
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Air Pollutants in Urban Centers Trigger Non-Viral Asthma Exacerbations Through Activation of Coordinated Airway Inflammatory Responses
34 Pages Posted: 13 Jan 2022
More...Abstract
Background: Asthma prevalence and severity have markedly increased with urbanization, and children in low-income urban centers 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 to respiratory virus induced exacerbations, are poorly understood.
Methods: We investigated the relationships among regional air pollutant levels, respiratory viral infections, lung function, and upper airway transcriptional signatures in a cohort of 208 urban children with exacerbation-prone asthma during reported respiratory illnesses, with particular focus on asthma exacerbations occurring in the absence of a respiratory virus. We then validated observed associations between regional air pollutant levels and non-viral exacerbations in an independent cohort of 189 urban children with persistent asthma.
Findings: We found that elevated air quality index (AQI) values, driven predominantly by elevated particulate matter less than 2.5µm (PM2.5) and ozone (O3), 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 PM2.5 with increased epithelial induction of tissue kallikreins, the IL-23/IL-17 axis, mucus hypersecretion, and barrier functions, and O3 with increased type-2 inflammation.
Interpretation: These results provide important mechanistic insights into the contributions of air pollution to the respiratory health and asthma exacerbation subtypes of urban children. Furthermore, they identify potential future targets for the prevention and management of asthma exacerbations.
Trial Registration: The MUPPITS1 study was registered on clinicaltrials.gov as NCT02502890. The ICATA study was registered on clinicaltrials.gov as NCT00377572.
Funding: Funded by the National Institutes of Health/ National Institute of Allergy and Infectious Diseases.
Declaration of Interest: All authors with the exception of L. Wheatley, S. Sigelman, P. Gergen, and A. Togias report grants from NIH/NIAID/DAIT during the conduct of study. M. Altman reports personal fees for consulting from Regeneron. M. Kattan reports consulting fees from Novartis. G. O’Connor reports consulting fees from AstraZeneca, and reports a grant from Janssen Pharmaceuticals paid to his employing institution. M. Gill reports consulting fees from the American Academy of Allergy, Asthma, and Immunology and the American Academy of Pediatrics. R. Gruchalla reports employment as a special government employee with the Center for Biologics Evaluation and Research, and consulting fees from the Consulting Massachusetts Medical Society. A. Liu is a Consultant for Phadia ThermoFisher, received non-monetary research support from Phadia Thermofisher and Propeller Health/ResMed, and research funding from Avillion; all funds paid to University of Colorado. S. Lovinsky-Desir reports funding from NIH/NHLBI and the Robert Wood Johnson Foundation. J. Pongracic reports provisions of study drug for other asthma studies from Glaxo SmithKline, Boehringer-Ingelheim, and Genentech/Novartis. C. Kercsmar reports personal fees from Glaxo SmithKline for service on a DSMB and royalties from UpToDate. G. K. Khurana Hershey reports advisory board fees from Hoth Therapeutics. E. Zoratti reports consulting fees from Wayne State University. S. Teach reports support from NIH/NHLBI and EJF Philanthropies and royalties from UpToDate. L. Bacharier reports grant support from the NIH/NHLBI, Sanofi, and Vectura, as well as personal fees from GlaxoSmithKline, Genentech, Novartis, Merck, DBV Technologies, Teva, Boehringer Ingelheim, AstraZeneca, WebMD/Medscape, Sanofi, Regeneron, Vectura, and Circassia. W. Busse reports grants from NIH/NHLBI, during the conduct of the study; personal fees from Novartis, Regeneron, AstraZeneca, GlaxoSmithKline, Genentech, Elsevier, Med Learning Group, Boston Scientific, Medscape. J. Gern reports grants from NIH, personal fees and stock options from Meissa Vaccines Inc., personal fees from AstraZeneca and Ena Therapeutics and a patent on methods for production of rhinoviruses. D. Jackson reports grants from NIH/NHLBI and GlaxoSmithKline, personal fees for DSMB from Pfizer and for consulting from Novartis, Sanofi-Regeneron, GlaxoSmithKline, Vifor Pharma and Astra Zeneca. R. Murphy, E. Whalen, P. LeBeau, A. Calatroni, L. Wheatley, S. Sigelman, P. Gergen, and A. Togias have nothing to disclose.
Ethical Approval: The MUPPITS1 and ICATA studies complied with all relevant ethical regulations. The MUPPITS1 study was approved by a central IRB (Western IRB), and a parent or legal guardian for each child signed written informed consent, and participants provided assent, before completing study procedures. The ICATA study was approved by the institutional review boards of all participating institutions and written informed consent was obtained from each participant or the participant's parent or legal guardian. Participants who were younger than 18 years of age provided assent.
Keywords: Asthma exacerbations, air pollutants, transcriptomics, network analysis
Suggested Citation: Suggested Citation