ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Air Pollutant Exposure-by-Gene Interactions Associated with Emphysema, Lung Structure, and Lung Function in SPIROMICS
Session Title
B12 - B012 THE AIR OUT THERE: INVESTIGATIONS IN AIR POLLUTION
Abstract
A1095 - Air Pollutant Exposure-by-Gene Interactions Associated with Emphysema, Lung Structure, and Lung Function in SPIROMICS
Author Block: V. E. Ortega1, L. M. Paulin2, J. D. Kaufman3, E. Ampleford1, H. Woo4, G. A. Hawkins1, X. Li5, I. Barjaktarevic6, S. P. Bhatt7, R. P. Bowler8, R. Barr9, C. B. Cooper10, D. Couper11, J. L. Curtis12, A. J. Gassett13, M. K. Han14, R. E. Kanner15, V. Kim16, F. J. Martinez17, W. C. Moore18, W. K. O'Neal19, R. Paine20, B. P. Smith20, B. Smith21, P. Woodruff22, E. A. Hoffman23, S. P. Peters24, D. A. Meyers25, E. R. Bleecker5, N. N. Hansel26, The Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) Investigators; 1Wake Forest School of Medicine, Winston-Salem, NC, United States, 2Pulmonary/Critical Care, Dartmouth Hitchcock Medical Center, Lebanon, NH, United States, 3Env/Occ Hlth, Medicine, Epidemiology, Univ of Washington, Seattle, WA, United States, 4Johns Hopkins University, Baltimore, MD, United States, 5Medicine, University of Arizona, Tucson, AZ, United States, 6Pulmonary and Critical Care, UCLA, Los Angeles, CA, United States, 7Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States, 8Natl Jewish Health, Denver, CO, United States, 9Presbyterian Hospital, Columbia University Medical Center, New York, NY, United States, 10Departments of Medicine and Physiology, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States, 11Biostatistics, Chapel Hill, NC, United States, 12Internal Medicine, Univ of Michigan Hlth System, Ann Arbor, MI, United States, 13University of Washington School of Public Health, Seattle, WA, United States, 14University of Michigan School of Medicine, Ann Arbor, MI, United States, 15Univ of Utah Sch of Med, Salt Lake City, UT, United States, 16Thoracic Medicine and Surgery, Temple Lung Center, Philadelphia, PA, United States, 17Weill Cornell Medical College, New York, NY, United States, 18Wake Forest Sch of Med, Winston-Salem, NC, United States, 19Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 20Univ of Utah, Salt Lake City, UT, United States, 21Columbia University, New York, NY, United States, 22Medicine, University of California, San Francisco, San Francisco, CA, United States, 23Univ of Iowa Carver Coll of Med, Iowa City, IA, United States, 24Internal Medicine, Wake Forest Univ Hlth Sciences, Winston-Salem, NC, United States, 25Genetics, Genomics, and Precision Medicine, University of Arizona, Tucson, AZ, United States, 26Johns Hopkins Univ, Baltimore, MD, United States.
