Combined assessment of pulmonary arterial enlargement and coronary calcification predicts the prognosis of patients with chronic obstructive pulmonary disease.

INTRODUCTION: In chronic obstructive pulmonary disease (COPD), chest computed tomography (CT) provides clinically important cardiovascular findings, which include diameter of pulmonary artery (PA), its ratio to the diameter of the aorta (PA:A ratio), and coronary artery calcium score (CACS). The clinical importance of these cardiovascular findings has not been fully assessed in Japan, where cardiovascular morbidity and/or mortality is reported to be much less compared with Western counterparts. METHODS: PA diameter and PA:A ratio were measured in 172 and 130 patients with COPD who enrolled in the Hokkaido COPD cohort study and the Kyoto University cohort, respectively. CACS was measured in 131 and 128 patients in each cohort. RESULTS: While the highest quartile group in PA diameter was associated with higher all-cause mortality compared to the lowest quartile group in both cohorts, individual assessments of PA:A ratio and CACS were not associated with the long-term clinical outcomes. When PA diameter and CACS were combined, patients with PA enlargement (diameter >29.5 mm) and/or coronary calcification (score >440.8) were associated with higher all-cause mortality in both cohorts. CONCLUSION: Combined assessment of PA enlargement and CACS was associated with poor prognosis, which provides a clinical advantage in management of patients with COPD even in geographical regions with lower risk of cardiovascular diseases.

Racial Segregation and Respiratory Outcomes among Urban Black Residents with and at Risk of Chronic Obstructive Pulmonary Disease.

Rationale: Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established.Objectives: To investigate whether racial residential segregation is associated with COPD morbidity among urban Black adults with or at risk of COPD.Methods: Racial residential segregation was assessed using isolation index, based on 2010 decennial census and baseline address, for Black former and current smokers in the multicenter SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), a study of adults with or at risk for COPD. We tested the association between isolation index and respiratory symptoms, physiologic outcomes, imaging parameters, and exacerbation risk among urban Black residents, adjusting for established COPD risk factors, including smoking. Additional mediation analyses were conducted for factors that could lie on the pathway between segregation and COPD outcomes, including individual and neighborhood socioeconomic status, comorbidity burden, depression/anxiety, and ambient pollution.Measurements and Main Results: Among 515 Black participants, those residing in segregated neighborhoods (i.e., isolation index ⩾0.6) had worse COPD Assessment Test score (ß = 2.4; 95% confidence interval [CI], 0.7 to 4.0), dyspnea (modified Medical Research Council scale; ß = 0.29; 95% CI, 0.10 to 0.47), quality of life (St. George's Respiratory Questionnaire; ß = 6.1; 95% CI, 2.3 to 9.9), and cough and sputum (ß = 0.8; 95% CI, 0.1 to 1.5); lower FEV1% predicted (ß = -7.3; 95% CI, -10.9 to -3.6); higher rate of any and severe exacerbations; and higher percentage emphysema (ß = 2.3; 95% CI, 0.7 to 3.9) and air trapping (ß = 3.8; 95% CI, 0.6 to 7.1). Adverse associations attenuated with adjustment for potential mediators but remained robust for several outcomes, including dyspnea, FEV1% predicted, percentage emphysema, and air trapping.Conclusions: Racial residential segregation was adversely associated with COPD morbidity among urban Black participants and supports the hypothesis that racial segregation plays a role in explaining health inequities affecting Black communities.

Personalized Variable vs Fixed-Dose Systemic Corticosteroid Therapy in Hospitalized Patients With Acute Exacerbations of COPD: A Prospective, Multicenter, Randomized, Open-Label Clinical Trial.

