Microplastic and plastic pollution: impact on respiratory disease and health

Abstract

Throughout their lifecycle, from production to use and upon disposal, plastics release chemicals and particles known as micro- and nanoplastics (MNPs) that can accumulate in the environment. MNPs have been detected in different locations of the human body, including in our lungs. This is likely a consequence of MNP exposure through the air we breathe. Yet, we still lack a comprehensive understanding of the impact that MNP exposure may have on respiratory disease and health. In this review, we have collated the current body of evidence on the implications of MNP inhalation on human lung health from in vitro, in vivo and occupational exposure studies. We focused on interactions between MNP pollution and different specific lung-resident cells and respiratory diseases. We conclude that it is evident that MNPs possess the capacity to affect lung tissue in disease and health. Yet, it remains unclear to which extent this occurs upon exposure to ambient levels of MNPs, emphasising the need for a more comprehensive evaluation of environmental MNP exposure levels in everyday life.

Shareable abstract

Micro- and nanoplastics (MNPs) evidently possess the capacity to affect lung tissue in disease and health. However, it remains unclear to what extent this occurs upon exposure to ambient levels of MNPs. https://bit.ly/3vHQsCA

Introduction

The widespread climate changes once forewarned to be linked to our appetite for fossil fuels are upon us [1–3]. One aspect of our fossil fuel dependence that often goes unnoticed is its link to plastic production. Currently, 460 million tonnes, equivalent to 9% of total oil production, is used to manufacture various plastics. Projections estimate this consumption will surge to 1231 million tonnes by 2060, representing at least 24% of our present-day oil production [4].

In addition to being responsible for an increasing part of our oil consumption, plastics are also responsible for widespread pollution. Throughout their lifecycle, from production to use and upon disposal, plastics release chemicals and particles known as micro- and nanoplastics (MNPs) that can affect human health. Marine biologist Richard Thompson was the first to recognise this emergent type of pollution in his seminal 2004 paper describing the long-term accumulation of microscopic fragments of plastic in the environment [5]. Since then, the problem of MNP pollution has been described most in the context of water pollution; however, realisation is dawning that MNPs are also prevalent in the air. In fact, a recent report from the World Health Organization estimated human exposure via inhalation could be as high as 3000 particles per day [6]. Given the established lung health risks associated with particle inhalation [7, 8], this new form of particle pollution raises concerns, especially in a world that exponentially increases its plastics use [9].

In this review, we have collated the current body of evidence on the implications of MNP inhalation on human lung health. Since the recent report by the World Health Organization has given an excellent overview of the current state of knowledge regarding general effects on lung health, we have briefly summarised their findings first [6]. We have subsequently focused on interactions between MNP pollution and different specific lung-resident cells and respiratory diseases for which data were available, i.e. asthma, COPD, lung cancer and interstitial lung diseases (ILDs). In instances of having sufficient data available, we refrained from including studies on the effects of spherical polystyrene MNPs due to their limited presence in the environment. When appropriate we have included evidence from leachable plastic additives that are incorporated to improve properties of plastic polymers.

Plastics, additives and MNPs

Plastics are synthetic polymers produced mostly from fossil fuels like oil. They are cheap, durable, versatile and heterogeneous, hence their ubiquitous presence in every aspect of our lives. Owing to their durability, plastics can take anywhere from decades to millennia to biodegrade [10]. Typically, environmental degradation is primarily through mechanical abrasion, resulting in smaller fragments. Fragments less than 5 mm in size are classified as microplastics (ranging between 5 mm and 1 µm) and those less than 1 µm are called nanoplastics [11]. Incidentally, MNPs can also originate from products that were specifically designed to contain these particles, e.g. personal hygiene products and cleaning agents. These abraded or designed MNPs come in many different shapes, with fibres and irregularly shaped fragments being the most common in air, water and sediment [12, 13].

Beyond the polymers, a variety of additives are used to enhance their properties, providing colour, improved flexibility, stability, water resistance, flame retardancy and ultraviolet protection. These include many substances with known health risks, such as bisphenols, phthalates, per- and poly-fluoroalkyl substances, and brominated and organophosphate flame retardants. During use these agents have been shown to leach out and contribute to adverse health effects of plastics use [14]. Whether they can also contribute to health effects of MNP exposure is unclear, but recent studies indicate that high exposure to microplastics could elevate levels of these additives beyond typical background exposure levels [15–18].

