Analysis of Prior Aspirin Treatment on in-Hospital Outcome of Geriatric COVID-19 Infected Patients.

Background and Objectives: Aspirin (ASA) is a commonly used antithrombotic drug that has been demonstrated to reduce venous thromboembolism. The aim was to analyze if geriatric COVID-19 patients undergoing a 100 mg/day Aspirin (ASA) treatment prior to hospitalization differ in hospital outcome compared to patients without previous ASA therapy. Materials and Methods: An observational retrospective study was carried out using an anonymized database including geriatric COVID-19 patients (March to April 2020) admitted to Madrid Hospitals Group. A group of COVID-19 patients were treated with low ASA (100 mg/day) prior to COVID-19 infection. Results: Geriatric ASA-treated patients were older (mean age over 70 years; n = 41), had higher frequency of hypertension and hyperlipidemia, and upon admission had higher D-dimer levels than non-ASA-treated patients (mean age over 73 years; n = 160). However, patients under ASA treatment did not show more frequent pulmonary thromboembolism (PE) than non-ASA-treated patients. ASA-treated geriatric COVID-19-infected patients in-hospital < 30 days all-cause mortality was more frequent than in non-ASA-treated COVID-19 patients. In ASA-treated COVID-19-infected geriatric patients, anticoagulant therapy with low molecular weight heparin (LMWH) significantly reduced need of ICU care, but tended to increase in-hospital < 30 days all-cause mortality. Conclusions: Prior treatment with a low dose of ASA in COVID-19-infected geriatric patients increased frequency of in-hospital < 30 days all-cause mortality, although it seemed to not increase PE frequency despite D-dimer levels upon admission being higher than in non-ASA users. In ASA-treated geriatric COVID-19-infected patients, addition of LMWH therapy reduced frequency of ICU care, but tended to increase in-hospital < 30 days all-cause mortality.

Albumin Binds COVID-19 Spike 1 Subunit and Predicts In-Hospital Survival of Infected Patients-Possible Alteration by Glucose.

(1) Background: This study aimed to analyze if the serum albumin levels of hospitalized SARS-CoV-2 (COVID-19) patients on admission could predict <30 days in-hospital all-cause mortality, and if glucose levels on admission affected this predictive ability. (2) Methods: A multicenter retrospective cohort of 1555 COVID-19-infected adult patients from public hospitals of the Madrid community were analyzed. (3) Results: Logistic regression analysis showed increased mortality for ages higher than 49 y. After adjusting for age, comorbidities and on-admission glucose levels, it was found that on-admission serum albumin ≥3.5 g/dL was significantly associated with reduced mortality (OR 0.48; 95%CI:0.36-0.62). There was an inverse concentration-dependent association between on-admission albumin levels and <30 days in-hospital all-cause mortality. However, when on-admission glucose levels were above 125 mg/dL, higher levels of serum albumin were needed to reach an association with survival. In vitro experiments showed that the spike protein S1 subunit of SARS-CoV-2 binds to native albumin. The binding ability of native albumin to the spike protein S1 subunit was decreased in the presence of an increasing concentration of glycated albumin. (4) Conclusions: On-admission serum albumin levels were inversely associated with <30 days in-hospital all-cause mortality. Native albumin binds the spike protein S1 subunit, suggesting that native albumin may act as a scavenger of the SARS-CoV-2 virus.

Paired CT Measures of Emphysema and Small Airways Disease and Lung Function and Exercise Capacity in Smokers with Radiographic Bronchiectasis.

