Introduction

Chronic rhinosinusitis (CRS) is a burdensome condition characterized by inflammation of the paranasal sinuses and nasal passages lasting 12 weeks or longer. CRS impacts an impressive number of people worldwide, with a prevalence ranging from 5–10% depending on diagnostic criteria [1]. Common symptoms of CRS include rhinorrhea, nasal congestion, hyposmia, and facial pain, which can negatively impact patient quality of life, often leading to sleep and mood disturbances [2, 3]. Furthermore, CRS represents a significant economic burden with $4–12.5 billion in healthcare costs, 11.5 million missed workdays, and another $12.8–13 billion in indirect costs due to loss of productivity, among other factors, in the United States [4–6].

CRS is a heterogeneous disease encompassing various subtypes with diverse underlying pathogenic mechanisms. While the exact etiology remains unknown, dysregulation within the immune system, particularly involving Type 1 T-helper cells, Type 2 T-helper cells, and Type 17 T-helper cells, is thought to play a central role in its pathogenesis. These cells contribute to the inflammatory cascade within the sinonasal mucosa, possibly contributing to epithelial barrier dysfunction and impaired mucociliary clearance, all of which are implicated in the pathogenesis of CRS [7, 8]. However, the exact relationship between this immune response and other factors, such as predisposition factors and triggers, remains unclear. This presents a significant challenge in managing and especially preventing disease.

There has been significant research linking exposures to lower airway disease. For example, common ambient air pollutants such as particulate matter (PM), ozone, and nitrogen oxides have been associated with increased incidence and disease severity of asthma, bronchitis, and chronic obstructive pulmonary disease (COPD), especially in vulnerable populations [9–11]. As the entrance to the lower airway, the nose and sinuses are similarly exposed; however, less evidence describes the association between environmental and occupational exposures and CRS. Of the commonly studied air pollutants such as carbon monoxide, lead, nitrogen oxides, ozone, sulfur oxides, and particle pollution (PM), PM has been the most well-studied in association with CRS, although other pollutants such as nitrogen oxides, ozone, and sulfur dioxide have also been found to be associated with increased CRS incidence [12–14]. Mechanistically, several in-vitro studies have corroborated these clinical associations by demonstrating that PM and ozone exposure can cause nasal epithelial cell barrier disruption and provoke a local pro-inflammatory response [15–17].

In addition to ambient air pollution, unique compounds encountered in occupational environments can negatively impact the upper and lower respiratory tracts and contribute to disease. Again, there is significant data to suggest that occupational exposures, like animal proteins, chemicals, and metals, can exacerbate lower airway disease [18–20], but the role of occupational exposures in CRS is more limited. This paper explores the current evidence regarding occupational exposures and their impact on CRS to identify key concepts and limitations and suggest future research strategies.

Methods

Data extraction, analysis, and quality assessment

PRISMA search methodology was followed for the study (Figure 1) [21]. Three investigators (A.S.M, C.P.W, E.H.B) extracted and described data using Microsoft Excel. Metrics extracted from each study included publication journal, publication year, publication country, study design, country of study population origin, sample size, age of study population, occupational variables, study methods used for measuring occupational variables, study criteria for defining CRS, analysis method, CRS outcomes, and limitations. Using the Oxford Centre for Evidence-based Medicine—2011 Levels of Evidence guidelines, each article was assigned a “level of evidence” based on the study design [24].

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Figure 1. 

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of literature search and study inclusion

Results

The literature query resulted in 1,189 total records. After removal of duplicates, 794 unique abstracts were screened. Nineteen studies met criteria and underwent data extraction (Figure 1). Study designs included prospective cohort, retrospective cohort, nested case-cohort, cross-sectional, and case-control, all of which were deemed to have level 3 evidence.

The 19 articles examined several types of occupational variables, ranging from occupational statuses like employed vs. unemployed to occupation types such as sales workers, agricultural workers, and homemakers, to specific exogenous compounds encountered through occupation like cooking fumes, paint/varnish, and metal smoke. Some studies further broke down occupational exposure into levels of exposure based on the duration of the exposure. Most of the studies determined these occupational variables by participant self-reports through surveys or interviews (11/19 articles, 57.9%) [25–35]. Other methods included abstraction from medical records or health databases (4/19, 21%) [36–39], employment records (3/19, 15.8%) [40–42], and confirmation via subject legal representatives (1/19, 5.3%) [43].

