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. 2019 Oct 23;20:229. doi: 10.1186/s12931-019-1198-4

Global prevalence of asthma-COPD overlap (ACO) in the general population: a systematic review and meta-analysis

Mostafa Hosseini 1, Amir Almasi-Hashiani 2, Mahdi Sepidarkish 3, Saman Maroufizadeh 4,✉
PMCID: PMC6813073  PMID: 31647021

Abstract

Background

Asthma-COPD overlap (ACO) is a term that encompasses patients with features of both asthma and COPD. To date, the global prevalence of ACO in the general population remains unknown. The objective of this study was to estimate the prevalence of ACO in the general population using a systematic review and meta-analysis.

Methods

A systematic search of ISI Web of Knowledge, MEDLINE/PubMed, and Scopus was performed up to May 2019 to identify studies reporting the prevalence of ACO. Reference lists from identified studies and relevant review articles were also searched. Eligibility criteria were studies reporting the prevalence of ACO, performed in general population, and published in English language. Pooled prevalence of ACO with 95% confidence interval (CI) was calculated using random effects Meta-analysis.

Results

A total of 27 studies were included in this meta-analysis. The Cochran Q test and I2 statistics revealed substantial heterogeneity among studies. Based on the random-effects model, the pooled prevalence of ACO was 2.0% (95% CI: 1.4–2.6%) in the general population, 26.5% (95% CI: 19.5–33.6%) among patients with asthma, and 29.6% (95% CI: 19.3–39.9%) among patients with COPD. In addition, for included studies, the global prevalence of asthma-only was 6.2% (95% CI: 5.0–7.4%) and COPD-only was 4.9% (95% CI: 4.3–5.5%).

Conclusion

We estimated the global prevalence of ACO based on population-based studies and found that 2.0% of the general population is affected. However, the prevalence of ACO depends on its diagnostic criteria. Therefore, there is a vital need to better define the ACO diagnostic criteria, management and treatment. It is worth noting that the limitations of the present study include lack of studies in some region of the world and small number of studies included in the subgroup analyses.

Keywords: Asthma, COPD, Asthma- COPD overlap, Prevalence, Meta-Analysis, Systematic Review

Background

Asthma and chronic obstructive pulmonary disease (COPD) are major public health problem and represent a leading cause of morbidity and mortality worldwide [1, 2]. Asthma and COPD are the most common chronic respiratory diseases worldwide each with a unique natural history and pathophysiology [1]. Asthma is usually characterized by chronic airway inflammation whereas COPD is characterized by persistent respiratory symptoms and chronic inflammation of the airways [3, 4]. However, patients can sometimes have clinical features of both diseases, and this condition has been termed asthma-COPD overlap (ACO), recommended by joint GINA (Global Initiative for Asthma) and GOLD (Global Initiative for Chronic Obstructive Lung Disease) guideline. According to this guideline, ACO is characterized by “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD”. Furthermore, many studies use the term asthma-COPD overlap syndrome (ACOS), but based on the recent change recommended by the GINA and GOLD in 2017, we will use ‘ACO’ as a term for this condition as it is not considered a single entity but a group of phenotypes [4]. Although asthma and COPD have been well defined, there is currently no consensus on the definition of ACO.

Most previous studies revealed that patients with ACO have more respiratory symptoms, more frequent exacerbations, poor quality of life, higher mortality rate, increased health care utilization, and higher prevalence of comorbidities than those with either asthma or COPD only [5–9].

Numerous population-based studies have been carried out to estimate the prevalence of ACO throughout the world, especially in the USA and Europe [10–36]. However, there is a considerable variation among the studies. The prevalence of ACO has varied widely in these studies from 0.3 to 5.0% in the general population, from 3.2 to 51.4% in patients with asthma, and from 12.6 to 55.7% in patients with COPD. Although there are currently a limited number of population-based studies in this context, it has been growing in recent years.

