Airways inflammation in chronic bronchitis: the effects of smoking and alpha(1)-antitrypsin deficiency

Airways inflammation in chronic bronchitis is thought predominantly to be a direct consequence of neutrophil recruitment and release of elastase in re sponse to factors such as cigarette smoke. The aims of this study were to a ssess the role of smoking and determine whether the serum elastase inhibito r alpha(1)-antitrypsin (alpha(1)AT) influenced the process. Airways inflammation was compared between patients with chronic obstructive bronchitis with (n=39) and without (n=42) severe alpha(1)AT deficiency. Th e authors assessed the sputum concentration of the neutrophil chemoattracta nts interleukin-8 (IL-8) and leukotriene (LT)B-4, myeloperoxidase (MPO) as a marker of neutrophil influx, neutrophil elastase activity and its natural inhibitors, alpha(1)AT and secretory leukoprotease inhibitor (SLPI), Final ly serum alpha(1)AT was measured to determine the degree of protein leakage (sputum sol serum alpha(1)AT ratio). Compared to current smokers, the exsmokers had a lower concentration of the chemoattractant IL-8 (p<0.05) and a lower MPO concentration, although this failed to reach conventional statistical significance (p=0.06). Patients w ith alpha(1)AT deficiency had greater inflammation in the larger airways wi th increased LTB4 (p<0.005), MPO (p<0.001), neutrophil elastase activity (p <0.01), protein leak (p<0.001), and were found to have a lower anti-protein ase screen with both reduced sputum (alpha(1)AT (p<0.001) and SLPI concentr ations (p<0.05). The reduction in sputum interleukin-8 levels in exsmokers may decrease neut rophil influx and thus explain the slower rate of neutrophil mediated progr ession of lung disease compared to subjects who continue to smoke. Patients with alpha(1)-antitrypsin deficiency had greater inflammation suggesting t hat alpha(1)-antitrypsin plays an important role in protecting the larger a irways from the inflammatory effects of elastase activity and may explain t heir more rapid progression of disease.