analysis of cell types in samples of sputum and bronchial brushing. • Human bronchial epithelial cells are known to secrete an array of inflammatory cytokines which play a role in immune responses in COPD. However, the regulatory mechanisms governing cytokine production in bronchial epithelia are largely unknown. TNF-a is a pro-inflammatory cytokine, known to be upregulated in COPD. IL-4 has been reported to induce IL-8 release by bronchial epithelial cells and to inhibit fibronectin release by these cells. TGF-i3 is an immunosuppressive cytokine, produced by many cells including airway epithelial cells and is involved in airway repair and fibronectin synthesis. We studied the cytokine interactions that might regulate TGF-i3 production using two epithelial cell lines {A549 and 16HBE). Cells were stimulated with various combinations ofTNF-a and IL-4 (20ng/ml) for 24h. TGFi3 and IL-4 production was measured by flow cytometry and immunohistochemical techniques. TNF-a significantly upregulated production of IL-4 from cultured epithelial cells. Unstimulated cells spontaneously released TGF-i3. The production of TGF-~ was significantly increased by PMA. TNF-a and IL-4 inhibited production of TGF-i3 by both epithelial cell lines. The inhibitory effect of TNF-a: and IL-4 on TGF-~ synthesis was additive. We conclude from our study that TNF-a induces IL-4 release from human epithelial cells and the inhibitory effect of IL-4 and TNF-a on TGF-i3 synthesis by these cells was additive. The inhibitory effect of IL-4 and TNF-a: on the regulatory cytokine TGF-i3 in the bronchial mucosa, may contribute to the progression of the inflammatory response and decrease in repair processes in COPD. • Respiratory Services, Green Lane Hospital. Auckland New Zealand Introduction: The anti Jo 1 antibody is known to be associated with adult dermatomyositis and polymyositis. A much smaller group of these patients present with lung disease. We reviewed this group of patients at our hospital. Methods: A retrospective case review of patients with documented anti Jo1 antibody and lung disease. Demographic information, age at presentation, diagnostic investigations, treatment and progress were documented. Results: 4 female patients age 40-47 presented with respiratory symptoms. Three required open lung biopsies for diagnosis; two had organizing pneumonitis and one follicular bronchiolitis. One patient has an accepted high resolution CT diagnosis of organizing pneumonitis. Three of the patients developed connective tissue diseases after the onset of respiratory disease {dermatomyositis (1), polymyositis (1) and one rheumatoid disease and one has no clinical manifestation of a connective tissue disease. Two patients developed respiratory disease before becoming positive for anti Jo 1 antibodies. All patients required treatment with corticosteroids and three were also treated with steroid sparing agents. Response was poor in all. Conclusion: This review highlights this small but important group of patients with anti Jo 1 antibody and lung disease. In this group symptoms of connective tissue disorders may develop after ~he onset of respiratory disease. These patients often respond poorly to treatment. Most adults are colonised with Haemophilus influenza, which is one of the major causes of respiratory infection. The role of the T lymphocyte and in particular the T-helper {Th or CD4) cell, in the immune response to haemophilus infection has not been established. Th cell function can be assessed by the measurement ofTh1 {IFN"'Y) orTh2 {IL-4, IL-5) cytokines that are produced following antigen exposure. Aims: To measure whether healthy adults produce a Th1 or Th2 response when exposed to non-typeable haemophilus influenza {NTHi) in vitro, using flow cytometry to measure intracellular cytokine production. Methods: Flow cytometry has been described to measure intracellular cytokine production to cytomegalovirus {CMV) infection. This technique is performed by adding antigen and costimulatory antibody {CD28 and CD49) to whole blood, which is incubated for 6 hours. Red blood cells were lysed and leucocytes fixed, permeabilised and stained with immunoflourescent antibodies for CD4, CD69, IFN-y, IL-2, IL-4, and IL-5. Binding of the antibodies to the cytokines is then measured using the flow cytometer. We validated this technique by screening 1 O subject's response to CMV antigen; 5 were responders with 0.63%±0.28 of Th cells producing IFN-y, consistent with a Th1 response. NTHi obtained from a child with conjunctivitis, was cultured on agar plates, washed and suspended at a concentration of 2.0 Mcfarlane units, heat inactivated and then disrupted by ultrasound sonication. 2 ml of blood was taken from 4 healthy male subjects. 1 ml of blood from each subject was exposed to 50µ1 of NTHi and the other ml served-as a control. The response to NTHi compared with control was measured using flow cytometry. Results: Three of the six subjects produced a distinctTh1 response with 0.17% of Th cells producing IFN-y, compared with control of 0.00%, with undetectable levels of IL-4 and IL-5. This result was comparable to that produced from the CMV group. This response was prevented by the addition of MHC-2 blocking antibody confirming the role of the Th cell. Conclusion: The results show that a Th1 response to NTHi can be measured by flow cytometry. Phospholipases A 2 {PLA 2 ) play crucial roles in diverse cellular responses, including phospholipid digestion and metabolism, host defense and signal transduction and providing precursors for eicosanoid generdtion. Mammalian tissues and cells generally contain more than one PLA2 enzyme, each of which is regulated independently and has distinct functions. Secreted PLA 2 (sPLA 2 ) found in plasma has been linked with inflammatory processes. One of the reported characteristics of the sPLA 2 is its ability to bind to heparin. Using specifically designed heparin affinity chromatography, sPLA 2 was partially purified from human plasma samples. The resulting enzyme preparation was assayed with a newly developed activity assay using a chromogenic lipid substrate 4-nitro-3-(octanoyloxy)-benzoic acid. The products of the sPLA 2 reaction were detected spectrophotometrically in a microplate assay. In optimized conditions the plasma sPLA 2 reaction followed Michaelis-Menten kinetics. Mean of sPLA 2 activities measured in plasma of 23 control subjects was 421.4±29.4 units [nmoles of product formed in 1 h per milligram of protein bound to the heparin column]. The amount of plasma needed for sPLA 2 activity assay is relatively small (0.5ml) and the assay is rapid, simple and very reproducible {mean of standard deviation observed in measurements was 4.95%). The assay was successfully used to analyse sPLA 2 activity in plasma from a cohort of 64 stable asthmatics (43 mild and 21 severe) and revealed a mean activity of 420.4±18.4 and 449.0±28.2 units respectively. Key words: PLA 2 , Asthma, plasma, assay. Department of Pharmacology. University of Melbourne. Victoria 3010. Hyperplasia and hypertrophy of airway smooth muscle contributes to airway wall thickening and hyperresponsiveness in asthma. Understanding the intracellular signalling of airway smooth muscle proliferation may provide new anti-asthma drug targets. Alm: In this study, the relative importance of the activity of the two distinct families of MAPKs (extracellular signalregulated kinase (ERK) and p38HOG) for the regulation of cyclin D1 levels and DNA synthesis was investigated using the inhibitors PD 98059 (ERK) and SB 203580 (p38HOG). Methods: Cyclin D1 protein and mRNA levels were examined by western and northern blotting, respectively. ERK phosphorylation was measured by western blotting, while kinase activity was measured following ERK immunoprecipitation. DNA synthesis was assessed by the incorporation of [3H]-thymidine into newly synthesised DNA. Results: Both thrombin (0.3 and 3 U/ml) and bFGF (0.3 and 3 nM) increased ERK phosphorylation and activity levels, cyclin D1 levels at 20 h and DNA synthesis between 24 and 28 h after mitogen addition. Although PD 98059 (30 µM) reduced ERK activity to baseline levels, it had no effect on cyclin D1 mRNA levels and reduced the increase in cyclin D1 protein levels in response to only the lower mitogen concentrations. PD 98059 completely prevented thrombin-stimulated DNA synthesis, whereas DNA synthesis in response to 3 nM bFGF was only partially inhibited (0.3 nM: 81 ± 11 %; 3 nM: 67 ± 10% inhibition). Conversely, SB 203580 (1 O µM) inhibited bFGF-stimulated DNA synthesis (0.3 nM: 56 ± 3.2; 3 nM: 92 ± 9. 7"/o inhibition), but had no significant effect on thrombin-stimulated DNA synthesis. SB 203580 did not reduce mitogen-stimulated cyclin D1 mRNA or protein levels. Conclusions: p38HOG contributes to the signalling of bFGF, but not thrombin-stimulated DNA synthesis through activity unrelated to the regulation of cyclin D1 levels. Key words: airway smooth muscle, signal transduction, extracellular signalregulated protein kinase, p38HOG. Amelia Scaffidi1.2, Philip Thompson1.2, Darryl Knight1.2. (1) Asthma & Aller1iy Research Institute, (2) Department of Medicine, University of Western Australia Nedlands, Western Australia. Introduction: OSM and LIF are members of the IL-6 family of cytokines and influence the behaviour of a variety of cell types. OSM has been shown to upregulate the production of epithelial anti-proteases and fibroblast-derived tissue inhibitor of metalloprotease and also induces the release of collagen from fibroblasts. We have recently demonstrated the widespread distribution of LIF mRNA within the lung and its release from human lung fibroblast cultures (HFL-1). Hypothesis: We hypothesised that OSM and LIF may play a role in airway remodelling by regulating fibroblast proliferation. Methods: We examined the proliferative effects of stimulating HFL-1 cultures with OSM (0.2, 2 and 20 ng/ml) or LIF (0.5 and 50 ng/ml). Proliferation was assessed via a MTS assay and direct cell counts at 24, 48 and 72 hr. Results: Both OSM and LIF enhanced the mitotic activity of HFL-1 in a time and dose dependent manner. Maximal proliferation in response to OSM was 42% above control and observed after 72 hrs, at a concentration of 2 ng/ml. Incubation with the cyclooxygenase 2 (COX-2) inhibitor nimuselide (2 µM) or the MAPK inhibitor PD98059 (10 µM) enhanced the mitogenic effect of OSM above control levels to 59% and 71% respectively. In comparison, LIF exerted its maximal effect at 48 hr at a concentration of 50 ng/ml, reaching an 80% increase in proliferation above control, which declined to 25% by 72 hr. Conclusion: These results demonstrate that OSM and UF induce fibroblast proliferation and that for OSM at least, COX-2 release as well as signalling via the MAPK pathway may act to modify this mitogenic effect. These data support the hypothesis that OSM and LIF contribute to airway remodelling and fibrosis. Key words: OSM, LIF, COX-2, fibroblasts, proliferation, asthma. Reid D MRCP., Snell GI FRACP., Ward R M Phil., Krishnaswamy R MSc., Zheng L MD., Ward CM Phil., Williams TJ FRACP., Walters EH DM, FRACP. Department of Respiratory Medicine, Alfred Hospital and Monash University Medical School, Melbourne, Victoria. The local generation of harmful reactive oxygen species (ROS) may contribute to the development of chronic rejection and irreversible airflow limitation (bronchiolitis obliterans syndrome -BOS) following lung transplantation (LT). Hypothesis: Chemically active iron and nitric oxide (NO)-derived radicals within the allograft may add to the oxidative burden. Methods: As a marker of potential iron load we determined the concentration of ferritin in bronchoalveolar lavage fluid (BALF) and assessed the relationship to haemosiderin-laden macrophages (HLM) in 14 stable LT recipients (sLTR) and 7 subjects with BOS. HLM were quantified using a haemosiderin-score (HS). BALF nitrite and albumin concentrations were also determined as markers of nitric oxide-derived oxidative stress and microvascular leakage. Results: BALF ferritin levels and HS were significantly higher in LTR than controls (p<0.01), but there was no difference between LT groups. There was a significant relationship between ferritin concentration and HS in LTR (r=0.7, p<0.01). BALF nitrite was significantly elevated in LTR compared to controls (p<0.01). There was a significant relationship between BALF nitrite and %neutrophils (r=0.4, p<0.01), particularly in BOS (r=0.9, p<0.01) but only a weak relationship to BALF ferritin (r=0.3, p=0.2) and no relationship to BALF albumin. In BOS patients there was a trend toward higher BALF albumin levels compared with controls (p=0.07) and a significant relationship to BALF ferritin (r=0.8, p=0.05) but no such relationship in sLTR. Conclusions: Our findings suggest the lung allograft could be subject to significant iron-generated oxidative stress over time which may be exacerbated by NO and neutrophilderived ROS. Microvascular leakage and plasma exudation may be an independent feature of established chronic rejection which potentiates the iron over-load and contributes to furth.er airway damage and remodelling. Puntarica Suwanprathes1.2, Glenn Hunt3, Antony Breslin\ Alvin lng1 and Meng Ngu2. The central control of cough is thought to arise from an ill defined region within the brainstem. The aim of this study was to identify, using c-fos immunohistochemistry, afferent pathways which are activated by mechanical stimulation of the larynx and trachea. Methods: In pentobarbital anaesthetised Wistar rats (n=7), the trachea was exposed and a small incision was made to insert a fine plastic tube to mechanically stimulate the larynx and trachea for 30 minutes. Rats who were similarly anaesthetised and whose trachea was cut but no tube inserted, acted as a control group (n=4). Rats remained anaesthetised for a further one hour before they were perfused and their brains processed for c-fos immunohistochemistry. Results: c-Fos immunoreactivity was increased in a number of brain regions in the rats receiving mechanical stimulation (p<0.05, one-way ANOVA). Heart Lung Transplant Unit\ St. Vincents Hospital and Department of Pharmacology2, University of Sydney, Sydney, Australia Longterm survival following lung transplantation (LT) is limited by the development of bronchiolitis obliterans (BO). Subepithelial fibrosis may be found in transbronchial biopsies (TBB) prior to the diagnosis of BO. In order to study the pathogenesis of BO we attempted to establish for the first time primary human fibroblast cell cultures from TBBs of LT recipients. One to two TBB samples of LT patients undergoing diagnostic or surveillance TBB were collected in sterile PBS supplemented with antibiotics. Biopsies were cut in 4 to B small pieces and placed onto 12 well culture plates or 25cm2 culture flasks and cultured under routine conditions (21 % 0 2 , 5%C0 2 , 37°C). Culture medium consisted of RPM\ 1640, 10% FCS,L-glutamine and HEPES. Fibroblast culture results of 50 consecutive TBBs were analysed. The 50 TBBs were performed in 30 LT recipients (13 CF, B emphysema, 4 PPH, 4 CFA, 1 VSD) who underwent bilateral (19), single (B) or heart-lung (3) transplantation. The indication for TBB were symptoms, a drop in FEV 1 and/or infiltrates on chest X ray in 27 and a surveillance or follow up procedure in 23 cases. The overall culture success rate was 54% (27/50) defined as cells reaching confluence to be further passaged. The culture success was independent of the age, the transplant procedure, the underlying lung disease, the indication for TBB (symptomatic/surveillance/ follow up), the result of histology in regard to rejection (A,JA 1 versus A.JA 3 ; BolB 1 versus B2'8 3 ) and the BOS stage. Bacterial/fungal colonisation of the bronchial tree was frequent but showed no negative influence on cell culture results. Fibroblasts could be cultured from 48% (11/23) of samples with a clinical diagnosis of pulmonary infection (BAL/TBB result) and from 52% (12/23) TBBs of patients without infection. Summary and concluslon: we have established a novel method of culturing primary human lung fibroblasts from lung transplant recipients. These cultures provide a unique in vitro model of human tissue to study pathogenetic mechanisms of bronchiolitis obliterans at an early stage. Alistair Wright1, Peter Holmes1, Steven Holdsworth2. A 31 year old woman presented at 9 weeks gestation. Her past history included an episode of pericarditis 5 years previously and a 2 year history of sinusitis and nasal congestion which had required surgery. At presentation the patient had a 4 week history of night sweats and an asymmetric po\yarthritis and a 1 week history of haemoptysis, dysphonia and intermittent epistaxis. Examination revealed a low grade fever and a number of tender, mildly swollen joints. Her nasal mucosa was erythematous and swollen. INVESTIGATIONS: A CXR revealed bilateral pulmonary infiltrates. The cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) was moderately elevated (titre = 124 ANCA units, normal = undetectable) and the ESR was 106mm/hr. Renal function was normal. A biopsy of her nasal mucosa revealed only non-specific inflammation. DIAGNOSIS: A diagnosis of Wegener's granulomatosis was made and pulse methylprednisolone was given. There was a prompt improvement in the patient's clinical condition with resolution of her haemoptysis and improvement in her voice and joint symptoms and normalisation of her inflammatory markers including the c-ANCA. ISSUES: The patient wished to continue her pregnancy. In view of (a) the possiple teratogenic effects of cyclophosphamide given in the first trimester of pregnancy and (b) of her prompt response to steroids and (c) the limited nature of her disease it was decided to withhold cyclophosphamide and to treat her with prednisolone and close observation. PROGRESS: The patient's health continued without complication until 34 weeks gestation when she represented with haemoptysis. She was treated with further pulse methy\prednisolone and the child was delivered. Following delivery cyc\ophosphamide was commenced. Both the mother and baby are currently well. SUMMARY: A literature search confirms this to be the first case of Wegener's granulomatosis diagnosed during the 1st trimester of pregnancy where there has been a: successful maternal and foetal outcome. Key words: Wegener's granulomatosis, pregnancy, prednisolone. Asthma & Alleroy Research Institute and Universitv of Western Australia Dept. of Medicine Sir Charles Gairdner Hospital Nedlands WA 6009. It has