Jolliffe David A, Kilpin Kate, MacLaughlin Beverley D, Greiller Claire L, Hooper Richard L, Barnes Neil C, Timms Peter M, Rajakulasingam Raj K, Bhowmik Angshu, Choudhury Aklak B, Simcock David E, Hyppönen Elina, Corrigan Christopher J, Walton Robert T, Griffiths Christopher J, Martineau Adrian R
Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AB, UK.
Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AB, UK.
J Steroid Biochem Mol Biol. 2018 Jan;175:88-96. doi: 10.1016/j.jsbmb.2016.11.004. Epub 2016 Nov 5.
Vitamin D deficiency is common in children with asthma, and it associates with poor asthma control, reduced forced expiratory volume in one second (FEV) and increased requirement for inhaled corticosteroids (ICS). Cross-sectional studies investigating the prevalence, determinants and clinical correlates of vitamin D deficiency in adults with asthma are lacking. We conducted a multi-centre cross-sectional study in 297 adults with a medical record diagnosis of ICS-treated asthma living in London, UK. Details of potential environmental determinants of vitamin D status, asthma control and medication use were collected by questionnaire; blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction, and participants underwent measurement of weight, height and fractional exhaled nitric oxide concentration (FeNO), spirometry and sputum induction for determination of lower airway eosinophil counts (n=35 sub-group). Thirty-five single nucleotide polymorphisms (SNP) in 11 vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4 CYP27A1, LRP2, CUBN, VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration, and to determine whether vitamin D status was independently associated with Asthma Control Test (ACT) score, ICS dose, FeNO, forced vital capacity (FVC), FEV or lower airway eosinophilia. Mean serum 25(OH)D concentration was 50.6nmol/L (SD 24.9); 162/297 (54.5%) participants were vitamin D deficient (serum 25(OH)D concentration <50nmol/L). Lower vitamin D status was associated with higher body mass index (P=0.014), non-White ethnicity (P=0.036), unemployment (P for trend=0.012), lack of vitamin D supplement use (P<0.001), sampling in Winter or Spring (P for trend <0.001) and lack of a recent sunny holiday abroad (P=0.030), but not with potential genetic determinants. Vitamin D status was not found to associate with any marker of asthma control investigated. Vitamin D deficiency is common among UK adults with ICS-treated asthma, and classical environmental determinants of serum 25(OH)D operate in this population. However, in contrast to studies conducted in children, we found no association between vitamin D status and markers of asthma severity or control.
维生素D缺乏在哮喘儿童中很常见，并且与哮喘控制不佳、一秒用力呼气量（FEV）降低以及吸入性糖皮质激素（ICS）需求增加有关。目前缺乏针对成年哮喘患者维生素D缺乏的患病率、决定因素及临床相关性的横断面研究。我们对英国伦敦297名有ICS治疗哮喘病历诊断的成年人进行了一项多中心横断面研究。通过问卷调查收集维生素D状态、哮喘控制及药物使用的潜在环境决定因素的详细信息；采集血样用于分析血清25(OH)D浓度和DNA提取，参与者接受体重、身高和呼出一氧化氮分数浓度（FeNO）测量、肺功能测定以及诱导痰检查以确定下气道嗜酸性粒细胞计数（n = 35的亚组）。使用Taqman等位基因鉴别分析对11个维生素D途径基因（DBP、DHCR7、RXRA、CYP2R1、CYP27B1、CYP24A1、CYP3A4、CYP27A1、LRP2、CUBN、VDR）中的35个单核苷酸多态性（SNP）进行分型。采用线性回归来确定与血清25(OH)D浓度独立相关的环境和遗传因素，并确定维生素D状态是否与哮喘控制测试（ACT）评分、ICS剂量、FeNO、用力肺活量（FVC）、FEV或下气道嗜酸性粒细胞增多独立相关。血清25(OH)D平均浓度为50.6nmol/L（标准差24.9）；162/297（54.5%）的参与者维生素D缺乏（血清25(OH)D浓度<50nmol/L）。较低的维生素D状态与较高的体重指数（P = 0.014）、非白人种族（P = 0.036）、失业（趋势P = 0.012）、未使用维生素D补充剂（P < 0.001）、在冬季或春季采样（趋势P < 0.001）以及近期没有国外阳光度假（P = 0.030）相关，但与潜在的遗传决定因素无关。未发现维生素D状态与所研究的任何哮喘控制指标相关。维生素D缺乏在接受ICS治疗的英国成年哮喘患者中很常见，血清25(OH)D的经典环境决定因素在该人群中起作用。然而，与在儿童中进行的研究不同，我们发现维生素D状态与哮喘严重程度或控制指标之间没有关联。
