key: cord-0037845-z9i5mk33
authors: nan
title: Beyond our pages()
date: 2012-05-29
journal: J Allergy Clin Immunol
DOI: 10.1016/s0091-6749(04)70038-x
sha: cc04e3a5c834fe41e151ad5c45f78b4929983bd6
doc_id: 37845
cord_uid: z9i5mk33

nan

Updated material concerning the severe acute respiratory syndrome (SARS) has appeared in recent issues of several journals. We have summarized some aspects of these reports to alert our readers, particularly since one might expect asthmatic individuals to experience greater morbidity from SARS infection.

SARS appears to be due to an infection by a novel coronavirus (Cv). 1, 2 The usual human-infecting Cv strains cause up to 30% of "colds" but only rarely cause pneumonia. However, animal-strain Cv can cause extensive epidemics of lower respiratory tract diseases in livestock and poultry. Current evidence suggests that the SARS-associated Cv is a previously unknown Cv strain, probably originating in nonhuman hosts, which has somehow acquired the capacity to infect human beings. Airborne transmission by both large droplets and droplet nuclei appears to allow this Cv to reach the alveoli, leading to a high incidence of pneumonia.

Information published in Morbidity and Mortality Weekly Report by the Centers for Disease Control and Prevention (CDC) 3 and elsewhere 4 has given an update on current SARS cases in the United States:

Prevalence (as of 6/18/03). According to the CDC, there have been 8465 SARS cases worldwide, of which 801 (9.5%) were fatal; 409 cases were reported in the United States. Of the individuals in the United States with suspect SARS, most had recently traveled to SARS-involved geographic areas; the remaining patients had close contact with suspected SARS cases in their immediate families or in their jobs as health care workers.

Diagnosis. In the case definition for SARS, the CDC continues to use clinical manifestations (fever, cough, dyspnea) and histories of recent travels in high-risk geographic areas and/or exposure to known cases of SARS. Suggestive laboratory features include lymphopenia, thrombocytopenia, and increased serum lactic dehydrogenase levels. 2 The CDC does not require abnormalities in chest radiographs for a diagnosis of SARS; the World Health Organization (WHO) case definition does include such radiographic abnormalities. 4 Diagnostic testing. At this time, specific tests for the novel Cv are usually not available in community laboratories. Specimens from SARS-suspect cases should be sent for testing to county/state health laboratories or to the CDC, in accord with instructions given locally. An RT-PCR test specific for RNA for the novel Cv has been positive in sputum specimens obtained within the first 10 days after the onset of fever in some patients with SARS, but results of such tests can be negative thereafter. Culture techniques are also being used in suitably equipped laboratories. Studies of antibody levels against this novel Cv must be carried out in duplicate serum specimens, the second specimen being obtained at least 21 days after the onset of fever.

Travel advisories. The WHO and the CDC recommend avoidance of nonessential travel to China, Hong Kong, Hanoi, and Singapore. Recently, travel to Toronto has also again been discouraged. Recent travelers to these areas who present with fever, cough, or dyspnea should be evaluated immediately and quarantined if indicated.

Angioedema, an uncommon and potentially fatal adverse reaction to treatment with angiotensin-converting enzyme (ACE) inhibitor drugs, is thought to be due to increased levels of bradykinin present when the kininase activity of ACE is inhibited. However, it is unclear why fewer than 1% of those treated with ACE inhibitor drugs manifest angioedema, sometimes only after weeks to months of treatment. Therefore, it has not been feasible to identify individuals at increased risk for ACE inhibitor-induced angioedema. It appears that another enzyme, aminopeptidase P, assumes a major role in catabolizing bradykinin and its active metabolite, des-Arg9bradykinin, when ACE is inhibited. This study assessed mean plasma levels of aminopeptidase P activity in 39 hypertensive individuals with previously documented ACE inhibitor-induced angioedema. These levels (16 nmol/mL/min) were significantly lower than the plasma levels in 39 age-/sex-matched hypertensive individuals with no previous reactions to ACE inhibitor treatment (23 nmol/mL/min) and the levels in 116 normal untreated controls (22 nmol/mL/min; P = .001). In contrast, there were no significant differences in the mean plasma levels of carboxypeptidase N, a minor catabolizer of bradykinin, in the 3 study groups. However, the authors found no correlation between plasma levels of aminopeptidase P and the time between the previous initiation of ACE inhibitor therapy and onset of angioedema episodes in individual patients. Thus, a predictor of angioedema reactivity to ACE inhibitor therapy might have been identified. However, it is still unclear why there is a variable time of onset of such angioedema and why it occurs only episodically when ACE inhibitor drugs are taken daily. 

