Chantal Darquenne

• Ph.D.
• Professor (Full) at University of California, San Diego

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 response...

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 brea...

Assessing the toxicity of airborne particulate matter or the efficacy of inhaled drug depends upon accurate estimates of deposited fraction of inhaled materials. In silico approaches can provide important insights into site- or airway-specific deposition of inhaled aerosols in the respiratory system. In this study, we improved on our recently devel...

Introduction: The deposition of inhaled medications is the first step in the pulmonary pharmacokinetic process to produce a therapeutic response. Not only lung dose but more importantly the distribution of deposited drug in the different regions of the lung determines local bioavailability, efficacy, and clinical safety. Assessing aerosol depositi...

Obstructive sleep apnea (OSA) is common in people living with 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)...

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 m...

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 ph...

The extrathoracic upper airway (UA) is the first line of defense to prevent inhaled toxicants from reaching the lungs. Intersubject variability in shape and volume of the UA is expected to have a significant impact on the deposition of inhaled aerosols filtered by this region. The goal of this study is to develop a quantitative understanding of how in...

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 C...

Obstructive sleep apnea (OSA) is highly prevalent in people living with HIV (PLWH), and might contribute to frequently reported symptoms and co-morbidities. 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 non-anatomical traits import...

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...

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...

Laboratory animals are often used to derive health risk from environmental exposure or to assess the therapeutic effect of a drug delivered by inhaled therapy. Knowledge of the in-situ distribution of deposited particles on airway and alveolar surfaces is essential in any assessment of these effects. A unique database including both high-resolution...

The development of predictive aerosol dosimetry models has been a major focus of environmental toxicology and pharmaceutical health research for decades. One-dimensional (1D) models successfully predict overall deposition averages but fail to accurately predict local deposition. Computational fluid-particle dynamics (CFPD) models provide site-speci...

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...

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 o...

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...

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)...

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 ax...

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...

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 inspi...

High altitude pulmonary edema (HAPE) is a potentially fatal condition affecting high altitude sojourners. The biggest predictor of HAPE development is a history of prior HAPE. Magnetic resonance imaging (MRI) shows HAPE-susceptible, with a history of HAPE, but not HAPE-resistant (a history of repeated ascents without illness) individuals develop gr...

Translational investigations in cystic fibrosis (CF) have a need for improved quantitative and longitudinal measures of disease status. To establish a non-invasive quantitative MRI technique to monitor lung health in patients with CF and correlate MR metrics with airway physiology as measured by multiple breath washout (MBW). Data were collected in...

Participant-level spirometry, multiple breath washout (MBW), and fractional lung density (FLD) data. (PDF)

After the presentation of 60 papers at the conference "Advancing Aerosol Dosimetry Research" (October 24-25, 2014 in Irvine, CA, USA), attendees submitted written descriptions of needed research. About 40 research needs were submitted. The suggestions fell into six broad categories: 1) Access to detailed anatomic data; 2) Access to subject-specific...

Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participat...

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...

Understanding the regional partition of deposition of inhaled particles within the lung is important for improving targeted delivery of inhaled aerosolized drugs. One factor affecting regional deposition is gravity. As the lung deforms under its own weight, changes in lung volume, in airway geometries, and in spatial patterns of ventilation distrib...

In silico models of airflow and particle deposition in the lungs are increasingly used to determine the therapeutic or toxic effects of inhaled aerosols. While computational methods have advanced significantly, relatively few studies have directly compared model predictions to experimental data. Furthermore, few prior studies have examined the infl...

to the editor: We appreciate the comments of our colleagues (see Ref. 6) and agree with many of the assertions made. We support the need for large-scale epidemiology and the value in confirming that HIV is indeed an important risk factor for OSA. We did not focus on diabetes or hypertension as suggested by the comments, because our goal was to disc...

While it is well recognized that pulmonary deposition of inhaled particles is lowered in microgravity (µG) compared to 1G, the absence of sedimentation causes fine particles to penetrate deeper in the lung in µG. Using quantitative magnetic resonance imaging (MRI), we determined the effect of gravity on peripheral deposition of fine particles. Aero...

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Abstract The deposition of aerosol in the human lung occurs mainly through a combination of inertial impaction, gravitational sedimentation, and diffusion. For 0.5- to 5-μm-diameter particles and resting breathing conditions, the primary mechanism of deposition in the intrathoracic airways is sedimentation, and therefore the fate of these particles...

Aerosolized drugs are increasingly being used to treat chronic lung diseases or to deliver therapeutics systemically through the lung. The influence of disease, such as emphysema, on particle deposition is not fully understood. Using magnetic resonance imaging (MRI), the deposition pattern of iron oxide particles with mass median aerodynamic diamet...

Image-based in silico modeling tools provide detailed velocity and particle deposition data. However, care must be taken when prescribing boundary conditions to model lung physiology in health or disease, such as in emphysema. In this study, the respiratory resistance and compliance were obtained by solving an inverse problem; a 0D global model bas...

