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. 2026 Jul 20;89(4):491–505. doi: 10.4046/trd.2025.0199

Visualizing Three Decades of Chronic Obstructive Pulmonary Disease and Airway Mucus Hypersecretion Research: A Bibliometric Analysis (1994–2024)

Naer An 1,2,*, Dongmei Wang 3,*, Dan Xu 1,2, Jiangyue Qin 4, Yanqiu Wu 1,2, Lijuan Gao 1,2, Fangying Chen 5, Zhenni Chen 6, Lian Liu 1,2,✉, Yongchun Shen 1,2,✉, Fuqiang Wen 1,2
PMCID: PMC13660862  PMID: 42473419

Abstract

Background

Chronic obstructive pulmonary disease (COPD) is a condition with high prevalence and mortality, causing a substantial disease burden. Airway mucus hypersecretion (AMH) is clinically associated with impaired pulmonary function, diminished quality of life, and increased mortality in COPD patients. The purpose of this bibliometric research was to identify research developments and emerging hotspots within the field of AMH and COPD by providing a comprehensive overview of the current research landscape.

Methods

The Web of Science core database was searched for publications addressing COPD and AMH from January 1, 1994, to December 31, 2024. A total of 1,405 publications were retrieved and subjected to bibliometric and visual analyses using CiteSpace, VOSviewer, and R software.

Results

From 1994 to 2024, both publication output and citation frequency in this field demonstrated a sustained upward trajectory. The United States of America occupies a prominent position in this domain, characterized by substantial collaborative networks and research productivity. While extensive inter-country and interinstitutional collaborations were evident, researcher-level collaborations remained relatively fragmented. Notably, Boucher, Richard C. received substantial recognition owing to his exceptional research productivity and citation impact. Keywords including exacerbations, autophagy, and mucus plugs exhibited the strongest citation bursts during 2023–2024.

Conclusion

This research illustrates the present landscape, focal points, and future directions in the fields of COPD and AMH. Researchers may benefit from obtaining a rapid synopsis, along with citations and innovative concepts, to facilitate and inform subsequent investigations.

Keywords: Chronic Obstructive Pulmonary Disease, Airway Mucus Hypersecretion, Bibliometric Analysis

Introduction

Chronic obstructive pulmonary disease (COPD), defined as a heterogeneous lung condition with persistent and typically progressive airflow limitation, arises from airway or alveolar abnormalities that induce chronic respiratory symptoms (dyspnea, cough, sputum production, and/or exacerbations) [1]. In 2017, chronic respiratory diseases affected more than 544 million individuals globally, with COPD accounting for approximately 55% of the total cases [2]. In 2021, there were 16.9 million new COPD cases globally [3]. As the third leading cause of death worldwide, COPD contributed to 4.72% of global mortality in 2020 and 3.7 million deaths in 2021 [4,5]. According to the Global Burden of Disease study, annual COPD-related mortality exceeds 3.3 million deaths [6]. In addition to substantial health impacts, COPD imposes severe economic burdens, with projected global costs reaching $4.326 trillion between 2020 and 2050 [7]. These factors collectively establish COPD as a critical public health challenge, generating multifaceted burdens on both individuals and healthcare systems.

The pathophysiology of airflow obstruction in COPD involves the interplay of chronic bronchitis (characterized by inflammation, mucus hypersecretion, and impaired clearance), emphysema (marked by alveolar destruction and airway collapse), and small airway narrowing [8]. Respiratory symptoms and recurrent exacerbations constitute key prognostic indicators, whereas a decrease in lung function remains central to disease staging [9]. Emerging evidence suggests that airway mucus hypersecretion (AMH) serves as a common pathogenic mechanism driving disease progression across distinct COPD phenotypes, leading to debilitating symptoms such as persistent cough and sputum production, accelerated lung function decline, frequent exacerbations, and increased mortality risk [10]. Typically, respiratory mucins function as barriers that protect epithelial cells through mechanical and immunological mechanisms [11,12]. However, chronic exposure to inhalational insults such as cigarette smoke induces the sustained release of prosecretory factors, promoting endocrine cell hypertrophy and goblet cell hyperplasia and leading to AMH [13]. This maladaptive process clinically manifests as accelerated lung function decline, recurrent infections, and elevated mortality risk [14]. Despite these advances, comprehensive analyses systematically characterizing global research trends in COPD-associated AMH currently remain scarce.

