Publications by authors named "Barry J Make"

155 Publications

Significant Spirometric Transitions and Preserved Ratio Impaired Spirometry Among Ever Smokers.

Chest 2021 Sep 27. Epub 2021 Sep 27.

Channing Division of Network Medicine, Brigham & Women's Hospital, Boston, MA.

Background: Emerging data from longitudinal studies suggest that preserved ratio impaired spirometry (PRISm), defined by proportionate reductions in FEV and FVC, is a heterogeneous population with frequent transitions to other lung function categories relative to individuals with normal and obstructive spirometry. Controversy regarding the clinical significance of these transitions exists (eg, whether transitions merely reflect measurement variability or noise).

Research Question: Are individuals with PRISm enriched for transitions associated with substantial changes in lung function?

Study Design And Methods: Current and former smokers enrolled in COPDGene with spirometry available in phases 1 through 3 (enrollment, 5-year follow-up, and 10-year follow-up) were analyzed. Postbronchodilator lung function categories were as follows: PRISm (FEV < 80% predicted with FEV/FVC ratio ≥ 0.7), Global Initiative for Chronic Obstructive Lung Disease stage 0 (FEV ≥ 80% predicted and FEV/FVC ≥ 0.7), and obstruction (FEV/FVC < 0.7). Significant transition status was affirmative if a subject belonged to two or more spirometric categories and had > 10% change in FEV % predicted and/or FVC % predicted between consecutive visits. Ever-PRISm was present if a subject had PRISm at any visit. Logistic regression examined the association between significant transitions and ever-PRISm status, adjusted for age, sex, race, FEV % predicted, current smoking, pack-years, BMI, and ever-positive bronchodilator response.

Results: Among subjects with complete data (N = 1,775) over 10.1 ± 0.4 years of follow-up, the prevalence of PRISm remained consistent (10.4%-11.3%) between phases 1 through 3, but nearly one-half of subjects with PRISm transitioned into or out of PRISm at each visit. Of the subjects, 19.7% had a significant transition; ever-PRISm was a significant predictor of significant transitions (unadjusted OR, 10.3; 95% CI, 7.9-13.5; adjusted OR, 14.9; 95% CI, 10.9-20.7). Results were similar with additional adjustment for radiographic emphysema and gas trapping, when lower limit of normal criteria were used to define lung function categories, and when FEV alone (regardless of change in FVC % predicted) was used to define significant transitions.

Interpretation: PRISm is an unstable group, with frequent significant transitions to both obstruction and normal spirometry over time.

Clinical Trial Registration: ClinicalTrials.gov; No.: NCT000608764; URL: www.clinicaltrials.gov.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.09.021DOI Listing
September 2021

Identifying a Heart Rate Recovery Criterion After a 6-Minute Walk Test in COPD.

Int J Chron Obstruct Pulmon Dis 2021;16:2545-2560. Epub 2021 Sep 4.

Rehabilitation Clinical Trials Center, Division of Respiratory and Critical Care Physiology and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.

Background: Slow heart rate recovery (HRR) after exercise is associated with autonomic dysfunction and increased mortality. What HRR criterion at 1-minute after a 6-minute walk test (6MWT) best defines pulmonary impairment?.

Study Design And Methods: A total of 5008 phase 2 COPDGene (NCT00608764) participants with smoking history were included. A total of 2127 had COPD and, of these, 385 were followed-up 5-years later. Lung surgery, transplant, bronchiectasis, atrial fibrillation, heart failure and pacemakers were exclusionary. HR was measured from pulse oximetry at end-walk and after 1-min seated recovery. A receiver operator characteristic (ROC) identified optimal HRR cut-off. Generalized linear regression determined HRR association with spirometry, chest CT, symptoms and exacerbations.

Results: HRR after 6MWT (bt/min) was categorized in quintiles: ≤5 (23.0% of participants), 6-10 (20.7%), 11-15 (18.9%), 16-22 (18.5%) and ≥23 (18.9%). Compared to HRR≤5, HRR≥11 was associated with (p<0.001): lower pre-walk HR and 1-min post HR; greater end-walk HR; greater 6MWD; greater FEV%pred; lower airway wall area and wall thickness. HRR was positively associated with FEV%pred and negatively associated with airway wall thickness. An optimal HRR ≤10 bt/min yielded an area under the ROC curve of 0.62 (95% CI 0.58-0.66) for identifying FEV<30%pred. HRR≥11 bt/min was the lowest HRR associated with consistently less impairment in 6MWT, spirometry and CT variables. In COPD, HRR≤10 bt/min was associated with (p<0.001): ≥2 exacerbations in the previous year (OR=1.76[1.33-2.34]); CAT≥10 (OR=1.42[1.18-1.71]); mMRC≥2 (OR=1.42[1.19-1.69]); GOLD 4 (OR=1.98[1.44-2.73]) and GOLD D (OR=1.51[1.18-1.95]). HRR≤10 bt/min was predicted COPD exacerbations at 5-year follow-up (RR=1.83[1.07-3.12], P=0.027).

Conclusion: HRR≤10 bt/min after 6MWT in COPD is associated with more severe expiratory flow limitation, airway wall thickening, worse dyspnoea and quality of life, and future exacerbations, suggesting that an abnormal HRR≤10 bt/min after a 6MWT may be used in a comprehensive assessment in COPD for risk of severity, symptoms and future exacerbations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S311572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427685PMC
October 2021

Optimal NIV Medicare Access Promotion: Patients With Hypoventilation Syndromes: A Technical Expert Panel Report From the American College of Chest Physicians, the American Association for Respiratory Care, the American Academy of Sleep Medicine, and the American Thoracic Society.

