Upper airway imaging and function in obstructive sleep apnea in people with and without HIV.

Obstructive sleep apnea (OSA) is common in people living with human immunodeficiency virus (HIV) (PLWH), but the underlying mechanisms are unclear. With improved long-term survival among PLWH, aging and obesity are increasingly prevalent in this population. These are also strong risk factors for the development of obstructive sleep apnea. We used magnetic resonance imaging (MRI) to measure upper airway (UA) anatomy and tongue fat content in PLWH with OSA (PLWH + OSA, n = 9) and in age-, sex-, and body mass index (BMI)-matched OSA controls (OSA, n = 11). We also quantified change in UA dimension during tidal breathing (during wakefulness and natural sleep) at four anatomical levels from the hard palate to the epiglottis along with synchronous MRI-compatible electroencephalogram and nasal flow measurements. All participants underwent on a separate night a baseline polysomnogram to assess OSA severity and an additional overnight physiological sleep study to measure OSA traits. We found no difference between the PLWH + OSA and the OSA control group in UA volume [PLWH + OSA: 12.8 mL (10.1-17.0), OSA: 14.0 mL (13.3-17.9), median (IQR)] or tongue volume [PLWH + OSA: 140.2 mL (125.1-156.9), OSA: 132.4 mL (126.8-154.7)] and a smaller tongue fat content in PLWH + OSA [11.2% (10.2-12.4)] than in the OSA controls [14.8% (13.2-15.5), P = 0.046]. There was no difference in the dynamic behavior of the UA between the two groups. When pooled together, both static and dynamic imaging metrics could be correlated with measures of UA mechanical properties. Our data suggest similar underlying UA physiology in OSA in subjects with and without HIV.NEW & NOTEWORTHY Obstructive sleep apnea is common in people living with human immunodeficiency virus (HIV), but the underlying mechanisms are unclear. We did not find differences in upper airway morphology using magnetic resonance imaging (MRI) during wake and natural sleep between people living with HIV (PLWH) with obstructive sleep apnea (OSA) and age, gender, and body mass index (BMI)-matched people with OSA but without HIV. Nor were there differences in tongue volume or changes in airway size during inspiration and expiration. MRI-derived anatomy was correlated with measures of airway collapse.

Magnetic Resonance Imaging of Aerosol Deposition.

Nuclear magnetic resonance imaging (MRI) uses non-ionizing radiation and offers a host of contrast mechanisms with the potential to quantify aerosol deposition. This chapter introduces the physics of MRI, its use in lung imaging, and more specifically, the methods that are used for the detection of regional distributions of inhaled particles. The most common implementation of MRI is based on imaging of hydrogen atoms (1H) in water. The regional deposition of aerosol particles can be measured by the perturbation of the acquired 1H signals via labeling of the aerosol with contrast agents. Existing in vitro human and in vivo animal model measurements of regional aerosol deposition in the respiratory tract are described, demonstrating the capability of MRI to assess aerosol deposition in the lung.

Aerosols, airflow, and more: examining the interaction of speech and the physical environment.

We describe ongoing efforts to better understand the interaction of spoken languages and their physical environments. We begin by briefly surveying research suggesting that languages evolve in ways that are influenced by the physical characteristics of their environments, however the primary focus is on the converse issue: how speech affects the physical environment. We discuss the speech-based production of airflow and aerosol particles that are buoyant in ambient air, based on some of the results in the literature. Most critically, we demonstrate a novel method used to capture aerosol, airflow, and acoustic data simultaneously. This method captures airflow data via a pneumotachograph and aerosol data via an electrical particle impactor. The data are collected underneath a laminar flow hood while participants breathe pure air, thereby eliminating background aerosol particles and isolating those produced during speech. Given the capabilities of the electrical particle impactor, which has not previously been used to analyze speech-based aerosols, the method allows for the detection of aerosol particles at temporal and physical resolutions exceeding those evident in the literature, even enabling the isolation of the role of individual sound types in the production of aerosols. The aerosols detected via this method range in size from 70 nanometers to 10 micrometers in diameter. Such aerosol particles are capable of hosting airborne pathogens. We discuss how this approach could ultimately yield data that are relevant to airborne disease transmission and offer preliminary results that illustrate such relevance. The method described can help uncover the actual articulatory gestures that generate aerosol emissions, as exemplified here through a discussion focused on plosive aspiration and vocal cord vibration. The results we describe illustrate in new ways the unseen and unheard ways in which spoken languages interact with their physical environments.

