Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma

Background: Although the role of eosinophils in airway inflammation in chro nic asthma has been extensively studied, a role for neutrophils has not bee n well characterized. Furthermore, prior studies have not systematically so ught or controlled for factors that might confound the relationship between cellular markers of inflammation and physiologic measures of airway functi on. Objective: The purpose of this study was to determine whether eosinophilic and neutrophilic inflammation independently contribute to abnormalities of airway function in asthma. Methods: Multivariate analysis of data collected during screening and enrol lment of 205 asthmatic adults for clinical trials was conducted to examine the relationships between cellular inflammation in induced sputum and FEV1 and methacholine responsiveness (PC20) while confounding factors were contr olled for. Results: We found that age, sex, ethnicity, and use of inhaled corticostero ids were important confounding factors of the relationship between cellular inflammation and airway function. When these factors were controlled for, multivariate analysis showed that eosinophil percentage in induced sputum i s independently associated with lower FEV1 and lower PC20 (P =.005 and P =. 005, respectively). In the same models, increased sputum neutrophil percent age is independently associated with lower FEV1 (P =.038) but not with PC20 (P =.49). Conclusions: These results suggest that both eosinophilic inflammation and neutrophilic inflammation independently contribute to abnormalities of FEV1 in asthma. Therapies directed specifically at control of neutrophilic infl ammation might be useful in improving airway caliber in patients with chron ic asthma.