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 alpha1-antitrypsin (alpha1AT) influenced the process. Airways
inflammation was compared between patients with chronic obstructive
bronchitis with (n=39) and without (n=42) severe alpha1AT deficiency. The authors assessed the sputum concentration of the neutrophil
chemoattractants interleukin-8 (IL-8) and
leukotriene (LT)B4,
myeloperoxidase (MPO) as a marker of neutrophil influx,
neutrophil elastase activity and its natural inhibitors, alpha1AT and
secretory leukoprotease inhibitor (SLPI). Finally serum alpha1AT was measured to determine the degree of
protein leakage (sputum
sol serum alpha1AT 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 alpha1AT 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 alpha1AT (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 alpha1-antitrypsin deficiency had greater
inflammation suggesting that alpha1-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.