Publications by authors named "Surya P Bhatt"

136 Publications

Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort.

Chest 2021 May 21. Epub 2021 May 21.

Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD.

Background: Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV progression in current smokers.

Research Question: Is use of ACEi and ARB associated with less progression of emphysema and FEV decline among individuals with COPD or baseline emphysema?

Methods: Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume <-950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15% of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated.

Results: Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV % predicted, 0.83; 95% CI, -0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema.

Interpretation: Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline.

Trial Registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.05.007DOI Listing
May 2021

Pulmonary Artery Enlargement is Associated with Exacerbations and Mortality in Ever-Smokers with Preserved Ratio Impaired Spirometry (PRISm).

Am J Respir Crit Care Med 2021 May 20. Epub 2021 May 20.

The University of Alabama at Birmingham School of Medicine, 9967, Pulmonary, Allergy, and Critical Care Medicine, Birmingham, Alabama, United States.

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http://dx.doi.org/10.1164/rccm.202103-0619LEDOI Listing
May 2021

Update in Chronic Obstructive Pulmonary Disease 2020.

Am J Respir Crit Care Med 2021 Jul;204(1):14-22

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

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http://dx.doi.org/10.1164/rccm.202102-0253UPDOI Listing
July 2021

Experimental characterization of speech aerosol dispersion dynamics.

Sci Rep 2021 02 17;11(1):3953. Epub 2021 Feb 17.

Department of Aerospace Engineering, Auburn University, Auburn, AL, 36849, USA.

Contact and inhalation of virions-carrying human aerosols represent the primary transmission pathway for airborne diseases including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Relative to sneezing and coughing, non-symptomatic aerosol-producing activities such as speaking are highly understudied. The dispersions of aerosols from vocalization by a human subject are hereby quantified using high-speed particle image velocimetry. Syllables of different aerosol production rates were tested and compared to coughing. Results indicate aerosol productions and penetrations are not correlated. E.g. 'ti' and 'ma' have similar production rates but only 'ti' penetrated as far as coughs. All cases exhibited a rapidly penetrating "jet phase" followed by a slow "puff phase." Immediate dilution of aerosols was prevented by vortex ring flow structures that concentrated particles toward the plume-front. A high-fidelity assessment of risks to exposure must account for aerosol production rate, penetration, plume direction and the prevailing air current.
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http://dx.doi.org/10.1038/s41598-021-83298-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889873PMC
February 2021

Ratio of FEV/Slow Vital Capacity of < 0.7 Is Associated With Clinical, Functional, and Radiologic Features of Obstructive Lung Disease in Smokers With Preserved Lung Function.

Chest 2021 Jul 1;160(1):94-103. Epub 2021 Feb 1.

Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.

Background: Mild expiratory flow limitation may not be recognized using traditional spirometric criteria based on the ratio of FEV/FVC.

Research Question: Does slow vital capacity (SVC) instead of FVC increase the sensitivity of spirometry to identify patients with early or mild obstructive lung disease?

Study Design And Methods: We included 854 current and former smokers from the Subpopulations and Intermediate Outcome Measures in COPD Study cohort with a postbronchodilator FEV/FVC ≥ 0.7 and FEV % predicted of ≥ 80% at enrollment. We compared baseline characteristics, chest CT scan features, exacerbations, and progression to COPD (postbronchodilator FEV/FVC, < 0.7) during the follow-up period between 734 participants with postbronchodilator FEV/SVC of ≥ 0.7 and 120 with postbronchodilator FEV/SVC < 0.7 at the enrollment. We performed multivariate linear and logistic regression models and negative binomial and interval-censored proportion hazards regression models adjusted for demographics and smoking exposure to examine the association of FEV/SVC < 0.7 with those characteristics and outcomes.

Results: Participants with FEV/SVC < 0.7 were older and had lower FEV and more emphysema than those with FEV/SVC ≥ 0.7. In adjusted analysis, individuals with postbronchodilator FEV/SVC < 0.7 showed a greater percentage of emphysema by 0.45% (95% CI, 0.09%-0.82%), percentage of gas trapping by 2.52% (95% CI, 0.59%-4.44%), and percentage of functional small airways disease based on parametric response mapping by 2.78% (95% CI, 0.72%-4.83%) at baseline than those with FEV/SVC ≥ 0.7. During a median follow-up time of 1,500 days, an FEV/SVC < 0.7 was not associated with total exacerbations (incident rate ratio [IRR], 1.61; 95% CI, 0.97-2.64), but was associated with severe exacerbations (IRR, 2.60; 95% CI, 1.04-4.89). An FEV/SVC < 0.7 was associated with progression to COPD during a 3-year follow-up even after adjustment for demographics and smoking exposure (hazard ratio, 3.93; 95% CI, 2.71-5.72). We found similar results when we examined the association of prebronchodilator FEV/SVC < 0.7 or FEV/SVC less than the lower limit of normal with chest CT scan features and progression to COPD.

Interpretation: Low FEV to SVC in current and former smokers with normal spirometry results can identify individuals with CT scan features of COPD who are at risk for severe exacerbations and is associated with progression to COPD in the future.

