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• Achieving and maintaining asthma control in an urban, lower socioeconomic population
• Icatibant, a bradykinin receptor-2 antagonist, for treatment of hereditary angioedema
• Omalizumab controls episodes of unprovoked anaphylaxis in 2 patients with mastocytosis
• Polymorphisms in integrin β3 are associated with asthma and allergy early in life
• Population-based data on food allergy in adults and food label challenges
• Patients with asthma respond to placebo: Believe and ye shall breathe
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Achieving and maintaining asthma control in an urban, lower socioeconomic population 

New guidelines recommend using an assessment of asthma control to guide therapy at regular visit intervals. The degree to which a population can achieve and maintain control of asthma remains unclear, particularly when barriers to care are minimized in a lower socioeconomic setting. In this issue of the Journal, Jones and coauthors (p 1445) report on 2185 children who received care in mobile clinics (Breathmobiles) at school sites across urban Los Angeles. Treatment was guided by an assessment of asthma control with longitudinal patterns viewable at each visit. By the sixth visit, the probability of ever meeting asthma control criteria was 98% for patients with mild disease, 96% for those with moderate disease, and 89% for those with severe disease (median visit interval, 7 weeks). After control criteria were first met, maintenance of control during a subsequent 2-year period was highly variable (39% of patients met criteria at >90% of subsequent visits, 48% at 50% to 89% of subsequent visits, and 13% at <50% of subsequent visits). Maintenance of asthma control was most closely associated with a regularly recorded provider estimate of adherence and visit interval. The findings provide new information on achieving and maintaining asthma control in a lower socioeconomic population along with information that may be useful for planning health services and improving outcomes in this setting.

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• Long-term asthma control is highly variable in a population receiving ongoing care in accordance with new guidelines.

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Icatibant, a bradykinin receptor-2 antagonist, for treatment of hereditary angioedema 

Hereditary angioedema due to a genetic C1 inhibitor deficiency is clinically characterized mainly by recurrent skin swellings, severe abdominal pain attacks, and potentially life-threatening laryngeal edema. Recent data suggest that bradykinin is the most important mediator for the underlying vasodilation and increased vasopermeability. Thus, blocking the bradykinin-2 receptor at the endothelium might result in an improvement of clinical symptoms. In this issue, Bork and coworkers (p 1497) report the results of an uncontrolled proof-of-concept study with Icatibant, a highly specific bradykinin receptor-2 antagonist, in patients with hereditary angioedema. They treated 15 patients during the first hours of 20 acute skin swellings and abdominal attacks, either intravenously or subcutaneously. The time to onset of symptom relief and the length of the treated attacks were determined and compared with those in a large number of untreated edema attacks that had occurred previously at similar locations in the same patient. The severity of symptoms was determined using a visual analog scale. In comparison with untreated attacks, Icatibant treatment reduced the mean time to onset of symptom relief by 97%. Within 4 hours, the symptoms improved considerably, and the course of the attacks was shortened. The report demonstrates the clinical usefulness of antagonizing bradykinin binding to bradykinin receptor-2 in hereditary angioedema.

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Omalizumab controls episodes of unprovoked anaphylaxis in 2 patients with mastocytosis 

Anaphylaxis is a potentially life-threatening event often associated with hypersensitivity to such substances as foods, drugs, and insect venoms. When a cause cannot be identified, the designation idiopathic is applied. Some patients with systemic mastocytosis experience idiopathic hypotensive episodes. In this issue of the Journal, Carter and coauthors (p 1550) report a reduction in idiopathic episodes of systemic hypotension in 2 patients with indolent systemic mastocytosis treated with omalizumab. Both patients required epinephrine, supportive care, and hospitalization prior to receiving study drugs, and an elevated serum tryptase was documented with these episodes. The first patient had pediatric-onset indolent systemic mastocytosis with a 10-year history of 4 to 6 anaphylactic episodes per year, and the second patient had adult-onset indolent systemic mastocytosis with a 6-year history of approximately 16 anaphylactic episodes prior to the initiation of omalizumab therapy. Neither patient experienced hypotensive episodes on monthly injections of omalizumab after 12 and 28 months of follow-up, respectively, at the time of this report. The authors have thus demonstrated a possible role for omalizumab in the treatment of unprovoked anaphylaxis in patients with mastocytosis. A prospective clinical trial is needed to investigate the clinical efficacy of omalizumab in the treatment of idiopathic anaphylaxis in mastocytosis.

