There is evidence for the involvement of a wide range of cell types in the pathogenesis of COPD, including neutrophils, macrophages and CD8+ T cells. Neutrophilic inflammation is observed in patients with α1-proteinase inhibitor (α1-PI) deficiency. Because α1-PI not only acts as an inhibitor of neutrophil serine proteinases such as neutrophil elastase, but also inhibits the cytotoxic and antimicrobial peptides neutrophil defensins, Wencker (Essen, Germany) studied neutrophil defensin levels in patients with α1-PI deficiency. Increased neutrophil defensin levels were found in the epithelial lining fluid of α1-PI deficiency patients, levels that correlated with neutrophil numbers and interleukin-8 levels. These observations lend further support to the hypothesis that neutrophil defensins might be one of the neutrophil products involved in the pathogenesis of emphysema associated with α1-PI deficiency. Therefore the treatment of patients with α1-PI deficiency with α1-PI, for instance with the use of α1-PI inhalation as reported by Vogelmeier (Munich, Germany), might potentially inhibit the proinflammatory activities of neutrophil defensins in addition to inhibiting neutrophil elastase.
The observations reported by Frankenberger (Munich, Germany) demonstrated an interesting approach to the study of macrophages in COPD. Analysis of induced sputum demonstrated that there is an increased proportion of CD14+ CD16+ macrophages in induced sputum from COPD patients. Because studies in peripheral blood have shown that CD14+ CD16+ monocytes represent a subpopulation of macrophages with a high proinflammatory activity, these studies indicate a novel approach to the study of macrophages in COPD. Eosinophilic inflammation has been found to be associated with exacerbations of chronic bronchitis. Qiu (London, UK) studied the expression of putative eosinophil chemotactic chemokines in exacerbations of chronic bronchitis, and showed an increase in eosinophil numbers and RANTES expression (shown by in situ hybridization) in bronchial biopsies of patients with chronic bronchitis during exacerbations. A trend towards an increase in MCP-4 and eotaxin expression was noted. The capacity of sputum from COPD patients to induce the migration of neutrophils in vitro across a double layer of cultured epithelial and endothelial cells was used by van Overveld (Antwerp, Belgium) to assess the anti-inflammatory effect of treatments with inhaled steroids or N-acetylcysteine. Treatment of patients with these drugs reduced the extent of sputum-induced neutrophil transmigration. Whereas steroids were active after 2 months of treatment and were ineffective after prolonged treatment (more than 4 months), N-acetylcysteine treatment was effective only after prolonged treatment (more than 4 months).