key: cord-0009716-ksvx06uj authors: nan title: ORAL PRESENTATIONS date: 2008-12-30 journal: Allergy DOI: 10.1111/j.1398-9995.1996.tb04793.x sha: 668283a79459eb1bb7ed8cd7eb45f75d3cbbe277 doc_id: 9716 cord_uid: ksvx06uj nan asthma can be avoided with proper prior mcdical a r c . At least 40% of asthmatics do not react appropriately to increasiiig asthma symptoms and more than half of the patients admittcd with acute asthma have had alarming asthma symptoms for one wcek prior to admission. In its study of deaths due to asthma in the early 1980s the British Thoracic Association rccommended that patients should measure thcir own pcak flow ratcs and treat deteriorating symptoms themselves. Guided asthma self management consists of efficient patient education and of symptom-and/or peak expiratory flow-bascd patient instructions in early asthma deteriorations. Several studies have shown that educational progrmmes of asthma both increase the patient's skill and improve the general outcome of asthma carc. Although self management practices have been suggested in several asthma guidelines, somewhat conflicting results exits concerning the efficacy of this treatment. Some of the self management studies have been either uncontrolled or have relied on retrospective data analysis. In a recent study (BUT 1996 ;312:748-52) we have compared the efficacy of guided self management of asthma with trational trcatmcnt. This onc year trial of 115 patients with mild to moderately seven disease randomised half of the patients to a traditional asthma care and half to a self management programme consisting 01 education about asthma and daily peak flow readings. The mean number of unscheduled visits to ambulatory care, days off work, and courses of antibiotics and prcdnisolonc per patient were lower in the self-management group than in thc traditionally trcatcd group (0.5 V.S. 1.0, p=0.04; 2.8 V.S. 4.8, p=0.02; 0.4 V.S. 0.9, p=0.009 and 0.4 V.S. 1.0, p=0.006, rcspcctively). In both groups hospitalisations due to asthma were rare and the spirometric values remained completely stable at the schedule visits. One year self management had a superior effec (8 quality of life points, 95% CI 2-15 points) on quality on life compared to traditional treatment. The self mangement was 4.5% more effective @< 0.0001) than the trational treatment in terms of healthy days (defined as day without incidents caused by asthma). Thc dircct health care costs were FIM 649 greater @=0.05) in the self management group, mainly due to the greater costs of counselling. The self management, however, resu!ted in a 2.412 FIM savings @=0.008) in indirect costs per patient and as a result the total costs of asthma (dircct and indirect costs) wcrc 1.762 FIM smaller @=0.09) per paticnt treated during the one ycar study period. Intervention thresholds of ~8 5 % of the optimal peak flow for doubling the dose of inhaled steroid for two weeks and of <70% of the optimal pcak flow for starting a course of oral steroids for one wcek worked well and the adherence of patients to the self management instructions was better than generally expected. There were four elements in our study: carly treatmcnt of deteriorating ainvay inflammation, pcak expiratory flow measurements per sc (changed lifestyle), patient education about asthma and possibly improved general compliancc with treatment. It is not possible to say which of thcsc is most important to the succcss of guided self management of asthma. Successful asthma self management requires a good patientprovidcr relationship and trcatment organization. Flexible access to assessmcnts when needed is fundamental. Sclf management mus not be implcmcntcd in such a way that the atient is left on his or her own after initiation of carc. I ducation and changed attitudesnot only among patients -:.re the prerequisiles for the implcmcntation of asthma self management. Greta Barnes National Asthma Training Centre, Stratford-upon-Avon, United Kingdom. Currcnt guidelines for the management of asthma in both children and adults recommend that most asthma therapy should he given by the inhaled route. Reasons given include that a fast onsct of action is obtained, the drug is delivered straigkl to the site of action, a smaller do.se is reyuircd and there is reduced potential for systemic side cffccts. In asthma, nebulisers arc uscd chiefly for the delivery of large doses of bronchodilator drugs or for patients who cannot use other devices. Pressurised mctcrcd dose inhalers (PMDIs) are the most commonly used devices being quick to use, compact, portable, multidose and cheap. However, unless the breath actuated version is uscd inhalation technique is not easy. The PMDI with spacer has all the practical advantages of the PMDI and is not difficult to use but is bulky. Dry powder devices (DPIs) arc generally easier to use than the conventional PMDI although there are differences between individual ?PIS in their efficiency in achieving pulmonary deposition. Clinicians are frequently encouraged to prescribe a specific therapy. Insufficicnt time may be spent considering an appropriate device for the patient which is often as important as the therapy to he prescribed. There arc numerour devices on the market at present and choice should he made with caw. 'Cheap' does not necessarily equal 'cost effective'. To aid compliance health profcssionals should not only considcr the treatment and device prescribed but should also explore the patient's health beliefs and attitude towards their condition. Modem asthma management has demanded a new approach with emphasis on the importance of developing a special anticipatory and organisational long-term approach. Patient assessment, education and follow-up is a continuing process. To improve compliance it is important to make sure the patient knows that he or she is at risk and to give them reassurance that their treatment is both safe and effective. Cost effectiveness in asthma therapy, Germany, It is now widely acknowledged that the pathology of asthma is predominantly an inflammatory process of the bronchial m u m a with smooth muscle contraction secondary to airway inflammation. The conccpt of airway inflammation in asthma and its control by anti-inflammatory therapy has provided more precise aims and the idea of long-term care for both adults and children. In general regular anti-inflammatory treatment reduces in tendency of the bronchi to respond to any endogeneous and exogeneous stimulus. A decreased bronchial hyperresponsiveness may help to diminish asthma exacerbations, nocturnal asthma, diurnal variations in lung fucnction, continuing symptoms and hospital admissions. Thus, an adequate managment of asthma may prevent long-term risk disease by that providing high cost effectiveness. With respect to long-term effects of prologed treatment with steroids questions many raise whether physicians can be sure that this treatment in entirely free of any advers effect, in particularon asthma itself. In literatur, for example, a lack of imfomation is found on which minimal dose of medication is required to contol asthma by that avoiding side effects and reduced cost effectiveness. Our understanding of asthma and its therapy has grown significantly over the two last decades. However, there is evidence that asthma is not well controlled in many patients. Numerous specialists state that hospital admissions and visits to emergency departments may reflect failures of primary preventive carc for asthma of out-paticnts. It is bclicved that specialist care allows greater cost effectiveness and the focusing of clinical cxpertise. However, in medical systems with tiered patient care the cooperation bctween specialists in out-patient clinics and gcncral practitioners is needed. Yet, there are grap of communication between specialists who arc well cxpcrienccd in asthma disease and general practitioners less educatcd in asthma who scc the patient not rarely at times of crisis. So, therc may be a great deal of improvement necessary in the care of asthma by general practitioners. ln the future it must be in primary care that thc really important improvement must take place. It could improve cost effectiveness because it should be more effective in reducing loss of work and hospital admissions and should be probably administratively cheaper. However, the most important task is patient education. Patients must learn what asthma is and what it means to be a chronic discasc. Patients and their families may lcarn that they can manage asthma effectively and, in most cases, live active lives. They need to be able to follow instructions and comply with treatment rccornmendations, Although these aspects of patient education have recieved more attention, research suggests that many patients emerge from their contacts with physicians ill prepared to carry out treatment plans. Many findings underline that physicians need better education themselves in the key skills needed for asthma management. The subject