Physiological and pathological considerations for aerosol deposition: expiration and models of deposition.

Theoretical models are often used to predict fractional and regional deposition of inhaled particles in the respiratory tract. The distribution of particle diameters in the aerosol, airway geometry, breathing pattern, and local flow profiles are major determinants of deposition in the lung. However, most models predicting deposition consider airway geometry to be fixed and concentrate on inspiratory events in their calculations. When particle losses during expiration are estimated, inspiratory and expiratory flow patterns and airspace geometry are usually considered to be similar with similar effects on deposition. The theme of this presentation will be the analysis of events during expiration that influence particle deposition. In the normal lung, during quiet breathing, experiments performed on excised lungs have suggested that convective forces may be different between inspiration and expiration that significantly affect deposition. Bennett and Smaldone, in excised dog lungs, by regulating the duty cycle of tidal breathing found that more particles deposited during inspiration than expiration and that the effects were density dependent. In human subjects with obstructive lung disease, the situation is reversed. Major differences in large airway geometry between inspiration and expiration can occur with each tidal breath. Once the FEV(1) decreases to about 60% of the FVC, flow-limiting segments (FLS) are known to form in central airways. Large pressure drops can occur over short lengths of airway indicating disturbed regions of convective streamlines that are not present during inspiration. Using radiolabeled monodisperse particles, Smaldone and Messina have determined that FLS can be a major determinant of deposition in central airways. Theoretical predictive models of particle deposition and clearance should consider inspiratory and expiratory differences in airway physiology in health and disease.     

Biomass smoke exposures: toxicology and animal study design

Aerosol deposition efficiency (DE) in the extrathoracic airways during mouth breathing is currently documented only for the inspiratory phase of respiration, and there is a need for quantification of expiratory DE. Our aim was to study both inspiratory and expiratory DE in a realistic upper airway geometry. This was done experimentally on a physical upper airway cast by scintigraphy, and numerically by computational fluid dynamic simulations using a Reynolds Averaged Navier–Stokes (RANS) method with a k-ω SST turbulence model coupled with a stochastic Lagrangian approach. Experiments and simulations were carried out for particle sizes (3 and 6?µm) and flow rates (30 and 60?L/min) spanning the ranges of Stokes (Stk) and Reynolds (Re) number pertinent to therapeutic and environmental aerosols. We showed that inspiratory total deposition data obtained by scintigraphy fell onto a previously published deposition curve representative of a range of upper airway geometries. We also found that expiratory and inspiratory DE curves were almost identical. Finally, DE in different compartments of the upper airway model showed a very different distribution pattern of aerosol deposition during inspiration and expiration, with preferential deposition in oral and pharyngeal compartments, respectively. These compartmental deposition patterns were very consistent and only slightly dependent on particle size or flow rate. Total deposition for inspiration and expiration was reasonably well-mimicked by the RANS simulation method we employed, and more convincingly so in the upper range of the Stk and Re number. However, compartmental deposition patterns showed discrepancies between experiments and RANS simulations, particularly during expiration.     

Inspiratory and expiratory aerosol deposition in the upper airway

Aerosol deposition efficiency (DE) in the extrathoracic airways during mouth breathing is currently documented only for the inspiratory phase of respiration, and there is a need for quantification of expiratory DE. Our aim was to study both inspiratory and expiratory DE in a realistic upper airway geometry. This was done experimentally on a physical upper airway cast by scintigraphy, and numerically by computational fluid dynamic simulations using a Reynolds Averaged Navier?Stokes (RANS) method with a k-? SST turbulence model coupled with a stochastic Lagrangian approach. Experiments and simulations were carried out for particle sizes (3 and 6 μm) and flow rates (30 and 60 L/min) spanning the ranges of Stokes (Stk) and Reynolds (Re) number pertinent to therapeutic and environmental aerosols. We showed that inspiratory total deposition data obtained by scintigraphy fell onto a previously published deposition curve representative of a range of upper airway geometries. We also found that expiratory and inspiratory DE curves were almost identical. Finally, DE in different compartments of the upper airway model showed a very different distribution pattern of aerosol deposition during inspiration and expiration, with preferential deposition in oral and pharyngeal compartments, respectively. These compartmental deposition patterns were very consistent and only slightly dependent on particle size or flow rate. Total deposition for inspiration and expiration was reasonably well-mimicked by the RANS simulation method we employed, and more convincingly so in the upper range of the Stk and Re number. However, compartmental deposition patterns showed discrepancies between experiments and RANS simulations, particularly during expiration.     

