Global research trends in influenza-associated acute lung injury/acute respiratory distress syndrome: a bibliometric analysis from 2010 to 2024

Introduction

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are critical lung conditions characterized by severe acute inflammation, which pose significant threats to patient life and health (1). ALI/ARDS is defined by acute hypoxic respiratory failure, pulmonary edema, and the progressive deterioration of respiratory function (2). These conditions are often caused by direct lung injury or an indirect systemic inflammatory response, which may result from pneumonia, extrapulmonary infections, trauma, blood transfusions, burns, aspiration, or shock (3). The diagnosis of ALI/ARDS is based on the criteria established by the Joint European-American Conference in 1994, which specify an oxygenation index [partial pressure of arterial oxygen (PaO₂)/fraction of inspired oxygen (FiO₂)] of less than 300 mmHg for ALI and less than 200 mmHg for ARDS. The 2023 global ARDS diagnostic standard improves clinical applicability and generalizability, especially in resource-limited areas, by incorporating peripheral oxygen saturation (SpO₂)/FiO₂ ratios and pulmonary ultrasound (4). Despite extensive basic and clinical research over recent decades, no effective treatment has yet been identified for ALI/ARDS.

Influenza is an acute viral respiratory infection caused by influenza viruses, which are classified into four types: A, B, C, and D. Types A and B are primarily responsible for widespread seasonal epidemics (5). In recent years, numerous studies have focused on the relationship between influenza and ALI/ARDS in an effort to identify new avenues for exploration. Research has shown that influenza viruses can cause severe respiratory infections and damage to the alveolar epithelium, suggesting that they may induce ALI/ARDS by damaging lung tissue (6-8). As research progresses, some studies have indicated that influenza may also cause lung damage through alternative mechanisms, providing valuable clues into the pathophysiology of ALI/ARDS (9,10).

Bibliometrics is an interdisciplinary approach that provides a comprehensive analysis of large volumes of scientific data, revealing both evolutionary trends within a specific field and emerging research areas (11). This study aims to statistically analyze and visualize various aspects of influenza-related ALI/ARDS research, including countries/regions, institutions, authors, co-cited journals/authors/references, and keywords. Software tools such as CiteSpace and VOSviewer were utilized to assess the research structure over the past 15 years, explore future research trends, and offer valuable insights for promoting further studies in this area (12). We present this article in accordance with the BIBLIO reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1117/rc).

Methods

Literature sources and search strategies

All publications included in this study were retrieved from the Web of Science Core Collection (WoSCC) database. Due to the stringent criteria and standards for data quality in bibliometric analysis software, we selected the WoSCC database as our primary source for data acquisition. However, it is important to note that the WoSCC database has limited coverage of non-English literature, which may restrict the global comprehensiveness and diversity of this study. To ensure the accuracy of the results, a literature search was conducted on October 23, 2024, using the search terms: TS = (“influenza” OR “flu”) AND (“acute lung injury*” OR “ALI” OR “acute respiratory distress syndrome*” OR “adult respiratory distress syndrome*” OR “respiratory distress syndrome*” OR “shock lung” OR “human ARDS” OR “ARDS”). The search covered the period from January 1, 2010, to October 23, 2024. A total of 2,045 publications were retrieved, excluding non-English literature and non-article or review document types. To ensure data consistency, we meticulously downloaded all relevant information and rigorously filtered out any irrelevant publications. This task was carried out diligently by three researchers, namely Jiajie Li, Jinxing Liu, and Y.W. After applying these criteria, 1,814 valid publications remained. These were saved in plain text format (download_**.txt), containing relevant information such as year of publication, country/region, affiliation, authors, journals, references, keywords, and more (Figure 1).

Figure 1 Flowchart depicting criteria for inclusion and exclusion of studies. WOS, Web of Science.

Statistical analysis

This study employed several software tools, including Microsoft Excel 2019, CiteSpace 6.1.R1, and VOSviewer 1.6.20, for visual analysis. Specifically, Microsoft Excel 2019 was employed to generate annual publication volume and citation trend graphs, along with related data, such as the annual publication volume by country. CiteSpace and VOSviewer were combined to visualize and analyze detailed publication information, including country/region, authors, journals, keywords, institutions, and references.

