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

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.

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.