Rationale: Air pollution exposures, including particulate matter (PM2.5), ozone (O3), and nitrogen oxides (NOx), are associated with COPD-related morbidity. We hypothesize that pollutant exposures interact with genomic variation related to altered lung function, emphysema, and lung structural alterations to drive COPD progression. Methods: Ten-year average concentrations of outdoor PM2.5, O3, NOx, and nitrogen dioxide (NO2) concentrations were estimated at the residences of 1,394 non-Hispanic Whites (NHW), 435 African Americans, and Hispanics (AAH) across seven SPIROMICS sites for genome-wide interaction studies (GWIS). GWIS models for lung function and CT scan-based lung structure consisted of site, age, sex, BMI, pack-years, census tract median household income, additive genotype, pollutant concentration, ancestral substructure, and genotype-by-pollutant interactions. Results: In NHW, the top interaction was a NOx-by-SNP interaction associated with emphysema (%voxels≤-950HFU) on RBFOX1 (rs67598351, pinteraction=1.54x10-7). NO2-SNP interactions associated with emphysema at an intergenic locus between RSPO2 and ANGPT1 (rs10086579, pinteraction=6.87x10-7) also reaching a genome-wide significant genotype effect (pgenotype=2.24x10-8). rs67598351 minor allele homozygotes (TT, N=28) and heterozygotes (CT, N=309) showed higher emphysema with increasing NOx exposure not observed in major allele homozygotes (CC, N=823, Figure-1A). In AAH, genome-wide significant PM2.5-SNP interactions associated with hyperinflation (%voxels≤-856HFU) at a locus distant from SEMA5A (rs13186697, pinteraction=1.21x10-8) and NO2-SNP interactions associated with emphysema in ZNF718 (rs7665922, pinteraction=3.04x10-8). rs7665922 minor allele homozygotes (CC, N=91) showed higher emphysema with increasing NO2 exposure while major allele homozygotes (TT, N=123) and heterozygotes (CT, N=219) showed the opposite (Figure-1B). In NHW, we identified nominally significant PM2.5-SNP interactions (p<9.9x10-7) for hyperinflation (rs11051391 near SINHCAF), O3-SNP interactions for hyperinflation (rs17079728 in SPATA13, rs11593840 in LRMDA), and NO2-SNP interactions for airway wall thickness, pi10 (rs4075947 near NEK6). In AAH, we identified nominally significant PM2.5-SNP interactions for hyperinflation (rs358980 in LMCD1-AS1), O3-SNP interactions for pi10 (rs75720263 near TSC22D2), NOx-SNP interactions for hyperinflation (rs113729874 in ENOX1) and post-bronchodilator FEV1 (rs4468361 near NTM), and NO2-SNP interactions for hyperinflation (rs2089001 in KHDRBS2) and FEV1 (rs587740 in TENM4, rs8052110 in WWOX). Conclusion: The genetic determinants of pollutant exposure effects in heavy smokers vary with ancestry, pollutants, and lung structure phenotypes. GWIS loci include those associated with nicotine use (RBFOX1, SEMA5A, NTM, NEK6), neutrophil migration to alveoli (RSPO2), intelligence measures (RBFOX1, LMCD1-AS1, NTM, TSC22D2, WWOX, TENM4), lung function (LRMDA, LMCD1-AS1, ENOX1, KHDRBS2), beta agonist response (SPATA13), and epigenetic regulation of hypoxia (SINHCAF) and severe asthma (ZNF718) demonstrating the complex genomic and socio-economic factors underlying the interaction between pollutant exposure and COPD progression.
Author Block: V. E. Ortega1, L. M. Paulin2, J. D. Kaufman3, E. Ampleford1, H. Woo4, G. A. Hawkins1, X. Li5, I. Barjaktarevic6, S. P. Bhatt7, R. P. Bowler8, R. Barr9, C. B. Cooper10, D. Couper11, J. L. Curtis12, A. J. Gassett13, M. K. Han14, R. E. Kanner15, V. Kim16, F. J. Martinez17, W. C. Moore18, W. K. O'Neal19, R. Paine20, B. P. Smith20, B. Smith21, P. Woodruff22, E. A. Hoffman23, S. P. Peters24, D. A. Meyers25, E. R. Bleecker5, N. N. Hansel26, The Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) Investigators; 1Wake Forest School of Medicine, Winston-Salem, NC, United States, 2Pulmonary/Critical Care, Dartmouth Hitchcock Medical Center, Lebanon, NH, United States, 3Env/Occ Hlth, Medicine, Epidemiology, Univ of Washington, Seattle, WA, United States, 4Johns Hopkins University, Baltimore, MD, United States, 5Medicine, University of Arizona, Tucson, AZ, United States, 6Pulmonary and Critical Care, UCLA, Los Angeles, CA, United States, 7Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States, 8Natl Jewish Health, Denver, CO, United States, 9Presbyterian Hospital, Columbia University Medical Center, New York, NY, United States, 10Departments of Medicine and Physiology, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States, 11Biostatistics, Chapel Hill, NC, United States, 12Internal Medicine, Univ of Michigan Hlth System, Ann Arbor, MI, United States, 13University of Washington School of Public Health, Seattle, WA, United States, 14University of Michigan School of Medicine, Ann Arbor, MI, United States, 15Univ of Utah Sch of Med, Salt Lake City, UT, United States, 16Thoracic Medicine and Surgery, Temple Lung Center, Philadelphia, PA, United States, 17Weill Cornell Medical College, New York, NY, United States, 18Wake Forest Sch of Med, Winston-Salem, NC, United States, 19Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 20Univ of Utah, Salt Lake City, UT, United States, 21Columbia University, New York, NY, United States, 22Medicine, University of California, San Francisco, San Francisco, CA, United States, 23Univ of Iowa Carver Coll of Med, Iowa City, IA, United States, 24Internal Medicine, Wake Forest Univ Hlth Sciences, Winston-Salem, NC, United States, 25Genetics, Genomics, and Precision Medicine, University of Arizona, Tucson, AZ, United States, 26Johns Hopkins Univ, Baltimore, MD, United States.
