Values for Methacholine and Exercise Challenge Tests
For methacholine challenge testing, a positive result is defined as a PC20 (provocative concentration causing a 20% fall in FEV1) of less than 8 mg/ml, with values less than 1 mg/ml indicating moderate to severe bronchial hyperresponsiveness. 1, 2
Methacholine Challenge Test Interpretation
Standard PC20 Classification
| PC20 (mg/ml) | Interpretation |
|---|---|
| > 16 | Normal bronchial responsiveness |
| 4.0-16 | Borderline bronchial hyperresponsiveness |
| 1.0-4.0 | Mild bronchial hyperresponsiveness (positive test) |
| < 1.0 | Moderate to severe bronchial hyperresponsiveness |
This classification system is recommended by the American Thoracic Society 1 and is reflected in FDA labeling for methacholine 2.
Calculation of PC20
PC20 is calculated using the following formula:
PC20 = antilog [log C1 + (log C2 - log C1)(20 - R1)/(R2 - R1)]
Where:
- C1 = second-to-last methacholine concentration (< 20% FEV1 decrease)
- C2 = last methacholine concentration (≥ 20% FEV1 decrease)
- R1 = % fall in FEV1 after C1
- R2 = % fall in FEV1 after C2
Clinical Significance of PC20 Values
- PC20 < 1 mg/ml: High specificity and positive predictive value for asthma 3
- PC20 1-4 mg/ml: Mild bronchial hyperresponsiveness, consistent with but not diagnostic of asthma
- PC20 4-16 mg/ml: Borderline bronchial hyperresponsiveness, may be seen in patients with allergic rhinitis without asthma
- PC20 > 16 mg/ml: Normal bronchial responsiveness, effectively rules out current asthma when symptoms are present 1, 3
Exercise Challenge Test Interpretation
For exercise challenge testing, a positive result is defined as a fall in FEV1 of >10% from baseline after standardized exercise 4.
The severity of exercise-induced bronchoconstriction (EIB) can be classified based on the maximum percent fall in FEV1:
- Mild: 10-24% fall in FEV1
- Moderate: 25-49% fall in FEV1
- Severe: ≥50% fall in FEV1
Important Considerations
Test Repeatability
Short-term repeatability studies show that 95% confidence intervals for repeat determinations of methacholine PC20 lie within ±1.5 doubling doses 1. This means if a PC20 is measured as 4 mg/ml, a repeat test 2 weeks later will give a PC20 between 1.5 and 12 mg/ml in 95% of cases.
False Positives and Negatives
False positives (PC20 < 8 mg/ml without asthma) may occur in:
- Patients with allergic rhinitis (about 30% have PC20 in borderline range)
- Smokers with COPD
- Recent respiratory infections
- After exposure to air pollutants 1, 2
False negatives may occur when:
- Patient is taking anti-inflammatory medications
- Testing occurs outside allergen season for seasonal asthma
- Occupational asthma is triggered by a specific agent not used in testing 1
Pretest Probability Considerations
The negative predictive power of methacholine challenge testing is >90% when the pretest probability of asthma is 30-70% 1. This makes it particularly useful for ruling out asthma in patients with suggestive symptoms but unclear diagnosis.
Alternative Approaches
Some researchers have proposed a 2-tiered protocol using PC10 (10% fall in FEV1) as an initial screening measure. A PC10 ≤ 1 mg/ml has shown high sensitivity (86%) and specificity (98%) for identifying bronchial hyperresponsiveness 5, potentially reducing the need for higher doses that might cause severe bronchoconstriction.
When interpreting these test results, always consider the clinical context, medication history, and presence of other conditions that might affect airway responsiveness to ensure accurate diagnosis and appropriate management of respiratory symptoms.