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U.S.A."],"published-print":{"date-parts":[[2018,1,30]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Lymphangioleiomyomatosis (LAM) is a destructive lung disease driven by neoplastic LAM cells with a mutated tumor suppressor gene\n                    <jats:italic>TSC1<\/jats:italic>\n                    or\n                    <jats:italic>TSC2<\/jats:italic>\n                    , leading to increased activity of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin). Beta-agonists may treat asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Human\n                    <jats:italic>TSC2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    skin fibroblasts and LAM cells from explanted lungs treated with sirolimus and the short-term, but not long-term, beta-agonist isoproterenol showed increased phospho-S6 levels and cell growth due to activation of a cAMP\/PKA-dependent pathway. Long-acting beta-agonists affect phospho-S6 content, leading to stabilization of lung function in LAM patients.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1719960115","type":"journal-article","created":{"date-parts":[[2018,1,16]],"date-time":"2018-01-16T11:41:25Z","timestamp":1516102885000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Effect of beta-agonists on LAM progression and treatment"],"prefix":"10.1073","volume":"115","author":[{"given":"Kang","family":"Le","sequence":"first","affiliation":[{"name":"Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy K.","family":"Steagall","sequence":"additional","affiliation":[{"name":"Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 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