The effect of mTOR inhibitors on respiratory infections in lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a destructive cystic lung disease. Mammalian target of rapamycin (mTOR) inhibitors are the primary treatment for LAM but it is unknown whether these immunosuppressing medications increase the risk for or the severity of respiratory infections in LAM patients. We searched multiple databases for original articles that reported the rate of respiratory infections in LAM patients treated with mTOR inhibitors or placebo. We calculated incidence rates for respiratory infections in these groups and incidence rate ratios for respiratory infections and severe respiratory infections in mTOR inhibitors treated versus placebo treated patients. 11 studies were included. There were 294 patients in the treatment groups and 93 patients in the placebo groups. Among subjects in placebo arms, the incidence rate of respiratory infections was 58.8 per 100 patient-years (95% CI 35.3–82.3 per 100 patient-years). The incidence-rate ratio (IRR) for respiratory infection among treated subjects was 0.71 (95% CI 0.50–1.02; p=0.06 compared to placebo subjects). The IRR for severe respiratory infections among treated subjects was 1.56 (95% CI 0.43–8.55; p=0.52). We found that respiratory infections are common in patients with LAM. Importantly, treatment with mTOR inhibitors does not increase the incidence of these infections and may be protective.