of cost cffcctiveness of modem asthma treatment is full of difficulties because the various factors underlying it differ from one country to another. The baqt to be done is to examine the broad picture and thc various factors which can be modified. Management plans must be tailored to meet individual paticnt needs and wherever possible should be practical ddd easy to maintain long term. The European Academy of Allergy and Clinical Immunology (EAACI) and the European Society of Pediatric Allergy and Clinical Immunology (ESPACI) have each published in 1995 a supplement of the present knowledge of adversc reactions to foods and their diagnostics. (1) (2) EAACI has proposed a new classification of adverse food reactions into toxic and nontoxic reactions. Non-toxic reactions include non-immune mediated reactions, i.e. food intolerance, and immune mediated reactions, i.e. food allergy. Allergic reactions can be either I&or non-lgE-mediated. Double-blind, placebo-controlled food challenge (DBPCFC) is widely acccpted as the most reliable method in the diagnosis of adverse reactions to foods. Demonstration of food-specific IgE antibodies either with RAST or skin tests refers to I@-mediated food allergy. In i n h t s unda the age of 1 ycar the tests suggest a relevant food allergy, because at this age it is more difficult to detect specific IgE, and the secondary development of tolerance has hardly taken place yet. (3) In older children the relevance of RAST and Skin test has to be confirmed by DBPLFC. In spite of the large amount of new knowledge on the field, the basic mechanisms of adverse reactions to foods are still poorly understood. The lack of standardized food antigens for the skin tests causes also difficulties. DBPCFC, with which all other tests are compared, is called the gold standard of diagnostics but remains itself unstandardized.(4) Especially delayed rcadions in food allergy are poorly understood. Confusion arises also from the fact that food allergy in infants, children and adults are being described simultaneously, although food allergy in infants is condidercd the main cause of atopic cczema, while in older persons there arc several pathogenctic mechanisms that may lead to the clinical picture. Allergy to basic foods like milk, egg, soy, cereals, fruits and vegetables is often discussed simultaneously, although thc nutritional role of milk and apple, for instance, is strikingly diffferent in infants. Also allergy to milk, egg, etc. has a favourable prognosis during the first 2-3 years of life, whereas allergic reactions to h i t s and vegetables in pollen-allergic p p l c tend to be permanent. R h b e n et a1. (5) have studied the applicability of skin prick test (SPT), basophil histamine release test, patch test and lymphocyte proliferation test in atopic children with either immediate or delayed cutaneous symptoms upon oral challenge to cow's milk. They showed that tests and lymphocyte proliferation tests were more often positive in children exhibiting delayed type reactions, whereas SPT and basophil histaminc release test were more often positive in children with immediate oral challenge reactions to cow's milk. Isolauri and lhjanmaa (6) confirmed this results in 183 patients with atopic eczema. Open and DBPCFC tests of one week's duration cach to cow's milk were pcrformed in all children (age 2-36 months), and both challenge types were positive in 54%. Jmmediate challcngc reactions appcared within 60 min from the beginning of the challenge and delayed-type symptoms within 34 hours on averange. SPT was positive in 48% and patch test in 61% of milk challenge-positive children. In patients with negative oral challcngc to cow's milk, SPT was positive in 16% and patch test in 18%. Sensitivity of SIT alone was 48% only, but with concomitant patch tcst it was a high as 86%. Acutc reactions to oral milk challenge correlated wcll with positivity in SPT, whereas delayed reactions were more often seen in patients with positive patch tests. The patch test panel for food allergy testing in our clinic has included also lyophilized egg, soy, whcat, ryc, barley and oats during thc last two and a half years in the diagnosis of all children under 2-3 years with atopic eczema or gastrointestinal symptoms. In SPT, ordinary flours have been used as test material. Positive SPT to wheat was found in 36% and patch test in 74% of 143 milk challenge-positive children. In 129 milk challenge-negative children, SF' T to wheat was positive in 26% and patch test in 64%. (7) These results suggcst that cereal allcrgy has bcen largcly neglwted. Similar results were published recently by Suomalainen et al. (8) . We have found an extensive panel of skin tests to help select suitable diets for infants to get them symptomless for challenge tests. Hannuksela (9) recommended division of food-allergic peoplc into three different age groups according to the time of appearance of symptoms: 1) infants undet 1 ycar of age, 2) older children and 3) adults. When symptoms appear for the first time during the first year of life, it is probable that the basic foods are responsible When they appear at 1-2 year or later, chocolate, cocoa, citrus fruits, lemonades and candies often end to be responsible. In children and adults with birch pollen allergy, fruits and vegetables often cause symptoms deaibed as oral allergy syndrome. Adults with atopic eczema are seldom suspected to being allergic to basic foods. This should, though, be the case when cczema is chronic and does not disappear cven in summer. Milk, fish and mreal allergy may occur, but the diagnosis is difficul. DBPCFC should be done for one week each under othcnvisc constant conditions, but there are many practical problems with adults, the psychological aspects not being the least. Therefore food allergy in infancy should be properly diagnosed and treated by dictary mcans until tolerance has developed, hoping that later symptoms could be diminished. The delayed-type allergy to foods may also be an IgE-mcdiatcd allergy, even in cases with low total IgE and no detectable specific IgE to foods. Thc reactions may occur via high-affinity IgE receptors expressed on Langerhans and dendritic cells leading to allergcn-specific T cell responces capable of promoting IgE production and delayed-type hypersensitivity reactions.(lO) If this is the case with atopic dermatitis, the definition of atopic eczema has to be rediscussed, maybe even delayed-type reactions should be classified as IgE-mediated reactions. DePt. of Dermatology, University Hospital, 9038 Tromso, Norway. The {requencies of atopic diseases show wide variations in different parts of the world. Atopic diseases are undoubtedly hereditary, but environmental factors have been made responsible for the increase reported in various parts of the world during the last few decades. Studies on atopic diseases from the northern parts of the Nordic countries are limited. Our studies were initiated by an interest in knowing whether geographical, ethnic, environmental or other factors might interfere with the frequency of atopic diseases. Atopic diseases were confirmed in 36% of 7-12 year old schoolchildren on the Varanger peninsula and the areas close to the Russian border, with 23% having atopic dermatitis (AD) and 18% mucous membrane atopy (MMA). A parental history of atopic diseases was reported by 37% of all children, occurring more frequently in mothers than in fathers. In families with no parental history of atopic diseases 41% of the children appeared to develop some kind of atopic disease; this increased to 63% with a single and to 75% with a double parental history. A strong cumulative effect was seen in cases with a parental history with identical symptoms in parents and children. Flexural lichenfied dermatitis was present in 88%, and 12% of the children had facial and extensor involvement with or without hand dermatitis. 