The prevalence of chronic obstructive pulmonary disease in high-altitude areas of China: a systematic review and meta-analysis

Introduction

Chronic obstructive pulmonary disease (COPD) remains a major public health problem, characterized by high prevalence and mortality rates, causing a significant socioeconomic burden globally. Epidemiological data indicate that the worldwide prevalence of COPD has reached 10.3%, with projections suggesting this figure will continue to rise due to increasing smoking rates in low- and middle-income countries, coupled with an accelerating aging population (1-3). The World Health Organization has listed COPD as the third leading cause of death worldwide (4). Approximately 3 million people die from COPD each year globally, with projections indicating that this figure may surpass 5.4 million by 2060 (5). As one of the countries with the heaviest burden of COPD in the world, the situation in China is particularly severe: the prevalence rate among people aged 20 years and above is 8.6%, and it is as high as 13.7% among those aged 40 years and above, a significant increase of 66–67% compared to a decade ago (6,7). In 2021, over 1.2 million individuals in China succumbed to COPD (8).

Globally, the total population residing at altitudes of 1,500 m or higher has reached 500.3 million individuals (9). Among this population, 81.6 million people live in areas situated at elevations of 2,500 m or above, while 14.4 million have established their homes in regions exceeding an altitude of 3,500 m (9). The prevalence of COPD in high-altitude areas is approximately 10%, with a notably higher incidence reported in Asia compared to Europe and America (10). In China, high-altitude regions mainly include the Qinghai-Xizang Plateau, the Yunnan-Guizhou Plateau, and the arid and cold areas in the northwest. These regions account for approximately one-fourth of the country’s total land area. The unique low-oxygen environment, extreme climatic conditions, and prevalent reliance on biomass fuels for daily living in these areas collectively present significant risk factors for COPD (11,12). Simultaneously, China’s aging population is accelerating at an unprecedented rate. Projections indicate that by 2050, individuals aged 60 years and above will surpass 400 million, with those aged 80 years and older reaching a staggering 150 million (13). The interplay between this demographic shift and high-altitude environmental challenges underscores that preventing and controlling COPD in China’s elevated regions poses formidable obstacles.

As one of the countries with the largest number of COPD patients, China lacks systematic research on the epidemiological characteristics of COPD in high-altitude areas. Therefore, this study aims to conduct a systematic review and meta-analysis of studies related to the prevalence of COPD in high-altitude areas in China, estimating the prevalence of COPD among individuals living at altitudes of 1,500 m or higher in China. We present this article in accordance with the PRISMA reporting checklist (14) (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1180/rc).

Methods

The meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO; identifier: CRD420251063646). The prespecified protocol elements included: (I) eligibility criteria (cross-sectional studies of individuals aged ≥15 years residing at ≥1,500 m altitude in China); (II) primary outcome (COPD prevalence); (III) predefined subgroups [sex, age, smoking exposure, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, and education level]; (IV) analysis plan (random-effects model meta-analysis with heterogeneity assessment and publication bias evaluation). No deviations from the approved protocol were observed during the execution of the study.

Data sources and searches

Two reviewers independently searched seven English databases (PubMed, Embase, Web of Science, Ovid, ProQuest, Scopus, and The Cochrane Library) and four Chinese databases [China National Knowledge Infrastructure (CNKI), Wanfang, Weipu, and China Biology Medicine disc (CBM)] for relevant studies from the establishment of the databases to May 17, 2025. The search terms were a combination of Medical Subject Headings (MeSH) and free text terms, including “Altitude”, “Plateau”, “Pulmonary Disease”, “Chronic Obstructive”, “COPD”, “Chronic Obstructive Pulmonary Disease”, “Prevalence”, “Epidemiology”, and related Chinese terms. The aim was to comprehensively assess the prevalence of COPD in high-altitude areas in China. The detailed search strategy and search terms are provided in Table S1.

Inclusion criteria and exclusion criteria

The studies included in this meta-analysis should meet the following criteria: (I) cross-sectional studies based on the Chinese population; (II) studies using random sampling methods; (III) clear diagnosis of COPD; (IV) clear altitude of the study area and ≥1,500 m; (V) age ≥15 years; (VI) report the prevalence of COPD in high-altitude areas (or provide the raw data allowing for the calculation of an estimate); (VII) the language is limited to Chinese or English. The diagnostic criteria for COPD conform to the GOLD, specifically, the ratio of forced expiratory volume in 1 second (FEV₁) to forced vital capacity (FVC) is less than 70% after the use of bronchodilators (BDs).

In contrast, the exclusion criteria apply to: (I) reviews, comments, animal studies, letters, conference reports, editorials and case reports; (II) other types of studies; (III) studies targeting specific populations in high-altitude environments, such as patients with sleep apnea, pulmonary embolism, pneumonia, lung cancer, and cardiovascular diseases; (IV) studies on COPD comorbidities; (V) studies on the prevalence of COPD in other high-altitude countries or regions; (VI) studies with incomplete information or insufficient data to calculate the prevalence. Additionally, if multiple studies were published based on the same sample, we selected the most comprehensive or the most recent one.

All the initially retrieved references were imported into EndNote X9, and duplicates were removed. Two reviewers independently screened the titles and abstracts of all studies. The full texts of studies that met the selection criteria were retrieved. Any disagreements were resolved through discussion.

Data extraction and quality assessment

Two reviewers independently retrieved the literature and extracted and recorded the data. Any disagreements regarding the extracted data were resolved through discussion. Figure 1 shows the literature search process. Table 1 presents the characteristics of the included studies, including the first author, publication year, study type, study location, region, time range, sampling method, sample size, altitude, COPD diagnostic criteria, pre-/post-BD, age, gender, GOLD classification, body mass index (BMI), smoking amount, biomass fuel, education level, ethnicity, tuberculosis history, prevalence, and response rate.

Figure 1 PRISMA 2020 flowchart illustrating the study selection process. CBM, China Biology Medicine disc; CNKI, China National Knowledge Infrastructure; COPD, chronic obstructive pulmonary disease; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

The quality of the included studies was independently evaluated by two researchers using the cross-sectional study evaluation criteria of the Agency for Healthcare Research and Quality (AHRQ) (21). This evaluation criterion includes 11 items. For each item, a “Yes” answer earns 1 point, and a “No” or “Unclear” answer earns 0 points, with a total score of 11 points. A score of 8–11 indicates high quality, 4–7 indicates moderate quality, and 0–3 indicates low quality (22). This study included articles with a score of ≥7. The details of the AHRQ assessment for each included study are provided in Table S2.

Research outcome and subgroup classification

The main outcome was the prevalence of COPD. For subgroup analysis, stratified by the following factors: (I) sex (male and female); (II) age (40–49 and ≥50 years); (III) ethnic groups (Han ethnicity and ethnic minority); (IV) educational level (middle school or below and high school or above); (V) cooking fuel types (biofuel and other fuels); (VI) smoking exposure (pack-years) (0, 1–19, and ≥20 pack-years); (VII) BMI (<18.5, 18.5–24, and >24 kg/m²); (VIII) GOLD stage (GOLD I, GOLD II, and GOLD III or IV); (IX) altitude (1,500–3,000 and >3,000 m).

Statistical analysis

We applied the Freeman-Tukey double arcsine transformation to stabilize the variance and used the DerSimonian-Laird random-effects model to calculate the pooled prevalence estimates with 95% confidence intervals (CIs), implemented via the metaprop command (23,24). We used the Q test and I² index to test the heterogeneity of the studies. If the Q test shows P<0.10 and I²>50%, there is heterogeneity among the studies (25). An I²<25% indicates low heterogeneity, 25–75% indicates moderate heterogeneity, and >75% indicates high heterogeneity (26). We estimated tau² (τ²) and 95% prediction interval by metan command. To address the issue of heterogeneity, subgroup analysis was conducted. Funnel plots, Begg’s test, and Egger’s test were used to check for publication bias. Sensitivity analysis (leave-one-out) was also performed to test the stability of the main results. In addition, we adopted a weighted integration strategy (using the weighted average method with sample size as the weight to calculate the combined mean and the weighted combined variance method with degrees of freedom as the weight to calculate the combined standard deviation) to obtain the combined statistics of pre-/post-BD FEV₁/FVC for multiple independent samples (Table 1). P<0.05 was considered statistically significant. All statistical analyses were performed using Stata 15.0 (Stata Corp, College Station, TX, USA).

Results

Study selection

We conducted a comprehensive search of electronic databases, yielding 1,000 potentially relevant articles. After the removal of duplicates, 662 records were retained. During the screening process for titles and abstracts, 92 studies were excluded due to their classification as review articles, editorials, animal experiments, conference reports, among other reasons. Subsequently, an additional 548 studies were excluded for various reasons including being conducted outside of China, focusing on comorbidities associated with COPD, addressing other diseases prevalent at high altitudes, or lacking pertinent content. Following a thorough review of the full texts of 22 studies, we excluded 10 studies that either did not specify the altitude of the study area or reported an altitude below 1,500 m; two studies were excluded due to incomplete data; and four studies were removed because they utilized the same sample. Ultimately, six studies met our criteria and were included in the systematic review and meta-analysis (15-20).