Chest 2021 Nov 30;160(5):e377-e387. Epub 2021 Jul 30.

Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, San Diego, CA.

The existing coverage criteria for home noninvasive ventilation (NIV) do not recognize the diversity of hypoventilation syndromes and advances in technologies. This document summarizes the work of the hypoventilation syndromes Technical Expert Panel working group. The most pressing current coverage barriers identified were: (1) overreliance on arterial blood gases (particularly during sleep); (2) need to perform testing on prescribed oxygen; (3) requiring a sleep study to rule out OSA as the cause of sustained hypoxemia; (4) need for spirometry; (5) need to show bilevel positive airway pressure (BPAP) without a backup rate failure to qualify for BPAP spontaneous/timed; and (6) qualifying hospitalized patients for home NIV therapy at the time of discharge. Critical evidence support for changes to current policies includes randomized controlled trial evidence and clinical practice guidelines. To decrease morbidity and mortality by achieving timely access to NIV for patients with hypoventilation, particularly those with obesity hypoventilation syndrome, we make the following key suggestions: (1) given the significant technological advances, we advise acceptance of surrogate noninvasive end-tidal and transcutaneous Pco and venous blood gases in lieu of arterial blood gases; (2) not requiring Pco measures while on prescribed oxygen; (3) not requiring a sleep study to avoid delays in care in patients being discharged from the hospital; (4) remove spirometry as a requirement; and (5) not requiring BPAP without a backup rate failure to approve BPAP spontaneous/timed. The overarching goal of the Technical Expert Panel is to establish pathways that improve clinicians' management capability to provide Medicare beneficiaries access to appropriate home NIV therapy. Adoption of these proposed suggestions would result in the right device, for the right type of patient with hypoventilation syndromes, at the right time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.06.083DOI Listing
November 2021

Haemoglobin as a biomarker for clinical outcomes in chronic obstructive pulmonary disease.

ERJ Open Res 2021 Jul 26;7(3). Epub 2021 Jul 26.

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

In COPD, anaemia is associated with increased morbidity, but the relationship between haemoglobin over its entire observed range and morbidity is poorly understood. Such an understanding could guide future therapeutic targeting of haemoglobin in COPD management. Leveraging the COPDGene study, we conducted a cross-sectional analysis of haemoglobin from COPD participants, examining symptoms, quality of life, functional performance, and acute exacerbations of COPD (AECOPD). Haemoglobin was analysed both as a continuous variable and categorised into anaemia, normal haemoglobin, and polycythaemia groups. Fractional polynomial modelling was used for continuous analyses; categorical models were multivariable linear or negative binomial regressions. Covariates included demographics, comorbidities, emphysema, diffusing capacity, and airflow obstruction. From 2539 participants, 366 (14%) were identified as anaemic and 125 (5%) as polycythaemic. Compared with normal haemoglobin, anaemia was significantly associated with increased symptoms (COPD Assessment Test score: p=0.006, modified Medical Research Council (mMRC) Dyspnoea Score: p=0.001); worse quality of life (St. George's Respiratory Questionnaire (SGRQ) score: p<0.001; Medical Outcomes Study Short Form 36-item Questionnaire (SF-36) General Health: p=0.002; SF-36 Physical Health: p<0.001), decreased functional performance (6-min walk distance (6MWD): p<0.001), and severe AECOPD (p=0.01), while polycythaemia was not. Continuous models, however, demonstrated increased morbidity at both ends of the haemoglobin distribution (p<0.01 for mMRC, SGRQ, SF-36 Physical Health, 6MWD, and severe AECOPD). Evaluating interactions, both diffusing capacity and haemoglobin were independently associated with morbidity. We present novel findings that haemoglobin derangements towards either extreme of the observed range are associated with increased morbidity in COPD. Further investigation is necessary to determine whether haemoglobin derangement drives morbidity or merely reflects systemic inflammation, and whether correcting haemoglobin towards the normal range improves morbidity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00068-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311135PMC
July 2021

Secondary polycythemia in chronic obstructive pulmonary disease: prevalence and risk factors.

BMC Pulm Med 2021 Jul 14;21(1):235. Epub 2021 Jul 14.

Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Secondary polycythemia is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, the prevalence of polycythemia in COPD and the contributing risk factors for polycythemia in COPD have not been extensively studied.

Methods: We analyzed the presence of secondary polycythemia in current and former smokers with moderate to very severe COPD at the five-year follow-up visit in the observational COPDGene study. We used logistic regression to evaluate the association of polycythemia with age, sex, race, altitude, current smoking status, spirometry, diffusing capacity for carbon monoxide (DLCO), quantitative chest CT measurements (including emphysema, airway wall thickness, and pulmonary artery to aorta diameter ratio), resting hypoxemia, exercise-induced hypoxemia, and long-term oxygen therapy.

