Chronic obstructive pulmonary disease (COPD) is a widely prevalent, preventable, and treatable chronic respiratory disorder characterized by persistent airflow limitation and progressive respiratory symptoms [1]. According to the World Health Organization (WHO), COPD has been the third leading cause of death globally, accounting for over 3 million deaths annually, with mortality rates continuing to rise, particularly in low- and middle-income countries. The Global Burden of Disease (GBD) Study estimates that COPD affects approximately 392 million individuals globally, significantly contributing to years lived with disability (YLDs) and disability-adjusted life years (DALYs) [2]. For the past decades, cigarette smoking (CS) has been identified as the primary risk factor for the development of COPD. However, recent data suggest that only a small proportion of smokers (15–20%) comprise the total COPD patient population, underscoring the critical role of other harmful exposures, such as ambient and household air pollution, occupational hazards, and dust exposure, in the development and progression of the disease [3]. The rising prevalence of COPD among non-smokers is a worrying concern globally.

Since the onset of the Industrial Revolution in the 18^th century, anthropogenic activities have significantly degraded air quality, with particulate matter (PM) pollution emerging as a major environmental health concern. As of 2024, WHO reports that 99% of the global population lives in regions where air pollution levels surpass recommended safety limits, resulting in approximately 6.7 million premature deaths annually due to exposure to both ambient (outdoor) and household air pollution. Among the most hazardous air pollutants is fine particulate matter (PM2.5), defined as airborne particles with an aerodynamic diameter of ≤2.5 micrometers (μm). Due to their ultrafine size and high specific surface area, PM2.5 particles efficiently adsorb toxic compounds, such as heavy metals, polycyclic aromatic hydrocarbons (PAHs), and sulfates, thereby enhancing their biological reactivity when inhaled [4].

Upon inhalation, PM2.5 particles evade mucociliary clearance and penetrate deeply into the alveolar regions, where they induce sustained pulmonary inflammation, oxidative stress, and cellular damage through mechanisms such as mitochondrial dysfunction, ferroptosis, and epigenetic modifications [5]. Epidemiological studies have demonstrated a dose-dependent correlation between PM2.5 exposure and the incidence, exacerbation, and mortality of respiratory diseases, including asthma, COPD, and lung cancer [6]. Importantly, long-term exposure to PM2.5 is linked to accelerated decline in lung function, increased hospitalization rates for COPD exacerbations, and heightened risk of lung cancer, particularly in urban populations and vulnerable subgroups, such as children, the elderly, and individuals with pre-existing cardiopulmonary conditions [7]. Given its widespread presence and profound pathological impacts, PM2.5 pollution remains a critical public health concern, necessitating the implementation of stringent regulatory policies and targeted mitigation strategies to reduce its disease burden.

We conducted a comprehensive literature search up to June 10, 2025, utilizing PubMed, Web of Science, CINAHL, and CNKI databases. We employed paired keyword searches, including "PM2.5", "particulate matter", "air pollutants", "environmental pollution", "COPD", and "respiratory diseases". A total of 2,714 articles were retrieved from the above database. After removing duplicates and excluding review articles, 80 studies were selected for inclusion in the present review.

Classification of PM

Atmospheric particulate matter (PM) represents a complex mixture of solid and liquid particles suspended in the air, varying significantly in size, composition, and origin [8]. Based on aerodynamic diameter, PM is categorized into three principal classes: coarse particles (PM10, 2.5–10 μm), fine particles (PM2.5, 0.1–2.5 μm), and ultrafine particles (UFPs, ≤0.1 μm). These fractions exhibit distinct deposition patterns within the respiratory tract, determining their pathogenic potential [9]. Coarse particles predominantly deposit in the nasopharyngeal and tracheobronchial regions, where mucociliary clearance mechanisms provide partial protection [10]. In contrast, PM2.5 penetrates more deeply into the bronchioles and alveolar spaces, while UFPs—due to their nanoscale dimensions—achieve nearly complete alveolar deposition and even systemic translocation across the air-blood barrier [11]. Although the lungs are the primary target for exposure to ambient pollution, particles can also be detected in other organs, including the liver [12], kidneys [13], heart [14], and brain [15]. Moreover, this characteristic of PM2.5 enhances its adsorption of toxic compounds, including transition metals and organic carcinogens. Mounting studies have suggested that smaller PM can induce more significant mitochondrial dysfunction and DNA damage at considerably lower mass concentrations than larger PM, highlighting their unique toxicological profile [16]. Both short- and long-term exposure to PM significantly impacts human health and is closely associated with a range of acute and chronic disorders.

