In 2013, eight workers involved in laying up fiberglass woven roving with polyester resins were reported to have obliterative bronchiolitis, a severe irreversible airway obstructive disease involving the small bronchioles (1, 2). Two of them received lung transplantation and one died while waiting for an organ donor. These cases echoed findings of past cohort studies. Two studies that followed up a large cohort of workers in 30 reinforced plastics manufacturing plants in the United States found elevated mortality risk due to non-malignant respiratory diseases, particularly obstructive airway diseases (3, 4). Another cohort study reported elevated mortality risk due to the code “Pneumoconiosis and other respiratory diseases” from the US reinforced plastic boat-building industry (5). However, a Danish cohort did not show the same risk (6).

Aside from case reports and death registry analysis, epidemiologic surveys using lung function tests and other biomarkers can provide pathophysiologic information for non-diagnosed and subclinical cases. Epidemiologic studies on the respiratory health of workers in fiberglass-reinforced plastics (FRP) manufacturing remain limited. Because styrene is one of the most abundant volatile compounds used in FPR and is the active diluent of polyester resin (36–45% of weight concentration), it is a major concern (7). Previous evidence on the effects of styrene exposure on lung function are mixed. Helal et al (8) and McCague et al (9) both report an association of styrene exposure and obstructive lung function impairment among workers in FRP manufacturing plants. However, Lorimer et al (10) do not report either obstructive or restrictive lung function impairment among workers involved in styrene monomer or polymer fabrication. Whether the observed lung function effects are related to styrene or the additives used in FRP is unknown. Another study reports on increased lung inflammation among workers exposed to FRP dusts related to cutting, grinding, and finishing processes (11). What kind of work process is most hazardous to the lungs is still not clear.

Identifying the health risk of a specific group with similar exposure is an important step in occupational health. In the light of previous case reports, all of which involve manually wiping the glue and laying up the FRP, we conducted this study to evaluate the respiratory effects associated with the lamination process.

Methods

Results

Overall, the study participants consisted of 113 employees, 63 from plant A and 50 from plant B. The proportions of female workers and educational attainment <13 years were higher among the laminators than among the non-laminators (table 1). There were no significant differences in age, tenure, and smoking habits between the two groups. The proportion of current and past smokers was much higher among male (19.7%) than female (4.7%) workers.

Geometric mean concentrations of styrene measured for laminating work amounted to 7.5 ppm in plant A and 16.5 ppm in plant B, ie, approximately 30–66 times higher than the geometric mean of 0.2–0.3 ppm measured (in plant B only) for the other jobs (table 2). In general, laminating in an enclosed space or over larger surfaces exposed workers to higher styrene concentrations, thus explaining the broad range of measured concentrations of 1.5–46 ppm in plant A and 2.7–71 ppm in plant B.

Laminators had a statistically higher prevalence of chronic cough than non-laminators (table 1). Laminators more commonly complained of cough during work at daytime and before sleep at night. There was a borderline significance in the difference of cough and wheeze relieved during holidays between the two groups, but there was no significant difference in phlegm production and nasal symptoms.

The pre-, post-, and between-shift changes of lung function revealed that after adjustments for confounding factors, laminators had significantly lower pre-shift FEV1 and FEV1/FVC, lower post-shift FVC and FEV1, and larger post-shift reduction of FVC compared to non-laminators (table 3). In terms of patterns of lung function impairment (table 4), laminators had higher prevalences of obstructive and overall (obstructive plus restrictive) impairments. The prevalence of post-shift reduction of FVC >10% was also higher among laminators. The tenure for lamination work was negatively associated with pre- and post-shift FVC or FEV1 (supplementary material www.sjweh.fi/show_abstract.php?abstract_ id=3924, table S2). We further stratified all participants in to three groups, non-laminators (never) and those with lamination tenure < or >6.14 years (the median among laminators), and found that only those with lamination tenure <6.14 years had significantly higher risk of obstructive and overall (obstructive plus restrictive) impairments (table S3).

