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Global prevalence of chronic obstructive pulmonary disease: systematic review and meta-analysis

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Mehdi Varmaghani 1,2, Mina Dehghani 2,3, Elham Heidari 2, Farshad Sharifi 4, Sahar Saeedi Moghaddam 2,5 and Farshad Farzadfar 2,6

1Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran. 2Non-Communicable Disease Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. 3Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. 4Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. 5Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran. 6Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. (Correspondence to: Farshad Farzadfar: This email address is being protected from spambots. You need JavaScript enabled to view it.).

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.

Aims: To synthesize data on the worldwide prevalence and severity of COPD by geographical region, age groups, and smoking status in a systematic review.

Methods: A systematic search was performed following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. International databases including PubMed, Scopus and Web of Science were searched for population-based studies published between January 2004 and May 2015 that reported the prevalence of COPD anywhere in the world. The prevalence of COPD was calculated based on World Health Organization (WHO) regions and sex and severity stages using metaprop. Meta-regression and subgroup analysis were applied to determine the sources of heterogeneity.

Results: Sixty papers were screened with a combined subject sample size of 127 598. The prevalence of post-bronchodilator COPD was 12.16% (10.91–13.40%). The pooled prevalence of COPD was 15.70% (13.80–18.59%) in men and 9.93% (8.73–11.13%) in women. Among all WHO regions, the highest prevalence was recorded in the Region of the Americas (14.53%), and the lowest was recorded in the South-East Asia Region/Western Pacific Region (8.80%). Meta-regression model variables were: sample size, WHO region, study quality score, level of gathering data, publication year, and sampling methods that justified 29.82% of heterogeneity detected among COPD prevalence rates worldwide.

Conclusions: Global prevalence of COPD among men is about 5% higher than among women. The most prevalent stage of COPD is stage 1.

Keywords: chronic obstructive pulmonary disease, spirometry, GOLD criteria, systematic review, meta-analysis.

Citation: Varmaghani M; Dehghani M; Heidari E; Sharifi F; Moghaddam SS; Farzadfar F. Global prevalence of chronic obstructive pulmonary disease: systematic review and meta-analysis. East Mediterr Health J. 2019;25(1):47–57. https://doi.org/10.26719/emhj.18.014

Received: 07/03/17; accepted: 14/09/17

Copyright © World Health Organization (WHO) 2019. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).

Introduction

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality globally. According to the Global Burden of Disease (GBD) study, COPD rose from the eighth to the fifth leading cause of global burden of disease from 1990 to 2013. In 2013, COPD was the fourth leading cause of death globally, and it is predicted that COPD will become the third leading cause by 2020 (1).

Emphysema and bronchitis can cause loss of daily function in many ways (2), and impose a massive and growing burden, both in direct and indirect costs to society. For example, in 2010, the cost of COPD in the United States of America was estimated at US$ 50 billion, which included US$ 30 billion of direct healthcare expenditure and US$ 20 billion of indirect costs (3). In Italy, as a European example, the total cost of a COPD patient has been calculated as €2706.70, of which €2460.40 is direct costs and €246.30 is indirect costs (4).

A recently published systematic review and meta-analysis that included studies based on different definitions of COPD without distinguishing between them reported the global prevalence of COPD (5), so the pooling of data based on these 2 different definitions was not reasonable. Thus, we undertook a new meta-analysis of COPD prevalence, according to data based on clinically distinct definitions separately. We analysed the worldwide COPD prevalence according to the standard definition of Global Initiative for Chronic Obstructive Lung Disease (GOLD). Additionally, we estimated the COPD prevalence by geographic regions, clinical severity stages, age groups, and smoking status.

Methods

Study design

The study was designed as a systematic review and meta-analysis of the published literature on COPD. It was performed according to Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines (7).