64% of the children showed mild and 33% moderate symptoms; only 3% had severe symptoms confirmed by clinical examination. Low levels of aerospores were found in homes and schools. Mould allergy is supposed to be a minor problem in this area. Domestic mites were found in some homes and there was a strong association between sensitization/atopy and the occurrence of domestic mites in mattress dust. Cat and dog allergens were found in large amounts and smoking was more common than in other parts of the country. In a Lappish population in a nearby area atopic diseases were found to be less frequent in the same age groups, i.e. a total of 20%. of which 12% had AD and 11% MMA. The occurrence of indoor allergens is supposed to be very high in this ethnic group. On the other hand, the Lapps spend most of their time outdoors, which may contribute to the low frequency of air passage allergy symptoms among them. The latter results are in accordance with a previous study of a non-Lappish population of schoolchildren o f the same age in a nearby area. atopic diseases in subarctic areas will be discussed. Various aspects of the occurrencdfrequency of National Public Health Institute. Helsinki, Finland. Immediate hyperscnsitivity rcactions to natural rubber latex (NRL) protcins havc been increasingly recogniced during the paqt 15 years. Currently, approximately 3% of hospital employees and 5-10% of physicians and nurses working in operation units are allcrgic to NRL. Manufacturcd NRL products, such as surgical and household gloves, catheters, condoms, baby pacifiers and toy balloons may contain allergenic proteins capable of eliciting type I allergic reactions. Recently, substantial progress has been made in the purification and molecular characterisation of several NRL allergens which has facilitated the assessment of their significance and given grounds for proper comparison of thc rcsults obtained by different rcscarchers. in kesh NRL, the source material for manufacturcd products, over 200 different polypeptides have been demonstrated by 2-dimensional immunoblotting but only some 25% thcm bound IgE antibodies from latex-allergic patient sera and can be considered as allergens. NRL-allergic patients frequently have allergic symptoms from a variety of foods, likc fruits and vegetables, but the molecular basis of these cross-allergies is currently poorly understood. Rubber elongation factor (REF) was first suggested to be the major allcrgen (Hev b 1) in NRL and the only allergen present in one latcx surgical glove' but more recent studies show that IgE-antibodies to highly purificd REF, detected by immunoblotting and ELSA, arc practically confincd to the subgroup of patients with spina bifida2. A 20 kD NRL protein, previously shown to bc the most important allcrgen for adult NRL-allergic patients, has been identified by amino acid Sequeiiciiig as prohevcin3. IgE antibodics to purified prolievein arc found in 70-80% of NRL-allergic patients and prohcvcin elicits positive SPT reactions in most NRL-allergic patients and can thus be considercd as a major NRL allergen. Attempts havc also been made to localise IgE-binding epitopes of prohcvcin. Only a minority (15%) of patients with antiprohevein IgE antibodies had IgE against the prohevein C-domain whereas IgE antibodies to purified hevein, the 43 amino acid Nterminal fragmcnt of provehein, were found in 56% of NRLallergic patient sera'. In the samc study Alenius et al. also showed that purified hevein elicited positive SPT rcactions in all patients showing IgE to the N-terminus of prohevein and that IgE-binding peptides purified from a brand of highly allergenic NRL gloves could be identified by amino acid sequencing and mass spectrometry as hevein molecules. Recent results of another group' confirm thc role of hcvein as a major NRL allergen. Adult NRL-allergic patients frequently recognise prohevein and hevein, whereas the majority of paediatric patients with spina bifida seem to react with REF and with a 27 kD protcin showing partial homology to REP. The amino acid Sequences of tryptic peptides kom the 27 kD protein and from a 23 kD protein described by Lu et al.' were in essence identical suggesting that these proteins are thc same or thcy reprcscnt different isomers or modifications of the same protein. A 36-kD NRL protein showed high homology to scvcral plant endo-l,3-~-glucosidascs and this protein bound IgE from 21% of NRL-allergic paticnt Sera and was therefore considered a significant NRL allergen3. Bcezhold et al.' rcportcd that NRL protcin bands with apparcnt M W of 46-kD and 110-kD had identical, previously unrecognised N-terminal amino acid scqucnces and that IgE antibodies from NRL-allergic patient scra bound frequently to the 46-kD sized protein. Hcvamine, a 29.6 kD NRL protein, has turned out to be unimportant as a NRL allergen. Information on molecularly charactcriscd NRL allcrgcns prescnt in gloves or other manufactured products is limitcd. More than 70% of the IgE binding capacity of one highly allcrgenic glove was attributable to hevein4, and REF has becn issolatcd from a glove brand'. Monoclonal antibody against a 23 kD NRL protein' recognised epitopes of this allergen in certain glove brands and epitopes of a 27 kD allergen havc likcwise been detected in manufactured NRL products'. NRL allergens or their epitopes remaining in NRL products represent a group of proteidpeptide molecules that are resistant to high tcmperatures and to a variety of chemicals used in the manufacturing processes. It can be thus anticipated that all significant NRL allergens extractablc from manufactured products are remarkably stable molecules. classified as major allergens. The most important of those is the 20 kD allergen (BDA20) which also appears in the urine, although in low quantities. More than 90% of the immunoblot-positive cattlc tenders have specific IgE against BDA20l. Othcr important allergens of COW dander are the 11 kD and 24 kD protcins. About one third of cow-asthmatic farmers had specific IgE to them. Our recent studies have allowed us to confirm the realtionship bctwcen BDA20 and Prahl's Bos d 2. In fact, the similar amino acid compositions of the two proteins had earlier pointed to this possibility but the final evidencc was obtained from immunochemical studies with anti-Bos d 2 antiserum (made available to us by Dr. Hansen). The spectrum of cow dander allergens is probably more complex than previously presumed. When we used more efficicnt analytical methods it turned out that there are two separate 22 kD allergens in the bovine dander. Moreover, the prcviously described 11 kD allcrgcn scems to be a dimer in its nativc form2. An important goal of thc allergen rescarch is the purification of allergens for diagnostic and therapeutical purposes. Monoclonal antibodies with a high specificity offcr an cfficicnt tool for detecting thc antigen. We utilized this property of our monoclonal antibodies for pyrifying the BDA20 from raw extract with immune affinity chromatography'. When an additional purification stcp was performed BDA20 was almost 100% pure. This preparation has been used successfully in skin tests, histaminc rclcasc assays and in the measurements of cellular and humoral rcsponses4. Anti-BDA20 monoclonal antibodies have also allowed us to devclop a vcry sensitive and rcliable immunometric ELISAS. We have applied it for measuring the concentrations of airborne BDA20 is dust samplcs collected from cowsheds. This method is also vcry suitable for estimating the BDA20 content of cow allergen extracts. Modern methods of molecular biology have madc possiblc a detailed analysis of primary structures of allcrgcns. We creatcd a cDNA library from bovine skin by isolating mRNA and spnthcsizing cDNA which was then cloncd to a bacteriophagc vector. The library was immunoscreened with cow-asthmatic patients' sera containing specific I@. Positive plaques were picked, subclonal, and eventually the cDNA was cloned to a high-levcl expression vector for the production of recombinant allergens. Recombinant DNA technology has allowed us to establish the necleotide and corresponding amino acid sequenccs of t h e cow allcrgcns: a protein related to oligomycin sensitivity-conferring protein of the mitochondrial adenosine tiisphosphate synthase complex', BDAll [which shows high homology to human psoriasin, a protcin expressed in psor i a s i~)~ and BDA20*. The analysis of the cDNA indicates that the bovine major allergen BDA20 comprises 172 amino acids, has a predicted molecular weight of 19.56 and pl of 4.48. Sequencc homology searches in the EMBL and SWISS-PROT libraries revealed that BDA20 shows significant similarities with proteins belonging to the functional group named lipocalins, and we think that homology comparisons (amipo acid homology of about 32%) warrant the admission of BD@ to this functionally important family. Ljpocalins are present in the various body fluids and secretions of seyeral 8animal species. They act as carries of small hydrophobic mblkules, such as Ftinoids and pheromones. Interestingly, the major mouse and rat are urinary allergens ( a 2 -e u g l o~u~G j a s c * I j p~l~k 3 T l i i s raises a question of possible commonv'alleri;enic properties of lipocalins and allergens in general. The biological function of BDA20 in the bovine skin is not known. The recombinant BDA20 appeart to be immunologically fully functional. An interesting finding was that the binding of monoclonal antibody or human IgE to BDA20 seems to be almost completcly dependent on the conformation of the molecule. This was observed in experiments in which various segments were deleted either fiom the N-or C-terminal end of BDAIM. After the modification of the molecule, antibody binding was practically lost. As expected, T-cell clones could be induced to proliferate with the fragments. We believe that this finding may have important consequences with regard to immunotherapy. It may become possible to alleviatc allergy with highly dcfined preparations that lack the adverse property of inducing immediate