Rationale: Air pollution exposures, including particulate matter (PM2.5), ozone (O3), and nitrogen oxides (NOx), are associated with COPD-related morbidity. We hypothesize that pollutant exposures interact with genomic variation related to altered lung function, emphysema, and lung structural alterations to drive COPD progression. Methods: Ten-year average concentrations of outdoor PM2.5, O3, NOx, and nitrogen dioxide (NO2) concentrations were estimated at the residences of 1,394 non-Hispanic Whites (NHW), 435 African Americans, and Hispanics (AAH) across seven SPIROMICS sites for genome-wide interaction studies (GWIS). GWIS models for lung function and CT scan-based lung structure consisted of site, age, sex, BMI, pack-years, census tract median household income, additive genotype, pollutant concentration, ancestral substructure, and genotype-by-pollutant interactions. Results: In NHW, the top interaction was a NOx-by-SNP interaction associated with emphysema (%voxels≤-950HFU) on RBFOX1 (rs67598351, pinteraction=1.54x10-7). NO2-SNP interactions associated with emphysema at an intergenic locus between RSPO2 and ANGPT1 (rs10086579, pinteraction=6.87x10-7) also reaching a genome-wide significant genotype effect (pgenotype=2.24x10-8). rs67598351 minor allele homozygotes (TT, N=28) and heterozygotes (CT, N=309) showed higher emphysema with increasing NOx exposure not observed in major allele homozygotes (CC, N=823, Figure-1A). In AAH, genome-wide significant PM2.5-SNP interactions associated with hyperinflation (%voxels≤-856HFU) at a locus distant from SEMA5A (rs13186697, pinteraction=1.21x10-8) and NO2-SNP interactions associated with emphysema in ZNF718 (rs7665922, pinteraction=3.04x10-8). rs7665922 minor allele homozygotes (CC, N=91) showed higher emphysema with increasing NO2 exposure while major allele homozygotes (TT, N=123) and heterozygotes (CT, N=219) showed the opposite (Figure-1B). In NHW, we identified nominally significant PM2.5-SNP interactions (p<9.9x10-7) for hyperinflation (rs11051391 near SINHCAF), O3-SNP interactions for hyperinflation (rs17079728 in SPATA13, rs11593840 in LRMDA), and NO2-SNP interactions for airway wall thickness, pi10 (rs4075947 near NEK6). In AAH, we identified nominally significant PM2.5-SNP interactions for hyperinflation (rs358980 in LMCD1-AS1), O3-SNP interactions for pi10 (rs75720263 near TSC22D2), NOx-SNP interactions for hyperinflation (rs113729874 in ENOX1) and post-bronchodilator FEV1 (rs4468361 near NTM), and NO2-SNP interactions for hyperinflation (rs2089001 in KHDRBS2) and FEV1 (rs587740 in TENM4, rs8052110 in WWOX). Conclusion: The genetic determinants of pollutant exposure effects in heavy smokers vary with ancestry, pollutants, and lung structure phenotypes. GWIS loci include those associated with nicotine use (RBFOX1, SEMA5A, NTM, NEK6), neutrophil migration to alveoli (RSPO2), intelligence measures (RBFOX1, LMCD1-AS1, NTM, TSC22D2, WWOX, TENM4), lung function (LRMDA, LMCD1-AS1, ENOX1, KHDRBS2), beta agonist response (SPATA13), and epigenetic regulation of hypoxia (SINHCAF) and severe asthma (ZNF718) demonstrating the complex genomic and socio-economic factors underlying the interaction between pollutant exposure and COPD progression.