Airborne plastics and human exposure

Studies in the last decade have clearly illustrated the pervasiveness of the MNP problem: none of the tested locations on Earth were free of microplastic contamination [19, 20]. Many studies have now also shown the presence of MNPs in a variety of indoor and outdoor locations, as elegantly reviewed by O’Brien et al. [12]. For human exposure, the size and aerodynamic diameter of MNPs are important: particles with an aerodynamic diameter less than 2.5 µm are considered respirable as they can penetrate deep into peripheral lung tissue; particles with an aerodynamic diameter between 2.5 and 100 µm are considered inhalable and will deposit in the smaller and larger airways, respectively. However, large fibres have been found to penetrate unexpectedly deep into peripheral lung tissue probably due to specific aerodynamic properties [21]. A significant challenge in estimating human exposure arises from many studies neglecting to report MNP concentrations for fractions smaller than 10 µm. This shortcoming, due to the limitations of current methodologies, means we cannot reliably estimate human exposure to the most respirable MNP fractions [6].

Generally speaking, levels of MNPs are higher in indoor air compared to outdoor air, especially in deposited dust. This is concerning because most people spend more than 90% of their time indoors [22]. Outdoor air concentrations in the different studies varied between less than 1 and more than 1000 MNPs·m⁻³ and for deposited dust between 0.5 and 1357 MNPs·m⁻²·day⁻¹. Reported indoor air concentrations varied from less than 1 to more than 1500 MNPs·m⁻³ and 475 to 19 600 microplastics·m⁻²·day⁻¹ in deposited dust. Of the plastic types found, polyethylene terephthalate, polyethylene and polypropylene were the most common [12], which reflects the ubiquitousness of these plastics in daily life materials like textiles and packaging.

Due to insufficient data of the amount of MNPs in the size fractions smaller than 10 µm, it is challenging to accurately determine human exposure [6]. However, the study of Liao et al. [23] proposes an upper limit of 1583±1181 MNPs·m⁻³ for particles between 5 and 30 µm. Based on this, and assuming a daily inhalation of 15 m³ of air, one can approximate a daily human exposure of around 3000 MNPs·day⁻¹ through inhalation.

Evidence for actual inhalation and exposure of lung tissue to MNPs is slowly increasing, although mass-based quantification is still lacking. A study by Pauly et al. [24] was the first to show evidence for the presence of synthetic fibres in lung tissue. This study investigated both lung tumours and adjacent unaffected lung tissue, and found that 83% of non-neoplastic lung specimens and 97% of malignant lung specimens contained synthetic and/or plant-based fibres. Unfortunately, they did not specify the types of synthetic fibres found. Three more recent studies, however, did investigate plastic particles and fibres in peripheral lung tissue, and found predominantly polypropylene and polyethylene/polyethylene terephthalate MNPs in lung tissue [25–27]. Whether fibre or particle MNPs are the most abundant type present in lung tissue is an open question as these studies came to different conclusions. This can be explained by a number of variations, including the small sample size of all three studies, the different geographical locations of the individuals sampled and the different analysis methods used. Optimal tissue digestion and analytical techniques are highly dependent on the chemical composition and size of MNPs, as elegantly reviewed by Di Fiore et al. [28]. Furthermore, proper blanks are essential to rule out external contamination [29].

In other studies, bronchoalveolar lavage was sampled to detect MNP presence in the lumen of the airways [30–34]. These studies found comparable types of MNPs as seen in lung tissue, particularly polypropylene and polyethylene/polyethylene terephthalate. However, again there was a lack of agreement regarding shape. Notably, the data from Chinese cohorts revealed significantly higher MNP counts per unit of lavage fluid compared to European cohorts. This disparity suggests that the Chinese participants might reside in areas with higher pollution levels than their European counterparts. However, the variance might also stem from different methodologies employed in measuring MNPs.

In summary, while there is definitive evidence supporting the inhalation of MNPs, accurately estimating human exposure remains a challenge. The types of MNPs identified in lung tissue align with those predominantly found in air and dust, reinforcing the notion that they are inhaled during exposure.

