Subclinical alveolar inflammation in rheumatoid arthritis: superoxide anion, neutrophil chemotactic activity and fibronectin generation by alveolar macrophages

Interstitial lung disease (ILD) can be detected by pulmonary function testing (PFT) in 30-40% of rheumatoid arthritis (RA) patients. We assessed by bronchoalveolar lavage (BAL) the patterns of alveolitis in 21 RA patients: group 1 comprised 12 patients without evidence of ILD, and group 29 patients with clinical ILD defined by abnormal pulmonary function tests and/or chest X-ray. Cellular characteristics of BAL were studied in both groups. In addition, alveolar macrophages (AM) from patients in group 1 were isolated, and three parameters of cellular activation were studied: superoxide anion, fibronectin and neutrophil chemotactic activity generation. Total cell counts were not increased in group 1 but significantly increased in group 2 compared to controls. In group 1, 5/12 patients had elevated lymphocyte percentage (greater than 18%) suggesting subclinical lymphocyte alveolitis. In contrast, neutrophil alveolitis (greater than 4%) was found in 7/9 patients in group 2, mean percentage 12.9 +/- 4.2, compared with 1.2 +/- 6.4% in controls and 1.9 +/- 0.5% in group 1. These changes were not correlated with disease duration nor rheumatoid factor titres. Marked elevation of lymphocyte percentage was observed in patients with abnormal serum beta-2-microglobulin. Alveolar macrophages from group 1 patients released increased amounts of superoxide anion (7260 +/- 2700 vs controls 850 +/- 120 URL/5.10(5) cells), neutrophil chemotactic activity (21 +/- 4.8 vs controls 8.1 +/- 0.7 cells/HPF), and fibronectin (6.1 +/- 1.6 vs controls 1.3 +/- 0.2 ng.10(6) cells/hour). Whether or not lymphocyte alveolitis and/or AM dysfunction are pathogenic mechanisms of subsequent interstitial lung disease in patients who are still free of symptoms remains to be determined.