Pulmonary function in patients receiving long-term low-dose methotrexate

Chest. 1996 Apr;109(4):933-8. doi: 10.1378/chest.109.4.933.


Study objective: Acute interstitial pneumonitis is the main pulmonary side effect during methotrexate (MTX) treatment for rheumatoid arthritis. The aim of the study was to determine the following: (1) the incidence of MTX-induced pneumonitis during low-dose long-term MTX treatment for chronic arthritis; (2) whether periodic pulmonary function tests were useful for detecting MTX pneumonitis before clinical symptoms; and (3) whether any subclinical abnormality of pulmonary function was present in asymptomatic patients receiving MTX treatment.

Design: Pulmonary function tests, including diffusing capacity for carbon monoxide (DCO) measurements, were performed in 124 patients receiving low-dose MTX for rheumatologic diseases at the time of initiating treatment, and then at 3 months, 6 months, and at 6-month intervals thereafter. Mean duration of treatment was 23 months.

Results: MTX treatment was interrupted in six patients for acute onset of clinical symptoms; criteria for diagnosis of MTX pneumonitis were fullfilled in four cases (incidence: 3.2%); no risk factor could be identified. No significant decrease in pulmonary function parameters could be observed before the onset of clinical symptoms of MTX pneumonitis, and this adverse effect could not be predicted by periodic function tests. A statistically significant decrease was found in FVC (-2.2%, p=0.04), FEV1 (-5.0%, p<0.001), and diffusing capacity per alveolar volume, DCO/VA (-4.8%, p=0.03), but not DCO (-1.3%, p>0.05), in the 118 other asymptomatic patients during MTX treatment.

Conclusion: We found minor subclinical alterations in pulmonary function in asymptomatic patients receiving low-dose long-term MTX treatment, but periodic pulmonary function tests did not allow us to detect MTX-induced pneumonitis before clinical symptoms. Therefore, we recommend that these tests should not be systematically performed while patients are receiving treatment.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Lung / drug effects*
  • Lung / physiopathology
  • Lung Diseases, Interstitial / chemically induced
  • Lung Diseases, Interstitial / diagnosis*
  • Lupus Erythematosus, Systemic / drug therapy
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Prospective Studies
  • Psoriasis / drug therapy
  • Respiratory Function Tests
  • Rheumatic Diseases / drug therapy
  • Risk Factors


  • Antirheumatic Agents
  • Methotrexate