BACKGROUND: Systemic corticosteroids for the treatment of COPD exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear. RESEARCH QUESTION: Is personalized-dose corticosteroid administered according to a dosing scale more effective than fixed-dose corticosteroid administration in hospitalized patients with COPD with exacerbations? STUDY DESIGN AND METHODS: This was a prospective, randomized, open-label trial. In-hospital patients with COPD with exacerbations were randomly assigned at a 1:1 ratio to either the fixed-dose group (receiving the equivalent of 40 mg of prednisolone) or the personalized-dose group for 5 days. The primary end point was a composite measure of treatment failure that included in-hospital treatment failure and medium-term (postdischarge) failure. Secondary end points were length of stay and cost. RESULTS: A total of 248 patients were randomly assigned to the fixed-dose group (n = 124) or personalized-dose group (n = 124). One patient in each group was not included in the intention-to-treat population because of incorrect initial COPD diagnosis. Failure of therapy occurred in 27.6% in the personalized-dose group, compared with 48.8% in the fixed-dose group (relative risk, 0.40; 95% CI, 0.24-0.68; P = .001). The in-hospital failure of therapy was significantly lower in the personalized-dose group (10.6% vs 24.4%; P = .005), whereas the medium-term failure rate, adverse event rate, hospital length of stay, and costs were similar between the two groups. After treatment failure, a lower additional dose of corticosteroids and a shorter duration of treatment were needed in the personalized-dose group to achieve control of the exacerbation. In the personalized-dose cohort, those receiving 40 mg or less had an average failure rate of 44.4%, compared with 22.9% among those receiving more than 40 mg (P = .027). INTERPRETATION: Personalized dosing of corticosteroids reduces the risk of failure because more patients were provided with a higher initial dose, especially > 60 mg, whereas 40 mg or less was too low in either group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02147015; URL: www.clinicaltrials.gov.

Trends and Inpatient Outcomes of Primary Heart Failure Hospitalizations with a Concurrent Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (from The National Inpatient Sample Database from 2004 to 2014).

Heart failure (HF) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are considered significant causes of morbidity and mortality worldwide. Concurrent presentation of HF with AECOPD can pose a diagnostic challenge due to an overlap in symptomatology. We queried the National Inpatient Sample (NIS) database to assess outcomes of HF hospitalizations with a secondary diagnosis of AECOPD. We performed a retrospective analysis of discharge data from the Healthcare Cost Utilization Project NIS between January 1, 2004, and December 31, 2014, with a primary diagnosis of HF with and without a secondary diagnosis of AECOPD. Data was abstracted from the NIS using International Classification of Disease 9 codes. Primary outcomes included mortality, length of stay, and inflation-adjusted cost of stay. During 2004-2014, a total of (n = 10,392,628) HF hospitalizations were identified without a secondary diagnosis of AECOPD while (n = 989,713) HF hospitalizations were identified with a secondary diagnosis of AECOPD. We identified higher mortality (3.25% vs 3.56%, p <0.001), length of stay (5.2 vs 6.1 days, p <0.001) and inflation-adjusted cost of stay (12,562 vs 13,072 USD, p <0.001) in HF hospitalizations with AECOPD when compared to HF without AECOPD from 2004 to 2014. We presented AECOPD as an independent predictor of mortality in patients admitted for HF. In conclusion, further interdisciplinary collaboration between pulmonologists and cardiologists is needed for the identification and stratification of patients who present with concurrent HF and COPD for better outcomes.

Strategies to prevent hospital readmission and death in patients with chronic heart failure, chronic obstructive pulmonary disease, and chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Readmission following hospital discharge is common and is a major financial burden on healthcare systems. OBJECTIVES: Our objectives were to 1) identify studies describing post-discharge interventions and their efficacy with respect to reducing risk of mortality and rate of hospital readmission; and 2) identify intervention characteristics associated with efficacy. METHODS: A systematic review of the literature was performed. We searched MEDLINE, PubMed, Cochrane, EMBASE and CINAHL. Our selection criteria included randomized controlled trials comparing post-discharge interventions with usual care on rates of hospital readmission and mortality in high-risk chronic disease patient populations. We used random effects meta-analyses to estimate pooled risk ratios for all-cause and cause-specific mortality as well as all-cause and cause-specific hospitalization. RESULTS: We included 31 randomized controlled trials encompassing 9654 patients (24 studies in CHF, 4 in COPD, 1 in both CHF and COPD, 1 in CKD and 1 in an undifferentiated population). Meta-analysis showed post-discharge interventions reduced cause-specific (RR = 0.71, 95% CI = 0.63-0.80) and all cause (RR = 0.90, 95% CI = 0.81-0.99) hospitalization, all-cause (RR = 0.73, 95% CI = 0.65-0.83) and cause-specific mortality (RR = 0.68, 95% CI = 0.54-0.84) in CHF studies, and all-cause hospitalization (RR = 0.52, 95% CI = 0.32-0.83) in COPD studies. The inclusion of a cardiac nurse in the multidisciplinary team was associated with greater efficacy in reducing all-cause mortality among patients discharged after heart failure admission (HR = 0.64, 95% CI = 0.54-0.75 vs. HR = 0.87, 95% CI = 0.73-1.03). CONCLUSIONS: Post-discharge interventions reduced all-cause mortality, cause-specific mortality, and cause-specific hospitalization in CHF patients and all-cause hospitalization in COPD patients. The presence of a cardiac nurse was associated with greater efficacy in included studies. Additional research is needed on the impact of post-discharge intervention strategies in COPD and CKD patients.