been proposed that dendritic cells (DC) play a key role in regulating the balance between Th1 and Th2 immunity, possibly through release of prostaglandins (PGs), and cytokines such as IL-12 and IL-10 Thus, understanding the regulation of cyclooxygenase (COX) expression and PG synthesis in DC may shed important light on the induction & regulation of allergic disease. As little is known about the regulation of COX-1 and COX-2 in human dendritic cells (DC), the expression of these enzymes in DC and monocytes was assessed by immunocytochemical staining and by intracellular flow cytometry of permeabilised cells. COX-2 staining was detected at low intensity in only a small minority of freshly isolated blood DC and monocytes, but was dramatically upregulated following exposure to LPS (10ng/ml). Intensification of staining was apparent by 4h, and reached maximal levels within 24h, with 80-90% of cells showing COX-2 expression. Exposure of freshly isolated blood DC and monocytes to GM-CSF & IL-4 for 24h did not alter COX-2 expression, whereas monocyte-derived DC (obtained by culturing monocytes with GM-CSF & IL-4 for 7 days) exhibited intense COX-2 staining which was further enhanced by exposure to LPS. In contrast, COX-1 staining was detected at low-moderate intensity in the DC & monocyte populations studied, and its expression was not appreciably altered by LPS. These findings indicate that both COX-1 and COX-2 can be detected in human DC. The expression of COX-2 in DC varies in response to inflammatory stimuli and/or cellular maturation, and the influence of other cytokines and tissue derived factors needs to be explored further. (1 l Physiotheraov Department Sir Charles Gajrdner Hospital, Perth 6009 and (2) School of Physiotherapy Curtin University of Technology. Perth, Western Australia 6008 Exercise training is an established component of the management of patients with chronic lung disease, however there is little data regarding the cost of such programs. Aim: To determine the outcomes and costs of an out-patient exercise program. Methods: 119 patients were referred during 1998. Eighty-five patients were assessed of whom 72 (63% ~th chronic obstructive lung disease) entered an 8 week exercise program. This was a continuous rolling program and patients attended twice per week. Classes were supervised by one physiotherapist with an average of 8 patients per class. Exercise consisted of a 20-30min walk at 60-85% estimated peak oxygen consumption followed by a 30min exercise circuit. Outcomes included exercise capacity (field walking tests) and quality of life (QOL [SF-36 and Chronic Respiratory Disease Questionnaire]). Also provided was a once per week maintenance exercise class for patients with end-stage lung disease who had completed the 8 week program. For costing purposes seven categories of service were considered including the 8 week program, the maintenance program and a program for lung volume reduction surgery (LVRS) patients. Analyses were based on 1998 physiotherapy salaries and the costs of consumables only. Results: Fifty-seven patients (36 males) completed the program (20.8% attrition). Mean (SD) age and FEV1 were 65.5 (9.3) years and 41.4 (23.7)%predicted. Significant improvements in exercise capacity and QOL were demonstrated following the 8 week program (p<0.05). The cost of this program was $249 per patient. The respective costs for the maintenance and LVRS programs were $427 and $766. Concluslons: Significant benefits in exercise capacity and QOL can be demonstrated from an out-patient exercise program and the cost of this type of program is modest. Key words: Exercise training, pulmonary rehabilitation, costs, outcomes Paul Cafarella, Pieter Walker and Peter Frith Repatriation General Hospital, Daws Rd, Daw Park, South Australia, 5041 There are psychological benefits from Pulmonary Rehabilitation (PR) (Mahler, 1998) . PR should improve perception of control over one's health, which in turn should benefit health related behaviour. Some studies have considered the influence of PR on sett efficacy, but none has assessed the effects of PR on health related perceptions of locus of control. Alm: To evaluate effects of PR on psychological morbidity and locus of control. The results imply that PR helps respiratory patients recognise that self-responsibility for actions influences their clinical state. They are less likely to leave symptoms to fate and more inclined to self monitor. PR appears to foster patient empowerment and self care. Pulmonary Rehabilitation is an important part of COPD management. In 1994 a Pulmonary Rehabilitation Programme {PRP) was developed to reduce dyspnoea, panic and anxiety and improve exercise tolerance, confidence, disease management skills, knowledge and overall quality of life in COPD. The aim of this study was to evaluate the effect of the PRP on exercise tolerance, quality of life, and readmission for people with COPD. Design: Cross-sectional analytic survey. Methods: PRP records were audited over a 54 month period. A 6 minute walk test with dyspnoea rating {BORG scale) and quality of life assessment {using CRDQ) were conducted prior to and at completion of our 7 week PRP. A hospital records search for COPD admissions {DRG177) between 1994 -1998 was conducted and readmissions compared between those who were referred and completed the PRP, and those who were referred but did not complete. Results: There were 316 referrals to the PRP of whom 172 (54%) completed the PRP. Exercise tolerance, perception of dyspnoea, and quality of life all improved significantly following participation in the programme. The 6 minute walk distance, mean{sd) improved by 65(137) metres from 283{157)m to 348(112)m following the PRP (p=0.005). Perceived dyspnoea during the walk test improved from 3.4(1.63) to 2.95 {1.20) {p=0.004) at 7 weeks follow up. 64% showed a clinically significant improvement in quality of life. The initial total CRDQ score was 63.1 (23.7) and improved to 81 .0{27.8) at completion (p=0.005). Those that completed the PRP had a significantly reduced chance of hospital readmission {22%) compared to the noncompletion group (48%) (p<0.05). Conclusions: A 7-week hospital based outpatient pulmonary rehabilitation programme improves exercise tolerance, perceived dyspnoea and quality of life in COPD. Participants who complete the PRP are less likely to be readmitted to hospital. Alternative care models may be needed for non-completers to reduce readmissions. Key words: pulmonary rehabilitation, quality of life, exercise tolerance Nomination for awards: Respiratory Nurses SIG poster prize Paul Cafarella and Peter Frith. Repatriation General Hospital, Daws Rd, Daw Park, South Australia, 5041 Carers, rather than the formal health care system, provide the bulk of personalised long term care. This burden results in physical and emotional health problems (Delisa and Gans, 1998) , and there is a link between a carer's psychological health and the quality of care received by the patient {Draper & Luscombe, 1998). While the benefits of pulmonary rehabilitation {PR) for patients are well recognised {Mahler, 1998), the effect of PR on the carers of respiratory patients has gone without assessment. Method: A controlled design {n=100) was used to assess the carers of respiratory patients from the Repatriation General Hospital {S.A.). Fifty carers were assessed before and after their respiratory patients completed PR. Carers in the control group did not have patients who had attended PR. Participants completed the Caregiver Strain Index {CS/), General Health Questionnaire (GHQ) and Katz Adjustment Scales. Results: T-tests for paired samples were used in the preliminary assessment of the data from patients who have currently completed study requirements. The results indicate that carers experience less burden (pre PR mean=5.22, sd=3.44 vs post PR mean=4.02, sd=2.73, p<0 .001) and lower levels of psychological morbidity (pre PR mean=3.72, sd=5.40 vs post PR mean=1.69, sd=2.69, p<0.001) following PR. Conclusions: The results indicate that not only patients, but also carers benefit from PR. The observed carer benefits of reduced strain and psychological morbidity are of relevance given the health problems associated with this role, and are consistent with the findings in nonrespiratory populations {Graham, 1997). Improved carer health status through PR may have positive effects for the care and therefore health of patients with COPD. Key words: COPD, pulmonary rehabilitation, carer strain, psychological morbidity Background: There is evidence for the efficacy of oxygen therapy in certain clinical situations. The aims of this study are to establish the current oxygen prescribing and oxygen saturation monitoring methods in the acute hospital setting and to develop a protocol for the effective and efficient use of oxygen therapy. Methods: An audit sheet and algorithm for oxygen use were designed. Using these sheets, patients on one acute medical (25) and one acute surgical (20) ward had a clinical assessment, which included a pulse oximetry. Analysis of each patient's medical history was performed. Results: 32% were administered oxygen with no indication. 32% had a documented Sp0 2 or Sa0 2 prior to institution of oxygen. 32% had oxygen applied by nursing staff with no medical staff order. 20% had no documentation of who ordered oxygen. Oxygen therapy was ordered on the drug chart in 12%. In terms of Sp0 2 monitoring, while on oxygen the frequency of assessment was 4-6 hourly in 68%, and in those off oxygen the frequency was >24 hourly in 32%. Conclusion: Oxygen is a drug and needs to be prescribed with the same care as other drugs. Based on literature review a protocol for the use and monitoring of oxygen therapy has been devised. Aim: The aim of the study was to evaluate the effect of an 8 weeks exercise programme prior to lung volume reduction surgery (LVRS) on the distance walked in 12 minutes (12MD) and to compare this with the 12MD following an 8 weeks and 6 months exercise programme post-operatively. Subjects: 25 patients with chronic airflow limitation referred to the pulmonary rehabilitation programme at Royal Prince Alfred Hospital for exercise training prior to LVRS were recruited. Methods: At initial assessment (A) all patients performed spirometry, two 12 minute walking tests (2 days apart) and completed the St George Quality of Life Questionnaire. Each patient was prescribed an individual exercise programme which included walking on the flat, stationary bicycling, arm cranking, upper and lower body weight training, and treadmill walking up an incline. Reassessment at the end of eight weeks training (B) included the same measurements as at A. Patients resumed exercise training at an appropriate level 1-3 weeks post LVRS and were reassessed 8 weeks (C) and 6 months later (D). ANOVA was used to compare results at A,B,C and D. A p<0.05 was considered significant. All data are presented as mean± SD. Results: 25 patients with severe airflow limitation (mean FEV 1 = 0.62 ± 0.16 L; mean FEV 1 /FVC ratio= 33.1 ± 10.4%) completed the 8 weeks training programme prior to surgery and 8 weeks training post-operatively. There was a mean increase in 12MD from A to B of 26.5% (p<0.001) and from A to C of 22.2% (p=0.06). The subgroup of 11 patients completing 6 months post-operative rehabilitation were reanalysed separately. Improvements in 12MD A to B=36.5% (p<0.001), A to C = 41.4% (p<0.05) and A to D =55.3% (p<0.001 ). Conclusions: Exercise training in patients with severe airflow limitation significantly improves 12MD. LVRS plus 8 weeks rehabilitation did not further significantly increase exercise capacity in the larger group of 25 patients. Significant improvements in 12MD at 6 months post-operatively in the subgroup of 11 patients suggests that eight weeks post-operatively may be too early to demonstrate peak changes in 12 MD following LVRS. Home based PAP (HPRP) offer the advantages of improved access, decreased cost and better long-term compliance than hospital based programs. We carried out a prospective study to examine the effectiveness of a very low intervention HPRP. Methods: 28 patients with stable COLD and breathlessness limiting daily activity underwent a 6 week HPRP. Lung function and functional exercise capacity (6 minute walk, endurance walk and maximal stair climb) were measured before and after the program. Exercise was prescribed using a simple algorithm based on performance in the initial functional exercise testing and performed daily at home. Supervision was limited to one initial home visit and a weekly phone call. Results: The mean FEV1/FVC and FEV1 were 35.6% and 37.9% of predicted. 11 patients withdrew because of poor motivation, recurrent exacerbations or loss to follow up. In the 17 subjects completing the program all measures of functional exercise capacity improved significantly: mean six minute walk by 44.4m (P< 0.01 ); mean endurance walk by 484.1 m (p<0.001 ); and mean stairs climbed by 10.6 (p<0.03). Lung function parameters and results of cardiorespiratory exercise testing did not change significantly. At mean 8.8 months of follow up 13/17 of subjects (76%) were still following a regular exercise program. Conclusions: A simple and low cost HPRP can achieve results comparable to published trials of more intensive PAP as well as good long term compliance. Patients who withdraw may be selected for the more supportive environment of a hospital based PAP. (6): 1843-1848). In the present study we investigated, in addition to the acute effect of mannitol: 1) the 24 hr retention ; and 2) the clearance rate 24 hours after inhalation of a single dose of mannitol in patients with bronchiectasis. Methods: Clearance of mucus was measured on 3 consecutive days in 8 patients with bronchiectasis, age 29 to 70 years. On each day, following inhalation of 99mTc-sulphur colloid aerosol (6 µm), lung images were collected over 2 hours and at 24 hr. Mannitol (330±68 mg) was inhaled from an Inhalator™ (Boehringer lngelheim) only on day 2. The key findings of the study were that: 1) Mannitol helped patients to clear mucus within 2 hr that would otherwise have taken 24 hr to clear from the whole right lung and all defined regions (p<0.02) and 2) the 24 hr retention of mucus was greatly reduced in all regions when the patients had inhaled the mannitol (p<0.02). The clearance in the peripheral region at 24 hr was more than double the day mannitol had been inhaled compared to the day without mannitol (29.1±4.3 vs 13.4 ±4.6 %) (p<0.003). However, a single dose of mannitol did not change the clearance rate or lung function beyond 24 hr (p>0.2). In conclusion, a single dose of mannitol increases clearance of mucus acutely and its effect may extend up to 24 hr. The optimum daily dose of mannitol and its long term clinical benefit need to be investigated. Laryngeal penetration and subsequent aspiration of particulate matter such as food and gastric contents, has the potential to cause lung damage through direct injury and infection. The act of swallowing is intimately coordinated with ventilation in order to minimise this risk. The frequency of aspiration during swallowing in COPD may be increased, however the relationship between ventilation and swallowing in this group has yet to be elucidated. Alm: This pilot study was undertaken to determine if there is (1) an increase in the incidence of laryngeal penetration and aspiration, (2) a decrease in the deglutition-apnoea interval and (3) a change in ventilation before and after swallowing (inspiration-swallow-expiration IES, exp-swallow-exp EES, expswallow-insp EIS and insp-swallow-insp llS) in patients with COPD. Methods: A group of COPD subjects (median (SD) age 74 years± 4.0, n=5, 3F:2M) with FEV1NC <50% and a group of control subjects (71 years± 6.8, n=4, 4F) had videofluoroscopy while swallowing 3ml, 5ml and 10ml boluses of high density liquid barium. Sternocleidomastoid EMG, respiratory flow at the nose and mouth and pulse oximetry were measured simultaneously. ResuHs: 3 out of the 5 COPD subjects had either laryngeal penetration or aspiration while swallowing at least one of the 3 boluses compared to O out of 4 of the control group. There was a consistent respiratory phase difference between COPD and controls (figure1 ). Inspiration immediately post swallow was only noted in COPD subjects (odds ratio 15:1 ). No difference was observed in the deglutition-apnoea interval regardless of bolus size or the presence of aspiration (p.=0.2-0.5). There was no evidence of arterial oxygen desaturation in any patient. Figure 1 . Conclusions: There appears to be a greater incidence of penetration or aspiration in the COPD group compared to controls in this small group of subjects. This may be due to the increased incidence of inspiration directly following swallowing in the COPD group. There was no difference in the deglutition-apnoea interval. • Cunnin>J!on D .. Teichtahl H .. Humphreys J. Department of Respiratory Medicine, Western Hospital, Victoria, Australia Background: IRCUs have been used to provide non-invasive positive pressure ventilation (NIPPV) and basic non-invasive monitoring for acutely ill respiratory patients in non intensive care (ICU) or high dependency (HOU) settings. An IRCU was established in the respiratory ward at our hospttal in May 1999. Aims: To evaluate patients admitted to IRCU and determine predictors of outcome in patients wtth acute exacerbations of COPD. ~: Demographic and physiological data were collected on all admissions to the IRCU. The data were analysed using a multiple logistic regression model to determine predictors of outcome.~ 60 patients were treated in the IRCU from May to October 1999. 