Results

Annual publication and citation trends

We collected 1,814 publications from the WoSCC, including 1,455 articles and 359 reviews, published in 720 journals between 2010 and 2024. These publications were cited a total of 80,047 times, with an average of 44.13 citations per publication. The annual number of publications and citation frequency related to influenza-associated ALI/ARDS are presented in Figure 2. Trend analysis reveals that the number of publications remained relatively stable from 2010 to 2019, followed by a significant increase in 2020, which peaked at 261 publications, before declining from 2021 to 2023. Citation frequency increased gradually from 2010 to 2019, then surged in 2020–2021, peaking at 16,612 citations in 2021, and subsequently declined in 2022–2023. These trends suggest that 2020 and 2021 represented a peak in research activity in this field, with a decrease in research intensity from 2021 onward.

Figure 2 Annual global publication and citation trends related to influenza and ALI/ARDS. ALI, acute lung injury; ARDS, acute respiratory distress syndrome.

Country and institutional analysis

A total of 411 countries/regions contributed to research on influenza and ALI/ARDS. Table 1 presents the top 10 countries and institutions by the total number of publications, with the United States leading with 604 publications, accounting for 33.297% of the total in this field. China follows with 404 publications (22.271%), while Germany has 139, Italy has 100, and Canada has 99. Figure 3A illustrates the annual publication volume of the top 10 countries based on publication quantity. The United States is recognized as a pioneer in this field, while China has been actively involved at all stages. Notably, in recent years, China has surpassed the United States in the number of annual publications.

Figure 3 Contributions of countries/regions and institutions in the field of influenza and ALI/ARDS. (A) Annual frequency of publications for the top 10 countries in terms of publications. (B) VOSviewer’s national/regional collaboration network. (C) Map of publication collaboration between countries/regions. (D) Institutional collaboration networks for publications on influenza and ALI/ARDS. ALI, acute lung injury; ARDS, acute respiratory distress syndrome.

In terms of global cooperation in this field, several countries/regions have already established partnerships. In Figure 3B, larger nodes represent countries or regions that have published more articles, while nodes with warmer colors indicate that a country has published a greater number of articles in recent years. Figure 3C displays regions representing countries, with larger regions signifying higher publication volumes. The lines connecting these regions illustrate the collaborative relationships between countries, revealing a positive correlation between the strength of cooperation and the number of publications. The results show that the United States and China, as the countries with the highest total number of publications, also exhibit the closest collaboration. Additionally, the United States has relatively strong cooperation with countries such as Germany and Canada.

Figure 3D primarily illustrates the collaboration among institutions. Table 1 indicates that the University of Toronto, Canada, leads with 32 publications, followed by Capital Medical University with 29, Fudan University with 28, The Ohio State University with 19, and the Centers for Disease Control and Prevention with 17 publications. As shown in Figure 3D, the University of Toronto, Capital Medical University, and the Chinese Academy of Medical Sciences have the most collaborations with other institutions.

Journal analysis

A total of 720 journals have published studies on ALI/ARDS associated with influenza. Table 2 presents the 10 journals with the highest number of publications. Frontiers in Immunology leads with 51 publications, followed by PLoS One with 45, Critical Care Medicine with 27, Critical Care with 26, and Scientific Reports with 23 articles.

A total of 8,041 journals were cited by the 1,814 publications analyzed. A visual network diagram of co-cited journals, generated using VOSviewer, is presented in Figure 4. Table 2 lists the 10 most co-cited journals, with the New England Journal of Medicine leading the list with 3,150 citations. It is followed by the American Journal of Respiratory and Critical Care Medicine with 2,093 citations, and JAMA-Journal of the American Medical Association with 2,066 citations. Other notable journals among the top 10 include The Lancet and Nature, cited 1,812 and 1,140 times, respectively. Notably, six of the top 10 journals have an impact factor (IF) greater than 10 as of 2024, indicating that the majority of references in the 1,814 publications come from high-impact journals. This suggests that the findings in this field are based on reputable sources, further supporting the credibility and scientific rigor of the research.

Figure 4 Visualization network of co-cited journals for influenza-related ALI/ARDS studies. ALI, acute lung injury; ARDS, acute respiratory distress syndrome.

Author analysis

A total of 11,403 researchers contributed to the study of influenza-associated ALI/ARDS across 1,814 publications. Figure 5A illustrates the collaboration between authors. Table 3 presents the 10 authors with the highest number of publications, with Professor Alain Combes of Sorbonne University, France, leading with 21 articles in this field. Professor Combes is a distinguished cardiologist whose research interests include extracorporeal mechanical support, membrane lung oxygenation, and the treatment of severe respiratory failure. He is widely recognized for his significant contributions to the field of acute respiratory failure (13). The Combes laboratory has also advanced the understanding of ALI/ARDS treatment by investigating extracorporeal membrane oxygenation (ECMO) as a therapeutic approach for severe ARDS (14).

