Which medication has a known association with pulmonary toxicity when used long-term?

Nitrofurantoin (Macrodantin) is associated with pulmonary toxicity when used long-term. This medication is primarily used for treating urinary tract infections, but its prolonged use can lead to serious lung complications. The mechanism behind this toxicity typically involves hypersensitivity reactions, pulmonary fibrosis, or, in some cases, chronic interstitial lung disease. Symptoms might include cough, dyspnea, and even pulmonary infiltrates seen on imaging studies.

In contrast, doxycycline is primarily an antibiotic used for a variety of infections and does not carry a known risk of pulmonary toxicity with long-term use. Levothyroxine is a thyroid hormone replacement therapy that, while important for managing hypothyroidism, is not associated with pulmonary issues. Metformin, widely used for managing type 2 diabetes, has its own range of side effects, but pulmonary toxicity is not among them. Thus, Nitrofurantoin stands out as the medication with a significant association with long-term pulmonary toxicity.