In vitro evidence for immunoregulatory, cytotoxic and other effects of MNPs on lung cells

Macrophages

One of the first cell types to encounter MNPs upon inhalation are resident alveolar macrophages present on the respiratory tract's mucosal lining. These alveolar macrophages are origin-wise distinct from monocyte-derived macrophages and location-wise different from tissue-resident macrophages present in the interstitium. The distinctive origin of alveolar macrophages and subsequent nurture of these cells by the specific alveolar micro-environment shapes their functional behaviour, which generally cannot be modelled well with monocyte-derived macrophages. We therefore only considered studies with primary alveolar macrophages or immortalised alveolar macrophage cell lines [35, 36]. NR8383 rat alveolar macrophages most efficiently phagocytosed 2–3 µm polystyrene particles compared to smaller or larger particles, likely due to the matching size of membrane ruffles on the macrophages [37]. Similar results were found for MH-S mouse alveolar macrophages [36]. Primary rat alveolar macrophages also size-specifically produced superoxide when exposed to polystyrene microspheres [38]. In human primary alveolar macrophages, 0.2–2 µm polyvinyl chloride particles consistently reduced cell viability. However, cytokine responses to polyvinyl chloride particles were shown to be very variable between donors and even between technical replicates [39].

While the knowledge specifically from alveolar macrophages is still limited, many studies have investigated the effects of MNPs on the behaviour and phenotype of monocyte-derived macrophage cell lines and primary macrophages derived from organs other than the lung. However, those findings are highly variable and undoubtedly dependent on macrophage origin and particle characteristics, such as size, material, charge and surface roughness.

Summarising, the size of MNPs appears to be an important determinant of phagocytic efficiency by alveolar macrophages. Yet, our understanding of the subsequent impact of MNPs on alveolar macrophage function remains quite limited.

Epithelial cells

The lung epithelial barrier, ranging from the upper airways to deep in the alveoli, plays an important role in protecting the lung from pathogens and environmental factors. The barrier is formed by different epithelial cell types, including goblet cells, club cells, ciliated cells and basal cells in the airways and alveolar epithelial type I and II cells in the alveoli. The integrity of this barrier is crucial for respiratory health, and studying possible cytotoxic and barrier disrupting effects of MNPs is therefore imperative.

Airway epithelium

In vitro, effects of MNPs on airway epithelial cell responses and integrity of the epithelial barrier have been studied in bronchial epithelial cell lines as well as primary nasal and bronchial epithelial cells. In BEAS2B cells, a bronchial epithelial cell line, polystyrene particles were found to be pro-inflammatory, cytotoxic and to affect barrier integrity. However, conflicting results have been described for the production of reactive oxygen species (ROS), likely caused by differences in particle characteristics between studies, such as surface roughness, charge and concentrations [40–42]. In primary nasal epithelial cells, both pristine polystyrene and non-pristine polyethylene terephthalate nanoplastics were internalised and induced ROS production, loss of mitochondrial membrane potential and inhibited the autophagy pathway [43, 44].

The main benefit of using primary epithelial cells, rather than epithelial cell lines, is their ability to differentiate into a pseudo-stratified epithelial layer when cultured on air–liquid interface. Especially the presence of ciliated cells and mucus-producing goblet cells is important when studying the effect of particles on these epithelial layers, as mucociliary clearance is one of the most crucial mechanisms in protecting the epithelial barrier from harmful pollutants [45]. Donkers et al. [46] exposed the air-side of pseudo-stratified bronchial epithelial cell layers to different sizes of polystyrene particles, high-density polyethylene, polyamide 6,6 fragments and even car tyre and ocean cleanup fragments. Cell viability was not affected and only small polyamide 6,6 fragments and high-density polyethylene fragments significantly decreased epithelial barrier function. Treatment with 10 µm polystyrene particles or supernatant of polyamide 6,6 fibres resulted in higher production of interleukin-6. Interestingly, this effect was not observed for smaller polystyrene particles, again indicating the specific responses to size [46].

