Oxidative Stress in Airway Diseases

Oxidative stress arises when the generation of reactive oxygen species (ROS) outpaces the antioxidant defence mechanisms of the airway, leading to cellular and molecular injury. In conditions such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, persistent ROS accumulation drives epithelial damage, mucus hypersecretion, smooth muscle contraction and extracellular matrix remodelling. Sources of excess ROS include activated inflammatory cells (neutrophils, eosinophils), mitochondrial dysfunction and inhaled pollutants or tobacco smoke. Under normal conditions, enzymatic antioxidants—superoxide dismutase, catalase and the glutathione system—and non-enzymatic scavengers maintain redox homeostasis. Disruption of this balance amplifies pro-inflammatory signalling, cytokine release and tissue fibrosis, contributing to airway hyperresponsiveness and decline of lung function. Advances in understanding redox-sensitive pathways have illuminated how oxidative stress underpins therapeutic resistance and disease chronicity, guiding the development of targeted antioxidant strategies to complement existing anti-inflammatory and bronchodilator treatments.

Research from Nature Portfolio

Recent studies have elucidated how a natural flavonol modulates remodelling in experimental asthma by targeting oxidative pathways. Administration of galangin in ovalbumin-sensitised animals reduced inflammatory cell infiltration, goblet cell hyperplasia and subepithelial fibrosis. Mechanistic analysis revealed that galangin attenuated TGF-β1-induced reactive oxygen species production, interrupting downstream MAPK signalling and thereby counteracting airway narrowing. These findings underscore the therapeutic potential of modulating redox-sensitive growth factor pathways to mitigate structural changes in chronic airway disease.

Oxidative Stress in Airway Diseases publication trend

The graph below shows the total number of articles in oxidative stress in airway diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can damage lipids, proteins and DNA when not neutralised by antioxidants.

Ferroptosis: A form of regulated cell death driven by iron-dependent lipid peroxidation under conditions of antioxidant depletion.

TGF-β1: A cytokine that promotes fibrosis and remodelling by stimulating extracellular matrix deposition and ROS production.

MAPK signalling: A family of kinase pathways that transduce oxidative and inflammatory signals to regulate cell proliferation and survival.

Nrf2/HO-1 pathway: A redox-sensitive transcriptional programme that induces antioxidant and cytoprotective enzymes, including haem oxygenase-1.

β2-adrenergic receptor: A G-protein-coupled receptor on airway smooth muscle whose oxidative modification can impair bronchodilator efficacy.

References

1. β-glucan nanoparticles alleviate acute asthma by suppressing ferroptosis and DNA damage in mice. Apoptosis (2024).
2. Agonists and hydrogen peroxide mediate hyperoxidation of β2-adrenergic receptor in airway epithelial cells: Implications for tachyphylaxis to β2-agonists in constrictive airway disorders. Biomedicine & Pharmacotherapy (2023).
3. Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways. Immunity Inflammation and Disease (2021).
4. Galangin attenuates airway remodelling by inhibiting TGF-β1-mediated ROS generation and MAPK/Akt phosphorylation in asthma. Scientific Reports (2015).