By using mathematical and statistical techniques, bibliometric analysis introduces an innovative scientific approach [15]. This methodology enables the identification of knowledge structure, development trends and research hotspots within specific fields through statistical assessment and data visualization [16]. Although bibliometric approaches have been extensively applied in medical research, no dedicated investigation has focused specifically on COPD-AMH research. To address this gap, we performed a thirty-year longitudinal analysis of this field. This approach allows researchers to efficiently map seminal contributions, track thematic evolution, and identify promising research directions.

Materials and Methods

1. Data sources and search strategy

This bibliometric analysis utilized data from the Web of Science Core Collection (WOSCC), recognized as the premier database for comprehensive coverage of global scientific literature [17]. The search was conducted globally over the past three decades from January 1, 1994, to December 31, 2024. Search terms focused on COPD and AMH according to Medical Subject Headings (MeSH), employing the following strategy: TS= (“chronic obstructive pulmonary disease” OR “COPD” OR “chronic airflow obstruction” OR “chronic obstructive lung disease”) AND TS= (“mucus” OR “airway mucus” OR “mucus hypersecretion” OR “airway mucus hypersecretion”). To minimize selection bias introduced by database updates, two investigators independently performed the literature screening in January 2025, and the concordance of the screening outcomes surpassed 0.9.

2. Inclusion and exclusion criteria

Eligibility criteria were defined as follows: (1) publications from 1994 to 2024; (2) peer-reviewed articles and reviews (excluding book chapters, conference proceedings, letters, retracted works, and editorials); (3) English-language publications; (4) exclusion of duplicate records; (5) exclusion of unpublished manuscripts; and (6) exclusion of publications lacking direct relevance. All retrieved articles contained fully documented and cited references. Figure 1 shows a flowchart of the search strategy and selection process of this study.

Figure 1.

Figure 1.

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Flowchart of the literature screening process.

3. Data analysis and visualization

Data analysis was conducted using VOSviewer (v1.6.19), CiteSpace (v6.4.R1), and R's bibliometrix package (v5.4.0). Annual publication trends were visualized via GraphPad Prism version 9.0 (GraphPad Software Inc., San Diego, CA, USA). The bibliometric analysis included temporal trends in publication/citation, geographic/institutional/authorial/journal contributions, collaboration networks, keyword co-occurrence clusters and burst detection. Bibliometric indicators such as the number of publications (Np) and citations excluding self-citations (Nc) are widely acknowledged in academia as essential metrics for assessing research productivity and impact [18]. The H-index integrates productivity and impact by establishing a benchmark linking Np with Nc. The Journal Citation Reports (JCR) provides the impact factor (IF), a widely accepted indicator for evaluating the quality and significance of medical journals.

4. Bibliometric analysis parameters

We extracted all keywords and standardized them (unifying singular and plural forms, British and American spellings, and merging synonyms). For CiteSpace, time slicing was set from 1994 to 2024 with 1-year intervals (yielding 31 time slices); node types analyzed included ‘Keyword’ and ‘Cited reference’ in separate analyses; node selection employed top n=50 per slice with g-index (k=25) thresholding to prioritize high-impact terms; network pruning used the Pathfinder network scaling method with sliced networks merged to eliminate weak links; cluster labeling utilized the log-likelihood ratio algorithm (p<0.05), extracting the top 100 most representative terms per cluster; and visualization employed the timezone view for temporal analysis and dual-map overlay for journal citation patterns. For VOSviewer, keywords with a frequency of ≥20 were retained for co-occurrence analysis using full counting methodology (each co-occurrence receiving a weight of 1); association strength normalization was applied with a resolution parameter of 1.0 for modularity optimization; network layout utilized the attraction-repulsion algorithm (repulsion=1, attraction=2) with 1,000 iterations for convergence; and keyword labels were proportionally scaled by occurrence frequency, with terms exceeding 100 occurrences manually verified for consistency. For R software, bibliometric analysis used bibliometrix package through the online Biblioshiny interactive interface, the specific workflow and parameters are clearly stated in Supplementary Materials and Methods.