Organoid culture with primary lung epithelial cells is another way to mimic a fully differentiated airway epithelium in vitro. We have shown that the presence of polyamide 6,6 fibres impaired the development and growth of both murine and human airway organoids. Comparable effects were observed for polyester fibres, although less pronounced. Components leaching from the polyamide 6,6 microfibers proved to be responsible for the observed effects during organoid development and differentiation. Interestingly, polyamide 6,6 microfibers or their leachate did not affect already established organoids, suggesting they may especially harm airways in development or undergoing repair [47]. In another study, lower concentrations of polyester fibres were not found to affect human airway organoid growth. However, exposure to polyester fibres did reduce the expression of club cell secretory protein SCGB1A1, which has been associated with airway inflammatory diseases [48].

Alveolar epithelium

Studying responses of alveolar epithelial cells in vitro is slightly more challenging because primary type II alveolar epithelial cells lose their phenotype when grown in cell culture flasks. The most used model for type II alveolar epithelial cells is therefore A549 cells, a carcinoma cell line. Studies using this cell line show that exposure to polystyrene microplastics can decrease cell proliferation/metabolic activity and change cell behaviour without significantly affecting cell survival [41, 49, 50]. Smaller polystyrene particles were internalised by the cells and induced pro-inflammatory responses and oxidative stress [41, 49, 50]. Similarly, for polyethylene microplastics, smaller particles were more cytotoxic and induced more nitrite production in A549 cells [51]. The impact of microplastic waste particles on cell function also appears to depend on particle size, with smaller beads causing more inflammatory responses than larger ones. However, these observed inflammatory responses may be due to absorbed pollutants or chemicals associated with waste-derived microplastic particles [52].

One way to maintain the phenotype of primary type I and II alveolar epithelial cells in vitro is organoid culture. We recently demonstrated that exposure to polyester or polyamide 6,6 fibres could lower the number of murine alveolar organoids, although less pronounced than their effect on airway organoids [47]. Another possibility, described by Yang et al. [53], is culturing primary alveolar type I and II epithelial cells together with endothelial cells and macrophages in a lung-on-a-chip model. Exposure of alveolar epithelial cells to polystyrene nanoparticles in this system reduced cell viability and barrier function, simultaneously with internalisation of nanoparticles and increased ROS production.

Altogether, MNPs affect cell viability, barrier function and oxidative stress responses in alveolar and airway epithelial cell lines as well as primary cell-based models. It is therefore likely that prolonged exposure of the epithelial barrier to MNPs can contribute to the development of lung disease.

Evidence of health effects from occupational exposures and animal models of exposure

Most evidence for induction of lung abnormalities after exposure to plastics is present in the field of occupational exposures. Evidence of individuals exposed to polyvinyl chloride developing radiographic abnormalities, pulmonary function impairment, cancer and/or dyspnoea was reported as early as the 1970s [54–62]. Initially these symptoms were called “meat-wrapper's asthma” by Sokol et al. [63] who reported induction of asthma symptoms in women cutting polyvinyl chloride packaging with a hot wire during their work as meat wrappers. However, other studies soon showed more adverse respiratory effects of working with polyvinyl chloride dust and polyvinyl chloride monomers [54–62]. These were then followed up by reports on adverse respiratory effects in people working with other plastics, such as nylon and polypropylene flock, and more recently reports of development of pulmonary fibrosis in young individuals working with engineered/artificial stone and lung nodules in dental professionals [64–102]. Outcomes of these studies will be discussed more specifically under the different respiratory diseases.

The number of animal studies investigating possible harmful effects of MNPs through different exposure routes is rapidly increasing, including studies on inhaled MNPs. Most inhalation studies focused on polystyrene particles of variable sizes, which were demonstrated to reach the lungs as well as many other organs upon inhalation [36, 103]. Polyethylene microspheres were even detected in the kidneys of neonates after intratracheal exposure of pregnant mice [104]. In the lung, inhalation of microplastics has been associated with increased influx of inflammatory cells and macrophage aggregation [105, 106]. Prolonged exposure of three different strains of mice to polystyrene, polypropylene or polyvinyl chloride resulted in variable inflammatory responses between different types of MNPs as well as between mice strains [106]. Intratracheal instillation of different sizes of polystyrene MNPs also induced pro-inflammatory responses and alveolar destruction in rats [107]. In the broader context of lung disease, several studies found fibrosis-associated patterns after inhaling microplastics [108–110]. Mice exposed to polystyrene microplastics developed pulmonary fibrosis in size- and dose-dependent manners [109, 110].