胸部 CT 扫描吸气相和呼气相与肺小气道病变的相关性研究

目的：探讨无症状长期吸烟者肺小气道损害的患者进行吸气相CT扫描,结合呼气相HRCT扫描,评价呼气相HRCT影像表现及相关参数在诊断小气道疾病方面应用价值。方法采用70例作为吸烟试验组,采用30例不吸烟对照组,均使用螺旋CT进行胸部深吸气末CT扫描,结合深呼气末HRCT扫描,重点观察呼气末的空气潴留影像,测量及计算相关参数,统计其与小气道病变的相关性。结果本研究从性别构成上显示男性吸烟者明显高于女性比例,吸烟组与对照组肺容积参数间差异均有统计学意义（ P ＜0．05）,分别包括吸气相肺容积、呼气相肺容积、吸气相低衰减区比例、呼气相低衰减区比例、吸气相平均肺野密度、呼气相平均肺野密度、呼气－吸气肺容积比、呼气－吸气平均肺野密度比率、呼气－吸气肺容积差和呼气－吸气平均肺野密度差;轻度与重度吸烟组的肺容积参数比较显示除Ins－LV在2组间差异有统计学意义（ P ＜0．05）,其余参数差异均无统计学意义（ P ＞0．05）。结论胸部呼气相HRCT扫描能够清晰的观察到空气潴留的特征表现,结合吸气相CT扫描,测量和计算相关参数等指标,对临床小气道病变的临床早期诊断具有重要意义,敏感性较高,是一种方便快捷,具有临床推广意义的的一种检查手段。     

Relative timing of inspiration and expiration affects respiratory sinus arrhythmia

1. The effect of a variation in inspiration and expiration times on heart rate variability was studied in 12 healthy subjects (mean age 30+/-6 years; five females). 2. Two 2 min trials of controlled breathing, with either short inspiration followed by long expiration or long inspiration followed by short expiration, were compared. Average expiration/inspiration time ratios were 1.0 and 3.4, respectively. The respiration rate in both trials was approximately 10 cycles/min. 3. In trials with short inspiration followed by long expiration, respiratory sinus arrhythmia (RSA; as measured by mean absolute differences and by the high frequency band) was significantly larger than in trials with long inspiration followed by short expiration. This effect could not be accounted for by differences in respiration rate or respiratory amplitude. The higher RSA during fast/slow respiration is primarily due to a more pronounced phasic heart rate increase during inspiration, indicating that inspiratory vagal blockade is sensitive to the steepness of inspiration. 4. Respiration rate and tidal volume are respiratory variables known to modulate RSA. The results of the present study indicate that RSA can also be modulated by a third respiratory variable, the expiratory/inspiratory time ratio.     

Analysis of particle deposition in the turbinate and olfactory regions using a human nasal computational fluid dynamics model.

The human nasal passages effectively filter particles from inhaled air. This prevents harmful pollutants from reaching susceptible pulmonary airways, but may leave the nasal mucosa vulnerable to potentially injurious effects from inhaled toxicants. This filtering property may also be strategically used for aerosolized nasal drug delivery. The nasal route has recently been considered as a means of delivering systemically acting drugs due to the large absorptive surface area available in close proximity to the nostrils. In this study, a computational fluid dynamics (CFD) model of nasal airflow was used with a particle transport and deposition code to predict localized deposition of inhaled particles in human nasal passages. The model geometry was formed from MRI scan tracings of the nasal passages of a healthy adult male. Spherical particles ranging in size from 5 to 50 microm were released from the nostrils. Particle trajectories and deposition sites were calculated in the presence of steady-state inspiratory airflow at volumetric flow rates of 7.5, 15, and 30 L/min. The nasal valve, turbinates, and olfactory region were defined in the CFD model so that particles depositing in these regions could be identified and correlated with their release positions on the nostril surfaces. When plotted against impaction parameter, deposition efficiencies in these regions exhibited maximum values of 53%, 20%, and 3%, respectively. Analysis of preferential deposition patterns and nostril release positions under natural breathing scenarios can be used to determine optimal particle size and flow rate combinations to selectively target drug particles to specific regions of the nose.     

