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Is there an association between ambient air pollutants and progression of emphysema and changes in lung function in the general population?
In this cohort study conducted between 2000 and 2018 that included 5780 participants in 6 US metropolitan regions followed up for a median of 10 years, there was a statistically significant association between baseline ambient concentrations of ambient ozone (O3), fine particulate matter (PM2.5), oxides of nitrogen (NOx), and black carbon with greater increases in emphysema assessed quantitatively using computed tomographic (CT) imaging. Concentrations of O3 and NOx, but not concentrations of PM2.5, over study follow-up were also associated with increases in emphysema. Baseline ambient O3 was significantly associated with a faster decline in forced expiratory volume in the first second (FEV1).
Long-term exposure to ambient air pollutants, especially O3, was significantly associated with increasing emphysema assessed quantitatively using CT imaging and with worsening lung function.
While air pollutants at historical levels have been associated with cardiovascular and respiratory diseases, it is not known whether exposure to contemporary air pollutant concentrations is associated with progression of emphysema.
To assess the longitudinal association of ambient ozone (O3), fine particulate matter (PM2.5), oxides of nitrogen (NOx), and black carbon exposure with change in percent emphysema assessed via computed tomographic (CT) imaging and lung function.
Design, Setting, and Participants
This cohort study included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) Air and Lung Studies conducted in 6 metropolitan regions of the United States, which included 6814 adults aged 45 to 84 years recruited between July 2000 and August 2002, and an additional 257 participants recruited from February 2005 to May 2007, with follow-up through November 2018.
Residence-specific air pollutant concentrations (O3, PM2.5, NOx, and black carbon) were estimated by validated spatiotemporal models incorporating cohort-specific monitoring, determined from 1999 through the end of follow-up.
Main Outcomes and Measures
Percent emphysema, defined as the percent of lung pixels less than −950 Hounsfield units, was assessed up to 5 times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scans (2010-2018). Spirometry was performed up to 3 times per participant (2004-2018).
Among 7071 study participants (mean [range] age at recruitment, 60 [45-84] years; 3330 [47.1%] were men), 5780 were assigned outdoor residential air pollution concentrations in the year of their baseline examination and during the follow-up period and had at least 1 follow-up CT scan, and 2772 had at least 1 follow-up spirometric assessment, over a median of 10 years. Median percent emphysema was 3% at baseline and increased a mean of 0.58 percentage points per 10 years. Mean ambient concentrations of PM2.5 and NOx, but not O3, decreased substantially during follow-up. Ambient concentrations of O3, PM2.5, NOx, and black carbon at study baseline were significantly associated with greater increases in percent emphysema per 10 years (O3: 0.13 per 3 parts per billion [95% CI, 0.03-0.24]; PM2.5: 0.11 per 2 μg/m3 [95% CI, 0.03-0.19]; NOx: 0.06 per 10 parts per billion [95% CI, 0.01-0.12]; black carbon: 0.10 per 0.2 μg/m3 [95% CI, 0.01-0.18]). Ambient O3 and NOx concentrations, but not PM2.5 concentrations, during follow-up were also significantly associated with greater increases in percent emphysema. Ambient O3 concentrations, but not other pollutants, at baseline and during follow-up were significantly associated with a greater decline in forced expiratory volume in 1 second per 10 years (baseline: 13.41 mL per 3 parts per billion [95% CI, 0.7-26.1]; follow-up: 18.15 mL per 3 parts per billion [95% CI, 1.59-34.71]).
Conclusions and Relevance
In this cohort study conducted between 2000 and 2018 in 6 US metropolitan regions, long-term exposure to ambient air pollutants was significantly associated with increasing emphysema assessed quantitatively using CT imaging and lung function.
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Corresponding Author: Joel D. Kaufman, MD, MPH, University of Washington, Box 354695, 4225 Roosevelt Way NE, Ste 100, Seattle, WA 98105 (firstname.lastname@example.org).
Accepted for Publication: June 24, 2019.
Author Contributions: Drs Kaufman and Barr had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The first authorship roles were shared by Drs Wang, Aaron, and Madrigano and last authorship roles were shared by Drs Kaufman and Barr.
Concept and design: Wang, Hoffman, Kinney, Sheppard, Smith, Vedal, Kaufman, Barr.
Acquisition, analysis, or interpretation of data: Wang, Aaron, Madrigano, Hoffman, Angelini, Yang, Laine, Vetterli, Sampson, Sheppard, Szpiro, Adar, Smith, Kirwa, Lederer, Diez Roux, Vedal, Kaufman, Barr.
