Direct bronchoprovocation test methods: history 1945–2018

ABSTRACTIntroduction: Bronchoprovocation inhalation challenge tests with direct acting stimuli (e.g. methacholine) are widely used clinically to aid in the diagnosis of asthma.Areas covered: The history of direct challenges with histamine and muscarinic agonists is reviewed. This began with parenteral administration of stimuli with responses monitored clinically and by VC, progressing to inhalation dose-response challenges monitored by FEV1 and FEV1/VC ratio, both (the challenge method and the technology to measure FEV1) developed by Robert Tiffeneau in the mid-1940s. Careful standardization of methods has become appreciated albeit after-the-fact. Recent guidelines recommend standardizing the methacholine PD20 at 400 μg above which a methacholine challenge is considered negative.Conclusions: The methacholine inhalation test is highly sensitive for a diagnosis of current asthma when symptoms under evaluation are clinically current and when methacholine is inhaled without deep inhalations. Under these circu...