Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

Influence of physical activity on the prognosis of COPD patients: the HADO.2 score - health, activity, dyspnoea and obstruction.

Objective: The aim of this study was to create a prognostic instrument for COPD with a multidimensional perspective that includes physical activity (PA). The score also included health status, dyspnoea and forced expiratory volume in 1 s (HADO.2 score). Methods: A prospective, observational, non-intervention study was carried out. Patients were recruited from the six outpatient clinics of the respiratory service of a single university hospital. The component variables of the HADO.2 score and BODE index were studied, and PA was measured using an accelerometer. The outcomes for the HADO.2 score were mortality and hospitalisations during follow-up and an exploration of the correlation with health-related quality of life at the moment of inclusion in the study. Results: 401 patients were included in the study and followed up for three years. The HADO.2 score showed good predictive capacity for mortality: C-index 0.79 (0.72-0.85). The C-index for hospitalisations was 0.72 (0.66-0.77) and the predictive ability for quality of life, as measured by R2, was 0.63 and 0.53 respectively for the Saint George's Respiratory Questionnaire and COPD Assessment Test. Conclusions: There was no statistically significant difference between the mortality predictive capacity of the HADO.2 score and the BODE index. Adding PA to the original BODE index significantly improved the predictive capacity of the index. The HADO.2 score, which includes PA as a key variable, showed good predictive capacity for mortality and hospitalisations. There were no differences in the predictive capacity of the HADO.2 score and the BODE index.

Physical activity and sedentary behaviour in patients admitted with COPD: Associated factors.

AIM: To establish amongst a cohort of patients admitted with Chronic Obstructive Pulmonary Disease which factors were associated with their level of Physical Activity and Sedentary Behavior prior to the admission event. METHODS: Prospective observational cohort study. Nine Spanish hospitals participated. Patients were recruited consecutively. Variables relating to the patients' clinical baseline status were recorded, including the COPD Assessment test, the HADS anxiety-depression test, comorbidities and the Yale Physical Activity Survey. Data relating to admission and up to two months after discharge were also recorded. RESULTS: 1638 COPD patients were studied, with a mean age of 72.39 (SD 10.33), 76.56 % male, FEV1 49.41 % (SD19.19), Charlson index 2. The level of PA at baseline was 30.79 points (SD 22.43). Multivariable linear regression analysis identified the following as being associated with low PA: older age, obesity, higher level of hemoglobin, lower score of Barthel index, which means disability, health related quality of life (EuroQoL-5d and CAT) and dyspnea. Variables associated with sedentary behavior were: older age, presence of obstructive apnea syndrome, higher disability, presence of depressive symptoms and dyspnea. CONCLUSIONS: In a cohort of hospitalized COPD patients, we have found several variables, some of them modifiable, associated with physical activity/inactivity and sedentary behavior.

Change in physical activity related to admission for exacerbation in COPD patients.

INTRODUCTION: The aim of this study was to determine the impact of hospitalizations on levels of physical activity (PA) and whether other factors were associated with subsequent changes in PA. METHODS: Prospective observational cohort study with a nested case-control study, with follow-up 60 days from the index hospital admission. Nine hospitals participated in the study. Patients were recruited consecutively. Several variables and questionnaires of the clinical baseline status of the patients were recorded including: the COPD Assessment Test (CAT), the Hospital Anxiety-Depression scale (HADS), comorbidities and the Yale Physical Activity Survey. Patients' data related to admission and up to two months after discharge were also recorded. RESULTS: 883 patients were studied: 79.7% male; FEV1 48%; Charlson index 2; 28.7% active smokers. The baseline PA level for the total sample was 23 points. A statistically significant difference in PA was found between patients readmitted up to 2 months after the index admission and those not readmitted (17vs. 27, p < 0.0001). Multivariable linear regression analysis identified the following as predictors of the decrease of PA from baseline (index admission) up to 2 months follow-up: admission for COPD exacerbation in the two months prior to the index admission; readmission up to 2 months after the index admission; baseline HAD depressive symptoms, worse CAT score, and patient-reported "need for help". CONCLUSIONS: In a cohort of admitted COPD patients, we identified a strong relationship between hospitalization for exacerbation and PA. In addition, some other potentially modifiable factors were found associated with the change in PA level after an admission.

Early Desaturation During 6-Minute Walk Test is a Predictor of Mortality in COPD.