Influence of government-driven quality assessment program on patients with chronic obstructive pulmonary disease.

BACKGROUND: The Korean Health Insurance Review and Assessment Service (HIRA) has launched the Chronic Obstructive Pulmonary Disease (COPD) Quality Assessment Program (CQAP) since 2014. We aimed to reveal the influence of this national program on clinical outcomes and the burden of COPD in Korea. METHODS: The CQAP is conducted annually. We used healthcare claims data linked with the results of the program provided by HIRA between May 2014 and April 2017. Patients were considered to have COPD if they visited a hospital for COPD management during the assessment term. Those who visited a medical institution for COPD and were prescribed COPD medications at least twice were assessed by the CQAP (assessed subjects, AS; not-assessed subjects, NAS). CQAP evaluated the pulmonary function test conduction rate, regular visitation rate, and prescription rates of COPD medications. RESULTS: Among the 560,000 patients with COPD, about 140,000 were assessed by the CQAP annually. In both groups, the pulmonary function test conduction rate and inhaled bronchodilator prescription rate improved since 2014. Compared to the NAS group, the risk of admission and all-cause mortality rate in the AS group were significantly reduced by 21.2% and 40.7%, respectively. In patients who were assessed for 3 consecutive years, all of the above variables were high at baseline and were not improved much from implementation of CQAP. In matching analysis, we observed this improvement to be limited in the COPD quality assessment year. CONCLUSIONS: The CQAP by the health insurance bureau has improved the management protocol and prognosis of COPD.

Muscle loss contributes to higher morbidity and mortality in COPD: An analysis of national trends.

BACKGROUND AND OBJECTIVE: COPD is the third most common cause of death worldwide and fourth most common in the United States. In hospitalized patients with COPD, mortality, morbidity and healthcare resource utilization are high. Skeletal muscle loss is frequent in patients with COPD. However, the impact of muscle loss on adverse outcomes has not been systematically evaluated. We tested the hypothesis that patients hospitalized for COPD exacerbation with, compared to those without, a secondary diagnosis of muscle loss phenotype (all ICD-9 codes associated with muscle loss including cachexia) will have higher mortality and cost of care. METHODS: The NIS database of hospitalized patients in 2011 (1 January-31 December) in the United States was used. The impact of a muscle loss phenotype on in-hospital mortality, LOS and cost of care for each of the 174 808 hospitalizations for COPD exacerbations was analysed. RESULTS: Of the subjects admitted for a COPD exacerbation, 12 977 (7.4%) had a secondary diagnosis of muscle loss phenotype. A diagnosis of muscle loss phenotype was associated with significantly higher in-hospital mortality (14.6% vs 5.7%, P < 0.001), LOS (13.3 + 17.1 vs 5.7 + 7.6, P < 0.001) and median hospital charge per patient ($13 947 vs $6610, P < 0.001). Multivariate regression analysis showed that muscle loss phenotype increased mortality by 111% (95% CI: 2.0-2.2, P < 0.001), LOS by 68.4% (P < 0.001) and the direct cost of care by 83.7% (P < 0.001) compared to those without muscle loss. CONCLUSION: In-hospital mortality, LOS and healthcare costs are higher in patients with COPD exacerbations and a muscle loss phenotype.

