Direct bronchoprovocation test methods: history 1945–2018

ABSTRACT

Introduction: 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 circumstances, a methacholine PD₂₀ > 400 μg excludes current asthma with reasonable certainty. PD₂₀ values >25 μg and ≤400 μg will have a variable specificity and positive predictive value for asthma which increases the lower the PD₂₀ and the higher the pre-test probability for a diagnosis of asthma. A PD₂₀ ≤25 μg has high specificity and low sensitivity for asthma.

KEYWORDS:

• Methacholine
• histamine
• methods standardization
• deep inhalation bronchoprotection
• airway hyperresponsiveness (ahr)
• asthma
• inhalation provocation tests

Acknowledgments

The authors thank Jacquie Bramley for assistance in preparation of this manuscript.

Declaration of interest

DW Cockcroft is a member of the medical advisory board of Methapharm Canada (manufacturers of methacholine). The remaining authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.