38 patients (68%) had COPD, 9 (15%) had obstructive sleep apnoea and'or obeslty/hypoventilation (OH), and 3 (5%) had bronchiectasis. The remainder had non-hypercapneic respiratory failure due to asthma, pneumonia or acute pulmonary oedema. NIPPV was used in 30 patients wtth acute hypercapneic respiratory failure (28 with acute exacerbation of COPD and 2 with OH). Ten of 38 patients with COPD (26%) had a poor outcome, defined as death (6 patients) or endotracheal intubation (ETI) (4 patients). All of the patients that died had a not for resuscttation order and no patients with a diagnosis other than COPD had a poor outcome. The patients who had a poor outcome were significantly older (73 vs 62 years, p;Q.002) and had a lower initial arterial pH (7.19 vs 7.30, p;().03) than those COPD patients who did well. In a multiple logistic regression model, age (p;().01) and initial arterial blood pH (p;Q.05) were significant predictors of poor outcome in patients with acute exacerbations of COPD. Chronic Airflow Limitation (CAL) is a major contributor to the burden of illhealth in Australia, and where hypoxia is present, can be treated with home oxygen therapy (HOT). At Flinders Medical Centre, a prospective longitudinal study has been undertaken to examine the impact of HOT on the quality of life of subjects with CAL. Methods: All eligible adult patients, aged less than 80 years, with a primary diagnosis of CAL who met the prescription guidelines of the Thoracic Society of Australia and New Zealand were offered HOT and invited to participate. After baseline assessment subjects were followed-up at 3, 6 and 12 months from commencement of HOT. The disease-specific Chronic Respiratory Disease Questionnaire (CRQ) was applied. A mean change in score from baseline equivalent to 0.5 per question was considered clinically significant. Results: Follow-up was available for 115 CAL patients, (male:female 58:57), mean age 69.3 years, prescribed HOT from January 1991 to July 1999. Based on Guyatt's clinically significant difference for the CRQ, 50% females experienced significant improvements in CRQ scores at three months, 42% at 6 months and 43% at 12 months with 21% patients experiencing significant deteriorations at 3 months, 22% at 6 months and 18% at 12 months. 41 % males experienced clinically significant improvements at 3 months, 33% at 6 months and 42% at 12 months with 19% experiencing clinically significant deteriorations at 3 months and 6 months and 20% at 12 months. Conclusion: More CAL patients were able to demonstrate clinically significant improvements in their quality of life after commencing HOT than clinically significant deteriorations. Key words: Chronic Airflow Limitation, home oxygen therapy, clinically significant difference Respiratory outreach nursing is an alternative care strategy which may reduce the burderi of chronic obstructive pulmonary disease (COPD) in terms of morbidity, mortality and costs to health care systems. Objective: To evaluate the effectiveness of such programmes for patients with COPD in terms of improving lung function, exercise tolerance and health related quality of life (HRQL) of patient and carer, and reducing mortality and hospital service utilisation. Methods: Randomised controlled trials of relevant studies were identified and assessed according to Cochrane Collaboration guidelines. Results: Four studies were found (total n=624) with intervention durations of 7-12 months (1 and 3 studies respectively). Meta-analysis demonstrated that mortality was not significantly reduced by the intervention, Peto Odds Ratio o. 72; 95% confidence interval 0.43, 1.21. However, post hoc subgroup analysis suggested that mortality was reduced by the intervention in patients with less severe respiratory disease. Significant HRQL improvements were reported in one study in moderate COPD, but not in a study in patients with severe disease. FEV 1 and exercise performance were not improved in the studies where data were available. Hospital admissions, reported in one study in patients with severe disease, were not reduced. Conclusions: Overall meta-analysis showed no benefits from outreach nursing visits for COPD. Post-hoc sub-group analysis indicated that there was improved mortality when more mild COPD subjects were targetted. One study suggests this group also has HRQL gains. Current data suggest there are no reductions in hospital utilisation and health care system costs. Studies of longer duration, enhanced by inclusion of pulmonary rehabilitation may identify subjects most likely to benefit. Key words: chronic obstructive pulmonary disease, outreach nurse. # currenVex smokers, data submitted for publication These results are consistent with the concept that SLPI in the presence of A 1 AT deficiency can protect the lung against the development of emphysema in the absence of cigarette smoking. Unlike lung volume reduction surgery, the benefits of surgery for giant bullae are not in dispute. However some patients have so little reserve that conventional surgery is not a viable option. Two such patients are presented with FEV 1 < 0.6 litres and hypercapnia. Both were bed-ridden and severely dyspnoeic on oxygen therapy. A surgical approach was devised by combining several approaches from the literature and adding the use of intra-cavity thoracoscopy. Both patients had surgery under epidural and local anaesthesia with excellent functional results. A sub-periosteal rib resection was performed, leaving the parietal pleura intact. Concentric purse-string sutures were then placed and lightly snugged to keep the bulla against the parietal pleura and the centre was incised with a scalpel. A 0° thoracoscope was then advanced to visualize the inside of the bulla, allowing direct identification of septa and bronchial openings. Various techniques could then be used to unify the bullae and control leaks. Talc slurry was sprayed onto the interior surface of the bulla. A 24 French Foley catheter was introduced through the purse-string sutures and its balloon inflated. This was pulled up against the parietal pleura, secured and connected to an underwater seal drain. Both patients reported immediate symptomatic relief. Improvements in FEV 1 , PaC0 2 and X-ray appearance were noted. The first patient survived 8 months, requiring oxygen on exertion. The other is fully active at 6 months without oxygen support. The patients described could easily have been denied a surgical solution for their dyspnoea. This procedure achieves hospital discharge and good quality of life, without imposing risks of thoracotomy, anaesthesia or ventilator dependence. Key words: Thoracoscopy, emphysema, lung volume reduction surgery. respectively, 19.5 and 18.2 years less than non-Aboriginal people. Of this excess mortality 10% in females and 7% in males is due to chronic nonspecific lung disease. The cause of this burden of disease is due to factors in addition to tobacco smoking. Methods: Cross-sectional survey of 202 adult residents (18-80 years) of a remote rural Aboriginal community. Spirometry, histamine challenge, respiratory symptoms and signs, and established and postulated risk factors for respiratory disease were assessed. Results: 44% of participants fulfilled criteria for one or more of chronic bronchitis (CB) (20%), recent wheeze (RW) (31%), or abnormal respiratory auscultation (18%). There was no significant difference in gender, age, marijuana use or positive skin prick reaction (> 3mm) between those with and without respiratory disease. There was a trend for bronchial hyperreactivity (BHR) (PD 20 FEV 1 < 3.8µmol histamine) in those with respiratory disease (12.1 vs 4.4% x2 p=0.08) and current or past tobacco smoking in men only (94.6 vs 81.6% x2 p=0.07). Lower PD 20 FEV 1 for histamine was significantly associated with respiratory disease (p<0.05) and particularly when using a cutoff of 15µmol. Low body mass index (BMI) was significantly associated with respiratory disease (p<0.05), particularly those with a BMI in the lower quartile(< 20kglm2) (X2 p<0.01). CB was associated with increasing age (43.6 (2.8(SEM)) compared to 38.4yrs (1.0(SEM)) p<0.05 ) and also a BMI <20kglm2 (X2 p<0.01). CB was not associated with tobacco use or PD 20 FEV 1 . BHR (X2 p<0.01) and PD 20 FEV 1 (p<0.01) were however associated with RW as was current tobacco smoking (X2 p<0.05). Conclusion: These findings demonstrate that BHR had a significant association with respiratory disease, particularly recent wheeze. Chronic bronchitis however was not found to be associated with BHR or tobacco smoking in contrast to recent wheeze which was associated with current smoking. The association between BMI and respiratory disease will require further prospective study. Elizabeth A Geelhoed, Philip J Thompson University Department of Medicine University of Western Australia and Asthma and Alleroy Research Institute Background: Informational databases provide an expedient means of assessing trends in mortality, disability and costs. Health data are primarily collected according to the International Classification of Diseases (ICD-CM), a coding system based on disease diagnosis. However, Chronic Obstructive Pulmonary Disease (COPD) presents a challenge in diagnostic coding as it may include emphysema, chronic bronchitis and obstructive asthma. Aim: To assess and analyse the national data set on COPD hospital admissions, classified according to ICD-9. Results: Four years of data from the National Hospital Morbidity Database were examined, using ICD-9-CM codes 490-492 & 496 as the primary diagnosis. Most COPD cases were recorded within a residual category labelled 'obstructive disease not otherwise specified' (code 496). The proportion attributed to this category varied from one state to another (50% to 80%). The coding classifications within COPD also demonstrated variation in admission detail. The proportion of admissions for emphysema increased throughout the period (8% to 12%) while the proportion for chronic bronchitis decreased (24% to 19%). These trends were also reflected in mortality rates derived from the Australian Bureau of Statistics. The mean length of hospital stay varied across ICD codes, with emphysema (10 days, SEM: 0.2) being longer than chronic bronchitis (8 days, SEM:0.2) (p<.001). Using the number of diagnoses as a proxy for comorbidity, patients with emphysema have significantly more comorbidity than patients with chronic bronchitis (p<.001 ). Conclusion: The widespread use of a residual coding category generates both variation in recording because of unclear definition and a lack of information regarding subclassifications of COPD. Retrospective analysis using ICD-9 coding definition for COPD patient groups is likely to provide imprecise outcomes due to the heterogeneity of the most utilised coding group. Acknowledgements: Astra Pharmaceuticals provides financial support to AARI for Health Economics Key words: COPD, ICD-9, epidemiology COPD is one of the leading discharge diagnoses for Australian hospitals. The reason for admission is not reflected in the Diagnosis Related Group (DRG) classification~ but evidence from overseas and from Flinders Medical Centre (SA) suggest that psychosocial factors are an important contributing factor to admissions. Aim: The Adelaide Collaboration on Chronic Obstructive Respiratory Disease (ACCORD) Project Team developed and implemented evidence-based clinical practice guidelines for use in hospitalised COPD patients, with an aim of identifying more accurately not only physiological but also psychosocial morbidity. Methods: The ACCORD guidelines were implemented in three "active" (A) hospitals over a 6 month period. Patterns of admission and DRGs were tracked before and during the intervention period in both A and "control" (C) hospitals. Patients completed the 28-item General Health Questionnaire at admission, 6 weeks after discharge, and 6 months later; a total score over 5 is considered to indicate significant psychiatric morbidity. Results: Mental health (MH) DRGs were recorded in less than 6% of patients in the pre-intervention period. At admission 72.5% of 506 patients had GHQ scores over 5. Six weeks after discharge 56.2% of 283 patients had significant psychiatric morbidity, and at 6 months 51.1% had GHQ >5. (The age-matched prevalence of psychiatric morbidity is 12.8%.) The main psychiatric diagnoses defined by the GHQ were Anxiety & Insomnia (55.7%) and Severe Depression (30.7%). There is a high level of psychiatric morbidity in patients admitted for treatment of COPD to SA Teaching Hospitals. Neither the overall psychosocial impact of COPD nor the specific psychiatric diagnoses were coded. This under-recognition of psychosocial morbidity needs urgent attention. HRCT is the gold standard for the diagnosis of emphysema in patients with airflow obstruction. A reduction in TLCO is also an indicator of the presence of emphysema in this group of patients. A previous study demonstrated a poor correlation between reduction in TLCO and HRCT finding of emphysema in a subgroup of patients with very severe airflow obstruction (1) . Nonetheless, in clinical practice, a reduction in TLCO is commonly interpreted as consistent with a diagnosis of emphysema. We wished to determine the relationship between the reduction of TL CO in the presence of severe airflow obstruction and the presence of emphysema on HRCT. We examined current or ex-smokers with irreversible airflow obstruction, FER <60%, FEV1<1.5 L, TLCO <15 mUmin/mmHg who had undergone HRCT. RESULTS: 95 out of 113 patients had reduced TLCO (mean = 37.5 %pred) and KCO (mean= 50.0 % pred) with HRCT evidence of emphysema, whereas 18 had reduced TL CO (mean = 53.9 %pred) and KCO (mean = 64.8 %pred) but no HRCT evidence of emphysema. CONCLUSION: These data suggest a reduction in TLCO does not necessarily equate with parenchymal abnormality in patients with severe smoking related airflow obstruction. The explanation for this reduction in TLCO in patients with severe airflow obstruction but no HRCT evidence of emphysema remains hypothetical. Ventilatory inhomogeneity leading to measurement error may be an explanation for this finding. Respirology (2000) 5, (Suppl.) Eaton TE, Rudkin S, Garrett JE. Department of Respiratory Services, Green Lane Hospital, New Zealand. The prescription of long term oxygen (LTOT) is underpinned by the measurement of arterial P0 2 , generally obtained by radial artery puncture. Cutaneous oximetry has not proved sufficiently reliable as an alternative. The use of ear lobe arterialised capillary blood has been proposed with several studies suggesting close agreement between arterial values. However, this technique is not widely used and the clinical utility remains uncertain. Consecutive patients with chronic respiratory disease undergoing assessment for LTOT were invited to participate. Simultaneous radial artery and arterialised ear lobe sampling was performed and procedural difficulties and patient discomfort detailed. Agreement between arterial and arterialised P0 2 was compared using the Bland and Altman method. One hundred patients were studied. Procedural difficulties (insufficient sample or air in sample) were similar for both procedures, however a clotted specimen occurred more frequently in the ear lobe arterialised sample. Seventy six sample pairs were available for comparison. Radial artery and arterialised P0 2 were in close agreement with a mean difference -0.30 kPa (95% Cl -0.54 to -0.006). However, based on the arterialised earlobe sample and using the absolute criterion (P0 2 :;; 7.3 kPa) for the prescription of LTOT, 10/57 (18%) patients would receive oxygen inappropriately. Conversely 6/19 (32%) patients would have been denied treatment. Radial artery puncture gave rise to significantly greater discomfort (p<0.0001) and level of concern (p<0.0001 ). Although patient preference strongly favours arterialised ear lobe sampling, procedural difficulties and insufficient accuracy mean that ear lobe sampling cannot replace radial artery puncture in the assessment of patients for the provision of LTOT. The objective of this study was to evaluate the Selim Chronic Lung Disease Questionnaire (a severity rating based on symptoms) in patients with chronic obstructive pulmonary disease (COPD) and asthma by correlating the Selim score to objective measurements of severity. This open study was conducted in hospital respiratory outpatient clinics. Consecutive patients with COPD and asthma had responses to the Selim Questionnaire recorded: FEV1 and FVC were measured and a patient self rating of severity of illness was documented. The Selim Questionnaire is based on 6 questions related to dyspnoea, cough, wheeze and sputum production, and asks patients to rate these over the previous three month interval. This report is from the initial 55: 32 females and 23 males age range 20-79 years. A correlation has been demonstrated between FEV1 and the total Selim score (see diagram). Considerable variation exists in cystic fibrosis (CF) phenotype and severity, even amongst individuals with identical CFTR mutations. There is significant individual variation in host inflammatory response, with increased TNF-a and IL-1 Ra concentrations in CF airways. Functionally relevant polymorphisms in cytokine genes have recently been characterised. The TNF2 polymorphism at position -308 of the TNF-a promoter is associated with TNF-a higher concentrations in vitro. Variable numbers of tandem repeats in intron 2 of the interleukin-1 receptor antagonist (IL-1 Ra), an anti-inflammatory cytokine, lead to alleles which have been associated with inflammatory diseases. We hypothesised that these polymorphisms influence phenotype in CF. Aim: To examine TN Fa promoter and IL-1 Ra polymorphisms as disease-modifying genes in CF. Methods: We recruited 73 adults with cystic fibrosis and 168 healthy anonymous blood donors. Genotypes were determined using PCR. Results: CF patients (55% female) had mean (SD) age 25.4 (6.4) years, BMI 21 (3) and FEV 1 56 (22) % predicted. Allele frequencies in CF were TNF2 19.9%, IL-1Ra*1 77.4%, IL-1Ra*2 21.9% and IL-1Ra*3 0.7%, which did not differ from controls. BMI was similar between TNF-a genotypes (1/1 20.9, 1/2 21.2, 21219.8). FEV 1 %pred did not differ between TNF-a genotypes (1/1 57%, 1/2 53%, 212 67%). There was a trend to over-representation of TNF2 in adults with CF who required lung transplantation. IL-1 Ra variants were not associated with BMI or lung function. Conclusions: Presently our data do not provide evidence forTNF-a and IL-1Ra polymorphisms as modifiers of BMI, FEV 1 or VC in CF. Recruitment is continuing to obtain adequate power and further detailed CF phenotyping, including key longitudinal clinical and physiological outcomes, is required to exclude an effect of cytokine gene polymorphisms. Key words: Cystic fibrosis, tumour necrosis factor-alpha, interleukin-1 receptor antagonist, polymorphisms. Dakin CJ, Henry R, Field P, Morton J. Respiratory Medicine Sydney Children's Hospital Randwick 2031. Despite the importance of pulmonary exacerbations (PE) in CF in both clinical and research settings, published evidence or consensus is lacking about the variables used to define an exacerbation. Hospitalisation, a surrogate measure, relies on uniformity among clinicians in diagnosis and treatment of PE. Aims: with CF the presence of pathogens in the lower airways correlated with