HUMAN TRACHEOBRONCHIAL DEPOSITION AND EFFECT OF A HISTAMINE AEROSOL INHALED BY EXTREMELY SLOW INHALATIONS

Twelve subjects inhaled the same amounts of histamine aerosol in both a normal provocation test and in a test with extremely slow inhalations (ESI), a method which gives deposition in small airways. The purpose was to compare dose-effect relationships in large (diameter >1 mm) and small (diameter <1 mm) ciliated airways. The effect on large airways was estimated by measurement of airway resistance (Raw), and the effect on small airways was measured by the single-breath nitrogen test phase III slope (N2-delta). Mouth and throat deposition of the histamine aerosol was calculated from human experimental data, and deposition in the lower airways was calculated using a computerised model for particle deposition in the lungs. The study showed that only half the dose inhaled with ESI (0.65 mg) of that inhaled with normal inhalations (1.3 mg), was needed to obtain the same degree of obstruction for large airways in spite of that the calculated deposition in large airways was 40% higher for normal inhalations than for ESI. The threefold stronger effect in large airways was probably caused by a more uniform distribution of particles within each generation with ESI compared to normal inhalations with particle deposition near the bifurcation. There was slightly higher N2-delta with ESI, and the calculated dose to the smaller airways for the same inhaled dose was 10 times higher with ESI than with normal inhalations.