House Dust Endotoxin Levels Are Associated with Adult Asthma in a US Farming Population
House Dust Endotoxin Levels Are Associated with Adult Asthma in a US Farming Population
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DOI：
10.1513/annalsats.201611-861oc
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发表时间：
2017-03-01
影响因子：
8.3
通讯作者：
London, Stephanie J.
中科院分区：
文献类型：
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作者：
Carnes, Megan Ulmer;Hoppin, Jane A.;London, Stephanie J.
基本原理：内毒素启动先天免疫系统的促炎反应。在儿童中的研究表明，室内灰尘中的内毒素暴露可能是哮喘的一个重要危险因素，但在成人人群中进行的研究很少。目的：探讨室内灰尘内毒素水平与哮喘及其相关表型的关系（喘息，特应性，肺功能）在一个大的美国农业人口。方法：从参与者的卧室（n = 2，485）收集灰尘，这些参与者参加了一项嵌套在农业健康研究中的哮喘病例对照研究（927例）。粉尘内毒素测定采用鲎试剂法。结果通过问卷调查、肺功能测定和抽血进行测量。我们使用线性和逻辑回归分析评估相关性。测量和主要结果：内毒素与当前哮喘显著相关（比值比[OR]，1.30; 95%置信区间[CI]，1.14-1.47），并且这种关系被早期农场暴露所改变（出生在农场：OR，1.18; 95%CI，1.02-1.37;未出生在农场：OR，1.67; 95%CI，1.26-2.20;交互作用P = 0.05）。特应性哮喘和非特应性哮喘都有显著的正相关性。内毒素与特应性或喘息均无关。仅在哮喘病例中，较高的内毒素与较低的FEV 1/FVC相关（相互作用P = 0.01）。对于哮喘，CD 14变异rs 2569190存在基因-环境交互作用（交互作用P = 0.16），而TLR 4变异rs 4986790和rs 4986791则无交互作用。与哮喘的关联程度取决于生命早期的农场暴露。此外，内毒素与哮喘患者的肺功能降低有关。
Rationale: Endotoxin initiates a proinflammatory response from the innate immune system. Studies in children suggest that endotoxin exposure from house dust may be an important risk factor for asthma, but few studies have been conducted in adult populations.Objectives: To investigate the association of house dust endotoxin levels with asthma and related phenotypes (wheeze, atopy, and pulmonary function) in a large U.S. farming population.Methods: Dust was collected from the bedrooms (n = 2,485) of participants enrolled in a case-control study of current asthma (927 cases) nested within the Agricultural Health Study. Dust endotoxin was measured by Limulus amebocyte lysate assay. Outcomes were measured by questionnaire, spirometry, and blood draw. We evaluated associations using linear and logistic regression.Measurements and Main Results: Endotoxin was significantly associated with current asthma (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.14-1.47), and this relationship was modified by early-life farm exposure (born on a farm: OR, 1.18; 95% CI, 1.02-1.37; not born on a farm: OR, 1.67; 95% CI, 1.26-2.20; Interaction P = 0.05). Significant positive associations were seen with both atopic and nonatopic asthma. Endotoxin was not related to either atopy or wheeze. Higher endotoxin was related to lower FEV1/FVC in asthma cases only (Interaction P = 0.01). For asthma, there was suggestive evidence of a gene-by-environment interaction for the CD14 variant rs2569190 (Interaction P = 0.16) but not for the TLR4 variants rs4986790 and rs4986791.Conclusions: House dust endotoxin was associated with current atopic and nonatopic asthma in a U.S. farming population. The degree of the association with asthma depended on early-life farm exposures. Furthermore, endotoxin was associated with lower pulmonary function in patients with asthma.