Search

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

Reynold A Panettieri Jr,1 Carlos A Camargo Jr,2 Tariq Cheema,3 Sherif G El Bayadi,4 Stanley Fiel,5 Tania M Vila,6 Renu G Jain,6 Dawn Midwinter,7 Byron Thomashow,8 Andrea Ludwig-Sengpiel,9 David A Lipson10,11 1Child Health Institute of New Jersey, Rutgers University School of Medicine, New Brunswick, NJ, USA; 2Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 3Breathing Disorder Center, Allegheny Health Network, Pittsburgh, PA, USA; 4Department of Medicine, St. Joseph’s Health/SUNY Upstate, Syracuse, NY, USA; 5Atlantic Health Systems/Morristown Medical Center, Morristown, NJ, 07960, USA; 6GSK, Research Triangle Park, NC, USA; 7GSK, Brentford, UK; 8Department of Medicine, Columbia University Medical Center, New York, NY, USA; 9KLB Gesundheitsforschung Lübeck GmbH, Lübeck, Germany; 10Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 11GSK, Collegeville, PA, USACorrespondence: Reynold A Panettieri Jr, Rutgers University School of Medicine, 89 French Street, Suite 4210, New Brunswick, NJ, 08901, USA, Tel +1 732-235-6404, Email rp856@rbhs.rutgers.eduBackground: In the FULFIL trial, once-daily single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) resulted in reduced moderate/severe exacerbation rates and conferred significant improvements in lung function and health status in patients with chronic obstructive pulmonary disease (COPD) versus twice-daily budesonide/formoterol (BUD/FOR) dual therapy.Methods: FULFIL was a Phase III, randomized, double-blind, double-dummy, parallel-group study. Patients ≥ 40 years of age with symptomatic COPD were randomized 1:1 to FF/UMEC/VI 100/62.5/25 mcg or BUD/FOR 400/12 mcg. In this post hoc analysis, patients were categorized by exacerbation history in the year prior to study entry (≥ 1 moderate/severe exacerbation [recent exacerbation] versus no recent exacerbation). Endpoints included annual rate of on-treatment moderate/severe exacerbations up to Week 24, annual rate of on-treatment severe exacerbations up to Week 24, change from baseline in trough forced expiratory volume in 1 second at Week 24, and change from baseline in health status as measured by St George’s respiratory questionnaire total score at Week 24.Results: Of the 1810 patients in the intent-to-treat population, 1180 (65%) had one or more moderate/severe exacerbation in the year prior to entry, while 630 (35%) patients did not. FF/UMEC/VI versus BUD/FOR significantly reduced moderate/severe exacerbation rates in the recent exacerbation subgroup (mean annualized rate: 0.19 vs 0.29; rate ratio [95% confidence interval [CI]]: 0.64: [0.45, 0.91]; p=0.014) and numerically reduced moderate/severe exacerbation rates in the no recent exacerbation subgroup (mean annualized rate: 0.29 vs 0.43; rate ratio [95% CI]: 0.67 [0.43, 1.04]; p=0.073). Severe exacerbation rates were numerically reduced with FF/UMEC/VI versus BUD/FOR treatment across both subgroups. FF/UMEC/VI conferred significant improvements in lung function and health status versus BUD/FOR, regardless of recent exacerbation history.Conclusion: FF/UMEC/VI reduced moderate/severe and severe exacerbation rates and improved lung function and health status versus BUD/FOR in patients with symptomatic COPD, regardless of recent exacerbation history.Keywords: COPD, exacerbations, severe exacerbations, triple therapy, ICS/LABA

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas

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 FEV1 progression in current smokers. Research Question Is use of ACEi and ARB associated with less progression of emphysema and FEV1 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 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 FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % 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

The COPD Assessment Test (CAT) was developed by a multidisciplinary group of international experts in chronic obstructive pulmonary disease (COPD) as a short, easy-to-use (paper or digital) tool to...

Contains fulltext : 220761.pdf (Publisher’s version ) (Open Access) Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue-->Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway-->Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P < 0.001] in the Tissue-->Airway group; r = -0.14 [P = 0.011] in the Airway-->Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."

Nancy K Leidy,1 Fernando J Martinez,2 Karen G Malley,1 David M Mannino,3 MeiLan K Han,4 Elizabeth D Bacci,5 Randall W Brown,6 Julia F Houfek,7 Wassim W Labaki,4 Barry J Make,8 Catherine A Meldrum,4 Wilson Quezada,9 Stephen Rennard,10 Byron Thomashow,9 Barbara P Yawn11 1Evidera, Patient-Centered Research, Bethesda, MD, USA; 2Weill Cornell Medicine, Joan & Sanford Weill Department of Medicine, New York, NY, USA; 3University of Kentucky, Preventive Medicine & Environmental Health, Lexington, KY, USA; 4University of Michigan, Division of Pulmonary & Critical Care Medicine, Ann Arbor, MI, USA; 5Evidera, Patient-Centered Research, Seattle, WA, USA; 6University of Michigan, Department of Health Behavior & Health Education, School of Public Health, Ann Arbor, MI, USA; 7University of Nebraska Medical Center College of Nursing, Omaha, NE, USA; 8National Jewish Health, Department of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, Denver, CO, USA; 9Columbia University Medical Center, Division of Pulmonary, Allergy, & Critical Care, New York, NY, USA; 10AstraZeneca, IMED Biotech Unit, Cambridge, UK & University of Nebraska Medical Center, Department of Medicine, Omaha, NE, USA; 11University of Minnesota, Department of Family & Community Health, Minneapolis, MN & COPD Foundation, Miami, FL, USA Background: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) 2: 37% vs 5%, p10: 86% vs 57%, p