Results: In a total of 1928 COPDGene participants with moderate to very severe COPD, secondary polycythemia was found in 97 (9.2%) male and 31 (3.5%) female participants. In a multivariable logistic model, severe resting hypoxemia (OR 3.50, 95% CI 1.41-8.66), impaired DLCO (OR 1.28 for each 10-percent decrease in DLCO % predicted, CI 1.09-1.49), male sex (OR 3.60, CI 2.20-5.90), non-Hispanic white race (OR 3.33, CI 1.71-6.50), current smoking (OR 2.55, CI 1.49-4.38), and enrollment in the Denver clinical center (OR 4.42, CI 2.38-8.21) were associated with higher risk for polycythemia. In addition, continuous (OR 0.13, CI 0.05-0.35) and nocturnal (OR 0.46, CI 0.21-0.97) supplemental oxygen were associated with lower risk for polycythemia. Results were similar after excluding participants with anemia and participants enrolled at the Denver clinical center.

Conclusions: In a large cohort of individuals with moderate to very severe COPD, male sex, current smoking, enrollment at the Denver clinical center, impaired DLCO, and severe hypoxemia were associated with increased risk for secondary polycythemia. Continuous or nocturnal supplemental oxygen use were associated with decreased risk for polycythemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12890-021-01585-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278596PMC
July 2021

Impact of a Medical Diagnosis on Decision to Stop Smoking and Successful Smoking Cessation.

Chronic Obstr Pulm Dis 2021 Jul;8(3):360-370

National Jewish Health, Denver Colorado, United States.

Introduction: Smoking cessation counseling is a central part of the Medicare guidelines for lung cancer screening. With increasing age, many heavy smokers eventually stop smoking, however, factors influencing the decision to stop smoking are poorly understood. We postulated that declining health or physician-diagnosis of a medical condition may be associated with successful smoking cessation.

Methods: A total of 4448 current and former smokers in Phase 2 of the COPD Genetic Epidemiology (COPDGene®) study answered a question about reasons for stopping smoking. Participants were classified as (n=3345), and (n=1003). Reasons cited for quitting were grouped as: medical diagnoses, social factors, symptoms. Logistic modeling of factors associated with successful quitting were adjusted for age, gender, race, and education.

Results: The most common factors cited for a quit attempt by all respondents were medical diagnoses (48%), followed by social factors (47%), and respiratory symptoms (36%). were more likely to be older, male, and non-Hispanic White. An adjusted model found increased age, White race, education beyond high school, and male sex favored successful quitting while the cited medical diagnoses, social factors, and "other" reasons were associated with unsuccessful quitting. Fagerstrom Nicotine Dependence scores were ³ 5 in 54% of the unsuccessful group compared to 45% for successful quitters(<0.0001) suggesting some increased nicotine dependence in the unsuccessful quitters.

Conclusions: Medical diagnosis was the most common factor cited for considering a quit attempt by both successful and unsuccessful quitters; however, successful quitting was influenced by demographic factors and potentially the severity of nicotine dependence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.2020.0167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428590PMC
July 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2020-215999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222105PMC
June 2021

Co-Morbidity Patterns Identified Using Latent Class Analysis of Medications Predict All-Cause Mortality Independent of Other Known Risk Factors: The COPDGene Study.

Clin Epidemiol 2020 27;12:1171-1181. Epub 2020 Oct 27.

Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Purpose: Medication patterns include all medications in an individual's clinical profile. We aimed to identify chronic co-morbidity treatment patterns through medication use among COPDGene participants and determine whether these patterns were associated with mortality, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and quality of life.

Materials And Methods: Participants analyzed here completed Phase 1 (P1) and/or Phase 2 (P2) of COPDGene. Latent class analysis (LCA) was used to identify medication patterns and assign individuals into unobserved LCA classes. Mortality, AECOPD, and the St. George's Respiratory Questionnaire (SGRQ) health status were compared in different LCA classes through survival analysis, logistic regression, and Kruskal-Wallis test, respectively.

Results: LCA identified 8 medication patterns from 32 classes of chronic comorbid medications. A total of 8110 out of 10,127 participants with complete covariate information were included. Survival analysis adjusted for covariates showed, compared to a low medication use class, mortality was highest in participants with hypertension+diabetes+statin+antiplatelet medication group. Participants in hypertension+SSRI+statin medication group had the highest odds of AECOPD and the highest SGRQ score at both P1 and P2.

Conclusion: Medication pattern can serve as a good indicator of an individual's comorbidities profile and improves models predicting clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CLEP.S279075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602898PMC
October 2020

Daily Activities: The Impact of COPD and Cognitive Dysfunction.

Arch Clin Neuropsychol 2021 Jul;36(5):acaa090 767 779-767

University of Iowa Carver College of Medicine, Department of Psychiatry, Iowa City, IA 52242, USA.

Objective: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation; however, pulmonary function does not fully account for patients' functional difficulties. The primary aim of the study was to determine the association between several domains of cognition and daily activity among those with COPD.

Method: Eighty-nine former smokers completed a neuropsychological battery including measures across multiple domains of cognition, pulmonary function measures, and daily activity questionnaires. Using a cross-sectional design, we compared daily activity between former smokers with and without COPD using two measures (St. George's Respiratory Questionnaire [SGRQ] Activity Subscale and Lawton Instrumental Activities of Daily Living [IADL] Scale) and examined the association between cognition and daily activity among those with COPD.

Results: As expected, former smokers with COPD reported more difficulty than those without COPD on both activity measures (SGRQ Activity Subscale p < .001; Lawton IADL Scale p = .040). Among former smokers with COPD, poorer delayed recall was associated with more difficulty with daily activities (SGRQ Activity Subscale) (p = .038) while adjusting for severity of airflow limitation, exercise tolerance, oxygen use, dyspnea, and symptoms of anxiety and depression.

