Publications by authors named "George R Washko"

263 Publications

Gene expression of oxidative stress markers and lung function: A CARDIA lung study.

Mol Genet Genomic Med 2021 Nov 19:e1832. Epub 2021 Nov 19.

Department of Pathology and Laboratory Medicine, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA.

Background: Circulating markers of oxidative stress have been associated with lower lung function. Our objective was to study the association of gene expression levels of oxidative stress pathway genes (ALOX12, ALOX15, ARG2, GSTT1, LPO, MPO, NDUFB3, PLA2G7, and SOD3) and lung function forced expiratory volume in one second (FEV ), forced vital capacity (FVC) in Coronary Artery Risk Development in Young Adults study.

Methods: Lung function was measured using spirometry and the Nanostring platform was used to estimate gene expression levels. Linear regression models were used to study association of lung function measured at year 30, 10-year decline in lung function and gene expression after adjustment for center, smoking, and BMI, measured at year 25.

Results: The 10-year decline of FEV was faster in highest NDUFB3 quartile compared to the lowest (difference = -2.09%; p = 0.001) after adjustment for multiple comparisons. The 10-year decline in FEV and FVC was nominally slower in highest versus lowest quartile of PLA2G7 (difference = 1.14%; p = 0.02, and difference = 1.06%; p = 0.005, respectively). The other genes in the study were not associated with FEV or FVC.

Conclusion: Higher gene expression levels in oxidative stress pathway genes are associated with faster 10-year FEV decline.
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http://dx.doi.org/10.1002/mgg3.1832DOI Listing
November 2021

Longitudinal association between muscle loss and mortality in ever-smokers.

Chest 2021 Nov 13. Epub 2021 Nov 13.

Department of Medicine, Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston MA.

Background: Body composition measures, specifically low weight or reduced muscle mass, are associated with mortality in chronic obstructive pulmonary disease (COPD), but the effect of longitudinal body composition changes is undefined.

Research Question: Is the longitudinal loss of fat-free mass (FFM) associated with increased mortality including in those with initially normal or elevated body composition metrics?

Study Design And Methods: Participants with complete data for at least one visit in the COPDGene (n=9,268) and ECLIPSE studies (1,760) were included and followed for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed sub-model for PMA and a Cox proportional hazards sub-model for survival were fitted on a joint distribution using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.

Results: Both cohorts demonstrated a left shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each one cm2 PMA loss, mortality increased 3.1% (95% CI 2.4, 3.7, p<0.001) in COPDGene, and 2.4% (95% CI 0.9, 4.0, p<0.001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity (BODE index quartiles) and was significant even in participants with initially greater than average PMA.

Interpretation: Longitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever-smokers.
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http://dx.doi.org/10.1016/j.chest.2021.10.047DOI Listing
November 2021

Interstitial Lung Abnormalities, Emphysema and Spirometry in Smokers.

Chest 2021 Nov 3. Epub 2021 Nov 3.

Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston MA. Electronic address:

Background: Most pulmonary conditions reduce forced vital capacity (FVC), but studies of patients with combined pulmonary fibrosis and emphysema demonstrate that reductions in FVC are less than expected when these two conditions coexist clinically.

Research Question: Do interstitial lung abnormalities (ILA), chest computed tomography (CT) imaging findings that may suggest an early stage of pulmonary fibrosis in undiagnosed individuals, affect the association between emphysema and FVC?

Study Design And Methods: Measures of ILA and emphysema were available in 9579 and 5277 participants from phases 1 (2007-2011) and 2 (2012-2016) of COPDGene, respectively. ILA were defined by Fleischner Society guidelines. Adjusted linear regression models were used to assess the associations and interactions between ILA, emphysema, measures of spirometry and lung function.

Results: ILA were present in 528 (6%), and 580 (11%), of participants in phases 1 and 2 of COPDGene, respectively. ILA modified the association between emphysema and FVC (P<0.0001 for interaction) in both phases. In phase 1, in those without ILA, a 5% increase in emphysema was associated with a reduction in FVC (-110 cc, 95% confidence interval [CI] -121, -100; P<0.0001) however, in those with ILA it was not (-11cc, 95% CI -53,31; P=0.59). In contrast, there was no interaction between ILA and emphysema on total lung capacity (TLC) nor on diffusing capacity of carbon monoxide (DLCO).

Interpretation: The presence of ILA attenuates the reduction in FVC associated with emphysema.
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http://dx.doi.org/10.1016/j.chest.2021.10.034DOI Listing
November 2021

Evolution of Obstructive Lung Function in Advanced Pulmonary Arterial Hypertension.

Am J Respir Crit Care Med 2021 Sep 23. Epub 2021 Sep 23.

University of California Los Angeles David Geffen School of Medicine, 12222, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Los Angeles, California, United States;

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http://dx.doi.org/10.1164/rccm.202105-1169LEDOI Listing
September 2021

Loss of Pulmonary Vascular Volume as a Predictor of Right Ventricular Dysfunction and Mortality in Acute Pulmonary Embolism.

Circ Cardiovasc Imaging 2021 Sep 21;14(9):e012347. Epub 2021 Sep 21.

University of Pennsylvania, Philadelphia. Division of Pulmonary and Critical Care Medicine (S.M.H., E.H., S.A., S.M., A.B.W., G.R.W., F.N.R.), Brigham and Women's Hospital, Harvard Medical School, Boston.

Background: In acute pulmonary embolism, chest computed tomography angiography derived metrics, such as the right ventricle (RV): left ventricle ratio are routinely used for risk stratification. Paucity of intraparenchymal blood vessels has previously been described, but their association with clinical biomarkers and outcomes has not been studied. We sought to determine if small vascular volumes measured on computed tomography scans were associated with an abnormal RV on echocardiography and mortality. We hypothesized that decreased small venous volume would be associated with greater RV dysfunction and increased mortality.

