Methacholine vs adenosine on intra and extrathoracic airway hyperresponsiveness in patients with cough variant asthma

Background:  Airway hyperresponsiveness (AHR) can be studied by bronchoprovocation test (BPT) using direct (methacholine – MCh) or indirect (adenosine 5′-monophosphate – AMP) stimuli. These two substances have not been compared in cough variant asthma (CVA). Objective:  We designed a randomized, single-blind, cross-over study to compare AMP and MCh in the detection of CVA. Additionally, we examined whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during MCh and AMP helped in the evaluation of CVA. Methods:  Patients with CVA with previous positive MCh BPT performed challenges with AMP and MCh. The variables were: (i) a provocative dose producing a 20% fall in forced expiratory volume in 1 s (FEV1) value (PD20MCh); (ii) a provocative dose producing a 25% fall in the maximal mid-inspiratory flow (FIF50) from baseline (PD25MCh) for MCh; (iii) a provocative concentration producing a 20% fall in FEV1 value (PC20AMP) and (iv) a provocative concentration producing a 25% fall in the FIF50 from baseline (PC25AMP) for AMP. Results:  All 113 patients with CVA responded to PD20MCh and 96% and 69% responded to PC20AMP, if we used PC20 ≤ 200 mg/ml or PC20 ≤ 100 mg/ml, respectively, with an excellent correlation between these two tests (r = 0.87 and 0.76, respectively). Extrathoracic AHR associated with AHR was found in 10% in MCh challenge and in 11% with AMP challenge and no patients had EAHR alone. Conclusion:  Adenosine challenges correlate well with MCh in patients with CVA. A minority (c. 10%) of CVA patients have EAHR as measured by these tests, while most had AHR as assessed with each of the challenge agents.