Biomarkers Show Potential in Predicting PM Exposure in Patients With COPD

Various biomarkers show potential in predicting the extent of particulate matter (PM) exposure in patients with chronic obstructive pulmonary disease (COPD), according to a study published in the Journal of Thoracic Disease.

Recent studies have correlated elevated levels of ambient PM in polluted air with COPD development. In the current study, researchers conducted a systematic review to evaluate if biomarkers help explain PM exposure effects in patients with COPD. To do so, they reviewed relevant studies with data on identifying PM biomarkers in patients with COPD published between January 1, 2012, and June 30, 2022.

Researchers identified 145 eligible studies but, after review, ultimately analyzed 22. The researchers organized the 50 relevant biomarkers found throughout into 4 mechanisms: oxidative stress, innate and adaptive immune systems, genetic regulation or inflammation, and epigenetic regulation of physiology and susceptibility.

Some studies reported an association between PM and oxidative stress biomarkers in patients with COPD. Oxidative stress develops when the production of reactive oxygen species (ROS) and antioxidant defense are unbalanced, disrupting redox homeostasis. The researchers found that PM concentration had a significant positive association with urinary surrogate markers of oxidate stress, namely 8-hydroxy-2’-deoxyguanosine (8-OHdG) and malondialdehyde (MDA); 8-OHdG forms due to hydroxyl radical attack on DNA and can help to evaluate the extent of DNA damage repair caused by ROS, whereas MDA is a product of fatty acid oxidation used to estimate the extent of lipid peroxidation.

One study examined the relationship between indoor black carbon exposure, 8-OHdG, and MDA in participants with COPD. The researchers found a positive association, suggesting that air pollution exposure resulted in lipid peroxidation and oxidative DNA damage in patients with COPD.

Researchers also discovered that chronic airway inflammation is involved in COPD development. Evidence within the examined studies suggested that interleukins predicted PM exposure in patients with COPD. More specifically, they found that levels of IL-6, an interleukin that acts as an anti-inflammatory and proinflammatory cytokine, exhibited associations with PM exposure.

C-reactive protein (CRP) and fractional exhaled nitric oxide (FeNO) levels are other inflammatory markers that predicted the extent of PM exposure in patients with COPD. CRP is a reproducible, well-standardized, readily available, and highly sensitive systemic marker of tissue damage and inflammation. Studies found CRP to consistently show a statistically significant positive association with the extent of PM exposure. Also, FeNo measurement is a noninvasive method that determines inhaled corticosteroid responsiveness. Several studies positively linked FeNO with PM, but further research is needed to identify minimally invasive methods to predict PM exposure for early COPD intervention.

Additionally, researchers found several studies about epigenetic changes. These are molecular changes in DNA structure and gene expression due to DNA methylation or acetylation that may mediate environmental effects on human health. One study found that some specific PM components might be associated with decreased methylation in patients with COPD. These changes are associated with inflammation and oxidative stress, all 3 playing significant roles in COPD’s pathophysiology.

Lastly, rarer PM-induced mechanisms result from innate and adaptive immune system mechanisms. Once patients inhale noxious particles, the particles left behind get deposited in the alveolar space where alveolar macrophages clear and process them via scavenger and toll-like receptors, activating innate and adaptive immune responses. One study found that higher indoor PM with a diameter of 2.5 μm or less (PM_2.5) was associated with increased black carbon in airway macrophages in patients with COPD (0.19 μm² increase per 10 μg/m³ indoor PM_2.5).

Overall, this review helped researchers discover several biomarkers that have been proposed to establish diagnosis and prevention strategies for air pollution­–related diseases. The researchers also found that some biomarkers were more useful in combination. They noted that measuring biomarkers related to PM exposure can be challenging as exposure is often chronic, with low to moderate exposure levels over time.

The researchers recognized that limitations affected their study. They could not quantify the confounding factors possibly affecting the biomarkers because most studies analyzed the relationship between a single biomarker and PM. Researchers also noted that the available literature lacked “longitudinal studies that investigated the temporal relationship between biomarkers and PM.” Because of this, more research is necessary.

“Future studies are needed to establish recommendations for regulation to reduce airborne PM, which could be used to develop strategies for prevention and management of environmental respiratory diseases,” the authors concluded.

Reference

Kim J, Kim NY, Kim WJ. Biomarkers of particulate matter exposure in patients with chronic obstructive pulmonary disease: a systematic review. J Thorac Dis. 2023;15(6):3453-3465. doi:10.21037/jtd-23-78