The global prevalence of ACO remains unknown, and no systematic review and meta-analysis of population-based studies has yet been conducted. On the other hand, due to the considerable heterogeneity among the reported prevalence of ACO, and its significant public health impact, the exact prevalence of ACO is critical for strategic plan and health policy. We therefore conducted a systematic review and meta-analysis of the published literature to examine this parameter. We examined the prevalence both in the general population and among patients with asthma or COPD to understand better the absolute burden of this condition.

Methods

This systematic review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist [37].

Search strategy

A systematic literature search was performed in ISI Web of Knowledge, MEDLINE/PubMed, and Scopus databases up to 30 May 2019 to identify studies reporting the prevalence of ACO. The search strategy in ISI Web of Knowledge is outlined in detail in Table 1. The other databases were searched with similar terms. Reference lists from identified studies and relevant review articles were also searched for studies eligible for inclusion.

Table 1.

Search strategy in database of ISI Web of Knowledge

Set Query Results
#1 (epidemiology) OR (incidence) OR (Prevalence) OR (Frequency) 3483569
#2 (“Asthma-chronic obstructive pulmonary disease overlap syndrome”) OR (“Asthma and chronic obstructive pulmonary disease overlap syndrome”) OR (“asthma-COPD overlap syndrome”) OR (“asthma-COPD overlap”) OR (“asthma-COPD”) OR (“ACOS”) OR (“mixed asthma-COPD phenotype”) OR (“Asthma combined with COPD”) OR (“coexistence of asthma and COPD”) OR (“COPD with asthmatic features”) OR (“overlap of asthma-COPD”) 1692
#3 (“Pulmonary Disease, Chronic Obstructive”) OR (“Chronic Obstructive Pulmonary Disease”) OR (“COPD”) OR (“asthma”) OR (“asthmatic”) OR (“Asthmatic Patient”) 237,190
#4 #1 AND #2 AND #3 258
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Outcomes

Our primary outcome of interest was prevalence of ACO in the general population. Secondary outcomes included the prevalence of ACO in patients with asthma and patients with COPD, prevalence of asthma-only, and prevalence of COPD-only. Table S1 presents definitions of asthma, COPD, and ACO in included studies.

Inclusion and exclusion criteria

The following inclusion criteria were used to select studies: (1) studies reporting the prevalence of ACO, (2) population-based studies, (3) studies published in English language. No time restriction for publication dates was used. The following articles were excluded: (1) studies with no usable data, (2) repeated or overlapping studies, and (3) reviews, meta-analysis, and case reports articles.

Data extraction and quality assessment

Data were abstracted independently by two authors (SM and AAH), and discrepancies were resolved by consensus. The following study characteristics were extracted: first author’s name, year of publication year, country, region, study name, study period, age, sample size, and prevalence of ACO (point or period prevalence). Study quality was assessed independently by two authors (SM and AAH) utilizing the Joanna Briggs Institute’s critical appraisal checklist for studies reporting prevalence data [38]. This tool includes 9 items each of which is rated as either yes, no, not clear, or not applicable [38].

Statistical analysis

All meta-analyses were performed using the Stata version 13.0 (Stata Corp, College Station, TX, USA). The Cochran Q test (P < 0.10 was considered indicative of significant heterogeneity) and the I2 statistic (values of 25, 50, and 75% were considered representing low, medium and high heterogeneity, respectively) were used to assess the heterogeneity between studies [39]. Due to the substantial heterogeneity between studies, pooled prevalence of ACO was calculated using a random-effects model. Potential sources of heterogeneity were explored through meta-regression and subgroup analyses with regard to the study region, year of publication, and study quality. Egger’s test and a visual inspection of funnel plots were used to assess the presence of publication bias [40, 41].

Results

Study selection

A flow diagram of the study selection process is presented in Fig. 1. A total of 787 articles were retrieved from the different sources. After removal of duplicates, 402 records remained. By screening titles and abstracts, we identified 47 articles; after the inclusion and exclusion criteria were applied, 27 articles remained.

Fig. 1.