levels of inflammation, respiratory system compliance and degree of air trapping. Introduction: Allergic bronchopulmonary aspergillosis (ABPA) shares some important similarities with cystic fibrosis {CF); hence the possibility that genetic factors may play a role in pathogenesis. We aimed to determine the frequency of cystic fibrosis conductance regulator (CFTR) gene mutations in asthmatics with and without ABPA. Methods: Patients were recruited prospectively from asthma clinic. A diagnosis of ABPA required satisfaction of all "essential diagnostic criteria"; asthma, skin prick test {SPT} positivity to Aspergil/us fumigatus (Af}, elevated serum total lgE > 1000 ng/ml, elevated serum Af specific lgE, history of pulmonary infiltrates on CXR or central bronchiectasis on CT. Blood samples were obtained from the following patient groups; atopic asthma SPT positive to Al with ABPA (n=36,(n=27 previously diagnosed and re-evaluated)}, SPT positive to Af without ABPA {n=26}, SPT negative to Al {n=31 }. Genomic DNA was screened for all the commonly occurring CFTR mutations using standard methods. Results: One of the 26 asthmatics SPT positive to Af without ABPA and 3 of 33 with ABPA were heterozygous for the delta F508 mutation. None of the 31 asthmatics SPT negative to Af carried the delta F508 mutation. Of the less common mutations, only R117H was identified; in one individual with ABPA and from another asthmatic SPT negative to Af. All patients found to carry a CFTR gene mutation had normal sweat chloride{< 40mM}. Conclusion: Extensive genotyping revealed the carrier rate in ABPA cases did not differ significantly from patient groups without ABPA. Indeed it was not different from the anticipated rate in the general population. Hence, the presence of a CFTR mutation does not appear to play a role in the aetiology of ABPA. This study was supported financially by the Health Research Council of New Zealand and the Green Lane Hospital Research and Education Fund. Jodi Hilton, Dominic Fitzgerald, David Cooper John Hunter Children's Hospital, Newcastle, Australia Cystic fibrosis related diabetes mellitus {CFRDM}, attributed to ongoing pancreatic fibrosis and destruction of beta islet cells, complicates CF in 5-24% of patients, whilst impaired glucose tolerance {IGT} occurs in up to 75%. The onset of CFRDM is usually insidious and associated with respiratory and nutritional deterioration. There is minimal information on the role of impaired glycaemic control in the period prior to the onset of CFRDM, nor its frequency in the paediatric population. Whilst implied, it remains unclear whether better management of the pre-diabetic stage will translate to slower progression to CFRDM or improved outcomes. [8.51, 10.82 ]. This represented an older age group, 14.5 compared to 11.8 years (p=0.047), but there was no significant difference in FBG 4.7 Vs 4.6mmol/L {p=0.64), or HbA1C 5.7 Vs 5.54% (p=0.31). Blood glucose at 2 hours after Lucozade™ load was significantly higher, 9.65 Vs 5.93 mmol/L {p<0.0001 ). Overall there was no influence of enteral feeding or liver disease, but there is a high probability of Type 2 error. Conclusions: In this small initial cohort of children, 37% have evidence of impaired glucose tolerance on OGTT, whilst only 3/11 had a HbA 1 C in the IGT range (6.1-7%). All patients with IGT had FBG <7.0mmol/L, including the 1 patient with an OGTT result in the CFRDM range (14.4mmol/L). Further evaluation is required of the true incidence of IGT in this population, due to uncertainty regarding influence on morbidity and progression to symptomatic CFRDM. Cystic Fibrosis is a life threatening chronic illness requiring many inpatient admissions for treatment. Reviews of the literature and discussions with staff and families reveal a complex array of difficulties associated with the longterm psychosocial management of a chronic illness. Families often bring unresolved issues from past admissions, which may be conflicting in regard to aspects of the treatment or their relationship with hospital staff. These feelings are often expressed in terms of having little power or control in relation to the general management of the illness while in hospital. Staff also speak of a loss of professional role when working with families that are seen to be 'difficult.' A level of stalemate therefore often develops with both families and staff unsure about how they could work more effectively together. Systems theory, feminist and psychodynamic theory can be used to identify and analyse areas of conflict, and structure the process of mediation and negotiation between patients and staff. Systems theory examines the relationships between individuals, the way in which they communicate and the meanings that develop out of those interactions, as well as examining the organisation of the family. Feminist theory examines the structural influences on a family living with a chronic illness and Psychodynamic theory examines the intrapsychic processes of the individual such as the unconscious, the impact of past history on behaviour and object relations theory which examines the bond between child and parent. The use of these theories allows for the development of appropriate interventions to produce an effective outcome for all parties to the process. This in turn may assist families to cope with the demands of a chronic illness as well as potentially reducing unplanned patient presentations. Background: Newborn screening for cystic fibrosis (CF) was introduced in Victoria in 1989. The primary screen is immunoreactiviytrypsinogen (IRT) measured from heel prick blood taken on day 4 of life. l'labies with an elevated (>99 1 h centile) !RT had either a second IRT measured at 4-6 weeks (1989) (1990) or mutation analysis for ti.F508 (1991) (1992) (1993) (1994) (1995) (1996) (1997) (1998) . Babies with an elevated second IRT or with one or two copies of ti.F508 were referred for a sweat test to confirm the diagnosis of CF. The aim of this study was to review newborn screening for CF in Victoria over the first ten years of the programme (1989) (1990) (1991) (1992) (1993) (1994) (1995) (1996) (1997) (1998) We have previously demonstrated that the human airway responds to addition of hypertonic saline to the airway surface liquid (.ApL) with a decrease in potential difference (PD). This response was rapid, reversible and blocked by amiloride pretreatment, suggesting that the additional saline decreased Na+ absorption. To further investigate this response, we have separated the responses to increased Na+, increased Cl", and increased osmolarity. The effect of topical application of various hypertonic solutions on the nasal PD was measured in 6 normal volunteers (Eur Respir J 1994 : 7: 2050 -2056 . Addition of (500 mM) sodium gluconate, (500 mM) N-methyl -D-glucamine (NMDG)-CI and ( Introduction; Colonisation of the cystic fibrosis (CF) airway by Pseudomonas aeruginosa (PA) stimulates the migration into the airway of activated polymorphonuclear neutrophils (PMN) which generate proteases and reactive oxygen species (ROS) which cause cell damage and ultimately lung destruction. Hypothesis; Iron may be part of the patho-immunological processes in CF because of its ability to both facilitate PA replication and catalyse the formation of toxic hydroxyl radicals. Methods; We determined the levels of total iron and ferritin within sputum from 21 CF patients admitted to our institution with an infective exacerbation of their bronchiectasis. We also assessed the sputum concentration of albumin as a marker of vascular leakage. Results: Sputum total iron and ferritin concentrations exceeded those found in normal serum (Table) and significantly correlated with sputum albumin levels (r=0.7, r=0.6, p<0.05, respectively). There were significant negative correlations between sputum total iron, ferritin and albumin concentrations and FEV1%predicted respectively, p<0.05 P-Adrenergic agonists are widely prescribed in patients with cystic fibrosis (CF).The physiologic rationale for their use includes a high incidence of acute bronchodilator reversibility (up to 95% of patients), improved mucociliary clearance (in-vivo) and increased ciliary beat frequency (invitro). However, there is a paucity of data assessing functional or clinically relevant outcomes, and p-agonists may reduce alveolar ventilation by increasing dead space. We sought to assess the effect of salbutamol on a functional outcome, exercise capacity, in adults with CF. METHODS: Randomised, placebo-controlled, double-blind, crossover study of adult CF outpatients with clinically stable disease. Each subject performed 2 maximal, incremental cycle ergometer exercise tests on separate days following inhalation of either salbutamol or placebo (6 puffs) metered-dose inhaler via a large volume spacer. Each patient, on 2 separate days, underwent histamine challenge and detailed respiratory function testing (with assessment for acute bronchodilator reversibility to salbutamol). RESULTS: 9 unselected patients (5 male) aged 17 to 25 were studied. Baseline (mean+/-SD) FEV1 was 71 +/-13.5% of predicted and bodymass index 21.8 +/-2.5. Lung function at the completion of exercise in the salbutamol arm improved significantly from pre-exercise (increase FEV1 16.1 +/-11 %, p<0.01 ), and this increase was significantly greater than the 5 +I-3.8% increase in the placebo arm (p=0.02). There was no difference between the 2 arms for maximal oxygen uptake (salbutamol arm 33.38 +/-6.2 ml/kg/min vs 32.42 +/-2.15, p=0.6) or maximal workload achieved (salbutamol arm 1185.2 +/-280.7 kpm vs 1209 +/-272.4, p=0.2). CONCLUSIONS: In this group of adult cystic fibrosis patients, inhaled Padrenergic agonists did not result in improved exercise capacity, despite a significant bronchodilation effect. These preliminary results do not provide support for the widespread use of P-Adrenergic agonists in adults with CF. Key words: cystic fibrosis, bronchodilator, p-adrenergic agonists, exercise. The presence of colonisation with 8urkholderia cepacia (8. cepacia) complex in patients with cystic fibrosis (CF) has been reported to be associated with adverse outcomes. Alms: To determine the r-ctuarial survival, morbidity and post transplantation prognosis of ou'1patients with CF colonised with 8. cepacia, with reference to the specific genomovar and strain. To evaluate the effectiveness of the centre's segregation policy. Methods: Retrospective review of spirometric, epidemiological and microbiological data on all patients whose primary CF care was obtained from an adult CF centre and were colonised with 8. cepacia. For each 8. cepacia colonised subject three age and gender matched case control subjects were randomly allocated. Phenotype and genomovar typing, random amplified polymorphic DNA (RAPD) strain type and 8. cepacia epidemic strain marker (BCESM) analyses were performed. The effect of 8. cepacia-colonisation on transplant-free survival was estimated by Cox's proportional hazards regression using the entire clinic population. Results: Fifteen patients were colonised with 8. cepacia of which 6/15 (40%) had died from CF related disease by August 1998 compared with 30/173 (17.3%) of the entire clinic population. Taking the combined end points of transplantation and death 8/15 (53.3%) of those colonised with 8. cepacia compared with 49/173 (28.3%) of the clinic population had either been transplanted or died. Cepacia status had a significant adverse effect on survival with a hazard ratio of 2.16 (95% Cl 1.0 to 4.69, p = 0.05). When those colonised with 8. cepacia were sub grouped according to genomovar and strain type: genomovar II was associated with 1/2 (50%) death, genomovar Ill RAPD 40, 3/3 (100%) deaths, genomovar Ill RAPD 10, 1/5 (20%) death. The remaining 5 subjects were found to be genomovar Ill with heterogeneous strains of which 1/5 (20%) died and two had lung transplantation and survived. Based on genomovar and strain types there has been no hospital transmission of 8. cepacia. Discussion. Colonisation with 8. cepacia had a significant adverse effect on survival within this study population. Genomovar and strain typing has been used to determine that the segregation policy in place has been effective in preventing cross-colonisation. There were trends towards lower pulmonary function and the data suggest prognosis is not uniform amongst specific genomovars and strains. Supported by the NHMRC and CHATA. Introduction A variety of bronchoscopic techniques is available at our institution for the palliation of inoperable locally advanced airway malignancy or to improve survival in lung carcinoma in situ.This study is a review of the use of Nd:YAG laser ablation and airway stents in such patients. It aims to establish their efficacy at our institution compared to other previously reported series. Method: We retrospectively reviewed the records of 36 patients treated for progressive airway malignancy (26 primary lung) with Nd:YAG laser ablation (n=34) and/or stent insertion (n=16). 33 patients had advanced inoperable tumours and 3 had lung carcinoma in situ. Results: Successful palliation was achieved following 93% of Nd:YAG laser ablations and 81% of stent insertions. At 6 months symptomatic benefit was maintained in 45% post stent and 29% post laser. For all procedures, patients with primary bronchogenic carcinoma achieved a shorter duration of benefit. In this group radiotherapy post procedure was effective with 47% maintaining local control at 4 months compared with 25% without adjuvant radiotherapy. 24 patients died during follow up, 13 from progressive airway obstruction, 8 from generalised disease and 2 from immediate procedure related complication. In patients with lung cancer, the presence of stage 4 disease pre procedure adversely affected survival. Kaplan-Meier survival curves will be presented for censoring. Conclusion: Nd:YAG laser therapy and airway stents are both effective, safe procedures for the palliation of symptomatic malignant airway obstruction as previously reported in larger patient series. Adjuvant radiotherapy was demonstrated to be beneficial. Selection of appropriate lung cancer patients should favour those without distant metastases. There is probably also a survival benefit although a prospective, randomised clinical study would be required to further evaluate this. The results of the first 24 matched pairs enrolled in this study are presented. There were 4 female and 20 male pairs with a mean age 59.8yrs (range 52-69yrs) and 69.5yrs (range 53-83yrs) respectively. Mean smoking history was respectively 56.8 and 57.9 pk yrs in the controls and lung cancer patients. Seven lung cancer patients and 10 controls had had asbestos exposure (no significant difference). Conclusions: The results of the analysis of the first 24 patient pairs enrolled in this study indicate that there is no excess exposure to asbestos in lung cancer patients compared with controls. Clarke C.P., Knight S.R., Daniel F.J., Berlangieri S.U. and Scott AM. Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084 Positron emission tomography (PET) has been available since 1992. While It was initially introduced for evaluation of cardiac and neurological disorders It has since been found to be most uselul in the detection and evaluation of cancer. A review of tts efficacy in lung cancer using F-18 fluorodeoxyglucose (FOG) as a marker has shown It to be of particular value in the following sttuations: 1 Evaluation of N 2 disease. An analysis of 70 patients wtth N 2 non small cell lung cancer (NSCLC) showed PET scanning was more reliable than CT scanning and in particular a negative PET scan was highly specific. 2 Evaluation of adrenal masses in patients wtth lung cancer. A study of 1 O patients showed a 90% accuracy for PET scanning. 3 Evaluation of response to Neo-adjuvant chemotherapy for lung cancer. A study of 20 patients has shown that generally the PET changes are more dramatic than the CT changes. 4 Evaluation of non-calcified lung nodules. In Australia 60% of such nodules are malignant. Even wedge resection can be hazardous in patients wtth poor pulmonary !unction or significant co-morbidtty and in these patients "cold'' nodules can be safely watched. 5 Whole body PET scans in patients wtth secondary lesions in the lung has confirmed whether or not the primary lesion is well controlled and has been able to show other occult metastases. 