Methods: A retrospective cohort of patients with intermediate risk pulmonary embolism admitted to Brigham and Women's Hospital between 2009 and 2017 was assembled, and clinical and radiographic data were obtained. We performed 3-dimensional reconstructions of vasculature to assess intraparenchymal vascular volumes. Statistical analyses were performed using multivariable regression and cox proportional hazards models, adjusting for age, sex, lung volume, and small arterial volume.

Results: Seven hundred twenty-two subjects were identified of whom 573 had documented echocardiography. A 50% reduction in small venous volume was associated with an increased risk of RV dilation (relative risk: 1.38 [95% CI, 1.18-1.63], <0.001), RV dysfunction (relative risk: 1.62 [95% CI, 1.36-1.95], <0.001), and RV strain (relative risk: 1.67 [95% CI, 1.37-2.04], <0.001); increased cardiac biomarkers, and higher 30-day and 90-day mortality (hazard ratio: 2.50 [95% CI, 1.33-4.67], =0.004 and hazard ratio: 1.84 [95% CI, 1.11-3.04], =0.019, respectively).

Conclusions: Loss of small venous volume quantified from computed tomography angiography is associated with increased risk of abnormal RV on echocardiography, abnormal cardiac biomarkers, and higher risk of 30- and 90-day mortality. Small venous volume may be a useful marker for assessing disease severity in acute pulmonary embolism.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.012347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462092PMC
September 2021

Genetic variation in genes regulating skeletal muscle regeneration and tissue remodelling associated with weight loss in chronic obstructive pulmonary disease.

J Cachexia Sarcopenia Muscle 2021 Sep 15. Epub 2021 Sep 15.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach.

Methods: Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low BMI (BMI < 20 kg/m ). In ECLIPSE and SPIROMICS, weight loss was calculated using available longitudinal visits. Stratified analyses were performed among African American (AA) and Non-Hispanic White (NHW) participants with COPD. Single variant and gene-based analyses were performed adjusting for confounders. Fine mapping was performed using a Bayesian approach integrating genetic association results with linkage disequilibrium and functional annotation. Significant gene networks were identified by integrating genetic regions associated with weight loss with skeletal muscle protein-protein interaction (PPI) data.

Results: At the single variant level, only the rs35368512 variant, intergenic to GRXCR1 and LINC02383, was associated with weight loss (odds ratio = 3.6, 95% confidence interval = 2.3-5.6, P = 3.2 × 10 ) among AA COPD participants in COPDGene. At the gene level in COPDGene, EFNA2 and BAIAP2 were significantly associated with weight loss in AA and NHW COPD participants, respectively. The EFNA2 association replicated among AA from SPIROMICS (P = 0.0014), whereas the BAIAP2 association replicated in NHW from ECLIPSE (P = 0.025). The EFNA2 gene encodes the membrane-bound protein ephrin-A2 involved in the regulation of developmental processes and adult tissue homeostasis such as skeletal muscle. The BAIAP2 gene encodes the insulin-responsive protein of mass 53 kD (IRSp53), a negative regulator of myogenic differentiation. Integration of the gene-based findings participants with PPI data revealed networks of genes involved in pathways such as Rho and synapse signalling.

Conclusions: The EFNA2 and BAIAP2 genes were significantly associated with weight loss in COPD participants. Collectively, the integrative network analyses indicated genetic variation associated with weight loss in COPD may influence skeletal muscle regeneration and tissue remodelling.
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http://dx.doi.org/10.1002/jcsm.12782DOI Listing
September 2021

Neighborhood Socioeconomic Deprivation in Young Adulthood and Future Respiratory Health: The CARDIA Lung Study.

Am J Med 2021 Sep 9. Epub 2021 Sep 9.

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

Purpose: There are limited data on the relationship between neighborhood level factors and their association with lung health independent of individual socioeconomic status. We sought to determine whether baseline neighborhood level socioeconomic deprivation in young adults is associated with greater 20-year decline in lung function and higher risk of future lung disease, independent of baseline individual income, education, and smoking status.

Methods: This multicenter population-based cohort study included 2689 participants in Coronary Artery Risk Development in Young Adults (CARDIA) for whom neighborhood deprivation was determined at year 10 (baseline for study) and who had complete lung function measurements at years 10 and 30. Baseline neighborhood deprivation was defined using 1990 Census blocks as a combination of 4 factors involving median household income, poverty level, and educational achievement. The outcomes were decline in lung function over 20 years (year 10 to 30) and odds of emphysema (year 25).

Results: In multivariable regression models, greater baseline neighborhood deprivation was associated with greater decline in lung function (-2.34 mL/year excess annual decline in forced expiratory volume in 1 second (FEV) in the highest versus lowest deprivation quartile (P = .014)). Furthermore, baseline neighborhood deprivation was independently associated with greater odds of emphysema (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.42-6.30).

Conclusions: Residence in neighborhoods with greater socioeconomic deprivation in young adulthood, independent of individual income and smoking, is associated with greater 20-year decline in forced expiratory volume in 1 second and higher risk of future emphysema.
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http://dx.doi.org/10.1016/j.amjmed.2021.07.048DOI Listing
September 2021

Predictors of lung function trajectories in population-based studies: A systematic review.

Respirology 2021 10 7;26(10):938-959. Epub 2021 Sep 7.

Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.

Despite the growing body of evidence on lung function trajectories over the life course and their risk factors, the literature has not been systematically synthesized. Publications related to lung function trajectories were identified from PubMed, EMBASE and CINAHL databases. Two authors independently identified publications for inclusion according to predefined selection criteria. Studies that modelled lung function trajectories and reported associated exposures were included. Meta-analyses could not be conducted due to heterogeneity in the exposures and methods used to model lung function trajectories. Nine publications were eligible for inclusion of which four used group-based trajectory modelling to model lung function trajectories, while five used latent profile analysis. Studies with repeated lung function measurements over the life course identified more trajectories than others. Only one study spanning from childhood to middle age reported catch-up trajectory. The following childhood risk factors for subnormal lung function trajectories were observed in at least across two studies: low birth weight, early wheezing, asthma, allergic sensitization, eczema, allergic rhinitis, lower respiratory tract infections, family history of asthma and second-hand smoke exposure. Adult active asthma and personal cigarette smoking were observed to be associated with accelerated decline lung trajectories. Our review identified 10 risk factors associated with the growth, catch-up, reduced plateau and decline trajectories of lung function. Intervention directed at childhood asthma and infections, and tobacco smoke exposure at all ages would help promote lung health and prevent subnormal lung function trajectories.
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http://dx.doi.org/10.1111/resp.14142DOI Listing
October 2021

Quantification of Arterial and Venous Morphologic Markers in Pulmonary Arterial Hypertension Using CT Imaging.