BACKGROUND: Oxygen desaturation during exercise is mainly observed in severe cases of chronic obstructive pulmonary disease (COPD) and is associated with a worse prognosis, but little is known about the type of desaturation that causes the greatest risk of mortality. MATERIAL AND METHODS: We studied all of the 6-min walk tests performed periodically at a tertiary hospital over a period of 12 years in patients with moderate or severe COPD. We classified patients as non-desaturators if they did not suffer a drop in oxygen saturation (SpO2 < 88%) during the test, early desaturators if the time until desaturation was < 1 min, and non-early desaturators if it was longer than 1 min. The average length of follow-up per patient was 5.6 years. RESULTS: Of the 319 patients analyzed, 126 non-desaturators, 91 non-early desaturators and 102 early desaturators were identified. The mortality analysis showed that early desaturators had a mortality of 73%, while it was 38% for non-early desaturators and 28% for non-desaturators, with a survival of 5.9 years compared to 7.5 years and 9.6 years, respectively (hazard ratio of 3.50; 95% CI 2.3-5.3; p < 0.0001). CONCLUSIONS: The early desaturation seen in patients with chronic obstructive pulmonary disease is associated with greater mortality and is likely responsible for the poor prognosis shown globally in patients who desaturate. The survival of patients with early desaturation is almost 4 years less with respect to non-desaturators, and they, thus, require closer observation.

Discriminant Validity of a Single Clinical Question for the Screening of Inactivity in Individuals Living with COPD.

Introduction: Quantifying physical activity in chronic obstructive pulmonary disease (COPD) with questionnaires and activity monitors in clinical practice is challenging. The aim of the present study was to analyse the discriminant validity of a single clinical question for the screening of inactive individuals living with COPD. Methods: A multicentre study was carried out in stable COPD individuals both in primary and tertiary care. Patients wore the Dynaport accelerometer for 8 days and then answered 5 physical activity questions developed for the study, referring to the week in which their physical activity was monitored. Receiver operating characteristic (ROC) curve analysis with physical activity level (PAL) as the gold standard reference was used to determine the best cut-off point for each of the 5 clinical physical activity questions tested. Results: A total of 86 COPD participants were analysed (males 68.6%; mean (SD) age 66.6 (8.5) years; FEV1 50.9 (17.3)% predicted; mean of 7305 (3906) steps/day). Forty-two (48.8%) participants were considered physically inactive (PAL ≤1.69). Answers to 4 out of 5 questions significantly differed in active vs inactive patients. The Kappa index and ROC curves showed that the answer to the question "On average, how many minutes per day do you walk briskly?" had the best discriminative capacity for inactivity, with an area under the curve (AUC) (95% Confidence interval (CI)) of 0.73 (0.63-0.84) and 30 min/day was identified as the best cut-off value (sensitivity (95% CI): 0.75 (0.60-0.87); specificity: 0.76 (0.61-0.88)). Conclusion: The present results indicate that self-reported brisk walk time lower than 30 min/day may be a valid tool for the screening of inactivity in individuals living with COPD in routine care, if more detailed physical activity measures are not feasible.

Validation of the Spanish Activity Questionnaire in COPD (SAQ-COPD) in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The Spanish Activity Questionnaire in COPD (SAQ-COPD) is a short, simple physical activity (PA) measurement instrument for patients with chronic obstructive pulmonary disease (COPD). In this study, we analyzed its validity and sensitivity to change. Methods: Prospective scale validation study. An accelerometer (DynaPort MoveMonitor®) and the Yale Physical Activity Survey (YPAS) were used as reference standards. The analyses examined the criterion validity (Spearman correlations), internal consistency (Cronbach's alpha), factorial structure, test-retest reliability (intraclass correlation coefficient, ICC), sensitivity to change and receiver operating characteristic (ROC) curve to classify patients with low PA. Results: A total of 300 patients diagnosed with COPD were analyzed (73% males, mean age 66 ± 8 years, 40.3% with severe airflow limitation). Cronbach's alpha was 0.60 and Spearman's correlations with accelerometer measurements of PA [number of steps, metabolic equivalents (MET), physical activity level (PAL)] and YPAS ranged from 0.37 to 0.53 (all p < 0.001). ICC was 0.69 (95% CI 0.61-0.74) and the area under the ROC curve to identify low PA was 0.65 (95% confidence interval: 0.58-0.73). Significant variations in SAQ-COPD scores were found between groups defined by YPAS for change. Conclusion: The SAQ-COPD questionnaire is a valid instrument for classifying PA in patients with COPD. Correlations with other instruments provide criterion validity and also demonstrate good sensitivity to change.

Trajectories of Severe Exacerbations of Chronic Obstructive Pulmonary Disease and Their Relationship with Mortality Risk.

