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Are the Reference Values for the Provocative Concentration of Methacholine Appropriate for Children?
Allan L Coates1, Myrtha E Reyna1,2, Cathy C Doyle3
1Division of Respiratory Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.
Insights
Pediatric breathing patterns may lead to higher methacholine deposition in the lungs per kilogram of body weight compared to adults. This finding could explain the unexpectedly high positivity rates in pediatric methacholine challenge tests.
Area of Science:
- Pediatric Pulmonology
- Respiratory Physiology
- Pharmacokinetics
Background:
- Preliminary pediatric studies show a high methacholine challenge test positivity rate (~30%) in 8-year-olds.
- Current methacholine testing guidelines for adults may not be directly applicable to children.
- Differences in breathing patterns may influence methacholine deposition in children versus adults.
Purpose of the Study:
- To investigate if pediatric breathing patterns result in greater lung deposition of methacholine on a per-kilogram body weight basis compared to adults.
- To provide a potential explanation for elevated methacholine test positivity in pediatric populations.
Main Methods:
- A breathing simulator generated age-appropriate breathing patterns for a 70 kg adult and 30/50 kg children.
- Methacholine aerosol was delivered using an AeroEclipse Breath Actuated nebulizer.
- Predicted lung deposition was calculated based on collected methacholine dose (≤5 μm particles) analyzed by HPLC, with particle size measured by laser diffraction.
Main Results:
- The predicted pulmonary dose of methacholine was 46.1 μg/kg (30 kg child), 48.6 μg/kg (50 kg child), and 36.1 μg/kg (70 kg adult).
- Pediatric breathing patterns resulted in a higher predicted pulmonary methacholine dose per kilogram of body weight compared to adult patterns.
Conclusions:
- Pediatric breathing patterns lead to increased methacholine deposition per unit of body weight.
- This finding supports the hypothesis that altered deposition may contribute to higher methacholine challenge test positivity in children.
- Further research may be needed to refine methacholine challenge testing protocols for pediatric populations.
Abstract:
Background: Preliminary data in a randomly selected pediatric cohort study in 8-year-olds suggested a rate of positivity to a methacholine challenge test that was unexpectedly high, roughly 30%. The current recommendation for a negative methacholine test is a 20% decrease in the forced expiratory volume in one second at a dose greater than 400 μg. This was derived from studies in adults using the obsolete English Wright nebulizer. One explanation for the high incidence of positivity in the study in 8-year-olds could be that children deposit more methacholine on a μg/kg basis than adults, due to differences in their breathing patterns. The purpose of this study was to determine if pediatric breathing patterns could result in a higher dose of methacholine depositing in the lungs of children based on μg/kg body weight compared with adults. Methods: An AeroEclipse Breath Actuated nebulizer delivered methacholine aerosol, generated from a 16 mg/mL solution, for one minute, using age-appropriate breathing patterns for a 70 kg adult and a 30 and 50 kg child produced by a breathing simulator. Predicted lung deposition was calculated from the collected dose of methacholine on a filter placed at the nebulizer outport, multiplied by the fraction of the aerosol mass contained in particles ≤5 μm. The dose of methacholine on the inspiratory filter was assayed by high performance liquid chromatography (HPLC). Particle size was measured using laser diffraction technology. Results: The mean (95% confidence intervals) predicted pulmonary dose of methacholine was 46.1 (45.4, 46.8), 48.6 (45.3, 51.9), and 36.1 (34.2, 37.9) μg/kg body weight for the 30 kg child, 50 kg child, and 70 kg adult, respectively. Conclusions: On a μg/kg body weight, the predicted pulmonary dose of methacholine was greater with the pediatric breathing patterns than with the adult pattern.
