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Chronic obstructive pulmonary disease patient care must include confirming a diagnosis with postbronchodilator spirometry. Because of the clinical heterogeneity and the reality that airflow obstruction assessed by spirometry only partially reflects disease severity, a thorough clinical evaluation of the patient should include assessment of symptom burden and risk of exacerbations that permits the implementation of evidence-informed pharmacologic and nonpharmacologic interventions. This guideline provides recommendations from a comprehensive systematic review with a meta-analysis and expert-informed clinical remarks to optimize maintenance pharmacologic therapy for individuals with stable COPD, and a revised and practical treatment pathway based on new evidence since the 2019 update of the Canadian Thoracic Society (CTS) Guideline. The key clinical questions were developed using the Patients/Population (P), Intervention(s) (I), Comparison/Comparator (C), and Outcome (O) model for three questions that focuses on the outcomes of symptoms (dyspnea)/health status, acute exacerbations, and mortality. The evidence from this systematic review and meta-analysis leads to the recommendation that all symptomatic patients with spirometry-confirmed COPD should receive long-acting bronchodilator maintenance therapy. Those with moderate to severe dyspnea (modified Medical Research Council ≥ 2) and/or impaired health status (COPD Assessment Test ≥ 10) and a low risk of exacerbations should receive combination therapy with a long-acting muscarinic antagonist/long-acting ẞ2-agonist (LAMA/LABA). For those with a moderate/severe dyspnea and/or impaired health status and a high risk of exacerbations should be prescribed triple combination therapy (LAMA/LABA/inhaled corticosteroids) azithromycin, roflumilast or N-acetylcysteine is recommended for specific populations; a recommendation against the use of theophylline, maintenance systemic oral corticosteroids such as prednisone and inhaled corticosteroid monotherapy is made for all COPD patients. [ABSTRACT FROM AUTHOR]

Individuals with COPD and preserved ratio impaired spirometry (PRISm) findings in clinical settings have an increased risk of cardiovascular disease (CVD). Do individuals with mild to moderate or worse COPD and PRISm findings in community settings have a higher prevalence and incidence of CVD compared with individuals with normal spirometry findings? Can CVD risk scores be improved when impaired spirometry is added? The analysis was embedded in the Canadian Cohort Obstructive Lung Disease (CanCOLD). Prevalence of CVD (ischemic heart disease [IHD] and heart failure [HF]) and their incidence over 6.3 years were compared between groups with impaired and normal spirometry findings using logistic regression and Cox models, respectively, adjusting for covariables. Discrimination of the pooled cohort equations (PCE) and Framingham risk score (FRS) in predicting CVD were assessed with and without impaired spirometry. Participants (n = 1,561) included 726 people with normal spirometry findings and 835 people with impaired spirometry findings (COPD Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 disease, n = 408; GOLD stage ≥ 2, n = 331; PRISm findings, n = 96). Rates of undiagnosed COPD were 84% in GOLD stage 1 and 58% in GOLD stage ≥ 2 groups. Prevalence of CVD (IHD or HF) was significantly higher among individuals with impaired spirometry findings and COPD compared with those with normal spirometry findings, with ORs of 1.66 (95% CI, 1.13-2.43; P =.01∗) (∗ indicates statistical significane with P <.05) and 1.55 (95% CI, 1.04-2.31; P =.033∗), respectively. Prevalence of CVD was significantly higher in participants having PRISm findings and COPD GOLD stage ≥ 2, but not GOLD stage 1. CVD incidence was significantly higher, with hazard ratios of 2.07 (95% CI, 1.10-3.91; P =.024∗) for the impaired spirometry group and 2.09 (95% CI, 1.10-3.98; P =.024∗) for the COPD group compared to individuals with normal spirometry findings. The difference was significantly higher among individuals with COPD GOLD stage ≥ 2, but not GOLD stage 1. The discrimination for predicting CVD was low and limited when impaired spirometry findings were added to either risk score. Individuals with impaired spirometry findings, especially those with moderate or worse COPD and PRISm findings, have increased comorbid CVD compared with their peers with normal spirometry findings, and having COPD increases the risk of CVD developing. [ABSTRACT FROM AUTHOR]