PURPOSE: Acute exacerbations of COPD (AECOPD) are important factors contributing to mortality risk. The rate of exacerbations varies overtime. An inconsistent pattern of exacerbation occurrence is a common finding. The mortality risk associated with such a pattern is not entirely clear. Our objective was to assess the risk of mortality associated with various possible patterns of AECOPD trajectories. METHODS: This is a multicenter historical cohort study. Four different exacerbation trajectories were defined according to the incidence of severe AECOPD requiring hospital admission 2 years before and after the date of the first visit to the respiratory clinic-Consistent non-exacerbators (NEx): no AECOPD before or after the index date; consistent exacerbators (Ex): at least one AECOPD both before and after the index date; converters to exacerbators (CONV-Ex): no exacerbations before and at least one AECOPD after the index date; converters to non-exacerbators (CONV-NEx): at least one AECOPD before the index date, and no exacerbations after said date. All-cause mortality risk for these trajectories was assessed. RESULTS: A total of 1713 subjects were included in the study: NEx: 1219 (71.2%), CONV-NEx: 225 (13.1%), CONV-Ex: 148 (8.6%), Ex: 121 (7.1%). After correcting for confounding variables, the group with the highest mortality risk was Ex. The CONV-Ex and CONV-Nex groups had a mortality risk between Ex and NEx, with no significant differences between them. CONCLUSION: Different possible trajectories of severe AECOPD before and after a first specialized consultation are associated with different mortality risks. An inconsistent pattern of exacerbations has a mortality risk between Ex and NEx, with no clear differences between CONV-Ex and CONV-NEx.

Evaluation of the multimorbidity network and its relationship with clinical phenotypes in chronic obstructive pulmonary disease: The GALAXIA study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition, in which taking into consideration clinical phenotypes and multimorbidity is relevant to disease management. Network analysis, a procedure designed to study complex systems, allows to represent connections between the distinct features found in COPD. METHODS: Network analysis was applied to a cohort of patients with COPD in order to explore the degree of connectivity between different diseases, taking into account the presence of two phenotypic traits commonly used to categorize patients in clinical practice: chronic bronchitis (CB+ /CB- ) and the history of previous severe exacerbations (Ex+ /Ex- ). The strength of association between diseases was quantified using the correlation coefficient Phi (ɸ). RESULTS: A total of 1726 patients were included, and 91 possible links between 14 diseases were established. Although the four phenotypically defined groups presented a similar underlying comorbidity pattern, with special relevance for cardiovascular diseases and/or risk factors, classifying patients according to the presence or absence of CB implied differences between groups in network density (mean ɸ: 0.098 in the CB- group and 0.050 in the CB+ group). In contrast, between-group differences in network density were small and of questionable significance when classifying patients according to prior exacerbation history (mean ɸ: 0.082 among Ex- subjects and 0.072 in the Ex+ group). The degree of connectivity of any given disease with the rest of the network also varied depending on the selected phenotypic trait. The classification of patients according to the CB- /CB+ groups revealed significant differences between groups in the degree of conectivity between comorbidities. On the other side, grouping the patients according to the Ex- /Ex+ trait did not disclose differences in connectivity between network nodes (diseases). CONCLUSIONS: The multimorbidity network of a patient with COPD differs according to the underlying clinical characteristics, suggesting that the connections linking comorbidities between them vary for different phenotypes and that the clinical heterogeneity of COPD could influence the expression of latent multimorbidity. Network analysis has the potential to delve into the interactions between COPD clinical traits and comorbidities and is a promising tool to investigate possible specific biological pathways that modulate multimorbidity patterns.

Predictors of short-term COPD readmission.

COPD readmissions have a great impact on patients' quality of life and mortality. Our goal was to identify factors related to 60-day readmission. We conducted a prospective observational cohort study with a nested case-control study, with 60 days of follow-up after the index admission. Patients readmitted were matched, by age, baseline forced expiratory volume in 1 s and month at admission, with patients admitted in the same period but not readmitted at 2 months. Data were collected on sociodemographic and clinical characteristics and health-related quality of life data at the index admission and events from discharge to readmission within 60 days. Conditional logistic (60-day readmission) and Cox (days to readmission) regression models were constructed. Both multivariable analyses identified the following as predictors: any admission in the preceding 2 months (OR: 2.366; HR: 1.918), hematocrit at ED arrival ≤ 35% (OR: 2.949; HR: 1.570), pre-existing cardiovascular disease (valvular disease or myocardial infarction) (OR: 1.878; HR: 1.490); NIMV at discharge (OR: 0.547; HR: 0.70); no appointment with a specialist after discharge (OR: 5.785; HR: 3.373) and patient-reported need for help at home (OR: 2.978; HR: 2.061). The AUC for the logistic model was 0.845 and the c-index for the Cox model was 0.707. EuroQol EQ-5D score before the admission was correlated with a lower risk of readmission (OR: 0.383; HR: 0.670). As conclusions, we have identified factors related to 60-day readmission and summarized the findings in easy-to-use scoring scales that could be incorporated into the daily clinical routine and may help establish preventive measures to reduce future readmissions.Registration: Clinical Trial Registration NCT03227211.

