What Can Big Data Teach Us About Air Pollution and Pneumonia?

FOR RELATED ARTICLE, SEE PAGE 39In this issue of CHEST, Wang et al1Wang J. Li D. Ma Y. et al.Long-term exposure to ambient air pollutants and increased risk of pneumonia in the UK Biobank.Chest. 2023; 164: 39-52Abstract Full Text Full Text PDF Scopus (1) Google Scholar present an analysis of participants in the UK Biobank, demonstrating that long-term exposure to air pollution is associated with an increased risk of pneumonia. Although the link between air pollution and lower respiratory tract infections is not a novel finding, most prior epidemiologic studies have focused on short-term pollutant exposures in the days or week before disease manifestation.2Horne B.D. Joy E.A. Hofmann M.G. et al.Short-term elevation of fine particulate matter air pollution and acute lower respiratory infection.Am J Respir Crit Care Med. 2018; 198: 759-766Crossref PubMed Scopus (227) Google Scholar,3Yee J. Cho Y.A. Yoo H.J. Yun H. Gwak H.S. Short-term exposure to air pollution and hospital admission for pneumonia: a systematic review and meta-analysis.Environ Health. 2021; 20: 6Crossref Scopus (42) Google Scholar Fewer studies have examined the chronic effects of pollutant exposure, in part because of the lack of cohorts with adequate data and sufficient statistical power to study this risk factor for a relatively rare outcome.4Neupane B. Jerrett M. Burnett R.T. Marrie T. Arain A. Loeb M. Long-term exposure to ambient air pollution and risk of hospitalization with community-acquired pneumonia in older adults.Am J Respir Crit Care Med. 2010; 181: 47-53Crossref PubMed Scopus (176) Google Scholar, 5Liu S. Lim Y.H. Chen J. et al.Long-term air pollution exposure and pneumonia-related mortality in a large pooled European cohort.Am J Respir Crit Care Med. 2022; 205: 1429-1439Crossref PubMed Scopus (10) Google Scholar, 6Kirwa K. Eckert C.M. Vedal S. Hajat A. Kaufman J.D. Ambient air pollution and risk of respiratory infection among adults: evidence from the multiethnic study of atherosclerosis (MESA).BMJ Open Respir Res. 2021; 8: e000866Crossref Scopus (13) Google Scholar FOR RELATED ARTICLE, SEE PAGE 39 To overcome this limitation, the authors use data that are available publicly through the UK Biobank (a prospective cohort study that enrolled 500,000 volunteers aged 40 to 69 years from 2006 to 2010 across England, Scotland, and Wales). Extensive biomarker and phenotypic data were collected from participants at baseline and linked with longitudinal health data, which included hospitalization and mortality records. In the current study, which includes 445,473 participants, incident pneumonia was defined based on International Classification of Diseases, Tenth Revision (ICD-10) codes at hospitalization. Exposure to four pollutant components (PM2.5, PM10, NO2, NOx) was estimated at home addresses in 2010 with the use of previously developed land-use regression models, which integrate pollutant levels at monitoring sites with geographic covariates, such as road use, and was assumed to represent long-term exposure levels.7Eeftens M. Beelen R. De Hoogh K. et al.Development of land use regression models for PM(2.5), PM(2.5) absorbance, PM(10) and PM(coarse) in 20 European study areas; results of the ESCAPE project.Environ Sci Technol. 2012; 46: 11195-11205Crossref PubMed Scopus (764) Google Scholar Analyses were adjusted for sociodemographic factors that included smoking status, preexisting lung diseases, and several proxies of individual-level socioeconomic status. Overall, the study provides confirmatory evidence that higher pollutant concentrations are associated with an increased risk of pneumonia hospitalization. Although the reported risk on an individual basis is small (6% to 12% per interquartile range of pollutant), the burden of disease that is attributable to pollution is large when applied over the general population. Results were robust to adjustment from individual-level confounders and consistent across multiple sensitivity analyses. Associations also persisted after restriction of the cohort to individuals with exposure to pollutant concentrations below current European Union limits and showed no evidence of a threshold effect below which there was no risk. This suggests that even low-level, chronic pollutant exposure imparts an increased risk of pneumonia. Importantly, the authors report an increased risk of pneumonia associated with air pollution exposure in ever smokers. The synergistic effect between smoking and air pollution is expressed on both additive and multiplicative scales to help contextualize the public health significance of the interaction.8Vanderweele T.J. Knol M.J. A tutorial on interaction.Epidemiol Methods. 