Contains fulltext : 194255.pdf (Publisher’s version ) (Open Access) BACKGROUND: Emphysema has considerable variability in its regional distribution. Craniocaudal emphysema distribution is an important predictor of the response to lung volume reduction. However, there is little consensus regarding how to define upper lobe-predominant and lower lobe-predominant emphysema subtypes. Consequently, the clinical and genetic associations with these subtypes are poorly characterized. METHODS: We sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort. CT densitometric emphysema was measured in each lung lobe. Random forest clustering was applied to lobar emphysema variables after regressing out the effects of total emphysema. Clusters were tested for association with clinical and imaging outcomes at baseline and at 5-year follow-up. Their associations with genetic variants were also compared. RESULTS: Three clusters were identified: minimal emphysema (n = 1,312), upper lobe-predominant emphysema (n = 905), and lower lobe-predominant emphysema (n = 796). Despite a similar amount of total emphysema, the lower-lobe group had more severe airflow obstruction at baseline and higher rates of metabolic syndrome compared with subjects with upper-lobe predominance. The group with upper-lobe predominance had greater 5-year progression of emphysema, gas trapping, and dyspnea. Differential associations with known COPD genetic risk variants were noted. CONCLUSIONS: Subgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD.

In patients with bronchiectasis, airway clearance techniques (ACTs) are important management strategies.What are the differences in patients with bronchiectasis and a productive cough who used ACTs and those who did not? What was the assessment of bronchiectasis exacerbation frequency and change in pulmonary function at 1-year follow up?Adult patients with bronchiectasis and a productive cough in the United States Bronchiectasis and NTM Research Registry were included in the analyses. ACTs included the use of instrumental devices and manual techniques. Stratified analyses of demographic and clinical characteristics were performed by use of ACTs at baseline and follow up. The association between ACT use and clinical outcomes was assessed with the use of unadjusted and adjusted multinomial logistic regression models.Of the overall study population (n = 905), 59% used ACTs at baseline. A greater proportion of patients who used ACTs at baseline and follow up continuously had Pseudomonas aeruginosa (47% vs 36%; P = .021) and experienced an exacerbation (81% vs 59%; P .0001) or hospitalization for pulmonary illness (32% vs 22%; P = .001) in the prior two years, compared with those patients who did not use ACTs. Fifty-eight percent of patients who used ACTs at baseline did not use ACTs at 1-year follow up. There was no significant change in pulmonary function for those who used ACTs at follow up, compared with baseline. Patients who used ACTs at baseline and follow up had greater odds for experiencing exacerbations at follow up compared with those patients who did not use ACTs.In patients with bronchiectasis and a productive cough, ACTs are used more often if the patients have experienced a prior exacerbation, hospitalization for pulmonary illness, or had P aeruginosa. There is a significant reduction in the use of ACTs at 1-year follow up. The odds of the development of a bronchiectasis exacerbation are higher in those patients who use ACTs continuously, which suggests more frequent use in an ill bronchiectasis population.

Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV(1)) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV(1) or FVC; 2) FEV(1)-BDR, BDR in FEV(1) but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV(1); and 4) Combined-BDR, BDR in both FEV(1) and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV(1) over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV(1)-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV(1) decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, −1.67; 95% confidence interval [CI], −2.68 to −0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03–1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05–1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58–0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV(1) and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

Background Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George's Respiratory Questionnaire (SGRQ) CB definition identifies patients with a similar clinical phenotype as classically defined CB. Whether the SGRQ CB definition is a predictor of future COPD exacerbations is unknown. Methods We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB+ or classic CB–, using the classic definition. In addition, subjects were divided into SGRQ CB+ or SGRQ CB–. Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates. Results There were 1,434 classic CB+ subjects and 2,290 SGRQ CB+ subjects. The classic CB+ group had a greater exacerbation frequency compared with the classic CB– group (0.69 ± 1.26 vs 0.36 ± 0.90 exacerbations per patient per year; P Conclusions The SGRQ CB definition identified more subjects at risk for future exacerbations than the classic CB definition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB.

BACKGROUND:Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE:We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. METHODS:Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n=1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n=1,895). Asubset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. RESULTS:COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. CONCLUSIONS:Patients with moderate-to-severe COPD and blood eosinophil counts of 300cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

The Long-Term Oxygen Treatment Trial demonstrated that long-term supplemental oxygen did not reduce time to hospital admission or death for patients who have stable chronic obstructive pulmonary disease and resting and/or exercise-induced moderate oxyhemoglobin desaturation, nor did it provide benefit for any other outcome measured in the trial. Nine months after initiation of patient screening, after randomization of 34 patients to treatment, a trial design amendment broadened the eligible population, expanded the primary outcome, and reduced the goal sample size. Within a few years, the protocol underwent minor modifications, and a second trial design amendment lowered the required sample size because of lower than expected treatment group crossover rates. After 5.5 years of recruitment, the trial met its amended sample size goal, and 1 year later, it achieved its follow-up goal. The process of publishing the trial results brought renewed scrutiny of the study design and the amendments. This article expands on the previously published design and methods information, provides the rationale for the amendments, and gives insight into the investigators' decisions about trial conduct. The story of the Long-Term Oxygen Treatment Trial may assist investigators in future trials, especially those that seek to assess the efficacy and safety of long-term oxygen therapy. Clinical trial registered with clinicaltrials.gov (NCT00692198).