Fig. 1

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Flow diagram showing search strategy

Study characteristics

The study characteristics of the included studies are summarized in Table 2. In total, we included 27 studies published since 2011, except for one study that published in 1996: twelve from Europe [10, 12, 13, 16, 17, 20, 23, 25, 28–30, 35], nine from the North America (United States and Canada) [11, 15, 18, 21, 26, 27, 32–34], three East Asia (China and Korea) [19, 22, 36], three from the Latin America and 6 low- and middle-income countries and Australia [14, 24, 31]. The majority of the included studies were published after 2015. As presented in Table S2, the risk of bias was low in the majority of the criteria in the included studies.

Table 2.

Description of the studies included in the meta-analysis

First author Pub. Year Country Region Study Study Period Age Sample Size Prevalence (%)
ACO Asthma-only COPD-only ACO in asthma patients ACO in COPD Patients
1 Walsh LJ [10] 1996 UK Europe NA NA > 4 38,865 0.3 8.4 0.8 3.2 25.4
2 Diaz-Guzman E [11] 2011 USA North America NHANES III 1988–2006 > 25 15,203 2.3 4.7 5.4 33.5 30.5
3 de Marco R [12] 2013 Italy Europe GEIRD 2007- ... 20–84 8360 2.1 6.7 5.2 23.8 28.9
4 Miravitlles M [13] 2013 Spain Europe EPI-SCAN 2006–2007 40–80 3802 1.8 NA 8.4 NA 17.4
5 Menezes AMB [14] 2014 Latin America Latin America PLATINO 2002–2004 > 40 5044 1.8 1.7 11.8 51.4 13.0
6 Pleasants RA [15] 2014 USA North America NC BRFSS 2007–2009 > 18 24,073 3.4 5.2 4.7 39.3 41.4
7 Lindström I [16] 2015 Finland Europe NA 2000–2001 30–63 3406 0.7 5.9 2.6 11.1 22.3
8 van Boven JF [17] 2016 Spain Europe MAJORICA 2012–2013 > 18 916,843 0.6 NA 2.5 NA 18.3
9 Kumbhare S [18] 2016 USA North America BRFSS 2012 > 35 80,498 3.2 5.6 6.0 36.6 35.0
10 Ding B [19] 2016 China East Asia China NHWS 2010–2013 > 18 59,935 0.6 1.4 2.7 30.7 18.6
11 Bonten TN [20] 2016 The Netherlands Europe NEO 2008–2012 45–65 5675 1.3 NA NA NA NA
12 Mannino DM [21] 2017 USA North America NHANES 2007–2012 20–79 12,964 1.9 5.0 11.4 27.0 14.0
13 Kim J [22] 2017 Korea East Asia KNHANES IV 2007–2009 > 19 11,656 2.2 5.8 8.4 27.7 20.8
14 Ferrante G [23] 2017 Italy Europe PASSI 2013–2015 18–69 108,705 1.0 3.4 2.6 NA NA
15 Bui DS [24] 2017 Australia Australia TAHS 2006–2008 45 1355 5.0 19.9 4.4 20.2 53.5
16 Baarnes CB [25] 2017 Denmark Europe DCH 1993–2013 50–64 57,053 1.2 2.1 5.9 35.9 16.4
17 Kendzerska T [26] 2017 Canada North America ICES 2002–2012 > 35 7,589,414 3.3 NA NA NA NA
18 Senthilselvan A [27] 2018 Canada North America CHMS 2007–2013 > 30 9059 1.6 6.6 2.2 19.3 41.9
19 Henriksen AH [28] 2018 Norway Europe HUNT 2006–2008 > 20 50,777 1.9 9.8 1.5 16.2 55.2
20 Ekerljung L [29] 2018 Sweden Europe WSAS 2008–2012 16–75 1172 3.4 NA NA NA NA
21 Mindus S [30] 2018 Northern Europe Europe GA2LEN and RHINE III 2008 and 2010–2012 > 40 25,429 1.0 6.5 1.4 13.1 40.8
22 Morgan BW [31] 2018 6 low- and middle-income countries CRONICAS, PRISA, and LiNK 2010- ... 35–92 11,923 3.8 13.6 4.8 21.7 43.8
23 Mendy A [32] 2018 USA North America NHNES 2007–2012 > 40 7570 1.0 NA NA 14.6 12.6
24 Kumbhare S [33] 2018 USA North America NHNES III NA NA 4434 2.8 2.7 7.7 51.2 27.0
25 Koleade A [34] 2018 Canada North America APS 2012 > 12 28,410 2.7 NA NA NA NA
26 Guerriero M [35] 2018 Italy Europe NA 2011–2012 20–79 1236 2.1 5.6 9.1 27.4 18.8
27 Kang HR [36] 2019 Korea East Asia NHIS–NSC 2003–2011 > 40 1,113,656 1.4 1.1 55.7
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ACO: Asthma-COPD Overlap; COPD: Chronic Obstructive Pulmonary Disease

