What is a methacholine (MCh) challenge?

From the Guidelines

A methacholine challenge is a diagnostic test used to assess airway hyperresponsiveness in patients suspected of having asthma, particularly useful when asthma is suspected but standard spirometry results are normal 1. The test involves inhaling increasing concentrations of methacholine, a substance that causes bronchoconstriction (airway narrowing) in sensitive individuals. The procedure typically starts with baseline spirometry measurements, followed by inhalation of nebulized methacholine in progressively higher doses, and lung function is measured using spirometry to detect any reduction in forced expiratory volume (FEV1) 1. A positive test is generally defined as a 20% or greater decrease in FEV1 from baseline, indicating airway hyperreactivity consistent with asthma 1. The test works because methacholine activates muscarinic receptors in airway smooth muscle, causing contraction and narrowing in hyperresponsive airways. Some key points to consider when performing a methacholine challenge include:

• The test is more useful in excluding a diagnosis of asthma than in establishing one, as its negative predictive power is greater than its positive predictive power 1
• Patients should avoid bronchodilators, antihistamines, and certain foods before testing as directed by their healthcare provider, as these can affect results
• The test may cause mild shortness of breath, cough, chest tightness, wheezing, chest soreness, or headache, but these symptoms are typically mild and short-lived 1
• The results of the test are based on the PC20 or the delivered dose of methacholine resulting in a 20% fall in FEV1 (provocative dose (PD20)), with the latter being the preferred method 1

From the FDA Drug Label

A positive methacholine challenge test is a ≥ 20% reduction in the FEV1 (after Provocholine oral inhalation) compared with the mean post-diluent FEV1. Calculate and record post-diluent FEV1 value before the methacholine challenge test is started Express airway hyperreactivity as the provocative Provocholine concentration (mg/mL) providing a fall in FEV1 of ≥ 20% (PC20) when the methacholine challenge test is dosed using either the 5-breath dosimeter method or the 2-minute tidal breathing method, or as the provocative Provocholine dose (mcg) providing a fall in FEV1 of ≥ 20% (PD20) when using the 2-minute tidal breathing method

A methacholine challenge is a test used to assess airway hyperreactivity by measuring the response of the airways to increasing concentrations of methacholine, a substance that can cause airway constriction. The test involves inhaling methacholine through a nebulizer and measuring the resulting change in FEV1 (forced expiratory volume in one second). A positive result is defined as a ≥ 20% reduction in FEV1 compared to the baseline value 2. The test can be used to diagnose asthma and other respiratory conditions, and to assess the severity of airway hyperreactivity 2.

Key points:

• The test involves inhaling methacholine through a nebulizer
• The response is measured by changes in FEV1
• A positive result is defined as a ≥ 20% reduction in FEV1
• The test can be used to diagnose asthma and other respiratory conditions
• The test can be used to assess the severity of airway hyperreactivity 2 2

From the Research

Definition of Methacholine Challenge

• A methacholine challenge is a medical test used to assess airway hyperresponsiveness, often in the diagnosis of asthma 3, 4, 5.
• The test involves inhaling increasing concentrations of methacholine, a substance that can trigger airway constriction, and measuring the response of the airways 5.
• The goal of the test is to determine the concentration of methacholine that causes a 20% drop in forced expiratory volume in 1 second (FEV1), known as the provocative concentration of methacholine producing a 20% fall in FEV1 (PC20) 3, 4.

Procedure and Safety

• The test is typically performed in a controlled medical setting, with the patient inhaling methacholine through a nebulizer or inhaler 5.
• The safety of the test has been established, even in patients with low baseline FEV1 values (< 60% predicted) 6.
• The test is generally well-tolerated, with few adverse sequelae reported 6.

Diagnostic Characteristics

• The methacholine challenge test has a sensitivity of 77% and a specificity of 96% for diagnosing asthma, with a threshold PC20 of 8 mg/mL 4.
• The test's performance characteristics can vary depending on factors such as race, atopy, and baseline FEV1 values 4, 7.
• The test can be used to rule out a diagnosis of asthma, but a positive result is not specific for asthma and can be seen in other conditions 5.

Comparison with Other Diagnostic Tests

• The methacholine challenge test has been compared to other diagnostic tests, such as the bronchodilation test with salbutamol, and has been found to provide different information 7.
• The methacholine challenge test may be more sensitive for diagnosing asthma than the bronchodilation test, but the two tests do not identify the same population of asthmatics 7.