Definitions

There are several different definitions of COPD in the literature. In this study, we used the GOLD definition (8): the presence of a post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 0.70. The stages of COPD were defined as follows: mild COPD or stage I: FEV1/FVC < 70% and FEV1 ≥ 80% predicted; moderate COPD or stage II: FEV1/FVC < 70% and 50% ≤ FEV1 < 80% predicted; severe COPD or stage III: FEV1/FVC < 70% and 30% ≤ FEV1 < 50% predicted; and very severe COPD or stage IV: FEV1/FVC < 70% and FEV1 < 30% predicted.

Search strategy

We searched PubMed, Scopus and Web of Science (ISI) databases for population-based studies published between January 2004 and May 2015 that reported the prevalence of COPD worldwide. The inclusion and exclusion criteria were applied to full-text articles. PubMed was searched using medical subject headings (MeSH) terms, and Scopus was searched using Emtree terms. We also considered all the references and related published systematic reviews in various regions. Figure 1 depicts the search flow diagram, and the search strategy is provided in Online Resource 1.

Inclusion and exclusion criteria

The study included the total sampling population (i.e., survey respondents or general population, population-based cohort studies and population-based case–control studies). From all sampling articles specific groups were excluded as well as studies published in languages other than English, studies using a definition of COPD other than the GOLD definition, and studies conducted before 2004. If the full-text of a study was unavailable, up to 3 requests were e-mailed to the corresponding authors. The reference lists of related systematic reviews were also checked for further studies that might be eligible for inclusion. Two independent reviewers examined the titles and the abstract, then the full texts of the studies to see if they met the inclusion criteria. In case of disagreement, the principal investigator made the final decision.

Data extraction

The data were extracted into a standardized Excel spreadsheet approved by the GBD investigators, including study variables such as name of first author, year of publication, study region, total sample size, response rate, age and sex of participants, number of subjects with COPD or point prevalence based on demographics and severity stages, and 95% confidence intervals of the point prevalence. All data were double-checked by another researcher to ensure it was accurate.

The included studies (6, 9–56) were from the following World Health Organization (WHO) regions: 2 from the African Region, 2 from the South-East Asia Region, 30 from the European Region, 4 from the Eastern Mediterranean Region, 13 from the Western Pacific Region, and 10 from the Region of the Americas. Also, 1 study that was conducted at an international level was included. Because of the scarcity of data, the Eastern Mediterranean Region was merged into the African Region, and South-East Asia Region was merged into the Western Pacific Region. The characteristics of the studies included are described in Table 1.

Study quality assessment

The quality of the studies was scored according to the GBD quality assessment checklist. The total study quality score ranged from 1 to 24 and was based on summing up the level of gathering data (subdistrict = 1, district = 2, provincial = 3, ≥ 2 provinces = 4, ≥ 2 subgroups = 5, and national = 6); sampling method (multilevel clustering random = 1, 1 level clustering random = 2, random simple sampling = 3, random stratified sampling = 4, and census = 5); sample size code ( 10 000 = 4); study design (case control = 1, cohort = 2, cross-sectional = 3); and response rate code ( 90% = 6).

Statistical analysis

The aggregated prevalence of COPD was calculated based on WHO region, sex, and severity stage using metaprop random effects analysis in Stata version 12. Forest plots illustrated both the pooled and individual data of the surveys. We used I2 for calculating the heterogeneity among the studies included. Meta-regression and subgroup analysis methods were used to determine the sources of heterogeneity. We carried out meta-regression based on quality assessment score, WHO regions, sample size, level of gathering data, publication year, and sampling methods. In addition, subgroup analysis was applied using regions, sex, and severity stages. In order to increase the data points, we estimated the post-bronchodilator COPD prevalence by crosswalking using a regression model from pre-bronchodilator data.

Results

Characteristics of the studies included

The primary search recognized 61 588 published papers, including 22 639 in PubMed, 15 916 in Web of Science and 23 033 in Scopus. From those, 15 578 articles were eliminated after removal of duplicates. Thereafter, 45 503 studies were excluded after reading the titles and abstracts. Finally, a total of 60 papers, with a combined subject sample size of 127 598, met the inclusion criteria (Figure 1).