Sources and composition of PM2.5

PM2.5 originates from both anthropogenic and natural emission sources, with its chemical composition varying markedly by geographic region and pollution type. Primary anthropogenic sources encompass fossil fuel combustion, such as vehicular exhaust and coal-fired power plants, as well as industrial processes like smelting and cement production, and biomass burning. Secondary formation occurs through atmospheric reactions involving sulfur dioxide (SO₂), nitrogen oxides (NO_x), and volatile organic compounds (VOCs), significantly contributing to regional PM2.5 burdens, particularly in the form of ammonium sulfate and nitrate aerosols [17].

Geochemical signatures reveal distinct compositional profiles: Urban PM2.5 in East Asia is typically sulfate-dominated, indicative of coal combustion emissions, whereas European cities exhibit higher nitrate fractions due to the prevalence of diesel vehicles [18,19]. Industrial areas are characterized by an enrichment of heavy metals, such as lead, cadmium, and arsenic, while rural regions affected by agricultural burning show elevated levels of potassium-containing particles and organic carbon [20]. Notably, traffic-derived PM2.5 contains abundant elemental carbon (EC) and polycyclic aromatic hydrocarbons (PAHs), components that are strongly associated with oxidative stress generation.

The toxic potential of PM2.5 is also composition-dependent. Water-soluble ions, such as sulfates and nitrates, facilitate radical generation through aqueous-phase chemical reactions, whereas transition metals like iron and copper are involved in Fenton reactions. Organic constituents, including PAHs and quinones, undergo metabolic activation to form DNA-adducting species [21]. This chemical heterogeneity necessitates source-specific risk assessment, as demonstrated by cohort studies that link traffic-related PM2.5 with stronger associations with COPD than crustal dust particles of equivalent size.

Epidemiological evidence

COPD is a major public health concern in China, with its prevalence among individuals aged ≥40 years increasing markedly from approximately 8.2% during 2002–2004 to 13.7% in 2012–2015. This 5.5 percentage point rise highlights the escalating burden of COPD, with ambient air pollution—particularly PM2.5—emerging as a critical environmental risk factor [22]. The COPD burden attributable to ambient PM2.5 exposure has shown a substantial increase from 1990 to 2019. Over the past two decades, both epidemiological and toxicological studies have progressively established a robust association between PM2.5 exposure and the incidence, severity, and mortality of COPD, thereby informing current understanding and policy interventions [23].

Initial research in the early 2000s primarily focused on smoking as the leading cause of COPD. However, with the rapid urbanization in China, air pollution has gained increasing recognition as a significant contributing factor. Early cross-sectional surveys revealed that regions with higher PM2.5 concentrations exhibited elevated COPD prevalence, even after adjusting for smoking rates Meta-analyses conducted during this period confirmed a positive correlation between long-term PM2.5 exposure and COPD morbidity, with particulate matter identified as a key driver of COPD mortality in low socio-demographic index (SDI) regions [24]. These findings suggested that air pollution could independently exacerbate the respiratory disease burden.

In 2020, a systematic review of 107 epidemiological studies revealed that chronic exposure to PM2.5 at levels below the WHO Air Quality Guidelines (AQG) mean annual exposure limit of 10 μg.m^-3 is correlated with heightened mortality rates due to respiratory diseases such as COPD, acute lower respiratory tract infection, and cardiovascular disease. Prolonged exposure to PM2.5 has been shown to provoke pulmonary inflammation, accelerate fibrosis, and impair lung function, particularly among vulnerable populations such as the elderly (≥60 years) and smokers [25]. Additionally, short-term exposure to PM2.5 has also been associated with increased airway inflammation and respiratory symptoms in COPD patients in China. Dose-response analyses have indicated that each 10 μg.m^-³ increase in PM2.5 concentration elevates the risk of hospitalization for COPD by 2.5%, with acute exacerbations (AECOPD) emerging as a critical concern [26]. Epidemiological data have demonstrated that COPD patients experience between 0.5 to 3.5 acute exacerbations annually, substantially contributing to mortality rates [27]. Currently, an expanding body of evidence suggests that exposure to even very low levels of PM2.5 is a genuine public health concern. Considering this new evidence, the WHO revised its AQG in 2021 to a recommended maximal annual average PM2.5 exposure of 5 μg.m^-3 [28].