Chest 2021 Jul 13. Epub 2021 Jul 13.

Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Background: Pulmonary hypertension is a heterogeneous disease, and a significant portion of patients at risk for it have CT imaging available. Advanced automated processing techniques could be leveraged for early detection, screening, and development of quantitative phenotypes. Pruning and vascular tortuosity have been previously described in pulmonary arterial hypertension (PAH), but the extent of these phenomena in arterial vs venous pulmonary vasculature and in exercise pulmonary hypertension (ePH) have not been described.

Research Question: What are the arterial and venous manifestations of pruning and vascular tortuosity using CT imaging in PAH, and do they also occur in ePH?

Study Design And Methods: A cohort of patients with PAH and ePH and control subjects with available CT angiograms were retrospectively identified to examine the differential arterial and venous presence of pruning and tortuosity in patients with precapillary pulmonary hypertension not confounded by lung or thromboembolic disease. The pulmonary vasculature was reconstructed, and an AI method was used to separate arteries and veins and to compute arterial and venous vascular volumes and tortuosity.

Results: A total of 42 patients with PAH, 12 patients with ePH, and 37 control subjects were identified. There was relatively lower (median [interquartile range]) arterial small vessel volume in subjects with PAH (PAH 14.7 [11.7-16.2; P < .0001]) vs control subjects (16.9 [15.6-19.2]) and venous small vessel volume in subjects with PAH and ePH (PAH 8.0 [6.5-9.6; P < .0001]; ePH, 7.8 [7.5-11.4; P = .004]) vs control subjects (11.5 [10.6-12.2]). Higher large arterial volume, however, was only observed in the pulmonary arteries (PAH 17.1 [13.6-23.4; P < .0001] vs control subjects 11.4 [8.1-15.4]). Similarly, tortuosity was higher in the pulmonary arteries in the PAH group (PAH 3.5 [3.3-3.6; P = .0002] vs control 3.2 [3.2-3.3]).

Interpretation: Lower small distal pulmonary vascular volume, higher proximal arterial volume, and higher arterial tortuosity were observed. These can be quantified by using automated techniques from clinically acquired CT scans of patients with ePH and resting PAH.
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http://dx.doi.org/10.1016/j.chest.2021.06.069DOI Listing
July 2021

An Integrative Genomic Strategy Identifies sRAGE as a Causal and Protective Biomarker of Lung Function.

Chest 2021 Jul 6. Epub 2021 Jul 6.

Framingham Heart Study, Framingham, MA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Electronic address:

Background: There are few clinically useful circulating biomarkers of lung function and lung disease. We hypothesized that genome-wide association studies (GWAS) of circulating proteins in conjunction with GWAS of pulmonary traits represents a clinically relevant approach to identifying causal proteins and therapeutically useful insights into mechanisms related to lung function and disease.

Study Question: Can an integrative genomic strategy using GWAS of plasma soluble receptor for advanced glycation end-products (sRAGE) levels in conjunction with GWAS of lung function traits identify putatively causal relations of sRAGE to lung function?

Study Design And Methods: Plasma sRAGE levels were measured in 6,861 Framingham Heart Study participants and GWAS of sRAGE was conducted to identify protein quantitative trait loci (pQTL), including cis-pQTL variants at the sRAGE protein-coding gene locus (AGER). We integrated sRAGE pQTL variants with variants from GWAS of lung traits. Colocalization of sRAGE pQTL variants with lung trait GWAS variants was conducted, and Mendelian randomization was performed using sRAGE cis-pQTL variants to infer causality of sRAGE for pulmonary traits. Cross-sectional and longitudinal protein-trait association analyses were conducted for sRAGE in relation to lung traits.

Results: Colocalization identified shared genetic signals for sRAGE with lung traits. Mendelian randomization analyses suggested protective causal relations of sRAGE to several pulmonary traits. Protein-trait association analyses demonstrated higher sRAGE levels to be cross-sectionally and longitudinally associated with preserved lung function.

Interpretation: sRAGE is produced by type I alveolar cells, and it acts as a decoy receptor to block the inflammatory cascade. Our integrative genomics approach provides evidence for sRAGE as a causal and protective biomarker of lung function, and the pattern of associations is suggestive of a protective role of sRAGE against restrictive lung physiology. We speculate that targeting the AGER/sRAGE axis may be therapeutically beneficial for the treatment and prevention of inflammation-related lung disease.
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http://dx.doi.org/10.1016/j.chest.2021.06.053DOI Listing
July 2021

Study protocol for a national cohort of adults focused on respiratory health: the American Lung Association Lung Health Cohort (ALA-LHC) Study.

BMJ Open 2021 07 5;11(7):e053342. Epub 2021 Jul 5.

Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

Introduction: The current framework for investigating respiratory diseases is based on defining lung health as the absence of lung disease. In order to develop a comprehensive approach to prevent the development of lung disease, there is a need to evaluate the full spectrum of lung health spanning from ideal to impaired lung health. The American Lung Association (ALA) Lung Health Cohort is a new, population-based, cohort study focused primarily on characterising lung health in members of the millennial generation without diagnosed severe respiratory disease. Participants will be enrolled for the baseline study visit starting in 2021, and funding will be sought to support future study exams as part of a longitudinal cohort study. This study will be crucial for developing a novel paradigm of lung health throughout the adult life course.