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 X 10(-8)) and PPP4R4/SERPINA1 (P = 1.01 X 10(-8)) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, similar to 0.6), and accounted for a mean 0.9-1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function.

Rationale: Chronic obstructive pulmonary disease (COPD) is often unrecognized and untreated.Objectives: To develop a method for identifying undiagnosed COPD requiring treatment with currently available therapies (FEV1

BACKGROUND: Lung volume reduction surgery (LVRS) has been shown to improve the clearance of carbon dioxide and minute ventilation (VE) in select patients with COPD. One variable often assessed in COPD is ventilatory efficiency (VE/VCO2). METHODS: We compared 55 LVRS subjects with 25 controls from the National Emphysema Treatment Trial. VE/VCO2 was calculated from cardiopulmonary exercise testing at baseline and 6-months. We sought to assess VE/VCO2 changes with LVRS compared with controls who only received standard medical care. RESULTS: At 6 months, the LVRS group significantly increased peak VO2, work load, VE, VCO2, and tidal volume while lowering peak and lowest VE/VCO2 (improved ventilatory efficiency) and end-tidal carbon dioxide pressure. The control group did not display these changes. The changes were greatest in the LVRS subjects who improved their exercise capacity after surgery (> 10 W). CONCLUSIONS: The changes were greatest in the LVRS subjects who showed the most functional improvement, indicating an association of improved ventilation with improved functional outcome.

RationaleThe demographic, physiological, and computed tomography (CT) features associated with pneumothorax in smokers with and without chronic obstructive pulmonary disease (COPD) are not clearly defined.ObjectivesWe evaluated the hypothesis that pneumothorax in smokers is associated with male sex, tall and thin stature, airflow obstruction, and increased total and subpleural emphysema.MethodsThe study included smokers with and without COPD from the COPDGene Study, with quantitative chest CT analysis. Pleural-based emphysema was assessed on the basis of local histogram measures of emphysema. Pneumothorax history was defined by subject self-report.Measurements and main resultsPneumothorax was reported in 286 (3.2%) of 9,062 participants. In all participants, risk of prior pneumothorax was significantly higher in men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.08-2.22) and non-Hispanic white subjects (OR, 1.90; 95% CI, 1.34-2.69). Risk of prior pneumothorax was associated with increased percent CT emphysema in all participants and participants with COPD (OR, 1.04 for each 1% increase in emphysema; 95% CI, 1.03-1.06). Increased pleural-based emphysema was independently associated with risk of past pneumothorax in all participants (OR, 1.05 for each 1% increase; 95% CI, 1.01-1.10). In smokers with normal spirometry, risk of past pneumothorax was associated with non-Hispanic white race and lifetime smoking intensity (OR, 1.20 for every 10 pack-years; 95% CI, 1.09-1.33).ConclusionsAmong smokers, pneumothorax is associated with male sex, non-Hispanic white race, and increased percentage of total and subpleural CT emphysema. Pneumothorax was not independently associated with height or lung function, even in participants with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

BACKGROUND The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV 1 ), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) requiring invasive mechanical ventilation (IMV) are associated with significant morbidity and mortality. Extracorporeal carbon dioxide removal (ECCO₂R) may facilitate extubation and ambulation in these patients and potentially improve outcomes.We assessed the feasibility of achieving early extubation and ambulation in subjects requiring IMV for exacerbations of COPD using single-site ECCO₂R.Five subjects with exacerbations of COPD with uncompensated hypercapnia requiring IMV were enrolled in this single-center, prospective, feasibility trial using a protocol of ECCO₂R, extubation, and physical rehabilitation. The primary endpoint was extubation within 72 hours of starting ECCO₂R.Mean preintubation pH and PaCO₂ were 7.23 ± 0.05 and 81.6 ± 15.9 mm Hg, respectively. All subjects met the primary endpoint (median duration, 4 h; range, 1.5-21.5 h). Mean duration of extracorporeal support was 193.0 ± 76.5 hours. Mean time to ambulation after extracorporeal initiation was 29.4 ± 12.6 hours. Mean maximal ambulation on extracorporeal support was 302 feet (range, 70-600). Four subjects were discharged home, and one underwent planned lung transplantation. Two minor bleeding complications occurred. There were no complications from mobilization on extracorporeal support.ECCO₂R facilitates early extubation and ambulation in exacerbations of COPD requiring IMV and has the potential to serve as a new paradigm for the management of a select group of patients. Rigorous clinical trials are needed to corroborate these results and to investigate the effect on long-term outcomes and cost effectiveness over conventional management.

