Quantitative Interstitial Abnormality Progression and Outcomes in the Genetic Epidemiology of COPD and Pittsburgh Lung Screening Study Cohorts

doi:10.1016/j.chest.2022.06.030

. 2023 Jan;163(1):164-175.

doi: 10.1016/j.chest.2022.06.030. Epub 2022 Jun 30.

Quantitative Interstitial Abnormality Progression and Outcomes in the Genetic Epidemiology of COPD and Pittsburgh Lung Screening Study Cohorts

Bina Choi¹, Najma Adan², Tracy J Doyle³, Ruben San José Estépar⁴, Rola Harmouche⁴, Stephen M Humphries⁵, Matthew Moll⁶, Michael H Cho⁶, Rachel K Putman³, Gary M Hunninghake³, Ravi Kalhan⁷, Gabrielle Y Liu⁷, Alejandro A Diaz⁸, Stefanie E Mason⁸, Farbod N Rahaghi⁸, Carrie L Pistenmaa⁸, Nicholas Enzer⁹, Clare Poynton¹⁰, Gonzalo Vegas Sánchez-Ferrero⁴, James C Ross⁴, David A Lynch⁵, Fernando J Martinez¹¹, MeiLan K Han¹², Russell P Bowler¹³, David O Wilson¹⁴, Ivan O Rosas¹⁵, George R Washko⁸, Raúl San José Estépar⁴, Samuel Y Ash⁸; COPDGene Study and Pittsburgh Lung Screening Study Investigators

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA. Electronic address: bchoi4@bwh.harvard.edu.
² Department of Biology, University of Washington, Bothell, WA.
³ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
⁴ Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA; Department of Radiology, Brigham and Women's Hospital, Boston, MA.
⁵ Department of Radiology, National Jewish Health, Denver, CO.
⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
⁷ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
⁸ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA.
⁹ Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA.
¹⁰ Department of Radiology, Brigham and Women's Hospital, Boston, MA.
¹¹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY.
¹² Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
¹³ Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, CO.
¹⁴ Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
¹⁵ Section of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX.

PMID: 35780812
PMCID: PMC9859724
DOI: 10.1016/j.chest.2022.06.030

Quantitative Interstitial Abnormality Progression and Outcomes in the Genetic Epidemiology of COPD and Pittsburgh Lung Screening Study Cohorts

Bina Choi et al. Chest. 2023 Jan.

. 2023 Jan;163(1):164-175.

doi: 10.1016/j.chest.2022.06.030. Epub 2022 Jun 30.

Authors

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA. Electronic address: bchoi4@bwh.harvard.edu.
² Department of Biology, University of Washington, Bothell, WA.
³ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
⁴ Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA; Department of Radiology, Brigham and Women's Hospital, Boston, MA.
⁵ Department of Radiology, National Jewish Health, Denver, CO.
⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
⁷ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
⁸ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA.
⁹ Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA.
¹⁰ Department of Radiology, Brigham and Women's Hospital, Boston, MA.
¹¹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY.
¹² Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
¹³ Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, CO.
¹⁴ Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
¹⁵ Section of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX.

PMID: 35780812
PMCID: PMC9859724
DOI: 10.1016/j.chest.2022.06.030

Abstract

Background: The risk factors and clinical outcomes of quantitative interstitial abnormality progression over time have not been characterized.

Research questions: What are the associations of quantitative interstitial abnormality progression with lung function, exercise capacity, and mortality? What are the demographic and genetic risk factors for quantitative interstitial abnormality progression?

Study design and methods: Quantitative interstitial abnormality progression between visits 1 and 2 was assessed from 4,635 participants in the Genetic Epidemiology of COPD (COPDGene) cohort and 1,307 participants in the Pittsburgh Lung Screening Study (PLuSS) cohort. We used multivariable linear regression to determine the risk factors for progression and the longitudinal associations between progression and FVC and 6-min walk distance, and Cox regression models for the association with mortality.

Results: Age at enrollment, female sex, current smoking status, and the MUC5B minor allele were associated with quantitative interstitial abnormality progression. Each percent annual increase in quantitative interstitial abnormalities was associated with annual declines in FVC (COPDGene: 8.5 mL/y; 95% CI, 4.7-12.4 mL/y; P < .001; PLuSS: 9.5 mL/y; 95% CI, 3.7-15.4 mL/y; P = .001) and 6-min walk distance, and increased mortality (COPDGene: hazard ratio, 1.69; 95% CI, 1.34-2.12; P < .001; PLuSS: hazard ratio, 1.28; 95% CI, 1.10-1.49; P = .001).