NA: Not available

Prevalence of ACO in the general population

As seen in Fig. 2, the lowest and highest prevalence of ACO in the general population was reported by Walsh et al. in UK (0.3%) [10] and Bui et al. in Australia (5.0%) [24], respectively. The Cochran Q test and I2 statistics revealed substantial heterogeneity among studies (Q(26) = 88,698.3, P < 0.001; I2 = 100%). Therefore, random effects model was used for statistical analysis. The pooled prevalence of ACO in the general population was 2.0% (95% CI: 1.4–2.6%) (Table 3). Furthermore, the shape of funnel plots did not reveal any evidence of obvious asymmetry (publication bias) (Fig. 3). Egger’s test also did not reveal any evidence of publication bias (P = 0.576).

Fig. 2.

Fig. 2

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Forest plot showing prevalence of ACO in the general population. Note. Squares represent study-specific prevalence estimates (size of the square denotes the study-specific statistical weight); Horizontal lines represent 95% confidence intervals (CIs); Diamond represents summary estimate of Prevalence with corresponding 95% CI.

Table 3.

Summary of meta-analysis results

Outcomes Pooled estimates Heterogeneity
NO. of studies Prevalence (95% CI) Model Chi square P I square
ACO 27 2.0% (1.4–2.6) Random 88,698.3 < 0.001 100%
Asthma-only 19 6.2% (5.0–7.4) Random 9163.5 < 0.001 99.8%
COPD-only 22 4.9% (4.3–5.5) Random 15,367.2 < 0.001 99.9%
ACO in asthma patients 19 26.5% (19.5–33.6) Random 17,000,000 < 0.001 100%
ACO in COPD patients 22 29.6% (19.3–39.9) Random 280,000,000 < 0.001 100%
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ACO Asthma-COPD Overlap, COPD Chronic Obstructive Pulmonary Disease, CI Confidence Interval

Fig. 3.

Fig. 3

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Funnel plot for assessing publication bias in meta-analysis for ACO in general population

Prevalence of asthma-only and COPD-only

For included studies, the global prevalence of asthma-only was 6.2% (95% CI: 5.0–7.4%) and COPD-only was 4.9% (95% CI: 4.3–5.5%).

Prevalence of ACO among patients with asthma or COPD

Prevalence of ACO among patients with asthma or COPD were reported in 19 and 22 studies, respectively. These values showed considerable variability in patients with asthma (ranging from 3.2 to 51.4%) and COPD (ranging from 13.0 to 55.7%). When these were pooled, the prevalence of ACO was 26.5% (95% CI: 19.5–33.6%) in patients with asthma and 29.6% (95% CI: 19.3–39.9%) in patients with COPD (see Figs. 4 and 5).

Fig. 4.

Fig. 4

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Forest plot showing prevalence of ACO in patients with asthma. Note. Squares represent study-specific prevalence estimates (size of the square denotes the study-specific statistical weight); Horizontal lines represent 95% confidence intervals (CIs); Diamond represents summary estimate of Prevalence with corresponding 95% CI.