RATIONALE AND OBJECTIVES: Bronchiectasis (BE) is associated with chronic obstructive pulmonary disease (COPD), but emphysema and small airways disease, main pathologic features of COPD, have been sparsely studied in BE. We aimed to objectively assess those features in smokers with and without radiographic BE and examine its relationships to airflow obstruction and exercise capacity. MATERIAL AND METHODS: We measured emphysema and small airways disease on paired inspiratory-expiratory computed tomography (CT) scans with the parametric response map (PRMEMPH and PRMSAD) method in 1184 smokers with and without radiographic BE. PRMSAD and PRMEMPH are expressed as the percentage of lung area. Clinical, spirometry, and exercise capacity data were measured with standardized methods. The differences in PRMSAD and PRMEMPH between subjects with and without radiographic BE were assessed using multivariable linear regression analysis, and their associations with FEV1 and six-minute walk test (6MWT) were assessed with generalized linear models. RESULTS: Out of 1184 subjects, 383 (32%) had radiographic BE. PRMEMPH but not PRMSAD was higher in subjects with radiographic BE than those without radiographic BE in adjusted models. Subjects with radiographic BE and PRMEMPH (defined as ≥5% on paired CTs) had lower FEV1 (least square mean, 1479 mL vs. 2350 mL p < 0.0001) and 6MWT (372 m vs. 426 m p = 0.0007) than those with radiographic BE alone in adjusted models. CONCLUSION: Smokers with radiographic BE have an increased burden of emphysema on paired CTs, and those with radiographic BE and emphysema have lower airflow and exercise capacity.

Contribution of Individual and Neighborhood Factors to Racial Disparities in Respiratory Outcomes.

Rationale: Black adults have worse health outcomes compared with white adults in certain chronic diseases, including chronic obstructive pulmonary disease (COPD).Objectives: To determine to what degree disadvantage by individual and neighborhood socioeconomic status (SES) may contribute to racial disparities in COPD outcomes.Methods: Individual and neighborhood-scale sociodemographic characteristics were determined in 2,649 current or former adult smokers with and without COPD at recruitment into SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). We assessed whether racial differences in symptom, functional, and imaging outcomes (St. George's Respiratory Questionnaire, COPD Assessment Test score, modified Medical Research Council dyspnea scale, 6-minute-walk test distance, and computed tomography [CT] scan metrics) and severe exacerbation risk were explained by individual or neighborhood SES. Using generalized linear mixed model regression, we compared respiratory outcomes by race, adjusting for confounders and individual-level and neighborhood-level descriptors of SES both separately and sequentially.Measurements and Main Results: After adjusting for COPD risk factors, Black participants had significantly worse respiratory symptoms and quality of life (modified Medical Research Council scale, COPD Assessment Test, and St. George's Respiratory Questionnaire), higher risk of severe exacerbations and higher percentage of emphysema, thicker airways (internal perimeter of 10 mm), and more air trapping on CT metrics compared with white participants. In addition, the association between Black race and respiratory outcomes was attenuated but remained statistically significant after adjusting for individual-level SES, which explained up to 12-35% of racial disparities. Further adjustment showed that neighborhood-level SES explained another 26-54% of the racial disparities in respiratory outcomes. Even after accounting for both individual and neighborhood SES factors, Black individuals continued to have increased severe exacerbation risk and persistently worse CT outcomes (emphysema, air trapping, and airway wall thickness).Conclusions: Disadvantages by individual- and neighborhood-level SES each partly explain disparities in respiratory outcomes between Black individuals and white individuals. Strategies to narrow the gap in SES disadvantages may help to reduce race-related health disparities in COPD; however, further work is needed to identify additional risk factors contributing to persistent disparities.

Platelet Apoptotic Response May Be Associated With the Capacity of Aspirin to Inhibit Platelets.

An inadequate platelet response to aspirin (ASA) has been identified in some patients under chronic ASA treatment. The aim of this study was to analyze if ASA-sensitive and ASA-resistant platelets have differences in their apoptotic capability. Clinically stable ischemic coronary patients who had been taking ASA (100 mg/d) for at least 9 months before inclusion were divided into ASA-resistant (n = 11) and ASA-sensitive (n = 13) groups as defined by the PFA-100 test. Platelets from ASA-sensitive patients showed higher expression of the proapoptotic proteins Bak and Bax than those from ASA-resistant patients, although only Bak protein remained different when the results were adjusted by age. In resting platelets, neither caspase-3 activity nor cytosolic cytochrome C levels were different between both experimental groups. Stimulation of platelets with calcium ionophore (10 nmol/L, A23187) increased caspase-3 activity (1.91-fold higher; P < 0.05) and cytosolic cytochrome C levels (1.84-fold higher; P < 0.05) to a higher degree in ASA-sensitive than in ASA-resistant platelets. In conclusion, ASA-sensitive platelets seem to be better prepared to undergo apoptosis during robust platelet activation.

