LOW-DOSE METHOTREXATE MAY CAUSE AIR TRAPPING IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Both rheumatoid arthritis (RA) and methotrexate (MTX) are reported to be associated with the development of pulmonary disease. To determine whether MTX enhanced the risk of developing abnormalities in pulmonary function in patients with RA, we prospectively studied 31 subjects (1 2 male, 19 female) with the diagnosis of classic RA for an average per iod of 4.4 yr (range, 1 to 5 yr). Each subject was placed on low-dose weekly MTX (mean 17 mg, range 2.5 to 40) for control of RA symptoms. O ther medications included nonsteroidal anti-inflammatory agents and pr ednisone if required for control of arthritis symptoms. No other immun osuppressive therapy was used. Each subject was evaluated by pulmonary function tests (PFT) and chest X-ray initially, and at 1, 2, 3.5, and 5 yr. Chest X-rays obtained initially and at the end of the study per iod were found to be normal. The percent predicted values for initial PFTs in the study group were within the normal range. From the beginni ng to the end of the observation period, the following mean changes in lung function were observed: 1.9% increase in TLC, 5.1% increase in r esidual volume (RV), 1.8% increase in FVC, 0.71% decrease in FEV(1), 1 4.7% improvement in alveolar-arterial oxygen (A-aO(2)) difference, and a 12.7% increase in single-breath diffusing capacity (DL(CO)). To det ermine whether MTX (average dose, weekly dose, or cumulative dose) was significantly related to changes in pulmonary function, we used multi variate techniques to control for the initial measure of lung function while assessing the relationship between MTX and the subsequent measu res of lung function. In addition, we controlled for age, sex, height, follow-up time, pack-years of cigarette smoking, and cumulative predn isone dosage. Our results indicate that the cumulative dose of MTX is independently related to small, but significant, increases in residual volume. Interestingly, the dose of corticosteroids was unrelated to c hanges in pulmonary function during the period of observation. These f indings indicate that low-dose MTX may cause mild degrees of air trapp ing in patients with RA, however, it does not appear to cause restrict ive lung function or abnormalities in gas exchange.