Results

1. Overview of publications and citations

This analysis encompassed 1,405 selected publications addressing COPD-AMH interactions from 1994 to 2024. The articles yielded a total Nc of 69,033, with an average Nc of 48.82 per article and a collective H-index of 128. Temporal trends in publication and citation patterns are presented in Figure 2. Despite these fluctuations, publication volumes demonstrated sustained overall growth, paralleled by steadily increasing citation counts.

Figure 2.

Figure 2.

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Publications and citations on chronic obstructive pulmonary disease and airway mucus hypersecretion from 1994 to 2024.

2. Analysis of countries/regions

A total of 383 countries/regions have contributed to COPD-AMH research over the past 30 years (Figure 3A). The top 10 productive countries accounted for more than 90% of the total publications (Table 1). The cooperation network of countries/regions is shown in Figure 3B. The influence of a country’s research publications on other countries participating in studies can be measured by the total link strength. The USA was at the forefront of the field of COPD and AMH, followed by the United Kingdom (UK) and China. Compared with other countries, the USA not only has the highest Np, Nc and H-index values, but also shows the most extensive international collaborations (Figure 3C).

Figure 3.

Figure 3.

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Contribution of Countries/Regions to the Research Regarding chronic obstructive pulmonary disease and airway mucus hypersecretion. (A) World map displaying the global distribution of the current research field. Different countries are indicated by different colors based on the number of publications. (B) Distribution and international cooperation of countries/regions involved in the current research field. The segment of different colors on the circle symbolizes a country/region, the length of the segment is directly correlated with the quantity of publications attributed to it. The interconnecting lines symbolize collaboration between different countries, and the thickness of the line reflects the frequency of the cooperation. (C) The number of publications of the top 10 most productive countries within the current focused field. SCP: single country publication; MCP: multiple country publication.

Table 1.

Top 10 most productive countries in field of chronic obstructive pulmonary disease and airway mucus hypersecretion

Rank Country Np Nc Total link strength H-index
1 United States of America 495 28,486 348 82
2 United Kingdom 224 15,283 310 58
3 China 214 4,746 68 30
4 Germany 109 4,990 168 35
5 Italy 99 4,609 123 31
6 Netherlands 87 5,074 164 37
7 Canada 78 4,313 95 28
8 Australia 58 3,070 82 26
9 Japan 58 2,615 1,433 19
10 France 57 2,097 31 27
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Np: number of publications; Nc: number of citations excluding self-citations.

3. Analysis of institutions

Among 4,913 contributing institutions, the top 10 accounted for over 25% of the publications (Table 2). The University of North Carolina (USA) led the path with 67 publications. Universities and hospitals constituted the primary research settings, with institutions in the USA being the leading contributors to this area over the last 30 years. According to the cooperation network, there were notably extensive alliances among institutions (Figure 4A).

Table 2.

Top 10 the most productive institutions in field of chronic obstructive pulmonary disease and airway mucus hypersecretion

Rank Institution Country Np Nc Total link strength H-index
1 University of North Carolina USA 67 4,429 153 38
2 University of Groningen Netherlands 46 3,134 142 28
3 University London Imperial Coll Sci Technol & Med UK 42 4,649 39 27
4 University of Alabama Birmingham USA 31 1,225 128 16
5 University of Michigan USA 29 1,489 156 17
6 Imperial College London UK 29 1,394 113 16
7 Temple University USA 28 1,648 146 22
8 Sichuan University China 28 571 35 15
9 National Jewish Health USA 27 1,600 174 15
10 University of California–San Francisco USA 26 3,716 119 13
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Np: number of publications; Nc: number of citations excluding self-citations.

Figure 4.

Figure 4.

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Visualization map of the distributions of institutions/authors/journals. (A) Visualization map of institutions. Each point on the map symbolizes a study object. The size of the node is positively correlated with the frequency of occurrence of the study objects. The connecting lines symbolize cooperative relationships between different study objects, and the thickness of the lines represents the strength of the relationship. The color of the nodes indicates the collaborative group. (B) Visualization map of authors. (C) Visualization map of journals. (D) Trend of the number of publications in the top 10 productive journals from 1994 to 2024.