The purpose of this study was to compare simultaneous measurements of tidal volume (Vt) by optoelectronic plethysmography (OEP) and spirometry during a maximal cycling exercise test to quantify possible differences between methods. Vt measured simultaneously by OEP and spirometry was collected during a maximal exercise test in thirty healthy participants. The two methods were compared by linear regression and Bland-Altman analysis at submaximal and maximal exercise. The average difference between the two methods and the mean percentage discrepancy were calculated. Submaximal exercise (SM) and maximal exercise (M) Vt measured by OEP and spirometry had very good correlation, SM R=0.963 (p

Summary The burden of chronic obstructive pulmonary disease (COPD) in the USA continues to grow. Although progress has been made in the the development of diagnostics, therapeutics, and care guidelines, whether patients' quality of life is improved will ultimately depend on the actual implementation of care and an individual patient's access to that care. In this Commission, we summarise expert opinion from key stakeholders—patients, caregivers, and medical professionals, as well as representatives from health systems, insurance companies, and industry—to understand barriers to care delivery and propose potential solutions. Health care in the USA is delivered through a patchwork of provider networks, with a wide variation in access to care depending on a patient's insurance, geographical location, and socioeconomic status. Furthermore, Medicare's complicated coverage and reimbursement structure pose unique challenges for patients with chronic respiratory disease who might need access to several types of services. Throughout this Commission, recurring themes include poor guideline implementation among health-care providers and poor patient access to key treatments such as affordable maintenance drugs and pulmonary rehabilitation. Although much attention has recently been focused on the reduction of hospital readmissions for COPD exacerbations, health systems in the USA struggle to meet these goals, and methods to reduce readmissions have not been proven. There are no easy solutions, but engaging patients and innovative thinkers in the development of solutions is crucial. Financial incentives might be important in raising engagement of providers and health systems. Lowering co-pays for maintenance drugs could result in improved adherence and, ultimately, decreased overall health-care spending. Given the substantial geographical diversity, health systems will need to find their own solutions to improve care coordination and integration, until better data for interventions that are universally effective become available.

The value of quantitative CT (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. The authors hypothesised that QCT-defined emphysema and airway abnormalities relate to St George's Respiratory Questionnaire (SGRQ) and Body-Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index (BODE).1200 COPDGene subjects meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD with QCT analysis were included. Total lung emphysema was measured using the density mask technique with a -950 Hounsfield unit threshold. An automated programme measured mean wall thickness (WT), wall area percentage (WA%) and 10 mm lumenal perimeter (pi10) in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE.In separate models predicting SGRQ score, a 1 unit SD increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p0.001). The comparable increase in SGRQ for a 1 unit SD increase in emphysema percentage in these models was relatively weaker, significant only in the pi10 model (for emphysema percentage, 1.45 points higher, p=0.01). In separate models predicting BODE, a 1 unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07-fold increase, p0.001; for WA%, 1.20-fold increase, p0.001; for pi10, 1.16-fold increase, p0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26-fold increase, p0.001).Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.

Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a dopamine beta-hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2x10(-7). No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p

The National Emphysema Treatment Trial (NETT) proved that lung volume reduction surgery (LVRS) was safe and effective in patients with certain clinical characteristics and using defined inclusion-exclusion criteria. Based on the selection criteria developed in that trial, we performed bilateral LVRS on 49 patients during the period of February 2004 until May 2009.Forty-nine patients underwent lung volume reduction by either median sternotomy (10) or video-assisted thoracoscopic surgery (39) selected according to NETT described parameters. Preoperative characteristics were the following: mean (±SD) age 62.5±6.6 years, preoperative FEV1 (forced expiratory volume in the first second of expiration) 691 cc (±159), % of predicted FEV1 25.3 (±6.2), preoperative Dlco (diffusing capacity of lung for carbon monoxide) 7.6 (±2.7), and % of predicted DLCO 27% (±7.3). All patients had upper lobe predominant disease and either low exercise capacity (n=23) or high exercise capacity (n=26) as defined by the NETT.There was no operative or 90-day mortality. Median length of stay was 8 days (interquartile range=6 to 10). Two patients required reintubation and tracheostomy but were decannulated prior to discharge. The BODE index (body mass index, airflow obstruction, dyspnea, and exercise capacity), a multidimensional predictor of survival in chronic obstructive pulmonary disease, improved -2.3 (±1.5, p0.0001) (missing data: 5 of 42, 11.9%) and the FEV1 improved 286 cc (±221, p0.0001), both 1 year after surgery. Probability of survival was 0.98 (95% CI [confidence interval]=0.94 to 1) at 1 year, and 0.95 (95% CI=0.88 to 1) at 3 years.Surgical lung volume reduction for emphysema can be performed in patients using selection criteria developed by the NETT with very low surgical risk and excellent midterm results. Surgical LVRS is the standard against which other nonsurgical treatments for advanced emphysema should be judged.

Background: Little is known about the actual treatment of patients with chronic obstructive pulmonary disease (COPD), either in the inpatient or outpatient settings. We hypothesized that there are substantial opportunities for improvement in adherence with current guidelines and recommendations. Methods: We reviewed the medical records of all patients hospitalized with acute exacerbation of COPD between January 2005 and December 2006 at 5 New York City hospitals. Results: There were 1285 unique patients with 1653 hospitalizations. Of these 1653, 83% were for patients with a prior history of COPD and 368 (22%) represented repeat admissions during our study period. The majority were treated during their hospitalization with a combination of systemic steroids (85%), bronchodilators (94%) and antibiotics (80%). There were 59 deaths (3.6%). Smoking cessation counseling was offered to 48% of active smokers. Influenza and pneumococcal vaccines were administered to half of eligible patients. On discharge, only 46.0% were prescribed maintenance bronchodilators and 24% were not prescribed any inhaled therapy. Even in the 226 unique patients (17.6%) readmitted at least once during course of the study, on discharge only 44.7% were prescribed maintenance bronchodilators and 23% were not prescribed any regular inhaled therapy. Conclusions: Patients hospitalized with acute exacerbation of COPD generally receive adequate hospital care, but there may be opportunities to improve care pharmacologically and with smoking cessation counseling and vaccination during and after hospitalization.