Risk factors and associated outcomes of hospital readmission in COPD: A systematic review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of unplanned readmission. There is need to identify risk factors for, and strategies to prevent readmission in patients with COPD. AIM: To systematically review and summarise the prevalence, risk factors and outcomes associated with rehospitalisation due to COPD exacerbation. METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Five databases were searched for relevant studies. RESULTS: Fifty-seven studies from 30 countries met the inclusion criteria. The prevalence of COPD-related readmission varied from 2.6 to 82.2% at 30 days, 11.8-44.8% at 31-90 days, 17.9-63.0% at 6 months, and 25.0-87.0% at 12 months post-discharge. There were differences in the reported factors associated with readmissions, which may reflect variations in the local context, such as the availability of community-based services to care for exacerbations of COPD. Hospitalisation in the previous year prior to index admission was the key predictor of COPD-related readmission. Comorbidities (in particular asthma), living in a deprived area and living in or discharge to a nursing home were also associated with readmission. Relative to those without readmissions, readmitted patients had higher in-hospital mortality rates, shorter long-term survival, poorer quality of life, longer hospital stay, increased recurrence of subsequent readmissions, and accounted for greater healthcare costs. CONCLUSIONS: Hospitalisation in the previous year was the principal risk factor for COPD-related readmissions. Variation in the prevalence and the reported factors associated with COPD-related readmission indicate that risk factors cannot be generalised, and interventions should be tailored to the local healthcare environment.

Effect of BMI on health care expenditures stratified by COPD GOLD severity grades: Results from the LQ-DMP study.

Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation, which is progressive and not fully reversible. In patients with COPD, body mass index (BMI) is an important parameter associated with health outcomes, e.g. mortality and health-related quality of life. However, so far no study evaluated the association of BMI and health care expenditures across different COPD severity grades. We used claims data and documentation data of a Disease Management Program (DMP) from a statutory health insurance fund (AOK Bayern). Patients were excluded if they had less than 4 observations in the 8 years observational period. Generalized additive mixed models with smooth functions were used to evaluate the association between BMI and health care expenditures, stratified by severity of COPD, indicated by GOLD grades 1-4. We included 30,682 patients with overall 188,725 observations. In GOLD grades 1-3 we found an u-shaped relation of BMI and expenditures, where patients with a BMI of 30 or slightly above had the lowest and underweight and obese patients had the highest health care expenditures. Contrarily, in GOLD grade 4 we found an almost linear decline of health care expenditures with increasing BMI. In terms of expenditures, the often reported obesity paradox in patients with COPD was clearly reflected in GOLD grade 4, while in all other severity grades underweight as well as severely obese patients caused the highest health care expenditures. Reduction of obesity may thus reduce health care expenditures in GOLD grades 1-3.

Causes of death among Federal Black Lung Benefits Program beneficiaries enrolled in Medicare, 1999-2016.

BACKGROUND: Coal miners with totally disabling pneumoconiosis are eligible for benefits through the Federal Black Lung Benefits Program (FBLP). We identify the causes of death among Medicare beneficiaries with a claim for which the FBLP was the primary payer and compare these causes of death to all deceased Medicare beneficiaries to better understand elevated death and disease among miners with occupational respiratory exposures. METHODS: From 1999 to 2016 Medicare data, we extracted beneficiary and National Death Index data for 28,003 beneficiaries with an FBLP primary payer claim. We summarized the International Classification of Diseases, Clinical Modification 10th revision-coded underlying causes of death and entity-axis multiple causes of death for 22,242 deceased Medicare beneficiaries with an FBLP primary payer Medicare claim and compared their causes of death to the deceased Medicare beneficiary population. RESULTS: Among deceased FBLP beneficiaries, the three leading underlying causes of death were chronic obstructive pulmonary disease, unspecified (J44.9, 10.1%), atherosclerotic heart disease (I25.1, 9.3%), and coal workers' pneumoconiosis (CWP) (J60, 9.2%). All diseases of the respiratory system combined (J00-J99) were the underlying cause of death for 29.1% of all beneficiaries, with pneumoconioses (J60-J64) as the underlying cause for 11.0% of all beneficiaries. CONCLUSIONS: Coal miners enrolled in Medicare with an FBLP primary payer claim were more likely to have specific respiratory and cardiovascular diseases listed as a cause of death than deceased Medicare beneficiaries overall, and were also more likely to die from CWP or any pneumoconioses.

Assessment of the Modified CHA2DS2VASc Risk Score in Predicting Mortality in Patients Hospitalized With COVID-19.