Summarising, based on both occupational exposure studies and animal inhalation studies, MNP exposure can impact the respiratory system to the extent that it could contribute to the development of known respiratory diseases, as will be elaborated on in the following sections.

Asthma and allergic rhinitis

Asthma is a chronic respiratory disease that can develop early in life and is defined by inflammation and airway narrowing. Although asthma is a very heterogeneous disease, roughly two types of asthma can be distinguished: non-allergic and allergic asthma. The latter is characterised by a strong T-helper (Th) 2 cell response upon exposure to environmental allergens, which can promote symptoms such as bronchial hyperresponsiveness and mucus hypersecretion [111]. Although there is a known connection between air pollution and asthma development [112, 113], the possible role of MNPs in asthma development and severity is not yet studied intensively. However, the “meat-wrapper's asthma” described in women cutting polyvinyl chloride, as discussed earlier, does suggest that high doses of inhaled plastics and/or leaching chemicals can induce asthma-like symptoms [61, 63]. Chen et al. [34] compared levels of microplastics in bronchoalveolar lavage fluid of children with community-acquired pneumonia and children with asthma. While more microplastics were found in bronchoalveolar lavage fluid of patients with severe community-acquired pneumonia compared to non-severe cases, no significant differences were found between patients with community-acquired pneumonia and asthma. It remains to be studied how these levels of microplastics relate to the levels in bronchoalveolar lavage fluid of healthy controls. However, in nasal lavages of healthy volunteers, fewer microplastics were detected than in nasal lavages of patients with allergic rhinitis, a disease often associated with allergic asthma [114].

In animal models, exposure of mice to 1–5 µm amino-resin spheres resulted in higher numbers of eosinophils and lymphocytes in bronchoalveolar lavage fluid, as well as higher numbers of macrophages in lung tissue, compared to controls. In house dust mite-treated mice, a model for allergic asthma, the number of macrophages increased even more drastically upon co-inhalation of microplastics, together with increased mucus production [105]. In addition, in ovalbumin-treated mice, another model for allergic asthma, ingestion of spherical polystyrene nanoparticles aggravated allergic asthma-related characteristics. This effect was not observed in control mice and co-stimulation with the plasticiser di(2-ethylhexyl)phthalate further exacerbated airway mucus hypersecretion, Th1/Th2 imbalance and oxidative stress levels [115]. Other plasticisers such as diisononyl phthalate have also been shown to induce allergic asthma by modulating the Th1/Th2 balance [116]. In addition to direct effects of MNPs on asthma severity, they can also serve as vectors for other allergens, e.g. pollen, endotoxins and viruses [117–119], and thereby contribute to allergic asthma physiology.

All in all, both occupational and animal exposure studies do suggest that MNPs or components leaching from MNPs can contribute to allergic asthma-related characteristics. It is therefore likely that exposure to the relatively high doses of MNPs found indoors can aggravate asthma symptoms and possibly trigger asthma exacerbations.

COPD

COPD is characterised by chronic bronchitis and/or emphysema and associated with a progressive decline in lung function. COPD can develop due to genetic risk factors or upon chronic exposure to irritants such as cigarette smoke [120]. Limited information is available on potential connections between MNP exposure and development and progression of COPD. To date, no studies have compared levels of MNPs in lung tissue from healthy controls and COPD patients. However, smoking is considered to be the primary risk factor for COPD development and recently microplastics of around 20–500 µm have been detected in cigarette smoke by Lu et al. [32]. In the same study, more and different microplastics were detected in bronchoalveolar lavage fluid of smokers compared to non-smokers. Previously, Huang et al. [121] also described trends towards more microplastics in the sputum of smokers and COPD patients compared to non-smokers and non-COPD patients, respectively.

While the challenges in detecting MNPs in air and lung tissue hamper association studies between MNP exposure and COPD development, several plastic additives have been associated with COPD in epidemiological studies. Bisphenol A levels in blood and urine have been shown to correlate positively with the incidence of COPD and COPD-related diseases [122, 123]. Specific polyaromatic hydrocarbons detected in urine have been linked to emphysema and chronic bronchitis, and certain phthalates have been associated with increased respiratory morbidity in COPD patients [124, 125].

