Impacts and Immune Mechanisms of Pollutant-Mediated Asthma and Airway Inflammation

Abstract

Air pollution is a major environmental risk factor contributing to the development, exacerbation, and persistence of asthma. A wide range of airborne pollutants, including particulate matter (PM), ozone (O₃), nitrogen dioxide, sulfur dioxide, diesel exhaust particles (DEPs), volatile organic compounds, and biological contaminants, can interact with the airway epithelium and immune system, leading to dysregulated inflammatory responses. Increasing evidence indicates that pollutant exposure induces epithelial injury, disrupts epithelial barrier integrity, promotes oxidative stress, and activates innate immune signaling pathways. These upstream events shape downstream adaptive immune responses and contribute to heterogeneous inflammatory patterns in asthma, including type 2 eosinophilic inflammation, non-type 2 neutrophilic inflammation, and mixed inflammatory phenotypes associated with severe or corticosteroid-resistant asthma. At the cellular and molecular levels, pollutants activate pattern-recognition receptors and redox-sensitive signaling cascades, including nuclear factor-kappa B, mitogen-activated protein kinase, PI3K/Akt, and inflammasome pathways. These cascades promote epithelial alarmin release, proinflammatory cytokine production, T-cell polarization, neutrophil recruitment, airway hyperresponsiveness, mucus hypersecretion, and structural remodeling. Pollutant-specific mechanisms, such as PM-induced NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation, O₃-mediated epithelial barrier disruption, DEP-driven interleukin-17A responses, and pollutant–allergen co-exposure, further contribute to the heterogeneity of pollutant-mediated asthma. While experimental models have provided valuable mechanistic insights, differences in exposure dose, duration, pollutant composition, and host immune context limit direct translation to real-world human exposure scenarios. This review summarizes current evidence on the impacts of air pollutants on asthma and the immune mechanisms underlying pollutant-mediated asthma. A better understanding of these epithelial–immune pathways may support improved risk assessment, prevention, and more personalized management of asthma in the context of increasing environmental pollution.

INTRODUCTION

Asthma is a chronic respiratory condition characterized by airway inflammation, airway hyperresponsiveness, and structural remodeling; its clinical course is often exacerbated by environmental factors.¹ Among these factors, air pollutants have emerged as important contributors to the development, exacerbation, persistence, and severity of asthma.² The increasing burden of pollutant-associated respiratory disease is closely linked to industrialization, urbanization, and westernized lifestyles, which have increased exposure to outdoor and indoor pollutants, altered microbial environments, and reduced contact with natural ecosystems.³,⁴

Air pollutants comprise the heterogeneous mixtures of particulate matter (PM) with aerodynamic diameters ≤ 10 µm (PM₁₀) and ≤ 2.5 µm (PM_2.5), gaseous pollutants such as ozone (O₃), nitrogen dioxide (NO₂), and sulfur dioxide (SO₂), volatile organic compounds, diesel exhaust particles (DEPs), and biological contaminants.³,⁵ These pollutants originate from diverse natural and anthropogenic sources including fossil fuel combustion, industrial emissions, vehicular exhaust, tobacco smoke, and indoor environments.³,⁶ Because pollutant composition, concentration, and exposure duration vary across geographic regions and environmental settings, their respiratory effects are heterogeneous and may differ according to pollutant type and host susceptibility.³

Epidemiological studies have consistently been associated with air pollutant exposure as well as with increased asthma incidence, symptom severity, acute exacerbations, impaired lung function, and persistent airway inflammation.⁷,⁸,⁹,¹⁰ Air pollutants can affect the respiratory tract by interacting with the airway epithelium, which represents the primary interface between inhaled environmental stimuli and the host immune system.¹¹ However, the biological mechanisms linking pollutant exposure to asthma pathogenesis are complex and remain incompletely integrated across pollutant types, immune pathways, and clinical outcomes.

