Feasibility of retinoids for the treatment of emphysema study

Chest. 2006 Nov;130(5):1334-45. doi: 10.1378/chest.130.5.1334.


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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Emphysema / diagnostic imaging
  • Emphysema / drug therapy*
  • Feasibility Studies
  • Female
  • Humans
  • Isotretinoin / adverse effects
  • Isotretinoin / blood
  • Isotretinoin / therapeutic use*
  • Keratolytic Agents / adverse effects
  • Keratolytic Agents / blood
  • Keratolytic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Quality of Life
  • Respiratory Function Tests
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Tretinoin / adverse effects
  • Tretinoin / blood
  • Tretinoin / therapeutic use*


  • Keratolytic Agents
  • Tretinoin
  • Isotretinoin