Some patients with chronic asthma develop irreversible airflow obstruction. Our aim was to assess whether reported duration of asthma and induced sputum cell counts were associated with pulmonary function in patients with asthma who did not smoke. Maximal forced expiratory volume in the first second (FEV(1)) was determined following a steroid trial (oral prednisolone, 30 mg/d [n = 92 patients]; or inhaled fluticasone, 2000 microg/d [n = 5]; for 2 weeks) and 2.5 mg of nebulized albuterol. Asthma history was recorded with duration from first diagnosis. All subjects were nonsmokers, or were to have stopped smoking > or =5 years previously and smoked < or =5 pack-years (n = 12). Induced sputum was obtained from 59 subjects for analysis of airway cell counts. Maximal FEV(1) was inversely associated with asthma duration (r = -0.47, P <0.0001), age (r = -0.40, P <0.0001), and the proportion of sputum neutrophils (r(s) = -0.50, P = 0.00004). After adjusting for age, both duration of disease and sputum neutrophils were independently associated with maximal FEV(1). Neutrophil activation, as measured by sputum myeloperoxidase levels, was positively associated with the proportion of sputum neutrophils (r(s) = 0.45, P = 0.0004) and inversely associated with maximal FEV(1) (r(s) = -0.59, P <0.0001). Long disease duration may be a predisposing factor for the development of irreversible airflow obstruction in patients with chronic asthma. The negative associations of sputum neutrophil count and activation with maximal FEV(1) suggest that neutrophils may be involved in the pathophysiology of irreversible airflow obstruction in asthma.