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Lymphangioleiomyomatosis (LAM) occurs predominantly in women in one of two forms: sporadic LAM and LAM associated with the autosomal dominant genetic disease tuberous sclerosis complex (TSC). Its clinical presentation includes dyspnoea, pneumothorax, chylothorax and renal angiomyolipoma. Many patients exhibit mild symptoms at the time of diagnosis, and their lung function then gradually declines. In the end-stage of LAM, lung transplantation is the only option. Due to mutations of either TSC1 or TSC2 gene, aberrant activation of mammalian/mechanistic target of rapamycin (mTOR) causes TSC and/or LAM.1 2 There were no effective therapeutics for LAM until the mTOR inhibitor rapamycin (sirolimus) exhibited efficacy in an open-label study published in 20083. The efficacy of this drug was confirmed in the randomised, double-blinded Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) trial.4 Primarily based on findings from the MILES study, sirolimus has been approved for the treatment of LAM in Japan and USA. In recent guidelines for LAM issued by the American Thoracic Society and the Japanese Respiratory Society, rapamycin is recommended for patients with reduced lung function.5
A real-world observational study by Bee and colleagues that appears in Thorax expanded our knowledge regarding two important questions: when and how much rapamycin could be used to treat LAM.6 In a prospective cohort comprising 47 patients during a 3-year follow-up, the authors found that (1) patients with LAM with a shorter duration of disease and less severely impaired lung function responded better to rapamycin; (2) different dosages of rapamycin produced similar benefits and (3) lower doses had fewer side effects. Therefore, early treatment with low-dose rapamycin may better preserve lung function …
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