hyperscnsitivity rcactions. Tbc yeats arc some of the most fascinating allergens because of their biologic propcrtics and thc rcsulting multiple form of exposure. We ger exposed to yeasts by foods, such as bread (Soccharomycer cerevisiae), wine (Succharomycesellipsaideus) and beer (Saccharomyces curlsbergensir), We inhale several yeasts as aeroallergens (Cryptococcus spp, Rhodotorula spp.), especially in moist conditions, both indoor and outdoor. Thc most important way of exposure to yeasts is, however, by saprophytic growth on the skin (Pityrosponun ovalelorbiculare) and the mucous membranes (Candido ulbicans). &cause of the unusual way of cxposure the clinical significance of yeast hypersensitivity remains disputed in several diseases. Most convincing evdence of hue yeast hypersensitivity has been found studying the role of saprophytic yeasts in atopic dermatitis of the h a d neck and shoulder region. Consequently the allergenic compositions of the yeasts involved to any extent in this type of atopic dermatitis have been studied most t b u g h l y (Pityroprwn ovule, Cundida albicans and Sacchuromyces cerevisiae). The first yeast to be characterized by IgE immunoblotting was C,ulbicuns and by now the allergcns of it have been charaderizcd in six studies. In the studies with small population sizes (nc50) the main allergens vary. In thc largest presented population of anti-C,albicans IgE positive individuals (n=lOs) the main allergen among altogether 44 IgE binding componcnets is a 46 kD protein band followed by a 27 kD band. The 46 kD componcnt of C.albicMs has been reumigzed as enolase enzyme. Another important antigen of C.albicuns is mannan, a plysaccharide. Both enolase and mannan are also the most important allergens of bakcr's yeast. ln fact, enolasc of Scerevisiue was the first yeast component to be recognized as a single allergen. Yhe IgE immublotting profiles af allergens of P.oribiculure and P.avule, different morphological forms of the yeast, differ. In the first presented analyses the major allergens of P.ovule were 25 kD and 9 kD bands and ones for P.orbiculare were 86, 76, 67, 28, 17, and 13 kD bands. Our own studies of P.ovale revealed the 9 kD, 96 kD and 20 kD bands to be the most important. We also found markcd IgE reactivity to P.ovale mannan by use of chemically purified mannan and nittocellulose RAST. The mannan stain could also be seen in IgE immunoblots as well. Stability of the yeast allergens is extremely poor in storagcd solution. Especially the enolases of Cdbicuns and S.cerevisiue are very labile allergens. The majority of the allergens of Cdbicans, P.ovale and S-cerevisiae lose their IgE-binding capacity when storagcd. On the contrary to proteins manna is a stable allergcn. The maximum storage times at +6"C in 50% glycerol are six month for C.albicans and one month for P.ovule and S,cerevisiue. The baker's yeast allergens are labile in the gastrointestinal tract as well. In an in vitro analysis only mannan and a 10 kD allergcn were stable after the gastric and duodenal conditions. These two allergens also appear to be thermostablc. Thc yeast allergens, despite of the great biological differences of ycasts, crossrcact. The main crossreacting allergens arc cnolasc and mannan. In IgE immunoblotting inhibition experiments thc IgE antibodies against enolases of C. albicans, C,utilir and S.cerevisiae crossread and so do the mannans of C. alhicanr, P.ovo1e and S. cerevisiaein RAST inhibition. In rcccnt years a great deal of information of yeast allcrgcns has become available. This information helps us to understand the rolc of yeasts as sensitizers and allcrgcns. In the coming years thc analysis of the immunomodulating properties of ycast allergens on human immune responses will be the most challcnging era of the yeast allergen rcsearch. Most, if not all, people are sensitized to mosquito bites in the early childhood. Cutaneous symptoms include immediate wheals and delayed bite papules, which tend to be more severe at the onset of the mosquito season. Systemic Arthus-type symptoms may occur but, in contrast to bee and wasp stings anaphylactic mosquito-bite reactions are very rare (1). Mosquito-bite wheal is IgE antibody mediated. With a sensitive immunoblot assay we could show saliva-specific IgE antibodies in almost all subjects with immediate skin reactivity to Aedes mosquitoes (2) . In addition, passive transfer experiments confirmed that saliva-specific IgE antibodies catl cause mosquito-bite whealing in vivo (3). When feeding female mosquitoes inject saliva into the skin. To characterize mosquito saliva antigens we immunized mice with the bites of Aedes communis (northern European species), Aedes aegypti (tropical and subtropical species) and Anopheles sfephensi (Asian species). The main A. communis saliva antigens were 22-, 30-, and 36-kD, A. ueppti saliva antigens 31-, 36-, and 46-kD and A. stephensi saliva antigen 46-kD proteins. Most of the saliva antigens appeared to be speciesspecific and cross-reactivity was observed only between saliva proteins of A. communis and A. punctor, two taxonomically closely related species. Human IgE and IgG4 antibodies from mosquito-sensitive children bound to the same saliva proteins confirming that these are also allergenic in man. At present, the fimction of mosquito saliva allergens is unknown. We could show saliva allergens in the female but not in the male A. communis saliva suggesting that these proteins are involved in blood feeding. We have partially sequenced the 22-kD saliva allergen from A. communis but it showed no homology to any known proteins. A gene expressing the 36-kD protein from A. uegypri salivary glands has also been isolated but the function and allergenic properties of this protein is not known (4). In conclusion, Aedes and Anopheles mosquito saliva contains several proteins which bind human IgE and IgG4 antibodies. In the future, isolation and production of saliva allergens may give tools for immune therapy in mosquito-bite allergy. R. Jolanki, L. Kanerva, T. Estlander Finnish Institute of Occupational Health (FIOH), Helsinki, Finland. Aims: The major types of rosin (colophony) are gum rosin, wood rosin and tall oil rosin. Gum rosin and tall oil rosin are the two dominating rosin types today. Tall oil rosin is obtained as a byproduct in the pulp industry. The aims of the study were to gathL.1 information on the sensitizing properties of tall oil rosin Methods: 99 patients who were patch tested to tali oil rosin (20" pet) during [1983] [1984] [1985] [1986] [1987] [1988] [1989] [1990] [1991] [1992] [1993] [1994] were included in the study. All the patient5 were also tested to standard colophony (gum rosin) (20% pet), '7 I were tested to abitol(lO% pet), 5 1 to abietic acid (1 0% pet), and 21 patients to pine and spruce resins from living trees (20% petj Results: Twenty-four patients got an allergic test reaction to colophony and 14 patients to tall oil rosin. All the 14 patients with an allergic patch test. to tall oil rosin were also positive to colophony, and 10 were positive to abietic acid (10 of 10 tested), 1 to abitol(1 of 10 tested) and 4 to the living tree resins (4 of 4 tested). The patients with an allergic patch test to colophony had the following allergic test reactions: 14 were allergic to tall oil rosin, 10 of 16 tested to abietic acid, 3 of 23 tested to abitol and all 6 tested to the tree resins. Conclusion: Tall oil rosin contains the same allergenic compounds 8s gum rosin. The differences in the amounts of the allergens are probably responsible for the lower fiequency of allergic reaction\ to tall oil rosin. The results support the view that skin contact to tall oil rosin may cause contact sensitization. During last years the significant increase in incidence of allergic diseases including occupational asthma is notable. Longterm studies showed that occupational asthma is polyethiological disease. The ethiological factors are divided into three main groups: sensitizers, irritants and substances with mixed mode action. Among industrial workers chemical haptens are the most common cause of asthma. At the moment asthma is very common disease in Russia especially in workers of chemical, textile, mining industry and machine building. In light, food, microbiological industries and agriculture there is a lot of factors of plant and animal origin which can cause occupational asthma. They are different fibres of plants, molds and bacteria colonising them etc. The sensitising ability of industrial allergen, the power of action, duration of exposure, its physical and chemical properties and hereditary predisposition and immune status of organism play an important role in development of asthma. Many inhaled irritants are non-inflammatory triggers that increase bronchi sensitivity and reactivity that leads to impairment of primary defence mechanisms. A number of studies gave the possibility t o elaborate the occupational asthma classification and solve some problems of its