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What Is New In Small Airways Research

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By Ves Dimov, M.D.
Assistant Professor of Medicine and Pediatrics
University of Chicago

Anti-IL5 antibody mepolizumab is effective in eosinophilic asthma

Mepolizumab, a humanized monoclonal antibody that binds to and inactivates interleukin-5 (IL5), has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma.

In a randomized, double-blind trial involving 135 patients with severe eosinophilic asthma, mepolizumab 100 mg was administered subcutaneously once a month for 5 months. The monoclonal antibody had a significant glucocorticoid-sparing effect, reduced exacerbations, and improved control of asthma symptoms.

In another randomized, double-blind trial, 576 patients with recurrent asthma exacerbations and eosinophilic inflammation despite high doses of inhaled glucocorticoids were assigned to receive mepolizumab either a 75-mg intravenous dose (IV) or a 100-mg subcutaneous dose (SC) once a month for 8 months. The rate of exacerbations was reduced by 47% (IV group) and by 53% (SC group). Exacerbations necessitating an ED visit or hospitalization were reduced by 32% in IV group and by 61% in SC group. FEV1 and ACQ-5 score also improved. The safety profile of mepolizumab was similar to that of placebo.

It is reasonable to consider anti–interleukin-5 therapy for patients with severe asthma who are receiving high doses of systemic glucocorticoids and who continue to have an elevated eosinophil count in sputum or blood.

Both studies were funded by GlaxoSmithKline and published in the New England Journal of Medicine.

Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keen ON, Yancey SW, Ortega HG, and Pavord ID. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. New England Journal of Medicine 2014; published online, September 8. (doi:10.1056/NEJMoa1403291)
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Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM et al. Mepolizumab treatment in patients with severe eosinophilic asthma. New England Journal of Medicine 2014; published online 8 September. (doi:10.1056/NEJMoa1403290)
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Nair P. Anti–interleukin-5 monoclonal antibody to treat severe eosinophilic asthma. New England Journal of Medicine 2014; published online 8 September. (doi:10.1056/NEJMe1408614)
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Image Source: Eosinophil, Wikipedia, public domain, Creative Commons license.


Children with highest exposure to allergens and bacteria during first year of life were least likely to have wheeze and allergic sensitization

The Urban Environment and Childhood Asthma study examined a birth cohort at high risk for asthma (n = 560) in Baltimore, Boston, New York, and St Louis.

Cumulative allergen exposure over the first 3 years was associated with allergic sensitization, and sensitization at age 3 years was related to recurrent wheeze. Reduced exposure to house dust bacterial content in the first year was associated with higher risk of atopy and atopic wheeze.

In contrast, first-year exposure to cockroach, mouse, and cat allergens was negatively associated with recurrent wheeze (odds ratio, 0.60, 0.65, and 0.75, respectively). Exposure to high levels of both allergens and bacteria (Firmicutes and Bacteriodetes) in the first year of life was associated with lower risk of atopy or wheeze.

Concomitant exposure to high levels of certain allergens and bacteria in early life might be beneficial. These findings suggest new preventive strategies for wheezing and allergic diseases.

Source: Lynch SV, Wood RA, Boushey H, Bacharier LB, Bloomberg GR et al. Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children. Journal of Allergy and Clinical Immunology 2014; 134(3): 593 -601. (doi:
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Omalizumab therapy is not associated with an increased risk of malignancy

The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma (EXCELS) assessed the long-term safety of omalizumab in a clinical practice setting as part of a phase IV FDA postmarketing commitment.

EXCELS was a prospective observational cohort study in patients aged 12 years or older with moderate-to-severe allergic asthma. There were 2 cohorts: omalizumab (taking omalizumab at baseline) and nonomalizumab (no history of omalizumab treatment). Median follow-up was 5 years for both cohorts. Crude malignancy rates were similar in the omalizumab and nonomalizumab cohorts, with a rate ratio of 0.84. Hazard ratio (omalizumab vs nonomalizumab) was 1.09.

Omalizumab therapy is not associated with an increased risk of malignancy.

Long A, Rahmaoui A, Rothman KJ, Guinan E, Eisner M et al. Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab. Journal of Allergy and Clinical Immunology 2014; 134(3): 560 – 567 (
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Last updated: Friday, September 12th, 2014