Furthermore, the aging population in China has further exacerbated COPD mortality, as older adults with pre-existing conditions exhibit heightened susceptibility to PM2.5 toxicity. Immunological decline and reduced physical activity in this demographic further intensify the adverse effects of air pollution [29]. Meanwhile, global reductions in smoking rates have partially offset COPD mortality growth, underscoring the multifactorial nature of the disease. Predictive models suggest that the interaction between persistent air pollution and aging may lead to an epidemiological turning point in COPD mortality by 2030 [30]. Key epidemiological studies examining the association between PM2.5 and COPD are presented in Table 1.

Experimental evidence

While robust epidemiological evidence establishes a link between ambient PM2.5 exposure and COPD, a detailed mechanistic understanding of the cellular and molecular pathways involved in PM2.5-induced COPD remains nascent. To elucidate the potential mechanistic pathophysiology, researchers have conducted both in vitro and in vivo experimental studies. The characteristic features of chronic inflammation, oxidative stress, and airway remodeling found in COPD have been replicated in experimental models following exposure to PM2.5. These experimental studies are summarized in Table 2 (in vivo) and Table 3 (in vitro), respectively, detailing the type, dose, and duration of PM2.5, along with the major effects observed in each study.

Effect of PM2.5 exposure on inflammation

The involvement of PM2.5 in the pathogenesis of COPD via inflammatory mechanisms has been extensively investigated in recent years. An increasing volume of evidence indicates that inflammation induced by PM2.5 significantly contributes to both the initiation and progression of COPD through complex interactions between innate and adaptive immune responses, ultimately leading to airway remodeling and a decline in lung function [31,32].

Upon inhalation, PM2.5 is recognized by alveolar macrophages and epithelial cells through pattern recognition receptors (PRRs), initiating downstream signaling pathways such as the NF-κB pathway [33]. This activation leads to the nuclear translocation of transcription factors and upregulation of pro-inflammatory cytokines and chemokines, which facilitate the recruitment and activation of neutrophils, eosinophils, and macrophages within the airways. Recent experimental studies have demonstrated that PM2.5 exposure induces an inflammatory phenotype in mice, characterized by immune cell infiltration and pro-inflammatory cytokine release via the NF-κB pathway. In COPD rat models, exposure to PM2.5 has been shown to exacerbate pulmonary inflammation, as evidenced by elevated inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and increased levels of interleukin-1β (IL-1β), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-4, which collectively contribute to further tissue damage [34]. Moreover, even a drastically lower PM2.5 exposure (5 μg.day^-1) was sufficient to induce COPD-like pathology, characterized by marked pulmonary inflammation, lung damage, and airway remodeling in mice [35].

Research using healthy human volunteers and primary cells has also provided compelling evidence regarding the adverse respiratory effects associated with PM2.5 exposure. Specifically, primary human nasal epithelial cells exposed to PM2.5 exhibited significantly compromised epithelial integrity, as indicated by reduced expression of tight junction protein, enhanced cellular permeability, and elevated secretion of pro-inflammatory cytokines [36]. These findings suggest that PM2.5-induced epithelial barrier dysfunction may serve as a critical pathogenic mechanism that heightens susceptibility to inflammatory respiratory disorders, such as rhinitis and chronic rhinosinusitis. Consistently, a notable investigation involving 32 volunteers exposed to ambient PM for just 5 hours documented measurable increases in nasal and bronchial inflammation markers [37]. This acute response pattern aligns with findings from animal models, collectively underscoring the immediate pro-inflammatory potential of PM2.5 exposure on the respiratory system.