In Silico Quantification of Intersubject Variability on Aerosol Deposition in the Oral Airway.

The extrathoracic oral airway is not only a major mechanical barrier for pharmaceutical aerosols to reach the lung but also a major source of variability in lung deposition. Using computational fluid dynamics, deposition of 1−30 µm particles was predicted in 11 CT-based models of the oral airways of adults. Simulations were performed for mouth breathing during both inspiration and expiration at two steady-state flow rates representative of resting/nebulizer use (18 L/min) and of dry powder inhaler (DPI) use (45 L/min). Consistent with previous in vitro studies, there was a large intersubject variability in oral deposition. For an optimal size distribution of 1−5 µm for pharmaceutical aerosols, our data suggest that >75% of the inhaled aerosol is delivered to the intrathoracic lungs in most subjects when using a nebulizer but only in about half the subjects when using a DPI. There was no significant difference in oral deposition efficiency between inspiration and expiration, unlike subregional deposition, which shows significantly different patterns between the two breathing phases. These results highlight the need for incorporating a morphological variation of the upper airway in predictive models of aerosol deposition for accurate predictions of particle dosimetry in the intrathoracic region of the lung.

Aerosol Transport Modeling: The Key Link Between Lung Infections of Individuals and Populations.

The recent COVID-19 pandemic has propelled the field of aerosol science to the forefront, particularly the central role of virus-laden respiratory droplets and aerosols. The pandemic has also highlighted the critical need, and value for, an information bridge between epidemiological models (that inform policymakers to develop public health responses) and within-host models (that inform the public and health care providers how individuals develop respiratory infections). Here, we review existing data and models of generation of respiratory droplets and aerosols, their exhalation and inhalation, and the fate of infectious droplet transport and deposition throughout the respiratory tract. We then articulate how aerosol transport modeling can serve as a bridge between and guide calibration of within-host and epidemiological models, forming a comprehensive tool to formulate and test hypotheses about respiratory tract exposure and infection within and between individuals.

Nitrogen-based lung clearance index: a valid physiological biomarker for the clinic.

Multiple breath washout (MBW) testing is increasingly used as a physiological measurement in the clinic, due in part to the availability of commercial equipment and reference values for MBW indices. Commercial N2 washout devices are usually based on indirect measurement of N2 concentration (CN2), by directly measuring either molar mass and O2 and CO2, or molar mass and CO2. We aim to elucidate the role of two potential pitfalls associated with N2-MBW testing that could override its physiological content: indirect N2 measurement and blood-solubility of N2. We performed MBW in 12 healthy adult subjects using a commercial device (MBWindirect) with simultaneous direct gas concentration measurements by mass spectrometry (MBWdirect) and compared CN2 between MBWdirect and MBWindirect. We also measured argon concentration during the same washouts to verify the maximal effect gas solubility can have on N2-based functional residual capacity (FRC) and lung clearance index (LCI). Continuous N2 concentration traces were very similar for MBWindirect and MBWdirect, resulting in comparable breath-by-breath washout plots of expired concentration and in no significant differences in FRCN2, LCIN2, Scond, and Sacin between the two methods. Argon washouts were slightly slower than N2 washouts, as expected for a less diffusive and more soluble gas. Finally, comparison between LCIN2 and LCIAr indicates that the maximum impact from blood-tissue represents less than half a LCI unit in normal subjects. In conclusion, we have demonstrated by direct measurement of N2 and twice as soluble argon, that indirect N2 measurement can be safely used as a meaningful physiological measurement.NEW & NOTEWORTHY The physiological content of N2 multibreath washout testing has been questioned due to N2 indirect measurement accuracy and N2 blood solubility. With direct measurement of N2 and twice as soluble argon, we show that these effects are largely outweighed by ease of use.

Peripheral lung effect of elexacaftor/tezacaftor/ivacaftor in adult cystic fibrosis.

Despite being an important patient group, adult cystic fibrosis patients with an FEV1 below 40%predicted have been excluded from clinical trials with elexacaftor/tezacaftor/ivacaftor. We conducted a real-life 3 months follow-up study in 14 adult CF patients (median FEV1 34%predicted) demonstrating significant treatment effects in terms of FEV1 (an increase of 12%predicted at 4 weeks, remaining stable thereafter). Corresponding decreases in lung clearance index LCI (by 31%predicted, down from baseline 247%predicted) and ventilation heterogeneity in the acinar compartment (Sacin) (by 411%predicted, down from baseline 798%predicted) suggest a distinct peripheral lung effect. One patient had intermittent treatment interruptions because of drug-induced liver injury. Our real-life data confirm that treatment with elexacaftor/tezacaftor/ivacaftor is effective in severely obstructive patients, and this is the first study to show time evolution of ventilation distribution improvement, pointing to the peripheral lung as the main site of treatment effect.

