Ozone differentially modulates airway responsiveness in atopic versus nonatopic guinea pigs

Abstract

While acute exposures to ozone (O(3)) can alter airway responsiveness, effects from long-term exposures at low concentrations are less clear. This study assessed whether such exposures could induce nonspecific hyperresponsiveness in nonatopic (nonsensitized) guinea pigs and/or could exacerbate the pre-existing hyperresponsive state in atopic (sensitized) animals, and whether gender was a factor modulating any effect of O(3). Responsiveness was measured during and following exposures to 0.1 and 0.3 ppm O(3) for 4 h/day, 4 days/wk for 24 wk in male and female nonsensitized animals, those sensitized to allergen (ovalbumin) prior to initiation of O(3) exposures, and those sensitized concurrently with exposures. Ozone did not produce hyperresponsiveness in nonsensitized animals, but did exacerbate hyperresponsiveness to both specific and nonspecific bronchoprovocation challenges in sensitized animals, an effect that persisted through at least 4 wk after exposures ended. Gender was not a factor modulating response to O(3). Induced effects on responsiveness were not associated with numbers of eosinophils in the lungs nor with any chronic pulmonary inflammatory response, but were correlated with antigen-specific antibodies in blood. This study supports a role for chronic O(3) exposure in the exacerbation of airways dysfunction in a certain segment of the general population, namely, those demonstrating atopy.

FIGURE 1

Baseline specific airway conductance (sGaw) as a function of time from start of exposures to O₃ or air for (A) NS, (B) PS, and (C) CS animals. Each point is the mean (±SE) for all animals at each time point. Significant differences between atmospheres at each time point are indicated by differing letter designations. Group sizes are 20/time point/atmosphere through wk 24, and 10/time point/atmosphere for wk 28–32.

FIGURE 2

PC50 as a function of time from the start of exposures to O₃ or air for (A) NS ACh, (B) PS ACh, (C) PS OA, (D) CS ACh, and (E) CS OA challenge hosts. Each point is the mean (±SE) for all animals at each time point. Significant differences between atmospheres at each time point are indicated by differing letter designations. Group size/time point/atmosphere for (A), (C), and (D), 20 through wk 24 and 10 for wk 28–32; for (B) and (E), 20 for wk 0 and 8–24, and 20 for wk 4, 28, and 32.

FIGURE 3

Gender comparison of ACh PC50 for air-exposed NS hosts. Each point is the mean (±SE) for all animals at each time point.

FIGURE 4

Cell differentials in lavage from NS, PS, and CS hosts sacrificed at wk 24 (A, C, and E, respectively) or after the postexposure period (B, D, and F, respectively). Each bar is the mean (±SE) for five male or five female guinea pigs exposed to the indicated atmosphere. Due to the various statistical comparisons within and between exposure cohorts, for simplicity, symbol designations for significance are not included in the figure. Details of statistical results are described in the text.

FIGURE 5

Cell differentials in blood from NS, PS, and CS hosts sacrificed at wk 24 (A, B, and D, respectively) or after the postexposure period (C and E, respectively). There was no postexposure blood differentials performed with the NS animals. Each bar is the mean (±SE) for five male or five female guinea pigs exposed to the indicated atmosphere. Due to the various statistical comparisons within and between exposure cohorts, for simplicity, symbol designations for significance are not included in the figure. Details of statistical results are described in the text.

FIGURE 6

OA-specific immunoglobulin levels in blood from animals sacrificed at wk 24 or after the postexposure period: (A) IgG₁ in PS, (B) IgG₁ in CS, (C) IgG₂ in PS, and (D) IgG₂ in CS animals. Values represent IgG concentration in blood relative to that of an IgG standard. Each bar is the mean (±SE) for five male or five female guinea pigs exposed to the indicated atmosphere. Due to the various statistical comparisons within and between exposure cohorts, for simplicity, symbol designations for significance are not included in the figure. Details of statistical results are described in the text.

FIGURE 7

Comparison of (A) nonspecific and (B) specific airway responsiveness in PS and CS hosts exposed to 0.3 ppm O₃. PC50 is expressed as the fraction of respective air controls. Each value is the mean (±SE) for 10 guinea pigs/protocol.