Dissociation between airway responsiveness to methacholine and responsiveness to antigen

Abstract

Dissociation between airway responsiveness to methacholine and responsiveness to antigen. A. Kamachi, Y. Nasuhara, M. Nishimura, T. Takahashi, Y. Homma, Y. Ohtsuka, M. Munakata. #ERS Journals Ltd 2002. ABSTRACT: Repeated aerosolized antigen challenges to brown Norway (BN) rats generate nonspecific airway hyperresponsiveness (AHR). On the other hand, some studies have demonstrated that repeated antigen challenge could attenuate antigenspecific AHR in BN rats. The authors questioned whether such dissociation in airway responses actually occurs when assessed in a single study in the same animals.The authors simultaneously measured AHR to methacholine and antigen-specific AHR in rats that were repeatedly exposed to aerosolized ovalbumin (OA) for 1 or 3 months after sensitization. Four days after the last challenge, airway responses to methacholine and OA, morphometry of the airways, the cell profile in bronchoalveolar lavage fluid, and cytokine messenger ribonucleic acid (mRNA) expression in the lungs were evaluated.The two types of AHR were modulated in opposite directions by repeated antigen challenges. The AHR to methacholine was significantly increased in the rats receiving antigen challenges compared with the control rats receiving saline challenges after sensitization; whereas, the antigen-specific AHR was significantly decreased. The number of alveolar macrophages in lavaged fluid and the expression of transforming growth factor-b 1 mRNA in lung tissue was significantly different between the antigenchallenged rats and the control rats.In conclusion, dissociation between nonspecific airway hyperresponsiveness and antigen-specific airway hyperresponsiveness in brown Norway rats after repeated antigen challenges was demonstrated. Sustained airway inflammation with macrophages and/or upregulation of transforming growth factor-b 1 messenger ribonucleic acid in the lung tissue may be responsible for this dissociation.

Sensitivity of disease parameters to flexible budesonide/formoterol treatment in an allergic rat model

“…This is in agreement with studies showing the enhanced bronchoconstrictor responses to methacholine in rodent models of allergic asthma [13,14]. We have chosen ELGV method since it is a rapid, quantitative, sensitive and reproducible technique that does not interfere with other experimental results.…”

Investigation of airway inflammation and asthma by repeated bronchoalveolar lavage combined with measurements of airway and lung tissue mechanics in individual rats

“…The earlier results relating to the effects of inhaled allergen are far more controversial. Some authors reported no effects of a single inhalation of OVA on the lung responsiveness [35,37], while others provided evidence of the development of BHR and lung inflammation following a single exposure to an aerosol of various allergens [33,34,38].…”

“…It is possible that ragweed and grass pollen extracts induce stronger stimuli to the immune system than does OVA [33]. Furthermore, lung inflammation and BHR have been provoked by a single OVA aerosol in highly inbred Brown-Norway rats [34,38]. Since genetic differences influence the expression of a complex immune disease [54,55], it seems plausible that the Wistar rats used in the present study do not develop a detectable BHR or airway inflammation after a single OVA inhalation in contrast with a more susceptible immune system in Brown-Norway rats.…”

“…Exposure to materials such as ozone [32], ragweed [33], ascaris suum extract [35] or most commonly ovalbumin (OVA) [34,[36][37][38] leads to chronic airway inflammation in animal models. Since such exposure causes an influx of various inflammatory cells into the mucosa and lamina, the inflammatory process in the airways has been assessed by analysing the cellular content of the bronchoalveolar lavage fluid (BALF) [32][33][34][35]38].…”

“…Since such exposure causes an influx of various inflammatory cells into the mucosa and lamina, the inflammatory process in the airways has been assessed by analysing the cellular content of the bronchoalveolar lavage fluid (BALF) [32][33][34][35]38]. BHR has been …”