Beyond the initial innate immune response, PM2.5 exposure has been shown to disrupt adaptive immunity, particularly by influencing the polarization of T helper cells. Experimental evidence suggests that PM2.5 promotes the differentiation of Th1 and Th17 while suppressing the function of regulatory T cells (Treg), leading to an imbalance that favors persistent inflammation. Th17 cells, through the release of their signature cytokine IL-17, stimulate epithelial cells and fibroblasts to produce additional pro-inflammatory mediators and matrix metalloproteinases (MMPs), thereby accelerating airway remodeling [38]. Furthermore, recent studies utilizing human bronchial epithelial cells (HBECs) have revealed that PM2.5 activates the non-canonical Wnt5a/Ror2 signaling pathway, which not only amplifies the production of inflammatory cytokines but also contributes to epithelial-mesenchymal transition (EMT), a critical process in airway wall thickening and fibrosis [39].

As PM2.5-induced lung injury progresses, a shift in macrophage polarization becomes evident. In early stages, M1 macrophages predominate, releasing pro-inflammatory cytokines that intensify tissue damage. In contrast, in chronic PM2.5 exposure models, there is a marked transition to M2 macrophages, which facilitate fibrotic changes via the IL-4/STAT6 signaling axis. This pathway upregulates matrix metalloproteinase-12 (MMP12), an enzyme that degrades elastin and other extracellular matrix (ECM) components, leading to the loss of alveolar structure and progressive airway destruction [40]. The resulting ECM remodeling, coupled with ongoing epithelial damage, establishes a self-perpetuating cycle of inflammation and tissue repair that characterizes advanced COPD.

Effect of PM2.5 on oxidative stress

Oxidative stress, characterized by an imbalance where increased levels of oxidants overwhelm the body’s intrinsic antioxidant defense mechanisms, plays a significant role in the pathogenesis of numerous chronic respiratory diseases. Its contribution to the development and progression of COPD resulting from PM2.5 exposure has been very well established.

PM2.5 exposure notably disrupts the pulmonary antioxidant defense system, as demonstrated by significant alterations in key oxidative stress biomarkers. Studies consistently report a depletion of reduced glutathione (GSH), an increase in oxidized glutathione (GSSG) levels, and a subsequent decrease in the GSH/GSSG ratio following PM2.5 exposure [41]. This critical redox couple serves as the primary cellular antioxidant buffer system, and its perturbation signifies severe oxidative stress. Additionally, PM2.5 suppresses the activity of superoxide dismutase (SOD), the first-line enzymatic defense against superoxide radicals, while elevating levels of malondialdehyde (MDA), a reliable marker of lipid peroxidation. These interconnected changes foster a pro-oxidant microenvironment that predisposes pulmonary tissues susceptible to oxidative damage.

The excessive ROS production triggered by PM2.5 initiates a cascade of pro-inflammatory signaling events. In both BALB/c murine models and human bronchial epithelial cells (BEAS-2B), PM2.5-induced ROS have been shown to upregulate the expression of intercellular adhesion molecule-1 (ICAM-1) via the activation of the IL-6/AKT/STAT3/NF-κB signaling axis [42]. This pathway constitutes a crucial connection between oxidative stress and pulmonary inflammation, as ICAM-1 facilitates leukocyte-endothelial adhesion and subsequent transendothelial migration, which are essential processes in the recruitment and infiltration of inflammatory cells into tissues. The persistent activation of this signaling network contributes to chronic inflammation, a hallmark feature of COPD pathogenesis.

Moreover, mitochondria are sensitive targets of PM2.5, and PM2.5 exposure induces profound mitochondrial dysfunction. Damaged mitochondria produce large amounts of ROS, resulting in intracellular redox imbalance and eventually leading to extensive mitochondrial damage. Detailed in vitro studies using human bronchial cells reveal that PM2.5 disrupts mitochondrial ultrastructure, impairs the electron transport chain function, and elevates mitochondrial-specific ROS (mtROS) production [43]. These changes lead to: (1) compromised oxidative phosphorylation and ATP synthesis; (2) disrupted mitochondrial dynamics, characterized by an imbalance in fusion and fission processes; (3) impaired mitophagy leading to the accumulation of damaged mitochondria; and (4) metabolic reprogramming towards glycolysis [44]. Importantly, dysfunctional mitochondria themselves become substantial sources of ROS, perpetuating a cycle of oxidative stress that exacerbates cellular injury. This mitochondrial-ROS feedback loop is particularly relevant in COPD, where persistent oxidative damage accelerates lung aging and contributes to progressive functional decline.

