Aerosol-derived airway dimensions of dog lungs in histamine-induced bronchoconstriction

Abstract

The single-breath aerosol recovery technique has been demonstrated to facilitate non-invasive assessment of effective airway diameters in anesthetized mechanically-ventilated dogs with normal airway geometry. In order to test the sensitivity of the method for the detection of magnitude and site of airway constriction, effective airway diameters were determined in dogs with airways maintained in sustained constriction by intravenous histamine. Monodisperse di- (2-ethyl-hexyl) sebacate particles (mean aerodynamic diameter ± SD, 1.17 ± 0.13 μm) were applied by the single-breath technique in nine anesthetized, paralyzed and mechanically-ventilated dogs (mean body wt. ± SD, 15.2 ± 2.4 kg; mean total lung capacity ± SD, 1102 ± 346 ml) during control conditions and steady airway constriction achieved by continuous infusion of histamine (∼ 1.7 mg kg −1 h −1). The rate of aerosol recovery during post-inspiratory breath-holding (0–10 s) was determined from instantaneous particle concentration continuously recorded at the airway opening by a miniature in-line aerosol photometer. For comparison between control and histamine-induced airway narrowing, airway diameters determined as function of volumetric lung depth were referred to the actual volume of the dog's total lung capacity and expressed as % TLC. Narrowing of airway diameters by intravenous histamine was maximal (∼ 50%) in the proximal airways (corresponding to 8% TLC) and the effect was continually fading towards peripheral airways. For deeper lung regions, i.e. beyond a volumetric depth of 19% TLC, no significant differences from control values were detectable. Airway resistance during histamine challenge, determined simultaneously by an interrupter technique, was increased by a factor of 5.7 and would be expected to result mainly from constriction of proximal airways. The marked reduction of TLC (−25%) and static (−26%) and dynamic (−38%) lung compliances (along with an increasing difference between the two) is interpreted to suggest that a major fraction of peripheral airways was constricted but was not recovered by the aerosol technique. This finding may be attributed to presence of marked unequal distribution of peripheral airway constriction, in which case effective aerosol-derived airway diameters would represent not arithmetic means but volume-weighted averages according to the fractional contribution to total airway volume at a given volumetric depth.