. Effect of lung function and mode of inhalation on penetration of aerosol into the human lung. The method using radioactive tracer particles has been applied to study the effect of the mode of inhalation of aerosols on the depth of deposition in the lungs of 50 patients with airways obstruction. The findings show that the penetration of particles is directly related to: (1) volume inspired per breath (VI); (2) forced expiratory volume in one second (FEVY); and inversely related to (3) flow rate during inhalation (V). In mathematical terms, alveolar deposition (%)= 40 3 (VI)+ 10-98 (FEV1)-0 75 (V)+40 4; for this regression F=4-41 and P<001.Topical administration of drugs into the bronchial tree by inhalation of aerosol often has advantages over the oral and parenteral routes, particularly in patients with reversible airways obstruction. The dose is relatively small (Lal et al., 1972) and response may be more rapid (Plit et al., 1972). The main benefit of this route, however, is that high levels of the drug are concentrated at the site of action in the lung, giving the desired therapeutic action while minimising undesired systemic side effects.The efficacy of topical therapy depends on the proportion of the inhaled drug which is deposited in the lung (Blackwell et al., 1974) and, for certain drugs, that proportion that is retained in the more peripheral parts (Godfrey et al., 1974). Some of the factors which determine penetrance of aerosol have long been known to particle physicists (Hatch and Gross, 1964
MethodThe tracer technique used here to assess depth of deposition and clearance of inhaled particles in humans has been fully reported by . Polystyrene particles (5±0 7 um) were generated by a spinning disc (May, 1949) and inhaled via the mouth of the patients seated upright. The particles were tagged unleachably (Few et al., 1970) with the gamma-emitting radionuclide teehnetium-99m (99mTc). The volume inspired in a single breath (Vi), 0 1 1, 0 30, 0 50, 0'75 or 0-88 litre, was randomly allocated to each patient and determined by an automatic valve. After inspiration there was an obligatory 3-second breath-holding pause before exhalation. The average flow rate during inhalation was measured by a pneumotachograph. The mean, range, and standard deviation (SD) of the flow rate during inhalation (V) for the 44 patients for whom measurements were available were 25'4 (13 3-50 4; SD±7 9) 1/min. Immediately after inhalation the patients washed out their mouths and then swallowed some water to remove radioaerosol from the oropharynx and oesophagus.Immediately afterwards and six hours later gamma radiation from the patients' lungs was counted by 194