Trial Registry: ClinicalTrials.gov; No.: NCT01969344T4; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.01.067DOI Listing
July 2021

Structural airway imaging metrics are differentially associated with persistent chronic bronchitis.

Thorax 2021 04 6;76(4):343-349. Epub 2021 Jan 6.

Division of Pulmonary and Critical Care Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.

Background: Chronic bronchitis (CB) is strongly associated with cigarette smoking, but not all smokers develop CB. We aimed to evaluate whether measures of structural airway disease on CT are differentially associated with CB.

Methods: In smokers between ages 45 and 80 years, and with Global Initiative for Obstructive Lung Disease stages 0-4, CB was defined by the classic definition. Airway disease on CT was quantified by (i) wall area percent (WA%) of segmental airways; (ii) Pi10, the square root of the wall area of a hypothetical airway with 10 mm internal perimeter; (iii) total airway count (TAC) and (iv) airway fractal dimension (AFD), a measure of the complex branching pattern and remodelling of airways. CB was also assessed at the 5-year follow-up visit.

Measurements And Main Results: Of 8917 participants, 1734 (19.4%) had CB at baseline. Airway measures were significantly worse in those with CB compared with those without CB: WA% 54.5 (8.8) versus 49.8 (8.3); Pi10 2.58 (0.67) versus 2.28 (0.59) mm; TAC 156.7 (81.6) versus 177.8 (91.1); AFD 1.477 (0.091) versus 1.497 (0.092) (all p<0.001). On follow-up of 5517 participants at 5 years, 399 (7.2%) had persistent CB. With adjustment for between-visits changes in smoking status and lung function, greater WA% and Pi10 were associated with significantly associated with persistent CB, adjusted OR per SD change 1.75, 95% CI 1.56 to 1.97; p<0.001 and 1.66, 95% CI 1.42 to 1.86; p<0.001, respectively. Higher AFD and TAC were associated with significantly lower odds of persistent CB, adjusted OR per SD change 0.76, 95% CI 0.67 to 0.86; p<0.001 and 0.69, 95% CI 0.60 to 0.80; p<0.001, respectively.

Conclusions: Higher baseline AFD and TAC are associated with a lower risk of persistent CB, irrespective of changes in smoking status, suggesting preserved airway structure can confer a reserve against CB.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225550PMC
April 2021

Trends and Geographic Variation in Acute Respiratory Failure and ARDS Mortality in the United States.

Chest 2021 04 22;159(4):1460-1472. Epub 2020 Oct 22.

Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL; Section of Cardiology, Birmingham Veterans Affairs Medical Center, Birmingham, AL. Electronic address:

Background: Despite numerous advances in the understanding of the pathophysiology, progression, and management of acute respiratory failure (ARF) and ARDS, limited contemporary data are available on the mortality burden of ARF and ARDS in the United States.

Research Question: What are the contemporary trends and geographic variation in ARF and ARDS-related mortality in the United States?

Study Design And Methods: A retrospective analysis of the National Center for Health Statistics' nationwide mortality data was conducted to assess the ARF and ARDS-related mortality trends from 2014 through 2018 and the geographic distribution of ARF and ARDS-related deaths in 2018 for all American residents. Piecewise linear regression was used to evaluate the trends in age-adjusted mortality rates (AAMRs) in the overall population and various demographic subgroups of age, sex, race, urbanization, and region.

Results: Among 1,434,349 ARF-related deaths and 52,958 ARDS-related deaths during the study period, the AAMR was highest in older individuals (≥ 65 years), non-Hispanic Black people, and those living in the nonmetropolitan region. The AAMR for ARF-related deaths (per 100,000 people) increased from 74.9 (95% CI, 74.6-75.2) in 2014 to 85.6 (95% CI, 85.3-85.9) in 2018 (annual percentage change [APC], 3.4 [95% CI, 2.2-4.6]; P = .003). The AAMR (per 100,000 people) for ARDS-related deaths was 3.2 (95% CI, 3.2-3.3) in 2014 and 3.0 (95% CI, 3.0-3.1 in 2018; APC, -0.9 [95% CI, -5.4 to 3.8]; P = .56). The observed increase in rates for ARF mortality was consistent across the subgroups of age, sex, race or ethnicity, urbanization status, and geographical region (P < .05 for all). The AAMR (per 100,000 people) for ARF (91.3 [95% CI, 90.8-91.8]) and ARDS-related mortality (3.3 [95% CI, 3.2-3.4]) in 2018 were highest in the South.

Interpretation: The ARF-related mortality increased at approximately 3.4% annually, and ARDS-related mortality showed a lack of decline in the last 5 years. These data contextualize important health information to guide priorities for research, clinical care, and policy, especially during the coronavirus disease 2019 pandemic in the United States.
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http://dx.doi.org/10.1016/j.chest.2020.10.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581392PMC
April 2021

A CT-Based Automated Algorithm for Airway Segmentation Using Freeze-and-Grow Propagation and Deep Learning.

IEEE Trans Med Imaging 2021 01 29;40(1):405-418. Epub 2020 Dec 29.