Since the modified CHA2DS2VASC (M-CHA2DS2VASc) risk score includes the prognostic risk factors for COVID-19; we assumed that it might predict in-hospital mortality and identify high-risk patients at an earlier stage compared with troponin increase and neutrophil-lymphocyte ratio (NLR). We aimed to investigate whether M-CHA2DS2VASC RS is an independent predictor of mortality in patients hospitalized with COVID-19 and to compare its discriminative ability with troponin increase and NLR in terms of predicting mortality. A total of 694 patients were retrospectively analyzed and divided into 3 groups according to M-CHA2DS2VASC RS which was simply created by changing gender criteria of the CHA2DS2VASC RS from female to male (Group 1, score 0-1 (n = 289); group 2, score 2-3 (n = 231) and group 3, score ≥4 (n = 174)). Adverse clinical events were defined as in-hospital mortality, admission to intensive care unit, need for high-flow oxygen and/or intubation. As the M-CHA2DS2VASC RS increased, adverse clinical outcomes were also significantly increased (Group 1, 3.8%; group 2, 12.6%; group 3, 20.8%; p <0.001 for in-hospital mortality). The multivariate logistic regression analysis showed that M-CHA2DS2VASC RS, troponin increase and neutrophil-lymphocyte ratio were independent predictors of in-hospital mortality (p = 0.005, odds ratio 1.29 per scale for M-CHA2DS2VASC RS). In receiver operating characteristic analysis, comparative discriminative ability of M-CHA2DS2VASC RS was superior to CHA2DS2VASC RS score. Area under the curve (AUC) values for in-hospital mortality was 0.70 and 0.64, respectively. (AUCM-CHA2DS2-VASc vs. AUCCHA2DS2-VASc z test = 3.56, p 0.0004) In conclusion, admission M-CHA2DS2VASc RS may be a useful tool to predict in-hospital mortality in patients with COVID-19.

Understanding resource utilization and mortality in COPD to support policy making: A microsimulation study.

Chronic obstructive pulmonary disease (COPD) poses a significant but heterogeneous burden to individuals and healthcare systems. Policymakers develop targeted policies to minimize this burden but need personalized tools to evaluate novel interventions and target them to subpopulations most likely to benefit. We developed a platform to identify subgroups that are at increased risk of emergency department visits, hospitalizations and mortality and to provide stratified patient input in economic evaluations of COPD interventions. We relied on administrative and survey data from Ontario, Canada and applied a combination of microsimulation and multi-state modeling methods. We illustrated the functionality of the platform by quantifying outcomes across smoking status (current, former, never smokers) and by estimating the effect of smoking cessation on resource use and survival, by comparing outcomes of hypothetical cohorts of smokers who quit at diagnosis and smokers that continued to smoke post diagnosis. The cumulative incidence of all-cause mortality was 37.9% (95% CI: 34.9, 41.4) for never smokers, 34.7% (95% CI: 32.1, 36.9) for current smokers, and 46.4% (95% CI: 43.6, 49.0) for former smokers, at 14 years. Over 14 years, smokers who did not quit at diagnosis had 16.3% (95% CI: 9.6, 38.4%) more COPD-related emergency department visits than smokers who quit at diagnosis. In summary, we combined methods from clinical and economic modeling to create a novel tool that policymakers and health economists can use to inform future COPD policy decisions and quantify the effect of modifying COPD risk factors on resource utilization and morality.

Epigenetic measures of ageing predict the prevalence and incidence of leading causes of death and disease burden.

