Comparison of direct and indirect bronchoprovocation testing using ventilator-acquired pulmonary mechanics in healthy...

Airway hyperresponsiveness (AHR) is a key feature of asthma and can be measured using bronchoprovocation. Direct (methacholine, MCh) or indirect (adenosine-5-monophosphate, AMP; or mannitol) bronchoprovocants are used in human patients, the latter inducing AHR only with pre-existing airway inflammation. The present study compared the responses to direct (MCh) and indirect (mannitol, AMP) bronchoprovocation in healthy and asthmatic cats (n=6/group). The order of bronchoprovocant was randomized using a published table of random numbers and there was a 1-month washout before crossover to the next treatment. Pulmonary mechanics were measured in anesthetized and mechanically ventilated cats using a critical care ventilator. Saline at baseline and increasing doses of each bronchoprovocant were aerosolized for 30 s, followed by 4 min of data collection between doses. The endpoint for each bronchoprovocant was reached when airway resistance exceeded 200% of baseline values (EC200Raw). There was a significant difference (P<0.001) in the airway response of asthmatic vs. healthy cats over the range of MCh concentrations, despite there being no significant difference in the EC200Raw between the groups. Response to MCh was significantly greater (P<0.05) in asthmatic than in healthy cats at MCh concentrations as low as 0.0625 mg/mL. For AMP, a small subset of asthmatics (n=2/6) responded at low concentrations; four asthmatic cats and all healthy cats failed to respond even to the highest concentrations of AMP. One asthmatic cat but no healthy cats responded to mannitol. In conclusion, MCh discriminated asthmatic from healthy cats but neither AMP nor mannitol was an effective bronchoprovocant in this model.