Chronic obstructive pulmonary disease (COPD) is a common lung disease, and quantitative CT-based bronchial phenotypes are of increasing interest as a means of exploring COPD sub-phenotypes, establishing disease progression, and evaluating intervention outcomes. Reliable, fully automated, and accurate segmentation of pulmonary airway trees is critical to such exploration. We present a novel approach of multi-parametric freeze-and-grow (FG) propagation which starts with a conservative segmentation parameter and captures finer details through iterative parameter relaxation. First, a CT intensity-based FG algorithm is developed and applied for airway tree segmentation. A more efficient version is produced using deep learning methods generating airway lumen likelihood maps from CT images, which are input to the FG algorithm. Both CT intensity- and deep learning-based algorithms are fully automated, and their performance, in terms of repeat scan reproducibility, accuracy, and leakages, is evaluated and compared with results from several state-of-the-art methods including an industry-standard one, where segmentation results were manually reviewed and corrected. Both new algorithms show a reproducibility of 95% or higher for total lung capacity (TLC) repeat CT scans. Experiments on TLC CT scans from different imaging sites at standard and low radiation dosages show that both new algorithms outperform the other methods in terms of leakages and branch-level accuracy. Considering the performance and execution times, the deep learning-based FG algorithm is a fully automated option for large multi-site studies.
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http://dx.doi.org/10.1109/TMI.2020.3029013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772272PMC
January 2021

A Risk Prediction Model for Mortality Among Smokers in the COPDGene® Study.

Chronic Obstr Pulm Dis 2020 Oct;7(4):346-361

University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: Risk factor identification is a proven strategy in advancing treatments and preventive therapy for many chronic conditions. Quantifying the impact of those risk factors on health outcomes can consolidate and focus efforts on individuals with specific high-risk profiles. Using multiple risk factors and longitudinal outcomes in 2 independent cohorts, we developed and validated a risk score model to predict mortality in current and former cigarette smokers.

Methods: We obtained extensive data on current and former smokers from the COPD Genetic Epidemiology (COPDGene) study at enrollment. Based on physician input and model goodness-of-fit measures, a subset of variables was selected to fit final Weibull survival models separately for men and women. Coefficients and predictors were translated into a point system, allowing for easy computation of mortality risk scores and probabilities. We then used the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) cohort for external validation of our model.

Results: Of 9867 COPDGene participants with standard baseline data, 17.6% died over 10 years of follow-up, and 9074 of these participants had the full set of baseline predictors (standard plus 6-minute walk distance and computed tomography variables) available for full model fits. The average age of participants in the cohort was 60 for both men and women, and the average predicted 10-year mortality risk was 18% for women and 25% for men. Model time-integrated area under the receiver operating characteristic curve statistics demonstrated good predictive model accuracy (0.797 average), validated in the external cohort (0.756 average). Risk of mortality was impacted most by 6-minute walk distance, forced expiratory volume in 1 second and age, for both men and women.

Conclusions: Current and former smokers exhibited a wide range of mortality risk over a 10- year period. Our models can identify higher risk individuals who can be targeted for interventions to reduce risk of mortality, for participants with or without chronic obstructive pulmonary disease (COPD) using current Global initiative for obstructive Lung Disease (GOLD) criteria.
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http://dx.doi.org/10.15326/jcopdf.7.4.2020.0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883903PMC
October 2020

Computed Tomography-based Airway Surface Area-to-Volume Ratio for Phenotyping Airway Remodeling in Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med 2021 01;203(2):185-191

UAB Lung Imaging Core.

Airway remodeling in chronic obstructive pulmonary disease (COPD) is due to luminal narrowing and/or loss of airways. Existing computed tomographic metrics of airway disease reflect only components of these processes. With progressive airway narrowing, the ratio of the airway luminal surface area to volume (SA/V) should increase, and with predominant airway loss, SA/V should decrease. To phenotype airway remodeling in COPD. We analyzed the airway trees of 4,325 subjects with COPD Global Initiative for Chronic Obstructive Lung Disease stages 0 to 4 and 73 nonsmokers enrolled in the multicenter COPDGene (Genetic Epidemiology of COPD) cohort. Surface area and volume measurements were estimated for the subtracheal airway tree to derive SA/V. We performed multivariable regression analyses to test associations between SA/V and lung function, 6-minute-walk distance, St. George's Respiratory Questionnaire, change in FEV, and mortality, adjusting for demographics, total airway count, airway wall thickness, and emphysema. On the basis of the change in SA/V over 5 years, we categorized subjects into predominant airway narrowing [positive ∆(SA/V) more than 0] and predominant airway loss [negative ∆(SA/V) less than 0] and compared survival between the two groups. Airway SA/V was independently associated with FEV/FVC (β = 0.12; 95% confidence interval [CI], 0.09-0.14;  < 0.001) and FEV% predicted (β = 20.10; 95% CI, 15.13-25.08;  < 0.001). Airway SA/V was also independently associated with 6-minute-walk distance, respiratory quality of life, and lung function decline. Compared with subjects with predominant airway narrowing ( = 2,914; 66.3%), those with predominant airway loss ( = 1,484; 33.7%) had worse survival (adjusted hazard ratio for all-cause mortality = 1.58; 95% CI, 1.18-2.13;  = 0.002). Computed tomography-based airway SA/V is an imaging biomarker of airway remodeling and provides differential information on predominant airway narrowing and loss in COPD. SA/V is associated with respiratory morbidity, lung function decline, and survival.
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http://dx.doi.org/10.1164/rccm.202004-0951OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874421PMC
January 2021

Deep neural network analyses of spirometry for structural phenotyping of chronic obstructive pulmonary disease.