Interpretation: The objective, longitudinal measurement of quantitative interstitial abnormalities may help identify people at greatest risk for adverse events and most likely to benefit from early intervention.

Keywords: 6-min walk test; interstitial lung disease; pulmonary fibrosis; pulmonary function test; radiology.

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Figures

**Figure 1**
Representative CT scan images of patients with quantitative interstitial abnormality (QIA) progression. A and B, A patient with no visible QIAs at baseline (A) who developed subtle evidence of QIAs at the bilateral bases after 5 years of follow-up (B). The percentage of this patient’s lung occupied by QIAs increased by 8.5% over 5 years, and he died approximately 6 months after his second CT scan was acquired. C and D, A patient with visually defined interstitial lung abnormalities (ILAs) at baseline (C) who showed progression of QIAs over the 5 years of follow-up (D). The percentage of this patient’s lung occupied by QIAs increased by 11.6% over the 5 years of follow-up, and he died shortly after his follow-up CT scan.

**Figure 2**
CONSORT diagrams for the COPDGene and PLuSS cohorts. CONSORT = Consolidated Standards of Reporting Trials; COPDGene = Genetic Epidemiology of COPD; PLuSS = Pittsburgh Lung Screening Study.

**Figure 3**
Box plots of baseline quantitative interstitial abnormalities (QIAs) in the participants with preserved ratio impaired spirometry (PRISm), participants in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0, or participants in GOLD stages 1 through 4. Boxes show medians and interquartile ranges; asterisks show means.

See this image and copyright information in PMC

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References

1. Washko G.R., Hunninghake G.M., Fernandez I.E., et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 2011;364(10):897–906. - PMC - PubMed
1. Doyle T.J., Washko G.R., Fernandez I.E., et al. Interstitial lung abnormalities and reduced exercise capacity. Am J Respir Crit Care Med. 2012;185(7):756–762. - PMC - PubMed
1. Doyle T.J., Hunninghake G.M., Rosas I.O. Subclinical interstitial lung disease: why you should care. Am J Respir Crit Care Med. 2012;185(11):1147–1153. - PMC - PubMed
1. Hunninghake G.M., Hatabu H., Okajima Y., et al. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med. 2013;368(23):2192–2200. - PMC - PubMed
1. Putman R.K., Hatabu H., Araki T., et al. Association between interstitial lung abnormalities and all-cause mortality. JAMA. 2016;315(7):672–681. - PMC - PubMed

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[1] Washko G.R., Hunninghake G.M., Fernandez I.E., et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 2011;364(10):897–906. - PMC - PubMed

[2] Washko G.R., Hunninghake G.M., Fernandez I.E., et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 2011;364(10):897–906. - PMC - PubMed

[3] Doyle T.J., Washko G.R., Fernandez I.E., et al. Interstitial lung abnormalities and reduced exercise capacity. Am J Respir Crit Care Med. 2012;185(7):756–762. - PMC - PubMed

[4] Doyle T.J., Washko G.R., Fernandez I.E., et al. Interstitial lung abnormalities and reduced exercise capacity. Am J Respir Crit Care Med. 2012;185(7):756–762. - PMC - PubMed

[5] Doyle T.J., Hunninghake G.M., Rosas I.O. Subclinical interstitial lung disease: why you should care. Am J Respir Crit Care Med. 2012;185(11):1147–1153. - PMC - PubMed

[6] Doyle T.J., Hunninghake G.M., Rosas I.O. Subclinical interstitial lung disease: why you should care. Am J Respir Crit Care Med. 2012;185(11):1147–1153. - PMC - PubMed

[7] Hunninghake G.M., Hatabu H., Okajima Y., et al. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med. 2013;368(23):2192–2200. - PMC - PubMed

[8] Hunninghake G.M., Hatabu H., Okajima Y., et al. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med. 2013;368(23):2192–2200. - PMC - PubMed

[9] Putman R.K., Hatabu H., Araki T., et al. Association between interstitial lung abnormalities and all-cause mortality. JAMA. 2016;315(7):672–681. - PMC - PubMed

[10] Putman R.K., Hatabu H., Araki T., et al. Association between interstitial lung abnormalities and all-cause mortality. JAMA. 2016;315(7):672–681. - PMC - PubMed

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Quantitative Interstitial Abnormality Progression and Outcomes in the Genetic Epidemiology of COPD and Pittsburgh Lung Screening Study Cohorts

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Quantitative Interstitial Abnormality Progression and Outcomes in the Genetic Epidemiology of COPD and Pittsburgh Lung Screening Study Cohorts

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