Contemporary management of COPD relies on exacerbation history to risk-stratify patients for future exacerbations. Multivariable prediction models can improve the performance of risk stratification. However, the clinical utility of risk stratification can vary from one population to another. How do two validated exacerbation risk prediction models (Acute COPD Exacerbation Prediction Tool [ACCEPT] and the Bertens model) compared with exacerbation history alone perform in different patient populations? We used data from three clinical studies representing populations at different levels of moderate to severe exacerbation risk: the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421; annual risk, 0.22), the Long-term Oxygen Treatment Trial (LOTT; N = 595; annual risk, 0.38), and Towards a Revolution in COPD Health (TORCH; N = 1,091; annual risk, 0.52). We compared the area under the receiver operating characteristic curve (AUC) and net benefit (measure of clinical utility) among three risk stratification algorithms for predicting exacerbations in the next 12 months. We also evaluated the effect of model recalibration on clinical utility. Compared with exacerbation history, ACCEPT showed better performance in all three samples (change in AUC, 0.08, 0.07, and 0.10, in SUMMIT, LOTT, and TORCH, respectively; P ≤.001 for all). The Bertens model showed better performance compared with exacerbation history in SUMMIT and TORCH (change in AUC, 0.10 and 0.05, respectively; P <.001 for both), but not in LOTT. No algorithm was superior in clinical utility across all samples. Before recalibration, the Bertens model generally outperformed the other algorithms in low-risk settings, whereas ACCEPT outperformed others in high-risk settings. All three algorithms showed the risk of harm (providing lower net benefit than not using any risk stratification). After recalibration, risk of harm was mitigated substantially for both prediction models. Exacerbation history alone is unlikely to provide clinical utility for predicting COPD exacerbations in all settings and could be associated with a risk of harm. Prediction models have superior predictive performance, but require setting-specific recalibration to confer higher clinical utility. [ABSTRACT FROM AUTHOR]

Asthma-COPD overlap (ACO) is a heterogeneous condition that describes patients who show persistent airflow limitation with clinical features that support both asthma and COPD. Although no single consensus definition exists to diagnose this entity, common major criteria include a strong bronchodilator reversibility or bronchial hyperreactivity, a physician diagnosis of asthma, and a ≥ 10-pack-year cigarette smoking history. The prevalence of ACO ranges from 0.9% to 11.1% in the general population, depending on the diagnostic definition used. Notably, patients with ACO experience greater symptom burden, worse quality of life, and more frequent and severe respiratory exacerbations than those with asthma or COPD. The underlying pathophysiologic features of ACO have been debated. Although emerging evidence supports the role of environmental and inhalational exposures in its pathogenesis among patients with a pre-existing airway disease, biomarker profiling and genetic analyses suggest that ACO may be a heterogeneous condition, but with definable characteristics. Early-life factors including childhood-onset asthma and cigarette smoking may interact to increase the risk of airflow obstruction later in life. For treatment options, the population with ACO historically has been excluded from therapeutic trials; therefore strong, evidence-based recommendations are lacking beyond first-line inhaler therapies. Advanced therapies in patients with ACO are selected according to disease phenotypes and are based on extrapolated data from asthma and COPD. Research focused on defining biomarkers and evidence-based treatment options for ACO is needed urgently. [ABSTRACT FROM AUTHOR]

Background: Prediction of future lung function will enable the identification of individuals at high risk of developing COPD, but the trajectory of lung function decline varies greatly among individuals. This study involved the development and validation of an individualized prediction model of lung function trajectory and risk of airflow limitation in the general population.Methods: Data were obtained from the Framingham Offspring Cohort, which included 4,167 participants ≥ 20 years of age and who had ≥ 2 valid spirometry assessments. The primary outcome was prebronchodilator FEV1; the secondary outcome was the risk of airflow limitation (defined as FEV1/FVC less than the lower limit of normal). Mixed effects regression models were developed for individualized prediction, and a machine learning algorithm was used to determine essential predictors. The model was validated in two large, independent multicenter cohorts (N = 2,075 and 12,913, respectively).Results: With 20 common predictors, the model explained 79% of the variation in FEV1 decline in the derivation cohort. In two validation datasets, the model had low error in predicting FEV1 decline (root mean square error range, 0.18-0.22 L) and high discriminative power in predicting risk of airflow limitation (C-statistic range, 0.86-0.87). This model was implemented in a freely accessible website-based application, which allows prediction based on flexible sets of predictors (http://resp.core.ubc.ca/ipress/FraminghamFEV1).Conclusions: The individualized predictor is an accurate tool to predict long-term lung function trajectories and risk of airflow limitation in the general population. This model enables identifying individuals at higher risk of COPD, who can then be targeted for preventive therapies. [ABSTRACT FROM AUTHOR]

Background: COPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations.Methods: Data were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18 months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change ≥ 48 h) and event-based (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed.Results: A total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score > 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs 5.0 [interquartile range, 2.0-7.0]; P = .01), and they were more likely to have baseline PSQI scores > 5 (50.3% vs 37.3%; P = .01). Higher PSQI scores were associated with increased symptom-based exacerbation risk (adjusted rate ratio, 1.09; 95% CI, 1.01-1.18; P = .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95% CI, 1.00-1.21; P = .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95% CI, 1.09-2.03).Conclusions: Higher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18 months' prospective follow-up. [ABSTRACT FROM AUTHOR]

