Sputum chemotactic activity in chronic obstructive pulmonary disease: effect of alpha1-antitrypsin deficiency and the role of leukotriene B4 and interleukin 8

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 alpha(1)-antitrypsin (alpha(1)-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) alpha(1)-AT deficiency (PiZ), was assessed using the under-agarose assay. The contribution of leukotriene B(4) (LTB(4)) and interleukin 8 (IL-8) to the chemotactic activity was examined using an LTB(4) 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 alpha(1)-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