PubMed2004
Epidemiological studies have reported that elevated levels of particulate air pollution in urban communities are associated with increases in attacks of asthma based on evidence from hospital admissions and emergency department visits. Principal pathologic features of chronic airway diseases, like asthma, are airway inflammation and mucous hypersecretion with excessive amounts of luminal mucus and increased numbers of mucus-secreting cells in regions of the respiratory tract that normally have few or no mucous cells (ie, mucous cell metaplasia). The overall goal of the present project was to understand the adverse effects of urban air fine particulate matter (PM2.5; < or = 2.5 pm in aerodynamic diameter)* on normal airways and airways compromised with airway inflammation and excess mucus. Our project was specifically designed to (1) examine the chemical and physical characteristics of PM2.5 and other airborne pollutants in the outdoor air of a local Detroit community with a high incidence of childhood asthma; (2) determine the effects of this community-based PM2.5 on the airway epithelium in normal rats and rats compromised with preexisting hypersecretory airway diseases (ie, animal models of human allergic airway disease--asthma and chronic bronchitis); and (3) identify the chemical or physical components of PM2.5 that are responsible for PM2.5 -induced airway inflammation and epithelial alterations in these animal models. Two animal models of airway disease were used to examine the effects of PM2.5 exposure on preexisting hypersecretory airways: neutrophilic airway inflammation induced by endotoxin challenge in F344 rats and eosinophilic airway inflammation induced by ovalbumin (OVA) challenge in BN rats. A mobile air monitoring and exposure laboratory equipped with inhalation exposure chambers for animal toxicology studies, air pollution monitors, and particulate collection devices was used in this investigation. The mobile laboratory was parked in a community in southwestern Detroit during the summer months when particulate air pollution is usually high (July and September 2000). We monitored the outdoor air pollution in this community daily, and exposed normal and compromised rats to concentrated PM2.5 from this local urban atmosphere. Rats in the inhalation studies were exposed for 1 day or for 4 or 5 consecutive days (10 hours/day) to either filtered air (controls) or concentrated ambient particles (CAPs) delivered by a Harvard ambient fine particle concentrator. Rats were killed 24 hours after the end of the exposure. Biochemical, morphometric, and molecular techniques were used to identify airway epithelial and inflammatory responses to CAPs. Lung lobes were also either intratracheally lavaged with saline to determine cellular composition and protein in bronchoalveolar lavage fluid (BALF) or removed for analysis by inductively coupled plasma-mass spectrometry (ICPMS) to detect retention of ambient PM2.5--derived trace elements. The Harvard concentrator effectively concentrated the fine ambient particles from this urban atmosphere (10-30 times) without significantly changing the major physicochemical features of the atmospheric particles. Daily CAPs mass concentrations during the 10-hour exposure period (0800-1800) in July ranged from 16 to 895 microg/m3 and in September ranged from 81 to 755 microg/m3. In general, chemical characteristics of ambient particles were conserved through the concentrator into the exposure chamber. Single or repeated exposures to CAPs did not cause adverse effects in the nasal or pulmonary airways of healthy F344 or BN rats. In addition, CAPs-related toxicity was not observed in F344 rats pretreated with bacterial endotoxin. Variable airway responses to CAPs exposure were observed in BN rats with preexisting allergic airway disease induced by OVA sensitization and challenge. Only OVA-challenged BN rats exposed to CAPs for 5 consecutive days in September 2000 had significant increases in airway mucosubstances and pulmonary inflammation compared to saline-challenged/air-exposed control rats. OVA-challenged BN rats that were repeatedly exposed to CAPs in July 2000 had only minor CAPs-related effects. In only the September 5-day exposure protocol, PM2.5 trace elements of anthropogenic origin (La, V, and S) were recovered from the lung tissues of CAPs-exposed rats. Recovery of these specific trace elements was greatest in rats with OVA-induced allergic airway disease. Additional laboratory experiments using intratracheal instillations of ambient PM2.5 samples were performed to identify bioactive agents in the CAPs to which rats had been exposed in the inhalation exposure component. Because the most pronounced effects of CAPs inhalation were found in BN rats with OVA-induced allergic airways exposed in September, we used ambient PM2.5 samples that were collected on 2 days during the September CAPs inhalation exposures to use for instillation. Ambient PM2.5 samples were collected, fractionated into soluble and insoluble species, and then compared with each other and with total PM2.5 for their effects in healthy BN rats and those with OVA-induced allergic airway disease. Intratracheal instillation of the insoluble fraction of PM2.5 caused mild neutrophilic inflammation in the lungs of healthy rats. However, total PM2.5 or the soluble or insoluble fractions instilled in rats with OVA-induced airway inflammation did not enhance the inflammation or the airway epithelial remodeling that was evident in some of the BN rats exposed to CAPs by inhalation. Therefore, the results from this instillation component did not suggest what fractions of the CAPs may have been responsible for enhancing OVA-induced airway mucosubstances and pulmonary inflammation observed in the inhalation exposure component. In summary, inhaled CAPs-related pulmonary alterations in the affected OVA-challenged rats appeared to be related to the chemical composition, rather than the mass concentration, to which the animals were exposed. Results of the trace element analysis in the lungs of CAPs-exposed BN rats exposed in September suggested that air particles derived from identified local combustion sources were preferentially retained in allergic airways. These results demonstrate that short-term exposures to CAPs from this southwestern Detroit community caused variable responses in laboratory rats and suggest that adverse biological responses to ambient PM2.5 may be associated more closely with local sources of particles and weather patterns than with particle mass.