Methods And Analysis: This study will leverage the existing infrastructure of the ALA Airways Clinical Research Centers network to enrol 4000 participants between ages 25 and 35 years old at 39 sites across the USA between April 2021 and December 2024. Study procedures will include physical assessment, spirometry, chest CT scan, accelerometry and collection of nasal epithelial lining fluid, nasal epithelial cells, blood and urine. Participants will complete questionnaires about their sociodemographic characteristics, home address histories and exposures, work history and exposure, medical histories, lung health and health behaviours and activity.

Ethics And Dissemination: The study was approved by the Johns Hopkins Medicine Institutional Review Board. Findings will be disseminated to the scientific community through peer-reviewed journals and at professional conferences. The lay public will receive scientific findings directly through the ALA infrastructure including the official public website. Deidentified datasets will be deposited to BioLINCC, and deidentified biospecimens may be made available to qualified investigators along with a limited-use datasets.
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http://dx.doi.org/10.1136/bmjopen-2021-053342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258664PMC
July 2021

Detection and Early Referral of Patients With Interstitial Lung Abnormalities: An Expert Survey Initiative.

Chest 2021 Jun 29. Epub 2021 Jun 29.

Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI.

Background: Interstitial lung abnormalities (ILA) may represent undiagnosed early-stage or subclinical interstitial lung disease (ILD). ILAs are often observed incidentally in patients who subsequently develop clinically overt ILD. There is limited information on consensus definitions for, and the appropriate evaluation of, ILA. Early recognition of patients with ILD remains challenging, yet critically important. Expert consensus could inform early recognition and referral.

Research Question: Can consensus-based expert recommendations be identified to guide clinicians in the recognition, referral, and follow-up of patients with or at risk of developing early ILDs?

Study Design And Methods: Pulmonologists and radiologists with expertise in ILD participated in two iterative rounds of surveys. The surveys aimed to establish consensus regarding ILA reporting, identification of patients with ILA, and identification of populations that might benefit from screening for ILD. Recommended referral criteria and follow-up processes were also addressed. Threshold for consensus was defined a priori as ≥ 75% agreement or disagreement.

Results: Fifty-five experts were invited and 44 participated; consensus was reached on 39 of 85 questions. The following clinically important statements achieved consensus: honeycombing and traction bronchiectasis or bronchiolectasis indicate potentially progressive ILD; honeycombing detected during lung cancer screening should be reported as potentially significant (eg, with the Lung CT Screening Reporting and Data System "S-modifier" [which indicates clinically significant or potentially significant noncancer findings]), recommending referral to a pulmonologist in the radiology report; high-resolution CT imaging and full pulmonary function tests should be ordered if nondependent subpleural reticulation, traction bronchiectasis, honeycombing, centrilobular ground-glass nodules, or patchy ground-glass opacity are observed on CT imaging; patients with honeycombing or traction bronchiectasis should be referred to a pulmonologist irrespective of FVC and diffusion capacity values; and patients with systemic sclerosis should be screened with pulmonary function tests for early-stage ILD.

Interpretation: Guidance for identifying clinically relevant ILA, with subsequent referral and follow-up, was established. These results lay the foundation for developing practical guidance on managing patients with ILA.
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http://dx.doi.org/10.1016/j.chest.2021.06.035DOI Listing
June 2021

Association between Cardiorespiratory Fitness and Bronchiectasis at CT: A Long-term Population-based Study of Healthy Young Adults Aged 18-30 Years in the CARDIA Study.

Radiology 2021 07 27;300(1):190-196. Epub 2021 Apr 27.

From the Division of Pulmonary and Critical Care Medicine (A.A.D., Y.O., G.R.W.) and Department of Radiology (J.C.R., R.S.J.E.), Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill (L.A.C., R.K.); Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill (M.A.S., R.K.); Department of Radiology, University of California, San Diego, San Diego, Calif (A.Y.); Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama School of Medicine, Birmingham, Ala (M.T.D.); and Department of Medicine, Penn Presbyterian Medical Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pa (G.T.).

Background Protective factors against the risk of bronchiectasis are unknown. A high level of cardiorespiratory fitness is associated with a lower risk of chronic obstructive pulmonary disease. But whether fitness relates to bronchiectasis remains, to the knowledge of the authors, unknown. Purpose To examine the association between cardiorespiratory fitness and bronchiectasis. Materials and Methods This was a secondary analysis of a prospective observational study: the Coronary Artery Risk Development in Young Adults cohort (from 1985-1986 [year 0] to 2015-2016 [year 30]). During a 30-year period, healthy participants (age at enrollment 18-30 years) underwent treadmill exercise testing at year 0 and year 20 visits. Cardiorespiratory fitness was determined according to the treadmill exercise duration. The 20-year difference in cardiorespiratory fitness was used as the fitness measurement. At year 25, chest CT was performed to assess bronchiectasis and was used as the primary outcome. Multivariable logistic models were performed to determine the association between cardiorespiratory fitness changes and bronchiectasis. Results Of 2177 selected participants (at year 0: mean age, 25 years ± 4 [standard deviation]; 1224 women), 209 (9.6%) had bronchiectasis at year 25. After adjusting for age, race-sex group, study site, body mass index, pack-years smoked, history of tuberculosis, pneumonia, asthma and myocardial infarction, peak lung function, and cardiorespiratory fitness at baseline, preservation of cardiorespiratory fitness was associated with lower odds of bronchiectasis at CT at year 25 (per 1-minute-longer treadmill duration from year 0 to year 20: odds ratio [OR], 0.88; 95% CI: 0.80, 0.98; = .02). A consistent strong association was found when cough and phlegm were included in bronchiectasis (OR, 0.72; 95% CI: 0.59, 0.87; < .001). Conclusion In a long-term follow-up, the preservation of cardiorespiratory fitness was associated with lower odds of bronchiectasis at CT. © RSNA, 2021 See also the editorial by Stojanovska in this issue.
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http://dx.doi.org/10.1148/radiol.2021203874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248949PMC
July 2021

Ambient air pollution exposure and radiographic pulmonary vascular volumes.

Environ Epidemiol 2021 Apr 18;5(2):e143. Epub 2021 Mar 18.

Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Exposure to higher levels of ambient air pollution is a known risk factor for cardiovascular disease but long-term effects of pollution exposure on the pulmonary vessels are unknown.

Methods: Among 2428 Framingham Heart Study participants who underwent chest computed tomography (CT) between 2008 and 2011, pulmonary vascular volumes were calculated by image analysis, including the total vascular volume and small vessel volume (cross-sectional area <5 mm; BV5 defined as small vessel volume). Using spatiotemporal models and participant home address, we assigned 1-year (2008) and 5-year (2004-2008) average concentrations of fine particulate matter (PM), elemental carbon (EC), and ground-level ozone (O), and distance to major roadway. We examined associations of 1- and 5-year exposures, and distance to road, with CT vascular volumes using multivariable linear regression models.

Results: There was a consistent negative association of higher O with lower small vessel volumes, which persisted after adjustment for distance to road. Per interquartile range (IQR) of 2008 O, BV5 was 0.34 mL lower (95% confidence intervals [CI], -0.61 to -0.06; = 0.02), with similar results for 5-year exposure. One-year EC exposure and closer proximity to road were weakly associated with small vessel volumes; BV5 was 0.18 mL higher per IQR of 2008 EC (95% CI, -0.05 to 0.42; = 0.13) and 0.40 mL higher per IQR closer proximity to road (95% CI: -0.10 to 0.89; = 0.12). PM was not associated with small vascular volumes; BV5 was 0.26 mL lower per IQR of 2008 PM (95% CI: -0.68 to 0.16; = 0.22).

Conclusions: Among community-dwelling adults living in the northeastern United States, higher exposure to O was associated with lower small pulmonary vessel volumes on CT.
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http://dx.doi.org/10.1097/EE9.0000000000000143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043731PMC
April 2021

Progression of traction bronchiectasis/bronchiolectasis in interstitial lung abnormalities is associated with increased all-cause mortality: Age Gene/Environment Susceptibility-Reykjavik Study.

Eur J Radiol Open 2021 10;8:100334. Epub 2021 Mar 10.

Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.

Purpose: The aim of this study is to assess the role of traction bronchiectasis/bronchiolectasis and its progression as a predictor for early fibrosis in interstitial lung abnormalities (ILA).

Methods: Three hundred twenty-seven ILA participants out of 5764 in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who had undergone chest CT twice with an interval of approximately five-years were enrolled in this study. Traction bronchiectasis/bronchiolectasis index (TBI) was classified on a four-point scale: 0, ILA without traction bronchiectasis/bronchiolectasis; 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; 2, ILA with mild to moderate traction bronchiectasis; 3, ILA and severe traction bronchiectasis and/or honeycombing. Traction bronchiectasis (TB) progression was classified on a five-point scale: 1, Improved; 2, Probably improved; 3, No change; 4, Probably progressed; 5, Progressed. Overall survival (OS) among participants with different TB Progression Score and between the TB progression group and No TB progression group was also investigated. Hazard radio (HR) was estimated with Cox proportional hazards model.

Results: The higher the TBI at baseline, the higher TB Progression Score (P < 0.001). All five participants with TBI = 3 at baseline progressed; 46 (90 %) of 51 participants with TBI = 2 progressed. TB progression was also associated with shorter OS with statistically significant difference (adjusted HR = 1.68, P < 0.001).

Conclusion: TB progression was visualized on chest CT frequently and clearly. It has the potential to be the predictor for poorer prognosis of ILA.
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http://dx.doi.org/10.1016/j.ejro.2021.100334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960545PMC
March 2021

The presence of emphysema on chest imaging and mid-life cognition.

ERJ Open Res 2021 Jan 15;7(1). Epub 2021 Mar 15.

Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA.

Background: Airflow obstruction is associated with cognitive dysfunction but studies have not assessed how emphysema, a structural phenotype of lung disease, might be associated with cognitive function independent from pulmonary function measured by spirometry. We aimed to determine the relationship between the presence of visually detectable emphysema on chest computed tomography (CT) imaging and cognitive function.

Methods: We examined 2491 participants, mean age of 50 years, from the Coronary Artery Risk Development in Young Adults study who were assessed for the presence of emphysema on chest CT imaging and had cognitive function measured 5 years later with a battery of six cognitive tests.

Results: Of those assessed, 172 (7%) had emphysema. After adjusting for age, sex, height, study centre, race, body mass index, education and smoking, visual emphysema was significantly associated with worse performance on most cognitive tests. Compared to those without emphysema, participants with emphysema performed worse on cognitive testing: 0.39 sd units lower (95% CI -0.53- -0.25) on the Montreal Cognitive Assessment, 0.27 sd units lower (95% CI -0.42- -0.12) on the Rey Auditory Verbal Learning Test, 0.29 sd units lower (95% CI -0.43- -0.14) on the Digit Symbol Substitution Test and 0.25 sd units lower (95% CI -0.42- -0.09) on letter fluency. Further adjustment for forced expiratory volume in 1 s (FEV), peak FEV and annualised FEV decline did not attenuate these associations.

Conclusions: The presence of emphysema on chest CT is associated with worse cognitive function, independent of airflow obstruction. These data suggest that emphysema may be a novel risk factor for cognitive impairment.
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http://dx.doi.org/10.1183/23120541.00048-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957295PMC
January 2021

Relationship between Emphysema Progression at CT and Mortality in Ever-Smokers: Results from the COPDGene and ECLIPSE Cohorts.

Radiology 2021 04 16;299(1):222-231. Epub 2021 Feb 16.

From the Division of Pulmonary and Critical Care Medicine, Department of Medicine (S.Y.A., A.A.D., S.E.M., F.N.R., C.L.P., G.R.W.), Applied Chest Imaging Laboratory (S.Y.A., R.S.J.E., A.A.D., S.E.M., F.N.R., C.L.P., G.V.S.F., G.R.W.), and Department of Radiology (R.S.J.E., G.V.S.F.), Brigham and Women's Hospital, 75 Francis St, PBB, CA-3, Boston, MA 02130; Departments of Biomedical Engineering and Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wis (S.B.F.); COPD Foundation, Washington, DC (R.T.S., D.M.); Lung Investigation Unit, Medicine, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, England (R.A.S.); Respiratory and Inflammation Therapy Area, Clinical Development, AstraZeneca, Mölndal, Sweden (L.H.N.); Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Nebraska Medical Center, Omaha, Neb (S.R.); Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Mich (M.K.H.); Department of Radiology, National Jewish Health, Denver, Colo (S.M.H., D.A.L.); and Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Department of Medicine, University of Pittsburgh, Pittsburgh, Pa (F.C.S.).

Background The relationship between emphysema progression and long-term outcomes is unclear. Purpose To determine the relationship between emphysema progression at CT and mortality among participants with emphysema. Materials and Methods In a secondary analysis of two prospective observational studies, COPDGene (, NCT00608764) and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE; , NCT00292552), emphysema was measured at CT at two points by using the volume-adjusted lung density at the 15th percentile of the lung density histogram (hereafter, lung density perc15) method. The association between emphysema progression rate and all-cause mortality was analyzed by using Cox regression adjusted for ethnicity, sex, baseline age, pack-years, and lung density, baseline and change in smoking status, forced expiratory volume in 1 second, and 6-minute walk distance. In COPDGene, respiratory mortality was analyzed by using the Fine and Gray method. Results A total of 5143 participants (2613 men [51%]; mean age, 60 years ± 9 [standard deviation]) in COPDGene and 1549 participants (973 men [63%]; mean age, 62 years ± 8) in ECLIPSE were evaluated, of which 2097 (40.8%) and 1179 (76.1%) had emphysema, respectively. Baseline imaging was performed between January 2008 and December 2010 for COPDGene and January 2006 and August 2007 for ECLIPSE. Follow-up imaging was performed after 5.5 years ± 0.6 in COPDGene and 3.0 years ± 0.2 in ECLIPSE, and mortality was assessed over the ensuing 5 years in both. For every 1 g/L per year faster rate of decline in lung density perc15, all-cause mortality increased by 8% in COPDGene (hazard ratio [HR], 1.08; 95% CI: 1.01, 1.16; = .03) and 6% in ECLIPSE (HR, 1.06; 95% CI: 1.00, 1.13; = .045). In COPDGene, respiratory mortality increased by 22% (HR, 1.22; 95% CI: 1.13, 1.31; < .001) for the same increase in the rate of change in lung density perc15. Conclusion In ever-smokers with emphysema, emphysema progression at CT was associated with increased all-cause and respiratory mortality. © RSNA, 2021 See also the editorial by Lee and Park in this issue.
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http://dx.doi.org/10.1148/radiol.2021203531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997617PMC
April 2021

Respiratory exacerbations are associated with muscle loss in current and former smokers.

Thorax 2021 06 11;76(6):554-560. Epub 2021 Feb 11.

Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objectives: Muscle wasting is a recognised extra-pulmonary complication in chronic obstructive pulmonary disease and has been associated with increased risk of death. Acute respiratory exacerbations are associated with reduction of muscle function, but there is a paucity of data on their long-term effect. This study explores the relationship between acute respiratory exacerbations and long-term muscle loss using serial measurements of CT derived pectoralis muscle area (PMA).

Design And Setting: Participants were included from two prospective, longitudinal, observational, multicentre cohorts of ever-smokers with at least 10 pack-year history.

Participants: The primary analysis included 1332 (of 2501) participants from Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and 4384 (of 10 198) participants from Genetic Epidemiology of COPD (COPDGene) who had complete data from their baseline and follow-up visits.

Interventions: PMA was measured on chest CT scans at two timepoints. Self-reported exacerbation data were collected from participants in both studies through the use of periodic longitudinal surveys.

Main Outcome Measures: Age-related and excess muscle loss over time.

Results: Age, sex, race and body mass index were associated with baseline PMA. Participants experienced age-related decline at the upper end of reported normal ranges. In ECLIPSE, the exacerbation rate over time was associated with an excess muscle area loss of 1.3% (95% CI 0.6 to 1.9, p<0.001) over 3 years and in COPDGene with an excess muscle area loss of 2.1% (95% CI 1.2 to 2.8, p<0.001) over 5 years. Excess muscle area decline was absent in 273 individuals who participated in pulmonary rehabilitation.

Conclusions: Exacerbations are associated with accelerated skeletal muscle loss. Each annual exacerbation was associated with the equivalent of 6 months of age-expected decline in muscle mass. Ameliorating exacerbation-associated muscle loss represents an important therapeutic target.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222105PMC
June 2021

Progression of Emphysema and Small Airways Disease in Cigarette Smokers.

Chronic Obstr Pulm Dis 2021 Apr;8(2):198-212

Department of Radiology, National Jewish Health, Denver, Colorado, United States.

Background: Little is known about factors associated with emphysema progression in cigarette smokers. We evaluated factors associated with change in emphysema and forced expiratory volume in 1 second (FEV) in participants with and without chronic obstructive pulmonary disease (COPD).

Methods: This retrospective study included individuals participating in the COPD Genetic Epidemiology study who completed the 5-year follow-up, including inspiratory and expiratory computed tomography (CT) and spirometry. All paired CT scans were analyzed using micro-mapping, which classifies individual voxels as emphysema or functional small airway disease (fSAD). Presence and progression of emphysema and FEV were determined based on comparison to nonsmoker values. Logistic regression analyses were used to identify clinical parameters associated with disease progression.

Results: A total of 3088 participants were included with a mean ± SD age of 60.7±8.9 years, including 72 nonsmokers. In all Global initiative for chronic Obstructive Lung Disease (GOLD) stages, the presence of emphysema at baseline was associated with emphysema progression (odds ratio [OR]: GOLD 0: 4.32; preserved ratio-impaired spirometry [PRISm]; 5.73; GOLD 1: 5.16; GOLD 2: 5.69; GOLD 3/4: 5.55; all ≤0.01). If there was no emphysema at baseline, the amount of fSAD at baseline was associated with emphysema progression (OR for 1% increase: GOLD 0: 1.06; PRISm: 1.20; GOLD 1: 1.7; GOLD 3/4: 1.08; all ≤ 0.03).In 1735 participants without spirometric COPD, progression in emphysema occurred in 105 (6.1%) participants and only 21 (1.2%) had progression in both emphysema and FEV.