Changes in health-related quality of life as a marker in the prognosis in COPD patients.

Chronic obstructive pulmonary disease (COPD) is understood as a complex, heterogeneous and multisystem airway obstructive disease. The association of deterioration in health-related quality of life (HRQoL) with mortality and hospitalisation for COPD exacerbation has been explored in general terms. The specific objectives of this study were to determine whether a change in HRQoL is related, over time, to mortality and hospitalisation. Overall, 543 patients were recruited through Galdakao Hospital's five outpatient respiratory clinics. Patients were assessed at baseline, and the end of the first and second year, and were followed up for 3 years. At each assessment, measurements were made of several variables, including HRQoL using the St George's Respiratory Questionnaire (SGRQ). The cohort had moderate obstruction (forced expiratory volume in 1 s 55% of the predicted value). SGRQ total, symptoms, activity and impact scores at baseline were 39.2, 44.5, 48.7 and 32.0, respectively. Every 4-point increase in the SGRQ was associated with an increase in the likelihood of death: "symptoms" domain odds ratio 1.04 (95% CI 1.00-1.08); "activity" domain OR 1.12 (95% CI 1.08-1.17) and "impacts" domain OR 1.11 (95% CI 1.06-1.15). The rate of hospitalisations per year was 5% (95% CI 3-8%) to 7% (95% CI 5-10%) higher for each 4-point increase in the separate domains of the SGRQ. Deterioration in HRQoL by 4 points in SGRQ domain scores over 1 year was associated with an increased likelihood of death and hospitalisation.

COPD in SARS-CoV-2 pandemic. baseline characteristics related to hospital admissions.

OBJECTIVE: To develop a predictive model for COPD patients admitted for COVID-19 to support clinical decision-making. METHOD: Retrospective cohort study of 1313 COPD patients with microbiological confirmation of SARS-CoV-2 infection. The sample was randomly divided into two subsamples, for the purposes of derivation and validation of the prediction rule (60% and 40%,respectively). Data collected for this study included sociodemographic characteristics, baseline comorbidities, baseline treatments, and other background data. Multivariable logistic regression analysis was used to develop the predictive model. RESULTS: Male sex, older age, hospital admissions in the previous year, flu vaccination in the previous season, a Charlson Index>3 and a prescription of renin-angiotensin aldosterone system inhibitors at baseline were the main risk factors for hospital admission. The AUC of the categorized risk score was 0.72 and 0.69 in the derivation and validation samples, respectively. Based on the risk score, four groups were identified with a risk of hospital admission ranging from 21% to 80%. CONCLUSIONS: We propose a classification system to identify COPD people with COVID-19 with a higher risk of hospitalization, and indirectly, more severe disease, that is easy to use in primary care, as well as hospital emergency room settings to help clinical decision-making. CLINICALTRIALS.GOV IDENTIFIER: NCT04463706.

A new, three-dimensional approach to the GOLD COPD assessment tool.

BACKGROUND: The 2-dimensional, 4-quadrant 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD A-D assessment tool (GOLD2017) does not include lung function variables to classify patients into different risk groups. The previous 2011 tool (GOLD2011) classified cases in the upper-quadrants (higher risk groups) regardless of whether they had a history of exacerbations or worse lung function. We hypothesized that a modified, three-dimensional classification (GOLD3D) that separately includes assessment of lung function and exacerbations history would improve the ability to predict adverse events. METHODS: A total of 1303 COPD patients were included in a historical cohort study. The ability of GOLD3D to predict outcomes (all-cause death and hospitalizations due to severe exacerbation) was compared with GOLD2017 and GOLD2011. RESULTS: Mean follow-up was 45.0 ± 28.0 months. Two hundred and twenty-eight patients (17.5%) died and 337 (25.9%) subjects suffered at least a severe exacerbation that required hospital admission. The area under the receiver-operating characteristics curve for mortality prediction was slightly but significantly higher for GOLD3D than for GOLD2011. The area under the curve for prediction of severe exacerbations was significantly higher for GOLD3D than for GOLD2011 and GOLD2017. A worse ventilatory obstruction was associated in most cases with a higher mortality risk and a higher exacerbation risk for the GOLD2017 A-D groups. CONCLUSIONS: The proposed GOLD3D classification system upgrades the previous ones, and is advantageous in predicting future adverse events.

Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade.

BACKGROUND: The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD. METHODS: We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities. RESULTS: 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity. CONCLUSIONS: The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD.