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Published on: July 10, 2018
Predictive factors for a shortened methacholine challenge protocol in children
Frédéric Proulx1, Sophie Laberge1, Nicoleta Macovoz2
1Sainte-Justine University Hospital Center, Division of Respiratory Medicine, Department of Pediatrics. Montréal, Québec, Canada; Université de Montréal, Montréal, Québec, Canada.
Insights
This study identified predictors to safely shorten the pediatric methacholine challenge test by quadrupling concentrations. Objective pulmonary function measures can personalize and expedite asthma diagnosis in children.
Area of Science:
- Pediatric Pulmonology
- Respiratory Medicine
- Clinical Diagnostics
Background:
- The methacholine challenge test is crucial for asthma diagnosis in children but is often time-consuming.
- Quadrupled concentration protocols shorten testing in adults, but their safety and efficacy in children are not well-established.
- Predictors for safely using a quadrupled concentration protocol in pediatric patients are currently unidentified.
Purpose of the Study:
- To identify clinical predictors associated with the preclusion of a quadrupled concentration protocol in children undergoing methacholine challenge testing.
- To establish criteria for safely omitting lower methacholine concentrations in pediatric asthma diagnosis.
Main Methods:
- A derivation cohort (n=399) and a validation cohort (n=195) of subjects under 18 years were analyzed.
- Eligibility to omit 0.5 mg/ml and 2.0 mg/ml methacholine concentrations was determined by PC20 values.
- Bivariate analysis identified baseline characteristics associated with precluding the quadrupled protocol; an algorithm was derived and validated.
Main Results:
- Specific pulmonary function measures, including baseline FEV1 ≤90% predicted, FEV1/FVC ≤0.8, FEF25-75 ≤70% predicted, and a ≥10% FEV1 decrease with prior concentration, precluded omitting 0.5 mg/ml.
- Baseline FEF25-75 ≤70% predicted and a ≥10% FEV1 drop with the previous concentration precluded omitting 2.0 mg/ml.
- The derived criteria achieved 74.0% sensitivity and 84.6% specificity in the validation cohort.
Conclusions:
- Objective pulmonary function measures were identified as predictors for safely shortening the pediatric methacholine challenge test.
- These findings support personalizing and expediting the methacholine challenge protocol in children by quadrupling concentrations.
- This approach has the potential to improve the efficiency of asthma diagnosis in pediatric populations.
Rationale:
Although the methacholine challenge test is useful in the diagnosis of asthma, it is time-consuming in children. While protocols that quadruple methacholine concentrations are widely used in adults to shorten testing time, this has not been evaluated in children. Studies have not identified predictors associated with the safe use of a quadrupled concentration protocol.
Objectives:
To identify clinical predictors associated with the preclusion of a quadrupled concentration protocol in children.
Methods:
We included subjects <18 years who performed a methacholine challenge tests between April 2016 to February 2017 (derivation cohort) and March 2017 to September 2017 (validation cohort). We determined the eligibility of a subject to omit the 0.5 mg/ml and 2.0 mg/ml concentrations based on their PC20 and identified baseline characteristics that are associated with the preclusion of the quadrupled protocol using bivariate analysis. The derived algorithm was applied to the validation cohort.
Results:
We included 399 and 195 patients in the derivation and validation cohorts, respectively. A baseline FEV1 ≤90% predicted, FEV1/FVC ≤0.8, FEF25-75 ≤70% predicted, and a decrease in FEV1 ≥10% with the previous concentration significantly precluded the omission of the 0.5 mg/ml concentration. A baseline FEF25-75 ≤70% predicted and a drop in FEV1 ≥10% with the previous concentration significantly precluded the omission of the 2.0 mg/ml concentration. Applying these 4 criteria to the validation cohort resulted in an overall sensitivity and specificity of 74.0% and 84.6%, respectively.
Conclusions:
We identified objective pulmonary function measures that may personalize and shorten the methacholine challenge protocol in children by quadrupling concentrations.
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