Figure 5 The author’s contributions to the field of influenza-related ALI/ARDS. (A) Visualization network of author collaborations on influenza-related ALI/ARDS studies. (B) Visualization network illustrating various co-cited authors. (C) Density plot depicting the distribution of citations among authors. ALI, acute lung injury; ARDS, acute respiratory distress syndrome.

The second-highest number of publications in this field is attributed to Professor Bin Cao from the Chinese Academy of Medical Sciences, who previously worked at Capital Medical University. His research focuses on the molecular and cellular mechanisms underlying ARDS caused by the influenza virus, as well as the epidemiology, clinical characteristics, and treatment of viral pneumonia (15). The third most prolific author is Professor Ian C. Davis from Ohio State University in the United States. His laboratory research primarily investigates the role of type II alveolar epithelial (ATII) cells at the single-cell level in a mouse model of influenza A-induced ARDS, with the goal of identifying potential new treatments for ARDS (16). Notably, Matthieu Schmidt, another top 10 author, is affiliated with Sorbonne University in France, and Li Hui is associated with Capital Medical University. These findings highlight the significant contributions made by the laboratories led by Professor Alain Combes and Professor Bin Cao to the advancement of research in this field.

The top 10 co-cited authors and their citation counts are presented in Table 3. Andy Davies, from the Karolinska Institute, Harvard University in the United States, ranks first with 195 citations, followed by Anand Kumar [174], Giles Peek [163], Marco Ranieri [159], and Menno D. T. de Jong [117]. Figure 5B illustrates the mapping of author co-citation relationships, while Figure 5C displays the impact of co-cited authors in the field through a density plot.

Analysis of co-cited references and reference citation bursts

The purpose of publication co-citation analysis is to identify highly influential publications within a specific field. A co-citation relationship exists when two papers are both cited as references in another article. The strength of this relationship is proportional to the frequency of co-citations, which reflects their impact on the field (17). Figure 6A presents a visual network diagram of co-cited references with at least 60 citations, generated using VOSviewer. Table 4 lists the detailed information, citation frequencies, and the corresponding author countries for the top 10 most-cited publications. The most-cited article is titled “Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome”, authored by Andy Davies et al., and published in the JAMA-Journal of the American Medical Association in 2009, with 198 citations. This study investigates the characteristics of patients with ARDS caused by the H1N1 influenza virus, treated with ECMO, and reports on morbidity, resource utilization, and patient outcomes. The findings suggest that ECMO is an effective treatment for patients with severe H1N1 influenza-associated ARDS, leading to a relatively favorable prognosis (18). Figure 6B illustrates the key themes identified through the clustering function of the log-likelihood ratio (LLR) algorithm in CiteSpace, which organizes keywords from co-cited references. The most prominent cluster, ranked #0, is related to H1N1, suggesting that the majority of the articles focus on influenza A (H1N1) research. Clusters ranked #1 and #2 are ECMO and thrombosis, respectively, highlighting their significance in the co-citation network.

Figure 6 Co-cited references analysis and citation bursts analysis in the field of influenza and ALI/ARDS. (A) Visualization network of co-cited references, each with at least 60 citations. (B) Cluster analysis diagram of co-cited references. (C) List of the top 15 references experiencing the most significant citation bursts. ALI, acute lung injury; ARDS, acute respiratory distress syndrome.

A citation burst refers to a significant increase in the number of citations within a short period, and burst detection can help identify active research areas and emerging trends within a network. Figure 6C displays the 15 references with the strongest citation bursts, with red bars indicating the onset and duration of these research hotspots. The earliest burst occurred in 2010, the latest in 2021, and the longest citation burst lasted 5 years. The most recent high citation burst is associated with the RECOVERY Collaborative Group, which published a study entitled “Effect of hydroxychloroquine in hospitalized patients with COVID-19” in the New England Journal of Medicine. This study examined the effects of hydroxychloroquine on hospitalized coronavirus disease 2019 (COVID-19) patients and found that the drug did not demonstrate significant efficacy, while potentially causing adverse effects (19). More importantly, this article is still in the burst phase of citation activity and provides clinical insights that may inform future treatments for influenza-induced ALI/ARDS with alternative therapies.

