The effects of steroid therapy on inflammatory cell subtypes in asthma

Cowan, Douglas C; Cowan, Jan O; Palmay, Rochelle; Williamson, Avis; Taylor, D Robin

doi:10.1136/thx.2009.126722

The effects of steroid therapy on inflammatory cell subtypes in asthma

¹ Dunedin School of Medicine, University of Otago, New Zealand

Correspondence to: Robin Taylor, University of Otago Medical School, Department of Medicine, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, 9001, New Zealand; robin.taylor{at}stonebow.otago.ac.nz

Received 8 September 2009
Accepted 15 November 2009
Published Online First 8 December 2009

Abstract

Rationale: Airway inflammation in asthma is heterogeneous, with different phenotypes. The inflammatory 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 inflammatory phenotypes in asthma after eliminating potentially confounding effects; to compare steroid response in EA versus NEA; 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 1000µg daily for 28+ days. Cut-points were ≥/<2% for sputum eosinophils and ≥/<61% for neutrophils. Results: After steroid withdrawal (n=94), 67% 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 (19.3% to 27.7%, p=0.024). 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 (F_ENO) (p=0.007). Lesser but significant changes occurred in NEA (i.e. paucigranulocytic asthma). F_ENO was the best predictor of steroid response in NEA for AHR (AUC 0.810), with an optimum cut-point of 33ppb.

Conclusions: After eliminating the effects of ICS and smoking, we were unable to identify a neutrophilic phenotype in our 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 absence of steroid response. In NEA this was best predicted by baseline F_ENO.