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In the present study the effects of a 3-day inhalation exposure to model compounds for ambient particulate matter were investigated: ammonium bisulfate, ammonium ferrosulfate, and ammonium nitrate, all components of the secondary aerosol fraction of ambient particulate matter (PM), and carbon black (CB, model aerosol for primary PM). The objective of this study was to test the hypothesis that secondary model aerosols exert acute pulmonary adverse effects in rats, and that rats with pulmonary hypertension (PH), induced by monocrotaline (MCT), are more sensitive to these components than normal healthy animals. An additional aim was to test the hypothesis that fine particles exert more effects than ultrafines. Healthy and PH rats were exposed to ultrafine (mass median diameter [MMD] approximate, equals 0.07-0.10 microm; 4 x 10(5) particles/cm(3)) and fine (MMD approximate, equals 0.57-0.64 micro;m; 9 x 10(3) particles/cm(3)) ammonium aerosols during 4 h/day for 3 consecutive days. The mean mass concentrations ranged from 70 to 420 microg/m(3), respectively, for ultrafine ammonium bisulfate, nitrate, and ferrosulfate and from 275 to 410 microg/m(3) for fine-mode aerosols. In an additional experiment, simultaneous exposure to a fine CB aerosol (0.6 microm; 2-9 mg/m(3)) and ammonium nitrate (0.4-18 mg/m(3)) was performed. Bronchoalveolar lavage fluid (BALF) analysis and histopathological examination were performed on animals sacrificed 1 day after the last exposure. Histopathology of the lungs did not reveal test atmosphere-related abnormalities in either healthy or PH rats exposed to the ammonium salts, or to a combination of CB + nitrate. Alveolar macrophages in rats exposed to CB only revealed the presence of black material in their cytoplasm. There were no signs of cytotoxicity due to the aerosol exposures (as measured with lactate dehydrogenase [LDH], protein, and albumin contents in BALF). Macrophages were not activated after MCT treatment or the test atmospheres, since no changes were observed in N-acetyl glucosaminidase (NAG). Cell differentiation profiles were inconsistent, partly caused by an already present infection with Haemophilus sp. However, we believe that the test atmospheres did not affect cell differentiation or total cell counts. The results show that at exposure levels of ammonium salts at least one order of magnitude higher than ambient levels, marked adverse health effects were absent in both healthy and PH rats.

Asthma is an inflammatory disease of the airways, and exacerbations of this disease have been associated with high levels of air pollution. The objective of this study was to examine whether ambient air pollution and/or allergen exposure induces inflammatory changes in the upper airways of asthmatics. Sixty patients with intermittent to severe persistent asthma visited the Hospital's Out Patient Clinic every 2 wk for a period of 3 mo, and on each visit a nasal lavage was obtained. Associations between nasal inflammatory parameters and seasonal allergens and/or air pollution exposures were analyzed using linear regression analysis. The study ran from July 3 to October 6, 1995, during which period ozone (8-h mean: 80 micrograms/m3) and PM10 (24-h mean: 40 micrograms/m3) were the major air pollutants; the major aeroallergen was mugwort pollen (24-h mean: 27 pollen grains/m3). Effects on both cellular and soluble markers in nasal lavage were demonstrated for both ozone and mugwort pollen, but not for PM10. Ambient ozone exposure was associated with an increase in neutrophils (112% per 100 micrograms/m3 increase in 8-h average ozone concentration), eosinophils (176%), epithelial cells (55%), IL-8 (22%), and eosinophil cationic protein (ECP) (19%). Increases in environmental mugwort pollen counts were associated with an increase in nasal eosinophils (107% per 100 pollen/m3) and ECP (23%), but not with neutrophils, epithelial cells, or lL-8. This study demonstrated that both ambient ozone and allergen exposure are associated with inflammatory responses in the upper airways of subjects with asthma, although the type of inflammation is qualitatively different.

