title: A pilot study of all-trans-retinoic acid for the treatment of human emphysema.
abstract: Emphysema results from progressive destruction of alveolar septae and was considered irreversible until all-trans-retinoic acid (ATRA) was shown to reverse anatomic and physiologic signs of emphysema in a rat model. To evaluate the feasibility of ATRA as a clinical therapy, 20 patients with severe emphysema were enrolled into a randomized, double-blind, placebo-controlled pilot study. Participants included 16 male and 4 female former smokers, two with alpha(1)-antitrypsin deficiency. Patients were treated with either 3 mo of ATRA (50 mg/m(2)/d) or 3 mo of placebo, followed by a 3-mo crossover phase. Plasma drug levels were followed and outcome measures included serial pulmonary function tests, blood gases, lung compliance, computed tomography (CT) imaging, and quality of life questionnaires. In general, treatment was well tolerated and associated with only mild side effects including skin changes, transient headache, hyperlipidemia, transaminites, and musculoskeletal pains. Plasma drug levels varied considerably between subjects and decreased significantly over time in 35% of the participants. Physiologic and CT measurements did not change appreciably in response to therapy. We conclude that ATRA is well tolerated in patients with emphysema, and trials evaluating higher doses, longer treatment, or different dosing schedules are feasible.
authors.affiliation: Pulmonary and Critical Care Medicine, UCLA School of Medicine, Los Angeles, CA 99095-1690, USA.
authors.forename: Jenny T
authors.initials: JT
authors.lastname: Mao
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Goldin
authors.forename: John
authors.initials: J
authors.lastname: Dermand
authors.forename: Grace
authors.initials: G
authors.lastname: Ibrahim
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Brown
authors.forename: Aletha
authors.initials: A
authors.lastname: Emerick
authors.forename: Michael F
authors.initials: MF
authors.lastname: McNitt-Gray
authors.forename: David W
authors.initials: DW
authors.lastname: Gjertson
authors.forename: Francine
authors.initials: F
authors.lastname: Estrada
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Michael D
authors.initials: MD
authors.lastname: Roth
mesh_terms: D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011656:Pulmonary Emphysema / Q000175:diagnosis / Q000188:drug therapy*; D011788:Quality of Life; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D014212:Tretinoin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014212:Tretinoin