Pathogenesis of obstructive sleep apnea in people living with HIV.

Obstructive sleep apnea (OSA) is highly prevalent in people living with human immunodeficiency virus (HIV) (PLWH), and it might contribute to frequently reported symptoms and comorbidities. Traditional risk factors for OSA are often absent in PLWH, suggesting that HIV or HIV medications might predispose to OSA. Therefore, we measured the anatomical and nonanatomical traits important for OSA pathogenesis in those with and without HIV. We recruited virally suppressed PLWH who had been previously diagnosed with OSA (PLWH + OSA) adherent to positive airway pressure (PAP) therapy, along with age-, sex-, and body mass index (BMI)-matched OSA controls. All participants underwent a baseline polysomnogram to assess OSA severity and a second overnight research sleep study during which the airway pressure was adjusted slowly or rapidly to measure the OSA traits. Seventeen PLWH + OSA and 17 OSA control participants were studied [median age = 58 (IQR = 54-65) yr, BMI = 30.7 (28.4-31.8) kg/m2, apnea-hypopnea index = 46 (24-74)/h]. The groups were similar, although PLWH + OSA demonstrated greater sleepiness (despite PAP) and worse sleep efficiency on baseline polysomnography. On physiological testing during sleep, there were no statistically significant differences in OSA traits (including Veupnea, Varousal, Vpassive, Vactive, and loop gain) between PLWH + OSA and OSA controls, using mixed-effects modeling to account for age, sex, and BMI and incorporating each repeated measurement (range = 72-334 measures/trait). Our data suggest that well-treated HIV does not substantially impact the pathogenesis of OSA. Given similar underlying physiology, existing available therapeutic approaches are likely to be adequate to manage OSA in PLWH, which might improve symptoms and comorbidities.NEW & NOTEWORTHY Clinical data suggest an increased risk of obstructive sleep apnea (OSA) in people living with HIV (PLWH), while OSA might account for chronic health issues in this population. We characterized the anatomical and nonanatomical OSA traits in PLWH + OSA compared with OSA controls, using detailed physiological measurements obtained during sleep. Our data suggest against a major impact of HIV on OSA pathogenesis. Available OSA management strategies should be effective to address this potentially important comorbidity in PLWH.

Reducing Aerosol-Related Risk of Transmission in the Era of COVID-19: An Interim Guidance Endorsed by the International Society of Aerosols in Medicine.

National and international guidelines recommend droplet/airborne transmission and contact precautions for those caring for coronavirus disease 2019 (COVID-19) patients in ambulatory and acute care settings. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, an acute respiratory infectious agent, is primarily transmitted between people through respiratory droplets and contact routes. A recognized key to transmission of COVID-19, and droplet infections generally, is the dispersion of bioaerosols from the patient. Increased risk of transmission has been associated with aerosol generating procedures that include endotracheal intubation, bronchoscopy, open suctioning, administration of nebulized treatment, manual ventilation before intubation, turning the patient to the prone position, disconnecting the patient from the ventilator, noninvasive positive-pressure ventilation, tracheostomy, and cardiopulmonary resuscitation. The knowledge that COVID-19 subjects can be asymptomatic and still shed virus, producing infectious droplets during breathing, suggests that health care workers (HCWs) should assume every patient is potentially infectious during this pandemic. Taking actions to reduce risk of transmission to HCWs is, therefore, a vital consideration for safe delivery of all medical aerosols. Guidelines for use of personal protective equipment (glove, gowns, masks, shield, and/or powered air purifying respiratory) during high-risk procedures are essential and should be considered for use with lower risk procedures such as administration of uncontaminated medical aerosols. Bioaerosols generated by infected patients are a major source of transmission for SARS CoV-2, and other infectious agents. In contrast, therapeutic aerosols do not add to the risk of disease transmission unless contaminated by patients or HCWs.

Deposition Mechanisms.