Keywords analysis

Keywords typically reflect the central themes of a research area, and a systematic analysis of these keywords can reveal the prevailing research trends within specific fields. To explore the research hotspots related to influenza and ALI/ARDS, we conducted a keyword co-occurrence analysis. The keyword network for this field is presented in Figure 7A, while Table 5 lists the top 10 most frequently occurring keywords. Among these, “acute lung injury”, “respiratory distress syndrome”, and “acute respiratory distress syndrome” ranked first, second, and fourth, respectively. Additionally, “infection” and “extracorporeal membrane oxygenation” ranked third and fifth, with 231 and 164 occurrences, respectively. These findings suggest that, over the past decade, research has primarily focused on the mechanisms of infection and the treatment of ALI/ARDS induced by the influenza virus.

Figure 7 Keyword visualization results in the field of influenza and ALI/ARDS. (A) Co-occurrence network diagram of keywords. (B) Graph showing clusters of keyword co-occurrences. (C) Timeline representation of keyword occurrences. (D) List of the top 15 keywords with the strongest citation bursts. ALI, acute lung injury; ARDS, acute respiratory distress syndrome.

The keyword clustering shown in Figure 7B provides additional insights into current developments in the field. Notably, clusters #0 “mechanical ventilation” and #1 “extracorporeal membrane oxygenation” are ranked first and second, respectively, among the 14 clusters. Both are treatment modalities for ALI/ARDS, with the distinction that “mechanical ventilation” serves as the first-line treatment, while “extracorporeal membrane oxygenation” is employed for patients who do not respond to conventional mechanical ventilation and experience severe hypoxemia (20). The clustering results indicate that the average contour value of the 14 clusters in the graph exceeds 0.8, reflecting good uniformity and suggesting that the analysis results are reliable (21). Additionally, a timeline plot of keywords, shown in Figure 7C, was constructed to examine the temporal trends within the study area as represented by each cluster.

The burst phenomenon of keywords was analyzed, and the top 15 keywords based on the frequency of outbreaks are shown in Figure 7D, ranked according to their outbreak timelines. The shortest outbreak duration was 1 year, while the longest lasted 7 years. Notably, “2009 influenza a (h1n1)” [2011–2018] received the longest attention. Other frequently used keywords, such as “cytokine storm” [2020–2024], “clinical characteristics” [2020–2024], and “covid 19” [2020–2024], may become future research hotspots. Among these, “cytokine storm” exhibited the highest citation burst intensity (14.74), followed by “critically ill patients” (14.61), “a (H1N1)” (13.36), “2009 influenza a (h1n1)” (12.16), and “a (h1n1) infection” (11.59). The remaining keywords had burst intensities below 10. Analyzing the clustering and mutation results of these keywords reveals a shift in research focus from influenza A (H1N1) to coronaviruses in recent years. More importantly, in-depth research has been conducted on the pathogenesis and clinical treatment of ALI/ARDS caused by coronaviruses.

Discussion

Overview of the study

This study analyzed the information regarding countries, institutions, journals, authors, keywords, and other relevant factors in ALI/ARDS literature related to influenza. The annual publication trend reveals a relatively stable volume of publications from 2010 to 2019, with a significant increase in 2020, likely associated with the outbreak of the novel coronavirus in 2019. The United States accounts for approximately one-third of the total publications in this field and maintains strong international collaborations. This dominance can be attributed to the country’s advanced research facilities and robust academic environment. In contrast, China should enhance its international cooperation to increase its global influence in this area. Additionally, the majority of the top 10 institutions are universities, indicating that higher education institutions play a central role in this field and contribute significantly to the research on this topic. Regarding journals, Frontiers in Immunology has published the largest number of articles in this field. Among the top 10 co-cited journals, five have an IF of 20 or higher [2024], reflecting the high credibility and influence of research in this area. In terms of authors, Professor Alain Combes from Sorbonne University, France, has the highest publication count, with 21 papers in this field. Among co-cited authors, Professor Andy Davies from the Karolinska Institute, Harvard University in the United States, ranks first with 198 citations. His approach to treating ALI/ARDS through ECMO has been widely discussed and cited by researchers.