BACKGROUND: Individuals of the same chronological age display different rates of biological ageing. A number of measures of biological age have been proposed which harness age-related changes in DNA methylation profiles. These measures include five 'epigenetic clocks' which provide an index of how much an individual's biological age differs from their chronological age at the time of measurement. The five clocks encompass methylation-based predictors of chronological age (HorvathAge, HannumAge), all-cause mortality (DNAm PhenoAge, DNAm GrimAge) and telomere length (DNAm Telomere Length). A sixth epigenetic measure of ageing differs from these clocks in that it acts as a speedometer providing a single time-point measurement of the pace of an individual's biological ageing. This measure of ageing is termed DunedinPoAm. In this study, we test the association between these six epigenetic measures of ageing and the prevalence and incidence of the leading causes of disease burden and mortality in high-income countries (n ≤ 9537, Generation Scotland: Scottish Family Health Study). RESULTS: DNAm GrimAge predicted incidence of clinically diagnosed chronic obstructive pulmonary disease (COPD), type 2 diabetes and ischemic heart disease after 13 years of follow-up (hazard ratios = 2.22, 1.52 and 1.41, respectively). DunedinPoAm predicted the incidence of COPD and lung cancer (hazard ratios = 2.02 and 1.45, respectively). DNAm PhenoAge predicted incidence of type 2 diabetes (hazard ratio = 1.54). DNAm Telomere Length associated with the incidence of ischemic heart disease (hazard ratio = 0.80). DNAm GrimAge associated with all-cause mortality, the prevalence of COPD and spirometry measures at the study baseline. These associations were present after adjusting for possible confounding risk factors including alcohol consumption, body mass index, deprivation, education and tobacco smoking and surpassed stringent Bonferroni-corrected significance thresholds. CONCLUSIONS: Our data suggest that epigenetic measures of ageing may have utility in clinical settings to complement gold-standard methods for disease assessment and management.

Assessment of comorbidities and prognosis in patients with COPD diagnosed with the fixed ratio and the lower limit of normal: a systematic review and meta-analysis.

BACKGROUND: Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) is not uniform, COPD guidelines recommend fixed ratio (FR), whereas ATS and ERS define airflow obstruction based on lower limit of normal (LLN). We aim to determine if there is difference between the two diagnostic criteria for morbidity, mortality, exacerbation. METHODS: Four databases and all relevant studies from the references were searched from inception to June 25, 2019, to find studies that described the rate of comorbidity, the exacerbation rates, mortality in COPD patients. Data analysis was performed using STATA/SE 14.0 and followed the standard of Cochrane Collaboration. A sensitivity analysis was performed to find the source of heterogeneity. RESULTS: Thirteen studies and 154,447 participants were finally included in this meta-analysis. The 11 cohort studies and 2 cross-sectional studies were all high-quality. Patients with airflow limitation according to either FR or LLN had higher mortality (HRFR+/LLN- = 1.27, 95% CI = 1.14-1.42; HRFR-/LLN+ = 1.83, 95% CI = 1.17-2.86) than those who met neither criteria. When compared with the FR-/LLN- criteria, those who met the FR criteria were more likely to exacerbate (HR FR+/LLN- = 1.64, 95% CI = 1.09-2.46; HR FR-/LLN+ = 1.58, 95% CI = 0.70-3.55). The meta-analysis for comorbidities showed no significant difference between patients who met neither criteria and those who met LLN or FR criteria. CONCLUSION: The patients with airflow limitations according to FR were more likely to exacerbate than those with LLN only. Patients that met either FR or LLN were more likely to have higher mortality than FR-/LLN-. There was no difference between the FR+/LLN- and FR-/LLN+ groups for the occurrence of comorbidities.

Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma. In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017. METHODS: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex. Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases. We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs. FINDINGS: In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990. Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia. The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically. Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms. Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%. However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%). In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD. In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes. Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world. Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions. Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men. Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region. INTERPRETATION: Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990. Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis. FUNDING: Bill & Melinda Gates Foundation.

Association Between Initiation of Pulmonary Rehabilitation After Hospitalization for COPD and 1-Year Survival Among Medicare Beneficiaries.

