How combined PFAS (per- and polyfluoroalkyl substances) and metals may contribute to chronic obstructive pulmonary disease

Abstract

This paper explores the combined impact of PFAS (per- and polyfluoroalkyl substances) and heavy metals on respiratory health, focusing on their potential synergistic or additive effects. Evidence suggests that co-exposure to these contaminants might exacerbate pulmonary inflammation, oxidative stress, and lung injury. Studies indicate that PFAS and heavy metals, both known for their persistence and bioaccumulation in the environment, can disrupt immune responses, increase susceptibility to respiratory infections, and contribute to the development and exacerbation of COPD (chronic obstructive pulmonary disease). Given the limited research on the joint effects of PFAS and metals, this paper aims to fill the knowledge gap by providing insights into their interactive effects on respiratory health. It underscores the importance of regulatory measures to limit emissions of these contaminants and public health initiatives to reduce exposure. By addressing the combined impact of PFAS and metals, effective strategies can be developed to protect respiratory health and mitigate the risks associated with environmental pollutants.

Introduction

Environmental factors play a significant role in respiratory health, influencing both the onset and exacerbation of respiratory conditions. Several key environmental factors have been implicated in respiratory health issues such as climate change (1, 2), air pollution (3, 4), occupational exposures (5, 6), indoor air quality (7, 8), and in some cases allergens (9), and respiratory infections (10, 11). According to Nishida and Yatera (12), ambient and occupational pollutants are implicated in various lung diseases and respiratory diseases. Eguiluz-Gracia et al (13) further emphasized that air pollution and climate change significantly impact respiratory health, with allergic rhinitis and asthma being common issues in Western countries. Researchers have also observed that the intersection of environmental, socioeconomic, and genetic factors can influence respiratory health outcomes (14, 15).

Per- and polyfluoroalkyl substances (PFAS) as air pollutants

Traditional air pollutants such as particulate matter (PM_2.5 and PM₁₀), carbon monoxide, volatile organic compounds (VOCs), and polycyclic aromatic hydrocarbons have established associations with respiratory discomfort and diseases (12, 16–18). PFAS are classified as emerging air pollutants because of their widespread industrial use and persistence in the environment (19, 20). PFAS are known to be associated with a wide variety of health issues/dysfunctions ranging from elevated cholesterol and liver enzyme levels (21) to cancers (e.g., endometrial, thyroid, and testicular cancers) (22). However, their effect on respiratory health is currently being studied (23, 24). Burbank and colleagues found an association between serum PFAS concentration and asthma exacerbations, and the correlation between perfluorooctanoic acid (PFOA) and asthma attacks was substantial in the adolescent age group (12–18-year-olds) (25). In another study, exposure of human bronchial epithelial cells to varied concentrations of PFAS such as short-chain (perfluorobutanoic acid, perflurobutane sulfonic acid and GenX) or long-chain (PFOA and perfluorooctane sulfonic acid (PFOS) revealed that PFOA and PFOS either as standalone or in a mixture had a priming and activating effect on NLRP3 inflammasome which could potentially contribute to asthma/airway hyper-responsiveness (26).

Metals as air pollutants

On the other hand, heavy metals like lead, mercury, and cadmium, are also found in the environment and can harm respiratory health. Occupational exposure to metals is the most common source of metal (including heavy metals) toxicity. It increases the risk of respiratory clinical outcomes such as lung cancers, bronchial asthma, pneumoconiosis, and chronic obstructive pulmonary disease (COPD) (27,28). Lung cancer risk has also been associated with occupational exposure to nickel dust and hexavalent chromium according to a recent study by Behrens et al (29).

Objectives of this review

COPD is a progressive lung disease characterized by airflow limitation, significantly impacting breathing and overall quality of life. Understanding the joint effects of PFAS and metals on respiratory health, including conditions like COPD, is crucial. Current research on the combined impact of these environmental contaminants on COPD is limited, with few epidemiological and mechanistic studies available. This review will explore how PFAS and metals interact to affect respiratory health, providing insights into their combined effects and implications for diseases like COPD.

PFAS: Ubiquitous environmental contaminants

PFAS (per- and polyfluoroalkyl substances) are pervasive environmental contaminants known for their widespread presence due to various industrial and consumer applications (30). These synthetic chemicals have been used in a variety of products, including firefighting foams, non-stick cookware, water-repellent fabrics, and food packaging, because of their resistance to heat, water, and oil. The unique chemical properties of PFAS, particularly their strong carbon-fluorine bonds, make them exceptionally durable and resistant to degradation. As a result, they are often referred to as “forever chemicals.”

Despite their utility, the persistence of PFAS in the environment and their potential adverse health effects have raised significant concerns (31). These substances can accumulate in the human body and the environment over time, leading to bioaccumulation and biomagnification. PFAS have been detected in water, soil, and air around the world, including remote areas far from any direct sources of contamination. Their widespread presence is attributed to both direct emissions from manufacturing and the degradation of consumer products containing PFAS (32).