Background: Azithromycin reduces pulmonary exacerbation (PEx) risk in cystic fibrosis (CF), but not all individuals benefit. The goal of this study was to discover blood protein biomarkers predictive of clinical response to azithromycin treatment in children and adolescents with CF.Methods: Novel proteomic technologies were applied to examine 188 serum and plasma protein samples from 40 patients with CF who were randomized to receive azithromycin in the AZ0004 trial. Early changes in blood protein levels from day 0 to day 28 of treatment were examined in relation to changes in FEV1 percent predicted and weight by days 28 and 168, and to predict PEx risk by day 168.Results: Early changes in the levels of 15 plasma proteins following 28 days of azithromycin significantly correlated with changes in FEV1 percent predicted from day 0 to day 28 (Q value < 0.10), but this finding was not sustained to day 168. Early changes in serum calprotectin levels following 28 days of azithromycin were predictive of PEx risk by day 168 of treatment (area under the curve = 0.76; 95% CI, 0.57-0.95). Based on a calprotectin cutoff to maximize test sensitivity (88%) and specificity (68%), 40% of subjects who had a calprotectin reduction less than the cutoff experienced at least one PEx compared with only 8% of subjects with calprotectin reduction greater than the cutoff.Conclusions: Early changes in blood protein biomarkers following azithromycin treatment were associated with short-term changes, but not longer term changes, in lung function. Early change in serum calprotectin level was predictive of response to azithromycin in terms of modifying PEx risk. [ABSTRACT FROM AUTHOR]

Background: COPD is an age-related disease. The role of cellular senescence in COPD has not been fully elucidated. This study examined the relationship between telomere length of peripheral blood leukocytes and clinical outcomes, including health status, rate of exacerbations, and risk of mortality in individuals with COPD.Methods: Using quantitative polymerase chain reaction, we measured the absolute telomere length (aTL) of DNA extracted from blood samples of 576 participants with moderate-to-severe COPD treated with either azithromycin or placebo for 12 months in the Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO) study. All participants were followed for approximately 13 months, during which time health status and exacerbations were carefully ascertained, and an additional 29 months for mortality. The rates of exacerbation and mortality were determined by dividing the aTL into two groups using the median value as the cutoff.Results: Participants with shorter telomere length had worse health status defined by higher St. George's Respiratory Questionnaire scores (β = -0.09, P = .034). In the placebo arm of the study, the rate of exacerbation (rate ratio, 1.50; 95% CI, 1.16-1.95; P = .002) and the risk of mortality (hazard ratio, 9.45; 95% CI, 2.85-31.36; P = .015) were significantly higher in the shorter telomere group than in the longer telomere group; these differences were not observed in the azithromycin arm (interaction P = .008 for exacerbation and interaction P = .017 for mortality) CONCLUSIONS: These data suggest that replicative senescence may help to predict poor outcomes in COPD. Shorter leukocyte telomere lengths may represent a clinically translatable biomarker for identifying individuals at increased risk of poor clinical outcomes in COPD. [ABSTRACT FROM AUTHOR]

Background: The BMI, obstruction, dyspnea, and exercise capacity (BODE) score is used to inform prognostic considerations for lung transplantation for COPD, but it has not been validated in this context. A large proportion of mortality in COPD is attributable to comorbidities that could preclude transplant candidacy. We hypothesized that patients with COPD who are selected as transplant candidates experience better survival than traditional interpretation of BODE scores might indicate.Methods: We performed a retrospective analysis of survival according to the BODE score for patients with COPD in the United Network of Organ Sharing (UNOS) database of lung transplantation candidates (n = 4,377) compared with the cohort of patients with COPD in which the BODE score was validated (n = 625).Results: Median survival in the fourth quartile of BODE score was 59 months (95% CI, 51-77 months) in the UNOS cohort and 37 months (95% CI, 29-42 months) in the BODE validation cohort. In models controlling for BODE score and incorporating lung transplantation as a competing end point, the risk of death was higher in the BODE validation cohort (subhazard ratio, 4.8; 95% CI, 4.0-5.7; P < .001). The risk difference was greatest in the fourth quartile of BODE scores (SHR, 6.1; 95% CI, 4.9-7.6; P < .001).Conclusions: Extrapolation of prognosis based on the BODE score overestimates mortality risk in lung transplantation candidates with COPD. This is likely due to a lower prevalence of comorbid conditions attributable to the lung transplantation evaluation screening process. [ABSTRACT FROM AUTHOR]

Background: Patients with COPD are often prescribed statin drugs due to the increased prevalence of cardiovascular disease. There is considerable debate about the benefits conferred by statin drugs in patients with COPD. This study evaluates the association of statin drug use with all-cause and lung-related mortality in patients with COPD.Methods: This study uses population-based administrative data for the province of British Columbia, Canada. A cohort of patients with COPD was identified based on individual patient prescription records. Statin drug exposure was ascertained in the 1-year period after the COPD diagnosis. The primary and secondary outcomes, all-cause and lung-related mortality, respectively, were evaluated in the 1-year period thereafter using multivariate Cox proportional hazards models and several definitions of medication exposure.Results: There were 39,678 patients with COPD that met the study inclusion criteria. Of them, 7,775 (19.6%) had received at least one statin drug dispensed in the exposure ascertainment window. There were 1,446 all-cause deaths recorded in the cohort in the 1-year period after exposure ascertainment. In multivariate analysis, the estimated hazard ratio (HR) for statin drug exposure was 0.79 (95% CI, 0.68-0.92; P = .0016), suggesting a 21% reduction in the risk from statin drug use on all-cause mortality. For lung-related mortality, there was also a considerable reduction in the risk for all-cause mortality from statin drug use (HR, 0.55; 95% CI, 0.32-0.93; P = .0254). These results were robust to different specifications of the exposure ascertainment window.Conclusions: This study shows that statin drug use in a population-based cohort of patients with COPD may confer benefits regarding reduced lung-related and all-cause mortality. [ABSTRACT FROM AUTHOR]