4. Analysis of authors

The 1,405 publications involved 7,528 authors, with 80% of the top 10 most productive authors from the USA (Table 3). Boucher, Richard C., emerged as the most influential researcher, with Np of 28, Nc of 3,086, and an H-index of 112. Collaboration clusters centered on Boucher, Richard C., Han, Meilan K., and Gosens, Reinoud, whereas independent researchers exhibited limited connectivity and lacked extensive collaboration (Figure 4B).

Table 3.

Top 10 authors in field of chronic obstructive pulmonary disease and airway mucus hypersecretion

Rank Author Country Institution Np Nc H-index Total link strength
1 Boucher, Richard C. USA University of North Carolina 28 3,086 112 273
2 Mall, Marcus A. Germany German Center for Lung Research Free University of Berlin 22 1,199 72 95
3 Kim, Victor USA Temple University 17 1,100 34 262
4 Han, Meilan K. USA National Jewish Health 18 1,318 66 334
5 Kesimer, Mehmet USA University of North Carolina 16 1,261 33 157
6 Criner, Gerard J. USA Temple University 15 1,146 82 247
7 Rowe, Steven M. USA University of Alabama Birmingham 15 690 54 42
8 O'Neal, Wanda K. USA University of North Carolina 13 1,635 59 175
9 Tarran, Robert USA University of North Carolina 13 606 36 19
10 Wen, Fuqiang China Sichuan University 13 260 43 54
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Np: number of publications; Nc: number of citations excluding self-citations.

5. Analysis of journals

In total, 480 journals published 1,405 articles on COPD and AMH. A significant portion of the journals were from American and European countries, with a focus on respiratory medicine and physiology. Figure 4C shows the connections and collaborations between the journals. The top 10 journals based on Np published 395 related articles (Table 4). The European Respiratory Journal was the most productive journal in this field (Np=56, Nc=5,487, IF=21). Figure 4D shows the 30-year publication trends of the top 10 journals.

Table 4.

Top 10 the most productive journals in field of chronic obstructive pulmonary disease and airway mucus hypersecretion

Rank Productive Journal Np Nc H-index IF (2025) JCR
1 European Respiratory Journal 56 5,487 37 21.0 3.97
2 American Journal of Respiratory and Critical Care Medicine 55 6,212 39 19.4 4.15
3 Chest 43 3,988 29 8.6 1.97
4 American Journal of Respiratory Cell and Molecular Biology 43 2,808 27 5.3 1.24
5 American Journal of Physiology-Lung Cellular and Molecular Physiology 39 2,076 23 3.5 1.35
6 International Journal of Chronic Obstructive Pulmonary Disease 36 542 14 2.8 0.62
7 Respiratory Medicine 34 1,289 19 3.1 0.99
8 Respiratory Research 33 1,359 18 5.0 1.34
9 PLOS ONE 30 857 18 2.6 0.91
10 Pulmonary Pharmacology and Therapeutics 26 922 18 2.8 0.89
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Np: number of publications; Nc: number of citations excluding self-citations; IF: impact factor; JCR: Journal Citation Indicator.

6. Analysis of citations

Citation analysis constitutes a crucial component of bibliometric research and scholarly impact assessment. Burst detection analysis (Figure 5A) identified the top 20 references with the strongest citation bursts in the COPD and AMH fields from 1994 to 2024. The article “Airway mucin concentration as a marker of chronic bronchitis” demonstrated the highest burst intensity (23.23). Most influential articles delved into the molecular and cellular mechanisms of chronic respiratory diseases in terms of inflammation, airway hyperreactivity, mucin hypersecretion, airway remodeling and oxidative stress.

Figure 5.

Figure 5.

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Top 20 references, dual-map overlay and corresponding disciplines. (A) Top 20 references with the strongest citation bursts. The timeline is represented by blue lines, whereas the burst period is represented by red segments. (B) Dual-map overlay and corresponding disciplines. The citing journals are on the left, the cited journals are on the right, and the colored path represents the citation relationship.

7. Analysis of citation relationships between research disciplines

Dual-map overlay analysis visualizes citation relationships between journals, thereby revealing instances of interdisciplinary crossover (Figure 5B). The most prominent stripe illustrates four principal citation pathways. The yellow pathway indicates that articles published in journals specializing in molecular/biological/immunology were frequently cited in molecular/biology/genetics and health/nursing/medicine journals. The green pathway signifies that articles from medicine/medical/clinical journals were predominantly cited in these same two journal categories.