The acute effects of the inhalation of air polluting agents have been examined by many research groups in both animal models and human beings. For instance, it is evident that exposure to ozone has toxic effects and can lead to lung function disturbances. For this reason it is likely that individuals suffering from COPD or asthma are groups especially at risk with respect to the effects of ozone. The majority of studies dealing with effects of air pollutants on pulmonary allergy are restricted to IgE mediated allergy (type I allergy). Again for ozone, in animal models for type I allergy it has been demonstrated that exposure can affect the induction as well as the effector phase of this type of hyperimmune reaction (e.g. allergic asthma). Recently it has been demonstration in animal models that non-IgE mediated "asthma' T cells, and notably Th1 cells, may play a crucial role. In a murine model it was demonstrated that low molecular weight compounds can induce delayed type hypersensitivity-like reactions in the respiratory tract, and that these reactions are associated with the induction of airway hyperreactivity. Such compounds include toluene diisocyanate (TDI), to which immune responses can be readily mounted, and which can cause occupational asthma through its sensitizing capability, but to which IgE is only detected in a minority of patients suffering from TDI-associated asthma. Effects of air pollutants on Th1 responses in the respiratory tract have not been studied so far. We have demonstrated that ozone can inhibit resistance to a an intratracheal challenge with Listeria monocytogenes, indicating suppression of Th1 immune responses. In addition, we have shown that ozone exposure suppresses pulmonary delayed type hypersensitivity induced by small molecular weight compounds, as well as the tracheal hyperreactivity that is induced during the development of these immune responses, again supporting the hypothesis of suppression of Th1 responses by ozone exposure. These phenomena may be due to activation of Th2 cell dependent reactions that in turn lead to a downregulation of Th1 mediated immunity, or to a direct effect on Th1 cells or other cell types that are crucial for delayed type hypersensitivity and related airway hyperresponsiveness in this model. These data indicate that exposure to air pollutants may have differential consequences on different types of immune responses in the respiratory tract.

It is widely accepted that humans exposed to known concentrations of ozone under controlled conditions exhibit reversible changes that affect the large and small airways as well as the alveolar region of the lung. Among the reversible changes, the induction of inflammatory responses in the lung are of major concern. Many of the cell types found in the lining of the nasopharyngeal region are similar to cells of the tracheal and bronchial lining. therefore, it has been suggested that the cellular responses in the nose to toxicants are likely to be similar to the lower airway at the same dose of the agent. If these pollutants are respiratory irritants, capable of causing cellular damage, effects may therefore be detected in the nasal passage. Experimental studies have shown that the inflammatory response in the nose may be predictive for the situation in the lung. In this paper we described the results of a feasibility study on the use of nasal lavage for epidemiological studies. Nasal lavages were performed in 12 volunteers, 5-7 times per volunteer during 2 months. Polymorph nuclear leukocytes (PMN's), immune mediators and markers for exudation were monitored in the nasal lavage (NAL). It was found that the procedure of the nasal lavage technique was minimally invasive, very well tolerated and no adverse side effect were observed. The leukocytes, the proteins myeloperoxidase (MPO), eosinophil cationic proteins myeloperoxidase (MPO), eosinophil cationic protein (ECP) and interleukin-8 (IL-8) were detectable in NAL of most volunteers, while tryptase IgE and IL-6 were not detectable. Exudation markers albumin, urea and uric acid were also detectable. The coefficient of variance (CV) values of the various cells and mediators varied between 13% and 137%. It was calculated that, except for the number of leukocytes and the concentration of ECP, it should be possible to detect ozone effects with a study-protocol of 6 repeated measurements among 35 children and an assumed 26% increase in cells or mediators per 100 micrograms O3 per m3. To measure increase in leukocytes number or in ECP concentration more children are needed. In conclusion, this pilot study has shown that it is possible to measure relevant biomarkers in NAL, and that these assays can be easily incorporated in epidemiological studies.

The effects of short-term exposure to ozone on control and elastase-induced emphysematous rats were examined to investigate whether emphysema would change the pulmonary susceptibility to oxidant air pollution. Emphysema was induced in rats after a single intratracheal instillation of 0.2 IU elastase/g body weight. Histologically, panacinar emphysema was apparent at 2, 4, 8, and 16 wk, that is, the total duration of the experiment. The diagnosis was confirmed by morphometry: the mean linear intercepts (MLI) of elastase-treated rats were significantly increased at all observation times, whereas the internal surface areas (ISA) of the elastase-treated rats were significantly decreased. In addition, pulmonary function tests provided supportive evidence for the diagnosis of emphysema. Respiratory system compliance and functional residual capacity showed a significant increase in elastase-treated rats. No differences in inspiratory capacity or in forced vital capacity between control rats and elastase-treated rats were observed. The above data are indicative for a rat model for elastase-induced emphysema. Short-term exposure to ozone of elastase-treated rats revealed panacinar emphysema, including an inflammatory response in the centroacinar region. No differences in MLI as well as in ISA between ozone-exposed rats (with or without emphysema) and their respective controls were observed. Short-term exposure to ozone induced an identical, significant increase in protein content, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and glutathione peroxidase activities in lungs of normal and emphysematous rats. Moreover, these results strongly suggest that emphysematous rats are not more susceptible to ozone than nonemphysematous rats.