Editors' ChoiceAsthma

Asthmatic Granulomatosis: A New Disease?

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Science Translational Medicine  08 Aug 2012:
Vol. 4, Issue 146, pp. 146ec143
DOI: 10.1126/scitranslmed.3004705

A new twist on an old disease? This may be the case with adult severe asthma. Asthma is common, affecting 25 million American adults and children. Despite a reduction in overall mortality over the past decade, asthma still claims the lives of nine patients each day in the United States. Severe asthma represents ~10% of all asthma, yet it incurs the greatest healthcare costs in asthma. In a new study of patients with severe asthma, Wenzel and colleagues attempt to better understand the pathobiology that so dramatically lowers the quality of life in these patients.

Wenzel et al. took open-lung biopsies from 19 patients with severe asthma. They found that 10 of these patients had pathology consistent with asthma (goblet cell hyperplasia and eosinophilia) in addition to a new pathologic finding: interstitial inflammation with airway-centric, nonnecrotizing granulomas. Consistent with these subtle lung interstitial abnormalities, at least 5 of the 10 cases had reduced diffusion capacity on lung function testing. The authors were careful to exclude confounding diseases such as hypersensitivity pneumonitis, sarcoidosis, aspiration, and pneumonia, but a majority of the patients had a family or personal history of autoimmune-like diseases. The 10 cases with granulomatous inflammation were then treated with immunosuppressant drugs, including methotrexate, mycophenolic acid, azathioprine, and/or infliximab. Interestingly, 9 of the 10 patients improved or maintained their lung function, with less reliance on systemic corticosteroid treatment. The authors concluded that a subset of severe asthma may manifest this granulomatous pathology and could, therefore, potentially benefit from immunosuppressant medications.

This study by Wenzel and colleagues opens doors for further research on the potential autoimmune mechanisms underlying a subset of severe asthma. Moreover, this is an example of “reverse translation,” in which a clinical observation may directly lead to efforts at the bench to better characterize underlying immunologic pathways and to identify biomarkers for the diagnosis and treatment of severe asthma. If we are lucky, finding this new “twist” may improve the lives of patients who suffer from severe asthma but are not being effectively treated.

S. E. Wenzel et al., Asthmatic granulomatosis: A novel disease with asthmatic and granulomatous features. Am. J. Respir. Crit. Care Med., 5 July 2012 (10.1164/rccm.201203-0476OC). [Abstract]

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