Abstract

Background: Neutrophil recruitment to the airway is thought to be an important component of continuing inflammation and progression of chronic obstructive pulmonary disease (COPD), particularly in the presence of severe α₁–antitrypsin (α₁–AT) deficiency. However, the chemoattractant nature of secretions from these patients has yet to be clarified.

Methods: The chemotactic activity of spontaneous sputum from patients with stable COPD, with (n=11) and without (n=11) α₁–AT deficiency (PiZ), was assessed using the under-agarose assay. The contribution of leukotriene B₄ (LTB₄) and interleukin 8 (IL-8) to the chemotactic activity was examined using an LTB₄ receptor antagonist (BIIL 315 ZW) and an IL-8 monoclonal antibody, respectively.

Results: Sputum neutrophil chemotactic activity (expressed as % n-formylmethionyl leucylphenylalanine (fMLP) control) was significantly higher in patients with α₁–AT deficiency (mean (SE) 63.4 (8.9)% v 36.7 (5.5)%; mean difference 26.7% (95% CI 4.9 to 48.4), p<0.05). The mean (SE) contribution of both LTB₄ and IL-8 (expressed as % fMLP control) was also significantly higher in α₁–AT deficient patients than in patients with COPD with normal levels of α₁–AT (LTB₄: 31.9 (6.3)% v 18.0 (3.7)%; mean difference 13.9% (95% CI –1.4 to 29.1), p<0.05; IL-8: 24.1 (5.2)% v 8.1 (1.2)%; mean difference 15.9% (95% CI 4.7 to 27.2), p<0.05). When all the subjects were considered together the mean (SE) contribution of LTB₄ (expressed as % total chemotactic activity) was significantly higher than IL-8 (46.8 (3.5)% v 30.8 (4.6)%; mean difference 16.0% (95% CI 2.9 to 29.2), p<0.05). This difference was not significantly influenced by α₁–AT phenotype (p=0.606).

Conclusions: These results suggest that the bronchial secretions of COPD patients with α₁–AT deficiency have increased neutrophil chemotactic activity. This relates to the increased levels of IL-8 and, in particular LTB₄, which accounted most of the sputum chemotactic activity in the patients with COPD as a whole. Increased chemotactic activity, together with inhibitor deficiency, may contribute to the more rapid disease progression seen in α₁–AT deficiency via increased neutrophil recruitment and release of neutrophil elastase.