ABSTRACT. Oral and nas al airways are entryways to the respiratory tract. Most people breathe through the nasal airway during rest or light exercise, then switch to oral r r r r r nasal breathing during heavy exercise or work. Resistance through the oral airways is much lower than through the n asal airways , so fewer aerosol particles are deposited in the oral airways. Aerosol drugs are usually delivered by inhalation to the lung via the oral route for that reason. Oral deposition data from humans are limited, and those available show great intersubject variability. The purpose of this study was to investigate the effects of particle size and breathing rate on the deposition pattern in a human or al airway cast with a de® ned geometry. The airway replica included the oral cavity, ph arynx, larynx, trachea, an d 3 generations of bronchi. The oral portion of the cast was molded from a dental impression of the oral cavity in a hum an volunteer, while the other airway portions of the cast were made from a cadaver. Nine different sizes of polystyrene latex¯uorescent particles in the size ran ge of 0.93± 30 m m were used in the study. Regional deposition was measured at a constant inspiratory¯ow rate of 15, 30, and 60 L min I 1 . Deposition in the oral airway appeared to increase with an increasinḡ ow rate an d particle diameter. Deposition at the highest¯ow rate of 60 L min I 1 was close to 90% for particles ) 20 m m. Particles ) about 10 m m deposited mainly in the oral cavity. Deposition ef® ciency has been found to be a unique function of the Stokes number, suggesting that impaction is the dominant deposition mech anism. Oral deposition can be approximated by a theoretical deposition model of inertial impaction in a 1808 curved tube, assuming perfect mixing in a turbulent ow. Our model suggests th at the minimum dimension near the larynx and the average cross-sectional area are important parameters for oral airway deposition; however, addition al data from the oral airway replica are needed to ascertain wh ether these are indeed the critical dimensions. Information from the present study will add to our knowledge of the deposition mech anism, the correlation of particle deposition with airway geometry, and eventually the best way to deliver aerosol drugs.

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Regional particle deposition efficiency and deposition patterns were studied experimentally in a human airway replica made from an adult cadaver. The replica includes the oral cavity, pharynx, larynx, trachea, and four generations of bronchi. This study reports deposition results in the tracheobronchial (TB) region. Nine different sizes of monodispersed, polystyrene latex fluorescent particles in the size range of 0.93-30 µm were delivered into the lung cast with the flow rates of 15, 30, and 60 l min −1 . Deposition in the TB region appeared to increase with the increasing flow rate and particle size. Comparison of deposition data obtained from physical casts showed agreement with results obtained from realistic airway replicas that included the larynx. Deposition data obtained from idealized airway models or replicas showed lower deposition efficiency. We also compared experimental data with theoretical models based on a simplified bend and bifurcation model. A deposition equation derived from these models was used in a lung dosimetry model for inhaled particles, and we demonstrated that there was general agreement with theoretical models. However, the agreement was not consistent over the large range of Stokes number. The deposition efficiency was found as a function of the Stokes number, bifurcation angle, and the diameters of parent and daughter tubes. An empirical model was developed for the particle deposition efficiency in the TB region based on the experimental data. This model, combined with the oral deposition model developed previously, can be used to predict the particle deposition for inertial effects with improved accuracy.

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While numerous devices, formulations, and spray characteristics have been shown to influence nasal deposition efficiency, few studies have attempted to identify which of these interacting factors plays the greatest role in nasal spray deposition. The deposition patterns of solutions with a wide range of surface tensions and viscosities were measured using an MRI-derived nasal cavity replica. The resulting spray plumes had angles between 29 degrees and 80 degrees and contained droplet sizes (D(v50)) from 37-157 microm. Each formulation contained rhodamine 590 as a fluorescent marker for detection. Administration angles of 30 degrees , 40 degrees , or 50 degrees above horizontal were tested to investigate the role of user technique on nasal deposition. The amount of spray deposited within specific regions of the nasal cavity was determined by disassembling the replica and measuring the amount of rhodamine retained in each section. Most of the spray droplets were deposited onto the anterior region of the model, but sprays with small plume angles were capable of reaching the turbinate region with deposition efficiencies approaching 90%. Minimal dependence on droplet size, viscosity, or device was observed. Changes in inspiratory flow rate (0-60 L/min) had no significant effect on turbinate deposition efficiency. Both plume angle and administration angle were found to be important factors in determining deposition efficiency. For administration angles of 40 degrees or 50 degrees , maximal turbinate deposition efficiency (30-50%) occurred with plume angles of 55-65 degrees , whereas a 30 degrees administration angle gave an approximately 75% deposition efficiency for similar plume angles. Deposition efficiencies of approximately 90% could be achieved with plume angles <30 degrees using 30 degrees administration angles. Both the plume angle and administration angle are critical factors in determining deposition efficiency, while many other spray parameters, including particle size, have relatively minor influences on deposition within the nasal cavity.

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Person-to-person transmission of influenza viruses occurs by contact (direct and fomites) and non-contact (droplet and small particle aerosol) routes, but the quantitative dynamics and relative contributions of these routes are incompletely understood. The transmissibility of influenza strains estimated from secondary attack rates in closed human populations is confounded by large variations in population susceptibilities. An experimental method to phenotype strains for transmissibility in an animal model could provide relative efficiencies of transmission. We developed an experimental method to detect exhaled viral aerosol transmission between unanesthetized infected and susceptible ferrets, measured aerosol particle size and number, and quantified the viral genomic RNA in the exhaled aerosol. During brief 3-hour exposures to exhaled viral aerosols in airflow-controlled chambers, three strains of pandemic 2009 H1N1 strains were frequently transmitted to susceptible ferrets. In contrast one seasonal H1N1 strain was not transmitted in spite of higher levels of viral RNA in the exhaled aerosol. Among three pandemic strains, the two strains causing weight loss and illness in the intranasally infected ‘donor’ ferrets were transmitted less efficiently from the donor than the strain causing no detectable illness, suggesting that the mucosal inflammatory response may attenuate viable exhaled virus. Although exhaled viral RNA remained constant, transmission efficiency diminished from day 1 to day 5 after donor infection. Thus, aerosol transmission between ferrets may be dependent on at least four characteristics of virus-host relationships including the level of exhaled virus, infectious particle size, mucosal inflammation, and viral replication efficiency in susceptible mucosa.