The Use of Methotrexate in Respiratory Diseases

Methotrexate (MTX), a folate analogue anti-metabolite, has long been recognized for its beneficial chemotherapeutic and immuno-modulatory effects and has therefore been used in the past 6 decades to treat a variety of malignant and autoimmune disorders. MTX has emerged in the past 2 decades, as a potential drug in the management of patients with chronic pulmonary diseases including airway hypersensitivity disorders, granulomatous diseases, and auto-immune disorders affecting the lung interstitium. Although bearing a unique hematologic and hepato-pulmonary toxicity profile, some dosing strategies and monitoring guidelines have been developed in order to ensure a safe utilization. The pulmonary toxicity has a variable clinicopathological presentation spectrum and a myriad of etiologic factors have been implicated in the pathophysiologic mechanisms including infectious, immunological, and direct toxic effects. In the hereby article, we present a brief review of the drug's of mechanism of action, dosing techniques and main side effects, after which MTX's role in the treatment of asthma, sarcoidosis and vasculitides involving the lung is discussed. The use of its salvage drug, leucovorin, is also reviewed.