Lower corticosteroid skin blanching response is associated with severe COPD

Susan J M Hoonhorst; Nick H T ten Hacken; Adèle T Lo Tam Loi; Leo Koenderman; Jan Willem J Lammers; Eef D Telenga; H Marike Boezen; Maarten van den Berge; Dirkje S Postma

doi:10.1371/journal.pone.0091788

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.

Authors

Susan J M Hoonhorst¹, Nick H T ten Hacken¹, Adèle T Lo Tam Loi², Leo Koenderman², Jan Willem J Lammers², Eef D Telenga¹, H Marike Boezen³, Maarten van den Berge¹, Dirkje S Postma¹

Affiliations

¹ University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the Netherlands.
² University Medical Center Utrecht, Department of Respiratory Medicine, Utrecht, the Netherlands.
³ University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.

Abstract

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

Substances

Adrenal Cortex Hormones

Associated data

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

Grants and funding

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.