Background CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

Comorbidities such as cardiac disease, diabetes mellitus, hypertension, osteoporosis, and psychological disorders are commonly reported in patients with chronic obstructive pulmonary disease (COPD) but with great variability in reported prevalence. Tobacco smoking is a risk factor for many of these comorbidities as well as for COPD, making it difficult to draw conclusions about the relationship between COPD and these comorbidities. However, recent large epidemiologic studies have confirmed the independent detrimental effects of these comorbidities on patients with COPD. On the other hand, many of these comorbidities are now considered to be part of the commonly prevalent nonpulmonary sequelae of COPD that are relevant not only to the understanding of the real burden of COPD but also to the development of effective management strategies.

Objectives: We hypothesized that lung-volume reduction surgery for pulmonary emphysema would improve body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index, a multidimensional predictor of survival in chronic obstructive pulmonary disease. We also aimed to identify preoperative predictors of improvement in the BODE index. Methods: In a prospective cohort study of patients undergoing lung-volume reduction surgery at our center, with the methodology of the National Emphysema Treatment Trial, we compared clinical characteristics before and 1 year after surgery with the Wilcoxon signed rank test. Changes in the BODE index were correlated with preoperative variables with the Spearman correlation coefficient. Results: Twenty-three patients with predominantly upper-lobe pulmonary emphysema underwent lung-volume reduction surgery (14 by video-assisted thoracoscopic surgery, 9 by median sternotomy). There were no postoperative or follow-up deaths. The BODE index improved from a median of 5 (interquartile range 4-5) before surgery to 3 (interquartile range 2-4) 1 year after surgery (P .0001). Improvements were seen in the lung function and dyspnea components of the BODE index. Lower preoperative 6-minute walk distance and lower postwalk Borg fatigue scores were each associated with greater improvement in the BODE index after 1 year. Conclusion: Lung-volume reduction surgery for pulmonary emphysema improved the BODE index in patients with predominantly upper-lobe disease. Lower preoperative 6-minute walk distance correlated with greater improvement in the BODE index.

Approximately 20% of patients hospitalized for COPD exacerbations in the United States will be readmitted within 30 days. The Centers for Medicare and Medicaid Services has recently proposed to revise the Hospital Readmissions Reduction Program to financially penalize hospitals with high all-cause 30-day rehospitalization rates after a hospitalization for COPD exacerbation on or after October 1, 2014.To report the results of a systematic review of randomized clinical trials evaluating interventions to reduce the rehospitalizations after COPD exacerbations.Multiple electronic databases were systematically searched to identify relevant studies published between January 1966 and June 2013. Titles, abstracts, and, subsequently, full-text articles were assessed for eligibility. Each study was appraised using predefined criteria.Among 913 titles and abstracts screened, 5 studies (1,393 participants) met eligibility criteria. All studies had a primary outcome of rehospitalization at 6 or 12 months. No study examined 30-day rehospitalization as the primary outcome. Each study tested a different set of interventions. Two studies (one conducted in Canada and one conducted in Spain and Belgium) showed a decrease in all-cause rehospitalization over 12 months in the intervention group versus comparator group (mean number of hospitalizations per patient, 1.0 vs. 1.8; P = 0.01; percent hospitalized, 45 vs. 67%; P = 0.028; respectively). The only study conducted in the United States found a greater than twofold higher risk of mortality in the intervention group (17 vs. 7%, P = 0.003) but no significant difference in rehospitalizations. It was unclear which set of interventions was effective or harmful.The evidence base is inadequate to recommend specific interventions to reduce rehospitalizations in this population and does not justify penalizing hospitals for high 30-day rehospitalization rates after COPD exacerbations.

The transcription factor early growth response (Egr)-1 is an immediate-early gene product rapidly and transiently expressed after acute tissue injury. In contrast, in this report we demonstrate that lung tissue from patients undergoing lung reduction surgery for advanced emphysema, without clinical or anatomical evidence of acute infection, displays a selective and apparently sustained increase in Egr-1 transcripts and antigen, compared with a broad survey of other genes, including the transcription factor Sp1, whose levels were not significantly altered. Enhanced Egr-1 expression was especially evident in smooth muscle cells of bronchial and vascular walls, in alveolar macrophages, and some vascular endothelium. Gel shift analysis with (32)P-labeled Egr probe showed a band with nuclear extracts from emphysematous lung which was supershifted with antibody to Egr-1. Egr-1 has the capacity to regulate genes relevant to the pathophysiology of emphysema, namely those related to extracellular matrix formation and remodeling, thrombogenesis, and those encoding cytokines/chemokines and growth factors. Thus, we propose that further analysis of Egr-1, which appears to be up-regulated in a sustained fashion in patients with late stage emphysema, may provide insights into the pathogenesis of this destructive pulmonary disease, as well as a new facet in the biology of Egr-1.