Investigating lymphocyte responses to allergens has been hindered by the low frequency of circulating allergen-specific lymphocytes. It has generally been assumed that allergens induce T H 2 responses because most cultured allergen-specific clones have a T H 2 phenotype. However, analysis of allergen-specific lymphocytes in nonallergic individuals has not been extensively examined. In the current paper, the investigators reported a new approach using carboxyfluorescein succinimidyl ester (CSFE) to detect allergen-specific lymphocytes by flow cytometry. The CSFE dye is equally distributed into dividing cells so that its level is a specific indication of the number of replication cycles that a cell has undergone. Accordingly, the investigators examined CSFE-low cells after culture in medium supplemented with peanut antigen. Comparison of (1) peanut-allergic individuals, (2) non-peanut-allergic individuals, and (3) individuals who had outgrown peanut allergy revealed interesting findings. Notably, T cells of peanut-allergic donors showed a T H 2 polarization; in contrast, T cells of individuals who had outgrown their allergies and T cells of nonallergic individuals showed T H 1 cytokine responses to peanut antigen. Similar results were seen in lymphocytes of individuals with egg allergy when the lymphocytes were cultured with ovalbumin. These results suggest that food antigens (in particular, peanut antigen) do not intrinsically induce T H 2 skewing but that the type of response depends on the donor's allergic status. The finding that lymphocytes of individuals who outgrow peanut allergy do not have a T H 2 skewing suggests that shifting of a T H 2 response to a T H 1 response underlies clinical tolerance to orally administered allergens. The application of this novel approach to examine antigen-specific T cells is likely to be informative in developing better strategies for immunotherapy. Effects of early-onset asthma and in utero exposure to maternal smoking on subsequent childhood lung function It has been suggested that in utero exposure to maternal smoking and early onset of asthma in infancy are independently associated with subsequent chronic decreases in lung function in childhood. This study compared the effects of these factors, present individually and in combination, within a population of 5933 participants in a Children's Health Study. As predicted, children without asthma who had previously been exposed in utero to maternal smoking showed decreased FEV 1 /forced vital capacity (FVC) ratios and FEF 25-75 . Among children without prior in utero exposure to maternal smoking, those with early-onset asthma had larger decreases in FEV 1 , FEV 1 /FVC, and FEF 25-75 than those with later-onset asthma. However, the largest decreases in pulmonary function were seen in children with both in utero tobacco smoking exposure and early-onset asthma (FEV 1 /FVC decreased approximately 9%; FEF 25-75 decreased approximately 28%). Somewhat surprisingly, there was no significant effect of postnatal environmental tobacco smoke exposure alone on childhood lung function. These findings suggest a possible additive effect of in utero tobacco exposure and early-onset asthma on childhood lung function, providing further evidence of the deleterious effects of maternal smoking during pregnancy. Such smoking during pregnancy might be particularly harmful in situations in which the child to be born is Articles of note . . . 

Although inhaled corticosteroids (ICSs) are recommended as first-line therapy for moderate to persistent asthma, there is still debate about the role and long-term effects of ICSs in the treatment of mild persistent asthma. This multi-institutional study was a randomized, double-blind trial carried out in 7241 subjects (aged 5 to 66 years) in 32 countries who had mild persistent asthma of less than 2 years' duration and no previous regular treatment with ICSs. A comparison was made of either (a) inhaled budesonide (400 µg/day in adults, 200 µg/day in children) or (b) placebo in addition to the preexistent asthma therapy. After the end of the study 3 years later, there had been a significantly lower frequency of acute asthma exacerbations in those receiving the budesonide treatment (3.3%) than in those treated with placebo (5.5%; P < .0001). There was also less prn (as-needed) use of systemic corticosteroids in the budesonide-treated subjects. The pre-bronchodilator FEV 1 was modestly better in the budesonide-treated individuals than in the placebo-treated individuals (mean, +2.24% at 1 year and +1.71% at 3 years; P < .001); the post-bronchodilator FEV 1 was also better in the budesonidetreated subjects. These effects of budesonide treatment were independent of the baseline lung function as well as of the types of baseline medication. In children less than 11 years old, the growth rate after 3 years was reduced by a mean of 1.34 cm in those treated with budesonide, most of this reduction (0.58 cm) occurring during the first year. These findings suggest that relatively early intervention with ICSs decreases the risk of acute asthma flares and the need for systemic steroid use and modestly improves airflow function. It remains to be seen whether the ICSassociated reduction in growth velocity is persistent or progressive. IgG Fc receptors (R) and complement are known to be critical effectors in acute inflammatory responses to immune complexes (ICs), but the exact interaction between these 2 key components has not been established. In the present study, the investigators used a mouse model of acute pulmonary IC-mediated hypersensitivity to determine the interaction between these 2 pathways. They first demonstrated that FcγRIII and C5aR knockout animals had diminished inflammatory responses to ICs. They subsequently localized the expression of FcγRIII and C5aR to alveolar macrophages and showed that administration of recombinant C5a powerfully modulated the expression of the FcγR. In particular, C5a caused upregulation of FcγRIII and downregulation of the inhibitory receptor FcγRII. Furthermore, they demonstrated that the expression of C5a during the acute inflammatory response kinetically correlated with FcγR modulation. These results establish that the C5a anaphylatoxin is a major regulator of FcγR-mediated responses in the lungs. The Toll-like receptor-4 (TLR4) is a critical molecule in mediating LPS-induced neutrophil responses; however, the exact mechanism involved has not been defined. In this study, the investigators aimed to determine whether TLR4 expression on neutrophils or on resident lung cells was critical for neutrophil recruitment. Through use of adoptive bone marrow transfer, chimeric mice expressing TLR4 either in leukocytes or in lung resident cells (endothelial cells) were examined for the contribution of TLR4 expression on these particular cells. Surprisingly, systemic LPS induced a dramatic increase in lung neutrophilia in mice lacking TLR4 selectively on leukocytes. In contrast, mice lacking TLR4 on lung resident cells (endothelium) showed a marked reduction in neutrophil sequestration into the lungs. These findings challenge the conventional view that LPS directly activates neutrophils to trap in the lungs; the results suggest instead that LPS effects involve a far more complicated pathway involving TLR4 signaling in endothelial cells.

SARS-associated coronavirus

Managing SARS amidst uncertainty

Severe acute respiratory syndrome (SARS) and coronavirus testing-United States

Severe acute respiratory syndrome (SARS) and coronavirus testing-United States

the WHO and the CDC have limited their suggested restrictions on travel to Beijing