Hoonhorst Susan J M, ten Hacken Nick H T, Lo Tam Loi Adèle T, Koenderman Leo, Lammers Jan Willem J, Telenga Eef D, Boezen H Marike, van den Berge Maarten, Postma Dirkje S
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.
University Medical Center Utrecht, Department of Respiratory Medicine, Utrecht, the Netherlands.
PLoS One. 2014 Mar 12;9(3):e91788. doi: 10.1371/journal.pone.0091788. eCollection 2014.
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.
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.
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.
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.
慢性阻塞性肺疾病（COPD）的特征是气道和肺组织持续的炎症及重塑过程导致慢性气流受限。炎症可通过皮质类固醇进行靶向治疗。然而，COPD患者的气道炎症对类固醇的反应通常比哮喘患者低。其潜在机制尚不清楚。本研究旨在通过皮质类固醇皮肤变白试验评估皮肤皮质类固醇不敏感性是否与COPD及其严重程度相关。
纳入COPD GOLD I-IV期患者（分别为27、24、22和16例）以及健康非吸烟者和吸烟者（分别为28例和56例）。通过皮质类固醇皮肤变白试验评估皮质类固醇敏感性。将布地奈德以8种对数递增浓度（0-100μg/ml）涂于受试者前臂。7小时后使用7分制量表（从正常皮肤到强烈变白）评估变白情况。所有受试者均进行肺功能测定和体容积描记法检查。
GOLD III期和GOLD IV期COPD患者的皮肤变白反应明显低于健康非吸烟者、吸烟者、GOLD I期和GOLD II期患者。其皮肤变白反应的剂量-反应曲线下面积值分别为586和243，而其他组分别为1560、1154、1380和1309，p<0.05。较低的第一秒用力呼气容积（FEV1）水平和较高的残气量/肺总量（RV/TLC）比值与较低的皮肤变白反应显著相关（分别为p = 0.001和p = 0.004）。GOLD I、II、III和IV期患者的年龄和吸烟包年数相似。
在本研究中，重度和极重度COPD患者的皮肤皮质类固醇敏感性低于轻度和中度COPD患者以及年龄和吸烟包年数相当的非COPD对照组。我们的研究结果共同表明，皮肤变白反应降低与具有早发性COPD表型的COPD患者亚组相符。