The volume and severity of pulmonary emphysema in individual lungs were measured by means of quantitative computed tomography (CT) studies in 28 patients (14 women, 14 men, median age 65 yr) who underwent either bilateral (n = 15) or unilateral (n = 13) lung volume reduction surgery (LVRS). Spirometric, total body plethysmographic, and CT data (at TLC and RV) were correlated before and after LVRS. Lung volumes determined by CT correlated well with volumes obtained by total body plethysmography (p0.0001). For individual lungs after LVRS, CT-derived mean lung capacity decreased 13% and residual volume 20% (p0.00001 for each), while mean total functional lung volume (TFLV, defined as the volume of lung with CT attenuation greater than -910 Hounsfield units) increased 9% (p0.01), and the mean ratio of the air space to tissue space volume (V(AS)/V(TS)) decreased more at RV (23%) than at TLC (14%) (p0.0005 for each). In contrast, unilateral LVRS did not affect exhalation from the unoperated lung (2% reduction in RV, p = NS). The magnitude of the postoperative response (CT-derived TLC, RV, TFLV, V(AS)/V(TS)) of each operated lung was comparable for unilateral and bilateral LVRS. Thus, a lung's response to LVRS was independent from that of the contralateral lung. Moreover, postoperative alterations in TFLV and FEV1 correlated significantly (r = 0.80, p0.0001), which suggests that the expansion of functioning tissue may contribute to the mechanism by which LVRS palliates airway obstruction.

Background/objectives Patients presenting with acute pulmonary embolism associated with hemodynamic compromise exhibit right ventricular enlargement and dysfunction on transthoracic echocardiogram. However, the degree of echocardiographic abnormalities among hemodynamically stable patients without preexisting cardiopulmonary disease during the acute stage of pulmonary embolism, and following treatment, is unknown. Therefore, this study was designed to assess the extent of right ventricular abnormalities detected on transthoracic echocardiogram in patients following acute pulmonary embolism and during treatment with anticoagulation or vena caval interruption. The extent of pulmonary vascular obstruction and complication rate on follow-up were also assessed. Design/interventions Sixty-four consecutive hemodynamically stable patients without preexisting known cardiopulmonary disorder presenting with acute pulmonary embolism and undergoing treatment with anticoagulation or inferior vena caval interruption were studied. All subjects underwent a two-dimensional transthoracic echocardiogram within 24 h of diagnosis. The degree of perfusion abnormality on lung scan was quantified. Twenty-six patients underwent follow-up echocardiogram and lung scan at 6 weeks. The echocardiographic findings were compared with those obtained from a group of normal control subjects matched for gender and age. Results Although the mean right ventricular end-diastolic areas did not differ (21.9±5.2 cm 2 vs 20.1±2.9 cm 2 for control subjects; p=not significant), the right ventricular end-systolic area was larger in comparison to our series of control subjects (14.6±5.1 cm 2 vs 11.7±2.0 cm 2 ; p=0.025). Fractional right ventricular area change was reduced in the patient group compared with the control subjects (34.3±9.0% vs 41.3±7.0%; p=0.003). The extent of right ventricular end-systolic area enlargement and decrease in fractional area change did not correlate with the degree of pulmonary vascular obstruction. Patients who were restudied at 6 weeks showed minimal improvement in echocardiographic findings, despite almost complete resolution of perfusion defects on lung scan. Conclusions The extent of right ventricular dysfunction in hemodynamically stable, previously normal patients with acute pulmonary embolism does not reflect the extent of the perfusion abnormalities. Further, right ventricular enlargement and systolic dysfunction are present and persistent despite treatment with heparin and warfarin therapy or vena caval interruption.

Background. Lung volume reduction surgery (LVRS) has shown early promise as a palliative therapy in severe emphysema. A number of patients, however, are not candidates for a bilateral operation, or exhibit a predominantly unilateral disease distribution. Methods. Over 20 months, we performed LVRS in 92 patients selected on the basis of severe hyperinflation with air trapping, diaphragmatic dysfunction, and disease heterogeneity. Twenty-eight patients underwent unilateral LVRS on the basis of asymmetric disease distribution, prior thoracic operation, or concomitant tumor resection. Results. Unilateral LVRS resulted in comparable improvements in exercise capacity and dyspnea as the bilateral procedure, with a similar perioperative mortality and actuarial survival to 24 months. Improvements in spirometric indices of pulmonary function, however, were less in patients undergoing unilateral than bilateral LVRS. Conclusions. In properly selected patients, unilateral LVRS provides functional and subjective benefits of comparable magnitude to those associated with a bilateral operation. Unilateral LVRS is therefore an option in the therapy of end-stage emphysema in patients with asymmetric disease distribution, a prior thoracic operation, or contraindications to sternotomy, and may have a role as a bridge to transplantation in selected cases.

The increasing number of treatment options for managing patients with chronic obstructive pulmonary disease (COPD) promises to improve the outcomes for COPD patients. However, determining which treatments are appropriate for individual patients has become increasingly complex. The COPD Foundation Guide for Diagnosis and Management of COPD was developed to be a practical, easy to use tool for clinicians. The Guide includes specific recommendations for diagnostic studies and treatments based on specific diagnostic criteria. This manuscript describes the rationale for the development of the Guide, the process used, the rationale for the specific recommendations and the plans for further development. The current recommendations of the COPD Foundation have been summarized in the form of Pocket Cards, which may be obtained from the Foundation at no charge (1-866-316-COPD (2673), www.copdfoundation.org).

We evaluated the prevalence of chronotropic incompetence (CI), a marker of autonomic dysfunction, and its prognostic value in patients with chronic obstructive pulmonary disease (COPD). We performed a retrospective analysis of 449 patients with severe COPD who underwent a cardiopulmonary exercise test, after excluding patients with lung volume reduction surgery, left ventricular dysfunction and those not in sinus rhythm. CI was defined as percent predicted heart rate reserve (%HRR). Events were defined as death or lung transplant during a median follow-up of 68 months. Median age was 61 years; median percent predicted forced expiratory volume in one second (%FEV1) of 25% and median %HRR of 33%. The hazard ratio for an event in the lowest quartile of %HRR, taking the highest quartile as reference, was of 3.2 (95% confidence interval: 2.1-4.8; p < 0.001). In a multivariate regression model, %HRR was an independent predictor of events. In conclusion, Cl was an independent and powerful outcome predictor in patients with severe COPD. (C) 2013 Elsevier B.V. All rights reserved.