Characteristics and quality assessment of included studies

Table 1 summarizes the basic characteristics and quality assessment results of the included studies. These studies involved 15,621 participants from six provinces in China. The AHRQ quality assessment tool was used to evaluate the six studies, with 2 (33.3%) classified as moderate quality and 4 (66.7%) as high quality. Figure 2 summarizes the prevalence of COPD in high-altitude areas of China.

Figure 2 A diagram showing the prevalence of COPD in regions with an altitude of 1,500 m or higher in China. COPD, chronic obstructive pulmonary disease.

Prevalence of COPD in high-altitude populations

The prevalence of COPD in high-altitude areas was found to be 10% (95% CI: 7–14%), with τ²=0.02 and a 95% prediction interval of 0.027–0.216, exhibiting significant heterogeneity (I²=97.9%, P<0.001; Figure 3). Subsequently, we conducted subgroup analyses to explore the sources of heterogeneity.

Figure 3 Forest plot of COPD prevalence in the population of high-altitude areas in China. CI, confidence interval; COPD, chronic obstructive pulmonary disease; ES, effect size.

Subgroup analysis

To further investigate the sources of heterogeneity, we conducted stratified meta-analyses based on gender, age, ethnicity, education level, cooking fuel type, smoking amount, BMI, GOLD stage, and altitude (Table 2). The prevalence of COPD significantly increased with age in high-altitude areas, with rates of 6% (95% CI: 3–10%) and 17% (95% CI: 11–25%) in the 40–49 and 50+ years age groups, respectively (P=0.004; Figure S1). In terms of ethnic distribution characteristics, no statistically significant difference in COPD prevalence was noted between Han and minority populations residing in high-altitude areas (12% vs. 11%, P=0.80; Figure S2). The prevalence of COPD attributed to biomass fuel combustion and other fuels was comparable (12% vs. 11%, P=0.86; Figure S3). Importantly, individuals with a cumulative smoking history of ≥20 pack-years demonstrated a significantly higher prevalence compared to non-smokers (19% vs. 3%, P=0.01; Figure S4). According to the GOLD classification criteria, the distribution of COPD prevalence among different severity grades showed significant differences (P=0.009; Figure S5). However, no statistically significant differences were identified in COPD prevalence among subgroups categorized by gender (13% vs. 7%, P=0.08; Figure S6), educational level (12% vs. 9%, P=0.46; Figure S7), altitude stratification (11% vs. 8%, P=0.35; Figure S8), and BMI (P=0.31; Figure S9). All subgroup analyses indicated high heterogeneity.

Sensitivity analysis

Leave-one-out sensitivity analyses confirmed the robustness of the pooled estimate. After sequentially removing each individual study, the COPD prevalence (Figure S10) showed only minimal changes, indicating the reliability of the findings.

Publication bias

Begg’s test, Egger’s test, and funnel plots were applied to assess potential publication bias across the six included studies. Although the funnel plot did not display obvious asymmetry and the Begg’s test (Z =1.50, P=0.13) and Egger’s test (t =1.72, P=0.16) were not statistically significant, the limited number of studies (k =6) reduces the power of these methods to detect bias. Consequently, the results should be interpreted with caution. The funnel-plot visualization is provided in Figure S11.

Discussion

This study ultimately included six studies, involving a total of 15,621 research subjects. The quality scores of the included literature ranged from 7 to 9, primarily consisting of medium and high-quality literature. Based on the results of heterogeneity tests (I²=97.9%, P<0.001), we adopted a DerSimonian-Laird random-effects model. Subgroup analyses were conducted across multiple dimensions, including gender, age, ethnicity, educational level, cooking fuel type, smoking amount, BMI, GOLD stage, and altitude. Although the funnel plot showed a symmetrical distribution and the Begg’s test and Egger’s test results indicated no significant publication bias, given the small number of studies, this result should be interpreted with caution. Through sensitivity analysis, which involved excluding individual studies one by one, it was found that the combined effect size did not change significantly, suggesting that the results of this study are relatively stable.

This meta-analysis is the first systematic assessment of the prevalence and risk factor stratification characteristics of COPD in areas of China with an altitude of ≥1,500 m. The study results show that the prevalence of COPD in high-altitude areas of China is 10%. Subgroup analysis showed that the prevalence of COPD was significantly higher in high-altitude populations over 50 years old and with more than 20 pack-years of smoke exposure. These findings provide important epidemiological evidence for formulating targeted COPD prevention and control strategies and also point the way for subsequent research on the relationship between high-altitude environments and the pathogenesis of COPD.