Exposure to PFAS has been linked to various health issues, including cancer, liver damage, immune system suppression, and developmental effects in children (33, 34). The potential for long-term health impacts has prompted increased scrutiny and regulatory efforts to manage and mitigate their impact. Governments and environmental agencies are working to establish limits for PFAS in drinking water and to phase out the use of certain PFAS in consumer products.

As scientific understanding of PFAS continues to evolve, efforts to address their environmental and health impacts are becoming more urgent. Research is ongoing to develop effective methods for detecting, removing, and destroying PFAS in the environment. Additionally, public awareness and advocacy are playing crucial roles in driving policy changes and promoting safer alternatives to PFAS in industrial and consumer applications (35).

Metals: Environmental presence and respiratory health impacts

Metals, including heavy metals like lead, mercury, and cadmium, are prevalent environmental contaminants that can have detrimental effects on respiratory health (36). These metals are introduced into the environment through various sources, including industrial processes, mining, smelting, fossil fuel combustion, and the improper disposal of metal-containing products. Their persistence in the environment and potential for bioaccumulation make them significant public health concerns.

Heavy metals are known for their toxicity even at low concentrations (37). Once released into the environment, they can contaminate air, water, and soil, leading to widespread exposure. Inhalation of metal particles or fumes is a primary route of exposure that directly impacts respiratory health (38). For example, inhaling lead particles can cause respiratory issues, as well as systemic effects such as neurotoxicity and developmental problems in children. Mercury vapor inhalation can lead to respiratory irritation, lung damage, and long-term neurological effects (39). Cadmium, often released from industrial processes and cigarette smoke, is particularly harmful to the lungs and has been associated with COPD, lung cancer, and other respiratory illnesses (40).

The mechanisms by which heavy metals impact respiratory health are varied. They can induce oxidative stress, inflammation, and damage to lung tissues (41, 42). These processes can exacerbate existing respiratory conditions such as asthma and bronchitis and increase the risk of developing new respiratory illnesses. Children, the elderly, and individuals with preexisting respiratory conditions are particularly vulnerable to the harmful effects of metal exposure.

Efforts to mitigate the impact of heavy metals on respiratory health include regulatory measures to limit emissions, the promotion of cleaner industrial practices, and the proper disposal and recycling of metal-containing products. Public health initiatives focus on monitoring air quality, educating communities about the risks of metal exposure, and providing resources for reducing exposure in high-risk areas (43).

Ongoing research aims to better understand the health effects of heavy metals and develop strategies for reducing their presence in the environment. Advances in air filtration technologies, soil remediation techniques, and alternative materials that reduce the need for toxic metals are critical components of these efforts (44). By addressing the sources and impacts of metal contamination, society can work towards a healthier environment and reduce the burden of respiratory illnesses linked to heavy metal exposure.

Overview of chronic obstructive pulmonary disease (COPD)

COPD is a progressive lung disease characterized by airflow limitation, which significantly impacts breathing and overall quality of life. COPD encompasses two main conditions: chronic bronchitis and emphysema, both of which contribute to the obstruction of airflow and difficulties in breathing (45).

Chronic bronchitis involves inflammation and narrowing of the bronchial tubes, which leads to increased mucus production and persistent coughing. Emphysema, on the other hand, is characterized by damage to the alveoli (air sacs) in the lungs, which impairs the lungs’ ability to exchange oxygen and carbon dioxide efficiently. The combination of these conditions results in the hallmark symptoms of COPD: shortness of breath, chronic cough, wheezing, and frequent respiratory infections (46).

The primary cause of COPD is long-term exposure to irritants that damage the lungs and airways. The most significant risk factor is cigarette smoking, accounting for the majority of COPD cases. However, non-smokers can also develop COPD due to exposure to secondhand smoke, air pollution, occupational dust and chemicals, and genetic factors such as alpha-1 antitrypsin deficiency (47).

The progression of COPD varies among individuals but generally worsens over time. As the disease advances, everyday activities such as walking, climbing stairs, and even dressing can become challenging. The impact on quality of life is substantial, often leading to physical limitations, social isolation, and emotional distress (48).

The diagnosis of COPD typically involves spirometry, a test that measures lung function by assessing the volume and speed of air a person can exhale. Additional tests, such as chest X-rays and CT scans, may be used to assess lung damage and rule out other conditions. Early detection and management are crucial to slowing the progression of COPD and improving the quality of life for those affected (49).

Management of COPD includes a combination of lifestyle changes, medications, and pulmonary rehabilitation (50). Smoking cessation is the most effective intervention to prevent the progression of COPD. Medications, such as bronchodilators and corticosteroids, help to relieve symptoms and reduce inflammation. Pulmonary rehabilitation programs provide exercise training, nutritional advice, and education to help patients manage their condition and maintain their independence (51).