Vibratory stimulation of expiratory muscles inhibits respiration

Induced vibration of the respiratory muscles alters the breathing pattern but controversy persists concerning the most effective site to vibrate, the relative merits of sustained versus phase-locked vibration, and the neural mechanisms involved. In this study we applied a sustained vibratory stimulus to the expiratory intercostal or the external oblique abdominal muscle and compared its effects on tidal volume, inspiratory duration and mean inspiratory flow. Our objective was to deduce from the changes in these respiratory variables whether the sensory input evoked by the vibratory stimulation modulated the central inspiratory drive, the termination of inspiration, or both. Subjects rebreathed from a spirometer which initially contained pure oxygen without a CO2 absorber. Either unilateral or bilateral sustained vibration (100 Hz, 2 mm amplitude) was applied to the 7th or 8th intercostal space anterior to the midaxillary line where the intercostal muscle is a single layer and functions in expiration. Bilateral chest wall vibration suppressed the tidal volume in 7 of 9 subjects. In 4 of 9 subjects, the inspiratory duration was shortened, reflecting premature termination of inspiration. In 5 of 9 subjects, the mean inspiratory flow was reduced, reflecting depression of the central inspiratory drive. Sustained abdominal vibration suppressed tidal volume and reduced inspiratory duration in 4 of 5 subjects. Thus, sustained vibration of either of the expiratory muscles resulted in a reduction in tidal volume. We concluded that sensory input initiated by sustained vibration of abdominal muscles acts centrally to suppress the level of activity in inspiratory neurons.     

The relationship between particle deposition in the anterior nasal passage and nasal passage characteristics.

The objective of this study was to examine the effects of nasal passage characteristics on anterior particle deposition during cyclical breathing. Forty healthy, nonsmoking, adult subjects participated in this study. Nasal passage characteristics such as nostril length, width, angle, ellipticity, and minimum nasal cross-sectional area were measured. The subjects inhaled a polydisperse radioactively tagged aerosol (mass median aerodynamic diameter = 5.4 microns, geometric standard deviation [GSD] = 1.3) into the nose and exhaled through the mouth. The amount of radioactivity in the nose was measured immediately after inhalation and thereafter for 54 minutes. At 52.5 minutes, subjects wiped the accessible portion of the anterior nose to remove any remaining activity. The difference in activity at 52 and 54 minutes was used as a measure of activity removed during the nose wipe. Percentage of activity in the nasal passage at 52 minutes and percentage of activity removed with the nose wipe were considered surrogates for particles deposited in the anterior nasal passage. A multiple regression analysis showed that the degree of ellipticity of the nostrils was significantly related to particle deposition in the anterior nasal passage. These results suggest that ellipticity of the nostrils may be a determinant of the amount of particle deposition in the anterior nasal passage.     

Inspiratory and expiratory high-resolution computed tomography (HRCT) in patients with chemical warfare agents exposure

Chemical warfare agents (CWA) including sulfur mustard (SM) were commonly used in Iran-Iraq war. Respiratory problems are the greatest cause of long-term disability among people who had combat exposure to SM. High-resolution computed tomography (HRCT) has been accepted as the imaging modality of choice in these patients. We used expiratory HRCT findings in comparison to inspiratory HRCT for demonstration of pulmonary damage in these patients. HRCT in deep inspiration as well as full expiration was performed in 473 patients with a history of chemical gas exposure during the war and the results were compared. The study was prospective during 1 yr. Of 473 patients, 366 (77.38%) showed normal HRCT in deep inspiration; however, on corresponding expiratory cuts, 263 (71.86%) had abnormalities. The most frequent abnormal finding in expiration was patchy air trapping (77.77%). We conclude that exposure to SM causes pulmonary complications resulting in disability in the affected patients; however, HRCT in inspiration is normal in most of the affected patients. Expiratory HRCT showed patchy air trapping as the most common finding, which is suggestive of small air way diseases such as bronchiolitis obliterans; therefore it is recommended to do HRCT both in deep inspiration and full expiration in patients with a history of CWA exposure.     

