Air pollution and alveolar health

Abstract

Exposure to air pollution has been associated with up to 9 million premature deaths per year worldwide, with the respiratory system a key site for its effects. Air pollution exposure is a well-established risk factor for the development and exacerbation of airways diseases and lung cancer, however relatively little is known regarding the risks associated with air pollution interacting with areas of gas exchange - the alveoli and pulmonary interstitium. In recent years, evidence has emerged identifying a role in the development and progression of sub-clinical interstitial lung abnormalities as well as progression and risk of exacerbation of fibrotic interstitial lung diseases. This review outlines the epidemiologic evidence that air pollution perturbs alveolar health. It considers the different components of ambient air pollution, how penetration to the alveoli is determined by particle size and whether the response to alveolar exposure may be modulated by personal susceptibility factors. We discuss potential acute and chronic pathogenic mechanisms of injury upon the pulmonary interstitium and how these may contribute to the development and/or progression of interstitial processes. Finally, we explore current knowledge gaps and the potential for air pollution interventions in vulnerable individuals to support alveolar homeostasis and so prevent disease development and/or progression.

FIGURE 1

Sources of air pollution at different locations within the respiratory tree. a) Summary of potential sources of air pollution including particulate matter by size fraction, ground-level ozone (O₃) and nitrogen dioxide (NO₂). b) Penetration of different air pollution sources identified in a) to sites within the respiratory tree. Both composition and size influence particulate matter penetration, with only particulate matter with aerodynamic diameter <2.5 μm typically capable of reaching the alveolar region. c) Overview of potential mechanisms of alveolar homeostasis perturbation by air pollution sources including oxidative stress, DNA damage, release of proinflammatory mediators, recruitment of inflammatory cells and translocation to the pulmonary capillaries. Figure created in BioRender (https://BioRender.com/mo0n0l0).

FIGURE 2

Proposed mechanisms of injury of the alveolus by particulate matter (PM). Innate immune cells are recruited to the alveolus to phagocytose PM particles, whilst oxidative stress, epigenomic alterations and local inflammation may promote type II alveolar epithelial cells to undergo apoptosis and/or cellular senescence. Cumulative exposures may lead to the shortening of telomeres, whilst dysregulation of epithelial–mesenchymal crosstalk may promote activation of fibroblasts and pro-fibrogenic mediators. Figure created in BioRender (https://BioRender.com/pix26ud).