Conclusions: The presence of emphysema is an important predictor of emphysema progression. In patients without emphysema, fSAD is associated with the development of emphysema. In participants without spirometric COPD, emphysema progression occurred independently of FEV decline.
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http://dx.doi.org/10.15326/jcopdf.2020.0140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237975PMC
April 2021

Qualitative emphysema and risk of COPD hospitalization in a multicenter CT lung cancer screening cohort study.

Respir Med 2021 01 20;176:106245. Epub 2020 Nov 20.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Lahey Hospital & Medical Center, Burlington, MA, 01805, USA.

Background: In the United States, 9 to 10 million Americans are estimated to be eligible for computed tomographic lung cancer screening (CTLS). Those meeting criteria for CTLS are at high-risk for numerous cardio-pulmonary co-morbidities. The objective of this study was to determine the association between qualitative emphysema identified on screening CTs and risk for hospital admission.

Study Design And Methods: We conducted a retrospective multicenter study from two CTLS cohorts: Lahey Hospital and Medical Center (LHMC) CTLS program, Burlington, MA and Mount Auburn Hospital (MAH) CTLS program, Cambridge, MA. CTLS exams were qualitatively scored by radiologists at time of screening for presence of emphysema. Multivariable Cox regression models were used to evaluate the association between CT qualitative emphysema and all-cause, COPD-related, and pneumonia-related hospital admission.

Results: We included 4673 participants from the LHMC cohort and 915 from the MAH cohort. 57% and 51.9% of the LHMC and MAH cohorts had presence of CT emphysema, respectively. In the LHMC cohort, the presence of emphysema was associated with all-cause hospital admission (HR 1.15, CI 1.07-1.23; p < 0.001) and COPD-related admission (HR 1.64; 95% CI 1.14-2.36; p = 0.007), but not with pneumonia-related admission (HR 1.52; 95% CI 1.27-1.83; p < 0.001). In the MAH cohort, the presence of emphysema was only associated with COPD-related admission (HR 2.05; 95% CI 1.07-3.95; p = 0.031).

Conclusion: Qualitative CT assessment of emphysema is associated with COPD-related hospital admission in a CTLS population. Identification of emphysema on CLTS exams may provide an opportunity for prevention and early intervention to reduce admission risk.
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http://dx.doi.org/10.1016/j.rmed.2020.106245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890561PMC
January 2021

The Association of Aging Biomarkers, Interstitial Lung Abnormalities, and Mortality.

Am J Respir Crit Care Med 2021 05;203(9):1149-1157

Division of Pulmonary and Critical Care Medicine and.

The association between aging and idiopathic pulmonary fibrosis has been established. The associations between aging-related biomarkers and interstitial lung abnormalities (ILA) have not been comprehensively evaluated. To evaluate the associations among aging biomarkers, ILA, and all-cause mortality. In the FHS (Framingham Heart Study), we evaluated associations among plasma biomarkers (IL-6, CRP [C-reactive protein], TNFR [tumor necrosis factor α receptor II], GDF15 [growth differentiation factor 15], cystatin-C, HGBA1C [Hb A1C], insulin, IGF1 [insulin-like growth factor 1], and IGFBP1 [IGF binding protein 1] and IGFBP3]), ILA, and mortality. Causal inference analysis was used to determine whether biomarkers mediated age. GDF15 results were replicated in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) Study. In the FHS, there were higher odds of ILA per increase in natural log-transformed GDF15 (odds ratio [95% confidence interval], 3.4 [1.8-6.4];  = 0.0002), TNFR (3.1 [1.6-5.8];  = 0.004), IL-6 (1.8 [1.4-2.4];  < 0.0001), and CRP (1.7 [1.3-2.0];  < 0.0001). In the FHS, after adjustment for multiple comparisons, no biomarker was associated with increased mortality, but the associations of GDF15 (hazard ratio, 2.0 [1.1-3.5];  = 0.02), TNFR (1.8 [1.0-3.3];  = 0.05), and IGFBP1 (1.3 [1.1-1.7];  = 0.01) approached significance. In the COPDGene Study, higher natural log-transformed GDF15 was associated with ILA (odds ratio, 8.1 [3.1-21.4];  < 0.0001) and mortality (hazard ratio, 1.6 [1.1-2.2];  = 0.01). Causal inference analysis showed that the association of age with ILA was mediated by IL-6 ( < 0.0001) and TNFR ( = 0.002) and was likely mediated by GDF15 ( = 0.008) in the FHS and was mediated by GDF15 ( = 0.001) in the COPDGene Study. Some aging-related biomarkers are associated with ILA. GDF15, in particular, may explain some of the associations among age, ILA, and mortality.
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http://dx.doi.org/10.1164/rccm.202007-2993OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314902PMC
May 2021

The Framingham Heart Study: Populational CT-based phenotyping in the lungs and mediastinum.

Eur J Radiol Open 2020 11;7:100260. Epub 2020 Sep 11.

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

The Framingham Heart Study (FHS) is one of the largest and established longitudinal populational cohorts. CT cohorts of the FHS since 2002 provided a unique opportunity to assess non-cardiac thoracic imaging findings. This review deals with image-based phenotyping studies from recent major publications regarding interstitial lung abnormalities (ILAs), pulmonary cysts, emphysema, pulmonary nodules, pleural plaques, normal spectrum of the thymus, and anterior mediastinal masses, concluding with the discussion of future directions of FHS CT cohorts studies in the era of radiomics and artificial intelligence.
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http://dx.doi.org/10.1016/j.ejro.2020.100260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495061PMC
September 2020

Distinguishing Smoking-Related Lung Disease Phenotypes Via Imaging and Molecular Features.

