Neutrophil activation in fibrosing alveolitis: a comparison of lone cryptogenic fibrosing alveolitis and systemic sclerosis.

Fibrosing alveolitis complicating systemic sclerosis (FASSc) carries a better prognosis than lone cryptogenic fibrosing alveolitis (CFA). We wanted to determine whether this improved prognosis is associated with differential neutrophil migration and activation in the lower respiratory tract. We therefore compared bronchoalveolar lavage (BAL) neutrophil numbers and levels of neutrophil-derived enzymes in FASSc, CFA and normal individuals. Bronchoalveolar lavage was performed on 45 subjects (FASSc n = 20; CFA n = 15; normals n = 10); cell counts and levels of neutrophil-derived enzymes, myeloperoxidase, elastase (total elastase and elastase/alpha 1 antitrypsin complexes), collagenase and lactoferrin were measured. Lung function testing was performed in subjects with fibrosing alveolitis. Significant differences in the levels of collagenase, myeloperoxidase and elastase/ alpha 1-antitrypsin complexes were present in the BAL fluid from the three groups. Patients with CFA had significantly higher neutrophil percentages and levels of collagenase and myeloperoxidase than those with FASSc. Disease extent, as judged by lung volumes and gas transfer, was comparable in the CFA and FASSc groups. Forced vital capacity (% predicted) was significantly lower in patients with evidence of increased neutrophil enzyme release than those without. We conclude that: 1) increased neutrophil migration to the lung is accompanied by release both of primary and secondary granule enzymes in cryptogenic fibrosing alveolitis; and 2) the lower amounts of neutrophil products in fibrosing alveolitis complicating systemic sclerosis may account for the improved prognosis, even when disease is as extensive as in cryptogenic fibrosing alveolitis.