JCI Insight 2020 07 9;5(13). Epub 2020 Jul 9.

UAB Lung Imaging Core.

BACKGROUNDCurrently recommended traditional spirometry outputs do not reflect the relative contributions of emphysema and airway disease to airflow obstruction. We hypothesized that machine-learning algorithms can be trained on spirometry data to identify these structural phenotypes.METHODSParticipants enrolled in a large multicenter study (COPDGene) were included. The data points from expiratory flow-volume curves were trained using a deep-learning model to predict structural phenotypes of chronic obstructive pulmonary disease (COPD) on CT, and results were compared with traditional spirometry metrics and an optimized random forest classifier. Area under the receiver operating characteristic curve (AUC) and weighted F-score were used to measure the discriminative accuracy of a fully convolutional neural network, random forest, and traditional spirometry metrics to phenotype CT as normal, emphysema-predominant (>5% emphysema), airway-predominant (Pi10 > median), and mixed phenotypes. Similar comparisons were made for the detection of functional small airway disease phenotype (>20% on parametric response mapping).RESULTSAmong 8980 individuals, the neural network was more accurate in discriminating predominant emphysema/airway phenotypes (AUC 0.80, 95%CI 0.79-0.81) compared with traditional measures of spirometry, FEV1/FVC (AUC 0.71, 95%CI 0.69-0.71), FEV1% predicted (AUC 0.70, 95%CI 0.68-0.71), and random forest classifier (AUC 0.78, 95%CI 0.77-0.79). The neural network was also more accurate in discriminating predominant emphysema/small airway phenotypes (AUC 0.91, 95%CI 0.90-0.92) compared with FEV1/FVC (AUC 0.80, 95%CI 0.78-0.82), FEV1% predicted (AUC 0.83, 95%CI 0.80-0.84), and with comparable accuracy with random forest classifier (AUC 0.90, 95%CI 0.88-0.91).CONCLUSIONSStructural phenotypes of COPD can be identified from spirometry using deep-learning and machine-learning approaches, demonstrating their potential to identify individuals for targeted therapies.TRIAL REGISTRATIONClinicalTrials.gov NCT00608764.FUNDINGThis study was supported by NIH grants K23 HL133438 and R21EB027891 and an American Thoracic Foundation 2018 Unrestricted Research Grant. The COPDGene study is supported by NIH grants NHLBI U01 HL089897 and U01 HL089856. The COPDGene study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Committee comprising AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, and Sunovion.
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http://dx.doi.org/10.1172/jci.insight.132781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406302PMC
July 2020

Airway Remodeling in Ferrets with Cigarette Smoke Induced COPD using µCT Imaging.

Am J Physiol Lung Cell Mol Physiol 2020 May 6. Epub 2020 May 6.

Deparment of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama, Birmingham, United States.

Rationale: Structural changes to airway morphology such as increased bronchial wall thickness (BWT) and airway wall area are cardinal features of chronic obstructive pulmonary disease (COPD). Ferrets are a recently established animal model uniquely exhibiting similar clinical and pathological characteristics of COPD as humans, including chronic bronchitis.

Objectives: Develop a µCT method for evaluating structural changes to the airways in ferrets, and assess whether the effects of smoking induce changes consistent with chronic bronchitis in humans.

Methods: Ferrets were exposed to mainstream cigarette smoke or air control twice daily for 6 months. µCT was conducted in vivo at 6 months; a longitudinal cohort was imaged monthly. Manual measurements of BWT, luminal diameter (LD), and BWT:LD ratio were conducted, and confirmed by a semi-automated algorithm. The square root of bronchial wall area (WA) vs. luminal perimeter was determined on an individual ferret basis.

Measurements And Main Results: Smoke exposed ferrets reproducibly demonstrated 34% increased BWT (P<0.001); along with increased LD, and BWT:LD ratio vs. air controls. Regression indicated the effect of smoking on BWT persisted despite controlling for covariates. Semi-automated measurements replicated findings. WA for the theoretical median airway luminal perimeter of 4 mm (Pi4) was elevated 4.4% in smoke exposed ferrets (P=0.015). Increased BWT and Pi4 developed steadily over time.

Conclusions: µCT-based airway measurements in ferrets are feasible and reproducible. Smoke exposed ferrets develop increased BWT and Pi4, changes similar to humans with chronic bronchitis. µCT can be used as a significant translational platform to measure dynamic airway morphological changes.
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http://dx.doi.org/10.1152/ajplung.00328.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468842PMC
May 2020

Smaller Left Ventricle Size at Noncontrast CT Is Associated with Lower Mortality in COPDGene Participants.

Radiology 2020 07 5;296(1):208-215. Epub 2020 May 5.