6 PET has proven the most useful modaltty when local recurrence is suspected but chest X-ray and CT are difficult to interpret because of fibrosis. We conclude that the routine use of PET scanning in patients wtth lung cancer has reduced the need for mediastinoscopy and needling of adrenal masses and gives confidence in decision making when dealing wtth solltary non-calcified nodules and secondary tumours in the lung. It shows promise in the evaluation of the response to Neo-adjuvant chemotherapy and is the investigation of choice when local recurrence is suspected but unproven .. Supported by NHMRC PET Scanning, Lung Cancer, Surgery The best pre-operative predictor of postoperative complications following lung resection remains unclear. Results from LVRS suggest that patients with severe emphysema can safely undergo thoracic resection of 'target' areas of lung with poor perfusion suggesting that even patients with severe emphysema and lung CA may be operable. We have elected to perform CA resection on patients with severe emphysema (FEV1 < 35% predicted), who would previously have been deemed inoperable, where it could be combined with unilateral LVRS. Between February and October 1999, surgery was performed on 5 patients with lung CA, an FEV1 < 35% predicted and appropriate 'target' areas of poor perfusion. Pre-operative and perioperative data are shown. There have been no deaths and none of the patients has required long-term oxygen. Two patients had prolonged (> 21 days) air leak and two required postoperative intravenous antibiotics. There were no episodes of reintubaton and all patients were discharged from the intensive care unit within 48 hours. We conclude that the applicability of previously established risk factors for lung resection may need to be reassessed. Fong KM1, Zoechbauer-Mueller s2, Virmani A2, Geradts J2, Gazdar AF2, Zimmerman PV1, Minna JD2 1Division of Thoracic Medicine, The Prince Charles Hospital; 2UT Southwestern Medical Center Dallas Texas USA Aberrant methylation of CpG islands in the promoter region of genes is a tumour acquired mechanism for inactivating the function of, tumour suppressor genes. Aim: To determine the frequency of gene promoter methylation of the following genes: p16, 06-methylguanine-DNAmethyltransferase (MGMT), death-associated protein kinase (DAPK), Ecadherin (ECAD), and glutathione S-transferase P1 (GSTP1). Methods: DNA was obtained from 107 resected NSCLC and corresponding normal lung tissue. After bisulphite modification, unique PCR primers allowed the detection of methylated DNA sequences from unmethylated sequences. Results: Aberrant promoter methylation was identified in 25% for p16, 18% for ECAD, 19% for DAPK, 6% for GSTP1, and 20% for MGMT, whereas it was not seen (or only at very weak levels in the corresponding normal tissues). At least one of these five genes were aberrantly methylated in 62% of resected NSCLC. As expected, aberrant methylation of p16 corresponded with p16 down-regulation, as detected immunohistochemically. Correlations for various aberrant methylation changes include other genetic changes, disease stage and survival. Conclusions: This study confirms that a large proportion of NSCLCs are characterised by aberrant promoter methylation in the five genes tested. As other genes are known to be aberrantly methylated in other human cancers, it is likely that more genes will be identified to be aberrantly methylated in lung cancer. If so, not only will methylation studies contribute to knowledge of the pathogenesis of lung cancer, but may also provide an early detection strategy as others have found that aberrant methylation can also be detected in the peripheral blood of lung cancer patients. Background and Aims: Medical thoracoscopy has high diagnostic efficacy in pleural effusions and the potential to perform pleurodesis in the same procedure, thereby' reducing the number of patient interventions. Because pleurodesis should be proceeded by tissue diagnosis, we investigated the role of frozen section at the time of thoracoscopy to determine if this could allow more combined procedures. Methods: Prospective evaluation of 11 patients with undiagnosed symptomatic pleural effusions. All underwent medical thoracoscopy under local anaesthesia and conscious sedation in the bronchoscopy suite. Biopsies for frozen section and conventional histology were submitted at thoracoscopy. In addition, closed pleural biopsies (CPB) were taken through the entrance port before proceeding to compare diagnostic sensitivity. Results: 11 patients had final diagnoses of 1) 6 benign and 2) 5 malignant (4 mesothelioma and 1 pleural synovial sarcoma). Frozen section concurred with the final histopathological diagnosis in 10/11 subjects, with 1 mesothelioma associated with extensive adipose tissue not detected. The diagnostic sensitivity for malignancy at thoracoscopy was 100%; the 6 benign cases have shown no evidence of disease progression or recurrence (mean follow up 4 months). In 7/11 subjects CPB results were consistent with thoracoscopic biopsies, with a sensitivity of only 40% for malignancy. One benign case along with all malignancies were pleurodesed with good radiological outcome. One patient with mesothelioma has a chronic pleurocutaneous fistulae at the intercostal catheter site undergoing slow resolution. The patient with mesothelioma and negative frozen section was pleurodesed at a second thoracoscopy three weeks later. Conclusions: Medical thoracoscopy is the preferred intervention in pleural effusions in which the aetiology remains undetermined after simple thoracentesis. Frozen section analysis during the procedure facilitates the possibility of doing combined procedures. Hopkins P, Fielding D Department of Respiratory Medicine, Princess Alexandra Hospital, Brisbane Background: An efficient diagnostic approach to exudative pleural effusions after an initial negative thoracentesis remains controversial. We conducted a retrospective review of patient records at the Princess Alexandra Hospital from 1994-99: 104 subjects who had undergone closed pleural biopsy (CPB) with thoracentesis for pleural effusion. Aim: 1) audit CPB with respect to diagnostic sensitivity and procedural aspects 2) consider the role of CPB in the diagnosis and management of pleural effusion. Results: Of 104 patients, 51 had final diagnoses of malignancy, 44 benign and 9 no final diagnosis. Adequate pleura was sampled in 82/104 subjects (79%). Only 30/51 (59%) malignancies were detected from the combined procedure of cytology pleural fluid and CPS with 19 requiring thoracoscopic or open pleural biopsy (OPB) and 2 bronchoscopy. Sensitivity of CPS/cytology for mesothelioma was 37% and the negative predictive value of a nonspecific biopsy 59%. In 39% of procedures, no sedation or analgesia was administered and 32% of biopsy specimens were not sent for microscopy. The sensitivity of taking 1 CPB was 0%, 2-4 51% and taking multiple biopsies 57%. Increasing volume of pleural fluid sent for cytological examination correlated with improved diagnostic sensitivity for malignancy. The complication rate was 16%. Conclusions: Procedural -The sensitivity of a single pleural biopsy is low and not appreciably improved beyond 2-4 percutaneous samples. There is a greater need for analgesia and sedation use during CPB along with a need to send specimens for microscopy and culture. Pleural fluid sent for cytology should be of at least 100 ml volume for improved diagnostic sensitivity. Diagnostic Role -Our reported sensitivity of CPB is similar to previous published studies. Nonspecific biopsy results are common and pose a significant limitation to this technique given the low negative predictive value for malignancy, particularly mesothelioma. At our institution this has led to an algorithm including medical thoracoscopy in a combined diagnostic and pleurodesis role. TGFP is a unique cytokine with potent pro-fibrotic and anti-inflammatory properties that make it an attractive agent for pleurodesis. We hypothesise that TGFP can produce pleural fibrosis effectively, quickly and without causing excessive pleural inflammation. Aims: To compare the 1) degree and 2) speed of pleurodesis and 3) histologic changes after intrapleural instillation of TGFP 2 and talc. Methods: 18 rabbits were given either TGFP 2 (1. 7µg) or talc slurry (400mg/kg) via a chest tube. 3 rabbits from each group were sacrificed at Days 1, 4 and 7. Pleurodesis was graded macroscopically from 1 (none) to 8 (>50% hemithorax). Histologically, pleural inflammation and fibrosis were graded from O to 4. Pleural thickening and area of collagen deposition were measured. Results: TGFP 2 induced excellent pleurodesis within 7 days. It produced more collagen deposition and pleural fibrosis. TGFP 2 also stimulated the production of large effusions of low inflammatory indices. . Mesothelioma develops in people exposed to asbestos and is characterised by a spread throughout the pleural space with tissue infiltration. Jn contrast to other lung carcinomas showing distant organ metastases early in the clinical course mesothelioma develops as a locally very aggressive tumour. Tumour proliferation is influenced by the composition of the extracellular matrix (ECM). ECM is regulated by de nova production, degradation by matrix metalloproteinases (MMP) and the action of the respective inhibitors. Furthermore different grow1h factors contribute to malignant cell proliferation. To investigate the role of MMPs in tumour progression in mesothelioma we analysed the supernatant of human mesothelioma cell lines under cell culture conditions for their ability to synthesise MMPs in the presence and absence of grow1h factors. Zymography and western blot were performed as previously described (AJRCCM 1997; 156:1987) . Three out of 5 primary human mesothelioma cell lines spontaneously synthesised MMP-2 propeptide but no other gelatinolytic MMP, especially no MMP-9. The MMP-2 pro-peptide could not be activated by the mesothelioma cells themselves. Following stimulation with transforming grow1h factor B MMP-2 expression increased in all mesothelioma. In contrast, stimulation with platelet derived grow1h factor did not influence MMP-2 expression. Summary and conclusion: MMP-2 is expressed by cultured human mesothelioma cells, especially if stimulated with transforming grow1h factor B. This might explain the pattern of local tumour progression in mesothelioma. In contrast, platelet derived grow1h factor had no effect on MMP 2 production. Diffuse panbronchiolitis is a chronic progressive pan-inflammatory condition affecting the respiratory bronchioles. It is most commonly seen in Japanese people and rarely reported outside the Far East. The condition has a poor prognosis due to the inefficiency of corticosteroids although erythromycin has been shown to be effective. Case: We report a case in a Chinese-born man who presented with symptomatic airway obstruction and nodular infiltrate on radiological investigation. Diagnosis was subsequently made on open lung biopsy and he was treated with roxithromycin 300mg daily. Clinically and radiologically he has had a good response after three months therapy. His lung function has improved with FEV1 of 1.2 (pre-diagnosis) to 2.5L, and FVC of 2.7 to 3.7L, with less air-trapping but unchanged indices of diffusion. Conclusion: Roxithromycin has been used successfully in this patient. It should be considered as an alternative therapy to erythromycin. Once daily administration and better tolerance may improve patient compliance. Exposure to both hard-and softwood dust has been shown to be associated with occupational asthma, chronic airflow obstruction, and respiratory symptoms. We conducted a cross sectional questionnaire study among 772 New Zealand sawmill workers (processing pinus radiata) focussing on respiratory symptoms. Preliminary results showed that asthma prevalence (current asthma medication, or shortness of breath or asthma attack(s) in past 12 months) in sawmill workers with moderate to high exposure to wood dust (based on job title) was significantly higher (19%; n=623) compared to non-or low wooddust-exposed workers (12%; n=147) (0R=1.8; p<0.05). Non-exposed workers included office workers (n=52), saw doctors (n=27) and various other job titles with an expected low exposure to wood dust (n=68). Twenty two percent of the moderate to high exposure workers reported wheezing, shortness of breath or chest tightness in relation to certain work tasks compared to only 8% among the low or non-exposed workers (OR=3; p<0.001 ). Also cough and cough with phlegm were reported more frequently (0R=1.8 and 1. 7; p<0.05) by the moderate to high exposure workers (34% and 28% versus 22% and 18%, respectively). Significant differences in smoking habits (but not in age and duration of employment) were found between both exposure groups. After adjusting for smoking, odds ratios for asthma and asthma symptoms in relation to work remained the same, whereas odds ratios for cough and cough with phlegm were only marginally decreased (0R=1.7 for both symptoms; p<0.05). In conclusion, preliminary results indicated that exposure to pine wood dust is associated with asthma and other airway symptoms. Due to the possible association between ambient air degradation and exacerbations of asthma, we have explored the response to the inhalation of fine carbon particles. Methods. The subjects were 8 patients (4 males) with stable asthma (mean age 40.6 yrs) receiving regular inhaled corticosteroid therapy supplemented with occasional use of inhaled ~-agonists.Their initial FEV 1 was 84% of predicted. Therapy was ceased at least eight hours prior to the study. All were atopic with positive skin reactions to at least three common allergens and with bronchial hyper-reactivity to lyophilised total rye grass pollen extract (mean PD 20 = 3.78 µg). Suspensions of carbon black particles in air were produced from a nebulizer/large particle trap device, the output of which produced 70% of the particles between 2.5 and 7 microns. The dust concentration was determined using a TSI Dustrak™ laser dust monitor. Single inhalations (RV to TLC) of particle suspensions of increasing concentrations, followed by breath-holding for 1 O seconds were carried out and FEV1 measured at 3, 10 and 20 minutes after inhalation and peak flow measurements were charted by the subjects on two occasions over the next 4-6 hours. Most subjects received four concentrations. Results. No subjects showed any symptoms or statistically significant falls in FEV 1 following particle inhalation at concentrations up to 55 mg/M3 (equivalent to a total retained dose of approximately 100 µg ). Late reactions did not occur. Conclusions. The lack of an acute bronchoconstrictive response to the inhaled dust is surprising and may have been due to the protection afforded by inhaled corticosteroid therapy or the total dose of particles delivered may be too small to elicit reactions which might be evident on more chronic exposure. Tube thoracostomy is commonly performed using a trocar, which provides rigidity and assists placement of the catheter tip into the desired position. Following the fatal impaling of a patient's myocardium in 1997, our hospital adopted a new technique for inserling and directing a trocar-free ICC by nasal speculum. AIM: To examine the indications for, problems with, and patient characteristics of those requiring thoracostomy tube placement in the department over the lasl 2 years since the change in technique. METHODS: 32 patients who required ICC placement in clinical management were recorded on a database for analysis. RESULTS: 13 patients (41%) had pneumothorax and 21 (66%) had pleural effusions (2 had both indications). Nine (28%) were performed emergently. The most frequent problems noted were significant pleural fluid leakage (19/21) and increased analgesia requirement (19/32). Thirty-four percent had misplacement of the catheter tip and in only 4 was the speculum too short (average BMI 30). There was low correlation between number of problems per patient•and their weight (r2=0.028) or BM\ (r2=0.155). Time taken for the procedure correlated modestly with number of problems per palient {r2=0.385) with the average time taken 23.7 minutes (range 5 -60 minutes). There have been no fatalities since conversion to the new technique; however, in one patient (BM\ 44.4) lhe procedure was abandoned for reasons of too short a speculum such that a trocar was required. CONCLUSION: Per-speculum ICC insertion is safe but appears to create more than the expected number of non-fatal complications of excess pleural fluid leak, poor directioning of the catheter tip and increased analgesia requirement because of the larger opening needed to accommodate the speculum. The procedure also takes longer to perform; however, a learning factor may account for this. Alms: Winter air pollulion in Christchurch is dominated by particulate from solid fuel domestic heating. The aim of the study was to explore the relationship between particulate air pollution and admissions to hospital with cardiorespiratory illnesses. Methods: Air pollution data (PM 10 ) were obtained from the Canterbury Regional Council monitoring station in the central city. The New Zealand Health Information Service provided data on admissions to the Princess Margaret and Christchurch Hospitals for the period June 1988 through December 1998 for both adults and children with cardiac and respiratory disorders. The relationship between PM 10 and admissions was explored using a time series analysis approach controlling for weather variables. Missing data were interpolated from carbon monoxide values for the same time period, which showed a close relationship with PM 10 • There was a significant association between PM 10 levels and cardiorespiratory admissions. For children and adults combined there was a 2.52% increase in respiratory admissions for each interquartile rise in PM 10 (interquartile value 14.8 mcg/m3). In adults there was a 1.26% rise in cardiac admissions for each interquartile rise in PM 10 . There was no relationship between PM 10 and admissions for appendicitis, the control condition selected. In keeping with international literature, there is evidence in Christchurch of a relationship between particulate levels and admissions with cardiac and respiratory illnesses. The size of the effect is in keeping with overseas data with the greatest impact seen on the respiratory system. Seema Mihrshahi, Jennifer Peat for the Childhood Asthma Prevention Study Team Clinical Epidemiology Unit, New Children's Hospital, Westmead, NSW 2145 INTRODUCTION: CAPS is a randomised controlled trial to evaluate the effectiveness of dietary modification and house dust mite allergen reduction as methods for the primary prevention of asthma. The results of the study will be compromised if compliance with either of the interventions is poor. The dietary intervention consists of supplying margarine and oils and addition of a supplement to the child's food each day. Compliance is assessed by parents self rating and nurse rating of margarine, ail and supplement use. The house dust mite intervention consists of washing the child's bedding every 3 months in an acaricidal wash; covering the child's mattress with an allergen impermeable mattress encasing; and removing sheepskins and soft toys. Compliance was assessed by completion of a laundry diary and by nurse observations of the presence of the impermeable mattress cover on the bed. As an objective measure, dust was collected from the child's bed and assayed for Der p 1. At one year, 83% of households in the active house dust mite allergen reduction group (n=117) had completed the acaricide wash and 81 % of children's beds had allergen impermeable mattress covers fitted. In children's beds, 58% in the active group had allergen levels below 10µg/g compared with only 29% in the control group (p<0.001). CONCLUSION: Compliance with the use of margarines and oils was high (94-96%) and there was good agreement between self-rating and nurse rating. Compliance with supplements, laundry routines and mattress covers was lower and will need to be improved. The finding that almost twice as many children's beds in the active group had allergen levels below 1 Oµg/g, is encouraging. Morgan, W Bruce, H van der Wall. Departments of Thoracic Medicine, Orthopaedic Surgery and Nuclear Medicine. Concord Hospital, NSW Introduction. Respiratory complications are common after arthroplasty with pulmonary thromboembolic disease (PTE) and fat embolism being the most serious. It is generally thought and taught that the high risk period for PTE is 7-10 days after surgery. As fat embolism from bone