There is a great interest in developing biomarkers to enable precision medicine and improve health outcomes of patients with COPD. However, biomarker development is extremely challenging and expensive, and translation of research endeavors to date has been largely unsuccessful. In most cases, biomarkers fail because of poor replication of initial promising results in independent cohorts and/or inability to transfer the biomarker from a discovery platform to a clinical assay. Ultimately, new biomarker assays must address 5 questions for optimal clinical translation. They include the following: is the biomarker likely to be (1) superior (will the test outperform current standards?); (2) actionable (will the test change patient management?); (3) valuable (will the test improve patient outcomes?); (4) economical (will the implementation of the biomarker in the target population be cost-saving or cost-effective?); and (5) clinically deployable (is there a pathway for the biomarker and analytical technology to be implemented in a clinical laboratory?)? In this article we review some of the major barriers to biomarker development in COPD and provide possible solutions to overcome these limitations, enabling translation of promising biomarkers from discovery experiments to clinical implementation. [ABSTRACT FROM AUTHOR]

Background: Up-to-date estimates of burden of diseases are required for evidence-based decision-making. The objectives of this study were to determine the excess costs of COPD and its trend from 2001 to 2010 in British Columbia, Canada.Methods: We used British Columbia's administrative health data to construct a cohort of patients with COPD and a matched comparison cohort of subjects without COPD. We followed each patient from the time of first COPD-related health-care event (or equivalent time for the comparison cohort). Direct medical costs (in 2010 Canadian dollars [$]) were calculated based on billing records pertaining to hospital admissions, outpatient services use, medication dispensations, and community care services. We determined the excess medical costs of COPD by calculating the difference in overall medical costs between the COPD and the comparison cohorts.Results: The COPD and comparison cohorts comprised 153,570 and 246,801 people, respectively (for both cohorts, mean age at entry was 66.9 years; 47.2% female patients). The excess costs of COPD during the study period were $5,452 per patient-year. Inpatient, outpatient, medication, and community care costs were responsible for 57%, 16%, 22%, and 5% of the excess costs, respectively. Excess costs increased by $296/person-y (P < .01), with hospital costs demonstrating the largest increase over time ($258/person-y; P < .01).Conclusions: The direct economic burden of COPD is high and has increased significantly between 2001 and 2010 over and above the increase in the health-care costs of the general population. Further investigation is required to elucidate the underlying reasons for the temporal increase in COPD direct costs. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a research study conducted to evaluate the relationship between serum bilirubin and chronic obstructive pulmonary disease (COPD) severity and progression in smokers with COPD. Topics covered include the prevalence and management of COPD, details relating to the serum bilirubin measured in the study participants, and the positive relationship of serum bilirubin to lung function and progression rate of airflow limitation in smokers.

The article discusses a study on the systematic review of blood-based biomarkers in cystic fibrosis pulmonary exacerbations (CFPE). The researchers studied a number of blood-based biomarkers including inflammatory cytokines, acute phase reactants and markers of oxidative stress. Results revealed the correlation of C-reactive protein with disease activity and changes in response to CFPE treatment. Several potential biomarkers were identified such as lactoferrin, calprotectin and myeloperoxidase.

Background: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) suppress ambient particulate matter, 10 μm (PM(10) )-induced inflammatory response in vitro. The aim of this study was to determine the effect of statins on PM(10) -induced lung inflammation in vivo.Methods: New Zealand white rabbits were exposed to either PM(10) (1.0 mg/kg) or saline by direct intratracheal instillation three times a week for 4 weeks lovastatin 5.0 mg/kg/d. BAL fluid was assessed for cell counts and proinflammatory cytokine levels. Lung inflammation was quantified using immunohistochemical techniques and morphometric methods. Ex vivo phagocytosis assay of alveolar macrophages using PM 10 particles was performed. Distribution of PM(10) particles in lung tissues and draining lymph nodes was quantified morphometrically to evaluate the clearance of PM(10) particles.Results: PM(10) exposure increased the production of IL-6 and IL-8, promoted the recruitment of macrophages and polymorphonuclear leukocytes into the lung, and activated these recruited leukocytes. Lovastatin significantly suppressed all these effects. Lovastatin increased the phagocytic activity of macrophages and promoted the migration of PM 10 -laden macrophages to the regional lymph nodes.Conclusions: Lovastatin attenuates the PM(10) -induced recruitment and activation of alveolar macrophages and polymorphonuclear leukocytes, reduces local proinflammatory cytokine production, and promotes the clearance of PM(10) particles from lung tissues to regional lymph nodes. These novel pleiotropic properties of statins are most likely to contribute to the downregulation of PM(10) -induced lung inflammation. [ABSTRACT FROM AUTHOR]

The article presents a study that assessed the efficacy of reductase inhibitors (statins) on ambient particulate matter, which induced lung inflammation. White rabbits, used as specimens were exposed to particulate matter or saline, and measured lung inflammation using immunohistochemical techniques and morphometric methods. It concluded that statins can suppress effects against lung inflammation and can promote the clearance of particulate matter.