Previous studies have described multiple mechanisms, through which pollutants may contribute to asthma, including epithelial barrier dysfunction, oxidative stress, innate immune activation, type 2 and non-type 2 inflammation, and airway remodeling.¹¹,¹²,¹³,¹⁴ Nevertheless, many reports have focused on individual pollutants or isolated signaling pathways, making it difficult to understand how these mechanisms collectively shape pollutant-mediated asthma. In addition, although in vitro and animal models have provided important mechanistic insights, differences in exposure dose, particle composition, and immune context compared with real-world human exposure necessitate cautious interpretation of translational relevance.

In this review, we summarize current evidence on the impacts of air pollutants on asthma and the immune mechanisms underlying pollutant-mediated asthma. We aim to provide an integrated perspective on how pollutant exposure contributes to asthma development, exacerbation, and disease progression.

AIR POLLUTANTS

Air pollutants consist of gases, solid particles, and liquid aerosols released into the atmosphere at concentrations that may exceed the natural capacity of the environment to disperse or neutralize them.³ They not only arise from a wide range of natural and anthropogenic sources, including fossil fuel combustion, industrial emissions, motor vehicles, domestic heating, tobacco smoke, and indoor environments, but also typically exist as complex mixtures rather than isolated components.³,⁶ The chemical composition and concentration of air pollutants vary substantially depending on geographic location, season, meteorological condition, and emission source, contributing to heterogeneity in exposure profiles and respiratory health effects.³

The U.S. Environmental Protection Agency criteria pollutants include PM, O₃, carbon monoxide (CO), NO₂, SO₂, and lead (Pb).³ Among these, PM, O₃, NO₂, and SO₂ are particularly relevant to respiratory diseases, including asthma. PM is commonly classified according to aerodynamic diameter as PM₁₀ and PM_2.5, with PM_2.5 being of particular concern because smaller particles can reach the lower respiratory tract and are consistently associated with adverse respiratory outcomes.⁵,⁷ O₃ is a secondary pollutant formed through photochemical reactions involving nitrogen oxides and volatile organic compounds, whereas NO₂ and SO₂ are largely derived from traffic-related combustion, industrial emissions, and fuel burning.³

In addition to outdoor chemical pollutants, indoor air pollutants and biological contaminants are important contributors to asthma-related morbidity. Biological contaminants include respiratory viruses and bacteria as well as aeroallergens such as animal dander, house dust mites, cockroach allergens, molds, and pollen.¹⁵ These exposures are especially relevant in indoor environments, where ventilation, humidity, microbial burden, and allergen accumulation can influence the intensity and duration of exposure. Infectious agents, particularly respiratory viruses, are among the most common triggers of asthma exacerbations, especially in children and individuals with pre-existing airway disease.¹⁵

The clinical relevance of air pollutants depends not only on pollutant type but also on exposure duration and exposure context. Chronic exposure, short-term exposure peaks, indoor accumulation, and combined exposure to chemical pollutants and biological contaminants may produce different respiratory effects.⁷,¹⁵ Therefore, pollutant classification should be interpreted together with exposure route, deposition pattern, duration, and host susceptibility when evaluating their contribution to asthma.

Collectively, air pollutants represent a heterogeneous group of environmental exposures with diverse sources, compositions, and exposure patterns. This heterogeneity is important because different pollutants may affect the airways through distinct exposure routes, deposition patterns, and biological interactions. Understanding these characteristics provides a foundation for interpreting the clinical impacts and immune mechanisms of pollutant-mediated asthma.

