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      COPD exacerbations and patient-reported outcomes according to post-bronchodilator FEV 1 – a post-hoc analysis of pooled data

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          Abstract

          Background

          Management strategies of chronic obstructive pulmonary disease (COPD) need to be tailored to the forced expiratory volume in one second (FEV 1), exacerbations, and patient-reported outcomes (PROs) of individual patients. In this study, we analyzed the association and correlation between the FEV 1, exacerbations, and PROs of patients with stable COPD.

          Methods

          This was a post-hoc analysis of pooled data from two cross-sectional studies that were previously conducted in Malaysia from 2017 to 2019, the results of which had been published separately. The parameters measured included post-bronchodilator FEV 1 (PB-FEV 1), exacerbations, and scores of modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George’s Respiratory Questionnaire for COPD (SGRQ-c). Descriptive, association, and correlation statistics were used.

          Results

          Three hundred seventy-four patients were included in the analysis. The PB-FEV 1 predicted was < 30% in 85 (22.7%), 30–49% in 142 (38.0%), 50–79% in 111 (29.7%), and ≥ 80% in 36 (9.6%) patients. Patients with PB-FEV 1 < 30% predicted had significantly more COPD exacerbations than those with PB-FEV 1 30–49% predicted (p < 0.001), 50–79% predicted (p < 0.001), and ≥ 80% predicted (p = 0.002). The scores of mMRC, CAT, and SGRQ-c were not significantly higher in patients with more severe airflow limitation based on PB-FEV 1 (p = 0.121–0.271). The PB-FEV 1 predicted had significant weak negative correlations with exacerbations (r = − 0.182, p < 0.001), mMRC (r = − 0.121, p = 0.020), and SGRQ-c scores (r = − 0.114, p = 0.028). There was a moderate positive correlation between COPD exacerbations and scores of mMRC, CAT, and SGRQ-c (r = 0.407–0.482, all p < 0.001). There were significant strong positive correlations between mMRC score with CAT (r = 0.727) and SGRQ-c scores (r = 0.847), and CAT score with SGRQ-c score (r = 0.851) (all p < 0.001).

          Conclusions

          In COPD patients, different severity of airflow limitation was not associated with significant differences in the mMRC, CAT, and SGRQ-c scores. Exacerbations were significantly more frequent in patients with very severe airflow limitation only. The correlation between airflow limitation with exacerbations, mMRC, and SGRQ-c was weak.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12890-023-02436-1.

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          Most cited references52

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          Standardisation of spirometry.

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            Susceptibility to exacerbation in chronic obstructive pulmonary disease.

            Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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              Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

              Summary Background Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide. Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study. The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year. Methods We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool. First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases. Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data. Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA. We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma. We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence. We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level. Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate. Findings In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990. There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population. From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9). In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0). The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9). Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply. Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI. The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum. Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke. Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD. Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma. Interpretation Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD. Deaths from COPD were eight times more common than deaths from asthma. In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs. Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD. Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions. Funding Bill & Melinda Gates Foundation.
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                Author and article information

                Contributors
                cschai@unimas.my
                nlcdiana@unimas.my
                sumastika@gmail.com
                dr.muhd.amin@gmail.com
                pramudita_1@hotmail.com
                yongkek@gmail.com
                liamck@ummc.edu.my
                Journal
                BMC Pulm Med
                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central (London )
                1471-2466
                28 April 2023
                28 April 2023
                2023
                : 23
                : 150
                Affiliations
                [1 ]GRID grid.412253.3, ISNI 0000 0000 9534 9846, Department of Medicine, Faculty of Medicine and Health Science, , University Malaysia Sarawak, ; Kota Samarahan, Sarawak, Malaysia
                [2 ]GRID grid.412253.3, ISNI 0000 0000 9534 9846, Department of Nursing, Faculty of Medicine and Health Science, , University Malaysia Sarawak, ; Kota Samarahan, Sarawak, Malaysia
                [3 ]Department of Medicine, Faculty of Medicine, University Technology MARA, Sungai Buloh, Selangor Malaysia
                [4 ]GRID grid.10347.31, ISNI 0000 0001 2308 5949, Department of Medicine, Faculty of Medicine, , University of Malaya, ; Kuala Lumpur, Malaysia
                Article
                2436
                10.1186/s12890-023-02436-1
                10148499
                37118725
                f9f81b56-fcec-49c9-b0f3-a5ae238a215e
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 4 March 2022
                : 15 April 2023
                Funding
                Funded by: Universiti Malaysia Sarawak
                Categories
                Research
                Custom metadata
                © The Author(s) 2023

                Respiratory medicine
                chronic obstructive pulmonary disease (copd),forced expiratory volume in one second (fev1),exacerbations,modified medical research council (mmrc),copd assessment test (cat),st george’s respiratory questionnaire for copd (sgrq-c)

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