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      Incidence and long-term outcome of severe asthma–COPD overlap compared to asthma and COPD alone: a 35-year prospective study of 57,053 middle-aged adults

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          Abstract

          Background

          Incidence and prognosis for severe asthma–COPD overlap is poorly characterized. We investigated incidence and long-term outcome for patients with asthma–COPD overlap compared to asthma and COPD alone.

          Materials and methods

          A total of 57,053 adults (aged 50–64 years) enrolled in the Danish Diet, Cancer, and Health cohort (1993–1997) were followed in the National Patients Registry for admissions for asthma (DJ45–46) and COPD (DJ40–44) and vital status. Asthma–COPD overlap was defined as at least one hospital admission for asthma and one for COPD (different time points), and incident asthma–COPD overlap as at least one of the diagnoses occurring after enrollment into the Diet, Cancer, and Health cohort.

          Results

          A total of 1,845 (3.2%) and 4,037 (7.1%) participants had admissions for asthma and COPD, respectively, with 662 (1.2%) participants with asthma–COPD overlap. Incidence rate of asthma–COPD overlap per 1,000 person-years was higher in women (0.73) than in men (0.54) ( P<0.02). Mortality rate was higher in asthma–COPD overlap (25.9 per 1,000 person-years) compared with COPD (23.1, P<0.05) and asthma (7.9, P<0.001) alone. Compared to COPD alone, mortality was higher in women with asthma–COPD overlap (19.6 and 25.5, respectively; P<0.01), and the excess mortality rate for asthma–COPD overlap patients was most prominent for younger age groups (12.9 compared to 7.2 and 4.6 for COPD and asthma alone, respectively; P<0.01).

          Conclusion

          This large population-based study revealed a higher incidence of severe asthma–COPD overlap in women compared to men, and furthermore that all-cause mortality is higher in women and younger subjects with asthma–COPD overlap compared with those with asthma or COPD alone.

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          Most cited references 32

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          Increased risk of exacerbation and hospitalization in subjects with an overlap phenotype: COPD-asthma.

          Several COPD phenotypes have been described; the COPD-asthma overlap is one of the most recognized. The aim of this study was to evaluate the prevalence of three subgroups (asthma, COPD, and COPD-asthma overlap) in the Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) study population, to describe their main characteristics, and to determine the association of the COPD-asthma overlap group with exacerbations, hospitalizations, limitations due to physical health, and perception of general health status (GHS). The PLATINO study is a multicenter population-based survey carried out in five Latin American cities. Outcomes were self-reported exacerbations (defined by deterioration of breathing symptoms that affected usual daily activities or caused missed work), hospitalizations due to exacerbations, physical health limitations, and patients' perception of their GHS obtained by questionnaire. Subjects were classified in three specific groups: COPD--a postbronchodilator (post-BD) FEV₁/FVC ratio of < 0.70; asthma--presence of wheezing in the last year and a minimum post-BD increase in FEV₁ or FVC of 12% and 200 mL; and overlap COPD-asthma--the combination of the two. Out of 5,044 subjects, 767 were classified as having COPD (12%), asthma (1.7%), and COPD-asthma overlap (1.8%). Subjects with COPD-asthma overlap had more respiratory symptoms, had worse lung function, used more respiratory medication, had more hospitalization and exacerbations, and had worse GHS. After adjusting for confounders, the COPD-asthma overlap was associated with higher risks for exacerbations (prevalence ratio [PR], 2.11; 95% CI, 1.08-4.12), hospitalizations (PR, 4.11; 95% CI, 1.45-11.67), and worse GHS (PR, 1.47; 95% CI, 1.18-1.85) compared with those with COPD. The coexisting COPD-asthma phenotype is possibly associated with increased disease severity.
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            The Coexistence of Asthma and Chronic Obstructive Pulmonary Disease (COPD): Prevalence and Risk Factors in Young, Middle-aged and Elderly People from the General Population

            Background The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described. This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors. Methods A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20–44 (n = 5163) 45–64 (n = 2167) and 65–84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Results A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65–84 years respectively. Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%). The prevalence of the overlap of asthma and COPD was 1.6% (1.3%–2.0%), 2.1% (1.5%–2.8%) and 4.5% (3.2%–5.9%) in the 20–44, 45–64 and 65–84 age groups. Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01). Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions. Conclusion Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects. The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research.
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              How representative are clinical study patients with asthma or COPD for a larger "real life" population of patients with obstructive lung disease?

              Evidence-based medicine is a corner stone in treatment decision making and large randomised, clinical trials are usually designed in order to provide highly significant results. This study was conducted in order to find out to what extend a "real life" patient population with obstructive lung disease could fit into criteria commonly used in clinical research trials. As a secondary aim of the study, we wanted to compare the OLD population recruited from GP's and specialist outpatient clinics, respectively. Eight-hundred and seventy prospective OLD patients were included. Criteria's for selecting asthma patients to a clinical trial were, absence of co-morbidity, FEV 50-85% of predicted, present or historical reversibility 12% last year, non-smoke or if ex-smoke a smoke burden less then 10 pack years. Only 5.4% of the study asthma patients met with these criteria. Additional criteria as being symptomatic and regular use of inhaled corticosteroids reduced the numbers of eligible asthma patients to 3.3% representing 1.3% of the entire population. The same procedure was applied for the COPD patients, requesting a FEV1 15 pack years) and absence of atopy. This selected 17% of the COPD population, representing 7% of the entire population. We conclude that "evidence based" treatment decisions for OLD are based on studies which include a very small and highly selected fraction of this patient population. It is questionable whether such data can extrapolated to a larger, "real life" population of patients with obstructive lung disease. Moreover, we found surprisingly minor differences between the Specialist and GP populations.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2017
                10 February 2017
                : 12
                : 571-579
                Affiliations
                [1 ]Department of Pulmonary Medicine, Hvidovre Hospital, Hvidovre
                [2 ]Center for Epidemiology and Screening, Department of Public Health, University of Copenhagen
                [3 ]Danish Cancer Society Research Center
                [4 ]Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
                Author notes
                Correspondence: Charlotte Suppli Ulrik, Department of Pulmonary Medicine, Hvidovre Hospital, 30 Kettegård Alle, Hvidovre 2650, Denmark, Tel +45 3862 2177, Email csulrik@ 123456dadlnet.dk
                Article
                copd-12-571
                10.2147/COPD.S123167
                5312695
                © 2017 Baarnes et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Respiratory medicine

                incidence, copd, asthma–copd overlap, acos, outcome, mortality, asthma

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