Diagnostic criteria for CRS varied among studies. Ten of the 19 studies (52.6%) followed, or partially followed, the EPOS or the ICAR for CRS diagnosis [25–28, 33–35, 39, 40]. Both of these require patients to have two or more symptoms of nasal congestion/blockage, nasal discharge, facial pain/pressure, and smell loss lasting more than 12 weeks, one of which must be either nasal congestion/blockage or nasal discharge, and evidence of objective disease on nasal endoscopy or CT scan [22, 23]. More specifically, seven of these ten used surveys that only covered EPOS symptom criteria [25, 26, 28, 29, 34, 35, 40]. Two studies required full EPOS criteria, including objective evidence [33, 39], while one study abstracted the CRS diagnosis and objective evidence from medical records but specified that the diagnosis had been previously made based on EPOS criteria [27]. Of the remaining nine studies, two (10.5%) diagnosed CRS based on objective findings alone [36, 41]. Three (15.8%) abstracted CRS diagnoses from medical records without specification of diagnostic criteria [30, 38, 43]. Three (15.8%) abstracted CRS diagnoses from medical records but required objective evidence to confirm the diagnosis [32, 37, 42]. One (5.3%) asked participants if they had a CRS diagnosis via survey [31]. More information about study characteristics can be found in Table 1.

Discussion

As the estimated global prevalence of CRS is 5–10% [1], it is critical to better understand predisposing preventable factors. Occupational exposures are an excellent target, as the relationship between occupational exposures and pulmonary disease is well recognized [9–11]. However, clear and specific evidence between occupational exposures and CRS is needed before implementing such strategies. We aimed to perform a scoping review to synthesize studies examining this relationship and summarize their evidence to better inform future research as a step toward identifying preventative measures. Our examination of 19 studies revealed a complex relationship between occupational exposures and CRS, influenced by several factors, including occupation types, specific compounds encountered, populations studied, and methodologies employed.

Study results must be interpreted only in the context of the populations examined in each specific study. Studies with more niche cohorts and smaller sample sizes reported higher rates of prevalence (42%, 55%, and 91%, respectively) [36, 37, 43]. Despite the small sample sizes, these results are still relevant and highlight the hazardous nature of the exposures in question and, thus, the danger of occupations such as military and disaster response. Studies with larger sample sizes but still unique populations are also not as generalizable but reinforce the fact that exposure to common ambient pollutants, especially PM, can contribute to CRS and emphasize that certain occupations, again usually military and disaster-response occupations like firefighters, may be at higher risk due to increased exposure quantity or duration [32, 38, 40, 42].

The most generalizable studies included those that examined large populations, but occupational details varied [25, 26, 28, 29, 31, 34, 35]. Of the studies with large sample sizes, four analyzed occupationally related compounds and found several compounds significantly associated with CRS diagnosis [25, 26, 28, 35]. These include a variety of exposures like gas, dust, damp environments, fumes, smoke, animals, cleaning agents, and strong acids that may be encountered more heavily in certain occupations like agriculture, construction, textile, and cleaning services. Additionally, Clarhed et al. [25] found an association between exposure to hair care products and cooking fumes and CRS, both of which can be occupationally related, as in barbers and chefs, and non-occupationally related, as encountered in everyday life. Other studies assessed occupation type and found associations with CRS, such as plant and machine operators [28, 31]. Lastly, some studies stratified their data by broad categories like employed, unemployed, blue collar, white collar, indoor job, and outdoor job [29, 34, 35]. None of the studies with broad employment categories found any significant associations with CRS diagnosis, most likely because the broad categories obscure any possible association, as the populations that fall into each category are too heterogeneous in their specific exposures (occupation type or compound encountered). So, despite their large sample sizes, their results are not clinically impactful when considering areas for intervention and prevention.

Four studies had relatively small sample sizes, and though they collected compound-specific data, compounds were lumped into larger categories (except for Nynäs et al. [33], who only examined moisture and mold exposure) [27, 29, 30]. These four studies found significant associations between compound exposure groups and CRS diagnosis, such as those exposed to vapors, gases, dust, or moisture. However, it is possible that only a few compounds within the larger group or a few occupations most heavily exposed to these compounds may be driving the association, or perhaps only the cumulative effect of all compounds drives the association. Given these possibilities, it is difficult to determine which occupations or work roles are specifically at risk, though some that certainly have exposure to such compounds include construction workers, textile workers, and mechanics. Additionally, two studies classified compounds as relevant or irrelevant based on expert physicians’ opinions [27, 30]. The lack of criteria for these decisions or a list of what was deemed relevant makes it difficult to draw or recommend interventions.

