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目的:探讨空气污染物对肺功能动态变化的影响，探索遗传因素在肺功能及其变化中的作用。方法:基于英国生物银行中14 506名拥有基线和随访2次完整肺功能测试数据的参与者，采用土地利用回归模型估算颗粒物［包括空气动力学直径≤2.5 μm和≤10 μm的可吸入颗粒物（PM 2.5和PM 10）］、二氧化氮（NO 2）和氮氧化物（NO x）浓度，利用基线和随访的肺功能测试结果计算肺功能年均变化值，使用遗传变异构建肺功能［第一秒用力呼气容积（FEV 1）、用力肺活量（FVC）、一秒率（FEV 1/FVC）］相关多基因风险评分（PRS），通过多元线性回归模型分析空气污染物浓度与肺功能变化的关联，并分析遗传因素对肺功能及其变化的影响。 结果:PM 2.5、PM 10、NO 2和NO x与FVC变化均呈负相关［PM 2.5：-6.66（95% CI：-9.92~-3.40）ml/年；PM 10：-0.40（95% CI：-0.77~-0.03）ml/年；NO 2：-1.84（95% CI：-2.60~-1.07）ml/年；NO x：-1.37（95% CI：-2.27~-0.46）ml/年］，且PM 2.5、PM 10、NO 2与FEV 1变化呈负相关［PM 2.5：-3.19（95% CI：-5.79~-0.59）ml/年；PM 10：-3.00（95% CI：-5.92~-0.08）ml/年；NO 2：-0.95（95% CI：-1.56~-0.34）ml/年］。肺功能PRS与基线肺功能（FVC、FEV 1和FEV 1/FVC）及肺功能变化均呈正相关（均 β>0，均 P<0.001）。在不同PRS分层分析中，空气污染物对肺功能变化的影响效应依旧显著，且不存在明显异质性。 结论:肺功能遗传评分与基线肺功能和肺功能变化显著相关，长期暴露于空气污染物会加速FVC、FEV 1等肺功能指标下降，在不同遗传风险评分的个体中空气污染物的效应一致。

Objective:To investigate the impact of air pollution on dynamic changes in lung function and further explore the association between genetic factors and lung function and its changes.Methods:Research data were from 14 506 participants in the United Kingdom Biobank with two complete baseline and follow-up lung function tests. Particulate matter [including particulate matter with aerodynamic diameter ≤2.5 μm and ≤10 μm (PM 2.5 and PM 10)], nitrogen dioxide (NO 2), and nitrogen oxides (NO x) concentrations were estimated using land-use regression models. Annual changes in lung function were calculated based on baseline and follow-up lung function tests. Polygenic risk scores (PRS) of lung function [forced expiratory volume in the first second (FEV 1), forced vital capacity (FVC), and the ratio of FEV 1 to FVC (FEV 1/FVC)] were constructed by genetic variations. The association between air pollution concentrations and lung function changes was analyzed by multiple linear regression models, and the impact of genetic factors on lung function and its changes was also assessed. Results:PM 2.5, PM 10, NO 2, and NO x showed a negative correlation with FVC changes [PM 2.5: -6.66 (95% CI: -9.92- -3.40) ml/year; PM 10: -0.40 (95% CI: -0.77- -0.03) ml/year; NO 2: -1.84 (95% CI: -2.60- -1.07) ml/year; NO x: -1.37 (95% CI: -2.27- -0.46) ml/year]. Additionally, PM 2.5, PM 10and NO 2 were also negatively correlated with changes in FEV 1 [PM 2.5: -3.19 (95% CI: -5.79- -0.59) ml/year; PM 10: -3.00 (95% CI: -5.92- -0.08) ml/year; NO 2: -0.95 (95% CI: -1.56- -0.34) ml/year]. PRS of lung function were positively correlated with baseline lung function (FVC, FEV 1, and FEV 1/FVC) and lung function changes (all β>0, all P<0.001). In different PRS stratification analyses, the effect of air pollution on lung function changes remained significant, and there was no apparent heterogeneity. Conclusions:PRS of lung function are significantly associated with baseline and lung function changes. Long-term exposure to air pollution accelerates the decline of lung function indicators such as FVC and FEV 1. The effects of air pollution are consistent in individuals with different genetic risk scores.