From the Division of Pulmonary and Critical Care, Department of Medicine, Applied Chest Imaging Laboratory (G.R.W., S.Y.A., F.N.R., C.E.C., C.L.P., A.A.D.), Department of Radiology, Applied Chest Imaging Laboratory (P.N., G.V.S.F., J.C.R., R.S.J.E.), Department of Anesthesia (G.Q.R.), and Division of Cardiology (A.M.S.), Brigham and Women's Hospital, 1249 Boylston St, Boston, MA 02215; Lung Health Center, University of Alabama at Birmingham, Birmingham, Ala (M.T.D., S.P.B., J.M.W.); Asthma and COPD Program, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill (R.K.); Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Mich (M.K.H.); BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (S.R.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Neb (S.R.); Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colo (K.Y., G.L.K., J.E.H.); and Respiratory Institute, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, Centro de Investigación Biomédica en Red Enfermedades Respiratorias, University of Barcelona, Barcelona, Spain (A.A.).

Background Smokers with chronic obstructive pulmonary disease (COPD) have smaller left ventricles (LVs) due to reduced preload. Skeletal muscle wasting is also common in COPD, but less is known about its contribution to LV size. Purpose To explore the relationships between CT metrics of emphysema, venous vascular volume, and sarcopenia with the LV epicardial volume (LV) (myocardium and chamber) estimated from chest CT images in participants with COPD and then to determine the clinical relevance of the LV in multivariable models, including sex and anthropomorphic metrics. Materials and Methods The COPDGene study (ClinicalTrials.gov identifier: NCT00608764) is an ongoing prospective longitudinal observational investigation that began in 2006. LV, distal pulmonary venous blood volume for vessels smaller than 5 mm in cross section (BV5), CT emphysema, and pectoralis muscle area were retrospectively extracted from 3318 nongated, unenhanced COPDGene CT scans. Multivariable linear and Cox regression models were used to explore the association between emphysema, venous BV5, pectoralis muscle area, and LV as well as the association of LV with health status using the St George's Respiratory Questionnaire, 6-minute walk distance, and all-cause mortality. Results The median age of the cohort was 64 years (interquartile range, 57-70 years). Of the 2423 participants, 1806 were men and 617 were African American. The median LV between Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 and GOLD 4 COPD was reduced by 13.9% in women and 17.7% in men ( < .001 for both). In fully adjusted models, higher emphysema percentage (β = -4.2; 95% confidence interval [CI]: -5.0, -3.4; < .001), venous BV5 (β = 7.0; 95% CI: 5.7, 8.2; < .001), and pectoralis muscle area (β = 2.7; 95% CI: 1.2, 4.1; < .001) were independently associated with reduced LV. Reductions in LV were associated with improved health status (β = 0.3; 95% CI: 0.1, 0.4) and 6-minute walk distance (β = -12.2; 95% CI: -15.2, -9.3). These effects were greater in women than in men. The effect of reduced LV on mortality (hazard ratio: 1.07; 95% CI: 1.05, 1.09) did not vary by sex. Conclusion In women more than men with chronic obstructive pulmonary disease, a reduction in the estimated left ventricle epicardial volume correlated with a loss of pulmonary venous vasculature, greater pectoralis muscle sarcopenia, and lower all-cause mortality. © RSNA, 2020
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http://dx.doi.org/10.1148/radiol.2020191793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299752PMC
July 2020

Heme metabolism genes Downregulated in COPD Cachexia.

Respir Res 2020 May 1;21(1):100. Epub 2020 May 1.

Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.

Introduction: Cachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.

Methods: We analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) (< 20 kg/m) and 1/3 criteria: decreased muscle strength (six-minute walk distance < 350 m), anemia (hemoglobin < 12 g/dl), and low fat-free mass index (FFMI) (< 15 kg/m among women and < 17 kg/m among men) in COPDGene. In ECLIPSE, cachexia was defined as weight-loss > 5% in the past 12 months or low BMI and 3/5 criteria: decreased muscle strength, anorexia, abnormal biochemistry (anemia or high c-reactive protein (> 5 mg/l)), fatigue, and low FFMI. Differential gene expression was assessed between cachectic and non-cachectic subjects, adjusting for age, sex, white blood cell counts, and technical covariates. Gene set enrichment analysis was performed using MSigDB.

Results: The prevalence of COPD cachexia was 13.7% in COPDGene and 7.9% in ECLIPSE. Fourteen genes were differentially downregulated in cachectic versus non-cachectic COPD patients in COPDGene (FDR < 0.05) and ECLIPSE (FDR < 0.05).

Discussion: Several replicated genes regulating heme metabolism were downregulated among participants with COPD cachexia. Impaired heme biosynthesis may contribute to cachexia development through free-iron buildup and oxidative tissue damage.
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http://dx.doi.org/10.1186/s12931-020-01336-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193359PMC
May 2020

Both Duration and Pack-Years of Tobacco Smoking Should Be Used for Clinical Practice and Research.

Ann Am Thorac Soc 2020 07;17(7):804-806

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

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http://dx.doi.org/10.1513/AnnalsATS.202002-133VPDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405110PMC
July 2020

A Dyadic Growth Modeling Approach for Examining Associations Between Weight Gain and Lung Function Decline.