Inspiratory and Expiratory High-Resolution Computed Tomography (HRCT) in Patients with Chemical Warfare Agents Exposure

Chemical warfare agents (CWA) including sulfur mustard (SM) were commonly used in Iran–Iraq war. Respiratory problems are the greatest cause of long-term disability among people who had combat exposure to SM. High-resolution computed tomography (HRCT) has been accepted as the imaging modality of choice in these patients. We used expiratory HRCT findings in comparison to inspiratory HRCT for demonstration of pulmonary damage in these patients. HRCT in deep inspiration as well as full expiration was performed in 473 patients with a history of chemical gas exposure during the war and the results were compared. The study was prospective during 1 yr. Of 473 patients, 366 (77.38%) showed normal HRCT in deep inspiration; however, on corresponding expiratory cuts, 263 (71.86%) had abnormalities. The most frequent abnormal finding in expiration was patchy air trapping (77.77%). We conclude that exposure to SM causes pulmonary complications resulting in disability in the affected patients; however, HRCT in inspiration is normal in most of the affected patients. Expiratory HRCT showed patchy air trapping as the most common finding, which is suggestive of small air way diseases such as bronchiolitis obliterans; therefore it is recommended to do HRCT both in deep inspiration and full expiration in patients with a history of CWA exposure.     

Procedure for evaluating changes in respiratory symptoms of experimentally asthma-induced guinea pigs by a personal computer.

An automated system was developed for evaluating changes in respiratory symptoms in guinea pigs over a long period with a personal computer. The data on breathing curves obtained with a body plethysmograph were analyzed to determine respiratory rate, expiration/inspiration ratio, ventilation ratio, and other parameters. With this system, respiratory changes in guinea pigs, such as increase or decrease of respiratory rate, expiration/inspiration ratio, and ventilation ratio, and death of animals could be easily observed. Investigation of delayed respiratory response to Candida albicans in sensitized guinea pigs and of the effects of SO2 or NO2 exposures on its response was carried out using this system. Respiratory changes in delayed respiratory response were mostly increased respiration rate and succeeding expiratory prolongation being noted just before death. In the influences of SO2 or NO2 exposure on delayed respiratory response, increase of respiratory rate in NO2 and expiratory and inspiratory prolongation in SO2 were found. This system should prove useful for evaluating changes in respiratory symptoms due to toxic agents, medicines, and air pollutants in small animals.     

Multiplicity of functional behavior of human intercostal muscles

Single motor unit activity from the 6th intercostal space in five healthy adults was analyzed during rebreathing, voluntary deep inspiration, Valsalve maneuver and phonation. Action potentials and pneumotach flow were stored on tape and fed to the computer for subsequent analysis. Spike-by-spike analyses revealed three functional types of intercostal motor units. One unit fired almost exclusively during inspiration and its firing was augmented by rebreathing and voluntary deep inspiration (phasic I unit). The second type fired continuously throughout the respiratory cycle with an increase in firing during expiration (tonic E unit); its activity was disrupted during phonation but not during rebreathing, suggesting a postural rather than respiratory function. The third type, silent during quiet breathing, was recruited during rebreathing, voluntary deep inspiration or Valsalve maneuver; its firing started in late inspiration and ceased in early expiration (phase-spanning I-E unit). The relationships between tidal volume and inspiratory time during rebreathing showed that the third type was recruited when tidal volume reached a critical 'volume threshold', suggesting that vagal volume feedback is essential for its activation.     

Central respiratory and cardiovascular effects in the rat of some putative neurotransmitter amino acids

Respiratory performance was studied in halothane anesthetized rats after intracerebroventricular (i.c.v.) injection of beta-alanine, taurine or glycine (0.01--1 mg). The amino acids induced a marked decrease in both respiratory frequency (f) and tidal volume (VT), which was immediate and longlasting. The respiratory depressant action of glycine could readily be reversed by strychnine, a glycine antagonist. Measurement of respiratory time intervals, inspiratory time (TI), expiratory time (TE) and total cycle duration (TTOT), after administration of the putative neurotransmitter amino acids revealed that the effects on f were due to prolongation of the duration of expiration. The duration of inspiration was principally unaltered, but mean inspiratory flow (VT/TI) and respiratory timing (TI/TTOT) decreased. In experiments employing the occluded breath technique, P0.1 was reduced in the same magnitude as the mean inspiratory flow (VT/TI). The results also showed a change in central (bulbopontine) setting for TE, while the setting to TI was unaltered. An inert amino acid, valine, which was administered i.c.v. in the same doses, had no effects on respiratory parameters. Apart from the effects on basal ventilation of beta-alanine, taurine and glycine, the CO2 induced respiratory response was blunted. These three amino acids also depressed heart rate and mean arterial pressure. Although relatively high doses were used to induce the respiratory effects, it may be hypothetised that the putative neurotransmitters beta-alanine, taurine and glycine may have a physiological role in the central regulation of breathing.     