8. Analysis of keywords

Among 5,435 keywords, 100 high-frequency keywords (≥20 occurrences) were categorized into four clusters (Figure 6A). The red cluster focuses on COPD diagnosis, management, and therapy. The green cluster highlights the biological mechanisms of airways and mucus, including gene expression and inflammation. The blue cluster is associated with asthma, inflammation, airway hyperresponsiveness, and cytokines. The yellow cluster pertains to cystic fibrosis (CF) and mucus clearance, emphasizing mucociliary clearance (MCC) and transmembrane conductance regulators. Temporal trend of keywords revealed that mucus plugs and autophagy as emerged as hot topics over the recent 2 years (Figure 6B).

Figure 6.

Figure 6.

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Visualization map of keywords. (A) Keywords co-occurrence clusters. (B) Timeline of research trends in the field of chronic obstructive pulmonary disease (COPD) and airway mucus hypersecretion. (C) Top 100 keywords with the strongest citation bursts. (D) Temporal evolution of autophagy-related research themes in COPD and airway mucus hypersecretion.

Burst detection analysis of the top 100 keywords (2004–2024) identified seven research frontiers in COPD mucus hypersecretion: “exacerbations,” “autophagy,” “mucus plugs,” “small airway obstruction,” “Pseudomonas aeruginosa,” “dendritic cells,” and “matrix metalloproteinases” (Figure 6C). Notably, acute exacerbations, autophagy, and mucus plugs exhibited the highest burst intensities. VOSviewer temporal mapping further positioned autophagy at the convergence of four critical pathological processes: oxidative stress, mitochondrial dysfunction, proteostasis, and apoptosis, illustrating an evolution from descriptive studies of oxidative damage toward mechanistic investigations of cellular quality control systems with strong functional coupling to established COPD pathogenesis (Figure 6D).

Discussion

1. General trends

COPD represents a major global health burden, contributing significantly to worldwide morbidity, mortality, and healthcare utilization [19]. AMH is one of the most important features of COPD, promoting bacterial colonization, exacerbation frequency and severity, and deterioration in lung function and health status [20]. Both major COPD phenotypes, chronic bronchitis and emphysema, exhibit significant correlations with AMH. Chronic bronchitis is characterized by airway goblet cell hyperplasia and submucosal gland hypertrophy, leading to marked AMH [21]. Th2 inflammatory cytokines, particularly interleukin 13 (IL-13), induce goblet cell metaplasia through the signal transducer and activator of transcription 6 (STAT6) signaling pathway, thereby promoting mucin 5AC (MUC5AC) synthesis [22]. Additionally, elevated reactive oxygen species in the chronic inflammatory milieu activate the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway, further amplifying mucus production [23]. High-resolution computed tomography (CT) revealed that approximately 30% of emphysema patients exhibit small airway mucus plugs, and these individuals demonstrate a significantly accelerated annual decline in forced expiratory volume in 1 second (FEV1) compared with those without mucus plugs [24]. Emphysema-related protease–antiprotease imbalances may indirectly stimulate mucus secretion via the activation of protease-activated receptor-2 (PAR-2) [25]. Large-scale cohort studies have confirmed that AMH is significantly associated with increased exacerbation frequency and mortality in COPD patients [26]. This bibliometric analysis revealed 1,405 COPD-AMH-related publications from 1994 to 2024, accumulating 69,033 total citations (Nc) with a mean citation rate of 48.82 per article. The sustained upward trajectory in annual publication and citation metrics reflects growing scientific interest in this research domain.

2. Analysis of distributions

Over the last 30 years, the USA and UK have contributed extensively to COPD-AMH research. Visual analysis identifies these nations as leading in research output and scholarly impact. This may be due to the higher incidence and mortality of COPD, and prioritization of disease management in these regions. In 2019, the age-standardized prevalence rates were 3,558.4 per 100,000 in high-income North America and 3,017.5 per 100,000 in Western Europe, while the corresponding age-standardized death rates were 31.2 and 19.2 per 100,000, respectively [27]. China and the USA were projected to face the largest macroeconomic burdens of COPD during 2020–2050, amounting to international dollar (INT) $1.363 trillion and INT$1.037 trillion, respectively, at constant 2017 prices [7].