Am J Epidemiol 2020 10;189(10):1173-1184

The relationship between body weight and lung function is complex. Using a dyadic multilevel linear modeling approach, treating body mass index (BMI; weight (kg)/height (m)2) and lung function as paired, within-person outcomes, we tested the hypothesis that persons with more rapid increase in BMI exhibit more rapid decline in lung function, as measured by forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and their ratio (FEV1:FVC). Models included random intercepts and slopes and adjusted for sociodemographic and smoking-related factors. A sample of 9,115 adults with paired measurements of BMI and lung function taken at ≥3 visits were selected from a pooled set of 5 US population-based cohort studies (1983-2018; mean age at baseline = 46 years; median follow-up, 19 years). At age 46 years, average annual rates of change in BMI, FEV1, FVC, and FEV1:FVC ratio were 0.22 kg/m2/year, -25.50 mL/year, -21.99 mL/year, and -0.24%/year, respectively. Persons with steeper BMI increases had faster declines in FEV1 (r = -0.16) and FVC (r = -0.26) and slower declines in FEV1:FVC ratio (r = 0.11) (all P values < 0.0001). Results were similar in subgroup analyses. Residual correlations were negative (P < 0.0001), suggesting additional interdependence between BMI and lung function. Results show that greater rates of weight gain are associated with greater rates of lung function loss.
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http://dx.doi.org/10.1093/aje/kwaa059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670871PMC
October 2020

Effect of Zephyr Endobronchial Valves on Dyspnea, Activity Levels, and Quality of Life at One Year. Results from a Randomized Clinical Trial.

Ann Am Thorac Soc 2020 07;17(7):829-838

Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.

Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation. analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported. A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool-PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George's Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy). At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains ( < 0.05 and  < 0.001, respectively). Reduction in CAT was through improvements in breathlessness ( < 0.05), energy level ( < 0.05), activities ( < 0.001), and increased confidence when leaving home ( < 0.05). The TDI measures of effort, task, and functional impairment were uniformly improved ( < 0.001). The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)-PRO, dyspnea domain, was significantly improved in the Zephyr Valve group. Improvements correlated with changes in residual volume and residual volume/TLC ratio. Patients with severe hyperinflated emphysema achieving lung volume reductions with Zephyr Valves experience improvements in multidimensional scores for breathlessness, activity, and psychosocial parameters out to at least 12 months.Clinical trial registered with www.clinicaltrials.gov (NCT01796392).
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http://dx.doi.org/10.1513/AnnalsATS.201909-666OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328183PMC
July 2020

COPD exacerbations: finally, a more than ACCEPTable risk score.

Authors:
Surya P Bhatt

Lancet Respir Med 2020 10 13;8(10):939-941. Epub 2020 Mar 13.

Division of Pulmonary, Allergy and Critical Care Medicine, and UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address:

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http://dx.doi.org/10.1016/S2213-2600(20)30049-7DOI Listing
October 2020

Clinical Significance of Bronchodilator Responsiveness Evaluated by Forced Vital Capacity in COPD: SPIROMICS Cohort Analysis.

Int J Chron Obstruct Pulmon Dis 2019 20;14:2927-2938. Epub 2019 Dec 20.

Department of Medicine, University of Utah, Salt Lake City, UT, USA.

Objective: Bronchodilator responsiveness (BDR) is prevalent in COPD, but its clinical implications remain unclear. We explored the significance of BDR, defined by post-bronchodilator change in FEV (BDR) as a measure reflecting the change in flow and in FVC (BDR) reflecting the change in volume.

Methods: We analyzed 2974 participants from a multicenter observational study designed to identify varying COPD phenotypes (SPIROMICS). We evaluated the association of BDR with baseline clinical characteristics, rate of prospective exacerbations and mortality using negative binomial regression and Cox proportional hazards models.

Results: A majority of COPD participants exhibited BDR (52.7%). BDR occurred more often in earlier stages of COPD, while BDR occurred more frequently in more advanced disease. When defined by increases in either FEV or FVC, BDR was associated with a self-reported history of asthma, but not with blood eosinophil counts. BDR was more prevalent in subjects with greater emphysema and small airway disease on CT. In a univariate analysis, BDR was associated with increased exacerbations and mortality, although no significance was found in a model adjusted for post-bronchodilator FEV.

Conclusion: With advanced airflow obstruction in COPD, BDR is more prevalent in comparison to BDR and correlates with the extent of emphysema and degree of small airway disease. Since these associations appear to be related to the impairment of FEV, BDR itself does not define a distinct phenotype nor can it be more predictive of outcomes, but it can offer additional insights into the pathophysiologic mechanism in advanced COPD.

Clinical Trials Registration: ClinicalTrials.gov: NCT01969344T4.
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http://dx.doi.org/10.2147/COPD.S220164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930016PMC
July 2020

Use of FEF25-75% to Guide IgG Dosing to Protect Pulmonary Function in CVID.

J Clin Immunol 2020 02 3;40(2):310-320. Epub 2020 Jan 3.

Department of Medicine, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL, 35233, USA.

