Time Course of Ozone-induced Neutrophilia in Normal Humans

Abstract

Five normal human subjects were exposed for 1 h to filtered air (FA) once and to 0.3 ppm O3 on 3 separate days. Bronchoalveolar lavage (BAL) fluid was obtained less than 1 h after FA and either less than 1, 6, or 24 h after O3 exposure. FEV1 was measured before the exposures and the BAL. The first aliquot [proximal airway (PA) sample] was analyzed separately from the pooled Aliquots 2 through 4 [distal airway and alveolar surface (DAAS) sample]. The data from the PA and DAAS samples were then combined to calculate the values that would have been obtained by pooling all BAL washes. FEV1 was significantly (p less than 0.05) decreased 1 h after O3 exposure, but it returned to preexposure values at 6 and 24 h after O3. The percent of neutrophils in the PA sample was significantly elevated at less than 1 h (3.7%) at 6 h (16.5%), and at 24 h (9.2%) after O3. The percent of neutrophils in the DAAS sample and calculated pooled values were significantly elevated at 6 h (4.1 and 7.6%) and at 24 h (5.1 and 5.8%) after O3. These data demonstrate that O3-induced symptoms, FEV1 decrements, and airway neutrophilia follow different time courses and indicate that the pooling of BAL washes may obscure the detection of an O3-induced bronchiolitis. The degree of neutrophilia in the BAL did not correlate with the sensitivity of the individual subjects when measured by acute changes in FEV1, suggesting a dichotomy of pathways that result in O3-induced airway neutrophilia and pulmonary function decrements.

Personally measured weekly exposure to NO<SUB>2</SUB> and respiratory health among preschool children

“…A number of studies have related immediate lung function responses to indices of airway inflammation determined 1±18 h after exposure, using higher O 3 burdens than employed in the present study [2,10,42]. SCHELEGLE et al [10] found no significant correlations between the immediate O 3 -induced FEV1 and the neutrophil responses at 1, 6 and 24 h post-exposure. However, a trend towards an inverse relationship was found at the 6 h timepoint.…”

“…Previously, increases in neutrophil numbers have been reported in BAL as early as 1 h post-exposure following a 2-h exposure to 0.4 ppm O 3 , [5] as well as in a proximal airway sample following exposure to 0.3 ppm O 3 for 1 h [10]. These studies utilized high exercise levels (60 L .…”

Is There an Association Between Lifetime Cumulative Exposure and Acute Pulmonary Responses to Ozone?

“…This lack of correlation may be at least in part due to different mechanisms responsible for airway injury/inflammation and for lung function changes after acute O 3 exposure. 38,39 The studies that have examined the relationship between acute O 3 -induced changes in FEV 1 and FVC and subsequent airway inflammation (up to 18 hours following exposure) have shown either no correlation or a negative one 5,8 although one study did show a significant correlation between acute increases in airway resistance (S Raw ) and subsequent airway inflammation. 40 More recently, a study by Weinmann et al in a small number of subjects showed that decrements in FEF measured isovolumetrically persist longer than other O 3 -induced acute decrements in lung function and suggested that these decrements correlate better with the acute O 3 -induced inflammatory response than changes in FEV 1 , FVC, and S Raw .…”

“…[1][2][3][4] Human studies have demonstrated that short-term exposure to O 3 causes acute changes in lung function as well as cellular and biochemical evidence of airway inflammation and injury. [5][6][7][8][9][10] Moreover, human studies have shown that with repeated short-term exposures, while oxidative injury continues to be present, some O 3 -induced physiologic and inflammatory responses undergo attenuation. [11][12][13][14][15] In addition, several studies have documented that subjects have attenuated lung function responses to acute controlled O 3 exposure during the summer months in areas that are characterized by high ambient O 3 concentrations.…”

Experimental Human Exposure to Air Pollutants Is Essential to Understand Adverse Health Effects

“…The 0.6 ppm O 3 exposure increased airway responsiveness for 24 hours (25). Five healthy humans exposed to O 3 at 0.3 ppm for 1 hour with exercise on four separate days induced cough, shortness of breath, chest discomfort on deep inspiration, throat irritation, chest congestion, and a fall in FEV 1 (26); analysis of BAL fluid showed a rise in the percent neutrophils from 3.7% at 1 hour, to 16.5% at 6 hours, and to 9.2% at 24 hours. Another study of 14 healthy athletes exposed to O 3 at 0.2 ppm for 4 hours with moderate exercise, followed by BAL 18 hours later, showed an increase in neutrophils from 2.1 6 3.0 after filtered air exposure to 7.6 6 3.9% after ozone exposure (P , 0.002) (27).…”