Chest
Original Research: Diffuse Lung DiseaseClinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers
Section snippets
Methods
We performed our study by using CT scanning and clinical and genetic data from the Genetic Epidemiology of COPD (COPDGene) Study, which has been described in detail elsewhere.15, 16 Briefly, 10,300 smokers between the ages of 45 and 80 years, with a history of at least 10 pack-years, were enrolled and underwent baseline testing, including an extensive interview, volumetric high-resolution CT scanning of the chest, and spirometric testing. COPDGene excluded Hispanics from the study, and the only
Results
A total of 8,345 participants had both clinical and objective imaging data available for analysis. Baseline characteristics of the entire cohort and subgroups are shown in Table 1. The distributions of interstitial changes in the cohort by lung zone are shown in Figure 2.
As shown in Table 2, in both the adjusted and unadjusted analyses, increasing amounts of interstitial features were associated with lower FEV1 % predicted, lower FVC % predicted, higher FEV1/FVC ratio, and a worse quality of
Discussion
In a large cohort of current and former smokers, we found that objectively detected interstitial features were associated with reduced lung function, worse quality of life, and increased mortality. In addition, for each copy of the minor allele of the MUC5B promoter polymorphism (rs35705950), more of the lung was affected by interstitial features. These associations were present even in participants who did not have visually defined ILA, in those with normal lung function, and in those without
Conclusions
We have developed and applied an objective analysis tool that quantifies interstitial changes on CT scans to a large cohort of smokers without known interstitial disease. Objective interstitial changes defined by this method were associated with reduced lung function, worse quality of life, and higher mortality, as well as a higher number of copies of a specific polymorphism in the promoter region of MUC5B. Additional work is needed to replicate these findings in other cohorts to help define a
Acknowledgments
Author contributions: S. Y. A. and G. R. W. take full responsibility for the content of this manuscript including the data and analysis. S. Y. A., R. H., J. C. R., R. S. J. E., and G. R. W. contributed to the study concept and design. All authors contributed to the acquisition, analysis, or interpretation of data. All authors contributed to the drafting of the manuscript. All authors contributed to the intellectual content. S. Y. A., R. K. P., A. A. D., and G. R. W. contributed to the
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2023, ChestCitation Excerpt :Multiple prior studies have demonstrated the clinical relevance of subtle interstitial findings on CT scans, such as areas of higher attenuation or QIAs, which have been measured by a variety of techniques and assessed in a range of cohorts.8-10,25-29 For example, in previous work, we had shown that objectively measured QIAs (previously called interstitial features), measured by a machine learning-based approach that uses lung density and distance from the pleural surface, are associated with decreased lung function, a shorter 6MWD, worse subjective dyspnea, and increased mortality.8-10 However, these and other studies have largely focused on cross-sectional associations or predictions of change in clinical metrics, rather than on the changes in the CT measures themselves over time.
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2021, ChestCitation Excerpt :Based on prior experience and expertise in this area, we selected a parsimonious list of imaging features to attempt to represent the breadth of both pulmonary and extrapulmonary quantitative CT metrics of lung disease.16-19 These included (1) the objective characterization of interstitial features and emphysema-like tissue with the use of a local histogram-based technique, (2) the measurement of pectoralis muscle area (expressed in square centimeters) that is performed on a single axial image above the level of the aortic arch, and (3) airway wall thickness as defined by the mean thickness of 6 segmental airways from each subject.20-29 Further details and supplemental analyses with an expanded list of quantitative measures are available in the Online Supplement.
Interstitial Lung Abnormalities and Early Interstitial Lung Disease
2021, Encyclopedia of Respiratory Medicine, Second EditionInterstitial lung abnormalities detected incidentally on CT: a Position Paper from the Fleischner Society
2020, The Lancet Respiratory MedicineCitation Excerpt :In general, these approaches are sensitive enough to detect ILD in patients at high risk and provide a more reproducible assessment than visual CT scoring.79 For ILAs, individuals with a lower percentage of normal lung by local histogram measurements had a higher prevalence of clinical impairment, poorer quality of life, higher risk of death, and association with the common variant in the promoter of the MUC5B gene (figure 6).17 Using a different local histogram-based system in 217 individuals undergoing resection for lung cancer, the fibrosis score correlated with the presence of ILAs and was an independent predictor of decreased disease-free survival.71
Drs Ash and Harmouche contributed equally to this work.
Drs San Jose Estepar and Washko contributed equally to this work.
FUNDING/SUPPORT: This study was funded by the National Institutes of Health [Grants 5-T32-HL007633-30 (S. Y. A., R. K. P.), R01-HL107246 (R. H., J. O. O., R. S. J. E., G. R. W.), R01-HL116933 (R. H., J. C. R., J. O. O., R. S. J. E., G. R. W.), R01-HL111024 (G. M. H.), P01-HL114501 (A. M. C., I. O. R., G. R. W.), and R01-HL089856 (J. C. R., D. A. L., R. S. J. E., G. R. W.)]; and Boehringer Ingelheim Pharmaceuticals, Inc. (G. R. W.).