Because both bradykinin and tachykinins have a potent inflammatory action, these molecules may be involved in the late allergic response. The role of these molecules in airway microvascular permeability during the late allergic response in sensitized guinea-pigs was investigated.Three weeks after ovalbumin sensitization, the animals were pretreated with bradykinin B 2 receptor antagonist HOE 140, neurokinin 1 receptor antagonist CP 96,345 or vehicle, 30 min before the ovalbumin inhalation challenge. The occurrence of the late allergic response was determined by a two-fold increase in the transpulmonary pressure from the baseline values. The microvascular permeability in the trachea was assessed by an index defined as the ratio of the area of vasculature labelled by Monastral blue dye (area density %).Significant microvascular permeability and eosinophil accumulation were observed during the late allergic response. Both the bradykinin and substance P concentrations in the bronchoalveolar lavage fluid were increased during the late allergic response. Pretreatment with HOE 140 suppressed the substance P elevation. Both HOE 140 and CP 96,345 also inhibited the airway microvascular permeability during the late allergic response without affecting the eosinophil accumulation in the airways.These findings suggest that bradykinin-mediated sensory nerve activation may play a role in microvascular permeability during the late allergic response in guinea-pigs.

Specific bronchial challenges provide information about the relationship between inhaled dose of allergen and change in lung function, but the intermediate pathways remain largely obscure. The aim of this study was to investigate the relationships between the early asthmatic response and 1) the inhaled dose of wheat flour, 2) the concentration of wheat flour, 3) the duration of the exposure, and 4) the deactivation of inhaled allergens and mediators.Thirty-one patients with occupational asthma to wheat flour were studied. Particle aerosols were generated by a computer-controlled aerosoliser and the results were expressed as the provocative dose causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20). The cumulative dose (from the beginning of the challenge), the last inhaled dose, and an estimated dose (taking into account exponential deactivation), were calculated.Twenty patients had high reactivity to flour (reaching a PD20 value). Eleven patients had intermediate reactivity (no measurable PD20 but significantly greater fall in FEV1 compared with lactose challenge). A better correlation between change in FEV1 and dose was obtained for the estimated dose than for the cumulative or last inhaled dose.The bronchial response to wheat flour can be measured by the individual specific hyperreactivity and is expressed by provocative dose of flour. However, deactivation of the allergen and mediators has to be taken into account. This problem can be addressed by using a mathematical model. Eur Respir J 2002; 20: 409-416.