Regarding research institutions, the University of North Carolina (USA) demonstrated exceptional productivity, and Imperial College London (UK) achieved the highest citation impact, which could be attributed to its renowned lung research institute with a significant number of well-trained researchers. For example, Boucher, Richard C. from the University of North Carolina, has written more than 616 articles in COPD, CF and related fields (H-index 105, cited 38,488 times), exerting considerable influence. Close cooperation between European, American and Asian countries remains essential for advancing this field. Through frequent international cooperation, these nations have fostered knowledge consolidation and progression.

With respect to researchers, 80% of the top 10 most productive authors were from the USA. The collaborative groups were represented mainly by highly influential researchers, whereas other researchers remained dispersed within the cooperation network with limited connectivity. This phenomenon may reflect: (1) dominance of developed nations in research funding and infrastructure, perpetuating resource disparities for peripheral teams; (2) multidisciplinary complexity of AMH mechanisms, wherein researchers from disparate fields employ heterogeneous experimental models and terminological frameworks; (3) privacy regulation conflicts impeding cross-jurisdictional data sharing for large-scale internation [28]; and (4) challenges including cross-time zone coordination, linguistic barriers, and travel expenses may diminish incentives for international collaboration [29].

Based on this structured analysis, we propose recommendations at three levels. At the national level, addressing geographical disparities requires establishing targeted funding mechanisms (e.g., mucin research funds), implementing cross-national data-sharing agreements, and constructing multilingual clinical databases. At the institutional level, the development of collaborative platforms (integrating electronic health records, lung function data, and imaging data) could enhance interinstitutional cooperation globally. At the researcher level, creating dedicated funding programs for transnational collaborations and developing artificial intelligence-powered collaboration matching systems may facilitate network expansion.

3. Influential authors and studies

Boucher, Richard C. (University of North Carolina) emerged as the most prolific contributor, investigating CF and COPD pathogenesis with particular emphasis on airway mucus and epithelial biology. Boucher's seminal review in the New England Journal of Medicine systematically characterized airway mucus obstruction in muco-obstructive lung diseases, including COPD, CF, primary ciliary dyskinesia, and non-CF bronchiectasis [30]. This review identified distinct epithelial pathomechanisms driving mucus hyperconcentration, which converge through shared pathways of mucus plaque/plug formation. His team further established mucus clearance as a critical innate immune mechanism modulated by airway hydration status [31]. These discoveries elucidated regulatory mechanisms of airway surface hydration mediated by nucleotide/nucleoside signaling and established biophysical principles governing mucus adhesion and the clinical consequences of impaired MCC.

The landmark article “Airway mucin concentration as a marker of chronic bronchitis” by Mehmet Kesimer (University of North Carolina, USA) garnered the highest burst strength (23.23), providing comprehensive insights into chronic bronchitis pathogenesis through mucin concentration [32]. This study utilized data from the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) cohort to validate the dual gel hypothesis, elucidating associations between airway mucin concentrations (total mucin, MUC5B, and MUC5AC) and the pathogenesis, disease severity, and diagnosis of chronic bronchitis. Elevated mucin concentrations were significantly associated with abnormal mucus secretion, airflow obstruction, and increased exacerbation frequency. Furthermore, the total mucin concentration has emerged as a potential biomarker for chronic bronchitis.

These authors and publications have established foundational knowledge for the physiology and interaction between COPD and airway mucus. Closer attention to the groundbreaking work of key investigators in this field will broaden perspectives and inspire innovations built upon their achievements.

4. Hotspots and frontiers

Keywords serve as indicators of the central themes and critical components within the literature, enabling identification of emerging topics and key trends, highlighting innovation areas, and guiding researchers across diverse domains [33]. Analysis of keyword frequency, centrality, and temporal distribution allows determination of current research themes and scientific prediction of future directions. We identified three primary focuses of this research: COPD diagnosis, management, and therapy; mucus composition, production and related signaling pathways; and asthma and CF as comparative disease models.