Histamine challenge and anterior nasal rhinometry: their use in the assessment of pseudoephedrine and triprolidine as nasal decongestants in subjects with hayfever.

1 Nasal airway resistance (NAR) was measured by anterior rhinometry in ten volunteers with allergic rhinitis. Measurements before and after challenge with three concentrations of histamine diphosphate showed significant rises in NAR for each challenge. 2 In a double-blind, crossover study with the same patients triprolidine (2.5 mg) and pseudoephedrine (60 mg) were shown to be equally effective in reducing the rise in NAR produced by histamine challenge to one nostril; both were significantly better than placebo. 3 The rise in NAR of both nostrils after histamine challenge to one nostril was significantly reduced after pseudoephedrine compared with placebo. This suggests that pseudoephedrine is effective in preventing reflex mucosal congestion in the unchallenged nostril. 4 No increase in the pulse rate or blood pressure of the volunteers was detected after either drug.     

Effect of race on fine particle deposition for oral and nasal breathing

Nasal efficiency for removing fine particles from inhaled air may be affected by variations in nasal structure associated with race. In 11 African American and 11 Caucasian adults (age 18-31 yr) we measured the fractional deposition (DF) of fine particles (1 and 2 mum mass median aerodynamic diameter) (MMAD) for oral and nasal breathing using individual breathing patterns previously measured by respiratory inductance plethysmography during a graded exercise protocol. DF for both nasal and mouth breathing was measured separately by laser photometry at the same tidal volume and breathing rate for resting and light exercise (20% of maximum work load) conditions. From these DF measures, nasal deposition efficiency (NDE) was calculated for each condition. For light exercise conditions, NDE for both 1- and 2-microm particles was less in African Americans versus Caucasians, 0.15 +/- 0.07 (SD) versus 0.24 +/- 0.11 for 1-microm particles (p = .03), and 0.29 +/- 0.13 versus 0.44 +/- 0.11 for 2-microm particles (p = .006). The racial differences in NDE were associated with racial differences in nasal resistance and nostril shape. These race-dependent nasal efficiencies are dosimetric factors that should be considered in modeling and assessing particulate dose from human exposure to air pollutants.     

Nasal spirometery

Nasal obstruction is a common symptom which is difficult to quantify clinically. Rhinomanometry, Acoustic Rhinometry and Forced Oscillation methods are available for estimating nasal resistance but, these require sophisticated machines. Because of limited availability of these techniques, this potential physiological measure has not been tapped fully for research and clinical purposes. Here, we describe the use of pulmonary spirometer with little modification for quantification of nasal flow. Nasal inspiratory and expiratory flow rates along with oral inspiratory and expiratory flow rates are used to derive different nasal resistance indices. This way of reporting nasal resistance is not new but, the data for these variables is currently not available in published literature. The reproducibility of nasal flow rates were tested as variation after one day and the interclass coefficient for inspiratory and expiratory nasal flow rates were found to be with in acceptable limits. Thus, nasal spirometery is able to describe the nasal resistance in a reliable manner and may be used to quantify nasal obstruction in pathological condition and also to study the physiological phenomenon like nasal cycle.     

Effect of Race on Fine Particle Deposition for Oral and Nasal Breathing

Abstract

Nasal efficiency for removing fine particles from inhaled air may be affected by variations in nasal structure associated with race. In 11 African American and 11 Caucasian adults (age 18–31 yr) we measured the fractional deposition (DF) of fine particles (1 and 2 μm mass median aerodynamic diameter) (MMAD) for oral and nasal breathing using individual breathing patterns previously measured by respiratory inductance plethysmography during a graded exercise protocol. DF for both nasal and mouth breathing was measured separately by laser photometry at the same tidal volume and breathing rate for resting and light exercise (20% of maximum work load) conditions. From these DF measures, nasal deposition efficiency (NDE) was calculated for each condition. For light exercise conditions, NDE for both 1- and 2-μm particles was less in African Americans versus Caucasians, 0.15 ± 0.07 (SD) versus 0.24 ± 0.11 for 1-μm particles (p = .03), and 0.29 ± 0.13 versus 0.44 ± 0.11 for 2-μm particles (p = .006). The racial differences in NDE were associated with racial differences in nasal resistance and nostril shape. These race-dependent nasal efficiencies are dosimetric factors that should be considered in modeling and assessing particulate dose from human exposure to air pollutants.     

