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Airway hyperresponsiveness to methacholine in 7-year-old children: sensitivity and specificity for pediatric
Chris Carlsten1, Helen Dimich-Ward, Alexander Ferguson
1Department of Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, University of British Columbia, Vancouver, BC. chris.carlsten@vch.ca
Insights
The PC(20) methacholine challenge test for childhood asthma diagnosis shows a PC(20) 3 mg/ml cut-off offers the best balance of sensitivity and specificity. This finding aids in understanding airway hyperresponsiveness in pediatric asthma diagnosis.
Area of Science:
- Pediatric Pulmonology
- Allergy and Immunology
- Diagnostic Accuracy in Asthma
Background:
- Understanding the operating characteristics of PC(20) cut-offs is crucial for diagnosing asthma in children.
- Current cut-offs for airway hyperresponsiveness lack comprehensive evaluation in pediatric populations.
- This study examines a unique birth cohort to address these knowledge gaps.
Purpose of the Study:
- To determine the sensitivity and specificity of various PC(20) cut-off values for diagnosing asthma in children.
- To evaluate incremental PC(20) thresholds for allergist-diagnosed asthma.
- To inform optimal cut-off selection for methacholine challenge testing.
Main Methods:
- A birth cohort of children at high risk for asthma underwent airway reactivity assessment at age 7.
- Methacholine PC(20) values were determined using standard techniques with interpolation.
- Asthma diagnosis was made by a pediatric allergist blinded to methacholine challenge results.
- Sensitivity and specificity were calculated for PC(20) cut-offs ranging from 1.0 to 8.0 mg/ml, analyzed via ROC curves.
Main Results:
- 20.1% of the 348 children were diagnosed with asthma.
- For all children and females, the optimal PC(20) cut-off was 3 mg/ml (sensitivity 80.0%, specificity 49.1%), and the balanced cut-off was 2 mg/ml (sensitivity 63.1%, specificity 64.7%).
- For males, both optimal and balanced PC(20) cut-offs were 2 mg/ml.
Conclusions:
- A PC(20) cut-off of 3 mg/ml provided the maximal sum of sensitivity and specificity for this high-risk pediatric asthma cohort.
- The choice of PC(20) cut-off should consider the desired balance between sensitivity and specificity for clinical application.
- Findings suggest that PC(20) 3 mg/ml is a valuable threshold for methacholine challenge testing in 7-year-olds at high risk for asthma.
Background:
The operating characteristics of PC(20) values used as cut-offs to define airway hyperresponsiveness, as it informs the diagnosis of asthma in children, are poorly understood. We examine data from a unique cohort to inform this concern.
Objective:
Determine the sensitivity and specificity of incremental PC(20) cut-offs for allergist-diagnosed asthma.
Methods:
Airway reactivity at age 7 was assessed in children within a birth cohort at high risk for asthma; PC(20) for methacholine was determined by standard technique including interpolation. The diagnosis of asthma was considered by the pediatric allergist without knowledge of the methacholine challenge results. Sensitivity and specificity were calculated using a cross-tabulation of asthma diagnosis with incremental PC(20) cut-off values, from 1.0 to 8.0 mg/ml, and plotted as receiver operator characteristic (ROC) curves. The "optimal" cut-off was defined as that PC(20) conferring maximal value for sensitivity plus specificity while the "balanced" cut-off was defined as that PC(20) at which sensitivity and specificity were most equal.
Results:
70/348 children (20.1%) were diagnosed with asthma. The optimal and balanced PC(20) cut-offs, both for all children and for females alone, were respectively 3 mg/ml (sensitivity 80.0%, specificity 49.1%) and 2 mg/ml (sensitivity 63.1%, specificity 64.7%). For males alone, the "optimal" and "balanced" PC(20) cut-offs were both 2 mg/ml.
Conclusion:
For this cohort of 7-year olds at high risk for asthma, methacholine challenge testing using a cut-off value of PC(20) 3 mg/ml conferred the maximal sum of specificity plus sensitivity. For contexts in which higher sensitivity or specificity is desired, other cut-offs may be preferred.
Related Concept Videos
Asthma I: Introduction
Asthma: Pathogenesis and Management
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
Asthma-IV: Diagnostic and Management
Clinical Assessment for Asthma:
This is the first step in diagnosing and managing asthma. It includes:
Asthma-II: Pathophysiology and Classification
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
Asthma-I: Introduction
Asthma III: Clinical Manifestations