In vitro, two studies have investigated the direct effect of MNPs on COPD-associated parameters in lung epithelial cells. In a bronchial epithelial cell line, exposure to polystyrene microparticles was found to decrease the protein expression of α₁-antitrypsin. A deficiency in this protein is an established risk factor for COPD development [40]. A comparable effect was observed after introducing polystyrene nanoplastics in a lung-on-a-chip model [53].

Summarising, the involvement of MNPs and leaching additives in COPD development and progression remains to be studied. Nevertheless, the elevated exposure to MNPs in smokers and modulating effects of MNPs on α₁-antitrypsin expression do suggest a plausible link worth investigating.

ILDs and lung malignancies

Research into occupational exposures has demonstrated that exposure to plastic materials, particularly during the manufacturing, processing or recycling of plastic products, may increase risks of a range of lung abnormalities, including malignancies and ILDs. The presence of dust and fumes can contribute to cellular damage and mutations within lung tissue, potentially initiating the development of ILDs and/or lung malignancies. Additionally, certain additives and chemicals used in plastics, such as plasticisers and flame retardants, have been linked to carcinogenicity as elegantly reviewed recently by the Minderoo-Monaco Commission on Plastics and Human Health [4].

ILDs encompass a spectrum of lung conditions that primarily affect the lung interstitium. These interstitial diseases are characterised by varying degrees of inflammation and/or fibrosis [126, 127], but a considerable portion of ILDs evolve into pulmonary fibrosis. This is an often-progressive disease characterised by excessive accumulation of extracellular matrix components in the interstitial spaces, resulting in thickening and stiffening of the interstitium and restricted breathing.

Inhalation of particulate matter, especially prevalent in the plastics industry, can also initiate the onset of a special type of ILD called pneumoconiosis. This type of ILD stems from a phenomenon known as frustrated phagocytosis, with macrophages failing to fully engulf and digest inhaled particles due to excessive size or indigestibility [128]. Trapped in a state of persistent activation, macrophages release a cascade of inflammatory mediators, which propagate extensive interstitial inflammation and/or fibrosis.

The inhalation of plastic dust or associated components may not only predispose individuals to an array of ILDs, but may also lead to lung malignancies as can be seen from the well-documented effects of exposure to polyvinyl chloride [59–61, 85, 129]. This type of plastic is produced through polymerisation of vinyl chloride monomers. The polyvinyl chloride industry was the focus of a major occupational health crisis in the mid-1970s when an increased frequency of a rare liver tumour was reported in workers exposed to polyvinyl chloride monomers [71]. Many studies in different parts of the world followed, showing increased risks of pneumoconiosis, lung fibrosis and lung cancer, and leading to measures to protect workers from exposure.

The prevalence of pneumoconiosis in workers from polyvinyl chloride industries was estimated to be around 3% [130]. The different studies found that exposure to 10–20 mg·m⁻³ polyvinyl chloride dust could trigger pneumoconiosis with granulomatous reactions of macrophages against polyvinyl chloride particles leading to associated interstitial fibrosis in humans [56, 75, 85]. Similarly, rats, guinea pigs and monkeys exposed to 10–13 mg·m⁻³ polyvinyl chloride dust for 4–22 months also developed a benign pneumoconiosis but with no effect on lung function [131, 132]. In addition, polyvinyl chloride monomers have been shown to induce pulmonary fibrosis, possibly through their interaction with proteins and the subsequent initiation of immunological responses directed towards these modified proteins [133]. Those same polyvinyl chloride monomers were also assumed to be the most probable cause of the increased lung cancer risk in polyvinyl chloride workers [64, 67, 69–71, 73, 78, 80, 82–84, 98]. However, a nested case–control study by Mastrangelo et al. [71] showed that the increased risk for lung cancer was also associated with exposure to polyvinyl chloride dust. Although polyvinyl chloride workers are now better protected, the increased domestic use of polyvinyl chloride particularly in flooring is concerning. Wear and tear of this type of floor in houses with polyvinyl chloride flooring will probably result in higher levels of this type of MNPs [134].

