Airways inflammation in chronic bronchitis:: the effects of smoking and α1-antitrypsin deficiency

Airways inflammation in chronic bronchitis is thought predominantly to be a direct consequence of neutrophil recruitment and release of elastase in response to factors such as cigarette smoke. The aims of this study were to assess the role of smoking and determine whether the serum elastase inhibitor 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. The authors assessed the sputum concentration of the neutrophil chemoattractants 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), Finally 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 with alpha(1)AT deficiency had greater inflammation in the larger airways with 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-proteinase screen with both reduced sputum (alpha(1)AT (p<0.001) and SLPI concentrations (p<0.05). The reduction in sputum interleukin-8 levels in exsmokers may decrease neutrophil influx and thus explain the slower rate of neutrophil mediated progression of lung disease compared to subjects who continue to smoke. Patients with alpha(1)-antitrypsin deficiency had greater inflammation suggesting that alpha(1)-antitrypsin plays an important role in protecting the larger airways from the inflammatory effects of elastase activity and may explain their more rapid progression of disease.