Effect of PM2.5 on cell death

The pathogenesis of COPD under PM2.5 exposure involves complex cellular processes, notably apoptosis and cellular senescence, which significantly contribute to pulmonary tissue damage and airway remodeling. These processes are mediated through distinct yet interconnected molecular pathways that warrant detailed examination.

Programmed cell death is a critical component of PM2.5-induced lung injury. Extensive research employing various model systems, including samples from COPD patients, human small airway epithelial cells (HSAEpCs), and lung tissues, has identified the p21 protein and the lncIL7R-EZH2 signaling axis as key regulators of PM2.5-induced apoptosis. This pathway operates through H3K27 trimethylation (H3K27me3) histone modifications, which concurrently modulate oxidative stress responses and apoptotic processes [45]. In vitro studies using BEAS-2B cells have demonstrated that PM2.5 exposure diminishes cell viability while upregulating apoptosis-related genes, primarily mediated through the activation of the NLRP3/caspase-1 inflammasome pathway. This activation not only facilitates apoptotic cell death but also intensifies pulmonary inflammation, as evidenced by increased inflammatory cell infiltration and cytokine release in COPD mouse models [46].

The PI3K/AKT/mTOR signaling axis emerges as another critical pathway in the pathogenesis of COPD induced by PM2.5 exposure. This pathway, which serves as a key regulator of autophagy, is notably suppressed upon exposure to PM2.5, resulting in disrupted autophagic flux within alveolar epithelial cells [47]. This disruption leads to impaired cellular homeostasis, creating an environment conducive to apoptotic cell death, which in turn contributes to progressive damage of lung tissue. This mechanism explains the observed association between chronic exposure to PM2.5 and accelerated alveolar destruction in COPD.

Beyond apoptosis, PM2.5 exposure induces cellular senescence, a permanent cell cycle arrest that contributes to the progression of COPD through distinct mechanisms. Experimental evidence demonstrates that PM2.5 triggers senescence in both rat and human airway smooth muscle cells (ASMCs) via activation of the autophagy-dependent GATA4/TRAF6/NF-κB signaling cascade. This pathway ultimately leads to the development of a senescence-associated secretory phenotype (SASP), marked by the sustained secretion of pro-inflammatory cytokines, growth factors, and enzymes involved in matrix remodeling [48]. The SASP not only perpetuates local inflammation but also drives pathological airway remodeling, a hallmark feature of advanced COPD.

Conventional medical therapy

Exacerbations of COPD induced by PM2.5 exposure present a substantial clinical challenge, necessitating advanced therapeutic interventions to address inflammation, oxidative stress, and cellular damage. Recent studies have identified several promising pharmacological agents that target specific molecular pathways implicated in the pathogenesis of PM2.5-induced COPD, thereby offering novel approaches to disease management.

Hydrogen sulfide (H₂S), an endogenous gaseous signaling molecule with potent antioxidant properties, has been identified as a potential therapeutic candidate for addressing PM2.5-induced COPD. Experimental studies using C57BL/6 mice and BEAS-2B bronchial epithelial cells have revealed that H₂S donors, such as sodium hydrosulfide (NaHS), can mitigate oxidative stress and inflammation by modulating the NLRP3/caspase-1 inflammasome pathway and reducing the expression of IL-1β, IL-18, and MMP-9 [49]. Additionally, H₂S enhances Klotho/Parkin-mediated mitophagy, thereby preserving mitochondrial function and reducing cellular senescence in airway epithelial cells, ultimately alleviating PM2.5-induced lung injury. Although the clinical application of H₂S-based therapies remains under exploration, preclinical evidence supports its potential efficacy in COPD management [50]. It is noteworthy, however, that while high concentrations of H₂S are detrimental to human health, exposure to low concentrations confers cytoprotective effects.

