Clinical control of asthma associates with measures of airway inflammation

Abstract

Background: Control of asthma is the goal of asthma management worldwide. The Global Initiative for Asthma defined control by a composite measure of clinical findings and future risk but without using markers of airway inflammation, the hallmark of asthma. We investigated whether clinical asthma control reflects eosinophilic inflammation in a broad population. Methods: Control of asthma was assessed over a period of 4 weeks in 111 patients with asthma: 22 totally controlled, 47 well controlled and 42 uncontrolled. Lung function, quality of life, airway hyperresponsiveness to AMP, sputum and blood eosinophils, exhaled nitric oxide (NO) and bronchial biopsies were obtained. Results: The 69 subjects with controlled asthma (totally and well controlled combined) had lower median blood eosinophil numbers, slope of AMP hyperresponsiveness, and alveolar NO levels than the 42 subjects with uncontrolled asthma: 0.18 (range 0.01-0.54) versus 0.22 (0.06-1.16) ×109/litre (p<0.05), 3.8 (-0.4-17 750) versus 39.7 (0.4-28 000) mg/ml (p<0.05) and 5.3 (1.5-14.9) versus 6.7 (2.6-51.7) ppb (p<0.05) respectively. Biopsies from subjects with controlled asthma contained fewer eosinophilic granules and more intact epithelium than uncontrolled subjects: 113 (6-1787) versus 219 (19-5313) (p<0.05) and 11.8% (0-65.3) versus 5.6% (0-47.6) (p<0.05) respectively. Controlled asthmatics had better Asthma Quality of Life Questionnaire scores than uncontrolled patients: 6.7 (5.0-7.0) versus 5.9 (3.7-7.0) (p<0.001). Conclusions: The level of asthma control, based on a composite measure of clinical findings, is associated with inflammatory markers, particularly eosinophilic inflammation, with little difference between totally controlled and well controlled asthma.