marrow should contain reticulo-endothelial cells, we hypothesised that these cells would take up colloid in the lung. We conducted a scintigraphic study designed to assess the occurrence of both diseases. Methods. Patients with previous PTE were excluded. Within 48 hours of surgery, tomographic lung studies were acquired after 99m Tc MAA injection. Pre and post-operative blood gases (ABG) and relevant chest radiography/CT were obtained. ABGs were analysed as the difference in alveolar-arterial oxygen gradients, pre and post-operatively (DA-al· Results Forty patients were studied (16F, 24M) with a mean age of 71 yr (Range: 36-88 yr). Of these, 16 were hip and 24 knee arthroplasties. Lung uptake of 99m Tc Colloid was present in 35% of cases (7/16 hips and 7/24 knees). Either focal or diffuse uptake was present. Diffuse uptake was associated with mottling in the lung perfusion studies. PTE was detected in 25 of 38 (66%) evaluable patients. There was no significant difference in the incidence or number of segments affected, between hip and knee arthroplasty. DA-a was significantly higher in patients with scan evidence either of PTE (p< 0.05) or fat embolism (P< 0.05). All patients recovered well and were free of respiratory symptoms at 6 months. Conclusion PTE immediately after arthroplasty is common and PTE should not be discounted as a clinical diagnosis in the early post-operative period. Prospective studies are needed to establish its natural course and whether intervention is of benefit. We have developed a simple test that appears able to demonstrate fat embolism to the lungs and that this is common after joint replacement surgery. The purpose of this descriptive study of the print media was to quantify the nature of the community health message and to gain an insight into how media stories on asthma are constructed. Method: Print media articles on any aspect of asthma were obtained from two media agencies, the Sydney Morning Herald and Associated Consolidated Press for the 40 month period from January 1995 to April 1998. This included daily metropolitan newspapers and non-daily print magazines available in Sydney. Content analysis was then undertaken on the news articles (n=160). The news articles were coded according to which newspaper or magazine published the article, controversial issues relating to asthma (where opposing views were given), type of message (information or action orientated), spokesperson, main themes and images created. Results: The vast majority of messages gave information (81 %), both sides of controversial issues were reported and each side received approximately the same coverage. The most frequently quoted spokesperson was from the medical profession (50%), however when sports personalities were quoted (5.6%) they received more coverage and space. One of the main themes which emerged, was asthma across the life span; however, the images that accompanied this theme revealed a story which indicated that asthma was gendered and that this image was consistent from childhood through to early adulthood. Conclusion: Within the limits of this study the media provided an important forum for discussion and interpretation of health messages on asthma. This study also found that when a story was accompanied by a picture the image created was one that reinforced typical feminine and masculine stereotypes in Western society. A questionnaire (AMPQ) was developed as part of The Alfred Inpatient Asthma Education Program (IAEP). The IAEP was developed to enable inpatients with asthma to receive an individualised education program that included consideration of health beliefs to promote positive health behaviour change and improve self-management. Aim: To develop the AMPQ as an instrument to assist the educator to explore and address attitudes to asthma -with the patient, in addition to assessing the educational needs of the person. Method: A 31-item questionnaire was devised in six sections: Health Beliefs, Causes of Asthma, Medications, Devices/ Techniques, Monitoring Asthma and Action Plan based on two previously published questionnaires. This was administered to 30 people admitted to Ward 5D at The Alfred with asthma over a two-month period. The responses to the questionnaire were summarised and nursing staff was asked to provide format evaluation on the AMPQ. Results: 19 (66%) patients held health beliefs that were consistent with positive health behaviour change. 20 (67%) understood what happens in the airways when they have symptoms. 12 (40%) reported they were smokers. 14 (47%) people were unsure about the role of their medications. 27 (90%) had been prescribed an aerosol steroid and of these 17 (58%) used a spacer. 19 (70%) reported forgetting to take their preventer and 7 (37%) forgot more than 6 times per week. 20 (67%) had a peak flow meter. Administration time was 10-15 mins. All the nurse educators were positive about the length of time involved and the information collected. Conclusion: The Asthma Management Profile Questionnaire provided useful information to educators about patient health beliefs and asthma management. This allowed the information delivered to be tailored to meet the specific needs of the patient in the context of their health beliefs. Background: Lung transplantation may allow prolongation and improved quality of life in end stage cystic fibrosis. It may, however hamper the treating team's ability to offer a consistent approach to palliative care. Objective: To describe a case that illustrates the contribution of the distinctive nursing ethic to a morally just outcome in the management of the terminal event in an adult with cystic fibrosis. Case discussion: A 59-year-old male with severe lung disease and substantially reduced quality of life was receiving inpatient treatment. The primary aim of medical management was the preservation of life to transplantation, including aggressive anti-microbial, nutritional and non-invasive ventilatory support. The patient's condition deteriorated prompting an honest and open discussion of treatment options with the patient. The goal of treatment was then changed (as a direct result of the intervention of the nurse and consistent with the expressed wishes of the patient) to ensure that suffering was minimized and dignity preserved. In the context of the caring relationship that exists between nurse and patient, the role of advocate was vital to ensuring that the wishes of the patient were reflected in the treatment goals. Conclusion: In the terminal phase, if possible, the patient should be given the opportunity to make an autonomous decision when to continue aggressive medical treatment or not. This should occur at a stage when the patient can make an informed choice about how and when they wish to die. The nurse has a pivotal role in this process. CAPS is a multicentre randomised controlled trial designed to determine whether certain interventions may reduce the incidence of asthma in children. AIM: the aim of this sub-study is to determine the main reasons for not participating in those subjects who were eligible to participate in CAPS. METHODS: Pregnant women whose unborn children were at high risk of developing asthma were identified using a short questionnaire at the antenatal clinics of 5 hospitals in western and south-western Sydney. Subjects were excluded if they had a cat at home, lived over 30km from the centre of recruitment, if the baby was delivered before 36 weeks gestation, if the baby had neonatal complications or a low birth weight. Eligible subjects were sent printed information about the study and telephoned to determine whether they wanted to participate. Their reasons for not participating in the study were recorded on the questionnaire. RESULTS: A total of 7375 women were screened and 1462 (20%) women were eligible for the study. A total of 871 women (60% of eligible population) declined to participate. The main reasons were: 42% were not interested or too busy to participate; 22% were ineligible for the study because they delivered early, were moving out of the area or for some other reason; 16% did not call back after three attempted contacts; 7% did not agree with the study interventions; 4% gave no reason; 3% said the study was too long; 2% cited medical reasons; 2% said family/marital problems were the main reasons they couldn't participate; and 2% cited other reasons. A total of six hundred and eighteen pregnant women (42% of the eligible population) have been successfully recruited into the study. CONCLUSIONS: Complexity and length of the study and amount of time available for the participants were the major factors involved in deciding not to participate in this research study. Recording the reasons for not participating in studies enabled us to have a better understanding of why people chose not to participate. This may have a bearing on the way a research project is presented to the general population and the way in which recruitment into research studies is planned. There are approximately 1500 spinal cord injured (SCI) persons in Victoria (900 quadriplegics), with most having a nearly normal life expectancy. In cross-sectional studies the prevalence of sleep disordered breathing (SDB) in quadriplegics is 2 to 5 times higher than in the general population (McEvoy, 1995; Short, 1992) . The reasons for this increased prevalence are unknown. Aims The aim of this study was to investigate the evolution of SDB in the first year following acute cervical SCI. Methods Assessments will commence as soon as possible post injury (<48 hrs) and comprised serial polysomnography (Compumedics™ PS2, Abbotsford, Australia) and respiratory function testing (flow-volume loops, MIPS & MEPS). Assessments were performed immediately post injury, at 2 weeks, 1, 3, 6 and 12 months. Evidence of undiagnosed SDB that may have existed prior to the SCI was quantified using the Maislin et al (Sleep 1995) multivariate apnoea prediction equation (MAP). Results Subject recruitment began in December 1998 and will continue for 1 year. As of 30111September1999, 67 patients had been admitted to the VSCS, 42 quadriplegic. Ten were excluded because they were older than 70, 2 because of an associated head injury and 3 declined to participate. Three have been ventilator dependent since admission, leaving 24 in the trial. Twelve subjects (11 men, average age 35, range 18-66 years) have been studied at 3 months. All had a restrictive ventilatory deficit (average VC 45%, range 14 -64%) and 10 of the subjects have SDB (RDI > 5), despite only 2 having a pre injury MAP likelihood of> 0.5, i.e. chance of pre-existing SDB of 75% (Cl 70-80% (3) Department of Applied Mathematics, The Australian National University Canberra ACT 0200. Surface tension (ST) properties are recognised as playing an important role in the maintenance of alveolar and small airway patency. In recent years, there has been interest in the role surface forces may play in thit control of upper airway patency. This concept is particularly relevant to the control of pharyngeal patency during sleep in the obstructive sleep apnea syndrome (OSAS). While the ST of saliva samples obtained from the oral cavity have been studied extensively there is little information describing the surface forces associated with ore-pharyngeal lining liquid. There are a number of approaches to the measurement of ST, however, many require relatively large samples of the liquid under study. We have now developed an approach which utilises small (microlitre) sample volumes. Methods: ST was quantified using the "pull-off" force technique1 in which ST is measured as the force required to separate two curved silica discs bridged by the liquid sample. After calibration with liquids of known ST, we measured the ST of 0.2µL samples of upper airway surface liquid (UASL) obtained (using 0.5mm ID polyethylene tubing attached to a 1 ml syringe) from ten adult subjects (4 females, 6 males) and from three sites within the upper airway. Results: There was no significant difference (P= 0. Introduction: Two groups in Toronto have shown improvement in cardiac function by non invasive means using nasal CPAP therapy. Their data however have not been rewoduced elsewhere. Therefore the aim of this study was to assess the effects of nasal CPAP on cardiac function in patients with cardiomyopathy and central sleep apnea (CSA). Methods: 5 adult male subjects (age: 67.8±8.7 yrs, BMI: 25.9±7.6 kglm2 (mean±SD)) with cardiomyopathy and CSA (central apnea/hypopnea index >120/hour) were studied before and after three months of nasal CPAP therapy set at a level to control any coexistent upper airway obstruction. Cardiac function (cardiac index (Cl), Pulmonary Artery Occlusion Pressure (PAOP), Systematic Vascular Resistance Index (SVRI) and Pulmonary Vascular Resistance Index (PVRI) was measured invasively by pulmonary artery catheter. Extravascular lung water (EVLW) was measured by double indicator dilution technique. CPAP compliance was measured objectively by measuring actual mask application time (Respironics Ariarn). In three subjects data were also collected after 12 months of CPAP treatment. Results: The mean CPAP compliance was 6.3± 0.7 hours per night and the mean pressure was 13±2.5 cmH 2 0. Introduction: The potential interactions between central sleep apnea (CSA), obstructive sleep apnea (OSA) and cardiac dysfunction are not well defined. Therefore the aim of the study was to assess the effect of 3 months nasal CPAP therapy on sleep disordered breathing in patients with (CSA) due to cardiomyopathy. Methods: 5 adult male subjects (age: 67.8±8.7 yrs, BMI: 25.9±7.6 kg/m2 (mean±SD)) with severe cardiomyopathy and CSA (central apnea/hypopnea index > 20/hour) were treated with nasal CPAP for 3 months after a CPAP pressure determination study. Three subjects continued CPAP for 12 months. Polysomnographic measurements were recorded after 3 and 12 months. A pulmonary artery catheter was used to measure Cardiac Index (Cl) invasively. All patients received standard medical therapy which was either unchanged or reduced during CPAP therapy. Results: Patients BMI did not change. The mean compliance was 6.3±0.7 hours per night and the mean pressure was 13±2.5 cmH 2 0. Introduction: Pharyngeal narrowing predisposes to obstruction during sleep. Alm: To determine the effects of neck position (NP), mouth opening (MO) and mandibular advancement (MA) on hypopharyngeal dimensions (antero-posterior (AP), lateral (L), cross-sectional area (XSA)). Methods: 5 healthy subjects (44±12 years (mean±SD)) were studied awake using a naso-pharyngoscope (tip in velopharynx) to visualize the hypopharynx. They were studied at 3 levels of MA (neutral, 5mm, maximum (7-10mm)), 3 levels of MO (teeth opposed, 10mm apart, 20mm apart) and 3 NP (neutral(0°), flexion(-20°), extension(+20°)). During tidal breathing, end-inspiratory images were stored digitally. AP and L dimensions were obtained from these images and expressed in units of epiglottic width to correct for magnification. XSA was calculated from AP and L. The separate effects of changes in NP, MO and MA on hypopharyngeal dimensions (AP, L, XSA) were determined relative to each baseline condition (neck neutral, teeth opposed, mandible neutral) (multiple regression). The carbon monoxide transfer factor (TLCO) and alveolar volume (VA) are routinely measured to assess the integrity of that part of the alveolar-capillary membrane accessible to respired gas. However, these physiological measurements are complex and there is no method available for validating the TLCO results. Aim: To develop a method for producing a known value for TLCO and VA to validate TLCO testing systems. Method: A 3.00 litre calibration syringe, 3-way tap and two gravimetric gas mixtures (BOC) containing accurately known Ne and CO concentrations were used to simulate the TLCO manoeuvre. One gas mixture ('inspired gas') contained 0.3000 ±0.0015% CO, and 0.4991 ±0.0025% Ne; the other mixture {'alveolar gas') contained 0.1002 ±0.0005% CO and 0.3507 ±0.0018% Ne. Theoretical TLCO and VA values were computed (target values) based on a 3.00 litre inspired volume, standardised breath-holding time of ten seconds and the accuracy range of the gas mixtures. Theoretical values were compared to results measured using a computerised TLCO system (MedGraphics Elite, MN, USA). Measured values of TLCO were standardised to a breath-hold time of ten seconds. Results: See and the TLCO and VA values obtained from the MedGraph1cs system were reproducible. VA was found to be accurately measured but TLCO was underestimated by 0.7 mUmin/mmHg. However, TLCO was within the target range when calculated using the measured inspired VC. This method can be easily adapted to other TLCO systems including those which use He or methane and can provide any physiological value for VA and TLCO. Conclusion: This TLCO validation method shows promise for confirming TLCO and VA measurements. Impulse oscillometry (IOS: Jaeger) is a rapid, non-invasive method of estimating airway resistance. Resistance (R.), measured at frequencies from 5Hz to 35Hz, peripheral reactance (X 5 ) and the respiratory impedance (Z,) are obtained during tidal breathing. Aim: To determine the repeatability of the indices obtained from !OS in patients before and after Ventolin. Method: 23 patients (aged 41-81yrs) produced two technically acceptable estimates of the indices from IOS, spaced 2 mins apart, each estimate being recorded over 30s -40s. Repeatability was reassessed 10 min after inhalation of 200µg of Vento I in via spacer using the one second forced expiratory volume (FEV 1 ) obtained from a volume-time curve using a wedge-bellows spirometer (Vitalograph). Results: For each index, the coefficients of repeatability and precision were obtained (British Standards Institute, 1979 (±SD) baseline FEV 1 was1.6 ± 0.71, FVC was 2.5 ± 1.0/, and FEV 1°/ oFVC was 65% (range 32% -77%). After Ventolin, FEV 1 was1.91 ±0.7/, FVC was 2.7 ± 0.9/, and FEV 1°/ oFVC was 66% (range 32% -88%). From IOS, mean baseline tidal volumes were 0.90 ± 0.41 I and 0.89 ± 0.45 /, and were not significantly different. After Ventolin, mean tidal volumes were 0.95 ± 0.30 I and 1.0 ± 0.4 I and were not significantly different. They were also not significantly different from baseline values. Conclusion: In these patients there is an improvement in the repeatability and precision of R 5 , Z, and X 5 obtained using !OS after administration of Ventolin via spacer device. Key words: Airways Resistance, Impulse Oscillometry Respirology (2000) 5, (Suppl.) Following