Conclusion: The findings suggest that cognition is associated with daily activity in patients with COPD. Future research should examine whether cognitive interventions may help to maximize patients' engagement in daily activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/arclin/acaa090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500183PMC
July 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.7.4.2020.0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883903PMC
October 2020

Validation of a method to assess emphysema severity by spirometry in the COPDGene study.

Respir Res 2020 May 1;21(1):103. Epub 2020 May 1.

Section of Respiratory Medicine, Department of Experimental and Clinical Medicine, University of Florence, Largo A. Brambilla 3, 50134, Florence, Italy.

Background: Standard spirometry cannot identify the predominant mechanism underlying airflow obstruction in COPD, namely emphysema or airway disease. We aimed at validating a previously developed methodology to detect emphysema by mathematical analysis of the maximal expiratory flow-volume (MEFV) curve in standard spirometry.

Methods: From the COPDGene population we selected those 5930 subjects with MEFV curve and inspiratory-expiratory CT obtained on the same day. The MEFV curve descending limb was fit real-time using forced vital capacity (FVC), peak expiratory flow, and forced expiratory flows at 25, 50 and 75% of FVC to derive an emphysema severity index (ESI), expressed as a continuous positive numeric parameter ranging from 0 to 10. According to inspiratory CT percent lung attenuation area below - 950 HU we defined three emphysema severity subgroups (%LAA < 6, 6-14, ≥14). By co-registration of inspiratory-expiratory CT we quantified persistent (%pLDA) and functional (%fLDA) low-density areas as CT metrics of emphysema and airway disease, respectively.

Results: ESI differentiated CT emphysema severity subgroups increasing in parallel with GOLD stages (p < .001), but with high variability within each stage. ESI had significantly higher correlations (p < .001) with emphysema than with airway disease CT metrics, explaining 67% of %pLDA variability. Conversely, standard spirometric variables (FEV, FEV/FVC) had significantly lower correlations than ESI with emphysema CT metrics and did not differentiate between emphysema and airways CT metrics.

Conclusions: ESI adds to standard spirometry the power to discriminate whether emphysema is the predominant mechanism of airway obstruction. ESI methodology has been validated in the large multiethnic population of smokers of the COPDGene study and therefore it could be applied for clinical and research purposes in the general population of smokers, using a readily available online website.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-020-01366-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195744PMC
May 2020

Machine Learning and Prediction of All-Cause Mortality in COPD.

Chest 2020 09 27;158(3):952-964. Epub 2020 Apr 27.

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA. Electronic address:

Background: COPD is a leading cause of mortality.

Research Question: We hypothesized that applying machine learning to clinical and quantitative CT imaging features would improve mortality prediction in COPD.

Study Design And Methods: We selected 30 clinical, spirometric, and imaging features as inputs for a random survival forest. We used top features in a Cox regression to create a machine learning mortality prediction (MLMP) in COPD model and also assessed the performance of other statistical and machine learning models. We trained the models in subjects with moderate to severe COPD from a subset of subjects in Genetic Epidemiology of COPD (COPDGene) and tested prediction performance in the remainder of individuals with moderate to severe COPD in COPDGene and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We compared our model with the BMI, airflow obstruction, dyspnea, exercise capacity (BODE) index; BODE modifications; and the age, dyspnea, and airflow obstruction index.

Results: We included 2,632 participants from COPDGene and 1,268 participants from ECLIPSE. The top predictors of mortality were 6-min walk distance, FEV % predicted, and age. The top imaging predictor was pulmonary artery-to-aorta ratio. The MLMP-COPD model resulted in a C index ≥ 0.7 in both COPDGene and ECLIPSE (6.4- and 7.2-year median follow-ups, respectively), significantly better than all tested mortality indexes (P < .05). The MLMP-COPD model had fewer predictors but similar performance to that of other models. The group with the highest BODE scores (7-10) had 64% mortality, whereas the highest mortality group defined by the MLMP-COPD model had 77% mortality (P = .012).

Interpretation: An MLMP-COPD model outperformed four existing models for predicting all-cause mortality across two COPD cohorts. Performance of machine learning was similar to that of traditional statistical methods. The model is available online at: https://cdnm.shinyapps.io/cgmortalityapp/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2020.02.079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478228PMC
September 2020

Carotid Artery Stiffness is Associated With Cognitive Performance in Former Smokers With and Without Chronic Obstructive Pulmonary Disease.

J Am Heart Assoc 2020 05 26;9(9):e014862. Epub 2020 Apr 26.

Medicine National Jewish Health Denver CO.

Background Heavy smokers perform worse on neuropsychological assessment than age-matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest amount of variance in cognition. The current objective was to determine whether carotid artery stiffness is associated with cognition in former smokers beyond the effects of amount of smoking and pulmonary function. Methods and Results Eighty-four former smokers including individuals across a spectrum of airflow limitation severity were included: 30 without chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] 0 with normal spirometry and lung computed tomography), 31 with mild-moderate chronic obstructive pulmonary disease (GOLD 1-2), and 23 with severe-very severe chronic obstructive pulmonary disease (GOLD 3-4). Participants completed questionnaires, spirometry, carotid ultrasonography, and neuropsychological testing. Multiple linear regression was used to determine whether carotid artery stiffness is associated with neuropsychological performance in 4 cognitive domains after adjusting for age, sex, pack-years of smoking, estimated premorbid intellectual functioning, and airflow limitation. Higher carotid artery β-stiffness index was associated with reduced executive functioning-processing speed in the fully adjusted model (β=-0.49, SE=0.14; =0.001). Lower premorbid intellectual function, male sex, and presence of airflow limitation (GOLD 1 or 2 and GOLD 3 or 4) were also associated with worse executive functioning-processing speed. β-Stiffness index was not significantly associated with performance in other cognitive domains. Conclusions Carotid artery stiffness is associated with worse performance on executive functioning-processing speed in former smokers beyond the effects of aging, amount of past smoking, severity of airflow limitation, and hypoxemia. Future research should examine whether carotid stiffness can be used to identify former smokers at risk for subsequent cognitive impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.014862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428572PMC
May 2020

The Association of Multiparity with Lung Function and Chronic Obstructive Pulmonary Disease-Related Phenotypes.