Immunoglobulin replacement therapy (IGRT) can protect against lung function decline in CVID. We tested whether increasing IgG dosage was beneficial in patients who exhibited a decline in forced expiratory flow at 25-75% (FEF25-75%) even though they were receiving IgG doses within the therapeutic range. Of 189 CVID patients seen over 12 years, 38 patients met inclusion criteria, were seen on ≥ 3 visits, and demonstrated a ≥ 10% decrease in FEF25-75% from visits 1 to 2. FEF25-75%, forced expiratory flow at 1 s (FEV1), and FEV1/FVC at visit 3 were compared among those with non-dose adjustment (non-DA) versus additional IgG dose adjustment (DA). Three FEF25-75% tiers were identified: top (> 80% predicted), middle (50-80%), and bottom (< 50%). DA and non-DA groups did not differ in clinical infections or bronchodilator use, although the non-DA group tended to use more antibiotics. In the top, normal tier, FEF25-75% increased in DA, but the change did not achieve statistical significance. In the middle moderate obstruction tier, visit 3 FEF25-75% increased among DA but not non-DA sets (11.8 ± 12.4%, p = 0.003 vs. 0.3 ± 9.9%, p = 0.94). Improvement in FEV1/FVC at visit 3 was also significant among DA vs. non-DA (7.2 ± 12.4%, p = 0.04 vs. - 0.2 ± 2.7%, p = 0.85). In the bottom, severe tier, FEF25-75% was unchanged in DA (- 0.5 ± 5.2%, p = 0.79), but increased in non-DA (5.1 ± 5.2%, p = 0.02). Among IGRT CVID patients with moderate but not severe obstruction as assessed by spirometry, increasing IgG dosage led to an increase in FEF25-75% and FEV1/FVC.
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http://dx.doi.org/10.1007/s10875-019-00730-4DOI Listing
February 2020

The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS.

Respir Res 2019 Nov 12;20(1):254. Epub 2019 Nov 12.

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

Background: Pulmonary and systemic inflammation are central features of chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated relationships between biologically active extracellular matrix components, or matrikines, and COPD pathogenesis. We studied the relationships between the matrikine acetyl-proline-glycine-proline (AcPGP) in sputum and plasma and clinical features of COPD.

Methods: Sputum and plasma samples were obtained from COPD participants in the SPIROMICS cohort at enrollment. AcPGP was isolated using solid phase extraction and measured by mass spectrometry. Demographics, spirometry, quality of life questionnaires, and quantitative computed tomography (CT) imaging with parametric response mapping (PRM) were obtained at baseline. Severe COPD exacerbations were recorded at 1-year of prospective follow-up. We used linear and logistic regression models to measure associations between AcPGP and features of COPD, and Kaplan-Meier analyses to measure time-to-first severe exacerbation.

Results: The 182 COPD participants in the analysis were 66 ± 8 years old, 62% male, 84% White race, and 39% were current smokers. AcPGP concentrations were 0.61 ± 1.89 ng/mL (mean ± SD) in sputum and 0.60 ± 1.13 ng/mL in plasma. In adjusted linear regression models, sputum AcPGP was associated with FEV/FVC, spirometric GOLD stage, PRM-small airways disease, and PRM-emphysema. Sputum AcPGP also correlated with severe AECOPD, and elevated sputum AcPGP was associated with shorter time-to-first severe COPD exacerbation. In contrast, plasma AcPGP was not associated with symptoms, pulmonary function, or severe exacerbation risk.

Conclusions: In COPD, sputum but not plasma AcPGP concentrations are associated with the severity of airflow limitation, small airways disease, emphysema, and risk for severe AECOPD at 1-year of follow-up.

Trial Registration: ClinicalTrials.gov: NCT01969344 (SPIROMICS).
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http://dx.doi.org/10.1186/s12931-019-1230-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852714PMC
November 2019

COPDGene 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease.

Chronic Obstr Pulm Dis 2019 Nov;6(5):384-399

Northeastern University, Boston, Massachusetts.

Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality.

Methods: Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined.

Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics.

Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.
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http://dx.doi.org/10.15326/jcopdf.6.5.2019.0149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020846PMC
November 2019

FEV1:FVC Thresholds for Defining Chronic Obstructive Pulmonary Disease-Reply.

JAMA 2019 10;322(16):1611-1612

Division of General Medicine, Columbia University Medical Center, New York, New York.

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http://dx.doi.org/10.1001/jama.2019.13960DOI Listing
October 2019

Metoprolol for the Prevention of Acute Exacerbations of COPD.

N Engl J Med 2019 12 20;381(24):2304-2314. Epub 2019 Oct 20.