IMPACTS OF AIR POLLUTANTS ON ASTHMA

Ambient air pollutant exposure is associated with a broad range of adverse asthma-related outcomes, including asthma development, symptom worsening, acute exacerbations, increased medication use, emergency department visits, hospitalization, and impaired lung function.⁷,⁸ These clinical effects vary according to pollutant type, exposure intensity, exposure duration, and host susceptibility. Children, older adults, individuals with pre-existing respiratory or cardiopulmonary disease, and socioeconomically vulnerable populations are disproportionately affected by pollutant exposure.⁹,¹⁰,¹⁶

PM is among the most consistently studied air pollutants in relation to asthma. PM_2.5 can reach the distal airways and has been associated with increased respiratory symptoms, reduced lung function, asthma exacerbations, and a higher risk of persistent airway disease.⁵,⁷ PM₁₀, which includes larger particles, such as dust, pollen, and mold fragments, may also aggravate respiratory symptoms, particularly in individuals with pre-existing asthma or allergic airway disease.³ These findings indicate that particle size, composition, and deposition pattern are important determinants of asthma-related respiratory effects.

O₃ and traffic-related gaseous pollutants also contribute substantially to asthma morbidity. Ground-level O₃, a major component of photochemical smog, is linked to airway irritation, symptom worsening, and exacerbation of asthma and other obstructive airway diseases.³,¹⁷ NO₂ exposure is associated with asthma incidence and exacerbations, particularly in traffic-related exposure settings, and may contribute to airway irritation, allergen sensitization, and airway hyperresponsiveness.⁸,¹⁰ SO₂ can provoke bronchoconstriction and symptom worsening in susceptible individuals and has been associated with increased asthma mortality in ecological analyses.¹⁸

Climate change further modifies the relationship between air pollution and asthma by altering pollutant levels, temperature extremes, and biological exposure patterns. Rising temperatures, stagnant air, and fossil fuel-related emissions can increase the formation and persistence of ground-level O₃ and other pollutants.¹⁶,¹⁹ In addition, climate change can alter the composition, diversity, and activity of the aerobiome, including airborne bacteria, fungi, and aeroallergens, thereby modifying respiratory exposure patterns.²⁰ These environmental changes may aggravate asthma symptoms and increase exacerbation risk through combined effects of chemical pollutants, biological exposures, and non-optimal temperatures.

Overall, air pollutants influence asthma through both direct respiratory effects and broader environmental interactions. Long-term exposure to pollutants such as PM_2.5, O₃, and NO₂ is more strongly associated with asthma development and persistent respiratory impairment, whereas short-term exposure peaks are more closely linked to acute symptom worsening and asthma exacerbations.⁷,⁸ These clinical impacts provide the basis for examining the immune mechanisms by which pollutants promote airway inflammation, alter inflammatory phenotypes, and contribute to pollutant-mediated asthma severity.

IMMUNE MECHANISMS IN POLLUTANT-MEDIATED ASTHMA

The respiratory tract serves as the primary interface between airborne pollutants and host immunity. Inhaled particulates and gases interact with airway epithelial cells and resident immune cells, which sense environmental stimuli and initiate intracellular signaling pathways that propagate multicellular inflammatory responses.¹³,¹⁴ In pollutant-mediated asthma, epithelial injury, barrier dysfunction, oxidative stress, and innate immune activation represent early upstream events that shape downstream adaptive immune responses and influence disease expression. Air pollutants can modulate multiple immune cell compartments, including epithelial cells, macrophages, neutrophils, dendritic cells, and lymphocytes. These integrated epithelial–immune pathways linking pollutant exposure to type 2 and non-type 2 inflammatory responses, airway remodeling, and corticosteroid resistance are summarized in the Figure and Table.

