title: Intersubject variability in particle deposition does not explain variability in responsiveness to methacholine.
abstract: How variable is the deposition of inhaled methacholine (MCH) in the respiratory tract during a challenge test? Does this variability contribute to the variability of airway responsiveness? To examine these questions we estimated the deposition of polydisperse MCH droplets by measuring the deposition of surrogate diethylhexyl sebacate (DEHS) droplets that were similar in size (1.5 microns) but monodisperse. Light scattering photometry and flow measurements were used to compute inspired and expired DEHS particle number. Deposition of DEHS during 4 breaths was measured twice at baseline and after every dose of MCH during an abbreviated challenge test in 16 subjects. Deposition was then compared with reactivity. Reactivity to MCH was expressed as the dose-response slope; it was calculated as percent final change in FEV1/cumulative dose MCH inhaled. Dose-response slopes ranged from zero (nonreactive) to -15.0 (very reactive) %/mumol (mean -3.2 +/- 5.3 SD). Seven subjects had a 20% or greater decrement in FEV1 after their highest MCH dose. Baseline DEHS deposition, which ranged from 66 to 84% (mean 77 +/- 5 SD), was not significantly different between responders and nonresponders and was not a significant predictor of the dose-response slope. Reactivity was significantly associated with an increase in deposition produced by MCH (p less than 0.007). This increase was small, however (relative change less than 7%), so that the effect on the deposited dose of MCH was minimal. We conclude that, with the breathing pattern used, individual differences in DEHS (and MCH) deposition were small and contributed little to intersubject variability of responsiveness to inhaled MCH.
authors.affiliation: Respiratory Biology Program, Harvard School of Public Health, Boston, Massachusetts 02115.
authors.forename: P J
authors.initials: PJ
authors.lastname: Anderson
authors.forename: E
authors.initials: E
authors.lastname: Garshick
authors.forename: J D
authors.initials: JD
authors.lastname: Blanchard
authors.forename: H A
authors.initials: HA
authors.lastname: Feldman
authors.forename: J D
authors.initials: JD
authors.lastname: Brain
mesh_terms: D000328:Adult; D000336:Aerosols; D001985:Bronchial Provocation Tests; D003652:Decanoic Acids / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000493:pharmacokinetics* / Q000494:pharmacology; D008875:Middle Aged; D010316:Particle Size
chemical_list: D000336:Aerosols; D003652:Decanoic Acids; D016210:Methacholine Chloride; C037634:di-2-ethylhexyl sebacate