The article discusses the risks associated with lung cancer in an individual with HIV infection before and after the use of combination antiretroviral therapy (cART). It reports that the incidence of lung cancer in HIV individuals is three times higher than non-HIV individuals, and briefly discusses the possible causes for the increased occurrence of lung cancer, which includes smoking, use of drugs, immunodeficiency. It provides information on interventions to reduce lung cancer mortality.

The article presents a study on the impact of global cardiovascular event (CVE) risk assessment on CVE and total mortality in U.S. adults with chronic obstructive pulmonary disease (COPD). The researchers found that global CVE risk improved prediction for both CVEs and total mortality in patients with COPD. The addition of global CVE risk scores to lung function data reportedly helped in improving risk stratification of patients with COPD for CVE and total mortality.

Background: COPD is a chronic inflammatory disorder with high risk of cardiovascular morbidity and mortality. Adiponectin is a hormone that has anti inflammatory, antidiabetic, and anti atherogenic activities. We investigated the relationship of serum adiponectin to health outcomes in COPD.Methods: We measured adiponectin levels in serum samples from participants of the Lung Health Study, who were smokers with mild to moderate airflow limitation. We determined the relationship of serum adiponectin to hospitalization and mortality using a Cox proportional hazards model and to baseline lung function measurements and bronchial reactivity using multiple regression methods.Results: Serum adiponectin concentrations were inversely related to hospitalizations and mortality from coronary heart disease (hazard ratio [HR], 0.73; 95% CI, 0.62-0.86) and to cardiovascular disease (HR, 0.83; 95% CI, 0.73-0.94) and positively related to deaths from respiratory causes (HR, 2.09; 95% CI, 1.41-3.11). However, serum adiponectin concentrations were not significantly related to total mortality (HR, 1.10; 95% CI, 0.93-1.29) or cancer-related mortality(HR, 1.11; 95% CI, 0.92-1.34). Serum adiponectin concentrations were significantly related to increased bronchial reactivity and an accelerated decline in lung function (both P , .0001). Smoking status had no material influence on serum adiponectin concentrations.Conclusions: Adiponectin is a complex serum biomarker in COPD that is associated with decreased risk of cardiovascular events but increased risk of respiratory mortality. Because serum adiponectin is not significantly influenced by smoking status, it is a very promising biomarker of cardiovascular outcomes in COPD. [ABSTRACT FROM AUTHOR]

The article investigates the relationship between serum adiponectin and health outcomes in chronic obstructive pulmonary disease (COPD). The authors measure adiponectin levels in serum samples from subjects who are smokers with mild to moderate airflow limitation. They conclude that adiponectin is a biomarker in COPD and is associated with decreased risk of cardiovascular events and increased risk of respiratory mortality. They add that adiponectin is not influenced by smoking status.

Lung cancer is the leading cause of cancer-related mortality in the United States and around the world. There are > 90 million current and ex-smokers in the United States who are at increased risk of lung cancer. The published data from the National Lung Screening Trial (NLST) suggest that yearly screening with low-dose thoracic CT scan in heavy smokers can reduce lung cancer mortality by 20% and all-cause mortality by 7%. However, to implement this program nationwide using the NLST inclusion and exclusion criteria would be extremely expensive, with CT scan costs alone > $2 billion per annum. In this article, we offer a possible low-cost strategy to risk-stratify smokers on the basis of spirometry measurements and emphysema scoring by radiologists on CT scans. [ABSTRACT FROM AUTHOR]

Background: Nearly 30% of all exacerbations of COPD do not have a clear etiology. Although pulmonary embolism (PE) can exacerbate respiratory symptoms such as dyspnea and chest pain, and COPD patients are at a high risk for PE due to a variety of factors including limited mobility, inflammation, and comorbidities, the prevalence of PE during exacerbations is uncertain.Methods: A systematic review of the literature was performed to determine the reported prevalence of PE in acute exacerbations of COPD in patients who did and did not require hospitalization. The literature search was performed using MEDLINE, CINAHL, and EMBASE, and complemented by hand searches of bibliographies. Only cross-sectional or prospective studies that used CT scanning or pulmonary angiography for PE diagnosis were included.Results: Of the 2,407 articles identified, 5 met the inclusion criteria (sample size, 550 patients). Overall, the prevalence of PE was 19.9% (95% confidence interval [CI], 6.7 to 33.0%; p = 0.014). In hospitalized patients, the prevalence was higher at 24.7% (95% CI, 17.9 to 31.4%; p = 0.001) than those who were evaluated in the emergency department (3.3%). Presenting symptoms and signs were similar between patients who did and did not have PE.Conclusions: One of four COPD patients who require hospitalization for an acute exacerbation may have PE. A diagnosis of PE should be considered in patients with exacerbation severe enough to warrant hospitalization, especially in those with an intermediate-to-high pretest probability of PE. [ABSTRACT FROM AUTHOR]