Figure. Pollutant-mediated immune pathways in asthma. Air pollutants, including PM_2.5/PM₁₀, O₃, NO₂, SO₂, DEPs, acrolein, and biological contaminants/aeroallergens, interact with the airway epithelium and immune system. (A) In the Th2 pathway, pollutant-associated epithelial barrier dysfunction, claudin alteration, and increased permeability may facilitate allergen penetration and epithelial alarmin release, including IL-25, IL-33, and TSLP. These epithelial-derived signals activate dendritic cells, ILC2s, and Th2 cells, leading to IL-4, IL-5, and IL-13 production, IgE production, eosinophilic inflammation, and mucus hypersecretion. (B) In the non-Th2 pathway, pollutants induce ROS-mediated oxidative stress and activate innate immune receptors, intracellular sensors, and inflammatory signaling pathways, including TLR4, RAGE, NLRP3/caspase-1, NF-κB, MAPK, and PI3K/AKT. These responses promote proinflammatory cytokine and mediator production, including IL-1β, IL-6, IL-8, TNF-α, and IL-18, and contribute to Th17/IL-17A responses, neutrophil recruitment, and NET formation.

PM, particulate matter; O₃, ozone; NO₂, nitrogen dioxide; SO₂, sulfur dioxide; DEP, diesel exhaust particle; IL, interleukin; TSLP, thymic stromal lymphopoietin; ILC2, type 2 innate lymphoid cell; IgE, immunoglobulin E; ROS, reactive oxygen species; TLR, Toll-like receptor; RAGE, receptor for advanced glycation end-products; NLRP3, NOD-like receptor family pyrin domain-containing protein 3; NF-κB, nuclear factor-kappa B; MAPK, mitogen-activated protein kinase; TNF, tumor necrosis factor; NET, neutrophil extracellular trap.

Table. Pollutant-related mechanisms and changes in asthma.

Pollutant	Related pathway	Representative mechanism	Changes in asthma
PM2.5/PM10	Oxidative stress and innate immune signaling	Oxidative stress, epithelial injury, innate immune activation, and fine particle-related NLRP3 inflammasome activation	Respiratory symptoms, reduced lung function, asthma exacerbation, and persistent airway disease
O3	Epithelial barrier dysfunction and oxidative stress pathway	Oxidative epithelial injury, tight junction disruption, claudin alteration, and epithelial barrier dysfunction	Airway irritation, symptom worsening, and asthma exacerbation
NO2	Oxidative stress related inflammatory response	Airway irritation, allergen sensitization, and airway hyperresponsiveness	Asthma incidence and exacerbation
SO₂	Bronchoconstrictive airway response	Bronchoconstriction and symptom worsening in susceptible individuals	Symptom worsening and asthma mortality in ecological analyses
DEP	Th2 and non-Th2 inflammatory pathway	Th2/Th17-skewed immune responses, IL-17A elevation, neutrophilic inflammation, and remodeling-related signaling	Severe asthma phenotype and corticosteroid-resistant neutrophilic inflammation
Acrolein	Epithelial barrier dysfunction	Epithelial or endothelial junctional disruption, CLDN5-related barrier alteration, and increased permeability	Increased permeability and pollutant–allergen interaction
Biological contaminants/aeroallergens	Th2 and mixed inflammatory pathway	Indoor biological exposure, allergen penetration, antigen presentation, epithelial alarmin release, and allergen-driven Th2 or mixed inflammatory responses	Asthma exacerbation trigger and allergen-driven airway inflammation

PM, particulate matter; NLRP3, NOD-like receptor family pyrin domain-containing protein 3; O₃, ozone; NO₂, nitrogen dioxide; SO₂, sulfur dioxide; DEP, diesel exhaust particle; IL, interleukin.

Epithelial barrier dysfunction and alarmin-mediated immune activation

Airway epithelial cells are not passive structural barriers but active immune regulators that sense inhaled pollutants and coordinate downstream inflammatory responses. Pollutant-induced epithelial injury can disrupt tight junction integrity, alter claudin expression, and weaken epithelial barrier function, thereby increasing epithelial permeability and facilitating the penetration of allergens and irritants.¹¹,²¹,²² O₃ is a representative pollutant that induces oxidative epithelial injury and barrier disruption by altering tight junction proteins, including claudins, and weakening epithelial integrity.¹⁷,²²,²³ Volatile aldehydes, such as acrolein, can also disrupt epithelial/endothelial junctional integrity and increase vascular permeability, in part through pathways involving CLDN5 and junction-associated signaling proteins.²⁴,²⁵,²⁶

