Researchers reveal why no level of air pollution is safe for respiratory health

By Priyanjana Pramanik, MSc.Reviewed by Susha Cheriyedath, M.Sc.Sep 9 2025

Tiny particles in polluted air trigger lung damage, chronic disease, and early deaths, making cleaner air a critical global health priority.

Review: Particulate matter air pollution: effects on the respiratory system. Image Credit: Lightspring / Shutterstock

In a recent review article in the Journal of Clinical Investigation, researchers Robert B. Hamanaka and Gökhan M. Mutlu at The University of Chicago, USA, synthesized toxicological studies and epidemiological evidence to explain how particulate matter (PM) causes impaired lung function, inflammation, and oxidative stress, thereby contributing to both chronic and acute respiratory illnesses.

Their conclusions sharpen the main message: particulate air pollution is a major environmental health risk and a significant cause of respiratory morbidity and mortality, with most excess deaths being cardiovascular, highlighting the urgent need for stricter air quality standards and effective public health interventions.

Sources and components of air pollution

Air pollution contains both gaseous components and PM. Gases include sulfur dioxide (SO₂), nitrogen oxides (NO, NO₂), ozone (O₃), and carbon monoxide (CO). PM consists of carbon-based particles combined with metals and transition metals (e.g., vanadium, cadmium, nickel), as well as organic compounds such as polyaromatic hydrocarbons (PAHs), nitrates, and sulfates.

PM is classified by size: PM10 (coarse), mainly originating from natural and industrial sources, typically remains in the upper airways; PM2.5 (fine) and PM0.1 (ultrafine or nanoparticles), primarily produced by fossil fuel combustion, penetrate deeply into the lungs, posing greater health risks.

Traffic and industrial emissions are the main contributors to PM and nitrogen dioxide. Sulfur dioxide from coal burning has decreased globally, but indoor biomass burning for cooking and heating remains a concern in developing regions.

Because pollutants are often co-produced, isolating individual effects is difficult. Nevertheless, PM2.5 is consistently linked to adverse cardiovascular and respiratory outcomes, prompting regulation under frameworks such as the U.S. Clean Air Act.

Evidence of health impacts

Historical smog events, such as the 1952 London smog, have highlighted the dangers of air pollution. Extensive studies confirmed associations between PM exposure and mortality, with a biphasic response showing stronger effects at lower concentrations.

Cohort studies confirm no safe threshold exists; even low-level PM exposure increases health risks, with mortality associations persisting below current guideline values and observed down to ~4 µg/m³.

Pollution reductions resulting from policies such as the U.S. Clean Air Act and China’s Air Pollution Prevention and Control Action Plan (APPCAP) have significantly improved life expectancy and prevented deaths. Temporary decreases during the 2008 Beijing Olympics reduced biomarkers of inflammation, and lockdowns for coronavirus disease 2019 (COVID-19) also demonstrated rapid health benefits.

However, wildfire smoke is now increasingly influencing annual PM2.5 averages, and events such as the 9/11 World Trade Center disaster underscore the persistent and emerging threats from acute, high-intensity particulate exposure.

Implications for respiratory disease

Air pollution is a significant contributor to respiratory illnesses and deaths, with fine particulate matter (PM2.5) consistently linked to asthma, chronic obstructive pulmonary disease (COPD), pneumonia, pulmonary fibrosis, lung cancer, and acute respiratory distress syndrome (ARDS).

Large-scale studies show that even modest increases in PM2.5 are associated with higher risks of respiratory hospitalizations and mortality, with no safe threshold identified. People with asthma are particularly vulnerable, as exposure worsens symptoms, increases emergency visits, and is strongly linked to new-onset asthma in children and has been associated with epigenetic changes such as FOXP3 hypermethylation.

Evidence from long-term cohorts, such as the Southern California Children’s Health Study, also shows reduced lung function growth in highly polluted areas. In COPD, air pollution accelerates disease progression, impairs lung function, and heightens the likelihood of hospital admission and death, while also contributing to new cases beyond smoking-related risks through oxidative stress pathways.

Pollutant exposure increases the rates of viral and bacterial infections, including influenza, tuberculosis, and COVID-19, by impairing macrophage function and mucociliary clearance. It is strongly linked to ARDS, with increased mortality observed during the pandemic due to amplified inflammatory responses.

Studies further reveal that PM2.5 worsens outcomes in pulmonary fibrosis, accelerating lung function decline and mortality, and drives lung cancer progression via IL-1β–mediated expansion of mutated cells, including in nonsmokers.

Among lung transplant patients, higher exposure levels are linked with chronic lung allograft dysfunction, reduced survival, and greater mortality, underscoring the pervasive respiratory impact of air pollution.

Underlying biological mechanisms

PM damages the lungs through multiple interconnected mechanisms. Experimental studies in animals, humans, and cultured cells show that inhaled PM triggers oxidative stress and inflammation, largely driven by mitochondrial reactive oxygen species (ROS) and activation of transcription factors such as NF-κB and NRF2.

This leads to the release of inflammatory cytokines, systemic immune responses, and oxidative injury, contributing to diseases like asthma, COPD, fibrosis, pneumonia, and lung cancer through persistent epithelial injury.

Mitochondrial dysfunction is a key factor, as PM accumulates in mitochondria, alters energy metabolism, and amplifies ROS production. These effects impair lung regeneration, promote epithelial injury, and disrupt mucociliary clearance, weakening defenses against pathogens and promoting fibrosis via IL-6–dependent pathways.

Chronic exposure may also induce premature cell aging (senescence) and fibrosis. PM alters immune function by impairing macrophage phagocytosis and cytokine responses, thereby dampening antiviral defenses and skewing T cell balance toward Th2/Th17 phenotypes, which increases vulnerability to infections and allergic diseases.

Additionally, air pollution causes epigenetic changes, such as global DNA hypomethylation and histone modifications, that influence long-term respiratory health. Finally, PM particles may act as carriers for viruses, enhancing deep lung deposition of pathogens.

Conclusions

The central message is clear: air pollution remains a major, modifiable risk factor for respiratory disease, with no level of exposure proven to be safe. Effective emission reductions and health mitigation strategies are vital.

A deeper mechanistic understanding of how pollutants damage tissues is essential, with new single-cell transcriptomic and epigenomic tools offering promise for advancing this knowledge. Improved pollutant measurement techniques, such as satellite monitoring, low-cost sensor networks, and land-use regression models, will enhance exposure assessments and improve the accuracy of environmental monitoring.

Identifying the most toxic components of particulate matter, like transition metals (e.g., vanadium), will inform targeted policies. These advances are especially critical for protecting children, older adults, and low-income populations who bear disproportionate burdens.