The article examines the obesity paradox in patients with peripheral arterial disease. Chronic obstructive pulmonary disease (COPD) is identitied as a cardiac risk factor, which preferentially affects underweight individuals. The results of the study suggest that the excess mortality among underweight patients was largely explained by the overrepresentation of individuals with moderate-to-sever COPD.

The article presents a study on the relationship between surfactant protein D (SP-D) and the progression of bronchial dysplasia in heavy smokers. It explains the methods which involved 71 ex-smokers and current heavy smokers, and the result of the SP-D and oxidized glutathione levels from the BAL fluid samples of the participants. It determines that SP-D levels in BAL fluid can be a potential biomarker to identify smokers who are at risk of early lung cancers.

The article reports on a systematic evaluation and meta-analysis of the efficacy of systemic antibiotics, corticosteroids and non-invasive positive pressure ventilation (NPPV) for treating patients with acute chronic obstructive lung disease (COPD). Results revealed that systemic corticosteroids can minimize treatment failures, NPPV can decrease the risk of in-hospital mortality and intubation, and antibiotics can minimize both mortality and treatment failures.

Background: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1).Methods: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking.Results: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers.Conclusions: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials. [ABSTRACT FROM AUTHOR]

The article discusses a trial which examined the effect of nocturnal noninvasive mechanical ventilation (NIMV) on heart rate variability (HRV), circulating natriuretic peptide levels and functional performance of patients with advanced chronic obstructive pulmonary disease. NIMV applied nocturnally over three months may improve HRV, reduce circulating natriuretic peptide levels and improve functional performance of the patients.

Studies the relationship between reduced functional expiratory volume (FEV) and cardiovascular mortality. Risk of death from ischemic heart disease; Epidemiological evidence indicating that reduced FEV is a marker for cardiovascular mortality independent of age, gender and smoking history.

Background: Low-grade systemic inflammation is commonly observed in conditions associated with reduced FEV1. Active cigarette smoking, which is a leading risk factor for decreased FEV1, can also independently induce systemic inflammation. Study objectives: To determine the independent contributions of active cigarette smoking and reduced FEV1 (as well as their potential interactions) on systemic inflammation. Design: Cross-sectional survey. Setting: The US general population. Participants: A total of 7,685 adult participants, ≥ 40 years of age, in the Third National Health and Nutrition Examination Survey, who had acceptable data on spirometry and laboratory measurements such as serum C-reactive protein (CRP). Measurements: The participants were stratified into four equal groups (quartiles) based on the percent predicted FEV1 values. Each group was further categorized as active smokers or nonsmokers according to serum cotinine level (ie, ≥ 10 or < 10 ng/mL). Serum levels of CRP, plasma fibrinogen, blood leukocytes, and platelets were compared across the predicted FEV1 quartile groups and across smoking status using multiple logistic regression models. Results: We found that active smoking by itself increased the odds of having elevated CRP levels by 63% (adjusted odds ratio [OR], 1.63; 95% confidence interval, 1.28 to 2.09). The adjusted OR for reduced FEV1 was 2.27 (95% confidence interval, 1.92 to 2.70). Having both risk factors increased the OR to 3.31 (95% confidence interval, 2.73 to 4.02). Similar findings were observed for blood leukocytes and plasma fibrinogen. Conclusion: These findings suggest an additive effect of active smoking and reduced FEV1 on markers of systemic inflammation and suggest their potential interactions in the pathogenesis of systemic complications observed in patients with poor lung function. [ABSTRACT FROM AUTHOR]

Study objectives: Children from poor families are much more likely to have emergency visits for asthma than those from nonpoor families, which may be related to financial access barriers to good preventive care for the poor. We sought to determine whether in a health-care system that provides free access to outpatient and hospital services, the disparities in the rates of emergency visits for asthma would be less apparent across the income gradient. Design: Longitudinal, population-based study. Setting: Alberta, Canada. Participants: All children born in Alberta, Canada between 1985 and 1988 (n = 90,845) were classified into three mutually exclusive groups based on the reported annual income of their parents from the previous year: very poor, poor, and nonpoor groups. Measurements and results: We compared the relative risk (RR) of emergency visits for childhood asthma among children of very poor, poor, and nonpoor families using a Cox proportional hazard model during a 10-year follow-up. We found that the very poor children were 23% more likely to have had an emergency visit for asthma than those from nonpoor families (RR, 1.23; 95% confidence interval [CI], 1.14 to 1.33), adjusted for a variety of factors. The poor group, however, had a similar risk of asthma emergency visits as the nonpoor group (RR, 0.97; 95% CI, 0.91 to 1.04). The average number of office visits for asthma was similar between the very poor and nonpoor groups. Conclusions: In a setting of universal access to health care, children of poor and nonpoor families had similar rates of asthma emergency visits; the very poor children, however, continued to experience an excess risk. These findings suggest that a universal health-care system can reduce, but not fully eliminate, the disparities in emergency utilization of asthma across income categories. [ABSTRACT FROM AUTHOR]