Damaged epithelial cells release epithelial alarmins, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), which activate dendritic cells and type 2 innate lymphoid cells (ILC2s) as well as downstream T-cell responses.²⁷,²⁸,²⁹,³⁰ Through these epithelial-driven pathways, pollutant exposure can amplify allergen-driven type 2 inflammation and contribute to mixed inflammatory responses. Pollutant–allergen co-exposure is particularly relevant because pollutants, such as PM_2.5, O₃, DEP, and acrolein, can compromise epithelial barrier integrity, facilitate allergen penetration, enhance antigen presentation, and amplify epithelial alarmin release.²¹,²⁴,³¹,³² These interactions may augment allergen-driven Th2 responses and, depending on exposure context, also contribute to Th17 or mixed inflammatory responses.²⁸,²⁹,³³ Thus, pollutant-induced barrier disruption may serve as an initiating event that links environmental exposure to both allergen-driven type 2 inflammation and mixed inflammatory responses in asthma.

Oxidative stress and innate immune signaling

Oxidative stress is a central mechanism by which air pollutants promote airway inflammation. Pollutants induce oxidant-mediated cellular damage primarily through reactive oxygen species (ROS) production in airway epithelial cells, alveolar macrophages, endothelial cells, and other resident airway cells.¹⁴,³⁴ Excess ROS can lead to mitochondrial dysfunction, lipid peroxidation, DNA damage, protein modification, and the activation of redox-sensitive transcription factors such as nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1).

Chemical pollutants, including O₃, NO₂, SO₂, volatile organic compounds, and combustion-derived particles, exert many pathogenic effects through oxidative injury. O₃ and NO₂ can oxidize membrane lipids and proteins, generating secondary reactive products; however, transition metals within PM_2.5 can catalyze hydroxyl radical formation.¹³,¹⁴,³⁵ DEP and volatile organic compounds may impair mitochondrial electron transport, resulting in increased mitochondrial ROS.³⁴ This oxidative burden activates redox-sensitive signaling cascades, including NF-κB, AP-1, and Mitogen-activated protein kinases (MAPKs), thereby amplifying the production of proinflammatory cytokines such as IL-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α.¹³,¹⁴

Exposure to PM, DEP, and other combustion-related pollutants can also activate epithelial and innate immune sensing through pattern-recognition receptors, including Toll-like receptors, NOD-like receptors, and the receptor for advanced glycation end-products.¹³,³⁶ These pathways trigger canonical inflammatory cascades, including NF-κB, MAPK, and PI3K/Akt signaling, leading to proinflammatory mediator release.³⁶,³⁷ Fine particles and nanoparticles can further activate the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, promoting caspase-1-dependent maturation of IL-1β and IL-18 and contributing to neutrophilic airway inflammation.¹⁴,³⁵ Previous studies, including our work, have shown that TiO₂ exposure in the airway epithelial cells and animal models is associated with oxidative stress-related protein alteration, cytoskeletal reorganization, inflammasome activation, and airway responsiveness.³⁸

Persistent pollutant exposure may impair the Nrf2–Keap1 antioxidant defense system, reducing epithelial resilience against oxidative injury.³⁹ In addition to ROS overproduction, pollutants can induce irreversible protein carbonylation, particularly in response to transition metals and volatile organic compounds. These modifications can alter enzyme activity, cytoskeletal organization, epithelial repair responses, and intracellular signaling, thereby amplifying inflammatory cascades and contributing to airway remodeling.¹⁴,³⁴,⁴⁰ Oxidative stress is also closely linked to endoplasmic reticulum stress and mitochondrial dysfunction, which can promote unfolded protein response activation, impaired energy metabolism, mitochondrial ROS release, and epigenetic changes that sustain proinflammatory immune phenotypes.¹⁴,³³,³⁴ Taken together, these oxidative and innate immune pathways provide a common mechanistic bridge between chemically diverse pollutants and persistent airway inflammation in pollutant-mediated asthma.