The success of inhalation therapy is not only dependent upon the pharmacology of the drugs being inhaled but also upon the site and extent of deposition in the respiratory tract. Similarly, the toxicity of environmental and industrial particulate matter is affected not only by the nature of the dust but also by the amount and spatial distribution of deposited particles in the lung. Aerosol deposition is primarily governed by the mechanisms of inertial impaction, gravitational sedimentation, Brownian diffusion, and, to a lesser extent, by turbulence, electrostatic precipitation, and interception. The relative contribution of these different mechanisms is a function of the physical characteristics of the particles, the lung structure, and the flow patterns. Large particles (>5 µm) tend to deposit mainly in the upper and large airways, limiting the amount of aerosols that can be delivered to the lung. Small particles (<2 µm) deposit mainly in the alveolar region, whereas particles in the size range 2-5 µm deposit preferentially in the central and small airways.

Particle Size Distributions.

The distribution of particles sizes within an aerosol is essential information for understanding the behavior of that aerosol. The number of particles within certain size ranges is given by distributions specified by a count distribution if referring to number of particles, or a mass distribution if referring to particle mass. The cumulative number, or mass, of particles less than a certain diameter is determined by integrating the relevant distribution, which allows definition of median diameters. The mass median diameter is a commonly specified diameter. For log-normal distributions, the spread of the distribution is given by the geometric standard deviation. Although particle size distributions of actual aerosols are discrete by nature, the use of continuous functions to describe them is a useful conceptual tool.

Innovative preclinical models for pulmonary drug delivery research.

Introduction: Pulmonary drug delivery is a complex field of research combining physics which drive aerosol transport and deposition and biology which underpins efficacy and toxicity of inhaled drugs. A myriad of preclinical methods, ranging from in-silico to in-vitro, ex-vivo and in-vivo, can be implemented.Areas covered: The present review covers in-silico mathematical and computational fluid dynamics modelization of aerosol deposition, cascade impactor technology to estimated drug delivery and deposition, advanced in-vitro cell culture methods and associated aerosol exposure, lung-on-chip technology, ex-vivo modeling, in-vivo inhaled drug delivery, lung imaging, and longitudinal pharmacokinetic analysis.Expert opinion: No single preclinical model can be advocated; all methods are fundamentally complementary and should be implemented based on benefits and drawbacks to answer specific scientific questions. The overall best scientific strategy depends, among others, on the product under investigations, inhalation device design, disease of interest, clinical patient population, previous knowledge. Preclinical testing is not to be separated from clinical evaluation, as small proof-of-concept clinical studies or conversely large-scale clinical big data may inform preclinical testing. The extend of expertise required for such translational research is unlikely to be found in one single laboratory calling for the setup of multinational large-scale research consortiums.

The Effect of Aging on Aerosol Bolus Deposition in the Healthy Adult Lung: A 19-Year Longitudinal Study.

Background: While it is recognized that peripheral lung structure and ventilation heterogeneity change with age, the effects of age on aerosol deposition in the healthy adult lung is largely unknown. Methods: A series of aerosol bolus inhalations were repeatedly performed in four healthy subjects over a period of 19 years (years = 0, 9, 15 and 19). For each series, a bolus of 1 µm particles was inhaled at penetration volumes (Vp) ranging from 200 to 1200 mL. Aerosol bolus deposition (DE), dispersion (H), and mode shift (MS) were calculated along with the rate of increase in these parameters with increasing Vp (slope-DE, slope-H, and slope-MS). Results: Slope-DE significantly increased from 0.040 ± 0.014 (mean ± standard deviation) at year 0 to 0.069 ± 0.007%/mL at year 19 (p = 0.02) with no significant difference in DE at shallow depth (Vp = 200 mL; 14% ± 4% at year 0 vs. 15% ± 7% at year 19, p = 0.25). There was no significant effect of age on either slope-H (0.44 ± 0.05 at year 0 vs. 0.47 ± 0.09 mL/mL at year 19, p = 0.6) or dispersion at shallow depth (192 ± 36 mL at year 0 vs. 220 ± 54 mL at year 19, p = 0.2). Slope-MS became significantly more negative with increasing age (-0.096 ± 0.044 at year 0 vs. -0.171 ± 0.027 mL/mL at year 19, p = 0.001) with no significant difference in MS at shallow depth (12 ± 10 at year 0 vs. 7 ± 15 mL at year 19, p = 0.3). Conclusions: These data suggest that (1) peripheral deposition increases with aging in the healthy lung, likely as a result of increasing closing volume with age; (2) alterations in the mechanical properties of healthy adult lungs with age occur uniformly; and (3) the significant increase in the magnitude of MS-slope with age is likely due to the concomitant increase in peripheral deposition and possible alterations in flow sequencing.