The co-occurrence of “asthma” and “cystic fibrosis” within the COPD-AMH keyword network reflects their established roles as comparative disease models rather than independent research foci. Asthma appears predominantly in studies examining shared mucus hypersecretion mechanisms, including MUC5AC overexpression and IL-13 signaling pathways [34,35], alongside clinical differential diagnoses distinguishing asthma-COPD overlap from pure COPD phenotypes. CF, conversely, serves as a reference framework for severe mucus pathology, with comparative analyses addressing cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, MCC impairment, Pseudomonas aeruginosa infection, and therapeutic interventions such as airway clearance techniques and hypertonic saline [36]. These patterns indicate that the COPD-AMH research community leverages both conditions as mechanistic benchmarks to contextualize mucus hypersecretion severity, therapeutic targets, and phenotypic heterogeneity within COPD.

Autophagy plays a critical, multifaceted role in COPD pathogenesis. This highly conserved homeostatic mechanism protects against environmental stressors, notably oxidative stress, by degrading damaged organelles and proteins via lysosomal pathways [37,38]. Its emergence as a research hotspot marks a paradigm shift from descriptive mucus characterization toward understanding cellular quality control failures as upstream drivers of mucus hypersecretion, suggesting therapeutic targeting may simultaneously address multiple COPD hallmarks. Recent evidence demonstrates that cigarette smoke and particulate matter increase oxidative stress and impair autophagic function in alveolar macrophages, resulting in protein aggregate accumulation, mitochondrial dysfunction, and defective bacterial clearance [39,40]. Autophagic dysregulation associates with diverse COPD pathologies, including inflammation, emphysema, mucus hypersecretion, ciliary dysfunction, airway remodeling, and bacterial infection [38], mediated through cell-type-specific mechanisms involving altered autophagosome protein expression (e.g., microtubule-associated protein 1 light chain 3 [LC3], sequestosome-1 [p62], autophagy-related 4 [ATG4]) and signaling pathways such as phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/mechanistic target of rapamycin (mTOR) [41-43]. These findings indicate that autophagy disruption represents a key pathological feature of COPD [44].

Mucus plugs represent a common finding on chest CT scans in COPD patients and are independently associated with disease severity. Their presence is correlated with a worse predicted FEV1% and more severe airflow limitation, independent of emphysema or airway wall thickening [45,46]. Notably, silent mucus plugs occur in 36% of COPD patients without cough or sputum symptoms and associate with increasing risk of future moderate-to-severe acute exacerbations [47]. Prognostically, mucus plugs are associated with increased all-cause mortality; high-burden patients exhibit significantly higher 10-year mortality [48]. CT-identified mucus plugs currently serve as valuable biomarkers for COPD risk stratification, particularly in asymptomatic individuals [49]. In summary, mucus plugs represent an independent predictor of COPD progression and adverse outcomes. Their assessment should be integrated into clinical management for stratification of high-risk patients and intervention, warranting further research into targeted mucoactive therapies.

Exacerbation is recognized as a risk factor for COPD progression and prognosis [9]. Exacerbation frequency serves as a critical metric for disease staging and predicts hospitalization risk, healthcare utilization patterns, and mortality [50]. While airway mucus covering healthy airways maintains essential host defense through pathogen entrapment and MCC mechanisms [51], AMH leads to excessive mucus accumulation in the airway lumen, obstructing the airway, limiting airflow, and accelerating lung function decline. Chronic inflammation impairs MCC, causes loss of surfactant substances, and alters mucus biophysical properties, resulting in recurrent airway infections, obstruction, and remodeling, ultimately establishing a vicious cycle [13]. Respiratory pathologies including COPD, asthma, and CF, which collectively affect 420 million individuals worldwide, demonstrate characteristic mucus dysregulation [52]. Severe fatal asthma patients exhibit markedly increased airway mucus [53]. Similarly, genetic mutations disrupt MCC through altered mucus biophysical properties, establishing obstructive and infectious impairments in CF [54].