Fig. 5.

Fig. 5

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Forest plot showing prevalence of ACO in patients with COPD. Note. Squares represent study-specific prevalence estimates (size of the square denotes the study-specific statistical weight); Horizontal lines represent 95% confidence intervals (CIs); Diamond represents summary estimate of Prevalence with corresponding 95% CI.

Subgroup analysis

Potential sources of heterogeneity were explored through subgroup analyses with regard to the study region, year of publication (before 2015 vs after 2015), and study quality (≤7 vs ≥8). According to our results, prevalence of ACO was not related to study region (P = 0.994), year of publication (P = 0.995), and study quality (P = 0.865) (Table 4).

Table 4.

Summary of meta-regression and subgroup analysis for prevalence of ACO in the general population

NO. of studies Prevalence of ACO (95% CI) I-square Meta-Regression P-Value
Region of study 0.994
Europe 12 1.3% (1.0–1.6) 99.1%
North America 9 2.5% (1.9–3.0) 99.1%
East Asia 3 1.4% (0.7–2.0) 99.7%
Year of publication 0.995
≤ 2015 7 1.8% (0.7–2.8) 99.4%
>  2015 20 2.1% (1.4–2.8) 100.0%
Study quality 0.865
Low and Moderate (< 8) 5 2.1% (0.7–3.4) 99.5%
High (≥8) 22 2.0% (1.3–2.6) 100.0%
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ACO Asthma-COPD Overlap, COPD Chronic Obstructive Pulmonary Disease, CI Confidence Interval

Discussion

ACO is a newly identified condition with apparently high prevalence, and evidently variable features, which is associated with a high burden of disease. Patients with ACO may have worse outcomes than those with either asthma- or COPD-only. Despite its high prevalence, few population-based studies have examined the prevalence of ACO, and as a result, the epidemiology of this condition remains poorly defined. Furthermore, until 2010 only one study has examined the prevalence of ACO in the population-based studies. Here we present a comprehensive overview of the prevalence of ACO in the general population as well as in patients with asthma-only and COPD-only. The overall prevalence of ACO in the general population was 2.0%. Heterogeneity was observed between included studies. This heterogeneity may be explained by differences in the definitions, diagnostic criteria, disease ascertainment methods, geographic region, population characteristics (e.g., age and smoking), study design, and inherent biases associated with observational studies.

Subgroup analysis was performed to assess ACO prevalence in different geographic regions. Most of the studies originated from either North America or Europe, but others came from Latin America, China, Korea, and six low- and middle-income countries. When stratification was performed by geographic region, no differences in ACO prevalence were found. Data were lacking for regions of Africa and Middle East, and Eastern Europe, so we could not examine the prevalence of ACO in these areas. Because data were lacking for regions of Africa and Middle East, and Eastern Europe, ACO estimates in this meta-analysis may overestimate or underestimate the global health burden. Thus, future population-based studies are required to estimate and compare the prevalence of ACO in the different geographic regions. Ideally, we would have investigated whether the year of study contributed significantly to the heterogeneity observed between included studies; however, the considerable overlap of the time periods prevented this analysis. Because of this limitation, we alternatively replace year of study with year of publication and found that ACO prevalence were not changed by year of publication.

Of included studies, only one study reported temporal trend of ACO prevalence, which indicated increasing prevalence in time [26]; however, additional population-based studies are necessary to confirm this finding. This upward trend may be explained by increasing prevalence of both asthma and COPD, and improvement in monitoring of patients. To date, only three studies from Canada, Denmark, and Taiwan examined the incidence of ACO in the general population, emphasizing that such data are missing in the literature. In these studies, the incidence per 1000 person-years was as follows: Canada, 2.1 [26]; Denmark, 0.64 [25]; and Taiwan, 0.70 [42].

