Air Pollution Exposure Laboratory, Division of Respiratory Medicine, Department of Medicine, Vancouver Coastal Health Research Institute, The University of British Columbia, Vancouver, British Columbia, Canada; and.
Manitoba Center for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Ann Am Thorac Soc. 2023 Jun;20(6):834-842. doi: 10.1513/AnnalsATS.202209-762OC.
Air pollution exposure is harmful to human airways, and its impacts are best studied using concentration-response relationships. However, most concentration-response research on airway health has investigated chronic exposures, with less being known about acute effects, which can be robustly studied using controlled human exposures. To investigate the concentration relationship between airway health measures and diesel exhaust (DE). We conducted a double-blind crossover study with 17 healthy nonsmokers exposed to filtered air and DE standardized to 20, 50, and 150 μg/m of particulate matter ⩽2.5 μm in aerodynamic diameter for 4 hours. Before, during, and up to 24 hours from the exposure start, we measured lung function, airway responsiveness, and airway inflammation using spirometry, methacholine challenge, and fractional exhaled nitric oxide (Fe), respectively. In addition, we measured nasal airway inflammation using differential cell counts and cytokines in nasal lavage and epithelial lining fluid at 24 hours. We assessed DE concentration responses and associations between outcomes using linear mixed effects models and repeated measures correlations, respectively, thereafter adjusting for multiple comparisons. DE exposure increased percentage ΔFe at 4 hours (β = 0.16 ± 0.06). Compared with filtered air, percentage ΔFe trended toward an increase at concentrations of 20 μg/m (β = 18.66 ± 8.76) and 50 μg/m (β = 19.33 ± 8.92) and increased significantly at 150 μg/m (β = 34.43 ± 8.92). In addition, DE exposure induced a trend toward increased nasal IL-6 at 24 hours (percentage difference, 0.88; 95% confidence interval, 0.08, 1.70). There were no effects of DE exposure on Fe at 24 hours, lung function, airway responsiveness, or nasal cell counts. DE induces a concentration-dependent increase in Fe, indicating that it may be a sensitive marker of an acute inflammatory response in the airways. We report responses at concentrations below those in previous controlled DE exposure studies, and we document particulate matter ⩽2.5 μm in aerodynamic diameter concentration-response estimates at exposure levels routinely experienced in the community and occupational settings. Clinical trial registered with www.clinicaltrials.gov (NCT03234790).
空气污染暴露对人体气道有害，其影响最好通过浓度-反应关系来研究。然而，大多数关于气道健康的浓度-反应研究都调查了慢性暴露，对急性效应的了解较少，而急性效应可以通过受控人体暴露来有力地研究。 为了研究气道健康测量值与柴油机排气（DE）之间的浓度关系。 我们对 17 名健康的不吸烟者进行了一项双盲交叉研究，他们暴露于过滤空气中，DE 标准化为 20、50 和 150μg/m，空气动力学直径 ⩽2.5μm，暴露时间为 4 小时。在暴露开始之前、期间和 24 小时内，我们分别使用肺活量计、乙酰甲胆碱挑战和呼出气一氧化氮分数（Fe）测量肺功能、气道反应性和气道炎症。此外，我们在 24 小时时使用鼻气道炎症的差异细胞计数和鼻灌洗液和上皮衬里液中的细胞因子进行测量。我们使用线性混合效应模型评估 DE 浓度反应，并使用重复测量相关性评估结果之间的关联，然后进行多次比较调整。 DE 暴露增加了 4 小时时的百分比 ΔFe（β=0.16±0.06）。与过滤空气相比，20μg/m（β=18.66±8.76）和 50μg/m（β=19.33±8.92）浓度下的百分比 ΔFe 呈增加趋势，150μg/m（β=34.43±8.92）浓度下的百分比 ΔFe 显著增加。此外，DE 暴露在 24 小时时诱导了 IL-6 鼻内增加的趋势（百分比差异，0.88；95%置信区间，0.08，1.70）。DE 暴露对 24 小时时的 Fe、肺功能、气道反应性或鼻细胞计数没有影响。 DE 诱导 Fe 浓度依赖性增加，表明它可能是气道急性炎症反应的敏感标志物。我们报告了低于先前受控 DE 暴露研究的浓度的反应，并且我们记录了在社区和职业环境中通常经历的暴露水平下空气动力学直径 ⩽2.5μm 的颗粒物浓度-反应估计值。在 www.clinicaltrials.gov 上注册的临床试验（NCT03234790）。
