Neutrophilic inflammation in severe persistent asthma

Airway inflammation in severe asthma is not well characterized but may invo lve neutrophils. We have compared induced sputum profiles in patients with asthma of varying severity and normal control subjects. We have also measur ed exhaled nitric oxide (NO) as a noninvasive marker of inflammation. Asthm a severity was based on clinical features before treatment and the minimum medication required to maintain asthma control at the time of sputum induct ion, and classified as (1) mild: treated with inhaled beta(2)-agonist occas ionally (n = 23; FEV1, 91%; peak expiratory flow (PEF) variability, 10.5%), (2) moderate: requiring medium dose inhaled steroids to maintain control ( n = 16; FEV1, 88%; PEF variability, 9.1%), and (3) severe: despite using in haled and oral steroids (n = 16; FEV I, 61%; PEF variability, 36.2%). The a sthmatic patients were nonsmokers with evidence of airway hyperresponsivene ss or reversible airway obstruction, and free of respiratory tract infectio n for at least 6 wk. Sputum revealed significantly increased neutrophil num bers in severe asthma (53.0 [38.4-73.5]%, p < 0.05) compared with mild asth ma (35.4 [29.8-46.1]%) and normal control subjects (27.7 [20.6-42.2]%). Int erleukin-8 (IL-8) and neutrophil myeloperoxidase (MPO) levels were increase d in asthmatic patients, with the highest levels in severe asthma. Eosinoph il numbers were increased in both mild and severe asthma, but interleukin-5 (IL-5) revels were highest in mild asthma, whereas eosinophil cationic pro tein (ECP) levels were highest in severe asthma. Exhaled NO levels were hig hest in asthmatic untreated with corticosteroids, but there was no signific ant difference between asthmatics using corticosteroids (Croups 2 and 3), r egardless of clinical asthma severity. This confirms the role of eosinophit s in asthma but suggests a potential role of neutrophils in more severe ast hma.