Estimated prevalence of COPD

The prevalence of post-bronchodilator COPD was calculated using a crosswalking method for 16 papers. The R2 of the regression model was 0.97. Using the random effects method, the prevalence of COPD in terms of post-bronchodilator COPD was 12.16% (10.91–13.40%) (Table 2). By regions, COPD prevalence ranged from 8.80% in the combined South-East Asia and Western Pacific Regions to 14.53% in the Region of the Americas. The pooled prevalence of COPD according to sex was 15.70% in men and 9.93% in women. The most common stage of COPD was stage I (7.06%) and the least common were stages III and IV (1.61%).

The COPD prevalence among different stages, both sexes, and WHO regions is shown in Online Resource 2. Furthermore, the COPD prevalence was calculated according to age groups and smoking status. The prevalence of COPD was increased from 5.28% in the < 50 years group to 21.38% in the ≥ 60 years group (Table 3). In terms of smoking status, the least prevalence was found with the never smoked group (7.20%) and the highest prevalence was in the current smokers (18.36%).

Meta-regression

Univariate and multivariate meta-regression analyses were conducted to detect sources of heterogeneity. Meta-regression model variables were: sample size, WHO Region, study quality score, level of gathering data, publication year, and sampling method (Table 4). In the univariate models, significant factors were WHO region, level of gathering data, and sample size. None of the factors could justify the total heterogeneity in the meta-analysis and the mentioned factors explained just 29.82% of the heterogeneity.

Discussion

We found that more than 12% of the general population of the world suffered from COPD. Among all the patients, 44.16% had mild COPD, 44.22% had moderate COPD, and the rest had severe COPD. Our results indicate a higher global prevalence of COPD than that in a previously published meta-analysis (5). The higher prevalence calculated in our study may have been because we considered more recent studies than the previous meta-analysis did. In addition, the previous meta-analysis did not distinguish between different COPD definitions (5). Moreover, it did not consider the severity of COPD, which is a critical factor in specific mortality and burden of COPD. The present study was designed to resolve these shortcomings. Another finding of our study was that the prevalence of COPD increased at a steady rate with ageing of population. These findings are consistent with previous studies (57, 58). Also, we observed that the prevalence of COPD among individuals who had ever smoked was more than twice as high as that among those who had never smoked. This finding confirms that smoking is one of the most important risk factors for COPD (59).

It seems that the prevalence of COPD is increasing. A worldwide prevalence of 8.9% was reported in 2006 (60), based on a meta-analysis of 37 papers, which was lower than the prevalence in the most recent analysis in 2015 (5). It is possible that the difference resulted from using different definitions of COPD. Furthermore, our results are consistent with the findings of some regional studies (61,62), in which the prevalence of COPD was closer to our results than others (5).

The prevalence of COPD is usually more common among men than women (63,64). Our meta-analysis also demonstrated a higher prevalence among men. This difference could be due to higher occupational risks (65) or higher rates of smoking among men (66). The highest prevalence of COPD was observed in the Region of the Americas and the lowest in the South-East Asia Region/Western Pacific Region. These results are consistent with the results of Adeloye et al. (5). Our pooled estimation of the prevalence for the regions is also close to the prevalence reported by regional studies (61,62). This variability of the prevalence between the different regions is partially explained by the level of industrialization, the prevalence of smoking, the geographic situation, and the ethnicities of the populations (67–69). Martin et al. reported a higher rate of COPD among those of white ethnicity than among other ethnicities (70). Eisner et al. concluded that communities with low socioeconomic status were at higher risk of COPD. They also observed a higher prevalence of COPD among populations with low education or income (71). A cohort study that followed a population of > 57 000 subjects for 35 years concluded that long-term exposure to traffic air pollutants may have contributed to the increase in COPD (72). In fact, some researchers believe that COPD would not really exist in the absence of smoking (73).