Novel Respiratory Disability Score Predicts COPD Exacerbations and Mortality in the SPIROMICS Cohort.

Rationale: Some COPD patients develop extreme breathlessness, decreased exercise capacity and poor health status yet respiratory disability is poorly characterized as a distinct phenotype. Objective: To define respiratory disability in COPD based on available functional measures and to determine associations with risk for exacerbations and death. Methods: We analyzed baseline data from a multi-center observational study (SPIROMICS). This analysis includes 2332 participants (472 with severe COPD, 991 with mild/moderate COPD, 726 smokers without airflow obstruction and 143 non-smoking controls). Measurements: We defined respiratory disability by ≥4 of 7 criteria: mMRC dyspnea scale ≥3; Veterans Specific Activity Questionnaire <5; 6-minute walking distance <250 m; St George's Respiratory Questionnaire activity domain >60; COPD Assessment Test >20; fatigue (FACIT-F Trial Outcome Index) <50; SF-12 <20. Results: Using these criteria, respiratory disability was identified in 315 (13.5%) participants (52.1% female). Frequencies were severe COPD 34.5%; mild-moderate COPD 11.2%; smokers without obstruction 5.2% and never-smokers 2.1%. Compared with others, participants with disability had more emphysema (13.2 vs. 6.6%) and air-trapping (37.0 vs. 21.6%) on HRCT (P<0.0001). Using principal components analysis to derive a disability score, two factors explained 71% of variance, and a cut point -1.0 reliably identified disability. This disability score independently predicted future exacerbations (ß=0.34; CI 0.12, 0.64; P=0.003) and death (HR 2.97; CI 1.54, 5.75; P=0.001). Thus, participants with disability by this criterion had almost three times greater mortality compared to those without disability. Conclusion: Our novel SPIROMICS respiratory disability score in COPD was associated with worse airflow obstruction as well as airway wall thickening, lung parenchymal destruction and certain inflammatory biomarkers. The disability score also proved to be an independent predictor of future exacerbations and death. These findings validate disability as an important phenotype in the spectrum of COPD.

A New Technique for Percutaneous Nephrolithotomy Using Retrograde Ureteroscopy and Laser Fiber to Achieve Percutaneous Nephrostomy Access: The Initial Case Report.

Background: Percutaneous nephrolithotomy (PCNL) serves as the gold standard minimally invasive procedure to remove large renal stones. The puncture is made from the skin to the chosen calix under fluoroscopic guidance, although this remains a challenging technique. We describe the initial case of retrograde holmium laser acquired nephrostomy access. Case Presentation: In this study, we present the case of a 48-year-old woman with right renal colic with imaging revealing a 2.6 cm staghorn stone. With institutional approval, we performed a new technique utilizing retrograde access with a flexible ureteroscope and a holmium laser fiber to achieve nephrostomy access for PCNL in the prone position. With the ureteroscope confirmed in the desired calix, the ureteroscope and laser fiber were aimed and fired toward the flank and thus creating a subcostal nephrostomy tract. PCNL was then carried out per standard of care lithotripsy techniques utilizing the holmium laser. Conclusion: In this initial case, percutaneous retrograde laser access allowed for desired caliceal nephrostomy access under direct vision.

Frailty and geriatric conditions in older patients with idiopathic pulmonary fibrosis.