Chronic Obstr Pulm Dis 2020 Apr;7(2):86-98

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Background: Apparent increased female susceptibility to chronic obstructive pulmonary disease (COPD) suggests sex hormones modulate disease pathogenesis. Little is known about associations between multiparity and lung function in smokers.

Research Question: We hypothesized that multiparity is associated with lung function and measures of emphysema and airway disease.

Study Design And Methods: Utilizing female participants from the 5-year follow up of the COPD Genetic Epidemiology (COPDGene) study we performed multivariable linear regressions to assess the effect of multiparity and number of pregnancies on forced expiratory volume in 1 second (FEV) percentage of predicted (% predicted), FEV/forced vital capacity (FVC), percent emphysema on computed tomography (CT) scans, and Pi10, a measure of airway thickening. We sampled never smokers and those with lower smoking exposure from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 dataset.

Results: We included 1820 participants from COPDGene and 418 participants from NHANES (321 never smokers, 97 ever smokers). In COPDGene, multiparity (beta coefficient [β] = -3.8, 95% confidence interval [CI]: [-6.5, -1.1], = 0.005) and higher number of pregnancies were associated with lower FEV % predicted. Multiparity was not associated with percent emphysema or Pi10. In individuals with no or mild obstruction, multiparity was associated with lower FEV % predicted. There was an interaction with multiparity and age on FEV % predicted ( = 0.025). In NHANES, there was no association between multiparity and FEV % predicted in never smokers or the lower smoking exposure group.

Interpretation: Multiparity was associated with lower FEV % predicted in current and former smokers in COPDGene study participants. These preliminary results emphasize the importance of smoking abstinence in women of child-bearing age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.7.2.2019.0166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454017PMC
April 2020

Luminal Plugging on Chest CT Scan: Association With Lung Function, Quality of Life, and COPD Clinical Phenotypes.

Chest 2020 07 1;158(1):121-130. Epub 2020 Feb 1.

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

Background: Mucous exudates occluding the lumen of small airways are associated with reduced lung function and mortality in subjects with COPD; however, luminal plugs in large airways have not been widely studied. We aimed to examine the associations of chest CT scan-identified luminal plugging with lung function, health-related quality of life, and COPD phenotypes.

Methods: We randomly selected 100 smokers without COPD and 400 smokers with COPD from the COPDGene Study. Luminal plugging was visually identified on inspiratory CT scans at baseline and 5-year follow-up. The relationships of luminal plugging to FEV, St. George's Respiratory Questionnaire (SGRQ) score, emphysema on CT scan (defined as the percentage of low attenuation area < 950 Hounsfield units [%LAA-950]), and chronic bronchitis were assessed using linear and logistic multivariable analyses.

Results: Overall, 111 subjects (22%) had luminal plugging. The prevalence of luminal plugging was higher in subjects with COPD than those without COPD (25% vs 10%, respectively; P = .001). In subjects with COPD, luminal plugging was significantly associated with FEV % predicted (estimate, -6.1; SE, 2.1; P = .004) and SGRQ score (estimate, 4.9; SE, 2.4; P = .04) in adjusted models. Although luminal plugging was associated with log %LAA-950 (estimate, 0.43; SE, 0.16; P = .007), its relationship with chronic bronchitis did not reach statistical significance (P = .07). Seventy-three percent of subjects with COPD with luminal plugging at baseline had it 5 years later.

Conclusions: In subjects with COPD, CT-identified luminal plugging is associated with airflow obstruction, worse health-related quality of life, and emphysema phenotype. This imaging feature may supplement the current clinical assessment of chronic mucus hypersecretion in COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2019.12.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339234PMC
July 2020

Five-year Progression of Emphysema and Air Trapping at CT in Smokers with and Those without Chronic Obstructive Pulmonary Disease: Results from the COPDGene Study.

Radiology 2020 04 4;295(1):218-226. Epub 2020 Feb 4.

From the Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, PO 85500, Postbox E.03.511, Utrecht, Utrecht 3508 GA, the Netherlands (E.P.); Division of Biostatistics and Bioinformatics (M.S., B.J.M.), Department of Radiology (S.H., D.A.L.), Division of Rheumatology, Department of Medicine (E.A.R.), and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine (J.D.C.), National Jewish Health, Denver, Colo; Thirona, Nijmegen, the Netherlands (E.M.v.R.); Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (E.M.v.R., J.P.C.); Departments of Biomedical Engineering, Radiology, and Internal Medicine, University of Iowa, Iowa City, Iowa (E.A.H.); Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Division of Pulmonary and Critical Care, University of Michigan Health System, Ann Arbor, Mich (M.K.H.); Department of Epidemiology, University of Colorado Denver, Denver, Colo (J.E.H.); and Channing Division of Network Medicine (E.K.S.) and Division of Pulmonary and Critical Care Medicine, Department of Medicine (E.K.S.), Brigham and Women's Hospital, Boston, Mass.