management and prevention. In the present study, rats were immunized intrademally w i t h 8 different OAAs in dioxane/paraffin oil. Blood was collected 4 weeks after immunisation and analysed by ELISA for specific IgE to rat serum albumin conjugates of the OAAs. Phthalic anhydride, mmellitic anhydride, methylhexahydrophthalic anhydride tetrahydrophthalic anhydride. and methyltetrahydrophthalic anhydride all showed elevated specific titres in the rat as well as in the GP model, while succinic anhydride was negative in both. The introduction of methyl groups seems 10 enhance the formation of antibodies. A reasonable agreement was found between the results of the GP and rat models. Also, the findings of the animal experiments are in agreement with findings from studies of exposed workers. Thus, the models may be useful for a better understanding of the sensitising potential of different OAAs and perhaps also other compounds. Fmiicrs and tlrcir Ianiilics arc cxposcd to sc\ C I ;~ Iiiological dusts iacluding aniinal dandcr. pollcn and molds A raiidoni saniplc of farmcr familics and non-fariniiig faniilics in Kuopio county was sclcctcd for computer-assistcd tclcpliorie intcrvicw (CATI). httogetllcr 772 :idults wcic iiilcrvicwrtl froiii 4(NI fwiiilics (221 f:iniicrs :iiKI slwoiiscs. SS I :illiili'i iii otlicr iioiifarniisg families). I l e farmcr faniilics had 232 childrcii and other families 646 childrcn. In adults, no significant diffcreius were found in the prevalence of self reported asthma anioiig faniicrs and thcir spouscs (5 %) compared with non-farming population (4 %). Thc prcvalcnccr of nllcrgic rliiiiitis wcrc 27 o/o :tiid 26 %, rcspcctivcly. Also dlcrgic conjunctivitis was :is coiiiiiion iii both groups. The lifc-time prcvalencc of atopic eczema was 17 % in farmers and W 96 in non-farming adults. ln childrcn, thc prevalence of astlrina was lowcr in farmcr faniilics (1 96) than in thc non-fanning faniilics (3 %). Ihc prcvalcncc of allcrgic rliiiiitis was also lowcr iii cliildrcii of farmer families (8 %) than in childrcn in the non-farming families (13 %). Atcvic ec7mia W~LF also lcss w)iiiiiioii in farmcr faiiiilie.. than in non-farming families. W c uwclude that highcr cxposurc to comnion allcrgcns docs not iiicrcasc the risk of ntopic dimascs. R. Savilahti', P. Roto2, J. Uittiz, T. Husman3 'Espoo Community Health Care Center, Espoo, Finland, Tampere Regional Institute of Occupational Health, Construction Section, Tampere, Finland, 3National Public Health Institute, Division of Environmental Health, Kuopio, Finland. The purpose of this study was to assess the effect of microbial cxposure due to moisture damage in a schoolbuilding on the respiratory symptoms and Serum immunoglobulin E QgE) levels of schoolchildren. The study group consisted of 367 children between the ages 7 and 10 years in a moisture- The prevalence of respiratory symptoms was 1.5 times higher for the exposed children than for the controls; in addition they had two times more wheezing and 1.6 times more shortness of breath than the unexposed childrcn, According to the questionnaire, 33.3% of the exposed children and 29.9% of the controls had had allergic symptoms earlier. Sixtythree percent of the exposed children had an elevated serum IgE level (r0.4 kUA) as compared with 33% of the controls. In the most contaminated classroom 84% of the children had an elevated IgE value. We conclude that moisture damage, and the microbial exposure associated with it, increases the risk of respiratory symptoms and elevated serum IgE among children attcnding moistureldamagcd schools. Background: In the lasl dccade, larw has been focussed upon as a c a w to seven IgE-mcdialcd nactions in man, i.e. during denlal. Gynecologic or surgical cxploration of patienu wirh glovcs or ~l t h~t e r s made of lakx rubber. Among risk gr~ups for this allergy arc newborns with defect neud crcst closure. denlal and hospital care p 3 ' S M d in m m t mucod or skin contact with latex. Exlfacu of latw from h e mbbw VCC contains IgE-binding pmleins from 2.5 Lo 120 kD in mo1ccu)ar size. Reaginic alhgy is dcmnstraled by aid of RAST tesLskin prick tesl(SpT) and provocations. The latter must be made cautiously because of risk for anaphylaxis. The prevalence of reaginic latex allergy accading 10 otha studies is obsaved to be 7% in atopic patienu ~s t e d with common airborne allergens, 3% in unselected hcalthy hospibl care personnel and 567.4% in nurses WOiLing in operation mms. Use of latex as material in furniture is i n c d n g . arc seen in broadly snsiliipd cuopics with rhinitis, asthma and eczema. Allergyprovoking activities =:Wearing latcx gloves. usc of condoms. using bcds with a latcx mattress.work in and visit to factories using adhesivc folic. working as a hair dresser, king patient or workhg in dentin's or dental hygienist practices. Conclusions: Latcx allergy may be more frequent than earlier supposed. Not only those. with risk occupations or chronically ill paticnts who arc rcpcatedly exposed u) latex during diagnostic prucedm should be investigated lor l a w allergy. Also broadly sensitized alopics and those with longlasling wposm should bc cxamined for possible latcx sensitization. Asthmatic patients who need regular or longstanding medication receive special reimbursement for antiasthmatic drugs in Finland. The diagnosis must be made by a specialist. All patients are registered by the Social Insurance Institution. This database provides nationwide information on the prevalence and incidence of persistent asthma. The register included lS0,OOO patients at the end of 1995, i.e 2.9% of the total population, ranging from 2.5% t o 4.1% in the 22 hospital districts. In 1986, the prevalence rate was 1,5%. The number has doubled among both genders since 1986, and the Bllllual growth has been about 10%. The prevalence has in relative terms increased most mong children, and their share of all patients has grown fiom 9% in 1986 to 14% in 1995. Prevalence rate among boys was 0.54% and among girls 0.29% in 1995. In the total population, the age-standrirdued rate was slightly higher among females (3.0%) than males (2.9%). Differences in the agespedic incidence rates increase the share of atopic asthma among patients. nus paper presents data on risk factors for asthma based on two crow sedional studies in @e same populaticn sample 6 years apart. In 1986 a cross-sectional study of respiratory diseases was performed in the northernmost province of Sweden. The first part ofthe study was a postal questionnaire survey. Completed answers were given by 5,698 (86%) subjects out of6,610. In 1992 the cohort was invited to a followup study, in which 87% (N4.932) ofthe participants in the 1986 y study participated. The cumulative incidence of asthma during the 6 y period was high, 3%. and was based on the question "Have you ever had asthma?" after exclusion ofall subjects with asthma or suspeded asthma in 1986. This indicates a mean annual incidence rate of asthma of 0,5/100/y. After family history of asthma (RR 4.0) both current and ex-smoking appeared to be important risk factors for asthma. Regarding smoking habits the hi&est incidence of asthma, 0,9/100/y, was seen in those who were smokers in 1986 but had stopped smoking in 1992. Ifthe risk to develope asthma in never smokers without asthma heredity was 1 in a linear regression model, the risk for ever smokers without asthma heredity was 1,s. in never smokers but with asthma heredity 4,3 and in ever smokers with asthma heredity 6.7; the risk increases mainly additively. In multiple logistic regression models also farming and employed in forestry were risk factors, as well as manual workers in industry and female sex. The profuse airway mucosal microcirculation has scvcral important functions in health and diseasc. One of its major roles lies in the process of extravasation and mucosal exudation of bulk plasma. This response is produced by allergic reactions, infcctious processes, occupational disease factors, inflammatory agcnts, and epithelial shedding. In contrast, simplc neurogenic irritants and metacholine-type challenge arc without exudativc effects. The extravasated plasma harbours adhesive and Ieukocytc-activating proteins (such as fibrinogen and fibronectin), proteases, immunoglobulins, cytokines and cytokine-mudolating proteins, and an endless variety of biologically active pcptides. The plasma exudate-derived dynamic molecular milieu of the inflamcd airway mucosa may cxplain in part why any translation of jxuh~ a l l data to in yiyr function may be fraught with disaster. Ncw data on epithelial restitution, after shedding suggest a pramount rok of plasma exudation in mucosal repair (as well as novel roles for both basal cells and ciliated cells). Shedding-tikc removal of the epithelial lining in a defined are promptly induccs extravasation and luminal entry of bulk plasma. A plasma-derived gel thus covcrs the denuded but intact bascment mcmbrane until a new flat epithelium has been