Knowledge base

By reviewing the most frequently cited literature, we gain a comprehensive understanding of the research on ALI/ARDS associated with influenza. The top 10 most cited studies primarily focus on critical care medicine and infectious diseases, with the majority published in 2009, coinciding with the H1N1 influenza pandemic. The clustering and burst detection analyses of co-cited literature reveal that the clinical treatment and underlying mechanisms of H1N1-related ALI/ARDS have garnered significant attention. In clinical practice, a variety of treatment approaches have been utilized for patients with severe H1N1-associated ALI/ARDS, with ECMO emerging as a key intervention. The two most cited studies both employed randomized controlled trials to compare the efficacy of ECMO versus conventional mechanical ventilation in ALI/ARDS patients. The results indicated that ECMO, compared to traditional ventilation, improves survival rates and may offer cost-effective benefits (18,22). It has been established that during influenza virus infection, the viral load and the resulting inflammatory response are central to the pathogenesis of the disease. Consequently, clinical treatment should focus on effective strategies to control viral replication and prevent excessive cytokine responses, thereby minimizing the risk of severe conditions such as ALI/ARDS (23). However, the precise mechanisms underlying influenza virus-induced ALI/ARDS remain unclear.

Notably, several highly cited studies have reported that younger individuals are more susceptible to critical illness following H1N1 influenza, while severe disease has been rarely observed in older populations. This disparity has been linked to more severe ARDS, shock, prolonged mechanical ventilation, and multisystem organ failure in younger patients (24-26). This highlights the importance of focusing on specific patient subgroups, such as obese and elderly individuals, particularly concerning their prognosis and complications. Obese patients demonstrate the “obesity paradox”: although obesity is an independent risk factor for ALI/ARDS—incidence rates are 5 to 15 times higher in individuals with a BMI ≥30 kg/m² compared to those of normal weight—some studies suggest that their mortality rates may be lower than those of normal-weight patients (27-29). This paradox may be attributed to altered inflammatory response thresholds due to chronic inflammation in obese individuals. While baseline levels of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α are elevated in obese patients, their plasma concentrations may decrease during ARDS onset, indicating reduced inflammation and a potentially better prognosis (30). Despite this, obese patients remain at increased risk for long-term complications, including a heightened susceptibility to pulmonary fibrosis. Obesity reduces chest wall and lung parenchymal compliance, increases airway resistance, and predisposes patients to obstructive sleep apnea, all of which elevate the risk of post-extubation respiratory failure (31). Non-invasive positive pressure ventilation or high-flow nasal cannula oxygen therapy may improve outcomes (32). Inflammatory factors released from adipose tissue may further exacerbate immune responses, increasing the likelihood of secondary bacterial infections, such as hospital-acquired pneumonia (33). Advanced age is also an independent risk factor for poor ARDS prognosis, with significantly higher mortality rates compared to younger patients—reported to be as high as 40–60% in some studies (34,35). Contributing factors include impaired neutrophil and macrophage function, leading to delayed pathogen clearance and uncontrolled inflammation (36). Additionally, common comorbidities, such as chronic obstructive pulmonary disease, heart failure, and diabetes, predispose elderly patients to multiple organ dysfunction syndrome (37). Furthermore, the diminished capacity for alveolar epithelial repair increases the risk of pulmonary fibrosis, adversely impacting long-term quality of life (38). In elderly patients, complications predominantly manifest as pulmonary and extrapulmonary issues. Pulmonary complications include viral pneumonia, secondary bacterial pneumonia, and pleural effusion (39). Extrapulmonary complications, particularly cardiovascular issues such as myocarditis, pericarditis, and heart failure, occur frequently, potentially due to direct influenza virus invasion of the myocardium or cytokine storms. Neurological complications, including encephalitis, meningitis, and Guillain-Barré syndrome, can also occur, increasing mechanical ventilation duration and mortality rates (40,41). Significant prognostic differences exist between obese and elderly patients with influenza-associated ALI/ARDS. Obesity may lead to a “paradoxical” prognosis due to altered inflammatory thresholds, while elderly patients face higher mortality due to immune senescence and multi-organ dysfunction. Both groups require individualized treatment strategies, including early intervention, precision mechanical ventilation, and complication prevention, to improve long-term quality of life (42).