Type 2 and non-type 2 inflammatory responses in pollutant-mediated asthma

Pollutant exposure can shape adaptive immune responses by altering the cytokine milieu that governs T-cell differentiation. CD4⁺ T cells, particularly Th2 and Th17 subsets, are influenced by epithelial-derived cytokines, dendritic cell activation, and innate immune signaling induced by pollutant exposure.³⁴,⁴¹,⁴² In allergen-rich environments, pollutants may enhance epithelial alarmin release and antigen presentation, thereby amplifying Th2 responses and promoting eosinophilic airway inflammation.²⁷,²⁸,²⁹,³⁰ In type 2 inflammation, activation of ILC2s and Th2 cells promotes IL-4, IL-5, and IL-13 production, leading to immunoglobulin E (IgE) production, eosinophil activation, mucus hypersecretion, and airway inflammation.²⁷,⁴³,⁴⁴

In contrast, pollutants that strongly induce oxidative stress, inflammasome activation, or epithelial injury may promote Th17-skewed and neutrophilic inflammation.³³,³⁵,⁴⁵ DEP exposure can promote Th2- and Th17-skewed immune responses and increase IL-17A, contributing to severe asthma phenotypes and corticosteroid-resistant neutrophilic inflammation.⁴⁵ Non-type 2 inflammation is particularly relevant to pollutant-associated severe asthma because it is often associated with neutrophilic inflammation, persistent symptoms, and reduced responsiveness to corticosteroids. Pollutant-induced IL-6, IL-8, TNF-α, IL-1β, IL-18, and IL-17 can promote recruitment and activation of neutrophils, which may further aggravate airway injury through the release of proteases, oxidants, and neutrophil extracellular traps.⁴⁵,⁴⁶,⁴⁷,⁴⁸

Pollutant-induced immune activation can also progress from acute airway inflammation to structural airway remodeling. Persistent epithelial injury, oxidative stress, and inflammatory cell recruitment may impair epithelial repair and sustain chronic inflammatory signaling. DEP exposure has been associated with inflammatory cytokine expression, goblet cell hyperplasia, fibrosis, and remodeling-related signaling pathways.⁴⁹,⁵⁰ In parallel, pollutant-induced epithelial growth and repair responses, mucus hypersecretion, and fibrosis may contribute to airflow limitation and sustained airway hyperresponsiveness.³³,⁵⁰ Oxidative stress, neutrophilic inflammation, IL-17-related pathways, inflammasome activation, and persistent epithelial injury may reduce corticosteroid responsiveness and contribute to severe or treatment-refractory asthma phenotypes.³¹,⁴⁵,⁴⁸,⁵¹ Collectively, these inflammatory pathways explain how pollutant exposure may contribute not only to asthma exacerbation but also to severe, remodeled, and treatment-refractory disease phenotypes.

CLINICAL IMPLICATIONS IN POLLUTANT-MEDIATED ASTHMA

Understanding pollutant-mediated immune mechanisms has important clinical implications for asthma prevention, risk assessment, and disease management. Because air pollutants can contribute to asthma development, exacerbation, airway inflammation, remodeling, and corticosteroid resistance, clinical evaluation of asthma should consider environmental exposure history in addition to conventional clinical features and inflammatory biomarkers. In particular, exposure to traffic-related pollutants, PM, O₃, tobacco smoke, indoor biological contaminants, and occupational or household irritants may provide useful context for interpreting symptom variability, exacerbation frequency, disease severity, and treatment responsiveness.

