Predictive factors for a shortened methacholine challenge protocol in children

Respir Med. 2020 Jan:161:105823. doi: 10.1016/j.rmed.2019.105823. Epub 2019 Nov 16.


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.

Keywords: Bronchoprovocation; Methacholine challenge; Pediatrics; Shortened protocol.

MeSH terms

  • Adolescent
  • Asthma / diagnosis*
  • Asthma / physiopathology
  • Child
  • Cohort Studies
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Methacholine Chloride*
  • Predictive Value of Tests
  • Retrospective Studies
  • Time Factors


  • Methacholine Chloride