BACKGROUND: Functional status, an important predictor of health outcomes in older patients, has not been studied in an IPF population. This study aimed to determine the prevalence of frailty and geriatric conditions in older patients with IPF. METHODS: IPF patients age ≥65 years were identified prospectively at the University of Michigan. Frailty was assessed using the Fried frailty phenotype. Questionnaires addressing functional status, geriatric conditions and symptoms were administered. Quantitative measurement of pectoralis muscle area was performed. Patient variables were compared among different frailty groups. RESULTS: Of the 50 participants, 48% were found to be frail and 40% had ≥2 geriatric conditions. Frailty was associated with increased age, lower lung function, shorter 6-min walk distance, higher symptom scores and a greater number of comorbidities, geriatric conditions and functional limitations (p < 0.05). Pectoralis muscle area was nearly significant (p = 0.08). Self-reported fatigue score (odds ratio [OR] = 2.13, confidence interval [CI] 95% 1.23-3.70, p = 0.0068) and diffusion capacity (OR = 0.54 CI 95% 0.35-0.85, p = 0.0071) were independent predictors of frailty. CONCLUSIONS: Frailty and geriatric conditions are common in older patients with IPF. The presence of frailty was associated with objective (diffusion capacity) and subjective (self-reported fatigue score) data. Longitudinal evaluation is necessary to determine impact of frailty on disease-related outcomes in IPF.

Reprint of: Voxel-Wise Longitudinal Parametric Response Mapping Analysis of Chest Computed Tomography in Smokers.

RATIONALE AND OBJECTIVES: Chronic obstructive pulmonary disease is a heterogeneous disease characterized by small airway abnormality and emphysema. We hypothesized that a voxel-wise computed tomography analytic approach would identify patterns of disease progression in smokers. MATERIALS AND METHODS: We analyzed 725 smokers in spirometric GOLD stages 0-4 with two chest CTs 5 years apart. Baseline inspiration, follow-up inspiration and follow-up expiration images were spatially registered to baseline expiration so that each voxel had correspondences across all time points and respiratory phases. Voxel-wise Parametric Response Mapping (PRM) was then generated for the baseline and follow-up scans. PRM classifies lung as normal, functional small airway disease (PRMfSAD), and emphysema (PRMEMPH). RESULTS: Subjects with low baseline PRMfSAD and PRMEMPH predominantly had an increase in PRMfSAD on follow-up; those with higher baseline PRMfSAD and PRMEMPH mostly had increases in PRMEMPH. For GOLD 0 participants (n = 419), mean 5-year increases in PRMfSAD and PRMEMPH were 0.3% for both; for GOLD 1-4 participants (n = 306), they were 0.6% and 1.6%, respectively. Eighty GOLD 0 subjects (19.1%) had overall radiologic progression (30.0% to PRMfSAD, 52.5% to PRMEMPH, and 17.5% to both); 153 GOLD 1-4 subjects (50.0%) experienced progression (17.6% to PRMfSAD, 48.4% to PRMEMPH, and 34.0% to both). In a multivariable model, both baseline PRMfSAD and PRMEMPH were associated with development of PRMEMPH on follow-up, although this relationship was diminished at higher levels of baseline PRMEMPH. CONCLUSION: A voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease.

Mortality and Exacerbations by Global Initiative for Chronic Obstructive Lung Disease Groups ABCD: 2011 Versus 2017 in the COPDGene® Cohort.

