Effects of steroid therapy on inflammatory cell subtypes in asthma

Cowan, D. C. , Cowan, J. O., Palmay, R., Williamson, A. and Taylor, D. R. (2010) Effects of steroid therapy on inflammatory cell subtypes in asthma. Thorax, 65(5), pp. 384-390. (doi: 10.1136/thx.2009.126722) (PMID:19996343)

Abstract

Rationale: Airway inflammation in asthma is heterogeneous with different phenotypes. The inflammatory cell phenotype is modified by corticosteroids and smoking. Steroid therapy is beneficial in eosinophilic asthma (EA), but evidence is conflicting regarding non-eosinophilic asthma (NEA). Objectives: To assess the inflammatory cell phenotypes in asthma after eliminating potentially confounding effects; to compare steroid response in EA versus NEA; and to investigate changes in sputum cells with inhaled corticosteroid (ICS). Methods: Subjects undertook ICS withdrawal until loss of control or 28 days. Those with airway hyper-responsiveness (AHR) took inhaled fluticasone 1000 μg daily for 28+ days. Cut-off points were ≥/<2% for sputum eosinophils and ≥/<61% for neutrophils. Results: After steroid withdrawal (n=94), 67% of subjects were eosinophilic, 31% paucigranulocytic and 2% mixed; there were no neutrophilic subjects. With ICS (n=88), 39% were eosinophilic, 46% paucigranulocytic, 3% mixed and 5% neutrophilic. Sputum neutrophils increased from 19.3% to 27.7% (p=0.024). The treatment response was greater in EA for symptoms (p<0.001), quality of life (p=0.012), AHR (p=0.036) and exhaled nitric oxide (p=0.007). Lesser but significant changes occurred in NEA (ie, paucigranulocytic asthma). Exhaled nitric oxide was the best predictor of steroid response in NEA for AHR (area under the curve 0.810), with an optimum cut-off point of 33 ppb. Conclusions: After eliminating the effects of ICS and smoking, a neutrophilic phenotype could be identified in patients with moderate stable asthma. ICS use led to phenotype misclassification. Steroid responsiveness was greater in EA, but the absence of eosinophilia did not indicate the absence of a steroid response. In NEA this was best predicted by baseline exhaled nitric oxide.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cowan, Douglas
• Authors: Cowan, D. C., Cowan, J. O., Palmay, R., Williamson, A., and Taylor, D. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Thorax
• Publisher: BMJ Publishing Group
• ISSN: 0040-6376
• ISSN (Online): 1468-3296