Dose‐response relationship of ozone‐induced airway hyperresponsiveness in unanesthetized guinea pigs

Abstract

The effect of ozone dose (the product of ozone concentration and exposure time) on airway responsiveness was examined in unanesthetized, spontaneously breathing guinea pigs. Airway responsiveness was assessed by measuring specific airway resistance (sRaw) as a function of increasing concentration of inhaled methacholine (Mch) aerosol (the concentration of Mch required in order to double the baseline sRaw: PC200Mch). The airway responsiveness was measured before and at 5 min, 5 h, and 24 h after exposure. A 30-min exposure to 1 ppm ozone (dose 30 ppm.min) did not change PC200Mch at any time after exposure. Both a 90-min exposure to 1 ppm ozone and a 30-min exposure to 3 ppm ozone, which are identical in terms of ozone dose (90 ppm.min), decreased PC200Mch to a similar degree. A 120-min exposure to 3 ppm ozone (360 ppm.min) produced a much greater decrease of PC200Mch at 5 min and 5 h after exposure, compared with low-dose exposure. There was a significant correlation between ozone dose and the change in airway responsiveness. In all groups, the baseline sRaw was increased by approximately 50% at 5 min after exposure, but there was no correlation between the changes in PC200Mch and the baseline sRaw. This study suggests that ozone-induced airway hyperresponsiveness in guinea pigs is closely related to ozone dose.

Combined effects of ozone and cigarette smoke on airway responsiveness and vascular permeability in guinea pigs

“…It has been well documented that airway hyperresponsiveness is experimentally induced by a single exposure to noxious gas including ozone and cigarette smoke [7,15,16,22,24,25,28]. These experimental models differ from clinical asthma in that alterations in airway responsiveness are usually transient and resolve completely in a period of hours to days.…”

“…4A,B,D,E). Our previous data in guinea pigs showed no significant correlation between the changes in baseline sRaw and the increase in airway responsiveness after ozone exposure [24]. Several human studies have shown that brief exposure to ozone causes changes in airway hyperresponsivehess in the absence of changes in pulmonary mechanics [10,13].…”

“…In all animals specific airway resistance (sRaw) and muscarinic responsiveness were determined immediately, 5 hr, and 24 hr after exposure. These conditions were based on our previous studies [24,25].…”

“…We have recently reported that acute single exposure to ozone or cigarette smoke increases airway responsiveness in a dose-dependent manner [24,25]. We designed the present study to examine the airway responsiveness and tracheal vascular permeability of guinea pigs exposed to a combination of ozone and cigarette smoke.…”

Differences between inhaled and intravenous bronchial challenge to detect O3-induced hyperresponsiveness

“…The increased responsiveness is usually demonstrated through pharmacological methods, i.e., the elaboration of dose-response curves with bronchoconstrictor agents. In laboratory animals, the most common ways to deliver these agents to the airways are the intravenous (22,23) and the inhalatory routes (14,17). Although extensively used to demonstrate this phenomenon, differences between inhaled and intravenously admin-istered agents have been very scantily investigated (18).…”