Pleomorphic carcinoma of the lung is a rare form of malignancy that can present similarly to other necrotising cavitary lung diseases. We present a case of a Caucasian woman who presented with recurrent haemoptysis and a right upper lobe cavitary lesion on CT scan. She underwent selective embolisation of the right bronchial artery by interventional radiology to control her haemoptysis. Positron emission tomography/CT scan was performed which showed significant fluorodeoxyglucose uptake in the right upper lobe cavitary lesion. There was a discussion among her providers about the aetiology of this lesion including infection and malignancy. Cultures from bronchoalveolar lavage and blood were negative for infection as the patient underwent right upper lobectomy which showed invasive sarcomatoid pleomorphic carcinoma with a minor component of acinar adenocarcinoma. She was diagnosed with stage IB (T2aN0M0) sarcomatoid pleomorphic carcinoma and underwent adjuvant chemotherapy after her lobectomy with recurrence and metastasis to her stomach and pancreas.

Impaired ventilation on cardiopulmonary exercise test (CPET) is seen in patients with chronic obstructive pulmonary disease (COPD). However, evaluation of the differences of abnormal gas exchange in COPD according to GOLD severity criteria is limited. A retrospective review was performed on all COPD patients referred for CPET at our center between 1998 and 2010. There were 548 patients compared according to GOLD severity. GOLD groups were significantly different from each other in regards to pressure of end-tidal carbon dioxide ( [Formula: see text] ) with progressively higher [Formula: see text] with increasing GOLD severity. Ratio of minute ventilation to carbon dioxide production ( [Formula: see text] ) and exercise capacity as measured by and [Formula: see text] % and work rate in watts% was inversely proportional to GOLD severity. Breathing reserve, minute ventilation, and tidal volume at peak exercise were significantly decreased with increasing disease severity between GOLD groups. We concluded that gas exchange is distinctive among different GOLD severity groups; specifically, GOLD 3 and 4 have a significantly higher [Formula: see text] and a significantly lower [Formula: see text] than GOLD 2.

Pulmonary hypertension with exercise is common in chronic obstructive pulmonary disease (COPD) and may contribute to exercise limitation in this disease. We aimed to determine the effects of treatment with sildenafil on exercise capacity in patients with COPD and emphysema.We performed a randomized, double-blind, placebo-controlled 2-period crossover trial of sildenafil thrice daily in ten adults with COPD and emphysema on CT scan without pulmonary hypertension. We randomized study participants to 4 weeks of sildenafil (or placebo) followed by a 1-week washout and then 4 weeks of placebo (or sildenafil). The 2 primary outcomes were the 6-minute walk distance and oxygen consumption at peak exercise.Sildenafil had no effect on 6-minute walk distance (placebo-corrected difference = -7.8 m, 95% confidence interval, -23.2 to 7.5 m, p = 0.35) or oxygen consumption at peak exercise (placebo-corrected difference = -0.1 ml/kg/min, 95% confidence interval -2.1 to 1.8 ml/kg/min, p = 0.89). Sildenafil increased the alveolar-arterial oxygen gradient (p = 0.02), worsened symptoms (p = 0.04), and decreased quality-of-life (p = 0.03). Adverse events were more frequent while receiving sildenafil (p = 0.005).Routine sildenafil administration did not have a beneficial effect on exercise capacity in patients with COPD and emphysema without pulmonary hypertension. Sildenafil significantly worsened gas exchange at rest and quality of life. (clinicaltrials.gov NCT00104637).

In response to the Agency for Healthcare Research and Quality statement questioning the usefulness of “screening spirometry,” the National Heart, Lung, and Blood Institute and the COPD Foundation held a consensus conference in June 2008 to establish a procedure to detect cases of COPD in the general population. Conference participants developed a three-stage approach, using a brief questionnaire, peak flow measurement with a pocket spirometer, and diagnostic quality spirometry. The overall objective of this study was to examine the usefulness of a simple questionnaire and peak flow measurement in screening for COPD in a self-selected population. We hypothesized that this combination would efficiently screen for clinically relevant COPD.We queried individuals attending public events regarding the presence of wheeze and/or asthma, mucus production, dyspnea, exposure to irritants, and tobacco use. Peak expiratory flow (PEF) was then measured with a pocket spirometer. If PEF was70% predicted, spirometry was performed. In order to estimate the false-negative rate, a random sample of every 10th participant was also selected for spirometry.Between June 2008 and December 2009, 5,761 adults completed the risk assessment questionnaire. The mean age of the respondents was 54 years, 58% were women, and 88% were white. Of these, 5,638 participants completed pocket spirometry, and 315 (5.6%) had PEF70% predicted. Of 5,323 with normal PEF, 651 underwent spirometry. The performance of PEF was assessed via positive and negative predictive values relative to a diagnosis of clinically significant airflow obstruction, defined as FEV(1)/FEV(6)the lower limit of normal and FEV(1)60% predicted. Of 4,238 subjects with at least two risk factors, 267 (6.3%) had PEF70%, compared with 48 of the 1,400 subjects (3.4%) with fewer than two risk factors (P.001). Based on 729 participants with acceptable spirometry, 63.1% (113 of 179) of those with abnormal PEF tested positive for clinically significant airflow obstruction, compared with 5.5% (30 of 550) with normal PEF (P.001). The estimated prevalence of significant COPD among the 5,638 screened was 8.7%, and sensitivity and specificity were 40.7% and 97.7%, respectively.A staged approach to COPD screening in adults is useful for detecting clinically significant airflow obstruction in our study population.