Background CT is used to quantify abnormal changes in the lung parenchyma of smokers that might overlap chronic obstructive pulmonary disease (COPD), but studies on the progression of expiratory air trapping in smokers are scarce. Purpose To evaluate the relationship between longitudinal changes in forced expiratory volume in 1 second (FEV) and CT-quantified emphysema and air trapping in smokers. Materials and Methods Cigarette smokers with and those without COPD participating in the multicenter observational COPDGene study were evaluated. Subjects underwent inspiratory and expiratory chest CT and spirometry at baseline and 5-year follow-up. Emphysema was quantified by using adjusted lung density (ALD). Air trapping was quantified by using mean lung density at expiratory CT and CT-measured functional residual capacity-to-total lung volume ratio. Linear models were used to regress quantitative CT measurements taken 5 years apart, and models were fit with and without adding FEV as a predictor. Analyses were stratified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage (GOLD 0, no COPD; GOLD 1, mild COPD; GOLD 2, moderate COPD; GOLD 3, severe COPD; GOLD 4, very severe COPD). Subjects with preserved FEV-to-forced vital capacity ratio and reduced FEV percentage predicted were categorized as having preserved ratio impaired spirometry (PRISm). Results A total of 4211 subjects (503 with PRISm; 2034 with GOLD 0, 388 with GOLD 1, 816 with GOLD 2, 381 with GOLD 3, 89 with GOLD 4) were evaluated. ALD decreased by 1.7 g/L (95% confidence interval [CI]: -2.5, -0.9) in subjects with GOLD 0 at baseline and by 5.3 g/L (95% CI: -6.2, -4.4) in those with GOLD 1-4 ( < .001 for both). When adjusted for changes in FEV, corresponding numbers were -2.2 (95% CI: -3.0, -1.3) and -4.6 g/L (95% CI: -5.6, -3.4) ( < .001 for both). Progression in air trapping was identified only in GOLD stage 2-4. Approximately 33%-50% of changes in air trapping in GOLD stages 2-4 were accounted for by changes in FEV. Conclusion CT measures of emphysema and air trapping increased over 5 years in smokers. Forced expiratory volume in one second accounted for less than 10% of emphysema progression and less than 50% of air trapping progression detected at CT. © RSNA, 2020
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2020191429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104704PMC
April 2020

Machine Learning Characterization of COPD Subtypes: Insights From the COPDGene Study.

Chest 2020 05 28;157(5):1147-1157. Epub 2019 Dec 28.

Department of Epidemiology, University of Colorado, Denver, Aurora, CO.

COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2019.11.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242638PMC
May 2020

Relationship between diffusion capacity and small airway abnormality in COPDGene.

Respir Res 2019 Dec 2;20(1):269. Epub 2019 Dec 2.

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

Impaired single breath carbon monoxide diffusing capacity (DLCO) is associated with emphysema. Small airways disease (SAD) may be a precursor lesion to emphysema, but the relationship between SAD and DLCO is undescribed. We hypothesized that in mild COPD, functional SAD (fSAD) defined by computed tomography (CT) and Parametric Response Mapping methodology would correlate with impaired DLCO. Using data from ever-smokers in the COPDGene cohort, we established that fSAD correlated significantly with lower DLCO among both non-obstructed and GOLD 1-2 subjects. The relationship between DLCO with CT-defined emphysema was present in all GOLD stages, but most prominent in severe disease. TRIAL REGISTRATION: NCT00608764. Registry: COPDGene. Registered 06 February 2008, retrospectively registered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-019-1237-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889734PMC
December 2019

Reduced Attention in Former Smokers with and without COPD.

Int J Behav Med 2019 Dec;26(6):600-607

Department of Psychiatry, University of Iowa Carver College of Medicine, 200 Hawkins Dr., W278GH, Iowa City, IA, 52242, USA.

Background: Attention difficulties are often reported by patients with chronic obstructive pulmonary disease (COPD); however, limited research exists using objective tests designed specifically to measure attention in this population. This study aimed to (1) identify specific attention deficits in COPD and (2) determine which demographic/clinical characteristics are associated with reduced attention.

Methods: Eighty-four former smokers (53 COPD, 31 no COPD) completed questionnaires, pulmonary function testing, and the Conner's Continuous Performance Test II (CPT-II). Participants with and without COPD were compared on CPT-II measures of inattention, impulsivity, and vigilance. CPT-II measures that differed significantly between the two groups were further examined using hierarchical regression modeling. Demographic/clinical characteristics were entered into models with attention as the dependent variable.

Results: Participants with COPD performed worse than those without COPD on CPT measures of inattention and impulsivity (i.e., detectability [discrimination of target from non-target stimuli], perseverations [reaction time under 100 ms], omissions [target stimuli response failures], and commissions [responses to non-target stimuli]). More severe COPD (measured by greater airflow limitation) was associated with poorer ability to detect targets vs. foils and perseverative responding after adjusting for age and other covariates in the model.

Conclusion: Former smokers with COPD experience problems with attention that go beyond slowed processing speed, including aspects of inattention and impulsivity. Clinicians should be aware that greater airflow limitation and older age are associated with attention difficulties, as this may impact functioning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12529-019-09826-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269072PMC
December 2019

COPD: A New Diagnostic Paradigm.

