Concentrations were higher in homes with tobacco smoking. Phenanthrene, for example, was 87 ng/m3 for homes with smoking and gas stove/heat versus 31 ng/m3 for nonsmoking homes with gas stove/heat. PAH concentrations are also likely to be higher where there is a high density of trucks, such as downtown Los Angeles, California, where DE was found to make up 32.7% of the fine particle mass . The following section will examine some of the experimental evidence for the potential causal role of PAHs in asthma, as well as complementary epidemiologic evidence from both the occupational and non-occupational literature. The experimental evidence that suggests an important mechanistic role for PAHs from DEPs in allergic respiratory illnesses has been extensively reviewed before , so the present section serves as a brief overview. Takenaka et al. showed that IgE production in purified B cells following the addition of IL-4 and CD40 monoclonal antibody was enhanced 20–360% by the addition of an extract of PAH from DEPs. The effect was replicated with 2,3,7,8-tetrachlorodibenzo-pdioxin, demonstrating that the action of the PAH extract was likely attributable to aromatic hydrocarbons rather than a DEP contaminant, possibly acting through aryl hydrocarbon receptor–mediated effects on nuclear activities. Tsien et al. also found in vitro enhancement of IgE production in human B cells using a total PAH extract of DEPs, as well as the major PAH component of DEPs, phenanthrene. Diaz-Sanchez et al. found that topical treatment of nasal epithelium with the corticosteroid drug fluticasone inhibited significant increases in cytokine messenger RNA for IL-4 and IL-5 after ragweed challenge,grow rack system but it did not block a greater cytokine mRNA production after DEP challenge.
The authors suggested that fluticasone was unable to inhibit a broad polyclonal activation because of an adjuvant like activity of DEPs. They cited earlier evidence that intranasal challenges with DEPs leads to significant increases in many cytokines , whereas allergens such as ragweed predominantly increase IL-5 . In addition, the increase in allergen-specific IgE with ragweed alone is less than a combined challenge with ragweed plus DEPs . Interestingly, Fujieda et al. found that DEPs plus ragweed exposure also drives in vivo isotype switching to IgE in nasal lavage cells from humans with ragweed allergy but not either exposure alone. PAHs from DEPs enhance IgE responses, but does DEP exposure induce initial atopic sensitization? Diaz-Sanchez et al. tested this using a neoallergen to which subjects could not have been previously exposed. When 10 atopic human volunteers were nasally immunized with KLH, anti-KLH immunoglobulin G and immunoglobulin A were produced after KLH challenge but not IgE. In 15 other subjects, the KLH immunization was preceded by DEP administration 24 hr previously. KLH challenge in 9 of these subjects led to the additional production of antiKLH–specific IgE. Clinical relevance of the nasal challenge studies to lower respiratory allergic responses remains to be established. Salvi et al. exposed 15 healthy subjects to clean air and DE on different days over 3 weeks and examined lung function, airway lavage, and bronchial biopsies 6 hr after 1-hr exposures . They saw increases in neutrophils and B lymphocytes in lavage fluids. Bronchial biopsies showed increased inflammatory cells and significant increases in expression of endothelial adhesion molecules and their ligands. Increases in neutrophils and platelets were found in peripheral blood. There were no significant changes in lung function, but the effect on the asthmatic lung remains to be tested. In summary, PAHs from fossil fuel combustion may contribute to worsening respiratory allergic responses and induction of the initial clinical expression . Potential targets for PAHs include antigen-presenting cells, macrophages, mast cells, respiratory epithelial cells, and possibly TH2 cells directly.
All of these cells are thought to possibly play a role in the adjuvant effects of DEPs on allergic inflammation . Experimental findings have shown that whereas DEPs alone have a nonspecific effect in increasing cytokine production, DEPs plus ragweed antigen selects against a TH1 profile while stimulating a TH2- type response . The clinical relevance of these experimental findings remains to be established, especially for asthma. The relevance to public health and to epidemiologic findings of air pollution health effects also remains to be established. The ability of PAHs to exacerbate disease severity among asthmatic individuals has not been directly investigated in an epidemiologic study. The following review of the epidemiologic literature involves complex exposure mixtures that contain relatively high concentrations of PAHs along with other potentially causal pollutants. Occupational Evidence for Respiratory Effects of DE Occupational exposures to DEP can be high, thus giving researchers the opportunity to examine associated health effects. Exposures range from 1 to 100 µg/m3 for 8-hr averages in occupations such as trucking or transportation where mixed automobile and truck exposures are expected. Exposures are much higher for other occupations such as underground mining, which uses diesel equipment operated in enclosed spaces, and range from 100 to 1,700 µg/m3 . A case report of three railroad workers is the only paper linking new-onset asthma to occupational DE exposures . The workers developed asthma after exposure to locomotive exhaust while riding immediately behind a lead engine. However, all had been working for the railroad for many years, which leaves open a role for chronic exposures. They had no previous history of asthma or other chronic lower respiratory disease and were nonsmokers. One subject had a history of seasonal rhinitis, and one had a family history of asthma and rhinitis, suggesting underlying susceptibility. The diagnosis was confirmed by spirometry, airways hyperreactivity to methacholine, and exercise challenge. Two workers showed reversibility in lung function deficits with an inhaled bronchodilator; the other showed reversibility 3 years later.