Pollutant-mediated asthma may involve type 2, non-type 2, or mixed inflammatory patterns, and this heterogeneity has implications for therapeutic responsiveness. Current asthma therapies predominantly target type 2 inflammation, including inhaled corticosteroids and biologic agents directed against IgE, IL-5, IL-5Rα, or IL-4Rα.⁵¹,⁵²,⁵³ These therapies have reduced exacerbations and improved clinical outcomes in patients with eosinophilic or allergic asthma. However, their efficacy may be limited in patients whose disease is driven predominantly by pollutant-associated oxidative stress, neutrophilic inflammation, inflammasome activation, or mixed inflammatory responses.

Targeting upstream epithelial and innate immune pathways may therefore be clinically relevant in selected patients with pollutant-mediated asthma. Tezepelumab, which targets TSLP, has demonstrated efficacy in a broad range of patients with severe, uncontrolled asthma, including those with lower type 2 biomarker levels.⁵⁴ This finding supports the clinical relevance of epithelial alarmin pathways, although their specific role in pollutant-mediated asthma requires further validation.

Mechanistic pathways activated by pollutants may help guide future studies on therapeutic targets in selected asthma phenotypes. DEP-induced IL-17A elevation has been associated with severe asthma-related inflammation, providing a mechanistic rationale for further investigation of IL-17-related pathways in selected asthma phenotypes.⁴⁵,⁴⁸ PM_2.5-induced activation of the NLRP3 inflammasome and caspase-1-dependent IL-1β/IL-18 production suggests that inflammasome-related pathways may be relevant in pollutant-exacerbated asthma.³⁵ In addition, pollutant-induced oxidative stress and epithelial barrier dysfunction provide a mechanistic rationale for investigating antioxidant or epithelial barrier-protective approaches, although further clinical validation is needed.¹²,³¹,³⁹

Beyond pharmacological approaches, reducing pollutant exposure remains an important component of asthma management. Strategies such as improving indoor air quality, reducing tobacco smoke and combustion-related exposures, minimizing exposure during high-pollution periods, and addressing pollutant–allergen co-exposure may help reduce asthma exacerbation risk. These approaches may be particularly important for children, older adults, individuals with severe asthma, patients with frequent exacerbations, and those living in highly polluted urban environments.

Overall, pollutant-mediated asthma should be understood as a clinically heterogeneous condition shaped by the interaction between environmental exposure, epithelial barrier dysfunction, oxidative stress, and inflammatory phenotype. Integrating exposure history with inflammatory phenotyping may help identify patients at risk for pollutant-associated exacerbations or poor treatment responsiveness. However, most pollutant-specific therapeutic approaches remain investigational, and further mechanistic and clinical studies are needed to determine how environmental exposure profiles can be incorporated into more personalized asthma management.

CONCLUSION

Air pollution remains a significant environmental threat to respiratory health and has substantial implications for the development, exacerbation, and persistence of asthma. Accumulating evidence indicates that key air pollutants, including PM, O₃, NO₂, DEPs, and biological contaminants, contribute to asthma pathogenesis through convergent epithelial and immune pathways. Pollutant-induced epithelial injury, barrier dysfunction, oxidative stress, and innate immune activation represent upstream events that shape downstream type 2, non-type 2, and mixed inflammatory responses.

These immune mechanisms provide a biological link between environmental exposures and clinically important asthma outcomes, including airway inflammation, mucus hypersecretion, airway remodeling, exacerbations, reduced lung function, and corticosteroid resistance. Although experimental studies have provided important mechanistic insights, translating these findings to real-world human exposure scenarios remains challenging because environmental pollutants occur as complex mixtures that vary by dose, duration, composition, and host susceptibility.

Future studies using exposure models that more accurately reflect human environmental conditions will be essential to clarify pollutant-specific immune signatures and their relevance to asthma phenotypes and treatment responsiveness. A deeper understanding of pollutant-mediated epithelial and immune mechanisms may ultimately support improved asthma prevention, risk stratification, and more personalized disease management in the context of increasing global environmental pollution.