Chest 2021 02 16;159(2):549-563. Epub 2020 Sep 16.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA; Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA.

Background: Chronic tobacco smoke exposure results in a broad range of lung pathologies including emphysema, airway disease and parenchymal fibrosis as well as a multitude of extra-pulmonary comorbidities. Prior work using CT imaging has identified several clinically relevant subgroups of smoking related lung disease, but these investigations have generally lacked organ specific molecular correlates.

Research Question: Can CT imaging be used to identify clinical phenotypes of smoking related lung disease that have specific bronchial epithelial gene expression patterns to better understand disease pathogenesis?

Study Design And Methods: Using K-means clustering, we clustered participants from the COPDGene study (n = 5,273) based on CT imaging characteristics and then evaluated their clinical phenotypes. These clusters were replicated in the Detection of Early Lung Cancer Among Military Personnel (DECAMP) cohort (n = 360), and were further characterized using bronchial epithelial gene expression.

Results: Three clusters (preserved, interstitial predominant and emphysema predominant) were identified. Compared to the preserved cluster, the interstitial and emphysema clusters had worse lung function, exercise capacity and quality of life. In longitudinal follow-up, individuals from the emphysema group had greater declines in exercise capacity and lung function, more emphysema, more exacerbations, and higher mortality. Similarly, genes involved in inflammatory pathways (tumor necrosis factor-α, interferon-β) are more highly expressed in bronchial epithelial cells from individuals in the emphysema cluster, while genes associated with T-cell related biology are decreased in these samples. Samples from individuals in the interstitial cluster generally had intermediate levels of expression of these genes.

Interpretation: Using quantitative CT imaging, we identified three groups of individuals in older ever-smokers that replicate in two cohorts. Airway gene expression differences between the three groups suggests increased levels of inflammation in the most severe clinical phenotype, possibly mediated by the tumor necrosis factor-α and interferon-β pathways.

Clinical Trial Registration: COPDGene (NCT00608764), DECAMP-1 (NCT01785342), DECAMP-2 (NCT02504697).
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http://dx.doi.org/10.1016/j.chest.2020.08.2115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039011PMC
February 2021

Quantitative Pectoralis Muscle Area is Associated with the Development of Lung Cancer in a Large Lung Cancer Screening Cohort.

Lung 2020 10 5;198(5):847-853. Epub 2020 Sep 5.

Department of Radiology, Lahey Hospital & Medical Center, Burlington, USA.

Background: Studies have demonstrated an inverse relationship between body mass index (BMI) and the risk of developing lung cancer. We conducted a retrospective cohort study evaluating baseline quantitative computed tomography (CT) measurements of body composition, specifically muscle and fat area in a large CT lung screening cohort (CTLS). We hypothesized that quantitative measurements of baseline body composition may aid in risk stratification for lung cancer.

Methods: Patients who underwent baseline CTLS between January 1st, 2012 and September 30th, 2014 and who had an in-network primary care physician were included. All patients met NCCN Guidelines eligibility criteria for CTLS. Quantitative measurements of pectoralis muscle area (PMA) and subcutaneous fat area (SFA) were performed on a single axial slice of the CT above the aortic arch with the Chest Imaging Platform Workstation software. Cox multivariable proportional hazards model for cancer was adjusted for variables with a univariate p < 0.2. Data were dichotomized by sex and then combined to account for baseline differences between sexes.

Results: One thousand six hundred and ninety six patients were included in this study. A total of 79 (4.7%) patients developed lung cancer. There was an association between the 25th percentile of PMA and the development of lung cancer [HR 1.71 (1.07, 2.75), p < 0.025] after adjusting for age, BMI, qualitative emphysema, qualitative coronary artery calcification, and baseline Lung-RADS® score.

Conclusions: Quantitative assessment of PMA on baseline CTLS was associated with the development of lung cancer. Quantitative PMA has the potential to be incorporated as a variable in future lung cancer risk models.
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http://dx.doi.org/10.1007/s00408-020-00388-5DOI Listing
October 2020

Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis.

Sci Adv 2020 Jul 8;6(28):eaba1983. Epub 2020 Jul 8.

Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.

We provide a single-cell atlas of idiopathic pulmonary fibrosis (IPF), a fatal interstitial lung disease, by profiling 312,928 cells from 32 IPF, 28 smoker and nonsmoker controls, and 18 chronic obstructive pulmonary disease (COPD) lungs. Among epithelial cells enriched in IPF, we identify a previously unidentified population of aberrant basaloid cells that coexpress basal epithelial, mesenchymal, senescence, and developmental markers and are located at the edge of myofibroblast foci in the IPF lung. Among vascular endothelial cells, we identify an ectopically expanded cell population transcriptomically identical to bronchial restricted vascular endothelial cells in IPF. We confirm the presence of both populations by immunohistochemistry and independent datasets. Among stromal cells, we identify IPF myofibroblasts and invasive fibroblasts with partially overlapping cells in control and COPD lungs. Last, we confirm previous findings of profibrotic macrophage populations in the IPF lung. Our comprehensive catalog reveals the complexity and diversity of aberrant cellular populations in IPF.
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http://dx.doi.org/10.1126/sciadv.aba1983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439502PMC
July 2020

Computerized Chest Imaging in the Diagnosis and Assessment of the Patient with Chronic Obstructive Pulmonary Disease.

Clin Chest Med 2020 09;41(3):375-381

Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.

Computerized tomography in chronic obstructive pulmonary disease (COPD) has been the subject of intense interest in the research and clinical community. Methods have been developed to objectively detect and quantify processes affecting the lung parenchyma, airways and vasculature, as well as extrapulmonary manifestations of the noxious effects of chronic inhalational exposures, such as tobacco smoke. This article provides a brief overview of image-based advances in COPD research and then discusses how these advances have translated to clinical care, finishing with a brief description of a path forward for the convergence of research and care at the bedside.
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http://dx.doi.org/10.1016/j.ccm.2020.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454015PMC
September 2020
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