Hokkaido University Center for Environmental and Health Sciences, North 12, West 7, Kita-ku, Sapporo 060-0812, Japan.
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan.
Environ Int. 2018 Dec;121(Pt 1):102-110. doi: 10.1016/j.envint.2018.08.046. Epub 2018 Sep 6.
Exposure to phthalates and phosphorus flame retardants (PFRs) is considered to be a risk factor for asthma and allergies. However, little is known about the contribution of loss-of-function mutations in the gene encoding filaggrin (FLG) gene, which are considered to be predisposing factors for eczema and asthma, to these associations. We investigated the associations between exposure to phthalates and PFRs in dust and eczema/wheeze among Japanese children, taking into consideration loss-of-function mutations in FLG.
This study was part of the Hokkaido study on Environment and Children's Health. Seven phthalates and 11 PFRs in household dust were measured by gas chromatography-mass spectrometry. Eczema and wheeze were assessed in children aged 7 years using the International Study of Asthma and Allergies in Childhood questionnaire. Eight FLG mutations previously identified in the Japanese population were extracted from cord blood samples. Children with one or more FLG mutations were considered to be positive for FLG mutations. The study included 296 children who had complete data (birth records, FLG mutations, first trimester and 7 years questionnaires, and phthalate/PFR levels). Odds ratios (ORs) and 95% confidential intervals (CIs) of eczema and wheeze were calculated for log-transformed phthalate/PFR levels by logistic regression. We also performed stratified analyses based on FLG mutations.
The prevalence rates of eczema and wheeze were 20.6% and 13.9%, respectively. Among children without any FLG mutations, tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP) increased the OR of wheeze, (OR: 1.22, CI: 1.00-1.48). Significant p values for trends were found between tris (2-butoxyethyl) phosphate (TBOEP) and eczema and di-iso-nonyl phthalate (DiNP) and eczema among children without any FLG mutations, respectively.
Despite our limited sample size and cross-sectional study design, the effects of indoor environmental factors on childhood eczema and wheeze were clearer in children without loss-of-function mutations in FLG than in children with mutations. Children with FLG mutations might already be cared for differently in terms of medication or parental lifestyle. Further studies in larger populations are warranted so that severity of symptoms and combinations of FLG mutations can be investigated.
接触邻苯二甲酸酯和磷系阻燃剂（PFRs）被认为是哮喘和过敏的危险因素。然而，人们对编码丝聚蛋白（FLG）基因的失活突变在特应性皮炎和哮喘中的作用知之甚少，而这些突变被认为是特应性皮炎和哮喘的易感因素。我们研究了日本儿童尘螨中邻苯二甲酸酯和 PFR 暴露与特应性皮炎/喘息之间的关系，同时考虑了 FLG 基因的失活突变。
本研究是北海道环境与儿童健康研究的一部分。通过气相色谱-质谱法测量了家庭尘埃中的 7 种邻苯二甲酸酯和 11 种 PFRs。采用国际儿童哮喘和过敏研究问卷调查了 7 岁儿童的特应性皮炎和喘息情况。从脐带血样本中提取了之前在日本人群中发现的 8 种 FLG 突变。有一个或多个 FLG 突变的儿童被认为是 FLG 突变阳性。该研究纳入了 296 名具有完整数据（出生记录、FLG 突变、妊娠早期和 7 岁时的问卷以及邻苯二甲酸酯/PFR 水平）的儿童。通过 logistic 回归计算了 log 转换后的邻苯二甲酸酯/PFR 水平与特应性皮炎和喘息的比值比（OR）及其 95%置信区间（CI）。我们还根据 FLG 突变进行了分层分析。
特应性皮炎和喘息的患病率分别为 20.6%和 13.9%。在没有任何 FLG 突变的儿童中，三（1,3-二氯-2-丙基）磷酸酯（TDCIPP）增加了喘息的 OR（OR：1.22，CI：1.00-1.48）。在没有任何 FLG 突变的儿童中，三（2-丁氧基乙基）磷酸酯（TBOEP）与特应性皮炎之间以及二异壬基邻苯二甲酸酯（DiNP）与特应性皮炎之间均存在显著的趋势 p 值。
尽管我们的样本量有限且研究设计为横断面研究，但在没有 FLG 功能丧失突变的儿童中，室内环境因素对儿童特应性皮炎和喘息的影响比有突变的儿童更明显。有 FLG 突变的儿童可能已经在药物治疗或父母生活方式方面得到了不同的照顾。需要在更大的人群中进行进一步的研究，以调查症状的严重程度和 FLG 突变的组合。
