Why is a methacholine (MCh) challenge performed?

Why is a Methacholine Challenge Test Performed?

A methacholine challenge test is primarily performed to diagnose bronchial airway hyperreactivity in patients with suspected asthma when traditional diagnostic methods have not established or eliminated the diagnosis. 1

Indications for Methacholine Challenge Testing

Methacholine challenge testing (MCT) is most valuable in the following scenarios:

• When asthma is suspected but spirometry before and after bronchodilator administration has not confirmed the diagnosis
• For patients with symptoms suggesting asthma such as:
  • Wheezing, dyspnea, chest tightness, or cough with exposure to cold air
  • Symptoms after exercise
  • Symptoms during respiratory infections
  • Symptoms following workplace inhalant exposures
  • Symptoms after allergen exposure
• In the evaluation of occupational asthma
• When the pretest probability of asthma is intermediate (30-70%)

Clinical Value of the Test

The methacholine challenge test has specific clinical utility:

1. Ruling out asthma: MCT is more useful in excluding a diagnosis of asthma than confirming one due to its high negative predictive value 1
2. Detecting airway hyperresponsiveness: The test assesses the degree of bronchial hyperreactivity, which is a key feature of asthma 2
3. Occupational asthma evaluation: It's particularly valuable in workplace-related respiratory symptoms 1
4. Monitoring treatment response: Sometimes used to assess response to asthma therapy, though this use is less established 1

How the Test Works

During a methacholine challenge test:

1. The patient inhales increasing concentrations of methacholine, a substance that causes bronchoconstriction in hyperreactive airways
2. Lung function (typically FEV1) is measured after each dose
3. A significant decrease in FEV1 (typically ≥20% from baseline) indicates airway hyperresponsiveness 1, 3
4. The test is considered positive if this threshold is reached, suggesting possible asthma

Interpreting Results

• Negative test: If no significant decrease in FEV1 occurs even at the highest methacholine concentration (PC20 > 16 mg/ml), asthma is unlikely 4
• Positive test: A significant decrease in FEV1 at low methacholine concentrations (PC20 < 1 mg/ml) has high specificity for asthma 4
• Borderline results: Values between these extremes are consistent with, but not diagnostic of, asthma 1

Important Considerations and Limitations

• False positives: Bronchial hyperresponsiveness can occur in conditions other than asthma, including COPD, allergic rhinitis, cystic fibrosis, and bronchitis 1, 2
• False negatives: Recent use of asthma medications, especially bronchodilators and corticosteroids, can suppress airway responsiveness 2
• Safety concerns: The test carries a risk of severe bronchoconstriction, requiring appropriate safety measures and contraindications to be observed 3

Contraindications

Methacholine challenge testing should not be performed in patients with:

• Baseline FEV1 < 60% predicted or < 1.5 L in adults 3
• Clinically apparent asthma or wheezing (due to risk of severe bronchoconstriction) 3
• Recent myocardial infarction or stroke (within 3 months) 1
• Uncontrolled hypertension or aortic aneurysm 3
• Hypersensitivity to methacholine or other parasympathomimetic agents 3

Conclusion

The methacholine challenge test serves as a valuable diagnostic tool when asthma is suspected but not confirmed through standard methods. Its greatest strength lies in its ability to rule out asthma when negative, while positive results must be interpreted in the context of the patient's clinical presentation and other diagnostic findings.