The prevalence of ACO among patients with COPD ranged from 12.6 to 55.7% with pooled prevalence of 29.6%. This finding is consistent with a recent meta-analysis, in which the ACO prevalence among patients with COPD in population-based studies was estimated to be 27.0% [8]. In our study, the prevalence of ACO among patients with asthma ranged from 3.2 to 51.4% with pooled prevalence of 26.5%. In previous studies, the prevalence of ACO among patients with asthma also has varied widely from 11.8 to 27.4% [43–47].

For included studies in this review, the global prevalence of asthma-only was 6.2% and COPD-only was 4.9%. In a recent meta-analysis, the global prevalence of COPD based on the GOLD definition was found to be 12.2% [48]. This difference may be due to the different diagnostic criteria and/or including high risk population in the analysis. According to Global Burden of Disease Study 2015, asthma and COPD were the most prevalent chronic respiratory disease, affecting 358 and 174 million people in 2015, respectively. Moreover, COPD and asthma caused 2.6 and 1.1% of global DALYs, respectively [49]. As a large proportion of patients with asthma and COPD have ACO, as well as a worse condition of ACO than asthma- and COPD-only, it is crucial to increase the awareness of ACO and provide clear management and treatment to reduce the disease burden.

This study has several limitations that should be taken into account when interpreting the results. First, there were no data on ACO prevalence for large regions such as Africa and Middle East, and Eastern Europe, thus the generalizability of the results may be limited. Further population-based studies, particularly in Asia and Africa, are required to better estimate the global prevalence and incidence of ACO. Second, regarding the issue that values of ACO prevalence depends on diagnostic methods, we could not perform subgroup analysis for this source of between-study heterogeneity. Third, the quality of the included studies was not optimal. Fourth, the number of studies included in the subgroup analyses was relatively small, so the prevalence of ACO in these subgroups may not be accurately represented. Fifth, although our search was comprehensive, we did not search some other database such as Embase, CINAHL and DOAJ, and include non-English language publications and non-published studies.

Conclusion

This study showed that 2.0% of the general population is affected by ACO. This finding indicates the considerable clinical impact and major burden posed by ACO. Given that there is no consensus on ACO definition in the literature, and the dependence of its prevalence on diagnostic method, it is important to provide clear diagnostic criteria, management and treatment for this condition.

Supplementary information

12931_2019_1198_MOESM1_ESM.docx (40.8KB, docx)

Additional file 1: Table S1. Definitions of asthma, COPD, and ACO in included studies. Table S2. Quality assessment of included studies in the meta-analysis using Joanna Briggs Institute’s .Critical appraisal checklist for studies reporting prevalence data.

Acknowledgements

Not applicable.

Abbreviations

ACO

Asthma-COPD overlap

ACOS

Asthma-COPD overlap syndrome

CI

Confidence Interval

COPD

Chronic obstructive pulmonary disease

GINA

Global Initiative for Asthma

GOLD

Global Initiative for Chronic Obstructive Lung Disease

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Authors’ contributions

SM: Study concept and design; Collection of data; Analysis and interpretation of the data; Drafting of the article. MH: Study concept and design; Collection of data; Interpretation of the data; Drafting of the article. AAH: Study concept and design; Collection of data; Analysis of the data; Drafting of the article. MS: Conception and design; Interpretation of the data; Drafting of the article. All authors approved the final version of the manuscript for submission.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Mostafa Hosseini, Email: mhossein110@yahoo.com.

Amir Almasi-Hashiani, Email: amiralmasi2007@gmail.com.

Mahdi Sepidarkish, Email: mahdi.sepidarkish@gmail.com.

Saman Maroufizadeh, Phone: +98-9351559663, Email: saman.maroufizadeh@gmail.com.

Supplementary information

Supplementary information accompanies this paper at 10.1186/s12931-019-1198-4.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

12931_2019_1198_MOESM1_ESM.docx (40.8KB, docx)

Additional file 1: Table S1. Definitions of asthma, COPD, and ACO in included studies. Table S2. Quality assessment of included studies in the meta-analysis using Joanna Briggs Institute’s .Critical appraisal checklist for studies reporting prevalence data.

Data Availability Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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