All three experienced asthma symptoms upon reexposure to locomotive DE, and one showed peak expiratory flow rate fall with work exposure. All developed persistent asthma with exacerbations occurring with various triggers including exertion, cold air, and passive smoke. One other paper reported a similar high-exposure event involving 13 railroad workers, two of whom complained of chest tightness and wheezing, but no other diagnostic data were provided . In addition to the above case report, a number of cross-sectional occupational studies of DE exposed workers have been conducted. An early study of 200 coal miners found no association between diesel exposure and respiratory health . A better-designed study by Reger et al. showed adverse effects in 823 miners in diesel coal mines frequency-matched to 823 miners in non-diesel coal mines by age, height, smoking status, and years underground. Persistent cough and phlegm were significantly higher in diesel exposed workers, but the opposite was found for dyspnea; there was no difference in wheezing. Compared with non-diesel workers, diesel workers also had significant decrements in FVC, FEV1, and forced expiratory flow rate at 75% and 90% of FVC but no evidence of obstruction using the ratio FEV1/FVC. Other studies were conducted by some of the same investigators in coal mines. One study of acute effects of DE during an 8-hr work shift in 90 coal miners compared diesel-exposed and unexposed miners . Investigators found that cross-shift deficits in FEV1, FVC, and forced expiratory flow rate at 50% of FVC were greater for diesel-exposed subjects, but not significant. The same group conducted a 5-year prospective study of 280 diesel exposed and 838 unexposed miners in different mines . They found no significant age-adjusted differences in 5-year changes in FEV1 or FVC, or in chronic cough, phlegm, or breathlessness. However, diesel-exposed western miners who, unlike the eastern miners,grow rack vertical provided the control group, showed a significant deficit in FEF50. An internal analysis of diesel-exposed workers based on cumulative years of diesel exposure was negative. A study by Gamble et al. of 283 diesel bus garage workers compared with blue-collar controls, showed garage workers had a significantly higher incidence of cough, phlegm, and wheezing adjusted for age, race, and smoking. However, pulmonary function was, on average, higher in garage workers than the controls by all race and smoking status categories adjusted for age and height. An internal comparison based on tenure showed progressively decreasing FEV1, FVC, and FEF50 adjusted for age, height, race, and smoking status. The internal comparison also showed a consistent increase in prevalence of dyspnea, wheeze, and cough with tenure.There was a non-significant increased trend in cough and dyspnea and a significant trend in phlegm by years of tenure in diesel-exposed jobs but no association with lung function adjusted for smoking, age, and height. The adjusted prevalence of cough and phlegm was also higher than that of a blue-collar comparison group, but lung function did not differ. None of the above papers compared groups based on any actual pollutant measurements. However, the same 259 salt miners discussed above were studied with personal samples of NO2 and respirable particles .
The personal samples were used to estimate cumulative exposure by tenure, with NO2 as a surrogate measure of diesel exposure . Cough, dyspnea, and pulmonary function were not associated with estimated cumulative NO2 or respirable particle exposure . Only phlegm was associated with the exposures. Gamble et al. also used personal samples of NO2 and respirable particles to assess acute effects in 232 of the 283 diesel bus garage workers in their previous paper discussed above. Both NO2 and respirable particles exposures were associated with increased post work shift symptoms of cough, difficult or labored breathing, chest tightness, and wheeze but not lung function. Attfield et al. studied 630 miners in six potash mines in New Mexico with different exposures and exposure durations to underground DE. They also used personal passive samples of NO2 . Internal analysis showed average percent predicted FEV1 and FVC were not associated with particular mines in nonsmokers or smokers . Lung function and symptoms were not associated with predicted cumulative NO2 exposure. However, when years of exposure were examined, lung function actually improved and there was no trend in symptoms , suggesting a harvesting effect that selected against workers with adverse pulmonary responses. Robertson et al. studied 44 matched pairs of coal miners differently exposed to NO2 and found no difference in respiratory symptoms or FEV1. Purdham et al. found that work shift changes in FEV1 among 17 stevedores employed in ferry operations did not differ from those of 11 office controls. Area measurements of NO2, formaldehyde, and acetaldehyde were also not different, but poor precision was possible. Other occupational studies have examined workers exposed to automobile exhaust, which can include diesel fumes as well. Studies by Speizer and Ferris compared two groups of policemen with different exposure levels to auto exhaust and found no significant differences in symptoms or pulmonary function. Ayres et al. showed tunnel workers had worse pulmonary function and more respiratory symptoms than bridge workers with lower exposures. Ulvestad et al. compared 221 tunnel workers with 205 heavy-construction workers. They found tunnel workers, but not heavy-construction workers, had significant decreases in percent predicted FVC and FEV1 with tenure, adjusted for smoking and atopy by radioimmunoassay test . Tunnel workers reported significantly more respiratory symptoms than referent workers, and prevalence of chronic obstructive pulmonary disease was also higher. However, in an earlier study there were no differences in the prevalence of respiratory symptoms between tunnel and turnpike workers, although both may have been highly exposed . A small study of 89 workers on roll-on roll-off ships, car ferries, and a bus garage showed significant FEV1 and FVC decrements during workdays after several days with no exposure . The above occupational studies, most of which are cross-sectional in design, reveal a mixed picture of adverse and null effects. Other pollutant exposures such as coal dust could have been responsible for positive associations in internal comparisons, as well as for positive and negative findings in between group comparisons because both groups were usually in occupational groups exposed to airborne pollutants. Control for adverse smoking effects, which were generally strong, may also have been inadequate or subject to undetected multi-collinearity or interaction. However, it is likely that the healthy worker effect strongly influenced findings. Therefore, the limited findings of adverse effects in working men supports the expectation of stronger associations in susceptible individuals in the general population, including people with current asthma, children, and the elderly.