abrupt removal of a brief respiratory stimulus, there is a slow decline in ventilation back to resting levels known as ventilatory afterdischarge (VAD). VAD has been proposed to stabilise breathing patterns and has been shown to be reduced in patients with Obstructive Sleep Apnea (OSA). Theoretically, it would appear a slow decline in upper airway dilator muscle activity would be necessary to accompany the VAD, to prevent upper airway collapse during this time. The purpose of the current study is therefore to investigate if such an upper airway afterdischarge exists and to compare its decay to that of an inspiratory pump muscle. METHODS: Healthy volunteers (n=7 to date) were exposed to multiple 45 second periods of hypoxia (9% 0 2 in N 2 ) abruptly terminated with one breath of 100% 0 2 . Ventilatory, inspiratory diaphragmatic and genioglossal muscle responses were measured during and after this intervention. The half times of decay were calculated for each variable. RESULTS: The mean of 63 trials are reported. The half time of decay in minute ventilation, diaphragmatic and genioglossal activity was not significantly different at 9.1 (2.3 (SEM)), 8.4 (2.4) and 9.3 {2.8) seconds respectively (p>0.05). CONCLUSIONS: Preliminary analysis of this study shows a slow decline in upper airway dilator muscle activity concurrent with the VAD, suggesting that upper airway afterdischarge exists in healthy volunteers. The time course of this decay appears to be of similar magnitude to that of VAD. If the upper airway afterdischarge is proportionately less than VAD in any situation or in any patient group, then the upper airway would theoretically be more prone to collapse. Investigation of this phenomenon in OSA patients, during sleep and between men and women is therefore important. Normal subjects can rate magnitudes of added resistive loads at rest and on exercise. Aim: To investigate if, during sub-maximal steady-state exercise normal subjects can estimate the magnitude of added inspiratory loads on the first or second breath after presentation and the effects of these loads on inspiratory flow. Methods: 12 normal subjects (6F: aged 20-21yr) were studied. Exercise levels of 33 and 66% of maximal ventilation (VE) were obtained from a maximal treadmill test (Balke protocol). At rest, at 33% and at 66% VE, resistors of A) 0, B) 0.3, C) 0.7, D) 1.3, E) 2.5 and F) 5.0 cmH 2 0-1.s were each presented 10 times, for 2 breaths, in a random order. Subjects estimated the magnitude of the resistor using a digital 100 mm visual analogue scale (VAS). Data were compared at rest, 33% and 66% VE using ANOVA and are given as mean± sem in the form (Rest: 33%: 66%). Results: There were significant differences (p<0.01) in VAS scores between exercise levels for resistors D (13.4 ± 2.3: 17.4 ± 2.7: 26.6 ± 3.5 mm) and F (42.3 ± 6.1: 50.4 ± 6.7: 60.4 ± 6.4 mm) but not B. Flow rate {l.s·1) significantly decreased {p<0.05) on the first breath after presentation for resistor D (33%; 1.0 ± 0.04 to 0.8 ± 0.05: 66%; 1.1 ± 0.06 to 0.87 ± 0.07) and F (33%; 1.09 ± 0.11 to 0.57 ± 0.09: 66%; 1.06 ± 0.11 to 0.64 ± 0.08). The likelihood of detecting a resistance on the first breath was greater from 0.7 cmH 2 0·1.s upwards on exercise. Conclusion: In normal subjects, steady-state exercise at 33% or 66% VE significantly influences estimation of the magnitude of added inspiratory resistances and decreases inspiratory flow of the first breath after presentation. The load is more likely to be detected on the first breath than the second at higher resistances. Impulse oscillometry (IOS: Jaeger) is a rapid, non-invasive method of estimating central resistance (R 5 ), peripheral reactance (X 5 ) and respiratory impedance (Z,) at a frequency of 5Hz during tidal breathing. Aim: To determine ii there is a relationship between R 5 , X 5 and Z, to the 1 s forced expiratory volume (FEV 1 ), forced vital capacity (FVC) and the FEV 1 /FVC ratio. Methods: 76 subjects (48M: 28F) aged 16 -82yr (mean 56.3 yr) were studied. All measurements were made in the upright sitting position. Estimates of R 5 , X 5 and Z, were made during resting tidal breathing over a 30s recording period. Measurements of FEV 1 and FVC were obtained using a wedge-bellows spirometer (Vitalograph, UK), with the highest value for each index obtained from three technically acceptable attempts being used. Relationships between each spirometric index and R 5 , X 5 and Z, from IOS were obtained using regression analysis. Results: Mean± SD values of FEV 1 were 1.9 ± 0.9 /, FVC were 2.95 ± 1.1 /, FEV 1 %FVC were 62.2 ± 13.1 (range 28% to 78%), R 5 were 0.54 ± 0.29 kPa.1-1 .s, x 5 were -0.25 ± 0.24 kPa.1-1.s and Zr were 0.59 ± 0.37 kPa.1-1.s. There were significant (p < 0.001) linear relationships between the spirometric indices and R 5 : Extracorporeal Membrane Oxygenation (ECMO) is a technique that when used appropriately, is often lifesaving. We describe the first recorded case of its use in pregnancy. Case: A 29 year old woman presented to a hospital with a 2 day history of dyspnoea, malaise and fevers. She was 25 weeks pregnant and had a past history of mild asthma. A chest X-ray showed bilateral consolidation, and she was admitted with a diagnosis of pneumonia and asthma. She deteriorated rapidly over the next day and had to be intubated. Despite full mechanical ventilation and paralysis her oxygen saturations were < 80%. It was felt that she should be transferred to a tertiary hospital for specialised obstetric care. To facilitate her transfer and improve her oxygenation it was decided that she should be commenced on ECMO. This was done and within 1 O minutes her saturations had improved remarkably to 99%. She was transferred without incident. Her condition stabilised and she was weaned off ECMO after 3 days and extubated several days later. She went into spontaneous labour at 30 weeks gestation. 3 months later mother and baby are in good health with no residual problems. Discussion: ECMO has been used for almost 30 years. It has been used extensively in the treatment of re)lpiratory failure in neonates, with survival rates of> 80%. In adults it has not had such a good reputation and until recently has been regarded as being fairly unsuccessful, with survival rates of < 10%. However, improved techniques and in particular better patient selection, have resulted in recent survival figures being reported as 60-70%. ECMO should be considered for young patients with acute reversible respiratory failure who have a 90% mortality risk with conventional treatment, as calculated by pulmonary compliance and vascular shunt measures. Its use in this case saved two young lives. ECMO is also a way of guaranteeing oxygenation when transferring highly unstable hypoxic patients. Several small studies have reported uniform success in transporting such patients. Portable machines are available that will fit inside an ambulance. There have been reports of ECMO in post partum patients but this is the first documented case of its use in pregnancy. Key words: ECMO, pregnancy, respiratory failure, transport C. Deaton (2), K. Lee (2), C.J. Spokes (2), G. Laszlo (1) We have observed that inspiratory flow significantly decreases on the first breath after the presentation of a resistor. The number of breaths needed to adapt to the presence of a resistor at different workloads has not been studied. Aim: To investigate ii, during sub-maximal steady-state exercise, inspiratory flow and pressure returns to pre-load values within 5 breaths of presentation. Methods: 6 normal subjects (3F: aged 21-22yr). An exercise level of 33% of maximal ventilation, obtained from a maximal treadmill test, was used and resistors of A) 0, B) 0.3, C) 0.7, D) 1.3, E) 2.5 and F) 5.0 cmH 2 o-1.s were each presented 10 times, for 5 breaths, in a random order. lnspiratory flow (l.s-1) and mouth pressure (cmH 2 0) were recorded throughout. Results: There were no significant effects on flow or pressure with resistors A or B. For resistors C to F, inspiratory flow significantly decreased (p<0.01) on the first breath alter presentation and had not returned to baseline after 5 breaths. lnspiratory pressure significantly increased (p<0.001) on the first breath after presentation and remained significantly greater than baseline after 5 breaths. Data are shown for resistor D as mean±sem. Conclusion: In normal subjects, inspiratory resistors of 0.7 cmH 2 0 and above significantly influence the inspiratory pressure and flow during steady-state exercise at 33% maximal ventilation. These changes indicate that adaptation, mainly through changes in inspiratory pressure occur in order to maintain an adequate tidal volume. Muscle sympathetic outflow is greatly elevated in awake patients suffering from the obstructive sleep apnoea syndrome (OSAS), with the increase in multi-unit burst activity being similar to that seen in congestiye heart failure (CHF). To increase our understanding of the neural mechanisms of sympathoexcitation, single-unit activity of 12 muscle vasoconstrictor neurones (recorded via tungsten microelectrodes in the peroneal nerves of 6 OSAS patients) was compared with that ol 16 neurones recorded in 8 CHF patients and 33 neurones recorded in 14 healthy controls (CTL). For both groups of patients the mean firing rates and firing probabilities were significantly higher than in the controls (Table) . However, while the percentages of cardiac intervals in which neurones generated 1, 2, 3 or 4 spikes were statistically identical in CHF and CTL, the OSAS patients generated significantly fewer solitary spikes and more double spikes. These firing properties were identical to those generated by 9 neurones during acute increases in sympathetic drive (inspiratory-capacity apnoea) in 5 controls. We conclude that the sympathoexcitation associated with OSAS differs from that of CHF, perhaps due to an acute sympathetic drive related to the resting hypopnoea in OSAS. Normal' lung function in rural Australian Aborigines RECRUITMENT IN THE CHILDHOOD ASTHMA PREVENTION STUDY (CAPS} Seema Mihrshahi1, Nicola Vukasin1, Samantha Forbes1, Craig Wainwright2 William Krause2 and Gabrielle Prater1 for the CAPS Team New Children's Hospital, Westmead, NSW 2145 2Department of Respiratory Medicine Clinical Epidemiology Unit Royal Melbourne Hospital Parkville, Victoria 3050. (2l Department qi Respiratory Medicine. Austin & Repatrjatjqn Medical Centre Heidelbera, Victoria 3081 (31 Respiratory Medicine Alfred Hospital Acknowledgements: Boehringer lngelheim, John Clarke-Advanced Biomedical, Victorian Tuberculosis and Lung Association, Contributing Centres Acknowledgements: Wines for these studies were kindly donated by Hardys BRL. Key words: Asthma, wine, sulfites. Acknowledgments: Sr D. Gillan Heparin is a glycosaminoglycan found naturally in mast cells and is rapidly inactivated by macrophages in the circulation. As an immunomodulatory agent heparin reduces the acute cutaneous reaction to allergens and inhibits bronchospasm in asthma. We studied the effect of this potentially useful therapy on pulmonary inflammation in CF. Methods: 4 adult CF patients (2 male, mean age 23 (18-25)) chronically colonised by Pseudomonas aeruginosa with stable disease and no history of past severe, or recent haemoptysis inhaled heparin 1000 units/kg/day as a single nebulised dose for 1 O days. Lung function and sputum samples were assessed at baseline and after the first dose, then again on Day 5 and 1 O of therapy. APTT levels were performed on Day 5 and 1 O. IL-8 in sputum supernatant was measured by ELISA. T-tests compared FEV1, FVC and IL-8 levels in sputum. Results: One patient had mild haemoptysis on Day 7 and ceased treatment. APTT remained in the normal range in all patients. There was no significant change in FEV1 or FVC (% predicted) between baseline and all subsequent measurements (p>0.2). IL-8 levels in sputum were extremely high (maximum 200ng/ml). There was wide intra-individual variation in IL-8 levels detected in sputum samples. No significant difference in IL-8 levels was demonstrated during or after heparin therapy (p>0.18). Riha. RL Rafter. LE Slaughter. RE Oliver WA The Prince Charles Hospital Queensland. Australia Background: CT has been established as the most accurate method for guiding fine needle aspiration (FNA) biopsies of intrathoracic masses, thereby allowing for cytological delineation of malignant from nonmalignant lesions. In January 1997, a database was established at a tertiary referral hospital specialising in cardiothoracic disorders to assess procedural outcomes and to quantify individual risk. Method: During a 2.5-year period (01.01. 1997 -30.06. 1999) , 315 FNA biopsies were performed on 312 patients (202 males, 11 O females) . Biopsies were performed with 3-5 mis of 1-% lignocaine injected into skin. A Greene 19g-biopsy needle was used under CT guidance and samples aspirated via a finer gauge needle passed through the outer needle. Data were recorded at the time of patient referral and procedure and were followed up. Results: The mean age of patients was 65+12.4 yrs (range 19. 1 -89.7yrs ). Forty-nine (16%) patients were aspirin/NSAIDs; 11 (3.5%) on anticoagulants. Diagnostic material was obtained in 72.7% of samples. Lung cancer represented 201 samples (96% NSCLC, 4% SCLC). Other malignancy was diagnosed in 22 (7%) cases. Cellular atypia was evident in 17 (5%) cases. Benign lesions were diagnosed in 6 (2%) cases. Non-specific features characterised 71 (22.5%) samples. Eleven aspirates proved false-ve and 4 false+ve for malignancy. The only complications recorded were pneumothorax in 40% of cases (17% requiring ICC) and haemoptysis in 3 cases. The mean % predicted values for FEV1 , VC and KCO did not correlate significantly with risk of pneumothorax. Conclusions: CT-guided FNA biopsy continues to be a reliable method of diagnosing intrathoracic lesions, thereby reducing the need for diagnostic thoracotomy. Diagnostic accuracy is high in lung cancer, though negative results do not preclude malignancy. Benign cytology may be of use in a clinical contex1 but is rarely useful in establishing a diagnosis. Pneumothorax, though a frequent complication, is significant in a relatively small number of patients. FR Lake (1), S Chapman (2), G Ryan (3), R Scicchitano (2), M Wilsher (4) (1) Evidence supporting the use of drugs in the treatment of CFA is limited with no placebo controlled trials being performed. More recently, HRCT has helped stratify patients into those with a poorer prognosis and poorer response to treatment (honeycombing on HRCT vs ground glass changes). However as the prognosis is poor, many physicians feel a need to treat patients with CFA. Methods: Using a postal questionnaire, respiratory physicians in Australia and New Zealand were asked about treatment of CFA using an example case of fibrotic CFA. The patient was a 65yo man with moderate symptoms for 6 months, exercise limitation to 1 OOm, moderately impaired lung function (50% predicted) and honeycombing on HRCT. Results: 168 responses to the questionnaire have been received. In regard to the sample case, 74% of respondents would recommend treatment following the results of initial investigations, while a further 23% would start treatment if there were a decline in symptoms or lung function. Only 3% would never commence treatment, the reasons being fibrosis on HRCT and lack of evidence for effectiveness of treatment. Of the 163 who would consider treatment, the majority (76%) would use Prednisolone/Prednisone (Pred) alone as initial therapy, 15% Pred/Cyclophosphamide and 6% Pred/Azathioprine. In addition, 3% would use methylprednisolone in the initial phase. If the patient deteriorated, the most common alternatives (>25% of respondents) considered were azathioprine, cyclophosphamide, cyclosporin and colchicine. Conclusions: A pro-active approach to treatment of a hypothetical case of fibrotic CFA is demonstrated in Australia and New Zealand. This may reflect the lack of good evidence supporting or refuting the role of therapy in CFA and a poor prognosis in this disease. Key words: Cryptogenic fibrosing alveolitis, drug therapy, questionnaire. J Malone, J Burdon, R Brownlee' Departments of Respiratory Medicine and Radiology', St Vincent's Hospital, Melbourne Background: Amiodarone toxicity is an unusual cause of diffuse parenchymal lung disease.Case studies: A series of four cases is presented, for which causation was either proven on biopsy or strongly suggested by clinical features. The clinical.radiological and histologic features are described in detail, and for three patients, serial respiratory function testing is reported. In all cases, a mixed alveolar and interstitial infiltrate was present. One case had severe hepatitis, and was also notable for the presence of marked peripheral blood eosinophilia. This patient developed pulmonary fibrosis and still required domiciliary oxygen five months after cessation of amiodarone.The remaining patients had complete resolution of their pulmonary infiltrates, however two had reduced carbon monoxide transfer documented at the end of the follow up period. Three patients were treated with corticosteroids. In the' remaining case.corticosteroid therapy was contra-indicated by low grade pulmonary infection and poorly controlled diabetes. This patient, nevertheless, had an excellent outcome. Comment: Amiodarone pulmonary toxicity is a rare event and needs to be considered in all patients treated with this drug. A review of the literature is presented, with recommendations for screening. James LeighResearch Unit. National Occupational Health and Safety Commission Sydney 2001 and Department of Thoracic Medicine Concord Hospital Sydney 2139 Between 1945 and 1980, 658 (535 male, 123 female) cases of malignant mesothelioma were identified in Australia and the condition was regarded as rare.Since 1981 Australia has maintained a complete national register for cases of malignant mesothelioma. This is a specific disease register with histologically confirmed notifications accepted from clinicians and medical records administrators. Cross checks using patient identified data are regularly carried out with all State cancer registries in Australia. Incidence has increased rapidly and is still increasing in both males and females. In 1999 the extrapolated annual incidence rate was 6.6 per 100,000 (male >20/year) (1982-85: 2.7) and 1.6 per 100,000 (female >20/year) (1982-85: 0.325) . Therefore, incidence rates are similar to bladder cancer in males and uterine cancer in females. As at 3 December 