The Journal of Allergy and Clinical Immunology
Volume 120, Issue 3 , Pages 489-490, September 2007

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Epidemic asthma during thunderstorms associated with Alternaria alternata sensitivity 

Sensitivity to the fungal spore Alternaria is associated with rapid onset near fatal asthma and fatal asthma. Alternaria spores are present in large numbers, especially during harvesting, and can be inhaled whole or as fragments. Farming practice at harvest before thunderstorms increases air counts of fungal spores and broken Alternaria. A direct causal effect of Alternaria or other fungal spores triggering thunderstorm-related asthma epidemics has not been established. A case control study by Pulimood et al (p 610) shows that 23 of 26 thunderstorm-related asthma cases were sensitive to Alternaria species. Controls were patients with summer seasonal asthma. Three of the 26 cases required ventilation for severe asthma. The only asthma-related death in Cambridge that year occurred on the day of the storm. High counts of fragmented Alternaria spores were associated with increased asthma admissions. The study concludes that Alternaria sensitization in grass pollen–allergic patients with seasonal asthma predicts susceptibility to thunderstorm asthma. The findings are clearly of significant public health importance in temperate climes. Vulnerable groups of subjects with asthma should be identified from clinical history and allergy skin test results. Collaboration between the Met Office and aeroallergen-counting centers should allow prediction of future epidemics, warning clinicians and at-risk groups in time.

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Risk of developing asthma in young children with atopic eczema 

The relationship between atopic eczema and asthma may not be as simple as previously assumed. Clinicians counseling parents of young children with atopic eczema commonly employ the “atopic march” model, depicting progression of atopic eczema in young children into asthma in the majority of children in later childhood. van der Hulst et al (p 565) conducted a systematic review to assess this risk of developing asthma in young children with atopic eczema. Thirteen prospective cohort studies, comprising a total of 5381 children, were included. From the included birth cohort studies, a pooled odds ratio of 2.14 was calculated for the risk of asthma in young children with atopic eczema compared with those without (see Figure). In studies of eczema cohorts, a prevalence of asthma in later childhood of 35.8% for eczema inpatients and 29.5% for a combined group of inpatients and outpatients was calculated. Although the risk of asthma in infants with eczema is twice as large as that in infants without eczema, the absolute risk (1 in 3) is much lower than commonly assumed. This has important consequences for counseling parents of infants with atopic eczema.

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IgE in the serum is a private decision 

In a detailed analysis of patients with high IgE atopic eczema, Lim et al (p 696) have looked for common traits in the IgE repertoire among different patients. Starting with the hypothesis that IgE antibodies from unrelated individuals react to identical or highly similar epitopes, they have analyzed the messenger RNA encoding the entire IgE repertoire and have compared similar-looking variable regions on the sequence level. Their results reveal that atopic individuals show strongly increased quantities of IgE-encoding transcripts as compared with healthy controls, although the number of B cells and plasma cells carrying IgE varies only moderately. In addition, the authors show that, at least in the blood, B cells generate a highly individual repertoire of IgE rearrangements regardless of common sensitizations shared among individuals. These rearrangements show signs of affinity maturation and display usage of the different heavy chain variable region families in a distribution identical to that reported for IgM and IgG. Thus, the production and formation of a given IgE molecule has implications defined by the individual rather than by the allergen itself. Finally, the authors have extended their findings to patients undergoing low-dose anti-IgE therapy for severe atopic eczema, and they could identify an increase in the proportion of IgG/IgE-specific mRNA, a good marker of the unexpected therapeutic success.

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Anti-IgE treatment of eosinophilic gastroenteritis and esophagitis 

Eosinophil-associated gastrointestinal disorders (EGIDs), including eosinophilic esophagitis and gastroenteritis, are being increasingly recognized in clinical practice. Despite this greater recognition, current therapy for EGIDs is inadequate. Improvements in therapy will require a greater understanding of disease pathogenesis. Using omalizumab as a means to “knock out” IgE in patients, this study examines the role of IgE in EGID pathogenesis, as well as the potential of anti-IgE as a therapeutic. Foroughi et al (p 594) performed an open-label clinical trial of omalizumab in 9 subjects with EGIDs and evidence of food allergy and/or atopy. Subjects received omalizumab every 2 weeks for a total of 16 weeks, whereas medication and diet were held constant. Peripheral blood eosinophilia decreased significantly after treatment. Duodenal and gastric antral tissue eosinophils also decreased markedly. In contrast, esophageal eosinophils did not improve and actually increased in several subjects, although no new esophageal symptoms were noted. EGID symptom scores improved during the study. These results demonstrate that IgE-dependent processes play a major role in the generation of the eosinophilic inflammation found in EGIDs. Taken together, the ability of this drug to decrease blood and tissue eosinophil counts and improve clinical symptoms provides encouraging evidence to support larger placebo-controlled clinical trials.

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R551 IL4R variant increases atopic asthma risk 

IL-4 and IL-13 are important regulators of allergy and asthma. IL-4 receptor α (IL-4Rα) enables immune cells, as well as some nonimmune cells, to respond to these molecules. Early evidence suggested that genetic variations in IL4R, which is the gene that encodes IL-4Rα, may be a risk factor for asthma. However, conflicting results have been reported over the past 10 years as to the significance of specific genetic variations in IL4R for increasing risk for asthma. In an attempt to resolve these apparently conflicting reports, Loza et al (p 578) performed an analysis combining the results of case-control studies that tested whether specific genetic variations in IL4R increase risk for asthma. They found that the Q551R variation was strongly associated with atopic asthma risk, those carrying the less frequent R551 variant having an approximately 80% higher risk for atopic asthma than those carrying the common Q551 form. No association with asthma risk was found for the I50V variation. These results may help us better understand why asthma develops in certain individuals. Further studies to test whether medications that target the IL-4R pathway are more effective for individuals carrying a “high-risk” IL4R variant are warranted.

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Maternal asthma and pregnancy outcomes 

In this month's Journal, Enriquez et al (p 625) describe an increased frequency of adverse pregnancy outcomes in women with asthma. In a Medicaid population (N = 140,299) with poor medication adherence and high rates of asthma emergency department visits, the authors describe dose-response relationships between asthma and exacerbated asthma with hypertensive disorders of pregnancy, membrane-related disorders, preterm labor, antepartum hemorrhage, cesarean delivery, and low birth weight. Asthma and exacerbated asthma were also associated in a dose-response manner with small decrements in birth weight. This study supports expert recommendations that, given the evident safety of asthma medications during pregnancy and the importance of adequate maternal oxygenation during pregnancy, asthma control during pregnancy should be maintained with comprehensive asthma treatment. Asthma is one of the most common chronic medical conditions complicating pregnancy, and pregnancy is a common occurrence in female patients of childbearing age. Both specialists treating asthma and our obstetric colleagues can improve the health of women and infants by stressing the importance of well-controlled asthma during pregnancy. By addressing women's concerns about asthma medication safety during pregnancy and reinforcing the importance of “breathing for two,” physicians can promote healthy pregnancy outcomes and illustrate the benefits of adequately controlled asthma.

PII: S0091-6749(07)01426-1

doi:10.1016/j.jaci.2007.07.028

The Journal of Allergy and Clinical Immunology
Volume 120, Issue 3 , Pages 489-490, September 2007

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