Lstablished. The gel is rich in fibroncctin-fibrin and other repair-promoting plasma-derived agents. Contrasting current cell culturc paradigms, rccpithelialisation ~IU&LQ occurs both promptly and at exceedingly high spceds. T'hc epithelial restituton process involves several physiological responses (plasma cxtravasation, secrctory effects), granulocyte rcsponses (migration and activation of neutrophils and eosinophils), and remodelling cffccts (proliferation of fibroblasts and smooth muscle cells, thickening of rcticular basemcnt mcmbrane, and growth of regional lymph nodes). Hcncc, shedding-restitution processes, as they cvolvc under b~ viva conditions, evoke several disease-like effects encompassing airway and organ pathophysiology, leukoscyte pathology, and airway remodelling. -Propccting thc epithelial lining from damagc and shedding emerges as an increasingly important goal of thc trcatmcnt of asthma and rhinitis. In this conipkx scheme exudative inflammation goes on either wilh thc cpithelium intaact (left) or with shedding-restitution as a prominent feature (right). In both kinds of inflammatory conditions plasma-derived adhesive proteins and other plasmaderived effectors solutcs contribute significantly to the molecular milieu of the lamina pmpria, the epithelium, and the mucosal surface. Notc that the cpithelial shedding-restitution process may be a driving forcc for asthma-likc cellular pathology and cxudative pathophysiology. A. Grahnbn PMC Quintles, Uppsala, Sweden. Inhaled corticosteroids (iGCS) have a favourablc bcnefit to risk ration whcn assessing thc ratio between topical airway activity and systemic (advcrsc) effects such as those on HPA-axis supprcssion and bonc metabolism. Inhaled corticosterojd therapy clearly has a much better bencfit to risk ratio than oral steroid therapy (1, 2) . Although this favourablc property of inhalcd corticosteroids has been extensively highlighted, dosedependent systemic effects do occur and somc of these systemic effects may limit the use of inhaled stcroids. Corticosteroids, when sytemically available, produce a number of dose (concentration) dependent biological effects. The most important effects from a safety point of vicw arc adrcnal Suppression, growth retardation and negative effects on: conncctive tissue, calcium-bone-, carbohydrate-and lipid metabolism. In addition to the systemic effects, local effects such as oral candidiasis, dysphonia, cough and throat irritation may occur when iGCS arc used (3). The frequency of local effects vary in different studies because of thc diffcrcnt critcria uscd for assessment. Based on controlled clinical trials and spontaneous adverse reaction reporting systems, regulatory agencies estimatc the frequency of local adverse effects to about 5%. Of the systemic effects, adrenal suppression and negative ffects on bone rnctabolism arc of a major safety concern. Adrenal suppression The magnitude of adrcnal suppression is dertcrmined by the systemic availability (absorption) of the deposited dose in the lungs. Magnitude of deposition is in turn determined by the efficiency of the inhaler device (4). Although a significant part of the inhaled dose is deposited in the oroparynx, and subject to gastrointestinal absorption, the additional systemic load is small due to a very efficient first-pass metabolism of modem inhaled steroids (2 90% for budesonide and fluticasone). The lung is a hihgly efficient absorbing organ due to a largc surface area and high pcrfusion. Most clinical studies have utilised morning plasma cortisol as a direct markcr for adrcnal suppression. In these studies, significant suppression has been seen only with very high doses (3) . It should be emphasised that morning cortisol is a relatively insensitive and highly variablc markcr for cortisol production since a single measurement does not reflect production rates and is subject to bias due to the cyclic nature of the cortisol production. In recent year, studies utilising pharmacokinetic methodology reflecting cortisol production rates, have shown that inhaled corticosteroids suppress cortisol productions in a dosc-dependent manncr. Short term (5 7 days) studies in healthy volunteers (5, 6) as well as in asthmatic patients (7, 8) Show that cortisol production is significantly suppressed within the clinically recommended dose range. The systemic potency (dcgrec of suppression) varies between steroids (and devices). Bone metabolism and growth retardation It is gcncrally accepted that in doses below 800 &day iGCS are relatively bee of bone mctabolism effects. In contrast to oral stcroids, osteoporosis has not been reported. Short term studies of surrogate markers for bone metabolism (osteocalcin, type I collagcn carboxy terminal propeptide) havc shown dosedependent effect on t h w markcrs (9). There is considerable debate as to the clinical significance of these findings. Since controlled, prospective longitudal studies are lacking, the risk of developing osteoporosis (especially in patients with other risk factors) cannot be adequately assessed. Short term, dose dependent, retardet growth in children treated with inhaled corticosteroids has been rcported (3). However, studies indicate that growth retardation seems to be a clinical feature of thc asthma disease itself and not specidly relatcd to the use of inhalcd corticosteroids. A controlled prospective long tcrm (up to 6 years) study in 216 kthmatic children revealed that budcsonidc in doses up to 400 &day did not adversely effect growth (10). Whether other more systemically potent corticosteroids lack negative effects on growth in unclear. Inhaled steroids have a favourable benefit risk to ratio, with few adverse effects. However, it is important to realise that treatment with inhaled steroids is not solcly topical. All inhaled steroids available on thc market are efficiently absorbed from the lungs and systemic effects will manifest in a dose-dependent manner. To minimize development of systemic advcrse effects, selection of an optimal dose regimen in relation to the systemic potcncy of the steroid is cssential. It should also be emphasised that an uncontrolled asthma carrics a much larger risk to the individual patient than potential advcrsc cffccts induced by inhaled steroids. In clinical practice today, the physician is confronted with many different inhaled formulations for the treatment of asthmq and must consider a number of inhaler aspects in order to make the right choice. As the amount of drug reaching the effector organ. for an inhaler tells us that there is great potential for improvement i~ inhaler design Using the W-do concept, it has been shown that it is advantageous, with respect to the balaaca between W e d and undesired dfects, to change from pMD1 to Tbbuhala It has also been shown, when comparing e 8. ssftnrtpmol pMDI and salbutamol Rotahalcr*/Diskhalero that it is more advaatugeous to use the pMDI than the corresponding Variability in thc dose naching the effector site can be of w~a s a~~i n availabilii at the effedw site can rms Rw the &cited response. In vim, the dose for Turbuhder than for pMDI, whereas the revttrPeiotnteinvivo(Beclonanetal.,JAerMed,1996).Thus, in a &&&I skuation, the DPI gives a more reproducible dose in the lungs than docs the pMDI This is probably a class phenomenon for DPIs, as the generation and inhalation of drug aerowl for DPIS, such as Turbuhaier, Diskhaler, etc., is a continuous process. For pMDI formulations, generation and inhalation of the drug aerosol is a non-continuous process and thus more o p~n to patient influence. There are dsa other aspects to consider when choosing the optimal inhaler and the pros and cons of the different inhalers must obviously be considered when making the choice uftintrtby, however, it is the patient who rnakes the choice. If the patiart is happy With the inhaler, hdshe will use it; thus an i n c r d c~mplimce could be the best "inhaler improvement" in the forneeable fiture The study of genetic determinants in multifactorial diseases, such as atopy and asthma, is complicated by phenocopies, incomplete penetrancc, variable expression, and locus and allelic heterogeneity, among other factors. To avoid problems caused by such heterogeneity, we are studying asthma in a genetically homogeneous population as a model for multifactorial diseases in general. Even though continuous population existed in Finland for thousands of years, vast regions in the east were settled only within the last 500 years. Migration created isolated, small but expanding breeding units that allowed for genetic drift to affect the frequencies of rare genes. Due to the short population history, original founding haplotypes have not been obscured by numerous successive recombinations, but linkage disequilibrium is commonly seen around rare founding genes in, e.g.. monogenic diseases. Such observations have recently facilitated the positional cloning of genes for an inherited form of epilepsy and congenital chloride