Drafting of the manuscript: Wang, Laine, Vedal, Kaufman, Barr.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Wang, Aaron, Madrigano, Angelini, Yang, Laine, Sampson, Szpiro, Adar, Kirwa, Vedal, Kaufman, Barr.
Obtained funding: Hoffman, Smith, Kaufman, Barr.
Administrative, technical, or material support: Wang, Hoffman, Angelini, Yang, Laine, Vetterli, Smith, Kirwa, Lederer, Kaufman.
Supervision: Hoffman, Laine, Smith, Lederer, Vedal, Kaufman.
Conflict of Interest Disclosures: Dr Wang reported receiving grants from University of Washington (US EPA RD831697, US EPA RD83479601-01, NIEHS K24ES013195, NIEHS P30ES07033) during the conduct of the study. Dr Aaron reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study, grants from the Stony Wold-Herbert Fund and the Alpha1 Foundation, and personal fees from Lancet Respiratory Medicine outside the submitted work. Dr Madrigano reported receiving grants from National Oceanic and Atmospheric Administration during the conduct of the study and personal fees from the NIH outside the submitted work. Dr Hoffman reported receiving grants from the NIH; is a founder and shareholder of VIDA Diagnostics, a company commercializing lung image analysis software developed, in part, at the University of Iowa; and holds patents for an apparatus for analyzing CT images to determine the presence of pulmonary tissue pathology (US6466687B1), an apparatus for image display and analysis (WO1990016056A1), and a method for multiscale meshing of branching biological structures (US20110093243A1). Dr Yang reported receiving grants from the NIH (NIH R01-HL121270) during the conduct of the study. Dr Sampson reported receiving grants from the EPA (RD831697, RD83479601-01) during the conduct of the study. Dr Sheppard reported receiving grants from the EPA during the conduct of the study and grants from the NIH and personal fees from the Health Effects Institute outside the submitted work. Dr Szpiro reported receiving grants from the EPA and the National Institute of Environmental Health Sciences during the conduct of the study and personal fees from Health Effects Institute and the Electric Power Research Institute outside the submitted work. Dr Smith reported receiving grants from the NIH during the conduct of the study and grants from Quebec Health Research Fund, AstraZeneca, and McGill University Health Center Research Institute outside the submitted work. Dr Lederer reported receiving personal fees from Roche, Sanofi Genzyme, Philips Respironics, Fibrogen, Global Blood Therapeutics, Boehringer-Ingelheim, Veracyte, and Galapagos outside the submitted work; institutional grant support from Fibrogen, Global Blood Therapeutics, and Boehringer-Ingelhim; performing unpaid consulting work for Galecto, Pliant Therapeutics, and Bristol-Myers Squibb; and is now a full-time employee of Regeneron Pharmaceuticals (but was a was a full-time employee of Columbia University during the conduct of the study). Dr Diez-Roux reported receiving grants from the EPA and the NIH during the conduct of the study and Wellcome Trust outside the submitted work. Dr Kaufman reported receiving grants from the EPA and the NIH during the conduct of the study and the US National Institutes for Occupational Safety and Health, the Health Effects Institute, the Kresge Foundation, and the Global Alliance for Clean Cookstoves outside the submitted work. Dr Vedal reported receiving grants from the EPA during the conduct of the study and support for a research chair from AXA Research Fund outside the submitted work. Dr Barr reported receiving grants from the COPD Foundation and the Alpha1 Foundation outside the submitted work and grants from the EPA and NIH during the conduct of the study. No other disclosures were reported.
Funding/Support: This article was developed under a STAR research assistance agreement, No. RD831697 (MESA Air) and RD-83830001 (MESA Air Next Stage), awarded by the US Environmental Protection Agency (EPA) and the University of Washington Center for Clean Air Research (UW CCAR, EPA RD83479601-01). It has not been reviewed by the EPA. The MESA Lung Study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute grants R01-HL077612, RC1-HL100543, R01-HL093081, R01-HL121270, and R01-HL130605. MESA was funded by National Institutes of Health/National Heart, Lung, and Blood Institute contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 and by grants UL1-TR-000040 and UL1-TR-001079 from NCRR; the work was also supported by grants K24ES013195, P30ES07033, and R01ES023500 from the National Institute of Environmental Health Sciences.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The views expressed in this article are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication.
Additional Contributions: The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.
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