Enhanced neutrophil response in chronic obstructive pulmonary disease

Background-Neutrophils are likely to play a major role in the inflammatory response seen in chronic obstructive pulmonary disease (COPD). This study s ought to address the hypothesis that an enhanced neutrophil response to pro inflammatory agents in COPD may contribute to their recruitment and activat ion in the lungs. Methods-Circulating neutrophils were obtained from 10 patients with COPD, e ight long term smokers with normal lung function, and eight healthy never s moking controls. The in vitro production of reactive oxygen species (ROS) w as measured by the NADPH oxidase method (respiratory burst) and the surface expression of several adhesion molecules (Mac-l, LFA-1 and L-selectin) was measured by flow cytometry. Measurements were obtained under basal conditi ons and after stimulation with phorbol myristate acetate (PMA) and tumour n ecrosis factor alpha (TNF alpha). mRNA levels of p22-phox (a subunit of NAD PH oxidase) and Mac-1 (CD11b) were also determined by reverse transcriptase polymerase chain reaction (RT-PCR). Results-Patients with COPD showed enhanced respiratory burst compared with smokers with normal lung function, both under basal conditions (mean (SE) f luorescence intensity (MFI) 15.1 (0.5) v 11.6 (0.5); mean difference -3.4 ( 95% CI of the difference -5.1 to -1.8), p <0.01) and after PIMA stimulation (MFI 210 (7) v 133 (10); mean difference -77 (95% CI of the difference -10 2 to -52), p<0.01). Mac-1 surface expression was also enhanced in patients with COPD, both under basal conditions (MFI 91 (5) v 45 (3); mean differenc e -46 (95% CI of the difference -61 to -31), p<less than>0.001) and after s timulation with TNFa (MFI 340 (15) v 263 (11); mean difference -77 (95% CI of the difference -119 to -34), p=0.001). These differences were also appar ent when patients with COPD were compared with non-smokers (p <0.05). The m RNA levels of p22-phox and Mac-1 (CD11b) were similar in patients with COPD and smokers with normal lung function, suggesting that the observed differ ences were due to post-transcriptional regulation. Conclusions-These results demonstrate an enhanced neutrophil response to pr oinflammatory agents in patients with COPD which may contribute to their en hanced recruitment and activation in the lungs of these patients. These fin dings support those of other studies which have indicated that the neutroph il is likely to play a major role in the pathogenesis of this disease.