title: Feasibility of retinoids for the treatment of emphysema study.
abstract: BACKGROUND
  Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema.
  
  
  METHODS
  One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema, defined by diffusing capacity of the lung for carbon monoxide (Dlco) [37.1 +/- 12.0% of predicted] and CT density mask (38.5 +/- 12.8% of voxels <- 910 Hounsfield units) [mean +/- SD] were enrolled into a randomized, double-blind, feasibility study at five university hospitals. Participants received all-trans retinoic acid (ATRA) at either a low dose (LD) [1 mg/kg/d] or high dose (HD) [2 mg/kg/d], 13-cis retinoic acid (13-cRA) [1 mg/kg/d], or placebo for 6 months followed by a 3-month crossover period.
  
  
  RESULTS
  No treatment was associated with an overall improvement in pulmonary function, CT density mask score, or health-related quality of life (QOL) at the end of 6 months. However, time-dependent changes in Dlco (initial decrease with delayed recovery) and St. George Respiratory Questionnaire (delayed improvement) were observed in the HD-ATRA cohort and correlated with plasma drug levels. In addition, 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels. Retinoid-related side effects were common but generally mild.
  
  
  CONCLUSIONS
  No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study. However, time- and dose-dependent changes in Dlco, CT density mask score, and health-related QOL were observed in subjects treated with ATRA, suggesting the possibility of exposure-related biological activity that warrants further investigation.
authors.affiliation: Division of Pulmonary and Critical Care, University of California, Los Angeles, CA 90095-1690, USA. mroth@mednet.ucle.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Roth
authors.forename: John E
authors.initials: JE
authors.lastname: Connett
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: D'Armiento
authors.forename: Robert F
authors.initials: RF
authors.lastname: Foronjy
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Friedman
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Goldin
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Louis
authors.forename: Jenny T
authors.initials: JT
authors.lastname: Mao
authors.forename: Josephia R
authors.initials: JR
authors.lastname: Muindi
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.forename: Joe W
authors.initials: JW
authors.lastname: Ramsdell
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Ries
authors.forename: Steven M
authors.initials: SM
authors.lastname: Scharf
authors.forename: Neil W
authors.initials: NW
authors.lastname: Schluger
authors.forename: Frank C
authors.initials: FC
authors.lastname: Sciurba
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Skeans
authors.forename: Robert E
authors.initials: RE
authors.lastname: Walter
authors.forename: Christine H
authors.initials: CH
authors.lastname: Wendt
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wise
mesh_terms: D000368:Aged; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004646:Emphysema / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007641:Keratolytic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012129:Respiratory Function Tests; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014212:Tretinoin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D007641:Keratolytic Agents; D014212:Tretinoin; D015474:Isotretinoin