Authors:
Barry J Make

Chronic Obstr Pulm Dis 2019 Nov;6(5):438-443

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, National Jewish Health, University of Colorado School of Medicine, Denver.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.6.5.2019.0172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020847PMC
November 2019

Pulmonary Subtypes Exhibit Differential Global Initiative for Chronic Obstructive Lung Disease Spirometry Stage Progression: The COPDGene® Study.

Chronic Obstr Pulm Dis 2019 Nov;6(5):414-429

Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora.

Rationale: We classified individuals into pulmonary disease subtypes based on 2 underlying pathophysiologic disease axes (airway-predominant and emphysema-predominant) and their increased mortality risk. Our next objective was to determine whether some subcomponents of these subtypes are additionally associated with unique patterns of Global initiative for chronic Obstructive Lung Disease (GOLD) spirometry stage progression.

Methods: After accounting for intra-individual measurement variability in spirometry measures between baseline (Phase 1) and the 5-year follow up (Phase 2) of the COPD Genetic Epidemiology (COPDGene) study, 4615 individuals had complete data that would characterize patterns of disease progression over 5 years (2033 non-Hispanic whites; 827 African Americans; 48% female). Individuals could express increased risk for mortality on one or both of the primary subtype axes (airway-predominant or emphysema-predominant) and thus they were further classified into 6 groups: high-risk airway-predominant disease only (APD-only), moderate-risk airway-predominant disease only (MR-APD-only), high-risk emphysema-predominant disease only (EPD-only), combined high-risk airway- and emphysema-predominant disease (combined APD-EPD), combined moderate-risk airway- and emphysema-predominant disease (combined MR-APD-EPD), and no high-risk pulmonary subtype. Outcomes were dichotomized for GOLD spirometry stage progression from Phase 1 to Phase 2. Logistic regression of the progression outcomes on the pulmonary subtypes were adjusted for age, sex, race, and change in smoking status.

Results: The MR-APD-only group was associated with conversion from GOLD 0 to preserved ratio-impaired spirometry (PRISm) status (odds ratio [OR] 11.3, 95% confidence interval [CI] 5.7-22.1) and GOLD 0 to GOLD 2-4 (OR 6.0, 95% CI 2.0-18.0). The EPD-only group was associated with conversion from GOLD 0 to GOLD 1 (OR 2.4, 95% CI 1.2-4.6), and GOLD 1 to GOLD 2-4 (OR 2.6, 95% CI 1.0-6.9). Conversion between PRISm and GOLD 2-4 (31%-38%) occurred in both the APD-only and the MR-APD-only groups.

Conclusion: Differential conversion occurs from GOLD 0 to PRISm and GOLD 0 to GOLD 1 based on groups expressing airway-predominant disease or emphysema-predominant disease independently or in combination. Airway-predominant and emphysema-predominant subtypes are highly important in determining patterns of early disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.6.5.2019.0155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020848PMC
November 2019

Subtypes of COPD Have Unique Distributions and Differential Risk of Mortality.

Chronic Obstr Pulm Dis 2019 Nov;6(5):400-413

Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora.

Background: Previous attempts to explore the heterogeneity of chronic obstructive pulmonary disease (COPD) clustered individual patients using clinical, demographic, and disease features. We developed continuous multidimensional disease axes based on radiographic and spirometric variables that split into an airway-predominant axis and an emphysema-predominant axis.

Methods: The COPD Genetic Epidemiology study (COPDGene) is a cohort of current and former smokers, > 45 years, with at least 10 pack years of smoking history. Spirometry measures, blood pressure and body mass were directly measured. Mortality was assessed through continuing longitudinal follow-up and cause of death was adjudicated. Among 8157 COPDGene participants with complete spirometry and computed tomography (CT) measures, the top 2 deciles of the airway-predominant and emphysema-predominant axes previously identified were used to categorize individuals into 3 groups having the highest risk for mortality using Cox proportional hazard ratios. These groups were also assessed for causal mortality. Biomarkers of COPD (fibrinogen, soluble receptor for advanced glycation end products [sRAGE], C-reactive protein [CRP], clara cell secretory protein [CC16], surfactant-D [SP-D]) were compared by group.

Findings: High-risk subtype classification was defined for 2638 COPDGene participants who were in the highest 2 deciles of either the airway-predominant and/or emphysema-predominant axis (32% of the cohort). These high-risk participants fell into 3 groups: airway-predominant disease only (APD-only), emphysema-predominant disease only (EPD-only) and combined APD-EPD. There was 26% mortality for the APD-only group, 21% mortality for the EPD-only group, and 54% mortality for the combined APD-EPD group. The APD-only group (n=1007) was younger, had a lower forced expiratory volume in 1 second (FEV) percent (%) predicted and a strong association with the preserved ratio-impaired spirometry (PRISm) quadrant. The EPD-only group (n=1006) showed a relatively higher FEV % predicted and included largely GOLD stage 0, 1 and 2 partipants. Individuals in each of the 3 high-risk groups were at greater risk for respiratory mortality, while those in the APD-only group were additionally at greater risk for cardiovascular mortality. Biomarker analysis demonstrated a significant association of the APD-only group with CRP, and sRAGE demonstrated greatest significance with both the EPD-only and the combined APD-EPD groups.