Background: The Global initiative for chronic Obstructive Lung Disease (GOLD) ABCD groupings were recently modified. The GOLD 2011 guidelines defined increased risk as forced expiratory volume in 1 second (FEV1) < 50% predicted or ≥ 2 outpatient or ≥ 1 hospitalized exacerbation in the prior year, whereas the GOLD 2017 guidelines use only exacerbation history. We compared mortality and exacerbation rates in the Genetic Epidemiology of COPD Study cohort (COPDGene®) by 2011 (exacerbation history/FEV1 and dyspnea) versus 2017 (exacerbations and dyspnea) classifications. Methods: Using data from COPDGene®, we tested associations of ABCD groups with all-cause mortality (Cox models, adjusted for age, sex, race and comorbidities) and longitudinal exacerbations (zero-inflated Poisson models). Results: In 4469 individuals (mean age 63.1 years, 44% female), individual distributions in 2011 versus 2017 systems were: A, 32.0% versus 37.0%; B, 17.6% versus 36.3%; C, 9.4% versus 4.4%; D, 41.0% versus 22.3%; (observed agreement 76% [expected 27.8%], Kappa 0.67, p<0.001). Individuals in group D-2011 had 1.1 ± 1.6 exacerbations/year (mean ± standard deviation [SD]) versus 1.4 ± 1.8 for D-2017 (median follow-up 3.7 years). Using group A as reference, for both systems, mortality (median follow-up 6.8 years) was highest in group D (D-2011, [hazard ratio] HR 5.2 [95% confidence interval (CI) 4.2, 6.4]; D-2017, HR 5.5 [4.5, 6.8]), lowest for group C (HR 1.9 [1.4, 2.6] versus HR 1.9 [1.3, 2.8]) and intermediate for group B (HR 2.6 [2.0, 3.4] versus HR 3.4 [2.8, 4.1]). GOLD 2011 had better mortality discrimination (area under the curve [AUC] 0.68) than GOLD 2017 (AUC 0.66, p<0.001 for comparison) but similar exacerbation rate prediction. Conclusions: Relative to the GOLD 2011 consensus statement, discriminate predictive power of the 2017 ABCD classification is similar for exacerbations but lower for survival.

Symptoms of anxiety and depression and use of anxiolytic-hypnotics and antidepressants in current and former smokers with and without COPD - A cross sectional analysis of the COPDGene cohort.

OBJECTIVES: To compare the frequency of anxiety/depressive symptoms and use of anxiolytic-hypnotics/antidepressants in smokers with and without COPD and to identify characteristics associated with having unmedicated symptoms. METHODS: Cross-sectional analysis of ambulatory, current/former smokers ≥10 pack years enrolled in the COPDGene study. We measured anxiety/depressive symptoms using the Hospital Anxiety and Depression Scale (subscales ≥8), recorded anxiolytic-hypnotic/antidepressant use, and defined unmedicated symptoms as elevated anxiety/depressive symptoms and not on medications. Regression analysis identified characteristics associated with having unmedicated symptoms. KEY RESULTS: Of 5331 current/former smokers (45% with and 55% without COPD), 1332 (25.0%) had anxiety/depressive symptoms. Anxiety symptoms were similar in frequency in smokers with and without COPD (19.7% overall), while depressive symptoms were most frequent in severe-very severe COPD at 20.7% (13.1% overall). In the entire cohort, 1135 (21.2%) were on medications. Anxiolytic-hypnotic use was highest in severe-very severe COPD (range 7.6%-12.0%), while antidepressant use showed no significant variation in smokers with and without COPD (range 14.7%-17.1%). Overall, 881 (66% of those with symptoms) had unmedicated symptoms, which was associated with African American race (adjusted OR 2.95, 95% CI 2.25-3.87), male gender (adjusted OR 1.93, 95% CI 1.57-2.36), no health insurance (adjusted OR 2.38, 95% CI 1.30-4.35), severe-very severe COPD (adjusted OR 1.48, 95% CI 1.04-2.11), and higher respiratory symptoms/exacerbation history (adjusted OR 2.21, 95% CI 1.62-3.02). CONCLUSIONS: Significant unmet mental health care needs exist in current and former smokers with and without COPD. One in five have unmedicated symptoms, identified by key demographic and clinical characteristics. PRIMARY FUNDING SOURCE: National Institutes of Health and The COPD Foundation.

Voxel-Wise Longitudinal Parametric Response Mapping Analysis of Chest Computed Tomography in Smokers.