Our study was a systematic approach for the estimation of COPD severity stages worldwide. We found that most subjects with COPD were in stage 2 (moderate) by GOLD definitions. These findings are important for adjusting the estimation of the global burden of COPD, since the years lived with a disability (YLDs) for COPD is calculated based on the years lost due to disability weight, which is substantially different among different COPD stages. For example, the weight of disability for COPD in the GBD study in 2013 was 0.019 for stage 1 but 0.408 for stage 4 (74).

Our meta-analysis found a high level of heterogeneity among the studies included. Subgroup analysis by sex and region could not relieve this heterogeneity. Besides, we found that WHO region, level of collection data, and sample size were more associated with heterogeneity. However, after adjusting for all factors, we could only account for about 30% of the heterogeneity. This finding is similar to many other meta-analyses of prevalence studies (60,75). This high heterogeneity of the prevalence may have been due to the variability of the prevalence in different populations and regions. It might also have been due to differences among studies regarding the years when they were conducted, their approach to population sampling, and data collection methods. In meta-analysis of prevalence, heterogeneity is more than expected for meta-analysis of relative risks. This could be due to significant real difference in the prevalence rates in various countries and regions (76).

The main limitations of our study were the lack of data for some key regions and inconsistency between the numbers of studies conducted in different regions, which led us to merge the data of 2 WHO regions. The fact that we only included English-language papers was another limitation, since many papers discussed the subject in other languages. Moreover, the age group distribution was inconsistent between some papers so that we could not extract data for all age groups; consequently, we could not standardize the results for age and sex.

However, a strength of our study was the use of a standard definition of COPD to estimate the pooled global prevalence of COPD. This approach eliminated the role of the variable definitions of COPD in the heterogeneity of results in different studies. Another strength of our study was reporting the severity of COPD stages.

Conclusion

It seems that the prevalence of COPD is higher in the Region of the Americas than in other regions. Because of the lack of data in some regions such as the Eastern Mediterranean Region and African Region, we recommend conducting research on the prevalence, incidence, and mortality rate of COPD in these regions.

Acknowledgements

We would like to thank Dr. Michael Hanna for proofreading the manuscript and providing suggestions for improvements.

Funding: None.

Competing interests: None declared.

Prévalence mondiale de la bronchopneumopathie chronique obstructive : analyse systématique et méta-analyse

Résumé

Contexte : La bronchopneumopathie chronique obstructive (BPCO) est l’une des principales causes de morbidité et de mortalité dans le monde.

Objectifs :Réaliser une synthèse des données relatives à la prévalence et à la gravité de la BPCO par régions géographiques, tranches d’âges et statut tabagique à partir d’une analyse systématique de la littérature médicale disponible.

Méthodes : Une recherche systématique a été réalisée conformément aux lignes directrices pour la méta-analyse des études observationnelles (MOOSE). Des recherches ont été lancées dans des bases de données internationales, notamment PubMed, Scopus et Web of Science, afin d’identifier les études populationnelles, publiées entre janvier 2004 et mai 2015, faisant état de la prévalence de la BPCO partout dans le monde. La prévalence de la BPCO a été calculée à l’aide du programme Metaprop en fonction des régions définies par l’Organisation mondiale de la Santé (OMS), du sexe et du stade de sévérité. Des méthodes de méta-régression et d’analyse de sous-groupes ont été appliquées afin d’identifier les sources d’hétérogénéité.

