Human variation in the peripheral air-space deposition of inhaled particles

Intersubject variability in both peripheral air-space dimensions and breathing pattern [tidal volume (VT) and respiratory frequency (f)] may play a role in determining intersubject variation in the fractional deposition of inhaled particles that primarily deposit in the lung periphery (i.e., distal to conducting airways). In healthy subjects breathing spontaneously at rest, we measured the deposition fraction (DF) of a 2.6-μm monodisperse aerosol by Tyndallometry while simultaneous measurements of VT and f were made. Under these conditions particle deposition occurs primarily in the peripheral air spaces of the lung. As an index of peripheral air-space size, we used measurements of aerosol recovery (RC) as a function of breath-hold time (t). In each subject, we measured RC (aerosol expired/aerosol inspired) of a 1.0-μm monodisperse aerosol as a function of breath-hold time for inspiratory capacity breaths of aerosol. The half-time (t( 1/2 )) (the breath-hold time to reach 50% RC with no breath hold) is proportional to a mean diameter (D) of air spaces filled with aerosol. In the 10 subjects studied, we found a variable DF, range 0.04-0.44 [0.25 ± 0.12 (SD)]. DF correlated most closely with 1/f, or the period of breathing (r = 0.96, P < 0.01). There was no significant correlation between DF and t( 1/2 ) as an index of peripheral air-space size. In fact there was little deviation in t( 1/2 ) in these normal subjects [coefficient of variation (CV) = 0.12]. Finally, when breathing patterns (VT and f) were controlled in six subjects, DF was much less variable than for the same subjects breathing spontaneously [CV = 0.13 (controlled) vs. CV = 0.6 (spontaneous)]. We conclude that normal intersubject variability in the peripheral air-space deposition of inhaled particles is primarily influenced by variation in breathing pattern.