RATIONALE AND OBJECTIVES: Chronic obstructive pulmonary disease is a heterogeneous disease characterized by small airway abnormality and emphysema. We hypothesized that a voxel-wise computed tomography analytic approach would identify patterns of disease progression in smokers. MATERIALS AND METHODS: We analyzed 725 smokers in spirometric GOLD stages 0-4 with two chest CTs 5 years apart. Baseline inspiration, follow-up inspiration and follow-up expiration images were spatially registered to baseline expiration so that each voxel had correspondences across all time points and respiratory phases. Voxel-wise Parametric Response Mapping (PRM) was then generated for the baseline and follow-up scans. PRM classifies lung as normal, functional small airway disease (PRMfSAD), and emphysema (PRMEMPH). RESULTS: Subjects with low baseline PRMfSAD and PRMEMPH predominantly had an increase in PRMfSAD on follow-up; those with higher baseline PRMfSAD and PRMEMPH mostly had increases in PRMEMPH. For GOLD 0 participants (n = 419), mean 5-year increases in PRMfSAD and PRMEMPH were 0.3% for both; for GOLD 1-4 participants (n = 306), they were 0.6% and 1.6%, respectively. Eighty GOLD 0 subjects (19.1%) had overall radiologic progression (30.0% to PRMfSAD, 52.5% to PRMEMPH, and 17.5% to both); 153 GOLD 1-4 subjects (50.0%) experienced progression (17.6% to PRMfSAD, 48.4% to PRMEMPH, and 34.0% to both). In a multivariable model, both baseline PRMfSAD and PRMEMPH were associated with development of PRMEMPH on follow-up, although this relationship was diminished at higher levels of baseline PRMEMPH. CONCLUSION: A voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease.

Heterogeneous burden of lung disease in smokers with borderline airflow obstruction.

BACKGROUND: The identification of smoking-related lung disease in current and former smokers with normal FEV1 is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) of less than 0.70 versus the predicted lower limit of normal (LLN) for diagnosis of airflow obstruction. We hypothesized that the discordant group of ever-smokers with FEV1/FVC between the LLN and 0.70 is heterogeneous, and aimed to characterize the burden of smoking-related lung disease in this group. METHODS: We compared spirometry, chest CT characteristics, and symptoms between 161 ever-smokers in the discordant group and 940 ever-smokers and 190 never-smokers with normal FEV1 and FEV1/FVC > 0.70 in the SPIROMICS cohort. We also estimated sensitivity and specificity for diagnosing objective radiographic evidence of chronic obstructive pulmonary disease (COPD) using different FEV1/FVC criteria thresholds. RESULTS: The discordant group had more CT defined emphysema and non-emphysematous gas trapping, lower post-bronchodilator FEV1 and FEF25-75, and higher respiratory medication use compared with the other two groups. Within the discordant group, 44% had radiographic CT evidence of either emphysema or non-emphysematous gas trapping; an FEV1/FVC threshold of 0.70 has greater sensitivity but lower specificity compared with LLN for identifying individuals with CT abnormality. CONCLUSIONS: Ever-smokers with normal FEV1 and FEV1/FVC <  0.70 but > LLN are a heterogeneous group that includes significant numbers of individuals with and without radiographic evidence of smoking-related lung disease. These findings emphasize the limitations of diagnosing COPD based on spirometric criteria alone.

Pulmonary vascular pruning in smokers with bronchiectasis.