Study objectives: Obstructive sleep apnea (OSA) is an independent risk factor for hypertension in the general population. Hypertension is, in turn, an important risk factor for the development and progression of congestive heart failure (CHF). Our objective was to determine whether OSA would be associated with elevated daytime BP in medically treated patients with CHF. Design: Cross-sectional study. Setting: Tertiary care, university-affiliated sleep disorders and heart failure clinics. Patients: Three hundred one consecutive patients with CHF. Measurements and results: We measured daytime BP and performed overnight sleep studies to assess for the presence of OSA. Among these patients, OSA was present in 121 patients (40%) and their systolic BP was significantly higher than in patients without OSA. Patients with OSA were 2.89 times (95% confidence interval, 1.25 to 6.73) more likely to have systolic hypertension (ie, BP ≥ 140 mm Hg) than those without OSA after controlling for other risk factors, including obesity. The degree of systolic BP elevation was directly related to the frequency of obstructive apneas and hypopneas. Conclusions: In medically treated patients with CHF, daytime systolic BP and the prevalence of systolic hypertension are significantly increased in patients with OSA, compared to those without OSA, independent of other potentially confounding factors. OSA may therefore have contributed to the presence of systolic hypertension in some of these patients. [ABSTRACT FROM AUTHOR]

Study objectives: To determine the short-term and long-term impacts of continuous positive airway pressure (CPAP) therapy on health-related quality of life (HRQL) in patients with obstructive sleep apnea (OSA). Design: Prospective longitudinal cohort study. Setting: University sleep disorders center. Patients: Three hundred sixty-five patients with an apnea-hypopnea index (AHI) ≥ 20 per hour of sleep and 358 patients with an AHI of < 20. Interventions: All patients with AHIs ≥ 20 received CPAP therapy; those with AHIs < 20 did not. The HRQL of all study participants was measured using the 36-item medical outcomes study short form (SF-36) questionnaire at baseline and then at 3 and 12 months of follow-up. Results: Although the SF-36 scores were similar at baseline, after 3 months of therapy, the CPAP group had higher adjusted emotional summary scores than did those who did not receive CPAP therapy (score increase, 1.72; 95% confidence interval [CI], 0.08 to 3.37). These improvements were maintained for 12 months. The gains in the SF-36 scores were most striking in the vitality domain (score increase, 10.52; 95% CI, 7.04 to 14.00 U increment). The severe OSA group (ie, AHIs ≥ 40) experienced the largest benefit. Their adjusted vitality scores were 12.3 U higher (95% CI, 8.0 to 16.6) than those persons without OSA (ie, AHIs < 5). Conclusions: CPAP therapy was associated with marked short-term and long-term improvements in the vitality of patients with moderate-to-severe OSA in the community. These findings suggest that CPAP therapy is effective in improving the long-term HRQL of patients with OSA. [ABSTRACT FROM AUTHOR]

Background: Aboriginals in Canada bear a disproportionately higher burden of some chronic illnesses than nonaboriginals. Although there is a greater prevalence of smoking, poor housing, and overcrowding in aboriginal than nonaboriginal communities, the rates of office and emergency visits for asthma and COPD among aboriginals are not well known. Study objective: To determine whether aboriginals require higher rates of asthma and COPD emergency and office visits than nonaboriginals. Setting: Population-based cohort of people residing in Alberta, Canada (population 2.8 million) between April 1, 1996, and March 31, 1997. Design: Retrospective cohort study. Results: We observed that aboriginals were 2.1 times (95% confidence interval [CI], 2.0 to 2.2) and 1.6 times (95% CI, 1.6 to 1.6) more likely to have an emergency and office visit for asthma or COPD, respectively, when compared to age-matched and sex-matched nonaboriginals. However, they were 55% (95% CI, 52 to 58%) less likely to see a specialist and 66% (95% CI, 63 to 70%) less likely to undergo spirometry than nonaboriginals. Conclusions: These findings indicate that aboriginals bear a disproportionately higher burden of asthma and COPD than nonaboriginals. However, lower use of spirometry and specialist services suggests that there might be access barriers to quality health care for aboriginals in Canada. [ABSTRACT FROM AUTHOR]

