Methacholine inhalation challenge: A shorter, cheaper and safe approach

Increased nonspecific bronchial hyperresponsiveness to pharmacological agents such as histamine or methacholine (MCh) is a hallmark of asthma. The measurement of airway reactivity is quite sensitive but testing is tedious, and time and money consuming. The present aim was, therefore, to design the shortest possible, yet safe inhalation challenge protocol applicable for a lung function referral centre. All records of studies performed in our institution during 1996 were analyzed retrospectively with a baseline ratio (bl) of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ≥0.7 (n=449). It was questioned what the initial dose should be, and whether some inhalation steps could have been skipped without losing pertinent information and/or causing an adverse response (a fall in FEV1>40%). When unavailable, provocative dose causing a 20% fall in FEV1 (PD20) values were obtained by linear inter- or extrapolation of the existing data. The present study showed that three-fold concentration steps could have been employed with minimal change in outcome. Only 15/449 patients (3.3%) would have experienced a severe response. Five subjects (of 169, 3.0%) with FEV1/FVCbl 0.7-0.8 reacted to inhalation up to 0.073 μmol. Four subjects (of 280, 1.4%) with FEV1/FVCbl≥0.8 reacted to inhalation up to 0.219 μmol. The authors suggest that: 1) an initial dose of 0.219 μmol (initial concentration=0.21 mg·mL^-1) may be used when the baseline ratio of forced expiratory volume in one second to forced vital capacity ≥0.8 and 0.073 μmol (initial concentration=0.07 mg·mL^-1) when the baseline ratio is <0.8; 2) a tripling dose protocol is easier to perform, cheaper and 30.2% faster, yet just as safe; and 3) other abbreviated protocols used in epidemiologic settings may not be applicable in a referral centre setting.