diarrhea. As reported in detail by T. Laitinen in this meeting, we used affected relative pair analysis and a family-based association strategy to study the chromosomal region 5q3 1 -q33, previously implicated in the regulation of IgE and bronchial hyperreactivity. No linkage of serum IgE levels to 16 physically ordered genetic markers in 5q31-q33 was detected by the study of altogether 108 sib or cousin pairs, and no significant haplotype associations with high or low IgE levels or the a$thma phenotype were detected in 157 nuclear families originating from a small geographical arca. These results suggest that other genetic factors remain unidentified that affect IgE levels and transmit susceptibility 10 bronchial hyperresponsitivity in this subpopulation. It has long been known that asthma runs in families but the genetic basis of this has, until recently, eluded definition. Debates over whether asthma is inherited as a recessive or dominant trait have long since passed with the recognition of the disease having a polygenic basis which accounts for up to 60% of the asthma phenotype. A single gene such as the polymorphism of the Fc,RI-/3 cham, as proposed by the Oxford group, while seemingly attractive, has proven difficult to reproduce in different family studies. The IL-Q gene cluster comprising IL-4, -13, -5, -9 and GM-CSF encoded on the long arm of chromosome 5 (Se,,,) may be considered in regulating IgE, mast cell, basophil and eosinophil responses. Four independent studies and one by our own group have shown either linkage or allelic association between polymorphic markers located in this region of the human genome and the occurrence of allergy and asthma. Other candidate loci for which some evidence for linkage has been found include the a chain of the T cell receptor (CD3), TNFa and the IL-5 receptor. Using anonymous markers in a random human genome search, at least ten "hot spots" have been located. With the recognition that early life events including nutrition, allergen and air pollutant exposure predispose to the later development of asthma and allied disorders provides an opportunity for using genetics to identify those who are at greatest risk of developing atopic disease and in whom early environmental and pharmacological primary prevention might be targeted. The next decade is likely to witness enormous advances in genetic and environmental influences on asthma towards the unified goal of prevention. To achieve this effectively co-operation and collaboration between those interested in genetics and those who believe that environmental factors take primacy in determining disease phenotype. Both ordinary skin prick test (SPT) and its modifications like prick-prick test, scratch test and scratch patch test can be used to detect immediate allergy to foods. There is no age limit for prick testing, In fact, the younger the patient is, the more reliable the results are. In children under one year of age, a positive prick test usually means clinical food allergy. In most older children and adults, a positive test result is valid only for skin sensitivity, not for allergy to ingested foods. Commercial food allergens are reliable in detecting allergy to stable food proteins l i e milk, egg, fish and soy. SPT is the golden standard for testing them. The allergens in fiuits and vegetables are so unstable that they should prefbably be tested as such. The prick-prick method is the method of choice for them. The fiuit or vegetable is pierced first with a prick test lancet and the skin immediately after that. Scratch test can also be used for testing h i t s and vegetables, and also dry allergens, such as flours and powdered spices. In scratch patch test, the scratch is covered with an epicutaneous test chamber or just by a piece of tape for 15 -20 minutes. It is somewhat more sensitive than scratch test but it is needed very seldom. In small children, the back skin is the most practical skin area for prick testing. In older children and adults, the volar aspects of the lower atms are used in most instances. The significance of positive prick tests should always be confirmed by peroral challenge tests. Dcrmatologists use epicutaneous patch testing with chemicals (c.g. nickel) to diagnose allergic contact dermatitis. Recently, several investigators have performed patch testing with protein allergens in atopic dermatitis (AD). It is clinically well known that some patients with AD experience exacerbation of their delayed symptoms after cow's milk challenge. Moreover, several of the patch test positive, cow's milk allergic children were negative in prick tests andor RAST. Although false positive patch test rcsults can occur, a parallcl prick and patch testing with cow's milk had a diagnostic sensitivity of 0.78 in infants with acute-onset and 0.92 in the delayed-onset cow's milk allergic symptoms (4). Ccrcal allcrgic AD children can also show positive patch tests although the type I tests @rick, RAST) are negative ( 5 ) . These results suggest that patch tests can significantly enhancc the diagnostic accuracy of food allergy in children with AD. At present, the value of food allcrgen patch tcsting in adults has not been evaluated in larger studies. Much research is also needed to standardize the allergens and vehicles used in the "atopy patch testing", and to elucidate the pathomechanism of patch test reactions to foods and aeroallergens. 'Dept. of Environmental Health, Stockholm City Council and The Boston Consulting Group Stockholm. A total system perspective on asthma patient care reveals t h t significant improvement potential may exist. Focusing on the patient with the disease as the relevant unit of management suggests t h ; betler outcomes could be achieved, measured by clinical results, cost andpatient satisfaction. In many countries expenditures for medical care services continue to rise. During the recent recession years in many countries, health care budgets have come under heavy pressure, but traditional cost-containment measures focused largely on separate cost components have not been very successful. A more fundamental change in how patient care is set up is required. For allergic diseases, e.g., asthma, this is highly relevant. Studies that take a total system perspective on a disease, i.e., that include both direct and indirect costs, patient outcomes, and patient satisfaction throughout the entire disease period, often provide many new perspectives and valuable insights into how one can affect the patient care outcome. There are very few studies where the total system effects in the community of asthmatic patients have been studied. When optimal use of resources is badly needed in health care, setting strict priorities becomes necessary. A systematic analysis of the use of resources in the health care system, insurancebased or private, including costs of pharmacological treatment and magnitude of sick leaves etc., is a required platform for discussion of possible changes of the distribution of and coordination between preventive, secondary, and tertiary activities within the health care system. A small pilot study of this kind described the chain of care in a limited number of asthmatic children, i.e., mapped the disease in a small sample of patients. The results will be presented at the congress. To study the patient care and cost drivers for asthma, several parameters have to be present or developed, such as information from patients records, record knowledge of the disease, assessment of severity and segmentation of patients, mapping of w e chains (episodes of care), and direct and indirect costs. This type of study also gives information about the more exact and true costs for patients with different seventy of asthma. It allows for studying the quality and effectiveness of care and comparison of treatment costs, indirect costs, and direct costs of different levels of care. Several broadly applicable findings emerged fiom the piIot study. An extension of computerized patient records combined with information about transactions will make it possible to evaluate the efficiency and quality of available health care strategies. It will also allow for comparison of the costeffectiveness of different forms of therapy. From the pilot study it could be concluded that in these four cases our current health care system does not allow for an effective follow-up of medical problems and economical results. Despite the small sample, the study highlighted the likelihood of achieving significant cost savings, improving quality, and enhancing patient satisfaction by taking a total system approach to patients with asthma. Improving health care is an objective that people around the world are struggling with, from politicians to government officials at all levels to hospital administraton, private as well as public, to individual physicians and nurses. With the simultaneous demand to reduce costs, it is a struggle that is both hard and often unsuccessful in