BACKGROUND: Animal and cellular studies support the importance of autophagy inhibition in lymphangioleiomyomatosis (LAM). In a cohort of subjects with LAM, we tested the hypothesis that treatment with sirolimus and hydroxychloroquine (an autophagy inhibitor) at two different dose levels is safe and well tolerated. Secondary end points included changes in lung function.

METHODS: This 48-week, two-center phase I trial evaluated the safety of escalating oral hydroxychloroquine doses ...

BACKGROUND: Preclinical studies have demonstrated that low-dose carbon monoxide (CO) can abrogate experimental lung fibrosis. To test the therapeutic role of inhaled CO, we designed a clinical study in patients with idiopathic pulmonary fibrosis (IPF).

METHODS: We conducted a multicenter, phase IIa, double-blinded, sham-controlled, clinical trial. Patients with IPF were randomized to treatment with inhaled CO at 100 to 200 parts per million or to inhaled 21% oxygen for 2 h daily, twice ...

Lymphangioleiomyomatosis (LAM) is a multisystem disease associated with progressive pulmonary disease that affects almost exclusively women. LAM is characterised pathologically by proliferation of abnormal smooth muscle-like cells carrying mutations in predominantly the tuberous sclerosis complex (TSC) gene TSC2 and, rarely, in TSC1 [1]. LAM can occur sporadically or in association with TSC. Mutations in the TSC genes lead to activation of the mammalian/mechanistic target of rapamycin ...