空气污染促进哮喘发展为COPD
2025/10/27
背景：在英国，约15%的哮喘患者同时患有慢性阻塞性肺疾病（COPD），但其潜在原因与机制仍未明确。作者旨在探讨环境空气污染与遗传易感性在哮喘进展为COPD过程中的作用。
方法：在UK Biobank基线期（2006–2010年）纳入46,832名哮喘患者。基于土地利用回归模型估算基线住址处的细颗粒物（PM2.5）和二氧化氮（NO₂）浓度，并构建反映联合暴露的“空气污染评分”。利用为“哮喘与COPD共存”所识别的新遗传信号计算多基因风险评分（PRS）。采用Cox比例风险回归，在校正协变量后评估环境空气污染与遗传评分对哮喘人群发生COPD的风险。
结果：在随访期间（中位数为10.84年），共有3,759名基线为哮喘的参与者发展为COPD。每四分位距（IQR）增量的PM2.5与NO₂分别对应发生COPD的风险比（HR）为1.07（95%CI：1.02–1.11）和1.10（95%CI：1.04–1.15）。在PM2.5为8 μg/m³、NO₂为12 μg/m³等较低浓度时即可出现不利影响。空气污染与遗传易感性之间存在显著的乘积交互作用；遗传风险评分最高的人群风险最大，每IQR空气污染评分增量的HR为1.13（95%CI：1.05–1.22）（交互作用检验P < 0.05）。
结论：环境空气污染与哮喘进展为COPD密切相关，尤其是遗传风险高的个体。
关键词：空气污染；遗传易感性；哮喘；慢性阻塞性肺疾病；疾病进展；细颗粒物；二氧化氮；多基因风险评分；土地利用回归；Cox比例风险模型；交互作用
Abstract
Background: In the UK, an estimated 15% of asthma patients have concurrent chronic obstructive pulmonary disease (COPD), yet the underlying causes and mechanisms remain largely unexplored. This study aimed to investigate the roles of both ambient air pollution and genetic susceptibility in the progression from asthma to COPD.
Methods:46 832 participants with asthma were recruited from the UK Biobank during the baseline period (2006–2010). Particulate matter with a diameter of 2.5 μm (PM2.5) and nitrogen dioxide (NO2) were estimated at baseline address using land-use regression models. Air pollution score reflected joint exposure to air pollution. Polygenic risk score was calculated using novel genetic signals identified for coexistence of asthma+COPD. Cox proportional hazards regression analysis was employed to quantify the risks of both ambient air pollution and genetic scores on incident COPD among asthmatics, adjusting for covariates.
Results：Over a median follow-up of 10.84 years, 3759 participants with asthma at baseline developed COPD. For an IQR increase in PM2.5 and NO2, the HR for developing COPD was 1.07 (95% CI: 1.02 to 1.11) and 1.10 (95% CI: 1.04 to 1.15), respectively. Adverse effects could be observed at concentrations as low as 8 µg/m3 for PM2.5 and 12 µg/m3 for NO2. A significant multiplicative interaction was identified between ambient air pollution and genetic susceptibility. Individuals with the highest genetic risk score exhibited the greatest risk, with an HR of 1.13 (95% CI: 1.05 to 1.22) per IQR increase in air pollution score (P interaction <0.05).
Conclusion：Ambient air pollution is strongly associated with progression from asthma to comorbidity COPD, particularly among individuals with high genetic risk.
方法：在UK Biobank基线期（2006–2010年）纳入46,832名哮喘患者。基于土地利用回归模型估算基线住址处的细颗粒物（PM2.5）和二氧化氮（NO₂）浓度，并构建反映联合暴露的“空气污染评分”。利用为“哮喘与COPD共存”所识别的新遗传信号计算多基因风险评分（PRS）。采用Cox比例风险回归，在校正协变量后评估环境空气污染与遗传评分对哮喘人群发生COPD的风险。
结果：在随访期间（中位数为10.84年），共有3,759名基线为哮喘的参与者发展为COPD。每四分位距（IQR）增量的PM2.5与NO₂分别对应发生COPD的风险比（HR）为1.07（95%CI：1.02–1.11）和1.10（95%CI：1.04–1.15）。在PM2.5为8 μg/m³、NO₂为12 μg/m³等较低浓度时即可出现不利影响。空气污染与遗传易感性之间存在显著的乘积交互作用；遗传风险评分最高的人群风险最大，每IQR空气污染评分增量的HR为1.13（95%CI：1.05–1.22）（交互作用检验P < 0.05）。
结论：环境空气污染与哮喘进展为COPD密切相关，尤其是遗传风险高的个体。
关键词：空气污染；遗传易感性；哮喘；慢性阻塞性肺疾病；疾病进展；细颗粒物；二氧化氮；多基因风险评分；土地利用回归；Cox比例风险模型；交互作用
（南方医科大学南方医院 黄海伦 龚钊乾 赵海金）
(Li G, Zhang K, Yang T, et al. Air pollution, genetic susceptibility and risk of progression from asthma to COPD[J]. Thorax, 2025: thorax-2024-222871. DOI: 10.1136/thorax-2024-222871.)
(Li G, Zhang K, Yang T, et al. Air pollution, genetic susceptibility and risk of progression from asthma to COPD[J]. Thorax, 2025: thorax-2024-222871. DOI: 10.1136/thorax-2024-222871.)
Background: In the UK, an estimated 15% of asthma patients have concurrent chronic obstructive pulmonary disease (COPD), yet the underlying causes and mechanisms remain largely unexplored. This study aimed to investigate the roles of both ambient air pollution and genetic susceptibility in the progression from asthma to COPD.
Methods:46 832 participants with asthma were recruited from the UK Biobank during the baseline period (2006–2010). Particulate matter with a diameter of 2.5 μm (PM2.5) and nitrogen dioxide (NO2) were estimated at baseline address using land-use regression models. Air pollution score reflected joint exposure to air pollution. Polygenic risk score was calculated using novel genetic signals identified for coexistence of asthma+COPD. Cox proportional hazards regression analysis was employed to quantify the risks of both ambient air pollution and genetic scores on incident COPD among asthmatics, adjusting for covariates.
Results：Over a median follow-up of 10.84 years, 3759 participants with asthma at baseline developed COPD. For an IQR increase in PM2.5 and NO2, the HR for developing COPD was 1.07 (95% CI: 1.02 to 1.11) and 1.10 (95% CI: 1.04 to 1.15), respectively. Adverse effects could be observed at concentrations as low as 8 µg/m3 for PM2.5 and 12 µg/m3 for NO2. A significant multiplicative interaction was identified between ambient air pollution and genetic susceptibility. Individuals with the highest genetic risk score exhibited the greatest risk, with an HR of 1.13 (95% CI: 1.05 to 1.22) per IQR increase in air pollution score (P interaction <0.05).
Conclusion：Ambient air pollution is strongly associated with progression from asthma to comorbidity COPD, particularly among individuals with high genetic risk.
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