Role of air pollutants in airway epithelial barrier dysfunction in asthma and COPD

Abstract

Chronic exposure to environmental pollutants is a major contributor to the development and progression of obstructive airway diseases, including asthma and COPD. Understanding the mechanisms underlying the development of obstructive lung diseases upon exposure to inhaled pollutants will lead to novel insights into the pathogenesis, prevention and treatment of these diseases. The respiratory epithelial lining forms a robust physicochemical barrier protecting the body from inhaled toxic particles and pathogens. Inhalation of airborne particles and gases may impair airway epithelial barrier function and subsequently lead to exaggerated inflammatory responses and airway remodelling, which are key features of asthma and COPD. In addition, air pollutant-induced airway epithelial barrier dysfunction may increase susceptibility to respiratory infections, thereby increasing the risk of exacerbations and thus triggering further inflammation. In this review, we discuss the molecular and immunological mechanisms involved in physical barrier disruption induced by major airborne pollutants and outline their implications in the pathogenesis of asthma and COPD. We further discuss the link between these pollutants and changes in the lung microbiome as a potential factor for aggravating airway diseases. Understanding these mechanisms may lead to identification of novel targets for therapeutic intervention to restore airway epithelial integrity in asthma and COPD.

Polyphenols, flavonoids and inflammasomes: the role of cigarette smoke in COPD

“…In the immunopathology of COPD, immune and nonimmune inflammatory alterations with oxidative stress imbalances are found, as well as changes in the protease/anti-protease ratio caused by direct and indirect genetic and epigenetic-environmental defects. COPD leads to irreversible tissue damage and chronic inflammation with aberrant tissue repairs, which induces chronic obstruction of the airway, bronchitis and systemic damage [2,9]. Evidence from a previous review suggested the role of inflammasomes in the pathogenesis of numerous chronic respiratory diseases and acute lung injuries, such as asthma, transfusion-related acute lung injury (ALI), ventilator-induced lung injury, COPD and pulmonary fibrosis [37].…”

“…Vitally, COPD can be caused by prolonged exposure to harmful particles, particulates and gases, infection with acute or chronic inflammatory conditions, or by injuries that include the airways, pulmonary vasculature and lung parenchyma. COPD is categorised by persistent airflow obstruction instigated by exposure to irritants; for instance, cigarette smoke (CS), dust and fumes [2]. Pulmonary injury comprises the phases of initiation (by exposure to CS, pollutants, infectious pathogens and agents), progression and consolidation.…”

The Role of ASIC1a in Inflammatory Immune Diseases: A Potential Therapeutic Target

“…Asthma is a chronic obstructive disease of the airways worldwide, characterized by airway inflammation and airway hyperreactivity (AHR) (Alwarith et al, 2020;Aghapour et al, 2022). Treatment of asthma is a complicated problem, current drug treatments mainly include long-term control treatments, such as inhaled corticosteroids, long-acting beta-agonists, and oral medications.…”

Recent developments in the immunopathology of COVID-19

“…The airway epithelial barrier interacts with the respiratory microbiome to shape the immune response in the lungs 79 . In addition, air pollution may contribute to chronic systemic inflammation and a higher prevalence of comorbidities such as cardiovascular and respiratory diseases which have been demonstrated to be risk factors for severe COVID-19 78,80,81 . Air pollution is also correlated with a higher expression of ACE2 receptor in the lung 82 .…”