What Is New In Small Airways Research
By Ves Dimov, MD
Allergist/Immunologist, Assistant Professor, University of Chicago
Anti-IL4/IL13 Antibody Dupilumab is Effective in Asthma with Elevated Eosinophil Levels
This study evaluated the efficacy and safety of dupilumab, a human monoclonal antibody to the alpha subunit of the interleukin-4 receptor in 52 patients with asthma. Dupilumab inhibits signaling by both IL-4 and IL-13 which trigger the same receptor unit.
The study population included patients with persistent, moderate-to-severe asthma and elevated eosinophil levels (a blood eosinophil count of at least 300 cells per micro liter or a sputum eosinophil level of at least 3%). All patients were treated with inhaled glucocorticoids (ICSs) plus long-acting beta-agonists (LABAs) at the beginning of the study.
Dupilumab (300 mg) or placebos were injected subcutaneously once a week for 3 months. Patients stopped LABAs at week 4 and stopped ICSs during week 6-9.
There was an 87% reduction in risk of asthma exacerbation with dupilumab (odds ratio, 0.08). Improvements were observed for most measures of lung function and asthma control.
Editor's note: At first glance, the response to dupilumab therapy is outstanding; however, as the NEJM editorial points out, this monoclonal antibody not the "magic bullet that cures asthma". The study shows efficacy only in a limited subpopulation of patients with asthma. Only 21% of those screened met the inclusion criteria. We do not know whether dupilumab will be effective in the much larger population of patients who use ICS/ LABAs and do not have eosinophilia. It is not clear if it offers any benefit if the patients had stayed on ICS/LABAs.
Wenzel S, Ford L, Pearlman D, Spector S, Sher L et al. Dupilumab in persistent asthma with elevated eosinophil. The New England Journal of Medicine, 2013 May; In press, published online ahead of print. (doi:10.1056/NEJMoa1304048)
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Wechsler M. Inhibiting Interleukin-4 and Interleukin-13 in Difficult-to-Control Asthma. The New England Journal of Medicine 2013, 21 May. (doi:10.1056/NEJMe1305426)
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Small airways diseases, excluding asthma and COPD: an overview in the journal of the European Respiratory Society
Small airways are usually defined as non-cartilaginous airways with an internal diameter of less than 2 mm. Located at a transitional zone between larger airways and lung interstitium, small airways may be affected in a wide variety of pathophysiological conditions.
Small airways diseases, excluding asthma and COPD, are associated with airway infections, connective tissue diseases and inflammatory bowel diseases, bone marrow and lung transplantation, common variable immunodeficiency disorders (CVID), diffuse panbronchiolitis, and diseases related to environmental exposures to pollutants, allergens and drugs. The diagnostic approach often involves a computed tomography scan and pulmonary function tests.
Treatment of small airways diseases is not well established due to the wide variety of causal factors and their often late diagnosis. Better and earlier identification should improve the possibilities to propose earlier treatments.
Source: Burgel PR, Bergeron A, Blic, J, Bonniaud P, Bourdin A et al. Small airways diseases, excluding asthma and COPD: An overview. European Respiratory Review 2013; 22(128): 131-147.
Against all odds: how does anti-IgE (omalizumab) treatment affect intrinsic asthma?
Pathogenetic concept and clinical trials support the view that anti-IgE treatment is specifically effective in allergic asthma. However, there is now growing clinical and mechanistic evidence suggesting that treatment with the anti-IgE antibody omalizumab can be effective in patients with intrinsic asthma.
There are currently two hypotheses that might explain the clinical effects of omalizumab in patients with intrinsic asthma. One hypothesis assumes that patients with intrinsic asthma have a localized allergy with elevated concentrations of allergen-specific IgE antibodies in the airways (similarly to another entity, local allergic rhinitis). In this scenario, anti-IgE treatment would reduce local allergic inflammation in the airways. Another hypothesis assumes that anti-IgE treatment reduces and IgE receptors on plasmacytoid dendritic cells (pDCs), and restores their antiviral activity, thus resulting in reduced disease severity and reduced exacerbation rates.
Large and well-controlled clinical trials with anti-IgE are warranted in patients with intrinsic asthma. In addition, there is a need to find new biomarkers which can identify patients with asthma who respond to anti-IgE treatment.
Source: Lommatzsch M, Korn S, Buhl R, Virchow JC. Against all odds: Anti-IgE for intrinsic asthma? Thorax 2013; Published online before print, 24 May. (doi:10.1136/thoraxjnl-2013-203738)