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Polymorphisms in integrin β3 are associated with asthma and allergy early in life 

Several recent studies have implicated integrins or related genes in the pathogenesis of asthma or allergic disease. In an earlier study from the same group, associations were reported with single nucleotide polymorphims (SNPs) in integrin β3 (ITGB3) and asthma and allergic sensitization in 4 populations, which included cases and controls of African and European descent. One European sample was the parents of child participants in a birth cohort study, the Childhood Onset of ASThma (COAST) Study. In this report, Thompson and colleagues (p 1423) describe the results of a follow-up study in the COAST children examining the effect of ITGB3 polymorphisms on allergy and asthma and gene-environment interactions in the first 6 years of life. The study revealed significant associations among SNPs in ITGB3 and asthma, wheezing, and IgE levels, suggesting an early role for this gene in the development of asthma. Specifically, SNPs at the 3′ end of the gene were significantly associated with IgE levels beginning at 1 year of age (see Figure), whereas an intronic SNP showed significant interaction effects with viral respiratory illness in infancy on asthma susceptibility. These findings suggest that genetic variation in ITGB3 contributes to asthma susceptibility and allergic sensitization with effects beginning early in life.

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• Children with the GG genotype had the highest IgE levels beginning at year 1.

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Population-based data on food allergy in adults and food label challenges 

Although there is an increasing interest in food allergies, few population-based studies have reported on the prevalence of allergies to numerous specific foods in adults and the problems that food-allergic adults face when reading food labels. In this issue, Vierk et al (p 1504) report that the prevalence of self-reported food allergy in a US Food and Drug Administration survey of adults in the United States was 9.1%, with 5.3% of respondents self-reporting a doctor-diagnosed food allergy. Prevalence of self-reported doctor-diagnosed allergy to specific foods ranged from 0.04% (soy) to 1.1% (milk/dairy). Almost 77% of these food-allergic respondents reported reading food labels to avoid allergenic foods, and a large portion considered certain label characteristics to be a serious problem for managing their food allergy. The Food Allergen Labeling and Consumer Protection Act of 2004 requires food label declaration of the source of each ingredient that is or contains protein derived from one of the 8 most common food allergens. Although food allergy is self-reported in this study, the findings provide needed population-based data on characteristics of food allergy and label use among US food-allergic adults. The authors recommend comparing the findings from this study with data collected after the January 1, 2006, effective date of the labeling law.

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Patients with asthma respond to placebo: Believe and ye shall breathe 

Published assertions that only subjective aspects of asthma, such as dyspnea, respond to placebo do not concur with the collective experience of clinicians and researchers. Asthma has long been believed to have a psychosomatic component; recent studies linking “stress” to increased asthma severity support the role of disease-relevant mind-body links. Despite the availability of objective measures of asthma activity, few investigators have chosen to study placebo in asthma. In this issue of the Journal, Kemeny and coauthors (p 1375) report on the placebo response in mild asthma, modulating bronchial hyperreactivity as measured by a methacholine inhalation challenge. They found in a randomized, double-blind study that pretreatment with a placebo (drug-free) inhaler resulted in nearly a doubling of methacholine PC₂₀ compared with baseline, almost one third of the improvement that followed salmeterol inhalation (see Figure). These findings validate the existence of an objective and large placebo response in asthma. They also provide a model system to study specific brain pathways that are responsible for processing perceived stimuli to modulate physiologic responses. Understanding the placebo response may also lead to novel therapeutic approaches to asthma and other diseases; such treatment, after all, is likely to induce adverse effects “no worse than placebo”!

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• Placebo inhalation significantly improves methacholine PC₂₀ in mild asthmatics.