Quantitative Mapping of Specific Ventilation in the Human Lung using Proton Magnetic Resonance Imaging and Oxygen as a Contrast Agent.

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation - the ratio of the fresh gas entering a lung region divided by the region's end-expiratory volume - in the human lung, using only inhaled oxygen as a contrast agent. Regional quantification of specific ventilation has the potential to help identify areas of pathologic lung function. Oxygen in solution in tissue shortens the tissue's longitudinal relaxation time (T1), and thus a change in tissue oxygenation can be detected as a change in T1-weighted signal with an inversion recovery acquired image. Following an abrupt change between two concentrations of inspired oxygen, the rate at which lung tissue within a voxel equilibrates to a new steady-state reflects the rate at which resident gas is being replaced by inhaled gas. This rate is determined by specific ventilation. To elicit this sudden change in oxygenation, subjects alternately breathe 20-breath blocks of air (21% oxygen) and 100% oxygen while in the MRI scanner. A stepwise change in inspired oxygen fraction is achieved through use of a custom three-dimensional (3D)-printed flow bypass system with a manual switch during a short end-expiratory breath hold. To detect the corresponding change in T1, a global inversion pulse followed by a single shot fast spin echo sequence was used to acquire two-dimensional T1-weighted images in a 1.5 T MRI scanner, using an eight-element torso coil. Both single slice and multi-slice imaging are possible, with slightly different imaging parameters. Quantification of specific ventilation is achieved by correlating the time-course of signal intensity for each lung voxel with a library of simulated responses to the air/oxygen stimulus. SVI estimations of specific ventilation heterogeneity have been validated against multiple breath washout and proved to accurately determine the heterogeneity of the specific ventilation distribution.

Upper airway dynamic imaging during tidal breathing in awake and asleep subjects with obstructive sleep apnea and healthy controls.

We used magnetic resonance imaging (MRI) to quantify change in upper airway dimension during tidal breathing in subjects with obstructive sleep apnea (OSA, N = 7) and BMI-matched healthy controls (N = 7) during both wakefulness and natural sleep. Dynamic MR images of the upper airway were obtained on a 1.5 T MR scanner in contiguous 7.5 mm-thick axial slices from the hard palate to the epiglottis along with synchronous MRI-compatible electroencephalogram and nasal/oral flow measurements. The physiologic data were retrospectively scored to identify sleep state, and synchronized with dynamic MR images. For each image, the upper airway was characterized by its area, and linear dimensions (lateral and anterior-posterior). The dynamic behavior of the upper airway was assessed by the maximum change in these parameters over the tidal breath. Mean upper airway caliber was obtained by averaging data over the tidal breath. There was no major difference in the upper airway structure between OSA and controls except for a narrower airway at the low-retropalatal/high-retroglossal level in OSA than in controls. Changes in upper airway size over the tidal breath ((maximum - minimum)/mean) were significantly larger in the OSA than in the control group in the low retropalatal/high retroglossal region during both wakefulness and sleep. In the four OSA subjects who experienced obstructive apneas during MR imaging, the site of airway collapse during sleep corresponded to the region of the upper airway where changes in caliber during awake tidal breathing were the greatest. These observations suggest a potential role for dynamic OSA imaging during wakefulness.

Pulmonary Delivery of Therapeutic and Diagnostic Gases.

The 21st Congress for the International Society for Aerosols in Medicine included, for the first time, a session on Pulmonary Delivery of Therapeutic and Diagnostic Gases. The rationale for such a session within ISAM is that the pulmonary delivery of gaseous drugs in many cases targets the same therapeutic areas as aerosol drug delivery, and is in many scientific and technical aspects similar to aerosol drug delivery. This article serves as a report on the recent ISAM congress session providing a synopsis of each of the presentations. The topics covered are the conception, testing, and development of the use of nitric oxide to treat pulmonary hypertension; the use of realistic adult nasal replicas to evaluate the performance of pulsed oxygen delivery devices; an overview of several diagnostic gas modalities; and the use of inhaled oxygen as a proton magnetic resonance imaging (MRI) contrast agent for imaging temporal changes in the distribution of specific ventilation during recovery from bronchoconstriction. Themes common to these diverse applications of inhaled gases in medicine are discussed, along with future perspectives on development of therapeutic and diagnostic gases.