Study objectives: To determine long-term compliance rates to continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnea enrolled in a comprehensive CPAP program in the community. Design: Prospective cohort longitudinal study. Setting: University sleep disorders center. Patients: Two hundred ninety-six patients with an apnea-hypopnea index (AHI) ≥ 20/h on polysomnography. Interventions: A CPAP device equipped with a monitoring chip was supplied. Within the first week, daily telephone contacts were made. Patients were seen at 2 weeks, 4 weeks, 3 months, and 6 months. Results: Of the 296 subjects enrolled, 81.1% were males. Mean ± SD AHI was 64.4 ± 34.2/h of sleep; age, 51 ± 11.7 years; and body mass index, 35.2 ± 7.9 kg/m². The mean duration of CPAP use was 5.7 h/d at 2 weeks, 5.7 h/d at 4 weeks, 5.9 h/d at 3 months, and 5.8 h/d at 6 months. The percentage of patients using CPAP ≥ 3.5 h/d was 89.0% at 2 weeks, 86.6% at 4 weeks, 88.6% at 3 months, and 88.5% at 6 months. There was a decrease in the Epworth Sleepiness Scale (ESS) score of 44% by 2 weeks of therapy. The patients continue to improve over the follow-up period, with the lowest mean ESS score observed at 6 months. With multiple regression analysis, three variables were found to be significantly correlated with increased CPAP use: female gender, increasing age, and reduction in ESS score. Conclusion: A population-based CPAP program consisting of consistent follow-up, "troubleshooting," and regular feedback to both patients and physicians can achieve CPAP compliance rates of > 85% over 6 months. [ABSTRACT FROM AUTHOR]

Study objectives: Despite their proven efficacy, inhaled steroids may be underused in the elderly asthmatic population. The objectives of this study were to determine if inhaled steroids are underused in the elderly asthmatic population, who are at a high risk for rehospitalization and mortality, and to identify certain risk factors that predict lower use of inhaled steroids in this group of patients. Design: Population-based, retrospective, cohort study using linked data from hospital discharge and outpatient drug databases. Participants: All people ≥ 65 years old in Ontario, Canada, who survived an acute exacerbation of asthma between April 1992 and March 1997. Measurements and results: Of the 6,254 patients, 2,495 patients (40%) did not receive inhaled steroid therapy within 90 days of discharge from their initial hospitalization for asthma. Patients > 80 years old were at a greater risk of not receiving inhaled steroid therapy, compared to those 65 to 70 years of age (adjusted odds ratio [OR], 1.23; 95% confidence interval [CI], 1.05 to 1.47). Patients with a Charlson comorbidity index of ≥ 3 were also at an increased risk of not receiving inhaled steroid therapy, compared to those having no comorbidities (adjusted OR, 3.45; 95% CI, 1.56 to 7.69). Moreover, receipt of care from a primary-care physician was independently associated with an elevated risk of not receiving inhaled steroid therapy, compared to receipt of care from respirologists/allergists (adjusted OR, 1.35; 95% CI, 1.10 to 1.61). Interpretation: Forty percent of Ontario patients ≥ 65 years old who experienced a recent acute exacerbation of asthma did not receive inhaled steroid therapy near discharge from their initial hospitalization for asthma. Nonreceipt of inhaled steroid therapy was particularly prominent in the older patients with multiple comorbidities. Moreover, those who received care from primary-care physicians were also less likely to receive inhaled steroid therapy,... [ABSTRACT FROM AUTHOR]

A letter is presented citing the authors' views on the biological markers of chronic obstructive pulmonary disease (COPD).

The author reflects the association of systemic inflammation and interleukin-6 (IL-6) to the chronic obstructive pulmonary disease (COPD), a tobacco-related disease. He asserts how serum C-reactive protein (CRP) and IL-6 and plasma P-selection levels were linked with reduced forced expiratory volume (FEV). He also contends that IL-6 can be used as biomarker in COPD because it regulates CRP and fibrogen in the liver.

The article assesses the use of a large administrative health database to show the association of inhaled corticosteroid therapy with reduction of all-cause mortality in patients with chronic obstructive pulmonary disease. The author stresses that the reduction in cardiovascular mortality related to the therapy makes the study interesting. He asserts that inhaled corticosteroid therapy has modest nonsignificant effect in decreasing the rate of respiratory deaths.

The article discusses the implications of systemic inflammation on the development of pulmonary hypertension in Chronic Obstructive Pulmonary Disease (COPD). Research studies showed that the walls of pulmonary arteries in patients with COPD are usually infiltrated with leukocytes, which if the disease becomes chronic leads to stiffness and failure of vessels to relax properly. Thus, systemic inflammation as an important factor in the pathogenesis of pulmonary hypertension has been hypothesized.

Editorial. Comments on the recognition of sleep-disordered breathing (SDB) as a risk factor for coronary atherosclerosis and heart disease. Evidence on the increase of systemic blood pressure and sympathetic drive; Support for the role of SDB in the pathogenesis of atherosclerosis; Link of elevated nocturnal oxygen desaturation index to risk of blood clots.