Several studies have identified that the pathogenesis of influenza virus-induced ALI and ARDS involves pulmonary epithelial and endothelial barrier dysfunction, inflammatory responses, and immune activation (43,44). The increased permeability of the pulmonary epithelium and endothelium can compromise the integrity of the pulmonary microvascular barrier. In healthy lungs, endothelial stability is maintained by vascular endothelial cadherin (VE-cadherin), an endothelial-specific adhesion protein essential for preserving the integrity of the pulmonary microvascular endothelial barrier (45). When oxidative stress occurs and the concentration of white blood cell signaling in the lungs increases, it can disrupt the activity of VE-cadherin junctions, leading to increased endothelial permeability and the accumulation of pulmonary edema (46,47). The alveolar epithelial barrier is similar to the endothelial barrier, with the key difference that the integrity of the alveolar epithelial barrier relies on calreticulin E. Under inflammatory conditions, neutrophils migrate by disrupting intercellular connections, leading to cell apoptosis and shedding, which causes epithelial damage and ultimately increases epithelial permeability (48). The study also found that miR-200c-3p, a small non-coding RNA, reduces angiotensin-converting enzyme 2 (ACE2) levels by upregulating nuclear factor-κB, which results in elevated angiotensin II levels and subsequent lung injury (49). Influenza viruses contribute to the development of ALI/ARDS through various mechanisms, including disruption of the alveolar barrier, inflammatory response, immune response, and oxidative stress (1,50-52). Therefore, further research is necessary to better understand the pathogenesis of various types of influenza-associated ALI/ARDS and to identify specific protective measures.

Research trends

A meticulous analysis of keywords in this field can reveal both current research priorities and emerging trends, guiding efforts to explore unresolved pathogenic mechanisms and novel therapeutic approaches. It is well established that H5N1 [2003], H1N1 [2009], and COVID-19 [2019] have caused significant harm to global public health (53-55). Only through continuous research can optimal strategies be developed to combat influenza virus infections. In recent years, the cytokine storm, triggered by the excessive release of various cytokines, has been identified as a key factor in the progression of COVID-19-related ALI/ARDS (56). Cytokine storm represents an exaggerated immune response in ALI/ARDS, involving multiple inflammatory pathways and cytokines that regulate and mediate lung injury. This response disrupts the alveolar-capillary barrier, increasing lung permeability, which leads to pulmonary edema and hypoxemia (57). During a cytokine storm, levels of TNF-α, interferon-γ, and IL-6 rise dramatically, further contributing to multi-organ dysfunction and the failure of critical pathways in patients with severe COVID-19 (58). It has been proposed that the combined effects of excessive cytokine signaling and cell death play a central role in the manifestation of these symptoms. Specifically, structural damage to the cell membrane results in vascular leakage and procoagulant endothelial formation, which triggers and amplifies ALI/ARDS in cytokine storm syndromes, including COVID-19 (59).

The current treatment for influenza-associated ALI/ARDS involves two primary approaches: mechanical ventilation and pharmacologic therapy (60). Mechanical ventilation is further categorized into traditional mechanical ventilation and ECMO. Traditional mechanical ventilation helps overcome alveolar collapse and lung atelectasis by delivering positive pressure ventilation, which enhances alveolar ventilation and improves oxygenation (61). In contrast, ECMO works by extracting venous blood from the body, oxygenating it and removing carbon dioxide through a membrane oxygenator, and then returning the blood to the body using a centrifugal pump, thereby supporting both gas exchange and circulation (62). While ECMO can significantly alleviate hypoxemia and prevent airway damage caused by mechanical ventilation as well as oxygen toxicity from prolonged hyperoxia, it also carries risks such as bleeding, hemolysis, nosocomial infections, and other complications (63,64). Therefore, to optimize the clinical use of ECMO, it is essential to establish a comprehensive system and protocol, ensure meticulous attention to detail during implementation, and strengthen the emergency preparedness of healthcare personnel, ultimately enhancing ECMO’s success rate. In recent years, mesenchymal stem cell (MSC) transplantation has gained widespread use in the treatment of various immune diseases (65-67) and holds significant promise for clinical applications in alternative therapies (68,69). Studies have shown that MSC transplantation in patients with H7N9-induced ARDS significantly reduces mortality, with no adverse effects detected during a 5-year follow-up after hospital discharge (70). The significance of vitamin D has grown with increasing research into its physiological effects. It is now widely used in three key areas: pharmaceutical preparations, food additives, and feed additives. Studies have shown that vitamin D not only inhibits viral replication by stimulating the production of various antimicrobial peptides but also decreases the levels of cytokines that promote inflammation, which can damage the lung lining and trigger pneumonia (71,72). Additionally, vitamin D enhances the levels of anti-inflammatory cytokines (73,74). These mechanisms suggest that vitamin D may play a crucial role in reducing the risk of influenza and the onset of ARDS (75-78). Consequently, high-dose vitamin D supplementation may help lower the risk of infection in patients with influenza and concurrent ALI/ARDS.

