Ozone-Induced Airway Inflammation and Hyperresponsiveness

Ground-level ozone is a pervasive oxidant air pollutant that injures the respiratory epithelium and provokes sterile inflammation and exaggerated bronchoconstriction. The initial insult arises from ozone-driven oxidative stress, which disrupts epithelial tight junctions and triggers regulated cell-death pathways, releasing alarmins and damage-associated molecular patterns (DAMPs). These mediators engage innate immune sensors—particularly inflammasomes and toll-like receptors—leading to caspase-1–dependent maturation of interleukin-1β and interleukin-18, and the downstream production of chemokines that recruit neutrophils and innate lymphoid populations. The inflammatory milieu amplifies airway hyperresponsiveness (AHR) and, with repeated exposures, fosters airway remodelling characterised by collagen deposition, smooth-muscle hypertrophy and emphysema-like airspace enlargement. Host factors such as obesity, sex and genetic background modulate susceptibility, while single-cell transcriptomic profiling has delineated key damage-sensing pathways across epithelial and immune cell types. Globally, elevated ozone levels contribute to asthma exacerbations, chronic obstructive pulmonary disease progression and diminished lung function. Therapeutic strategies under investigation include antioxidants, kinase inhibitors and receptor modulators aimed at restoring barrier integrity, curbing inflammation and reducing hyperreactivity.

Research from Nature Portfolio

Recent murine studies have quantified the divergent effects of acute versus chronic ozone exposure on airway structure and function. Single high-dose challenges provoke rapid epithelial disruption, protein leakage into the bronchoalveolar space, neutrophil influx and AHR, all of which are reversible. In contrast, repeated exposures induce peribronchiolar fibrosis, collagen deposition and emphysema-like enlargement of distal airspaces, as revealed by automated morphometric analysis correlating structural remodelling with persistent hyperresponsiveness. Complementary work has uncovered a central role for the caspase-1–interleukin-1 axis in neutrophilic inflammation: prolonged low-dose ozone generates mitochondrial reactive oxygen species and cytosolic mitochondrial DNA in macrophages, activating inflammasomes and driving IL-17A production by γδ T cells. Pharmacological inhibition of caspase-1 or blockade of IL-1 signalling markedly attenuates both airway inflammation and hyperresponsiveness in these models.

Ozone-Induced Airway Inflammation and Hyperresponsiveness publication trend

The graph below shows the total number of articles in ozone-induced airway inflammation and hyperresponsiveness across all publications each year (not limited to Nature Index journals).

Technical terms

Airway hyperresponsiveness (AHR): Exaggerated constriction of bronchial smooth muscle in response to non-specific stimuli.

Oxeiptosis: Reactive oxygen species–driven regulated cell-death pathway distinct from apoptosis and necrosis.

Damage-associated molecular patterns (DAMPs): Endogenous molecules released by injured or dying cells that activate innate immune responses.

Inflammasome: Cytosolic multiprotein complex that activates inflammatory caspases, leading to maturation of IL-1β and IL-18.

Oxidative stress: Imbalance between oxidant production and antioxidant defences, resulting in cellular and tissue injury.

Alarmins: Endogenous danger signals released by stressed or necrotic cells to alert and activate immunity.

Aryl hydrocarbon receptor (AhR): Ligand-activated transcription factor that senses environmental chemicals and regulates immune and barrier functions.

References

1. Ozone-induced lung injury and inflammation: Pathways and therapeutic targets for pulmonary diseases caused by air pollutants. Environment International (2025).
2. Acute Respiratory Barrier Disruption by Ozone Exposure in Mice. Frontiers in Immunology (2019).
3. Ozone-Induced Oxidative Stress, Neutrophilic Airway Inflammation, and Glucocorticoid Resistance in Asthma. Frontiers in Immunology (2021).
4. Ozone-induced IL-17A and neutrophilic airway inflammation is orchestrated by the caspase-1-IL-1 cascade. Scientific Reports (2016).
5. Functional and morphological differences of the lung upon acute and chronic ozone exposure in mice. Scientific Reports (2018).
6. Sex-specific IL-6-associated signaling activation in ozone-induced lung inflammation. Biology of Sex Differences (2016).
7. Effect of Obesity on Acute Ozone-Induced Changes in Airway Function, Reactivity, and Inflammation in Adult Females. PLOS ONE (2016).
8. Ozone-Induced Aryl Hydrocarbon Receptor Activation Controls Lung Inflammation via Interleukin-22 Modulation. Frontiers in Immunology (2020).