From the Lung Health Center, University of Alabama at Birmingham (M.T.D., S.P.B., J.M.W., E.W.), and Birmingham Veterans Affairs (VA) Medical Center (M.T.D., J.A.D.C., J.M.W.) - both in Birmingham; the University of Minnesota (H.V., E.S.H., S.L., J.E.C.) and the Minneapolis VA Medical Center (K.M.K.), Minneapolis, HealthPartners Minnesota, Bloomington (C.M.), and Mayo Clinic, Rochester (P.D.S.) - all in Minnesota; New York-Presbyterian (NYP)-Columbia University Medical Center (K.B.), NYP-Weill Cornell Medical Center (R. Kaner, F.J.M.), NYP-Queens Medical Center (A.S.), and NYP-Brooklyn Methodist Medical Center (J.A.W.) - all in New York; Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Los Angeles (R.C., W.W.S.), the University of California, San Francisco-Fresno, Fresno (V.V.J.), and the University of California, San Francisco, San Francisco (S.C.L.) - all in California; Brigham and Women's Hospital, Boston (C.E.C.); Temple University School of Medicine, Philadelphia (G.J.C.); the Ann Arbor VA Medical Center (J.L.C.) and the University of Michigan Health System (M.K.H.) - both in Ann Arbor; the Cleveland Clinic, Cleveland (U.H.); Northwestern University, Chicago (R. Kalhan); the University of Vermont, Burlington (D.K.); the University of Washington, Seattle (A.A.L.); Louisiana State University, New Orleans (M.R.L.); National Jewish Health, Denver (B.J.M.); the Cincinnati VA Medical Center, Cincinnati (R.J.P.); the University of Maryland, Baltimore (R.M.R.); the University of Pittsburgh, Pittsburgh (F.C.S.); and North Florida-South Georgia Veterans Health System, Gainesville (P.S.S.).

Background: Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.

Methods: In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol.

Results: A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group.

Conclusions: Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.).
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http://dx.doi.org/10.1056/NEJMoa1908142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416529PMC
December 2019

Lung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI Pooled Cohorts Study.

Lancet Respir Med 2020 01 9;8(1):34-44. Epub 2019 Oct 9.

University of Pittsburgh, Pittsburgh, PA, USA.

Background: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease.

Methods: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (≥17 years), two recruited middle-aged and older adults (≥45 years), and two recruited only elderly adults (≥65 years) with examinations done between 1983 and 2014. FEV decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption.

Findings: 25 352 participants (ages 17-93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3-20), FEV decline at the median age (57 years) was 31·01 mL per year (95% CI 30·66-31·37) in sustained never-smokers, 34·97 mL per year (34·36-35·57) in former smokers, and 39·92 mL per year (38·92-40·92) in current smokers. With adjustment, former smokers showed an accelerated FEV decline of 1·82 mL per year (95% CI 1·24-2·40) compared to never-smokers, which was approximately 20% of the effect estimate for current smokers (9·21 mL per year; 95% CI 8·35-10·08). Compared to never-smokers, accelerated FEV decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (<10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV decline in current smokers consuming less than five cigarettes per day (7·65 mL per year; 95% CI 6·21-9·09) was 68% of that in current smokers consuming 30 or more cigarettes per day (11·24 mL per year; 9·86-12·62), and around five times greater than in former smokers (1·57 mL per year; 1·00-2·14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results.

Interpretation: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage.

Funding: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency.
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http://dx.doi.org/10.1016/S2213-2600(19)30276-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261004PMC
January 2020

Reply to Gagnon : Video Teleheath and Pulmonary Rehabilitation: Need for a Better Understanding.

Am J Respir Crit Care Med 2020 01;201(1):120

University of Alabama at BirminghamBirmingham, Alabama.

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http://dx.doi.org/10.1164/rccm.201907-1486LEDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938150PMC
January 2020

Adult Life-Course Trajectories of Lung Function and the Development of Emphysema: The CARDIA Lung Study.

Am J Med 2020 02 29;133(2):222-230.e11. Epub 2019 Jul 29.

Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.

Background: Peak lung function and rate of decline predict future airflow obstruction and nonrespiratory comorbid conditions. Associations between lung function trajectories and emphysema have not been explored.

Methods: Using data from the population-based CARDIA Study, we sought to describe the prevalence of visually ascertained emphysema at multiple time points and contextualize its development based upon participant's adult life course measures of lung function. There were 3171 men and women enrolled at a mean age of 25 years, who underwent serial spirometric examinations through a mean age of 55 years. Trajectories for the change in percent-predicted forced expiratory volume in one second (FEV) were determined by fitting a mixture model via maximum likelihood. Emphysema was visually identified on computed tomographic scans and its prevalence reported at mean ages of 40, 45, and 50 years.

Results: We identified 5 trajectories describing peak and change in FEV: "Preserved Ideal," "Preserved Good," "Preserved Impaired," "Worsening," and "Persistently Poor." Ever smokers comprised part of all 5 trajectories. The prevalence of emphysema was 1.7% (n = 46; mean age of 40 years), 2.5% (n = 67; mean age of 45 years), and 7.1% (n = 189; mean age of 50 years). Of those with emphysema at a mean age of 50 years, 18.0% were never smokers. Worsening and poor lung health trajectories were associated with increased odds of future emphysema independent of chronic tobacco smoke exposure (odds ratio 5.06; confidence interval, 1.84-13.96; odds ratio 4.85; confidence interval, 1.43-16.44).

Conclusions: Lower peak and accelerated decline in FEV are risk factors for future emphysema independent of smoking status.
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http://dx.doi.org/10.1016/j.amjmed.2019.06.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980254PMC
February 2020

Imaging Small Airway Disease: Probabilities and Possibilities.

Authors:
Surya P Bhatt

Ann Am Thorac Soc 2019 Aug;16(8):975-977

University of Alabama at Birmingham Lung Imaging Core, University of Alabama at Birmingham Lung Health Center, and Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

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http://dx.doi.org/10.1513/AnnalsATS.201903-231EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774743PMC
August 2019
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