ATS Pulmonary Function Laboratory Manual

ATS Pulmonary Function Laboratory Management & Procedure Manual | 3rd Edition

Effective Date: 2018 Version #2

Chapter 12

Procedure Name: Methacholine Challenge Test

Purpose or Principle Asthma is a chronic inflammatory disorder of the airways. The airway inflammation contributes to airflow limita- tion, bronchial hyperresponsiveness, respiratory symptoms, and disease chronicity. The airflow limitation (or air- way narrowing) is reversible either spontaneously or with treatment. There is also an associated increase in existing bronchial hyperresponsiveness to a variety of stimuli (1, 2). Improvement in airflow following inhalation of a bronchodilator is generally accepted as indicative of revers- ible airway obstruction. However, the evaluation of bronchial hyperresponsiveness is often indicated, especially in patients with unclear or nonspecific symptoms (e.g., symptoms of asthma with normal spirometry and no broncho- dilator response). Bronchial provocation (challenge) testing may be performed with a variety of stimuli that can be divided into two groups: direct and indirect agents. Direct stimulants provoke airway constriction by acting directly on the bronchial smoothmuscle receptors, bron- chial vascular endothelial cells, and mucus-producing cells. Direct stimulants include methacholine and histamine. Indirect stimulants provoke airway constriction indirectly by releasing a number of mediators from inflamma- tory cells within the airway. These mediators then stimulate specific receptors on bronchial smooth muscle. Indirect stimulants include exercise, eucapnic hyperventilation, mannitol, adenosine, allergens, and hypertonic and hypo- tonic aerosols. The 1999 ATS Guideline for methacholine challenges recommended the 2-minute tidal breathing method and the 5-breath dosimeter method (3). Although calculations estimated that the dose of methacholine delivered at each step would be twice as high with the tidal breathing method, it was expected that deep breaths with a 5-second breath-hold at total lung capacity (TLC) would allow better distribution and retention of the aerosol and early studies did suggest that the two delivery methods gave similar results (3). More recent studies show small differences, consistent with those dose-delivery considerations, in patients with more severe asthma, reacting to low levels of methacholine, but results are less comparable in patients with less airway hyperresponsiveness (4–6).This means that patients who would be considered to have mild hyperresponsiveness by the 2-minute tidal breathing method will be considered normal by the dosimeter method. This false negative rate was 25% of all tests and 50% of those with mild-moderate airway hyperresponsiveness in one series (7). This effect is seen in those considered normal and those with mild asthma, but is lost with more severe disease (6–9). For these reasons, methods requiring deep inhalations to TLC during aerosol delivery are no longer recommended, and only the tidal breathing method will be described in this procedure (10).

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