Refractory Airway Type-2 Inflammation in a Large Subgroup of Asthmatics treated with Inhaled Corticosteroids

Publication date: Available online 7 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Michael C. Peters, Sheena Kerr, Eleanor M. Dunican, Prescott G. Woodruff, Merritt L. Fajt, Bruce D. Levy, Elliot Israel, Brenda R. Phillips, David T. Mauger, Suzy A. Comhair, Serpil C. Erzurum, Mats W. Johansson, Nizar N. Jarjour, Andrea M. Coverstone, Mario Castro, Annette T. Hastie, Eugene R. Bleecker, Sally E. Wenzel, John V. Fahy
BackgroundAirway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients on high dose inhaled corticosteroids (ICS) is uncertain.ObjectiveTo determine if airway type 2 inflammation persists in patients treated with ICS and to evaluate the clinical features of patients with steroid resistant airway type-2 inflammation.MethodsWe used qPCR to generate a composite metric of type-2 cytokine gene expression (type 2 Gene Mean, "T2GM") in induced sputum cells from healthy controls, severe asthma patients on ICS (n=174), and non-severe asthma patients on ICS (n=85). We explored relationships between asthma outcomes and the T2GM, and the utility of non-invasive biomarkers of the airway T2GM.ResultsThe sputum cell T2GM in asthma subjects was significantly increased in asthma subjects and remained high following treatment with intramuscular triamcinolone. We used the median value for the T2GM as a cutoff to classify "steroid-treated type 2-low" (stT2-low) and "steroid-resistant type 2-high" (srT2-high) subgroups. Compared to patients with stT2-low asthma, those with srT2-high asthma were older age and had more severe asthma. Blood eosinophil cell counts predicted srT2-high asthma when BMI was < 40, but not when it was ≥40, whereas, blood IgE strongly predicted srT2-high asthma when age was < 34 years but not when it was ≥34.ConclusionDespite ICS therapy many asthmatics have persistent airway type 2 inflammation, (srT2-high asthma) and these patients are older and have more severe disease. Body weight and age modify the performance of blood-based biomarkers of airway type-2 inflammation.



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