Importance: Meta-analyses have suggested that initiating pulmonary rehabilitation after an exacerbation of chronic obstructive pulmonary disease (COPD) was associated with improved survival, although the number of patients studied was small and heterogeneity was high. Current guidelines recommend that patients enroll in pulmonary rehabilitation after hospital discharge. Objective: To determine the association between the initiation of pulmonary rehabilitation within 90 days of hospital discharge and 1-year survival. Design, Setting, and Patients: This retrospective, inception cohort study used claims data from fee-for-service Medicare beneficiaries hospitalized for COPD in 2014, at 4446 acute care hospitals in the US. The final date of follow-up was December 31, 2015. Exposures: Initiation of pulmonary rehabilitation within 90 days of hospital discharge. Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. Time from discharge to death was modeled using Cox regression with time-varying exposure to pulmonary rehabilitation, adjusting for mortality and for unbalanced characteristics and propensity to initiate pulmonary rehabilitation. Additional analyses evaluated the association between timing of pulmonary rehabilitation and mortality and between number of sessions completed and mortality. Results: Of 197 376 patients (mean age, 76.9 years; 115 690 [58.6%] women), 2721 (1.5%) initiated pulmonary rehabilitation within 90 days of discharge. A total of 38 302 (19.4%) died within 1 year of discharge, including 7.3% of patients who initiated pulmonary rehabilitation within 90 days and 19.6% of patients who initiated pulmonary rehabilitation after 90 days or not at all. Initiation within 90 days was significantly associated with lower risk of death over 1 year (absolute risk difference [ARD], -6.7% [95% CI, -7.9% to -5.6%]; hazard ratio [HR], 0.63 [95% CI, 0.57 to 0.69]; P < .001). Initiation of pulmonary rehabilitation was significantly associated with lower mortality across start dates ranging from 30 days or less (ARD, -4.6% [95% CI, -5.9% to -3.2%]; HR, 0.74 [95% CI, 0.67 to 0.82]; P < .001) to 61 to 90 days after discharge (ARD, -11.1% [95% CI, -13.2% to -8.4%]; HR, 0.40 [95% CI, 0.30 to 0.54]; P < .001). Every 3 additional sessions was significantly associated with lower risk of death (HR, 0.91 [95% CI, 0.85 to 0.98]; P = .01). Conclusions and Relevance: Among fee-for-service Medicare beneficiaries hospitalized for COPD, initiation of pulmonary rehabilitation within 3 months of discharge was significantly associated with lower risk of mortality at 1 year. These findings support current guideline recommendations for pulmonary rehabilitation after hospitalization for COPD, although the potential for residual confounding exists and further research is needed.

Respiratory events associated with concomitant opioid and sedative use among Medicare beneficiaries with chronic obstructive pulmonary disease.

BACKGROUND: Opioids and sedatives are commonly prescribed in chronic obstructive pulmonary disease (COPD) patients for symptoms of dyspnoea, pain, insomnia, depression and anxiety. Older adults are advised to avoid these medications due to increased adverse events, including respiratory events. This study examines respiratory event risks associated with concomitant opioid and sedative use compared with opioid use alone in older adults with COPD. METHODS: A 5% nationally representative sample of Medicare beneficiaries with COPD and opioid use between 2009 and 2013 was used for this retrospective cohort study. Current and past concomitant use were identified using drug dispensed within 7 days from the censored date: at respiratory event, at death, or at 12 months post index. Concomitant opioid and sedative use were categorised into no overlap (opioid only), 1 to 10, 11 to 30, 31 to 60 and >60 days of total overlap. The primary outcome was hospitalisation or emergency department (ED) visits for respiratory events (COPD exacerbations or respiratory depression). Propensity score matching was implemented and semi-competing risk models were used to address competing risk by death. RESULTS: Among 48 120 eligible beneficiaries, 1810 (16.7%) concomitant users were matched with 9050 (83.3%) opioid only users. Current concomitant use of 1 to 10, 11 to 30 and 31 to 60 days was associated with increased respiratory events (HRs (95% CI): 2.8 (1.2 to 7.3), 9.3 (4.9 to 18.2) and 5.7 (2.5 to 12.5), respectively), compared with opioid only use. Current concomitant use of >60 days or past concomitant use of ≤60 days was not significantly associated with respiratory events. Consistent findings were found in sensitivity analyses, including in subgroup analysis of non-benzodiazepine sedatives. Additionally, current concomitant use significantly increased risk of death. CONCLUSION: Short-term and medium-term current concomitant opioid and sedative use significantly increased risk of respiratory events and death in older COPD Medicare beneficiaries. Long-term past concomitant users, however, demonstrated lower risks of these outcomes, possibly reflecting a healthy user effect or developed tolerance to the effects of these agents.

Trends and risk factors of mortality and disability adjusted life years for chronic respiratory diseases from 1990 to 2017: systematic analysis for the Global Burden of Disease Study 2017.