Gregory D Salinas1, James C Williamson1, Ravi Kalhan2, Byron Thomashow3, Jodi L Scheckermann4, John Walsh5, Maziar Abdolrasulnia1, Jill A Foster11CE Outcomes, LLC Birmingham, AL, USA; 2Asthma-COPD Program, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 3Division of Pulmonary, Allergy, Critical Care, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA; 4Boehringer-Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 5COPD Foundation, Miami, FL, USAPurpose: Even with the dissemination of several clinical guidelines, chronic obstructive pulmonary disease (COPD) remains underdiagnosed and mismanaged by many primary care physicians (PCPs). The objective of this study was to elucidate barriers to consistent implementation of COPD guidelines.Patients and methods: A cross-sectional study implemented in July 2008 was designed to assess attitudes and barriers to COPD guideline usage.Results: Five hundred US PCPs (309 family medicine physicians, 191 internists) were included in the analysis. Overall, 23.6% of the surveyed PCPs reported adherence to spirometry guidelines over 90% of the time; 25.8% reported adherence to guidelines related to long-acting bronchodilator (LABD) use in COPD patients. In general, physicians were only somewhat familiar with COPD guidelines, and internal medicine physicians were significantly more familiar than family physicians (P < 0.05). In a multivariate model controlling for demographics and barriers to guideline adherence, we found significant associations with two tested guideline components. Adherence to spirometry guidelines was associated with agreement with guidelines, confidence in interpreting data, ambivalence to outcome expectancy, and ability to incorporate spirometry into patient flow. Adherence to LABD therapy guidelines was associated with agreement with guidelines and confidence in gauging pharmacologic response.Conclusions: Adherence to guideline recommendations of spirometry use was predicted by agreement with the recommendations, self-efficacy, perceived outcome expectancy if recommendations were adhered to, and resource availability. Adherence to recommendations of LABD use was predicted by agreement with guideline recommendations and self-efficacy. Increasing guideline familiarity alone may have limited patient outcomes, as other barriers, such as low confidence and outcome expectancy, are more likely to impact guideline adherence.Keywords: COPD, primary care, barriers, guideline adoption

To determine how increased ventilatory demand impacts ventilatory kinematics, we compared the total chest wall volume variations (V(CW)) of male and female endurance-trained athletes (ET) to untrained individuals (UT) during exercise. We hypothesized that training and gender would have an effect on V(CW) and kinematics at maximal exercise. Gender and training significantly influenced chest wall kinematics. Female ET did not change chest wall end-expiratory volume (V(CW,ee)) or pulmonary ribcage (V(RCp,ee)) with exercise, while female UT significantly decreased V(CW,ee) and V(RCp,ee) with exercise (p0.05). Female ET significantly increased pulmonary ribcage end-inspiratory volume (V(RCp,ei)) with exercise (p0.05), while female UT did not change V(RCp,ei) with exercise. Male ET significantly increased V(RCp,ei) with exercise (p0.05); male UT did not. Men and women had significantly different variation of V(CW) (p0.05). Women demonstrated the greatest variation of V(CW) in the pulmonary ribcage compartment (V(RCp)). Men had even volumes variation of the V(RCp) and the abdomen (V(Ab)). In conclusion, gender and training had a significant impact on ventilatory kinematics.

Pulmonary hypertension, a common manifestation of advanced sarcoidosis, is thought to result from fibrosis with chronic hypoxia and destruction of small vessels, extrinsic compression of pulmonary arteries, or granulomatous vasculitis. We report a case of sarcoidosis-associated pulmonary hypertension due to fibrosing mediastinitis. Our patient presented with cough and dyspnea on exertion and was found to have pulmonary artery enlargement, pulmonary venous compression, and mediastinal soft tissue enhancement on magnetic resonance imaging. Pulmonary hypertension was confirmed by right heart catheterization and sarcoidosis was diagnosed by histologic examination of tissue obtained at mediastinoscopy. Treatment with steroids resulted in decreased pulmonary artery pressures as well as symptomatic improvement. While pulmonary hypertension is a common complication of sarcoidosis, fibrosing mediastinitis is an unusual etiology that should be considered by clinicians.

Potential candidates for lung volume reduction surgery should undergo extensive evaluation and preparation to minimize perioperative risks and optimize surgical outcomes. Initial screening includes spirometry, diffusion capacity, lung volumes by body plethysmography, and high-resolution computerized tomography scanning. Patients who have been successfully screened must complete a preoperative pulmonary rehabilitation program of 6–10 weeks duration. During the pulmonary rehabilitation program, medical therapy should be maximized. Postrehabilitation studies include cardiopulmonary exercise testing, arterial blood gas analysis, oxygen titration, six-minute walk, and cardiac testing. The evaluation process aims at defining the severity and distribution of emphysema and attempts to eliminate those who do not meet criteria outlined by the National Emphysema Treatment Trial. Optimal candidates have upper-lobe–predominant emphysema and acceptable operative risks.