Intersubject variability in particle deposition does not explain variability in responsiveness to methacholine.

Area of Science:

• Respiratory Physiology
• Pulmonary Medicine
• Pharmacology

Background:

• Airway hyperresponsiveness is a hallmark of asthma.
• Methacholine (MCH) challenge tests are used to assess airway responsiveness.
• Variability in MCH deposition may influence test results.

Purpose of the Study:

• To quantify the variability of inhaled methacholine (MCH) deposition in the respiratory tract.
• To determine if deposition variability contributes to intersubject differences in airway responsiveness.
• To investigate the relationship between MCH deposition and airway reactivity.

Main Methods:

• Diethylhexyl sebacate (DEHS) droplets (1.5 microns) were used as surrogates for MCH deposition measurement.
• Light scattering photometry and flow measurements assessed DEHS deposition during 4 breaths.
• Deposition was measured at baseline and after MCH doses in 16 subjects.
• Airway responsiveness was quantified as the dose-response slope of FEV1 change versus cumulative MCH dose.

Main Results:

• Baseline DEHS deposition ranged from 66-84% (mean 77%), with no significant difference between responders and non-responders.
• Baseline deposition did not predict the dose-response slope.
• MCH reactivity was associated with a small, non-significant increase in DEHS deposition (relative change <7%).

Conclusions:

• Individual differences in inhaled methacholine (MCH) deposition are minimal with the breathing pattern used.
• Deposition variability contributes little to the intersubject variability of airway responsiveness to MCH.
• Factors other than deposition likely explain most of the variability in MCH challenge test outcomes.