Despite the chronic nature of COPD, advancements in treatment and increased awareness of the disease offer hope for better outcomes. Ongoing research is aimed at developing new therapies and improving existing ones, with a focus on reducing symptoms, preventing exacerbations, and ultimately enhancing the quality of life for individuals living with COPD.

Interaction of PFAS and metals in promoting chronic obstructive pulmonary disease

The interaction of PFAS (per- and polyfluoroalkyl substances) and metals in the environment may significantly promote COPD. Both PFAS and metals are persistent environmental contaminants known to have adverse health effects, particularly on the respiratory system. When these substances coexist in the environment, their combined impact can exacerbate health conditions and contribute to the development and progression of COPD (52–54).

PFAS are synthetic chemicals widely used in various industrial and consumer products due to their heat, water, and oil resistance. They are known for their persistence in the environment and potential to bioaccumulate in living organisms. PFAS exposure has been linked to several health issues, including respiratory problems. These chemicals can induce inflammation, oxidative stress, and immune system dysfunction, all of which are contributing factors to respiratory diseases such as COPD (26, 55).

Metals, particularly heavy metals like lead, mercury, and cadmium, are also prevalent environmental contaminants with known toxicity. Exposure to heavy metals can occur through various routes, including inhalation of contaminated air. Heavy metals can damage lung tissues, induce oxidative stress, and cause chronic inflammation (56). These effects are directly associated with the development and exacerbation of COPD.

When PFAS and heavy metals coexist in the environment, their combined effects on respiratory health can be synergistic. For instance, both PFAS and metals can induce oxidative stress, leading to an overproduction of reactive oxygen species (ROS) and subsequent damage to lung cells. This oxidative damage can impair lung function and contribute to the chronic inflammation characteristic of COPD. Additionally, both contaminants can disrupt immune responses, which would make the lungs more susceptible to infections and exacerbations of COPD (57, 58).

Furthermore, the co-exposure to PFAS and heavy metals may enhance the bioavailability and toxicity of each other. For example, PFAS can alter the absorption and distribution of metals in the body, potentially increasing their toxic effects on the lungs. Similarly, metals can affect the metabolism and elimination of PFAS, leading to prolonged exposure and greater cumulative damage to the respiratory system (59).

The interaction of PFAS and heavy metals in the environment can have significant and synergistic effects on respiratory health, particularly in the development and progression of COPD. Both PFAS and heavy metals independently trigger inflammatory pathways, but their combined presence can lead to a heightened activation of pro-inflammatory cytokines and chemokines, exacerbating chronic inflammation in the lungs and accelerating COPD progression (60, 61). This inflammation is further compounded by their interference with normal lung repair mechanisms (62, 63). Both contaminants can impair the regeneration of damaged epithelial cells and extracellular matrix components, leading to structural changes in the airways and alveoli that are characteristic of COPD.

Additionally, PFAS and metals may disrupt mucociliary clearance, affecting the function of cilia and mucus production in the respiratory tract. This disruption can result in the accumulation of pollutants and pathogens in the lungs, increasing the risk of respiratory infections and exacerbations of COPD. Exposure to these contaminants can also lead to epigenetic modifications, such as DNA methylation and histone acetylation, which alter the expression of genes involved in lung function and immune responses, thereby contributing to the development and progression of COPD (64–66).

The oxidative stress generated by PFAS and metals is another critical factor. While both scenarios independently produce reactive oxygen species (ROS), their combined exposure can create a more significant oxidative burden, overwhelming antioxidant defenses and resulting in extensive lung tissue damage and inflammation. Moreover, PFAS, known as endocrine disruptors, and heavy metals, which can interfere with hormonal balance, can together affect the regulation of hormones crucial for lung health, such as glucocorticoids, potentially worsening COPD symptoms (67, 68).

Finally, both PFAS and heavy metals can hinder the body’s natural detoxification processes (69, 70). This impairment leads to the accumulation of toxic substances in lung tissues, further contributing to respiratory damage and the progression of COPD. The combined effects of these contaminants create a complex and multifaceted challenge for respiratory health, emphasizing the need for comprehensive strategies to mitigate their impact.

Conclusion

Research on the combined impact of PFAS and metals on respiratory health is still emerging, but the existing evidence highlights the need for a comprehensive approach to address environmental contaminants. Regulatory measures to limit emissions of both PFAS and heavy metals and public health initiatives to reduce exposure are critical steps in mitigating their impact on respiratory health and preventing COPD.

Understanding the interaction between PFAS and metals is essential for developing effective strategies to protect public health. Ongoing research aims to elucidate the mechanisms of their combined toxicity and identify interventions to reduce the risk of COPD and other respiratory diseases associated with environmental contaminants. By addressing these interactions, we can work towards a healthier environment and improve respiratory health outcomes for affected populations.