There are few studies looking at the pulmonary circulation in subjects with bronchiectasis. We aimed to evaluate the intraparenchymal pulmonary vascular structure, using noncontrast chest computed tomography (CT), and its clinical implications in smokers with radiographic bronchiectasis. Visual bronchiectasis scoring and quantitative assessment of the intraparenchymal pulmonary vasculature were performed on CT scans from 486 smokers. Clinical, lung function and 6-min walk test (6MWT) data were also collected. The ratio of blood vessel volume in vessels <5 mm2 in cross-section (BV5) to total blood vessel volume (TBV) was used as measure of vascular pruning, with lower values indicating more pruning. Whole-lung and lobar BV5/TBV values were determined, and regression analyses were used to assess the differences in BV5/TBV between subjects with and without bronchiectasis. 155 (31.9%) smokers had bronchiectasis, which was, on average, mild in severity. Compared to subjects without bronchiectasis, those with lower-lobe bronchiectasis had greater vascular pruning in adjusted models. Among subjects with bronchiectasis, those with vascular pruning had lower forced expiratory volume in 1 s and 6MWT distance compared to those without vascular pruning. Smokers with mild radiographic bronchiectasis appear to have pruning of the distal pulmonary vasculature and this pruning is associated with measures of disease severity.

NT-proBNP in stable COPD and future exacerbation risk: Analysis of the SPIROMICS cohort.

BACKGROUND: High N-terminal pro-brain natriuretic peptide (NT-proBNP) during COPD exacerbations is associated with worse clinical outcomes. The prognostic value of NT-proBNP measured during clinical stability has not been well characterized. METHODS: We studied SPIROMICS participants 40-80 years of age with COPD GOLD spirometric stages 1-4. The association between baseline NT-proBNP and incident COPD exacerbations within one year of follow-up was tested using zero-inflated Poisson regression models adjusted for age, gender, race, body mass index, current smoking status, smoking history, FEV1 percent predicted, COPD Assessment Test score, exacerbation history, total lung capacity on chest CT and cardiovascular disease (any of coronary artery disease, myocardial infarction or congestive heart failure). RESULTS: Among 1051 participants (mean age 66.1 years, 41.4% women), mean NT-proBNP was 608.9 pg/ml. Subjects in GOLD stage D had the highest mean NT-proBNP. After one year of follow-up, 268 participants experienced one or more COPD exacerbations. One standard deviation increase in baseline NT-proBNP was associated with a 13% increase in the risk of incident exacerbations (incident risk ratio 1.13; 95% CI 1.06-1.19; p < 0.0001). This association was maintained in participants with and without cardiovascular disease. CONCLUSION: Baseline NT-proBNP in COPD is an independent predictor of respiratory exacerbations, even in individuals without overt cardiac disease. The impact of detection and treatment of early cardiovascular dysfunction on COPD exacerbation frequency warrants further investigation.

Visual Estimate of Coronary Artery Calcium Predicts Cardiovascular Disease in COPD.

BACKGROUND: COPD is associated with cardiovascular disease (CVD), and coronary artery calcification (CAC) provides additional prognostic information. With increasing use of nongated CT scans in clinical practice, this study hypothesized that the visual Weston CAC score would perform as well as the Agatston score in predicting prevalent and incident coronary artery disease (CAD) and CVD in COPD. METHODS: CAC was measured by using Agatston and Weston scores on baseline CT scans in 1,875 current and former smokers enrolled in the Genetic Epidemiology of COPD (COPDGene) study. Baseline cardiovascular disease and incident cardiac events on longitudinal follow-up were recorded. Accuracy of the CAC scores was measured by using receiver-operating characteristic analysis, and Cox proportional hazards analyses were used to estimate the risk of incident cardiac events. RESULTS: CAD was reported by 133 (7.1%) subjects at baseline. A total of 413 (22.0%) and 241 (12.9%) patients had significant CAC according to the Weston (≥ 7) and Agatston (≥ 400) scores, respectively; the two methods were significantly correlated (r = 0.84; P < .001). Over 5 years of follow-up, 127 patients (6.8%) developed incident CVD. For predicting prevalent CAD, c-indices for the Weston and Agatston scores were 0.78 and 0.74 and for predicting incident CVD, they were 0.62 and 0.61. After adjustment for age, race, sex, smoking pack-years, FEV1, percent emphysema, and CT scanner type, a Weston score ≥ 7 was associated with time to first acute coronary event (hazard ratio, 2.16 [95% CI, 1.32 to 3.53]; P = .002), but a Agatston score ≥ 400 was not (hazard ratio, 1.75 [95% CI, 0.99-3.09]; P = .053). CONCLUSIONS: A simple visual score for CAC performed well in predicting incident CAD in smokers with and without COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Pectoralis muscle area and mortality in smokers without airflow obstruction.