Inhalation characteristics and their effects on in vitro drug delivery from dry powder inhalers Part 1. Inhalation characteristics, work of breathing and volunteers'' preference in dependence of the inhaler resistance

A test inhaler with exchangeable air flow resistances encompassing the range of commercial DPIs has been used to study the inspiratory flow curves of 39 healthy adult volunteers. A strong increase in mean Peak Inspiratory Flow Rate (PIFR) has been obtained with decreasing inhaler resistance, varying between 160 1/min for a resistance equivalent to the Rotahaler and 50 1/min for the simulated Inhalator Ingelheim at maximum inspiratory effort. The volunteers experienced on average 55% of maximum effort as comfortable (expressed in PIFR) and gave preference (82%) to relative high air flow resistances in the range of 0.4-0.9 × 10⁵ (N^0.5·s·m⁻⁴). It has been calculated that the real amount of work of breathing does not increase with increasing air flow resistance at comfortable inspiration mode. At maximum inspiration, the amount of work performed through a high resistance inhaler (1.5 × 10⁵) is approx. 70% of that through a low resistance device (0.4 × 10⁵). The calculated mean PIFR of 62 1/min at maximum effort through an air flow resistance of 0.9 × 10⁵, equivalent to the Turbuhaler, is in good agreement with PIFR-values of 68.5 vs. 59 1/min from two other studies with asthmatic patients through this device. It has, therefore, been concluded that the flow curves of healthy volunteers may be used to predict the range of PIFRs for asthmatics through the same air flow resistances.     

In vivo measurement of fine and coarse aerosol deposition in the nasal airways of female Long-Evans rats.

Experimental data on fine and coarse aerosol deposition in the nasal airways of animals are essential in appropriately using toxicological studies to assess the potential risk to human health from exposure to airborne pollutants. However, such data are scarce. The objective of this study was to determine aerosol deposition efficiencies for the nasal airways in Long-Evans rats for particles with diameters ranging from 0.5 to 4 microm. Polystyrene latex (PSL) microspheres in steady-state and pulsatile flows were passed through the nasal airways for simulated inspiratory and expiratory scenarios. Average flow rates ranged from 220 to 640 ml/min. Deposition increased sharply with increasing particle inertia for all exposure scenarios. Expiratory deposition efficiency appeared to be somewhat higher than inspiratory deposition efficiency for both steady-state and pulsatile flow conditions. Pulsatile flow yielded significantly higher deposition than steady-state flow. This result emphasizes the importance of considering fluid accelerations inherent in normal breathing when determining aerosol deposition that is dominated by inertial impaction. Variability in the data, which was suspected to result primarily from the difficult surgical procedure, was in excess of expected intersubject variability. The results of this study will be incorporated into extrapolation-modeling and risk-assessment activities for inhaled pollutants.     

Numerical simulation of air flow and medical-aerosol distribution in an innovative nebulizer hood.

The use of a hood to administer therapeutic aerosols to wheezy infants has many advantages and was found as efficient as administration using a mask. The aim of the present study is to investigate numerically the airflow induced drug dispersion inside the hood. Drug droplet dispersion is examined with respect to three breathing phases: inspiration, expiration, and apnea. The governing equations describing the airflow and the trajectories of drug droplets were solved using the FLUENT 6.1 Computational Fluid Dynamics (CFD) software package. The geometry and mesh were generated with the GAMBIT package. The velocity field of the air and the trajectories of drug droplets inside the funnel--the tube that delivers the drug from the nebulizer to the infant's mouth--and close to its exit are robust and do not show any appreciable differences among the three breathing phases studied. However, in other parts of the hood, air velocity, and particle motion largely depend on the infant's breathing and physiological state. The efficiency of drug delivery to the mouth during inspiration is found to be as high as 84%, whereas it is much smaller in the other two (common) breathing phases examined. Our results may be utilized to improve the hood design and to increase its efficacy for administration of aerosolized medications to infants.