2014; 3: 33-72Crossref Scopus (598) Google Scholar Specifically, measures of additive interaction, such as the relative excess risk caused by interaction, imply that reducing exposure to air pollution in ever smokers would result in a greater reduction in pneumonia hospitalizations compared with the same intervention in never smokers. Although this categorization designates ever smokers as a susceptible population, it does not address whether current and former smokers have differential risk of pneumonia associated with air pollution exposure. Understanding whether quitting smoking has the additional benefit of reducing the risk of adverse pollutant-related health effects could be a powerful tool to help motivate smoking cessation. The authors also found an increased risk of pneumonia associated with higher air pollution exposure among older adults and individuals with lower incomes. Whether the intersectionality of older age and lower income may further exacerbate pneumonia risk associated with air pollution exposure was not explored. These data have the potential to add to the health equity conversation, because socioeconomic status often spatially covaries with pollution exposure, with poorer communities living in areas with both higher concentrations of and more hazardous pollutant components. The disproportionate impact of pollution on individuals with lower socioeconomic status highlights compounding effects from high pollution exposure, diminished baseline health, and a lack of resources to mitigate adverse effects from air pollution.9Hooper L.G. Kaufman J.D. Ambient air pollution and clinical implications for susceptible populations.Ann Am Thorac Soc. 2018; 15: S64-S68Crossref Scopus (55) Google Scholar Despite the considerable strengths of this study, the lack of granularity in both the exposure and outcome ascertainment introduces some uncertainty in the interpretation of findings. The reliance on ICD-10 codes from hospitalizations to capture cases leads to a substantial risk for disease miscategorization and also misses individuals with less severe pneumonia who were treated as outpatients. Mechanistically, it is impossible to disentangle whether exposure to air pollution increases hospitalization for pneumonia caused by increased transmission vs greater severity of disease. Additionally, by lumping all causes of pneumonia into one category, the authors cannot determine whether pollution imparts variable risk for pneumonia depending on the specific pathogen. This detail is particularly salient in the context of an ongoing global pandemic; mounting evidence suggests that air pollution exposure specifically increases morbidity and mortality rates from COVID-19.10Hernandez Carballo I. Bakola M. Stuckler D. The impact of air pollution on COVID-19 incidence, severity, and mortality: a systematic review of studies in Europe and North America.Environ Res. 2022; 215: 114155Crossref Scopus (13) Google Scholar There are also potential spatial and temporal biases in pollution estimates. Participation in the UK Biobank was clustered around the 22 largely urban assessment sites, with most volunteers living within 25 miles of an assessment site. Although this resulted in a geographically diverse population across multiple countries, spatial clustering may have induced unmeasured confounding by region and was not controlled for in the analysis. The authors also used a cross-sectional average of pollution exposure in year 2010 as a proxy for long-term exposure. Although temporal trends in pollutant concentrations were on average relatively stable over the 10-year period, some regions may have experienced greater changes in air quality than others. The authors acknowledge this limitation and somewhat alleviate concerns by performing a sensitivity analysis that uses time-varying pollutant concentrations. Perhaps a greater consideration is whether the results from this study are generalizable to other populations, such as those in more rural settings; those who might live in proximity to known high-pollutant emitters; or those with more diverse socioeconomic status, race, and/or ethnicity. Participation in the UK biobank was based on convenience sampling rather than random selection, with a substantial “healthy-volunteer” effect. Participants lived in less socioeconomically deprived areas: more than 95% were White, and 85% were urban residents.11Fry A. Littlejohns T.J. Sudlow C. et al.Comparison of sociodemographic and health-related characteristics of UK Biobank participants with those of the general population.Am J Epidemiol. 2017; 186: 1026Crossref PubMed Scopus (1308) Google Scholar All of these sociodemographic factors have complex intersections with air pollution exposure that may bias causal inference. Although the large sample sizes in biorepositories may confer statistical power, estimates may be skewed and should be evaluated carefully in terms of generalizability and external validity.12Keyes K.M. Westreich D. UK Biobank, big data, and the consequences of non-representativeness.Lancet. 2019; 393: 1297Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Future studies should focus on recruiting cohorts, particularly from susceptible populations, to provide data that can inform equitable public health interventions. None declared. Long-term Exposure to Ambient Air Pollutants and Increased Risk of Pneumonia in the UK BiobankCHESTVol. 164Issue 1PreviewLong-term exposure to air pollutants was associated with an increased risk of pneumonia, especially in individuals who smoke. Full-Text PDF