Glycogen synthase kinase-3β (GSK-3β) serves as a pivotal regulator of inflammatory responses, influencing NF-κB, STAT, and β-catenin signaling. In murine models and human bronchial epithelial cells (HBECs) exposed to PM2.5, pharmacological inhibition of GSK-3β has been shown to attenuate pulmonary inflammation by suppressing JNK phosphorylation and NF-κB activation, thereby reducing the release of pro-inflammatory cytokines (e.g., TNF-α, IL-6). This strategy may augment existing anti-inflammatory therapies, such as corticosteroids, by targeting upstream signaling mechanisms that drive COPD exacerbations [51].

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is elevated in COPD patients and contributes to increased oxidative stress and inflammation. Dimethylarginine dimethylaminohydrolase 1 (DDAH1), the enzyme responsible for the degradation of ADMA, exerts protective effects in PM-exposed mice by reducing p65 phosphorylation and Bax-mediated apoptosis, while simultaneously enhancing antioxidant defenses, such as SOD1 and peroxiredoxin 4 (Prdx4). Therapeutic approaches targeting the enhancement of DDAH1 activity or the reduction of ADMA accumulation may improve vascular and airway function in COPD [52].

In addition, melatonin is a naturally occurring hormone with anti-inflammatory and antioxidant properties, which has shown efficacy in ameliorating PM2.5-induced COPD exacerbations. Studies in BEAS-2B cells and murine models reveal that melatonin inhibits the PERK/eIF2α/ATF4/CHOP endoplasmic reticulum (ER) stress pathway, thereby reducing apoptosis and airway inflammation. Given its favorable safety profile, melatonin may serve as an adjunctive therapy for COPD patients experiencing high exposure to PM2.5 [53].

Although these emerging therapies demonstrate potential, their clinical practice necessitates further validation through randomized controlled trials. Key considerations include: (1) the use of combination therapies that targeting multiple pathways (e.g., Nrf2 activation in conjunction with anti-inflammatory agents); (2) personalized medicine approaches tailored to individual genetic and environmental risk factors; (3) comprehensive long-term safety assessments, especially concerning the chronic use of novel agents like H₂S donors and GSK-3β inhibitors. The advancing understanding of the pathogenesis of COPD induced by PM2.5 exposure has facilitated the development of targeted pharmacological interventions aimed at mitigating oxidative stress, inflammation, and cellular apoptosis. Future research should focus on optimizing these therapies for clinical application, particularly among high-risk populations with prolonged exposure to PM2.5.

Traditional Chinese Medicine (TCM) therapy

Although Western medicine primarily provides symptomatic management of COPD through the use of bronchodilators and anti-inflammatory agents, Traditional Chinese Medicine (TCM) has gained recognition as a complementary approach with considerable therapeutic promise. Recent studies highlight the efficacy of TCM formulations and bioactive compounds in alleviating PM2.5-induced COPD through anti-inflammatory, antioxidant, and immunomodulatory mechanisms. This review summarizes key findings regarding the role of TCM in the prevention and treatment of COPD, with an emphasis on its molecular mechanisms and preclinical evidence.

Previous studies have demonstrated that the Bufei Yishen Formula, a clinically prescribed TCM formulation, exerts notable efficacy in the management of COPD. The combination of its active constituents has also been indicated to suppress macrophage activation and reduce PM2.5-induced pulmonary inflammation [54]. Notably, this ingredient combination exhibits beneficial effects on mitochondrial function by inhibiting mitochondrial oxidative stress through the enhancement of SIRT3-mediated deacetylation of FOXO3 [55]. Moreover, it exerts notable anti-oxidative and anti-inflammatory properties by modulating the miR-155/FOXO3a signaling pathway in the COPD rat model [56]. In addition, various natural polysaccharides derived from medicinal herbs, such as astragalus polysaccharides (APS) and codonopsis polysaccharides (CPS), have also been found to offer protective effects against PM2.5-induced COPD. In murine models of COPD, APS, and CPS significantly reduced systemic and pulmonary inflammation by inhibiting the hyperactivation of alveolar macrophages. Furthermore, these polysaccharides have also been shown to mitigate oxidative stress and improve lung function, suggesting their potential as adjunctive therapies for COPD sufferers who are exposed to environmental pollutants [57].

