Nakamura Y, Suzuki R, Mizuno T, Abe K, Chiba S, Horii Y, Tsuboi J, Ito S, Obara W, Tanita T, Kanno H, Yamauchi K
Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
Department of Cardiovascular Surgery, Iwate Medical University School of Medicine, Morioka, Japan.
Clin Exp Allergy. 2016 Sep;46(9):1152-61. doi: 10.1111/cea.12710. Epub 2016 May 3.
Several gene variants identified in bronchial asthmatic patients are associated with a decrease in pulmonary function. The effects of this intervention on pulmonary function have not been fully researched.
We determined the effects of high-dose inhaled corticosteroids (ICSs) on decreased pulmonary function in asthmatic Japanese patients with variants of IL13 and STAT4 during long-term treatments with low to mild doses of ICS.
In this study, 411 patients with bronchial asthma who were receiving ICSs and living in Japan were recruited, were genotyped, and underwent pulmonary function tests and fibreoptic examinations. The effects of 2 years of high-dose ICSs administered to asthmatic patients who were homozygous for IL13 AA of rs20541 or STAT4 TT of rs925847 and who progressed to airway remodelling were investigated.
High-dose ICS treatment increased the pulmonary function of patients homozygous for IL13 AA of rs20541 but not of patients homozygous for STAT4 TT of rs925847. The increased concentrations of the mediators IL23, IL11, GMCSF, hyaluronic acid, IL24, and CCL8 in bronchial lavage fluid (BLF) were diminished after high-dose ICS treatment in patients homozygous for IL13 AA of rs20541.
IL13 AA of rs20541 and STAT4 TT of rs925847 are potential genomic biomarkers for predicting lower pulmonary function. The administration of high-dose ICSs to asthmatic patients with genetic variants of IL13 AA may inhibit the advancement of airway remodelling. The genetic variants of STAT4 TT did not respond to high-dose ICSs. Therefore, using medications other than ICSs must be considered even during the initial treatment of bronchial asthma. These genetic variants may aid in the realization of personalized and phenotype-specific therapies for bronchial asthma.
在支气管哮喘患者中鉴定出的几种基因变异与肺功能下降有关。这种干预对肺功能的影响尚未得到充分研究。
我们确定了高剂量吸入性糖皮质激素（ICS）对长期接受低至中等剂量ICS治疗的携带IL13和STAT4变异的日本哮喘患者肺功能下降的影响。
在本研究中，招募了411名正在接受ICS治疗且居住在日本的支气管哮喘患者，对其进行基因分型，并进行肺功能测试和纤维光学检查。研究了对rs20541的IL13 AA纯合子和rs925847的STAT4 TT纯合子且已进展为气道重塑的哮喘患者给予2年高剂量ICS的效果。
高剂量ICS治疗增加了rs20541的IL13 AA纯合子患者的肺功能，但未增加rs925847的STAT4 TT纯合子患者的肺功能。在rs20541的IL13 AA纯合子患者中，高剂量ICS治疗后支气管灌洗液（BLF）中介质IL23、IL11、GMCSF、透明质酸、IL24和CCL8的浓度升高有所减轻。
rs20541的IL13 AA和rs925847的STAT4 TT是预测肺功能较低的潜在基因组生物标志物。对携带IL13 AA基因变异的哮喘患者给予高剂量ICS可能会抑制气道重塑的进展。STAT4 TT基因变异对高剂量ICS无反应。因此，即使在支气管哮喘的初始治疗期间，也必须考虑使用ICS以外的药物。这些基因变异可能有助于实现支气管哮喘的个性化和表型特异性治疗。