These effects of polyvinyl chloride are somewhat unique, as occupational exposure to synthetic flocking material induced a variety of similar but also different symptoms [68, 74, 79, 99–102]. Flocking involves the process of applying synthetic fibres, known as “flock”, to adhesive-coated surfaces to create a velvet-like texture to those surfaces. These synthetic fibres are most often polyamide (nylon), but other plastics such as polypropylene and polyester are also used for flocking [79, 102]. The process of flocking can create inhalable and respirable fine fibres and particulate matter, particularly during the cutting and application of the fibres, with reported concentrations of up to 7 mg·m⁻³ for nylon and 700 000 fibres·m⁻³ for polyester [135, 136]. Exposure to flock was not only associated with interstitial inflammation/fibrosis and lung cancer, but also with inflammation in and around the airways, particularly with nylon flock [68, 74, 79, 99–102, 137]. These effects were also partly reproduced in rats exposed to nylon or polypropylene fibres or particles [138–141]. The reasons for the specific airway-related effects of nylon are not clear, but our recent study into the effects of polyamide 6,6 fibres suggests this may be caused by polyamide 6,6 inhibiting airway epithelial differentiation [47]. In a series of in vitro experiments using lung organoids, we showed that differentiation of airway epithelium from lung-resident epithelial stem cells was inhibited by a still unknown component leaching from polyamide 6,6. This was specific for polyamide 6,6 as polyester fibres did not inhibit airway differentiation to the same extent.

Recently, alarming reports of another form of plastic-associated pneumoconiosis related to silicosis have been published [88, 90–96, 142]. Silicosis is the most widespread form of pneumoconiosis and manifests as a fibrotic ILD, stemming primarily from prolonged occupational exposure to respirable crystalline silica. Typically, its progression is insidious, developing over several decades as workers inhale fine silica particulates. Clusters of silicosis with an accelerated and rapidly fatal form of the disease were noted among engineered stone countertop workers in many countries [88, 90–96, 142]. This engineered material, also known as artificial, synthetic or quartz conglomerate stone, is produced by mechanical crushing of quartz and combining this with polymer resins, dyes and glass, which are then all subjected to high heat to create a surface that resists damage, serving as an alternative to traditional marble or granite kitchen countertops.

A critical distinction between engineered and natural stone products is the significantly higher silica content in the former and the presence of polymer resin consisting of unsaturated polyester, epoxy or acrylic. Engineered stone contains about 90% silica, substantially more than the 3–30% typically found in natural stone [143]. The polymer resins used in the composition of engineered stone could also play a role in the health issues observed. Processing of engineered stone not only releases silica particles, but also polyacrylate MNPs [144]. Workers exposed to polyacrylate MNPs were found to develop shortness of breath and pleural effusions, and had granulomas and fibrosis in lung tissue with evidence of polyacrylate nanoparticles in the cytoplasm of epithelial cells [145]. Similarly, two dental care workers frequently exposed to acrylic plastics and silica developed granulomas [97]. A study in rats intratracheally exposed to polyacrylate and silica nanoparticles reported a similar histological pattern [146]. Although the primary cause of this rapid form of silicosis is inhalation of silica dust, the interaction between the silica particles and the resin components during the manufacturing and finishing processes may contribute to the onset, progression and/or severity of the disease. Further research is needed to elucidate the potential synergistic effect of silica and polymer resins.

Additional evidence supporting the potential role of MNPs in the development of ILDs and/or lung cancer emerges from research examining the presence of tyre wear MNPs. These particles are a byproduct of mechanical abrasion, and an escalating body of scientific literature suggests their significance as a prevalent environmental contaminant [147–149]. A recent white paper from the Netherlands Organization for Applied Scientific Research (TNO) underscores this concern, identifying tyre wear as the foremost contributor to outdoor MNP pollution in the Netherlands [150]. While epidemiological investigations into the health effects of inhaled tyre wear particles remain complex due to confounding pollutants common in road-side environments, animal studies provide insight into potential consequences. One study involving mice demonstrated that exposure to tyre wear-derived MNPs precipitated pathological fibrotic alterations in lung tissue [108]. Conversely, rat-based studies presented inconsistent outcomes, revealing only a mild pulmonary inflammatory response [151, 152]. These findings indicate a nuanced relationship between tyre wear exposure and lung health necessitating further studies.

