Ozone-induced decrements in FEV1 and FVC do not correlate with measures of inflammation.

Abstract

In order to test the hypothesis that changes in lung function induced by ozone (O3) are correlated with cellular and biochemical indices of respiratory tract injury/inflammation, we exposed 20 healthy subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and SRaw) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with isolated left main bronchus proximal airway lavage (PAL) and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following end points: total and differential cell counts, and total protein, fibronectin, interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. The study population was divided into two groups, least-sensitive (n = 12; mean O3-induced change in FEV1 = -7.0%) and most-sensitive (n = 8; mean O3-induced change in FEV1 = -36.0%). We found a significant O3 effect on SRaw (p<0.001) and lower respiratory symptoms (p<0.001) for all subjects combined, but no significant differences between the least- and most-sensitive groups. Ozone exposure increased significantly percent neutrophils in PAL (p=0.01); percent neutrophils, total protein, and IL-8 in bronchial fraction (p<0.001, p<0.001, and p<0.01, respectively); and percent neutrophils, total protein, fibronectin, and GM-CSF in BAL (p<0.001, p<0.001, p<0.01, p=0.05, respectively) for all subjects combined; there were no significant differences, however, between least- and most-sensitive groups. Our results indicate that levels of O3-induced symptoms and respiratory tract injury/inflammation were not correlated with the magnitude of decrements in FEV1 and FVC.

Bronchial reactivity of healthy subjects: 18–20 h postexposure to ozone

“…Toxicity of O 3 to epithelial surfaces is primarily attributed to reactive oxygen species and ozonation of unsaturated fatty acids present in lung lining fluids (29). Early (3-h) and late (18-to 20-h) responses in the human after whole lung exposure to O 3 include an influx of protein, inflammatory cells, and mediators into airway and alveolar surface fluids (2,4,35). The presence of these cellular and biochemical markers of injury at the epithelial surface and the increased diffusivity of small molecules within the submucosa postexposure (14) have led to speculation that exposure to O 3 modulates bronchial smooth muscle tone and responsiveness to nonspecific challenge (24).…”

Toxicologic methods: controlled human exposures.

“…Care must be taken during the procedure to avoid prolonged balloon inflation, as some subjects may experience significantly decreased arterial oxygen tension during occlusion of the airway. The technique has been used successfully in both healthy volunteers and subjects with mild asthma (35). A modification of this technique has been used to study the effects of 03 exposure in healthy and asthmatic subjects (36).…”

“…For example, retention of insoluble 2 pm particles was increased 50% in subjects with COPD compared with healthy subjects, and the increased deposition correlated with the severity of obstruction (87). The (19,35). Furthermore, the mechanisms by which pollutant exposure contributes to respiratory mortality may differ from those responsible for excess cardiovascular mortality.…”

A theoretical basis for investigating ambient air pollution and children's respiratory health.

“…NO2 also has acute effects, but only at levels exceeding 2.0-4.0 ppm (1). The effects include decrements in forced expiratory volume in 1 sec (FEVI) and forced vital capacity, cough and chest discomfort, lung injury and inflammation, and changes in airway responsiveness (5)(6)(7)(8). Changes in pulmonary function have also been observed in children at summer camp and athletes exposed to ambient air pollution during outside activities (6,9).…”

“…Airway hyperreactivity persists after 03-induced changes in FEV, resolve and the degree of reactivity is not associated with the magnitude of spirometric changes, suggesting an independent mechanism for hyperreactivity (14 respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD). The inflammatory response involves increased numbers of macrophages, neutrophil infiltration, increased cellular protein permeability following the production of a broad range of inflammatory cytokines, and increased arachidonic acid metabolites (8,(15)(16)(17)(18). In addition to the inflammatory response, a large body of evidence suggests that acute NO2 exposure at environmental levels may adversely affect other aspects of immune function including macrophage function, resulting in decreased airway clearance and increased risk of infection.…”