Ventilation heterogeneity measured by multiple breath inert gas testing is not affected by inspired oxygen concentration in healthy humans.

Multiple breath washout (MBW) and oxygen-enhanced MRI techniques use acute exposure to 100% oxygen to measure ventilation heterogeneity. Implicit is the assumption that breathing 100% oxygen does not induce changes in ventilation heterogeneity; however, this is untested. We hypothesized that ventilation heterogeneity decreases with increasing inspired oxygen concentration in healthy subjects. We performed MBW in 8 healthy subjects (4 women, 4 men; age = 43 ± 15 yr) with normal pulmonary function (FEV1 = 98 ± 6% predicted) using 10% argon as a tracer gas and oxygen concentrations of 12.5%, 21%, or 90%. MBW was performed in accordance with ERS-ATS guidelines. Subjects initially inspired air followed by a wash-in of test gas. Tests were performed in balanced order in triplicate. Gas concentrations were measured at the mouth, and argon signals rescaled to mimic a N2 washout, and analyzed to determine the distribution of specific ventilation (SV). Heterogeneity was characterized by the width of a log-Gaussian fit of the SV distribution and from Sacin and Scond indexes derived from the phase III slope. There were no significant differences in the ventilation heterogeneity due to altered inspired oxygen: histogram width (hypoxia 0.57 ± 0.11, normoxia 0.60 ± 0.08, hyperoxia 0.59 ± 0.09, P = 0.51), Scond (hypoxia 0.014 ± 0.011, normoxia 0.012 ± 0.015, hyperoxia 0.010 ± 0.011, P = 0.34), or Sacin (hypoxia 0.11 ± 0.04, normoxia 0.10 ± 0.03, hyperoxia 0.12 ± 0.03, P = 0.23). Functional residual capacity was increased in hypoxia (P = 0.04) and dead space increased in hyperoxia (P = 0.0001) compared with the other conditions. The acute use of 100% oxygen in MBW or MRI is unlikely to affect ventilation heterogeneity.NEW & NOTEWORTHY Hyperoxia is used to measure the distribution of ventilation in imaging and MBW but may alter the underlying ventilation distribution. We used MBW to evaluate the effect of inspired oxygen concentration on the ventilation distribution using 10% argon as a tracer. Short-duration exposure to hypoxia (12.5% oxygen) and hyperoxia (90% oxygen) during MBW had no significant effect on ventilation heterogeneity, suggesting that hyperoxia can be used to assess the ventilation distribution.

Regional Ventilation Is the Main Determinant of Alveolar Deposition of Coarse Particles in the Supine Healthy Human Lung During Tidal Breathing.

BACKGROUND: To quantify the relationship between regional lung ventilation and coarse aerosol deposition in the supine healthy human lung, we used oxygen-enhanced magnetic resonance imaging and planar gamma scintigraphy in seven subjects. METHODS: Regional ventilation was measured in the supine posture in a 15 mm sagittal slice of the right lung. Deposition was measured by using planar gamma scintigraphy (coronal scans, 40 cm FOV) immediately postdeposition, 1 hour 30 minutes and 22 hours after deposition of 99mTc-labeled particles (4.9 µm MMAD, GSD 2.5), inhaled in the supine posture (flow 0.5 L/s, 15 breaths/min). The distribution of retained particles at different times was used to infer deposition in different airway regions, with 22 hours representing alveolar deposition. The fraction of total slice ventilation per quartile of lung height from the lung apex to the dome of the diaphragm at functional residual capacity was computed, and co-registered with deposition data-apices aligned-using a transmission scan as reference. The ratio of fractional alveolar deposition to fractional ventilation of each quartile (r) was used to evaluate ventilation and deposition matching (r > 1, regional aerosol deposition fraction larger than regional ventilation fraction). RESULTS: r was not significantly different from 1 for all regions (1.04 ± 0.25, 1.08 ± 0.22, 1.03 ± 0.17, 0.92 ± 0.13, apex to diaphragm, p > 0.40) at the alveolar level (r22h). For retention times r0h and r1h30, only the diaphragmatic region at r1h30 differed significantly from 1. CONCLUSIONS: These results support the hypothesis that alveolar deposition is directly proportional to ventilation for ∼5 µm particles that are inhaled in the supine posture and are consistent with previous simulation predictions that show that convective flow is the main determinant of aerosol transport to the lung periphery.