the medium or long term. In times when many cost-saving programs in health care are producing unpleasant side effects in terms of lower quality and lower patient satisfaction, it is enlightening to see the improvement potential shown with a system perspective on asthma w e . Cost-effcctivc (CE) analysis for diffcrcnt trcatmcnt stratcgies has bccome more important because of limited social resourccs for health care. Critical evaluation of treatment strategies as a wholc is important and makes possible to select thosc programmes which arc cffectivc also economically. In CE analysis thc casts of treatment are related to some types of clinical effectiveness measures. To find out which is the least costly way to achieve a ccrtain goal, the goal has to be specified (1) . Is the goal of trcatmcnt to improve outcomes, prcvcnt progression of asthma, reduce exacerbations or rcducc duration of asthma? Most frequently used measurcs arc nccd of health scrviccs, lungfunctions, quality or life years gained or symptomless days. It should be noticed that thc situation of mild asthmatics is different fiom that of moderatc or scvcrc cases. Amount of emergency visits, hospital admissions, improvement in lungfunctions, sickness days etc tcll morc about the effectiveness of therapy of moderate or severe asthmatics than that of mild ones. On the other hand the functions of mild asthmatics are often so good from thc beginning that it is difficult to show any significant improvement in the intervention sudies The costs of asthma include both medical and nonmedical resources as well as indircct economic losses and the psychosocial impact. In 1991 prcvalence of asthma was about thrce timcs grcatcr than ten ycars carlicr. In 1995 according to a Social Insurance Institution's interview study 3.8% of men and 4.7% of womcn stated asthma to be their longtcm discasc. Total costs of asthma were in the beginning of 1994 about 25 milliard, of which about 37 million FIM for sickness leaves. In the end of 1994 asthma was the third most common chronic disease after hypertonia and coronary heart disease. In 1994 approximately 4.7% of population, that is about 240 000 patients, received rcimbursment for prcscriptions of anti-asthma drugs in Finland. In Finland asthma mortality has long rcmained around loo/ ycar, but after 1992 it decreased to a 60-70 lcvel although thc prevalence has increased (2). It is supposed that it is CE if asthma is diagnoscd aftcr thc very first symptoms, and effective treatment is then started. Actually we don't know thc proportion of patients who will develop more severe asthma if untreated or undertreated (3). Selroos has pointed out that the longer astmasymptoms lasted before effective treatment was started the worse wcrc thc lungfunctions after 3 years follow-up (4). International studies have shown that care of asthmatics by specialist reduced the use of medical healthcare (5, 6). There are no such studies from Finland. In our country lungspecialists have until now had main responsability for studies and treatment of asthma patients in lungclinics. It is very important to do longtcrm follow-up studies of the CEness of diffcrcnt trcatnicnt graduation. From the economical standpoint inhalcd anti-inflammatory mediation appears to improve resource use efficncy (7) . Thc b s t o n group calculated the costs of asthma iri Finland according to different categories of asthma. Costs of severe asthma paticnts arc about 50 OOO FIWpatient and for mild asthmatics they are 4000 FIM per year. The social, nonmedical cost are least 40% of total costs. If wc comparc to earlier amount of pensions and sickness leaves in Finland and the situation now, one can suppose that the treatment with anti-inflammatory medication has been CE. Already now the amount of sickness lcavcs has decreased by 30 OOO from 1990 to 1994 and that is in spitc of increased prevalenve (2) . Neither effective drugs nor early started treatment will help if the patient is not willing to use medication. Asthma patient education and self managemcnt programme are shown to be CE in many studics aftcr 6-12 months follow-up (2, 8, 9 ). In the sudy of 'l'iauner et al. the follow-up time was three years and the result was the same (10). Generally the use of emergency services and the need for hospital treatments have dccrcased. Educational interventions appear to be effective in improving patient self-management and alherence to medication. Muhlhauscr suggests that a teaching programme and regular asthma treatment are associated with reduction in morbidity in moderate to scvcre asthma patients (11). Asthma is a chronic condition and therefore long-term effectiveness of intervention is important. In my study the CEness of intcnsive education for selfmanagcment for few asthma patients was calculated. There were 76 new asthmatics in the intervention group available for analysis aftcr 3 ycars, mean age 39.4 y m , 23 mcn. They were randomly selected from 160 ncw asthma patients. All Between the groups the differences in the changes of lungfunctions aftcr one year's treatment were significant in FEVl (p< 0.01) and nealy significant in Forced vital capacity (FVC), Forced expiratory volyme per cent (FEV%) and Peak expiratory flow (PEF) p< 0.05 tcsted by t-test. When thc CEness is calculated with quality of life indcx thcrc was not any diffcrence between the groups although all thc cxtra costs for intcrvention were included in thc calculation for the first trcatmcnt year. The follow-up will be interesting, to see can the advantage gaincd during thc education be reserved over a numer of years. CE treatmcnl is a wholc starting from early diagnosis, etrcctive trcatmcnt, patient education, self-management, and good patient compliance. Treatment can be effective if all these parts function correctly. The Public Health Centre of Almhult, Sweden. Good health can't be measured in terms of money, but bad health can indeed. The purpose of the study was to determine if patient education of asthmatics besides improving the condition of the patient, also results in economic savings, and if so, to what extent. Chronic illnesses, i.e. asthma, generate heavy expenses of various types for both patients and society. It is of high priority to find possibilities to reduce these costs. The results from six different studies from Sweden (4), USA (1) and Finland (1) will be presented. They represent different models of patient education, most of them connected with out-patient care. The number of emergency visits, days of hospital care, days off work, number of physician visits and medication (antibiotics) costs have been compared before and after the patient education started. The costs have then been calculated for these various consequences. The results shows that substantial economic savings are possible with relatively small and cheep inputs. The conclusion is that a well organized patient education for asthmatics results in both improved health and economic savings for both patients and society. The purpose of this study was to assess the antiasthnwic activity of a magnesium sulphate aerosol (solution osmolarity 260 &OM, pH 6.6) using a randomised design. Forty-three patients (20 men, 23 women, aged 19-55) with mild and moderate atopic bronchial asthma were divided in two groups. The fmt group was treated with a inhalation of magnesium sulphate (a single dose contained 2.5 mmol Mg+2) for two weeks. The second group received placebo (isotonic saline aerosol) for the same time. The single dose of magnesium sulphate aerosol had no greater bronchodilator activity than placebo but, sigmfkantly decreased bronchial hyper-reactivity to acetylchoiie (ACH) and graded physical exercise (GPE). After long-term treatment bronchial conductivity did not significantly differ h m its initial mean in both groups of asthmatics. However, the aerosol of magnesium sulphate, unlike placebo, reduced bronchial hyper-reactivity to ACH and GPE. We concluded that magnesium sulphate aerosol can reduce nonspecific bronchial hyper-reactivity and mast cell secretion in atopic asthmatics. Two hundred and sixty-seven patients with mild-moderatc asthma (mean age 50 years; mean morning PEF 294 Umin) and not using anti-inflammatory medication participated in a doubleblind, randomized, placebo-controlled parallel group study consisting of a 2-week run-in and a 6-week treatment period. They received Pulmicort Turbuhaler 100 pg, 200 pg, 400 pg or placebo Turbuhaler twice daily. Already after treatment for 1 week morning PEF had increased significantly in all Pulmicorf groups; 23, 22 and 27 LJmin @=0.037, 0.020 and 0.004 compared with the 5 Umin increase in the placebo group). During week 6 the mean increases were 15, 45, 53 and 71 Umin in the placebo group and the 100 pg, 200 pg and 400 pg b.i.d. Pulmicort groups, respectively. All Pulmicort doses were significantly superior to placebo (p4.042, 0.004 and 0.000, respectively). A statistically significant dose response was found; Jonckheere test, p