BACKGROUND: Low muscle mass is associated with increased mortality in the general population but its prognostic value in at-risk smokers, those without expiratory airflow obstruction, is unknown. We aimed to test the hypothesis that reduced muscle mass is associated with increased mortality in at-risk smokers. METHODS: Measures of both pectoralis and paravertebral erector spinae muscle cross-sectional area (PMA and PVMA, respectively) as well as emphysema on chest computed tomography (CT) scans were performed in 3705 current and former at-risk smokers (≥10 pack-years) aged 45-80 years enrolled into the COPDGene Study between 2008 and 2013. Vital status was ascertained through death certificate. The association between low muscle mass and mortality was assessed using Cox regression analysis. RESULTS: During a median of 6.5 years of follow-up, 212 (5.7%) at-risk smokers died. At-risk smokers in the lowest (vs. highest) sex-specific quartile of PMA but not PVMA had 84% higher risk of death in adjusted models for demographics, smoking, dyspnea, comorbidities, exercise capacity, lung function, emphysema on CT, and coronary artery calcium content (hazard ratio [HR] 1.85 95% Confidence interval [1.14-3.00] P = 0.01). Results were consistent when the PMA index (PMA/height2) was used instead of quartiles. The association between PMA and death was modified by smoking status (P = 0.04). Current smokers had a significantly increased risk of death (lowest vs. highest PMA quartile, HR 2.25 [1.25-4.03] P = 0.007) while former smokers did not. CONCLUSIONS: Low muscle mass as measured on chest CT scans is associated with increased mortality in current smokers without airflow obstruction. TRIAL REGISTRATION: NCT00608764.

Handgrip Strength in Chronic Obstructive Pulmonary Disease. Associations with Acute Exacerbations and Body Composition.

RATIONALE: Handgrip strength (HGS) predicts mortality in the elderly, but its determinants and clinical significance in chronic obstructive pulmonary disease (COPD) has not been defined. OBJECTIVES: We tested associations of HGS with pectoralis muscle area (PMA), subcutaneous adipose tissue (SAT), imaging characteristics, and lung function in smokers with COPD, and evaluated the cross-sectional and longitudinal associations of HGS with acute respiratory events. METHODS: We analyzed demographic, clinical, spirometry, HGS, and imaging data of 272 subjects with COPD, obtaining measures of airway thickness, emphysema, PMA, and SAT from chest computed tomography scans. We tested associations of lung function and imaging characteristics with HGS, using linear models. HGS association to acute respiratory events at enrollment and during follow-up (mean, 2.6 years) was analyzed using adjusted logistic models. RESULTS: HGS correlated with PMA, SAT, forced expiratory volume, and airway thickness, but not with body mass index or emphysema severity. In adjusted regression models, HGS was directly (ß, 1.5; 95% confidence interval [CI], 0.1-3.0) and inversely (ß, -3.3; 95% CI, -5.1 to -0.9) associated with one standard deviation of PMA and SAT, respectively, independent of body mass index and emphysema. In regression models adjusted for age, sex, body mass index, race, pack-years smoked, current smoking, chronic bronchitis, FEV1% predicted, emphysema, and airway metrics, HGS was associated with exacerbation risk; in cross-sectional analyses, there was an increment of 5% in the risk of exacerbations for each 1-kg decrement in HGS (risk ratio, 1.05; 95% CI, 1.01-1.08), and there was a similar risk during follow-up (risk ratio, 1.04; 95% CI, 1.01-1,07). CONCLUSIONS: In ever-smokers with COPD, HGS is associated with computed tomography markers of body composition and airway thickness, independent of body mass index and emphysema. Higher HGS is associated with lower exacerbation frequency.