OBJECTIVE: To describe the temporal and spatial trends of mortality and disability adjusted life years (DALYs) due to chronic respiratory diseases, by age and sex, across the world during 1990-2017 using data from the Global Burden of Disease Study 2017. DESIGN: Systematic analysis. DATA SOURCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017. METHODS: Mortality and DALYs from chronic respiratory diseases were estimated from the Global Burden of Disease Study 2017 using DisMod-MR 2.1, a Bayesian meta-regression tool. The estimated annual percentage change of the age standardised mortality rate was calculated using a generalised linear model with a Gaussian distribution. Mortality and DALYs were stratified according to the Socio-demographic index. The strength and direction of the association between the Socio-demographic index and mortality rate were measured using the Spearman rank order correlation. Risk factors for chronic respiratory diseases were analysed from exposure data. RESULTS: Between 1990 and 2017, the total number of deaths due to chronic respiratorydiseases increased by 18.0%, from 3.32 (95% uncertainty interval 3.01 to 3.43) million in 1990 to 3.91 (3.79 to 4.04) million in 2017. The age standardised mortality rate of chronic respiratory diseases decreased by an average of 2.41% (2.28% to 2.55%) annually. During the 27 years, the annual decline in mortality rates of chronic obstructive pulmonary disease (COPD; 2.36%, uncertainty interval 2.21% to 2.50%) and pneumoconiosis (2.56%, 2.44% to 2.68%) has been slow, whereas the mortality rate for interstitial lung disease and pulmonary sarcoidosis (0.97%, 0.92% to 1.03%) has increased. Reductions in DALYs for asthma and pneumoconiosis have been seen, but DALYs due to COPD, and interstitial lung disease and pulmonary sarcoidosis have increased. Mortality and the annual change in mortality rate due to chronic respiratory diseases varied considerably across 195 countries. Assessment of the factors responsible for regional variations in mortality and DALYs and the unequal distribution of improvements during the 27 years showed negative correlations between the Socio-demographic index and the mortality rates of COPD, pneumoconiosis, and asthma. Regions with a low Socio-demographic index had the highest mortality and DALYs. Smoking remained the major risk factor for mortality due to COPD and asthma. Pollution from particulate matter was the major contributor to deaths from COPD in regions with a low Socio-demographic index. Since 2013, a high body mass index has become the principal risk factor for asthma. CONCLUSIONS: Regions with a low Socio-demographic index had the greatest burden of disease. The estimated contribution of risk factors (such as smoking, environmental pollution, and a high body mass index) to mortality and DALYs supports the need for urgent efforts to reduce exposure to them.

GOLD Classifications, COPD Hospitalization, and All-Cause Mortality in Chronic Obstructive Pulmonary Disease: The HUNT Study.

Purpose: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published three classifications of COPD from 2007 to 2017. No studies have investigated the ability of these classifications to predict COPD-related hospitalizations. We aimed to compare the discrimination ability of the GOLD 2007, 2011, and 2017 classifications to predict COPD hospitalization and all-cause mortality. Patients and Methods: We followed 1300 participants with COPD aged ≥40 years who participated in the HUNT Study (1995-1997) through to December 31, 2015. Survival analysis and time-dependent area under receiver operating characteristics curves (AUC) were used to compare the discrimination abilities of the GOLD classifications. Results: Of the 1300 participants, 522 were hospitalized due to COPD and 896 died over 20.4 years of follow-up. In adjusted models, worsening GOLD 2007, GOLD 2011, or GOLD 2017 categories were associated with higher hazards for COPD hospitalization and all-cause mortality, except for the GOLD 2017 classification and all-cause mortality (ptrend=0.114). In crude models, the AUCs (95% CI) for the GOLD 2007, GOLD 2011, and GOLD 2017 for COPD hospitalization were 63.1 (58.7-66.9), 60.9 (56.1-64.4), and 56.1 (54.0-58.1), respectively, at 20-years' follow-up. Corresponding estimates for all-cause mortality were 57.0 (54.8-59.1), 54.1 (52.1-56.0), and 52.6 (51.0-54.3). The differences in AUCs between the GOLD classifications to predict COPD hospitalization and all-cause mortality were constant over the follow-up time. Conclusion: The GOLD 2007 classification was better than the GOLD 2011 and 2017 classifications at predicting COPD hospitalization and all-cause mortality.