Sputum was collected from 51 out of 63 participants in plant A: 12 could not produce sputum after hypertonic saline inhalation, while 2 were excluded due to inadequate sputum quality (squamous cell >20% of total cells). Laminators had higher percentages of neutrophils and lymphocytes, and lower percentage of macrophages than non-laminators (table 5). The percentage of neutrophils in the induced sputum was associated with the cross-shift reduction in FEV1 and FEV1/FVC, while the percentage of lymphocytes was negatively associated with post-shift FVC and FEV1 (table S1). The percentage of macrophages was positively associated with post-shift FEV1/FVC and cross-shift changes in FEV1 and FEV1/FVC (table S1).

Discussion

In this cross-sectional study in two FRP manufacturing plants, we found that laminators chronically exposed to moderately high styrene levels exhibited an excess of respiratory complaints (mainly cough), impaired spirometry and signs of pulmonary inflammation when compared to non-laminators.

The prevalence of chronic cough (generally non-productive) was higher among laminators than non-laminators, even though the former had fewer smokers. Cough was a more common complaint during work at daytime and before sleep at night, but with recovery the next morning. Airway symptoms (cough or wheeze) also improved during holidays or days-off. These respiratory symptoms are suggestive of asthma and may explain why such affected workers were likely to be treated as asthmatic patients, thereby ending up with irreversible fixed airway obstructive disease, as noted in published reports (1, 2). Progressive dry cough, dyspnea, and occasional wheeze are the main symptoms of bronchiolitis obliterans (17, 18). In patients with flavoring-related bronchiolitis obliterans cough improved after leaving employment, but dyspnea did not disappear (18). Thus, regular check-up of respiratory symptoms, including persistent cough or cough with wheeze that are related to work, may provide useful information for identifying workers with significant pulmonary problems caused by exposure to the FRP lamination process.

The laminators had an elevated risk of obstructive lung function impairment. This is consistent with previous case reports and epidemiologic studies (1, 2, 8, 9). An epidemiologic study that used styrene as an indicator of exposure to FRP-related resins also demonstrated a higher risk of obstructive lung function impairment in the high exposure group (8, 9). However, styrene effect was not a consistent factor in other studies. A cohort study with analysis of mortality data revealed that increased risk of non-malignant respiratory death was not positively correlated to the cumulative dosage of styrene exposure (3). An epidemiologic study in a styrene producing industry also did not show a risk of obstructive or restrictive impairment due to styrene exposure (10). Although the present study does not tell us whether styrene or other chemicals is the causal agent, our findings point to laminating as the critical exposure. Consequently, laminators are the group requiring active preventive interventions.

Workers involved in the FRP lamination process using the open-molding method are usually exposed to the highest levels of evaporated chemicals from polyester resins (7). Aside from styrene, several chemicals are added to the resins. Peroxides like methylethylketone peroxide (1–1.5%) or benzoyl peroxide are used as initiators or catalysts to initiate the curing process. Peroxide catalysts require dimethyl aniline (0.1–0.3%) to be effectively activated at room temperature. Promoters such as cobalt naphthenate (0.3–1%) are also added to resins to increase the cure rate. However, no toxicologic information is available for these aforementioned additives in terms of respiratory toxicity or bronchiolitis obliterans. Regarding the filaments, the diameter of the fibers in the woven roving or mat used for the hand lay-up lamination of yacht construction is >10 micrometers, which makes it less likely to be directly inhaled into deep airways. Sometimes, the laminators need to eliminate air bubbles in the composite by hand-holding grinders, which break down glass fiber and resins into inhalable particles. But their overall dust exposure is not as high as that in grinding workers. Therefore, despite that we cannot completely exclude the possibility of filament-related respiratory effect, it is more likely other causal agents play more important roles. Although the causal agent remains unclear, applying closed molding, such as vacuum-assisted resin transfer molding, as well as adequately wearing respirators with organic vapor cartridges have been reported to be effective for reducing personal exposure to FRP-related chemicals (7).

Increased cross-shift reduction in FVC suggests restrictive lung function effects of acute exposure to FRP lamination-related substances. However, the pathophysiology is not identified or described in this study because of the lack of information on total lung capacity and post-bronchodilator lung function. It can only be speculated that the change may be related to processes in the small rather than large airways (mainly FEV1/FVC). Small airway diseases can present as a reduction in FVC due to occlusion or dynamic collapse of small bronchioles (19, 20). Some cases of bronchiolitis obliterans have restrictive or mixed restrictive and obstructive lung function impairment (18, 21). In the light of previous research on flavoring-related bronchiolitis obliterans, a survey using pre-bronchodilator spirometry has demonstrated a high prevalence of restrictive lung function impairment among flavoring workers (22). A spectrum ranging from obstructive to restrictive lung diseases is suggested for such toxic chemical inhalation (23). Therefore, FRP workers with either an obstructive or restrictive ventilatory defect on pre-bronchodilator spirometry need more detailed lung function assessments.

