Chronotropic incompetence predicts mortality in severe obstructive pulmonary disease

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

Can CAPTURE Be Used to Identify Undiagnosed Patients with Mild-To-Moderate COPD Likely to Benefit from Treatment?

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)11 60%–80% predicted) who may also benefit from diagnosis and treatment. Methods: Data from the CAPTURE development study were used to test its sensitivity (SN) and specificity (SP) differentiating mild-to-moderate COPD (n=73) from no COPD (n=87). SN and SP for differentiating all COPD cases (mild to severe; n=259) from those without COPD (n=87) were also estimated. The modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT™) were used to evaluate symptoms and health status. Clinical Trial Registration: NCT01880177, https://ClinicalTrials.gov/ct2/show/NCT01880177?term=NCT01880177&rank=1. Results: Mean age (+SD): 61 (+10.5) years; 41% male. COPD: FEV1/FVC=0.60 (+0.1), FEV1% predicted=74% (+12.4). SN and SP for differentiating mild-to-moderate and non-COPD patients (n=160): Questionnaire: 83.6%, 67.8%; PEF (≤450 L/min; ≤350 L/min): 83.6%, 66.7%; CAPTURE (Questionnaire+PEF): 71.2%, 83.9%. COPD patients whose CAPTURE results suggested that diagnostic evaluation was warranted (n=52) were more likely to be symptomatic than patients whose results did not (n=21) (mMRC \u3e2: 37% vs 5%, p10: 86% vs 57%, p Conclusion: CAPTURE (450/350) may be useful for identifying symptomatic patients with mild-to-moderate airflow obstruction in need of diagnostic evaluation for COPD

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Feasibility and Acceptability of Utilizing a Smartphone Based Application to Monitor Outpatient Discharge Instruction Compliance in Cardiac Disease Patients around Discharge from Hospitalization

The purpose of this study was to determine the feasibility and acceptability of utilizing a smartphone based application to monitor compliance in patients with cardiac disease around discharge. For 60 days after discharge, patients’ medication compliance, physical activity, follow-up care, symptoms, and reading of education material were monitored daily with the application. 16 patients were enrolled in the study (12 males, 4 females, age 55 ± 18 years) during their hospital stay. Five participants were rehospitalized during the study and did not use the application once discharged. Seven participants completed 1–30 days and four patients completed >31 days. For those 11 patients, medication reminders were utilized 37% (1–30-day group) and 53% (>31-day group) of the time, education material was read 44% (1–30) and 53% (>31) of the time, and physical activity was reported 25% (1–30) and 42% (>31) of the time. Findings demonstrated that patients with stable health utilized the application, even if only minimally. Patients with decreased breath sounds by physical exam and who reported their health as fair to poor on the day of discharge were less likely to utilize the application. Acceptability of the application to report health status varied among the stable patients

Comorbidities in Chronic Obstructive Pulmonary Disease

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

Optimizing Bronchodilator Therapy in Emphysema

The treatment objectives for chronic obstructive pulmonary disease (COPD) include relieving symptoms such as dyspnea and cough, slowing the accelerated decline in lung function, decreasing exacerbations, and improving quality of life. All major guidelines for COPD management recommend beginning treatment with bronchodilators. There are several classes of bronchodilators, including β-agonists, anticholinergics, and phosphodiesterase inhibitors, each with a specific mechanism of action. The overall approach to managing stable COPD involves a stepwise increase in treatment. Because of the progressive nature of emphysema, such an approach often involves combining bronchodilators from different pharmacologic classes. This review focuses on the pharmacologic properties of various bronchodilators and on recent studies that have examined combination therapy as a means to optimize treatment

Introducing the COPD Foundation Guide for Diagnosis and Management of COPD, Recommendations of the COPD Foundation

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). Read More: http://informahealthcare.com/doi/abs/10.3109/15412555.2013.80130

Questionnaires and pocket spirometers provide an alternative approach for COPD screening in the general population

Background: 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. Methods: 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 was \u3c 70% predicted, spirometry was performed. In order to estimate the false-negative rate, a random sample of every 10th participant was also selected for spirometry. Results: 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 PEF \u3c 70% 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 FEV1/FEV6 \u3c the lower limit of normal and FEV1 \u3c 60% predicted. Of 4,238 subjects with at least two risk factors, 267 (6.3%) had PEF \u3c 70%, compared with 48 of the 1,400 subjects (3.4%) with fewer than two risk factors (P \u3c .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 \u3c .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. Conclusions: A staged approach to COPD screening in adults is useful for detecting clinically significant airflow obstruction in our study population