Effects of steroid therapy on inflammatory cell subtypes in asthma

• Published in: Thorax Vol. 65; no. 5; pp. 384 - 390
• Main Authors: Cowan, Douglas C, Cowan, Jan O, Palmay, Rochelle, Williamson, Avis, Taylor, D Robin
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Thoracic Society 01.05.2010; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adolescent; Adult; Aged; Androstadienes - pharmacology; Androstadienes - therapeutic use; Asthma; Asthma - drug therapy; Asthma - pathology; Asthma - physiopathology; Biological and medical sciences; Breath Tests - methods; Bronchial Provocation Tests - methods; Cardiology. Vascular system; Chronic obstructive pulmonary disease, asthma; Clinical trials; eosinophil; Eosinophils - drug effects; Female; Fluticasone; Forced Expiratory Volume - drug effects; Genotype & phenotype; Glucocorticoids - pharmacology; Glucocorticoids - therapeutic use; Humans; inflammatory cell; Male; Medical sciences; Middle Aged; neutrophil; Neutrophils; Neutrophils - drug effects; Nitric oxide; Nitric Oxide - metabolism; Phenotype; Pneumology; Pulmonary Eosinophilia - drug therapy; Pulmonary Eosinophilia - pathology; Pulmonary Eosinophilia - physiopathology; Respiratory Hypersensitivity - drug therapy; Respiratory Hypersensitivity - pathology; Respiratory Hypersensitivity - physiopathology; Smoking; Spirometry; Sputum - cytology; Steroids; Young Adult; Steroid; Lung disease; Corticosteroid; Typing; Respiratory disease; Asthma; Treatment; Bronchus disease; Anesthesia; Obstructive pulmonary disease; Circulatory system; Inflammatory cell; Immunosuppressive agent; Cardiology; Subtype
• ISSN: 0040-6376; 1468-3296; 1468-3296
• DOI: 10.1136/thx.2009.126722

RationaleAirway 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).ObjectivesTo 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).MethodsSubjects 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.ResultsAfter 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.ConclusionsAfter 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.