It has been found that a balanced immune response mediated by the TRIF and MyD88-driven pathways provides the most effective host cell-intrinsic antiviral defense against severe acute respiratory syndrome coronavirus (SARS-CoV) infection (79). A key player in this process is the Toll-like receptor (TLR), a pattern recognition receptor that detects viral double-stranded RNA and initiates the innate immune response to invading pathogens (80). TRIF is a crucial signaling molecule involved in TLR3-mediated signaling, while MyD88 is a pivotal adaptor protein required for multiple TLR signaling pathways and plays an essential role in the in vivo innate immune response to mouse-adapted SARS-CoV infection (81). In recent years, researchers have extensively investigated the gut microbiome, revealing a bidirectional regulatory relationship between the lung and intestinal microbiota (82). Specifically, gut microbiota can migrate through the gut-lung axis, thereby altering the composition of the lung microbiome. This process significantly impacts the progression of ALI and ARDS (83,84). Based on this finding, targeted therapeutic approaches to modulate the gut microbiome are expected to offer effective treatment strategies for ALI/ARDS. For instance, recent studies have demonstrated that astragaloside IV can influence the gut-lung axis, modulating the lung and intestinal microbiota in rats with ALI. This action appears to involve reducing inflammatory factor levels and alleviating damage to the lungs and colon. Further research has shown that these beneficial effects are closely associated with the inhibition of the PI3K/AKT/mTOR signaling pathway by astragaloside IV (85). However, the study has limitations, and additional validation is necessary to determine whether modulation of the gut microbiome and its metabolites can attenuate lung and colon injury through PI3K/AKT/mTOR signaling pathway modulation. In conclusion, based on the above analysis, it is anticipated that investigating the pathogenesis of ALI/ARDS induced by novel influenza outbreaks will be a key area of future research. Moreover, future studies in this field will likely focus on exploring specific therapeutic strategies targeting various pathogenic mechanisms to address the significant public health impact of influenza and concurrent ALI/ARDS.

Strengths and limitations

Unlike previous studies, this study is the first to analyze influenza-associated ALI/ARDS using bibliometric methods. Furthermore, the analysis and visualization were carried out with the aid of software tools, such as the online bibliometric analysis platform and CiteSpace, which facilitated the presentation of results in a clear and comprehensive manner. While the analysis and visualization in this study are relatively thorough and objective, certain limitations must be acknowledged. First, the publication search was conducted up to October 23, 2024, and was restricted to English-language articles in the WoSCC database, meaning that newly published articles after this date were not included. Additionally, there is a potential for selection bias in the literature screening process.

Conclusions

This bibliometric analysis demonstrates that the United States and China are the leading countries in the field of ALI/ARDS research related to influenza. The United States ranks first with 604 publications, followed by China with 404. The University of Toronto and Capital Medical University are the most prominent institutions in this area. Regarding journals, Frontiers in Immunology has published the highest number of articles. Professor Alain Combes is the most prolific author, while Andy Davies is the most influential co-cited author. Over time, the research focus has shifted from the H1N1 influenza virus to coronaviruses. Notably, substantial research has been conducted on the pathogenesis and clinical treatment of ALI/ARDS caused by coronaviruses. Keywords such as “cytokine storm”, “clinical characteristics”, and “COVID-19” have surged in prominence, suggesting that these topics will continue to dominate future research. The future direction of research in this field will likely center on developing specific treatments based on the pathogenesis of ALI/ARDS induced by emerging influenza strains.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the BIBLIO reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1117/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1117/prf

Funding: This study was supported by the National Key Research and Development Program of China (No. 2023YFF0724803), the National Science Foundation of China (No. 82260930), National Chinese Medicine Multidisciplinary Cross-Innovation Team Project (No. ZYYCXTD-D-202201), the Yunnan University of Chinese Medicine Joint University-Institute Fund for Diannan School of Medicine (No. XYLH202329), and the Innovative Scientific Research Fund for First-Class Disciplines of Chinese Medicine in Yunnan Province (No. ZYXZD202401).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1117/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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