Lower corticosteroid skin blanching response is associated with severe COPD

PLoS One. 2014 Mar 12;9(3):e91788. doi: 10.1371/journal.pone.0091788. eCollection 2014.


Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by ongoing inflammatory and remodeling processes of the airways and lung tissue. Inflammation can be targeted by corticosteroids. However, airway inflammation is generally less responsive to steroids in COPD than in asthma. The underlying mechanisms are yet unclear. This study aimed to assess whether skin corticosteroid insensitivity is associated with COPD and COPD severity using the corticosteroid skin blanching test.

Methods: COPD patients GOLD stage I-IV (n = 27, 24, 22, and 16 respectively) and healthy never-smokers and smokers (n = 28 and 56 respectively) were included. Corticosteroid sensitivity was assessed by the corticosteroid skin blanching test. Budesonide was applied in 8 logarithmically increasing concentrations (0-100 μg/ml) on subject's forearm. Assessment of blanching was performed after 7 hours using a 7-point scale (normal skin to intense blanching). All subjects performed spirometry and body plethysmography.

Results: Both GOLD III and GOLD IV COPD patients showed significantly lower skin blanching responses than healthy never-smokers and smokers, GOLD I, and GOLD II patients. Their area under the dose-response curve values of the skin blanching response were 586 and 243 vs. 1560, 1154, 1380, and 1309 respectively, p<0.05. Lower FEV1 levels and higher RV/TLC ratios were significantly associated with lower skin blanching responses (p = 0.001 and p = 0.004 respectively). GOLD stage I, II, III and IV patients had similar age and packyears.

Conclusions: In this study, severe and very severe COPD patients had lower skin corticosteroid sensitivity than mild and moderate COPD patients and non-COPD controls with comparable age and packyears. Our findings together suggest that the reduced skin blanching response fits with a subgroup of COPD patients that has an early-onset COPD phenotype.

Trial registration: ClinicalTrials.gov NCT00807469 NCT00848406 NCT00850863.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / pharmacology*
  • Aged
  • Case-Control Studies
  • Color
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pigmentation / drug effects
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Skin / blood supply*
  • Skin / drug effects*
  • Smoking


  • Adrenal Cortex Hormones

Associated data

  • ClinicalTrials.gov/NCT00807469
  • ClinicalTrials.gov/NCT00848406
  • ClinicalTrials.gov/NCT00850863

Grant support

This study was funded by grant T1-108 from Top Institute Pharma, with partners Nycomed, GlaxoSmithKline, University Medical Center Groningen (UMCG), and University of Groningen (RUG) (NCT00807469 and NCT00850863); and the Royal Netherlands Academy of Arts and Sciences (NCT00848406). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.