Department of Medicine, University of Washington, Seattle, WA, USA; Systems Immunology Division, Benaroya Research Institute, Seattle, WA, USA.
Columbia University, New York, NY, USA.
Lancet Planet Health. 2023 Jan;7(1):e33-e44. doi: 10.1016/S2542-5196(22)00302-3.
Asthma prevalence and severity have markedly increased with urbanisation, and children in low-income urban centres have among the greatest asthma morbidity. Outdoor air pollution has been associated with adverse respiratory effects in children with asthma. However, the mechanisms by which air pollution exposure exacerbates asthma, and how these mechanisms compare with exacerbations induced by respiratory viruses, are poorly understood. We aimed to investigate the associations between regional air pollutant concentrations, respiratory illnesses, lung function, and upper airway transcriptional signatures in children with asthma, with particular focus on asthma exacerbations occurring in the absence of respiratory virus.
We performed a retrospective analysis of data from the MUPPITS1 cohort and validated our findings in the ICATA cohort. The MUPPITS1 cohort recruited 208 children aged 6-17 years living in urban areas across nine US cities with exacerbation-prone asthma between Oct 7, 2015, and Oct 18, 2016, and monitored them during reported respiratory illnesses. The last MUPPITS1 study visit occurred on Jan 6, 2017. The ICATA cohort recruited 419 participants aged 6-20 years with persistent allergic asthma living in urban sites across eight US cities between Oct 23, 2006, and March 25, 2008, and the last study visit occurred on Dec 30, 2009. We included participants from the MUPPITS1 cohort who reported a respiratory illness at some point during the follow-up and participants from the ICATA cohort who had nasal samples collected during respiratory illness or at a scheduled visit. We used air quality index values and air pollutant concentrations for PM, PM, O, NO, SO, CO, and Pb from the US Environmental Protection Agency spanning the years of both cohorts, and matched values and concentrations to each illness for each participant. We investigated the associations between regional air pollutant concentrations and respiratory illnesses and asthma exacerbations, pulmonary function, and upper airway transcriptional signatures by use of a combination of generalised additive models, case crossover analyses, and generalised linear mixed-effects models.
Of the 208 participants from the MUPPITS1 cohort and 419 participants from the ICATA cohort, 168 participants in the MUPPITS1 cohort (98 male participants and 70 female participants) and 189 participants in the ICATA cohort (115 male participants and 74 female participants) were included in our analysis. We identified that increased air quality index values, driven predominantly by increased PM and O concentrations, were significantly associated with asthma exacerbations and decreases in pulmonary function that occurred in the absence of a provoking viral infection. Moreover, individual pollutants were significantly associated with altered gene expression in coordinated inflammatory pathways, including PM with increased epithelial induction of tissue kallikreins, mucus hypersecretion, and barrier functions and O with increased type-2 inflammation.
Our findings suggest that air pollution is an important independent risk factor for asthma exacerbations in children living in urban areas and is potentially linked to exacerbations through specific inflammatory pathways in the airway. Further investigation of these potential mechanistic pathways could inform asthma prevention and management approaches.
National Institutes of Health, National Institute of Allergy and Infectious Diseases.
哮喘的患病率和严重程度随着城市化的发展显著增加，而低收入城市中心的儿童患哮喘的发病率最高。户外空气污染与哮喘儿童的不良呼吸影响有关。然而，空气污染暴露如何加重哮喘，以及这些机制如何与呼吸道病毒引起的加重相比较，仍知之甚少。我们旨在研究区域空气污染物浓度、呼吸道疾病、肺功能和哮喘儿童上呼吸道转录特征之间的关联，特别关注在没有呼吸道病毒的情况下发生的哮喘加重。
我们对 MUPPITS1 队列的数据进行了回顾性分析，并在 ICATA 队列中验证了我们的发现。MUPPITS1 队列招募了 208 名年龄在 6-17 岁之间的儿童，他们居住在美国 9 个城市的城市地区，患有易患哮喘的疾病，并在报告呼吸道疾病期间对他们进行了监测。最后一次 MUPPITS1 研究访问是在 2017 年 1 月 6 日。ICATA 队列招募了 419 名年龄在 6-20 岁之间的参与者，他们患有持续性过敏性哮喘，居住在美国 8 个城市的城市地区，招募时间为 2006 年 10 月 23 日至 2008 年 3 月 25 日，最后一次研究访问是在 2009 年 12 月 30 日。我们纳入了在随访期间报告过呼吸道疾病的 MUPPITS1 队列的参与者和在呼吸道疾病期间或定期就诊时采集了鼻腔样本的 ICATA 队列的参与者。我们使用了美国环境保护署提供的空气质量指数值和 PM、PM、O、NO、SO、CO 和 Pb 的污染物浓度，涵盖了两个队列的年份，并将每个参与者的每个疾病的数值和浓度进行了匹配。我们使用广义加性模型、病例交叉分析和广义线性混合效应模型的组合，研究了区域空气污染物浓度与呼吸道疾病和哮喘加重、肺功能和上呼吸道转录特征之间的关联。
在 MUPPITS1 队列的 208 名参与者和 ICATA 队列的 419 名参与者中，我们对 MUPPITS1 队列的 168 名参与者（98 名男性参与者和 70 名女性参与者）和 ICATA 队列的 189 名参与者（115 名男性参与者和 74 名女性参与者）进行了分析。我们发现，空气质量指数值的增加（主要是由 PM 和 O 浓度的增加引起的）与哮喘加重和病毒性感染引起的肺功能下降显著相关。此外，个别污染物与协调的炎症途径中的基因表达改变显著相关，包括 PM 增加上皮组织激肽的诱导、粘液分泌过多和屏障功能以及 O 增加 2 型炎症。
我们的发现表明，空气污染是居住在城市地区的儿童哮喘加重的一个重要独立危险因素，并且可能通过气道中的特定炎症途径与加重有关。对这些潜在机制途径的进一步研究可以为哮喘的预防和管理方法提供信息。
美国国立卫生研究院，国家过敏和传染病研究所。