Recently, Curcumin, the principal bioactive compound derived from Curcuma longa, has garnered significant attention due to its extensive pharmacological properties, particularly its anti-inflammatory and antioxidant effects. In both in vivo and in vitro studies, curcumin was shown to counteract PM2.5-induced inflammation and oxidative stress by regulating the PTEN/PI3K/AKT signaling pathway. This modulation not only decreased the release of inflammatory cytokines but also protected against alveolar damage, highlighting curcumin’s potential role in the management of COPD [58]. Lentinan, another polysaccharide extracted from Lentinula edodes, demonstrates strong immunomodulatory and anti-inflammatory properties. Previous studies have revealed that lentinan suppresses PM2.5-induced pulmonary inflammation by inhibiting the GARP/TGF-β/SMAD pathway, thereby reducing EMT and fibrosis. Furthermore, lentinan exhibits metal-chelating effects, neutralizing toxic heavy metals present in PM2.5 and offering additional cytoprotection [59].

Taken together, existing evidence highlights the therapeutic potential of TCM in addressing PM2.5-induced COPD through mechanisms that include the inhibition of oxidative stress, suppression of inflammation, and immunomodulation. Nonetheless, further investigation is required to clarify the specific molecular pathways involved and to optimize clinical applications. Future research should prioritize the standardization of TCM formulations, the execution of large-scale clinical trials, and the exploration of synergistic effects with conventional therapies. Integrating TCM into COPD management could facilitate the development of a more comprehensive and personalized treatment strategy to effectively combat this condition.

In this review, we summarized the existing literature on the cellular and molecular mechanisms linking PM2.5 exposure to the development of COPD, and assessed advancements in innovative therapeutic agents for COPD within both contemporary and traditional medical frameworks. Given the involvement of inflammatory responses, immune dysregulation, oxidative stress, mitochondrial dysfunction, apoptosis, and cellular senescence during COPD progression, alongside the documented influence of PM2.5 on these pathways, it is plausible that PM2.5 contributes to COPD pathogenesis through the concurrent activation of multiple pathways (Figure 1).

However, the heterogeneous composition of PM2.5, encompassing metals, organic compounds, and microbial elements, complicates mechanistic studies, and the toxicological contributions of individual components remain ambiguous. Furthermore, the impact of PM2.5 on COPD and the corresponding therapeutic management have been elucidated mostly based on various in vitro and animal studies; nonetheless, large-scale randomized controlled trials (RCTs) are imperative to confirm the clinical benefits. Furthermore, during the development of novel therapeutics, comprehensive assessment of drug toxicity profiles is imperative, necessitating extensive preclinical validation to ensure human safety. PM2.5, as an environmental risk factor for sustained population exposure, has garnered significant academic interest. Moreover, the influence of other contaminants on respiratory disorders is similarly significant and must not be disregarded. An urgent necessity exists to enhance and strengthen pertinent research to clarify their pathogenic mechanisms and investigate effective prevention and control techniques. Additionally, future research should focus on biomarker-guided therapies, incorporating omics technologies to identify patient subgroups that would derive the greatest benefit from TCM interventions. This might unveil novel preventive/therapeutic strategies for mitigating PM2.5-induced COPD and associated exacerbations. Simultaneously, systematic interventions targeting pollution sources are essential, which include the stringent enforcement of air pollution prevention regulations, enhanced control of industrial emissions, the clean retrofitting of mobile sources, and the optimization of the energy structure to achieve synergistic reductions in multi-pollutant emissions.

Not Applicable.

All data analyzed during this study are included in this published article.

The authors declare that they have no competing interests.

This work was financially supported by the National Natural Science Fund of China [82374263].

Yangzi Dong: Investigation, Methodology, Formal analysis, Writing – original draft. Huiyu Yue: Methodology, Writing – original draft. Mengyao Hu: Methodology, Formal analysis. Yingying Li: Methodology, Formal analysis. Tiantian Liu: Funding acquisition. Jing Wang: Conceptualization, Supervision, Writing – review & editing.