5. Structural gaps and integrative opportunities

Our analysis of the COPD-AMH keyword co-occurrence network and temporal evolution reveals three notable structural gaps. First, despite temporal proximity of “autophagy” and “mucus plugs” as recent hotspots, limited direct connectivity between them suggests that mechanistic links between defective autophagy and physical mucus plugging remain underexplored. We propose investigating impaired mitophagy in ciliated cells to bridge cellular quality control with mucus rheology. Second, although “exacerbations” exhibits prolonged burst duration and elevated strength, it demonstrates weak external linkage to “autophagy,” “airway remodeling” and “small airway obstruction,” indicating disconnect between acute and chronic disease research. Integrative longitudinal designs tracking autophagy markers, mucus plug burden, and remodeling across stable and exacerbation states could bridge this divide. Third, “dendritic cells” and “autophagy” exhibit high potential yet low integration, given emerging recognition of immunometabolism in COPD, we suggest exploring how autophagy in antigen-presenting cells modulates mucus hypersecretory responses, thereby connecting immunometabolism with established airway biology. These integrative directions may address key translational gaps in the current literature.

6. Strengths and limitations

This bibliometric analysis has several strengths. First, it represents the first comprehensive bibliometric analysis spanning 30 years (1994 to 2024) in COPD-AMH research, systematically revealing dynamic trajectory from basic mechanistic exploration to clinical translation. Second, overcoming the limitations of previous fragmented reviews, this study integrates multiple analytical tools (CiteSpace, VOSviewer, and R) to quantify the distribution, collaboration and co-occurrence patterns, providing data-driven support for research prioritization. Third, the study highlights existing challenges by revealing collaboration networks characterized by macrolevel cohesion yet microlevel fragmentation.

Nevertheless, several limitations warrant consideration. First, exclusive reliance on WOSCC excludes relevant gray literature and non-Science Citation Index (SCI) indexed sources, potentially compromising exhaustiveness of the literature coverage. Second, English-language restrictions introduce cultural-geographic bias in knowledge representation. Additionally, the exclusion of book chapters, conference papers, letters, etc., may overlook valuable information. Third, this study acknowledges publication bias and citation bias. Studies published in high-impact journals or by prestigious institutions tend to receive higher citation rates, while negative or neutral findings may be systematically underrepresented. Despite these limitations, comprehensive coverage of the WOSCC database coupled with systematic 30-year bibliometric analysis provides robust empirical evidence for mapping disciplinary trajectories and identifying knowledge epicenters. Future research should employ appropriate tools facilitating large-scale cross-platform literature integration to minimize biases.

In conclusion, this study employs bibliometric analysis to systematically evaluate three decades of COPDAMH research, identifying key contributing countries, institutions, authors and journals. While extensive collaboration exists between countries and institutions, researcher-level networks remain relatively fragmented. Seminal publications have elucidated the pathophysiological mechanisms underlying COPD progression. Current research hotspots typically focus on mucus plugs, autophagy, and exacerbation. Future studies should further explore the interaction between COPD and AMH and clarify more innovative, evidence-based interventions to support clinical decision making.

Footnotes

Authors’ Contributions

Conceptualization: An N, Wang D. Methodology: An N, Wang D. Formal analysis: An N, Wang D, Xu D, Qin J, Wu Y, Gao L, Chen F, Chen Z. Data curation: An N, Wang D. Funding acquisition: Shen Y. Software: An N, Wang D. Validation: An N, Wang D, Xu D, Qin J, Wu Y, Gao L, Chen F, Chen Z. Investigation: An N, Wang D, Xu D, Qin J, Wu Y, Gao L, Chen F, Chen Z. Writing - original draft preparation: An N, Wang D. Writing - review and editing: An N, Wang D, Liu L, Shen Y, Wen F. Approval of final manuscript: all authors.

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Acknowledgments

The raw data used in this study were derived from the Web of Science (WoS) Core Collection database. The cleaned and processed dataset generated during the current study is available in the Supplementary Materials and Methods.

Funding

This work was supported by the Hainan Provincial Key Research and Development Program (ZDYF2026SXLH037), the National Natural Science Foundation of China (82170046, 31871157), the 1•3•5 Project for Disciplines of Excellence, West China Hospital of Sichuan University (RHM24207), the Program from Science and Technology Department of Sichuan Province (2022YFS0104, 2024NSFSC1522, 2024NSFSC1526, and 2024YFFK0279), the Program from Science and Technology Projects of Tibet Autonomous Region, China (Grant No. XZ202501ZY0120, XZ202501JD0009, and XZ202501ZR0033). The funder had no role in the design, data collection, data analysis, and reporting of this study.

Supplementary Material

Supplementary material can be found in the journal homepage (http://www.e-trd.org).

Supplementary Materials and Methods

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