Beyond the general development of CRS, three studies assessed how occupational exposures relate to disease severity by examining objective findings, quality of life measures, the rate of ESS, and steroid doses [27, 30, 39]. Primary outcomes in two of these studies were the number of ESS performed on CRS patients, and they found that patients with more ESS were more likely to have reported relevant occupational exposure [27, 30]. This indicates that certain exposures may not only contribute to CRS development but also influence CRS disease and make it more difficult to treat. However, it is important to note that conclusions from these studies must be interpreted in the context of small sample sizes (n = 546, n = 364) and seemingly subjective determination of occupational exposure relevancy, as previously mentioned. Velasquez et al. [39] findings that any exposure to VGDFFiM, or diesel fumes resulted in a higher rate of ESS and steroid dosage support a similar conclusion. Interestingly, however, Velasquez et al. [39] also noted no significant differences in Lund-Mackay scores of patients with differing levels of exposure. This finding emphasizes that the relationship between exposure and severity of CRS may vary depending on how severity is specifically defined across studies.

Another limitation of the current literature includes the diagnostic criteria of CRS. These varied in using objective findings, subjective symptoms, or both in the diagnosis. The diagnostic criteria including both symptoms and objective findings is essential, as it embodies both the pathological changes and their impact on human functioning. Using one or the other does not fully characterize the CRS disease burden. Furthermore, common methods of abstracting data on CRS amongst studies differed, including self-reports via survey and medical record review. Self-reporting is of concern as there is a high risk of recall and response bias. Use of medical records may also be unreliable if there is no information on the type of physician giving the diagnosis, as some may not follow appropriate criteria.

In summary, moderate evidence supports an association between occupational exposures and CRS, with the strongest relationships being seen in military and disaster-response occupations. This data is corroborated by basic science studies that have hypothesized possible mechanisms by which such exposures can upregulate inflammatory pathways and impair mucociliary clearance, both of which underly the pathogenesis of CRS. Multiple in vitro studies have demonstrated that PM stimulates nasal epithelial cells, macrophages, and fibroblasts to release pro-inflammatory cytokines [44, 45]. One proposed mechanism by which this occurs is through the upregulated expression and release of specific microRNA (miRNA) in response to PM that promotes the M1 polarization of macrophages, propagating inflammation [16]. Similarly, exposure to diesel exhaust particles and Asian sand dust results in a similar release of pro-inflammatory cytokines from nasal fibroblasts, such as IL-6 and IL-8, although via different mechanisms [44, 46]. Asian sand dust has also been shown to work synergistically with microbes like Aspergillus fumigatus to increase microbial growth and biofilm formation, further stimulating an inflammatory response [47]. PM has also been shown to negatively impact mucociliary clearance. For example, exposure to PM2.5 and hog barn dust increases mucin-protein production, leading to thickened and viscous mucous and impaired ciliary action [48, 49]. Over time, chronic leads to a blunting of the mucociliary response [50]. Furthermore, PM, especially less than 2.5 microns, can disrupt the nasal epithelial barrier through oxidative stress, leading to the downregulation of tight junction proteins [15].

Unfortunately, the heterogeneity of populations, methodologies, and independent and dependent variables limits the ability to draw specific conclusions about the relationship between certain occupational exposures and the development of CRS. To better characterize these relationships, large studies with diverse populations and a clear definition of CRS that includes both objective evidence of disease and detailed exposures are needed. Occupational variables should be as inclusive and specific as possible, ideally including occupation type and exogenous compounds. Compound exposure may be inferred from occupation type, but methods would ideally be based on reliable databases or matrices relevant to the population location.

Conclusions

In conclusion, the relationship between occupational exposures and CRS is multifaceted and complex. While evidence supports a general association between occupational exposures and CRS, drawing specific conclusions remains challenging due to heterogeneity across studies. Moving forward, future research endeavors must address limitations such as small sample sizes, overly broad occupational categories, differing CRS diagnostic criteria, and different methods of gathering data. By adopting rigorous methodologies and standardized criteria, researchers can enhance our understanding of the relationship between occupational exposures and CRS diagnosis, ultimately informing preventative measures and interventions to mitigate the burden of CRS on the individual and population levels.