Interpretation: Among current and former smokers, individuals in the highest 2 deciles for mortality risk on the airway-predominant axis and the emphysema-predominant axis have unique associations to spirometric patterns, different imaging characteristics, biomarkers and causal mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.6.5.2019.0150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020845PMC
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.6.5.2019.0149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020846PMC
November 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.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1908142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416529PMC
December 2019

Diffusing Capacity of Carbon Monoxide in Assessment of COPD.

Chest 2019 12 25;156(6):1111-1119. Epub 2019 Jul 25.

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD. Electronic address:

Background: Diffusing capacity of the lung for carbon monoxide (Dlco) is inconsistently obtained in patients with COPD, and the added benefit of Dlco testing beyond that of more common tools is unknown.

Objective: The goal of this study was to determine whether lower Dlco is associated with increased COPD morbidity independent of emphysema assessed via spirometry and CT imaging.

Methods: Data for 1,806 participants with COPD from the Genetic Epidemiology of COPD (COPDGene) study 5-year visit were analyzed, including pulmonary function testing, quality of life, symptoms, exercise performance, and exacerbation rates. Dlco percent predicted was primarily analyzed as a continuous variable and additionally categorized into four groups: (1) Dlco and FEV > 50% (reference); (2) only Dlco ≤ 50%; (3) only FEV ≤ 50%; and (4) both ≤ 50% predicted. Outcomes were modeled by using multivariable linear and negative binomial regression, including emphysema and FEV percent predicted among other confounders.

Results: In multivariable analyses, every 10% predicted decrease in Dlco was associated with symptoms and quality of life (COPD Assessment Test, 0.53 [P < .001]; St. George's Respiratory Questionnaire, 1.67 [P < .001]; Medical Outcomes Study Short Form 36 Physical Function, -0.89 [P < .001]), exercise performance (6-min walk distance, -45.35 feet; P < .001), and severe exacerbation rate (rate ratio, 1.14; P < .001). When categorized, severe impairment in Dlco alone, FEV alone, or both Dlco and FEV were associated with significantly worse morbidity compared with the reference group (P < .05 for all outcomes).

Conclusions: Impairment in Dlco was associated with increased COPD symptoms, reduced exercise performance, and severe exacerbation risk even after accounting for spirometry and CT evidence of emphysema. These findings suggest that Dlco should be considered for inclusion in future multidimensional tools assessing COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2019.06.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242635PMC
December 2019

Physiologic Insights from the COPD Genetic Epidemiology Study.

Chronic Obstr Pulm Dis 2019 07;6(3):256-266

Los Angeles Biomedical Research Institute, Harbor-University of California, Los Angeles Medical Center, Torrance.

COPD Genetic Epidemiology Study (COPDGene) manuscripts have provided important insights into chronic obstructive pulmonary disease (COPD) pathophysiology and outcomes, including a better understanding of COPD phenotypes relating computed tomography (CT) anatomic data to spirometric and patient-reported outcomes. Spirometry significantly underdiagnoses smoking-induced lung disease, and there is a marked improvement in sensitivity and specificity with CT scanning. This review also highlights the COPDGene exploration of specific spirometry phenotypes (e.g.,PRISm), contributors to spirometric decline, composite physiologic measures, asthma-COPD overlap (ACO) syndrome, consequences of bronchodilator responsiveness, newer methods to assess small airway dysfunction, and spirometric correlates of comorbid diseases such as obesity and diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.6.3.2019.0128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872216PMC
July 2019

Identifying Smoking-Related Disease on Lung Cancer Screening CT Scans: Increasing the Value.

Chronic Obstr Pulm Dis 2019 Jul;6(3):233-245

Division of Pulmonary Medicine National Jewish Health, Denver, Colorado.

Background: Lung cancer screening (LCS) via chest computed tomography (CT) scans can save lives by identifying early-stage tumors. However, most smokers die of comorbid smoking-related diseases. LCS scans contain information about smoking-related conditions that is not currently systematically assessed. Identifying these common comorbid diseases on CT could increase the value of screening with minimal impact on LCS programs. We determined the prevalence of 3 comorbid diseases from LCS eligible scans and quantified related adverse outcomes.

Methods: We studied COPD Genetic Epidemiology study (COPDGene) participants (n=4078) who met criteria for LCS screening at enrollment (age > 55 years, and < 80 years, > 30 pack years smoking, current smoker or former smoker within 15 years of smoking cessation). CT scans were assessed for coronary artery calcification (CAC), emphysema, and vertebral bone density. We tracked the following clinically significant events: myocardial infarctions (MIs), strokes, pneumonia, respiratory exacerbations, and hip and vertebral fractures.

Results: Overall, 77% of eligible CT scans had one or more of these diagnoses identified. CAC (> 100 mg) was identified in 51% of scans, emphysema in 44%, and osteoporosis in 54%. Adverse events related to the underlying smoking-related diseases were common, with 50% of participants reporting at least one. New diagnoses of cardiovascular disease, emphysema and osteoporosis were made in 25%, 7% and 46%, of participants respectively. New diagnosis of disease was associated with significantly more adverse events than in participants who did not have CT diagnoses for both osteoporosis and cardiovascular risk.

Conclusions: Expanded analysis of LCS CT scans identified individuals with evidence of previously undiagnosed cardiovascular disease, emphysema or osteoporosis that corresponded with adverse events. LCS CT scans can potentially facilitate diagnoses of these smoking-related diseases and provide an opportunity for treatment or prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.6.3.2018.0142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872218PMC
July 2019
-->