1999, there were 5806 cases in Australia, almost all of them fatal. Pleural:peritoneal ratio was found to be 18:1 (male), 6:1 (female). Positive asbestos exposure history was obtained in 85% of cases. Mean latency from first exposure was 37 years. Common exposure histories were: repair and maintenance of asbestos materials (13%), shipbuilding (3%), asbestos cement production (4%), railways (3%), power stations (3%), boilermaking (3%), Wittenoom (5%), wharf labour (2%), paraoccupational, hobby, environmental (4%), carpenter (4%), builder (6%), navy (3%), plumber (2%), brake linings (2%), and multiple (12%). The pattern of exposure is shifting away from the older traditional industries towards product, domestic and environmental exposure. The incidence is still increasing and assuming peak amphibole exposure occurred about 1965 and peak chrysotile about 1975, peak incidence is not expected until about 201 0. These incidence rates are the highest national rates in the world. The estimated number of cases still to occur in Australia is about 10,000 by 2020. The International Labour Organisation classification of radiographs for the pneumoconioses is awalidated, economical and clinically & epidemiologically extremely useful tool in assessing for the presence and progression of asbestosis (Hilt et al 1992) . The correlation between the ILO classification and functional parameters is however modest. The most densely corcentrated zone determines the profusion score without regard for heterogeneity among the 6 radiographic zones thus it may not accurately represent the true disease burden. AIM: To examine the correlations between ILO score for small-opacity profusion and parameters of functional impairment (%predicted FVC, %predicted DLCO and %predicted V02max) with and without a correction for profusion heterogeneity. METHOD: Two scorers (GBM & AWM) independently classified CXRs from 52 patients with asbestosis assigning profusion scores for each separate zone individually. The sum of the six zones' scores was averaged to provide a "corrected for heterogeneity" ILO score per radiograph.Each radiograph was also scored by conventional ILO criteria. The "corrected" and conventional profusion scores were then tested for correlation against ventilatory function, gas exchange and exercise test results for these 52 subjects. RESULTS: ILO Flow resistive work of nasal breathing (WONS) and nasal power (NP) values are known to be consistent, subject specific, predictors of the 'switching point' ventilation from nasal to ore-nasal breathing during exercise. Methods: To investigate the relationship between NP and nasal ventilation (V) within an individual subject, we studied 13 healthy, adult subjects (6 males, 7 females; age: 27.8(6.2 SD) yrs); who performed a progressive, graded exercise task (30 to 140-230 watts in 2 minute, 30 watt steps) on a cycle ergometer while breathing only via the nose. Tidal volume (Vr) was monitored using an integrated nasal airflow signal obtained with a nasal mask and pneumotachograph. Trans-nasal pressure was calculated as the difference between nasal mask pressure and Oro-pharyngeal pressure (measured using a stoppered mouthpiece, with no flow in a patent oral pathway). lnspiratory WONS Qoules per breath, mean of 5 steady-state breaths) was measured by planimetry from pressure-volume plots constructed from the trans-nasal pressure and Vr data at each level of exercise. lnspiratory NP was calculated as inspiratory WONS x respiratory rate (i.e. joules/sec or watts) and increased progressively with exercise. The relationship between NP and V for each subject was mathematically fitted using the function NP=aVb (where a and b are constants, R 2 > 0.91 ). Recently, we demonstrated for the first time that asthmatic patients spontaneously breathe exclusively via the nasal route when asymptomatic but switch to oro-nasal breathing during an acute exacarbation. We have now examined the sensitivity to external inspiratory nasal loading for switching the route of breathing in asymptomatic asthmatic patients (6 females; age= 31.8(11.7 (SD) yrs; FEV1 = 83(4.2) % predicted), and healthy subjects (2 females, 2males; age = 31.0(13.5) yrs; FEV1 = 101 (14.8) % predicted). Methods: Subjects breathed via a dual compartment face mask with attached nasal and oral pneumotachographs. Starting with exclusive nasal breathing, subjects inspired via a one-way valve connected to a chamber in which a constant negative pressure (inspiratory load) was maintained. Progressively increasing external loads were applied until subjects spontaneously switched to ore-nasal breathing. The external load at which this occurred was termed the 'switching load'. Standard posterior rhinomanometry was subsequently employed for measuring nasal resistance at the 'switching load'. The total nasal resistive load (NRL) was calculated as the sum of the 'switching load' resistance and nasal resistance (at 0.4 1/sec inspiratory flow). Results: The 'switching load' for the healthy subjects was -5.5 (2.1) (SEM) cmH 2 0 and tended to be lower for asthmatic patients (-3.5 (0.7) cmH 2 0), although this difference did not achieve significance (p=0.3, unpaired \-test). However, the NRL for healthy subjects was 6.3(2.03) cmH 2 0/1/sec and did not differ from that for the asthmatic patients (6.0(1.9) cmH 2 0Nsec; p=0.9). Conclusion: The total NRL at which asthmatic patients switch to oro-nasal breathing is not different from that at which healthy subjec~s switch. Thus, asymptomatic asthmatic patients do not appear to demonstrate enhanced sensitivity to switching of breathing route in response to increased nasal loading. (± 9.0) weeks with the MAS was associated with a small improvement in daytime somnolence (mean Epworth Sleepiness Score 12.0 ± 4.9 c.I. 9.9 ± 3.1, p = 0.07) and significant side effects. 15 patients (83%) reported difficulty using the MAS and 38% use the device for less than 3 nights a week. CONCLUSION: The use of the MAS resulted in a small but statistically significant reduction in indices of OSAS. A significant number of patients had difficulty tolerating the device with 38% failing to achieve satisfactory compliance. Respirology (2000) Background. The anatomical dead space (VD) represents the luminal volume of the conducting airways not involved in gas exchange. Its measurement, using a single-breath nitrogen washout technique, is influenced by initial lung volume and the pause between inspiration and expiration of the test gas. It is unclear whether the flow rate of the expired gas influences VD. Alm. To measure the VD at varying expiratory flow rates on different days in normal subjects and determine whether a suitable range could be found that would provide consistent VD values. 1 Methods. 2 male subjects were recruited, aged 42(TD) and 29(PW). They had no history of respiratory disease. A modified Fowler's method utilised a single-breath nitrogen wash out after oxygen inhalation to measure VD. Subjects exhaled to FRC then inhaled 1L of 100% oxygen from a reservoir bag at about 0.5Usec. After an inspiratory pause of less than 1 second the expired volume and nitrogen concentration were simultaneously recorded. The VD was taken as the volume that coincided with the arithmetic mean of the phase II slope of the nitrogen washout curve. The procedure was repeated at varying expiratory flow rates on 4 different days. Results. Subject TD had 63 readings taken with an expiratory flow varying from 253ml/sec to 1278ml/sec. VD ranged from 188-372ml. PW had 52 readings with flow varying from 264-1231 ml/sec. VD ranged from 191-396ml. VD did correlate with expiratory flow in both subjects (R2 0.82 for TD, R 2 · 0.90 for PW). VD values between flows of 350-700ml/sec were relatively consistent. Over the 4 days TD averaged 255ml (range of averages 249-262), coefficient of variation 9.9%. PW averaged 242ml (233-250), coefficient of variation 8.8%. Conclusion. Expiratory flow rates do alter VD and need to be controlled. The lower VD at slow flow rates probably results from increased time for mixing at the interface. The larger VD at higher flows is probably artifactual. Using the arithmetic mean for VD calculation may introduce error. We also compared the reproducibility of FVC and FEV 6 . Methods: We analysed data from consecutive patients referred to our laboratory for spirometry. FEV 1 /FVC was compared with FEV 1 /FEV 6 and FEV 6 with FVC. Results: Compared to FEV 1 /FVC using FEV 1 /FEV 6 the sensitivity for obstruction was 94.6% and for restriction 92.6%; the specificity for obstruction was 97.4% and for restriction 100% The intra-subject coefficient of variation was 3.4 for FEV 6 & 4.5% for FVC. Conclusions: FEV 6 is more reproducible than FVC and is an acceptable alternative to FVC for diagnosing airway obstruction. FEV 6 is a good spirometric predictor of a restrictive pattern.Key words: Spirometry, reproducibility, obstruction, restriction. The mean (sd) heart rates before arterial puncture were BB (11.5) with placebo and B5 (13.2) with AnGel (p= 0.5), and after the puncture were 89(13.4) and B4(13.6) respectively (p=0.4). Twelve subjects in each group said that they would prefer to have gel applied next time they had an arterial puncture. Two subjects in the placebo group reported slight tingling sensation at the site of the puncture after the procedure. Conclusion: Local AnGel is not effective in the reduction of pain during arterial puncture when applied for 30 minutes prior to the procedure. This is an important finding suggesting widespread use of local anaesthetic in this setting is not justified. Key words: arterial puncture; local anaesthetic. The SASQ was able to be completed by patients, produced low scores in normal people, had different scores between people with and without OSA, and had poor correlation with ROI and Al, but good correlation with ESS and MAP. It was answered reliably and was responsive when OSA was treated. Key words: sleep apnoea, questionnaire. A Wright', H Nie12, A Ramsden2, P Holmes', N Freezer1. 1.Monash Medical Centre Clavton, Victoria Australia.2.Ritchie Centre, Monash University. Noninvasive positive pressure ventilation (NIPPV) can effectively treat patients with acute respiratory failure. However, the performance of the NIPPV ventilators at high respiratory rates has not been described. AIM: To examine and compare the performance of NIPPV ventilators across a range of respiratory rates. METHOD: A spontaneously breathing respiratory model was built and connected, in turn, to 4 different ventilators capable of providing NIPPV. They are designated ventilator A, B, C, D. Each device was set up in a spontaneous mode to deliver, when triggered, an inspiratory pressure of 1 O cmH 2 0 and an expiratory pressure of 5 cmH 2 0. The respiratory model breathed at respiratory rates between 1 O and 50 breaths per minute. The respiratory model was similar to a normal thorax, having a compliance of 100 ml/ cmH 2 0 and a resistance of 2.4 cmH 2 0.sec.L-1, but different in that the inspiratory to expiratory rate was fixed at a ratio of 1 :1 and that both phases of respiration were active. RESULTS: 4.6 5.6 6.4 7.5 9 CONCLUSION: As the respiratory rate increased beyond 30 breaths/min. the devices failed to deliver effective bilevel ventilation. Key words: Noninvasive ventilation, ventilator performance, respiratory model. We undertook a retrospective review of 35 (20 men, 15 women) consecutive neutropenic patients with pulmonary infiltrates who failed to respond to conventional neutropenic antibiotic protocol. These patients were referred for bronchoscopy with washings, brushings, lavages and bronchial biopsies obtained. The age range was 17-77 years, with the commonest cause for neutropenia being chemotherapy. The mean duration of neutropenia and antibiotic therapy was 14 days (2-40 days) and 11 days (1-40 days) respectively. The yield from all types of specimens was low. The extent of the radiological involvement did not influence the yield. The commonest results obtained were growth of bacteria and fungi which were difficult to interpret without a histological correlation. The procedure overall impacted on the management of 8 patients. It was useful in excluding an infective cause and allowing rationalization of antimicrobial therapy in non critically ill patients but was disappointing in aiding the management of the critically ill where mortality remained high. However, the procedure was safe with a low complication rate despite the presence of hypoxaemia and thrombocytopenia. Open lung biopsy provided a diagnosis of pneumocystis in 2 cases when bronchoscopy was negative. In conclusion, bronchoscopy in this setting proved to be disappointing even with lavage specimens in identifying an infectious cause. Perhaps in conjunction with the routine use of transbronchial biopsies, we can improve the yield of this procedure and render it a useful diagnostic tool in the management of these patients without the elevated risk of complications which often accompanies other invasive pulmonary procedures. Purified streptokinase is now frequently used intra-pleurally to treat empyema thoracis replacing the older preparation (Varidase™) which contains streptococcal DNase as well as streptokinase. Our clinical impression was that the purified preparation was less effective than Varidase. To investigate whether DNase was contributing to easier drainage of pus we have measured pus viscosity using a simple viscosometer. Pus from three soft issue abscesses drained surgically and from six patients with empyema thoracis was studied. Pus samples were incubated with normal saline (as control) and with streptokinase, Varidase, human recombinant DNase (Pulmozyme™) and a mixture of streptokinase and Pulmozyme.Purified streptokinase had little effect on pus viscosity with mean reduction of 11 . DNase thus significantly reduces pus viscosity whereas streptokinase has little effect and may work simply by breaking down loculations in empyema thoracis. Combining streptokinase with DNase may be of clinical benefit in empyemas where pus viscosity is high. Treatment of empyema thoracis with fibrinolytic enzymes if simple tube drainage fails is increasing in popularity. Recent work 1.2 suggests that streptokinase may break down fibrinous loculations in empyemas but has no effect on pus viscosity whereas DNase does reduce pus viscosity and may facilitate drainage.An 82 year old lady presented with pneumococcal pneumonia and subsequently developed an empyema. Treatment with intravenous antibiotics and intercostal tube drainage for five days failed to improve the empyema and a second intercostal drain was inserted. Streptokinase in standard doses (250,000U daily for 3 days) was instilled into the pleural cavity but the empyema persisted. The patient refused surgical intervention. She was treated with intrapleural human recombinant DNase 5mg daily for 3 days. This resulted in drainage of further 700ml of pus with clinical and radiological improvement.We believe this is the first use of human recombinant DNase in treating empyema thoracis in man. BACKGROUND: Inhaled hypertonic saline via an ultrasonic nebuliser can be effectively used to induce coughing and sputum production for the diagnosis of diseases of the lower respiratory tract. However the place of this technique in populations with ready access to fibre-optic bronchoscopy (FOB) remains controversial. AIM: To compare sputum induction with FOB in the assessment of patients with lower respiratory tract diseases. METHOD: Induced sputum samples (20mls of 6% saline given as continuous nebuliser) were taken from 16 consecutive patients referred to the primary investigator with one or more of the following two indications for FOB: (a) haemoptysis for investigation (in patients age >40yo, a smoking history and an abnormal CXR) and/ or (b) possible TB (with a significant clinical risk of TB and negative sputum smears). All induced sputum procedures were well tolerated with no adverse effects seen. All patients proceeded on the same day to FOB. The type of specimen taken at FOB was at the discretion of the bronchoscopist. Specimens from both investigations were sent to the same laboratory and were analysed with cytology and microscopy and culture, including AFB. RESULTS: Adequate induced sputum specimens were obtained in 11 of the 16 patients. The FOB included general washings (n=15), brushings (n=10), lavage (n=5), biopsy (n=5). In total 8 patients received definitive diagnoses. 5 malignancies (2 small cell, 2 adenocarcinomas and 1 squamous cell lung cancer), MTB was diagnosed in two patients and an atypical TB was diagnosed in one patient. 7 of these 8 patients with diagnoses had adequate induced sputum specimens. Bronchoscopy diagnosed all 8 cases while the induced sputum technique diagnosed only 2 of the malignancies also seen on bronchoscopy (odds ratio in favour of bronchoscopy = 7:1). CONCLUSION: In our small, heterogeneous group of patients, sputum induction did not provide additional diagnoses to FOB. Key words: Fibre-optic bronchoscopy, sputum induction. In New Zealand and Australia trans-thoracic needle aspiration (TNA) is not a commonly used method of obtaining diagnostic material in communityacquired pneumonia (CAP). Conventional culture techniques usually require more than 24hrs to yield a microbiological diagnosis. Molecular techniques have recently been shown to increase the diagnostic yield by 33% to 44%. Pneumothorax is the most common complication and has been reported in up to 30% of procedures. There is variation in the use of radiological guidance for TNA. Methods: Prospective study of all patients admitted to our hospital with CAP. TNA was performed on patients in whom there were no contraindications and from whom informed consent was obtained. For TNA to proceed certain chest ultrasound features were required. The complication rate of TNA and the patient's perceptions of the procedure were recorded. Results: 84 patients have been enrolled to date. 18 patients were asked to undergo TNA, 13 patients consented, 3 did not meet the ultrasound requirement, 10 patients had TNA. There were no pneumothoraces, 4 patients experienced pain during the procedure, and 1 patient would not have had a repeat procedure. Conclusions: TNA is not associated with an unacceptable complication rate and patients find it an acceptable procedure. TNA in combination with molecular techniques may improve the accuracy and reduce the time to microbiological diagnosis. Key words: pneumonia, trans-thoracic needle aspiration, complications.