Résultats : Au total, 60 articles ont été analysés portant sur un échantillon composite de 127 598 sujets. La prévalence de la BPCO après utilisation d’un bronchodilatateur était de 12,16 % (10,91 à 13,40 %). La prévalence globale de la BPCO était de 15,70 % (13,80 à 18,59 %) chez les hommes et de 9,93 % (8,73 à 11,13 %) chez les femmes. Sur l’ensemble des régions OMS, la prévalence la plus forte était enregistrée pour les Amériques (14,53 %) et la plus faible pour l’Asie du Sud-Est/le Pacifique occidental (8,80 %). Les variables du modèle de méta-régression utilisé incluaient la taille de l’échantillon, la région, le score de la qualité de l’étude, le niveau des données recueillies, l’année de publication et la méthode d’échantillonnage, justifiant ainsi l’hétérogénéité de 29,82 % associée aux taux de prévalence de la BPCO à travers le monde.

Conclusions : La prévalence mondiale de la BPCO chez les hommes s’avère supérieure d’environ 5 % à celle observée chez les femmes. Le stade 1 de la BPCO est celui ayant la prévalence la plus élevé.

معدل الانتشار العالمي لمرض الانسداد الرئوي المزمن: استعراض منهجي وتحليل تلوي

مهدي ورمقاني، مينا دهقاني، إلهام حيدري، فرشاد شريفي، سحر سعيدي مقدم، فرشاد فرزادفر

الخلاصة

الخلفية: يُعَدُّ مرض الانسداد الرئوي المزمن أحد الأسباب الرئيسية التي تسبب المراضة والوفيات على مستوى العالم.

الأهداف: هدفت هذه الدراسة إلى جمع البيانات حول معدل الانتشار العالمي لمرض الانسداد الرئوي المزمن ومدى شدته حسب المنطقة الجغرافية والفئات العمرية وحالة التدخين، وذلك من خلال استعراض منهجي للمواد الطبية المنشورة.

طرق البحث: أُجري بحث منظَّم اتبع التحليل التلوي للمبادئ التوجيهية الخاصة بالدراسات الرصدية في علم الوبائيات. وتم البحث في قواعد البيانات الدولية، بما في ذلك ، PubMed وScopus وWeb of Science  عن الدراسات القائمة على السكان التي أبلغت عن معدل انتشار مرض الانسداد الرئوي المزمن في أي مكان بالعالم، والمنشورة في الفترة بين يناير/كانون الثاني 2004 ومايو/أيار 2015. وتم حساب معدل انتشار مرض الانسداد الرئوي المزمن بناءً على أقاليم منظمة الصحة العالمية والجنس ومراحل شدة المرض باستخدام برنامج Metaprop الإحصائي. وطُبِقت أساليب التحوف التلوي وتحليل المجموعات الفرعية لتحديد مصادر عدم التباين.

النتائج: استُعرضت 60 ورقة بحثية إجمالاً، وبلغ مجموع حجم العينة 127.598 شخصًا. وبلغ معدل انتشار مرض الانسداد الرئوي المزمن ما بعد إعطاء موسع للقصبات 12.16% (10.91–13.40%). وبلغ مجموع معدل انتشار مرض الانسداد الرئوي المزمن 15.70% (13.80–18.59%) بين الرجال، و9.93% (8.73–11.13%) بين النساء. ومن بين أقاليم منظمة الصحة العالمية، سُجِّل أعلى معدل انتشار في إقليم الأمريكتين (14.53%)، وأقل معدل انتشار في إقليم جنوب شرق آسيا/إقليم غرب المحيط الهادئ (8.80%). وفي نموذج التحوف التلوي، شملت المتغيرات ما يلي: حجم العينة، والأقاليم، ومستوى جودة الدراسة للبيانات المُجمَّعة، وسنة النشر، وأساليب أخذ العينات، والتي توضح 29.82% من عدم التباين المكتشف بين معدلات انتشار مرض الانسداد الرئوي المزمن على مستوى العالم.

الاستنتاجات: يبدو أن معدل الانتشار العالمي لمرض الانسداد الرئوي المزمن بين الذكور أعلى بنسبة 5% تقريبًا عنه بين النساء. وأكثر المراحل انتشارًا من المرض هو المرحلة الأولى.

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