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

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). 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. 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. All 113 patients with CVA responded to PD₂₀MCh and 96% and 69% responded to PC₂₀AMP, if we used PC₂₀ 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.