Airway Hyperresponsiveness in Asthma: Measurement and Clinical Relevance

Airway hyperresponsiveness is a characteristic feature of asthma, and its measurement is an important tool in its diagnosis. With a few caveats, methacholine bronchial provocation by a 2-minute tidal breathing method is highly sensitive; a negative test result (PC₂₀ > 16 mg/mL, PD₂₀ > 400 μg) rules out current asthma with reasonable certainty. A PC₂₀ value of less than 1 mg/mL/PD₂₀ value of less than 25 μg is highly specific (ie, diagnostic) but quite insensitive for asthma. For accurate interpretation of the test results, it is important to control and standardize technical factors that have an impact on nebulizer performance. In addition to its utility to relate symptoms such as cough, wheeze, and shortness of breath to variable airflow obstruction (ie, to diagnose current asthma), the test is useful to make a number of other clinical assessments. These include (1) evaluation of patients with occupational asthma, (2) evaluation of patients with exercise-induced respiratory symptoms, (3) evaluation of novel asthma medications, (4) evaluation of relative potency of inhaled bronchodilators, (5) as a biomarker to adjust anti-inflammatory therapy to improve clinical outcomes, and (6) in the evaluation of patients with severe asthma to rule out masqueraders such as laryngeal dysfunction. The actual mechanism of altered smooth muscle behavior in asthma that is assessed by direct (eg, methacholine) or indirect (eg, allergen) bronchial provocation remains one of the most fundamental questions related to asthma that needs to be determined. The test is underutilized in clinical practice.