There are significant geographical differences in the prevalence of COPD in China. Compared with other regions of the country, the prevalence of COPD in areas with an altitude of ≥1,500 m is higher than that in Hunan Province (5.06%), Guangzhou City (7.4%), and Anhui Province (9.8%) (27,28). Some studies have shown that the three regions with the highest prevalence of COPD in China are located in parts of Sichuan, Gansu, Shanxi, Guizhou, and Yunnan (29). Notably, these high-prevalence areas are all located in the plateau regions of China, which is highly consistent with the conclusion of this study regarding the impact of altitude on the prevalence of COPD, further supporting the potential role of altitude in the development of COPD.

This study found that the prevalence of COPD in high-altitude areas of China is approximately 10%, which is consistent with the research results of Xiong et al. (10) on the prevalence of COPD in high-altitude areas worldwide. The prevalence among men was 13.0%, higher than the national average for men (12.4%), and among women it was 7.0%, significantly higher than the national average for women (5.1%) (30). This phenomenon may be closely related to the characteristics of the population in plateau areas. Sangeetha et al. (31) analyzed the gene polymorphisms of two specific loci (rs28929474 and rs17580) of the SERPINA1 gene and found a positive correlation between COPD and gene mutations, indicating that individuals at high altitudes are more susceptible to the effects of these mutations. However, alpha-1 antitrypsin deficiency caused by the SERPINA1 gene is rare in China. Additionally, indoor air pollution may also play a significant role (32). In high-altitude areas, residents primarily rely on the combustion of solid fuels for heating and cooking, and poor ventilation conditions in households further exacerbate indoor air pollution levels (33). Commonly used fuel types (such as animal dung) release a substantial amount of small and medium-sized toxic particles during combustion, which can severely damage the respiratory system (34). A meta-analysis showed that the risk of COPD in people exposed to biomass fuel increased by 2.65 times (35). The prevalence of COPD caused by biomass fuel combustion in plateau areas is 12%, which is comparable to the prevalence of COPD caused by other fuel combustion (11%). This may be due to the fact that the particulate matter (PM) produced by fuel combustion can promote oxidative stress responses and lung inflammation (36). Among these, Toll-like receptors (TLRs) play a key role in maintaining and regulating the adaptive immune response to PM (37). Becker et al. (38,39) found that Toll-like receptor 4 (TLR4) antagonists blocked the production of interleukin-6 (IL-6) in alveolar macrophages (AMs) caused by PM, while Toll-like receptor 2 (TLR2) inhibitors blocked the production of interleukin-8 (IL-8) in bronchial epithelial cells triggered by PM. Furthermore, PM can directly stimulate AM to produce pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) (40). PM-mediated oxidative stress can generate reactive oxygen species (ROS) through changes in mitochondrial function and disruption of intracellular calcium homeostasis or via the activation of redox-sensitive signaling pathways that promote the expression of inflammatory cells and pro-inflammatory genes (41). Based on these findings, we suggest promoting the transformation of the energy structure in high-altitude areas, vigorously encouraging the use of clean energy sources such as solar and wind energy, while also enhancing health education for residents to raise their awareness of the hazards of air pollution, thereby effectively reducing the incidence of COPD.

Several studies conducted in Colombia, Peru, and Kyrgyzstan have demonstrated that the prevalence of COPD increases with altitude (32,42,43). However, some studies have reached conflicting conclusions. For instance, the PLATINO team discovered that the prevalence of COPD among adults over 40 years old in five major Latin American cities—Mexico City (average altitude 2,240 m), Caracas (average altitude 950 m), São Paulo (average altitude 800 m), Santiago (average altitude 543 m), and Montevideo (average altitude 35 m)—was 7.8%, 12.1%, 15.8%, 16.9%, and 19.7%, respectively, indicating that higher altitudes are associated with lower prevalence of COPD (44,45). The following reasons may account for this phenomenon. In terms of survivor bias, individuals with long-term exposure to high-altitude, hypoxic environments who inherently have poor lung function or comorbid respiratory diseases tend to face a higher mortality rate (46-48). Over time, the surviving population undergoes adaptive changes in lung function—such as increased FVC, FEV₁, and tidal volume—which leads to the lower prevalence observed in cross-sectional surveys (49). Regarding risk factors, a cross-sectional study by Guo et al. (16) conducted in the altitude range of 2,100–4,700 m noted a significant positive correlation between smoking and the incidence of COPD. However, in regions at higher altitudes (≥3,000 m), the smoking rate among respondents was relatively low. Additionally, this lower prevalence may be associated with the relative scarcity of medical resources and low coverage of lung function testing in high-altitude areas (16). From a physiological perspective, mutations in the susceptibility locus of peroxisome proliferator-activated receptor alpha (PPARA)—a gene critical for high-altitude adaptation—increase the risk of developing COPD (50). As a key gene in high-altitude adaptation, PPARA exhibits higher expression levels in Xizang populations residing in plateau regions (51). Under hypoxic conditions, the activity of prolyl hydroxylases (PHDs) is inhibited, leading to the accumulation and nuclear translocation of hypoxia-inducible factor-2α. This process subsequently upregulates the expression of PPARA and its downstream associated genes, thereby sustaining cellular homeostasis and decreasing the risk of COPD (52). Moreover, the lower prevalence of COPD in high-altitude areas may also be attributed to factors such as underdiagnosis of the disease, atypical respiratory symptoms among residents, and lower educational levels of the population (53). Our study found that the prevalence of COPD was 11% in populations living at altitudes of 1,500–3,000 m, and only 8% in those at altitudes of >3,000 m. While higher altitude exerted a slight positive effect on reducing prevalence, the difference in prevalence between the two groups was not statistically significant. This may be due to insufficient sample size; future studies should expand the sample size and control for potential confounding factors.

