Validation of a non-invasive technique to assess development of airway hyperreactivity in an animal model of immunologic pulmonary hypersensitivity

Abstract

Airway hyperreactivity (AHR) is considered to be a prominent and consistent feature of the asthmatic. Accordingly, in developing animal models of asthma, it is important to have methodologies available for repeated assessment of airway reactivity (AR). We have described a methodology to assess AR in conscious minimally restrained guinea pigs, AR being quantified as the airborne concentration of histamine (mg m-3) necessary to produce a mild airway constriction. The present study sought to validate that methodology by assessing its ability to detect changes in AR associated with immediate-onset pulmonary hypersensitivity responses. Guinea pigs were sensitized by intraperitoneal injection of ovalbumin (OA) and challenged with OA aerosol 3 weeks later. All animals developed severe immediate-onset airway constrictive responses. AR was assessed 1 h later, upon return to normal breathing patterns. Hyperreactivity was apparent from response to 0.50 mg m-3 histamine when compared with 2.10 mg m-3 histamine needed for baseline response. In control, sham sensitized animals AR remained at 2.12 mg m-3 after OA inhalation challenge. The results demonstrate the ability of this methodology to detect airway hyperreactivity to histamine resulting from a pulmonary hypersensitivity response. By requiring neither surgery nor any invasive procedure, the technique is appropriate for serial measurements of AR as is needed in development of an animal model for asthma, a chronic airway disease.