Susceptibility to bronchiolitis obliterans related to FRP chemicals is unknown, although some relevant clues have been provided in previous literature. First, only a small number of cases are reported to have severe obstructive lung disease and the symptoms often manifest shortly after employment (6–12 months), whereas other co-workers do not have the same symptoms or illness even under similar working conditions (1, 2). Second, there is a high risk of non-malignant respiratory mortality among FRP workers with less than one year of employment (5), and this risk is not related to cumulative exposure (3). Our research found that only workers with <6.14 years of employment in lamination have a higher risk of obstructive ventilatory disorder, which is consistent with previous research. Our study showed that a small percentage of workers experienced a cross-shift drop in lung function, suggesting an acute response. These “responders” may be the susceptible subgroup. Further longitudinal studies are needed to assess long-term respiratory outcomes among them.

The present study revealed an elevated percentage of sputum neutrophils rather than eosinophils among laminators. This is consistent with results by McCague et al (9) who showed suppressed exhaled nitric oxide levels, an indicator of eosinophilic airway inflammation. The association of neutrophils and cross-shift FEV1 and FEV1/FVC reduction also suggests a neutrophil-mediated response to airway injury and inflammation. In other words, sputum neutrophils might be used as an intermediate biomarker for the respiratory toxicity of FRP-lamination-related exposure. This finding is in line with previous literature showing that neutrophilic airway inflammation has been associated with toxic inhalation and chronic airway diseases, including bronchiolitis obliterans and chronic obstructive pulmonary diseases (24–26).

The elevated percentage of induced sputum lymphocytes among laminators, and its association with post-shift lung capacity, suggests that lymphocytes associated inflammation also play a role in the laminating related respiratory effect. A previous study has demonstrated an increased lymphocyte percentage in induced sputum in several interstitial lung diseases (27) in contrast to airway diseases like asthma or chronic bronchitis (28). Further animal studies or lymphocyte subset analysis may advance knowledge as to the pathophysiologic response to inhalational exposure in the lamination process.

The percentage of sputum macrophages in laminators was lower than that in non-laminators. Alveolar macrophages usually play a defensive role in respiratory exposure to pathogens and particulate matters (29). A previous study has shown an increase in the number of macrophages in bronchoalveolar lavage among workers exposed to FRP grinding dust (11). An animal study showed that wood dust could increase alveolar macrophages (30). Therefore, the observed reduction in its percentage in laminators may be related to lower dust exposure compared to employees involved in grinding and woodwork, and a relative increase in numbers of neutrophils and lymphocytes. The positive association between macrophage and cross-shift lung function change in this study also suggests a protective role of macrophages in respiratory physiology.

This study has some strengths. First, we conducted field research before and after work on Monday, which minimized the effect of exposures on the previous days. Therefore, the impact on preshift lung function is likely to be related to chronic exposures and the effect on cross-shift lung function changes linked to acute exposures. Second, the laminators who participated in this study usually remained in hand lay-up work in FRP manufacturing rather than moving around different kind of processes, which minimized the interference from other exposures, such as wood dust, painting, and FRP grinding dust. Third, this study included exposed and non-exposed groups in the same plant, which minimized bias related to environmental exposure (eg, ambient air pollution).

Some limitations are noteworthy. First, the study’s cross-sectional design may have caused an underestimation of the health hazards due to the healthy worker or healthy worker survival effect. Airway symptoms, such as cough or dyspnea, may alert workers to leave work. Since we have already observed the effects on lung function, the healthy worker effect may have prevented us from observing more severe cases of impaired respiratory function. Second, grouping laminators into a single exposure group may underestimate the health effects in the extremely high exposure groups, such as those more commonly working in an enclosed structure or with large surface lamination processes. The incomplete and differential measurement of styrene in the two plants prevented us from assessing the exposure–response relationship for the entire data set. Finally, as this is a simple cross-sectional study without long-term follow-up, reversed causality should be cautiously considered.