Age and smoking are well-established risk factors for COPD (54). The research conducted by Laniado-Laborin et al. (55) confirmed a positive correlation between the prevalence of COPD and age in high-altitude areas. Their study showed that the prevalence of COPD in the 40–49, 50–59, and ≥60 years age groups was 6%, 11%, and 21%, respectively, indicating a significant increase in COPD prevalence among the high-altitude population with age. This is consistent with our research conclusion. We found that in high-altitude areas, the prevalence rate of COPD among people aged 40–49 years was 6%, significantly lower than the 17% among those aged 50 years and above, but higher than the national prevalence rate of 5.1% for the 40–49 years age group (6). The COPD prevalence rate among people over 50 years in high-altitude areas was notably higher than the national average for those over 40 (13.7%) (7). Furthermore, Adeloye et al. (2) noted that tobacco use is one of the primary contributors to the heightened burden of COPD in developing countries. Data from this study revealed that the prevalence of COPD in non-smokers in plateau areas was only 3%, whereas it reached 19% in individuals with a smoking history of ≥20 pack-years. These findings suggest that in high-altitude regions, particular attention should be given to pulmonary function screening for individuals aged 50 years and older, and health education for residents should be enhanced to improve their understanding of smoking hazards, ultimately reducing the risk of COPD effectively.

There are some limitations in this meta-analysis. First, due to the relatively small number of studies on the prevalence of COPD in the Chinese population living at an altitude of ≥1,500 m, the number of included studies is limited, which may affect the representativeness of the results. To avoid overfitting in meta-regression and type I errors, this study only conducted descriptive subgroup comparisons of altitude and did not perform continuous variable meta-regression. Second, due to the inability to obtain detailed data from the original studies, this research was unable to conduct an in-depth exploration of the risk factors related to the prevalence of COPD. Third, the cross-sectional study design included in this analysis may have inherent limitations such as selection bias and information bias that are difficult to completely avoid. Finally, there was significant heterogeneity among the included studies, and subgroup analysis did not reduce the heterogeneity. It should be noted that the inclusion of individuals aged ≥15 years to fully describe the epidemiological characteristics at high altitudes leads to limitations in direct comparison due to the difference in age structure from the national survey of individuals aged ≥20 years. Future studies should prioritize the use of age-standardized prevalence estimates to enable more accurate population comparisons; at the same time, large-scale, multi-center studies should be conducted to further verify the conclusions of this study and provide more reliable evidence-based support for the prevention and control of COPD in high-altitude areas.

Conclusions

This study is the first to systematically assess the characteristics of COPD in China’s plateau areas at or above 1,500 m. The combined prevalence rate is 10%, significantly higher than that in low-altitude cities. The prevalence rate is significantly increased among those aged 50 years or above and those who have smoked for at least 20 pack-years, suggesting that middle-aged and elderly people and heavy smokers in the plateau should be prioritized for screening and intervention. It provides a basis for formulating COPD prevention and control strategies with plateau characteristics. In the future, large-sample, multi-center, and age-standardized prospective studies are needed to verify the impact of high-altitude environments on the pathogenesis of COPD and specific risk factors.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1180/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1180/prf

Funding: This work was supported by the National Natural Science Foundation of China (82460009) and the Gansu Province Key Research and Development Program (22YF7FA083).

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1180/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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