Recently, the health implications of inhaling polyurethane particles were pushed into the spotlight due to issues surrounding non-invasive ventilation equipment manufactured by Philips Respironics. These devices are commonly used to treat obstructive sleep apnoea, a disorder often associated with and affecting the outcome of several chronic respiratory diseases. Initial research aimed at determining whether individuals using these devices are at greater risk for health problems showed that, despite a necessity for more anti-obstructive medication, they did not seem to have an increased risk of lung cancer [65, 153]. Similarly, rodent models subjected to substantial concentrations of polyurethane dusts did not exhibit lung tumour formation. However, they did experience interstitial inflammation accompanied by pulmonary fibrosis, indicating that inhaling elevated levels of these particles has the potential to be harmful [154–157]. This underscores the importance of ongoing research and stringent safety standards in the manufacturing processes of medical devices, especially those directly impacting respiratory health.

Summarising, occupational MNP exposures in the plastics and engineered stone industries are linked to increased risks of ILDs and lung cancer, largely due to inhalation of dust, fumes and carcinogenic additives. Notably, polyvinyl chloride and synthetic fibres used in flocking have been associated with specific pneumoconiosis, while workers handling engineered stone products face an emerging form of rapid-onset silicosis, potentially aggravated by high silica content and polymer resins. Additionally, environmental concerns regarding tyre wear as an emerging significant source of MNPs are mounting. Despite these findings, mechanistic insights into the physiological effects of such exposures are still lacking and warrant further comprehensive research.

Perspectives and conclusion

The impact of a variety of MNPs has been studied in the context of respiratory disease and health, ranging from in vitro studies in lung-derived cell lines to inhalation exposure studies in rodents and occupational exposure studies in humans (figure 1). In vitro studies have taught us that MNP uptake in alveolar macrophages or lung epithelial cells is largely dependent on MNP size and can induce pro-inflammatory and oxidative stress responses. In vivo inhalation studies generally indicate an influx of inflammatory cells and pro-inflammatory responses, underlining the important role of the immune system upon exposure to environmental pollutants and its complex interplay with other resident lung cells that can contribute to pathologies such as fibrosis when dysregulated. Yet, the knowledge on biological mechanisms is still rather limited. Observed responses are often MNP- and model-specific, making it challenging to investigate the mechanisms and downstream effects that we need to better understand the biological processes behind the pathologies described in human cases of high occupational exposure levels.

FIGURE 1.

An overview of the impact of micro- and nanoplastics (MNPs) on respiratory health as determined by in vitro exposure studies, in vivo inhalation studies and occupational exposure studies. Figure partially created with BioRender.com.

To date, a notable discrepancy exists between the types of MNPs studied in in vitro experiments and the types of plastics that have been associated with development of asthma, pulmonary fibrosis or lung cancer in occupational exposure studies. Although it is evident that inhalation of high doses of nylon or polyvinyl chloride can impact lung health, in vitro studies on these plastics are scarce and focused on polystyrene particles instead. Additionally, particles studied in vitro and in vivo are mostly pristine and spherical, while responses to environmentally relevant, weathered particles or a mix of different particles can be entirely dissimilar. Furthermore, the doses applied are often significantly higher than estimated levels in the air we breathe and therefore acute rather than chronic responses are investigated. To improve the relevance of in vitro and in vivo studies, we need to enhance our knowledge on the characteristics and levels of MNP in our daily environments. This needs to be combined with improved techniques to detect and analyse the levels and characteristics (i.e. size, plastic type and shape) of MNPs in lungs of healthy controls and patients with lung disease to evaluate possible links between MNP inhalation and development, progression and/or severity of lung diseases such as asthma and COPD.

Concluding, it is evident that MNPs possess the capacity to affect lung tissue in disease and health. Yet, it remains unclear to which extent this occurs upon exposure to ambient levels of MNPs, emphasising the need for a more comprehensive evaluation of environmental MNP exposure levels in everyday life.

Questions for future research

• Comprehensive evaluation of environmental MNP exposure levels in everyday life.

• Improved methods to detect and characterise MNPs in healthy and diseased lung tissue.

• Focus on studying environmentally relevant particles and related biological mechanisms.