title: Lower corticosteroid skin blanching response is associated with severe COPD.
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.
authors.affiliation: 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.
authors.forename: Susan J M
authors.initials: SJ
authors.lastname: Hoonhorst
authors.affiliation: 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.
authors.forename: Nick H T
authors.initials: NH
authors.lastname: ten Hacken
authors.affiliation: University Medical Center Utrecht, Department of Respiratory Medicine, Utrecht, the Netherlands.
authors.forename: Adèle T
authors.initials: AT
authors.lastname: Lo Tam Loi
authors.affiliation: University Medical Center Utrecht, Department of Respiratory Medicine, Utrecht, the Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
authors.affiliation: University Medical Center Utrecht, Department of Respiratory Medicine, Utrecht, the Netherlands.
authors.forename: Jan Willem J
authors.initials: JW
authors.lastname: Lammers
authors.affiliation: 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.
authors.forename: Eef D
authors.initials: ED
authors.lastname: Telenga
authors.affiliation: 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.
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.affiliation: 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.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berge
authors.affiliation: 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.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000368:Aged; D016022:Case-Control Studies; D003116:Color; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010858:Pigmentation / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects*; D012907:Smoking
chemical_list: D000305:Adrenal Cortex Hormones