Specific Ventilation Imaging (SVI) uses proton MRI to quantitatively map the distribution of specific ventilation (SV) in the human lung, using inhaled oxygen as a contrast agent. To validate this recent technique, we compared the quantitative measures of heterogeneity of the SV distribution in a 15mm sagittal slice of lung obtained in 10 healthy s...

Exposure to extraterrestrial dusts is an almost inevitable consequence of any proposed planetary exploration. Previous studies in humans showed reduced deposition in low-gravity compared with normal gravity (1G). However, the reduced sedimentation means that fewer particles deposit in the airways, increasing the number of particles transported to t...

Lung deposition of >0.5μm particles is strongly influenced by gravitational sedimentation, with deposition being reduced in microgravity (μG) compared to normal gravity (1G). Gravity not only affects total deposition but may also alter regional deposition. Using gamma scintigraphy, we measured the distribution of regional deposition and retention o...

The toxic or therapeutic effect of an inhaled aerosol is highly dependent upon the site and extent of deposition in the lung. A novel MRI-based method was used to quantify the spatial distribution of particles in the rat lung. Rats were exposed to 0.95 μm-diameter iron oxide particles in a controlled manner (N = 6) or to particle-free air (N = 6)....

Lunar dust may be a toxic challenge to astronauts. While deposition in reduced gravity is less than in normal gravity (1 G), reduced gravitational sedimentation causes particles to penetrate deeper in the lung, potentially causing more harm. The likely design of the lunar habitat has a reduced pressure environment and low-density gas has been shown...

An investigation of airflow is essential in understanding the fate of aerosol particles in healthy and diseased lungs. Emphysema is a heterogeneous disease that results in destroyed pulmonary tissue, alveolar space enlargement and oxygen delivery impairment. A numerical model of the entire lung will assist in understanding the ventilation and aeros...

The aerosol bolus technique can be used to estimate the degree of convective mixing in the lung; however, contributions of different lung compartments to measured dispersion cannot be differentiated unambiguously. To estimate dispersion in the distal lung, we studied the effect of gravity and airway asymmetry on the dispersion of 1 μm-diameter part...

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. This article reviews the main mechanisms affecting the transport and deposition of inhaled aerosol in the human lung. Aerosol deposition in both the healthy and diseased l...

Rodents have been widely used to study the environmental or therapeutic impact of inhaled particles. Knowledge of airway morphometry is essential in assessing geometric influence on aerosol deposition and in developing accurate lung models of aerosol transport. Previous morphometric studies of the rat lung performed ex situ provided high-resolution...

Most previous computational studies on aerosol transport in models of the central airways of the human lung have focused on deposition, rather than transport of particles through these airways to the subtended lung regions. Using a model of the bronchial tree extending from the trachea to the segmental bronchi (J Appl Physiol 98: 970-980, 2005), we...

Although the major mechanisms of aerosol deposition in the lung are known, detailed quantitative data in anatomically realistic models are still lacking, especially in the acinar airways. In this study, an algorithm was developed to build multigenerational three-dimensional models of alveolated airways with arbitrary bifurcation angles and spherica...

Knowledge of the fate of aerosols in the lung is needed to understand the efficiency of inhaled drug therapy. Invasive animal experiments and imaging allows for detailed quantitative comparison with computational modeling. In this study we built a three-dimensional (3D) airway tree model using rat magnetic resonance images. A custom 3D finite eleme...

Detailed knowledge of the fate of aerosols in the lung is essential in understanding the effect of exposure to airborne particulate matter and infectious agents and in assessing the efficiency of inhaled drug therapy. Detailed, yet non-invasive, studies of peripheral aerosol deposition are almost impossible in humans. Thus, understanding the fate o...

Venous gas bubbles occur in recreational SCUBA divers in the absence of decompression sickness, forming venous gas emboli (VGE) which are trapped within pulmonary circulation and cleared by the lung without overt pathology. We hypothesized that asymptomatic VGE would transiently increase ventilation-perfusion mismatch due to their occlusive effects...

Obtaining in vivo data of particle transport in the human lung is often difficult, if not impossible. Computational fluid dynamics (CFD) can provide detailed information on aerosol transport in realistic airway geometries. This paper provides a review of the key CFD studies of aerosol transport in the acinar region of the human lung. It also descri...

Accurate modeling of air flow and aerosol transport in the alveolated airways is essential for quantitative predictions of pulmonary aerosol deposition. However, experimental validation of such modeling studies has been scarce. The objective of this study is to validate CFD predictions of flow field and particle trajectory with experiments within a...

Lunar dust presents a potential toxic challenge to future explorers of the moon. The extent of the inflammatory response to lunar dust will in part depend on where in the lung particles deposit. To determine the effect of lowered gravity, we measured deposition of 0.5 and 1 μm diameter particles in six subjects on the ground (1G) and during short p...

Both deposition and clearance of inhaled particles in the human lung will be altered in the low gravity environment on the lunar surface. Studies to measure both aspects will be used to assist in setting exposure standards to lunar dust.

Aerosol mixing resulting from turbulent flows is thought to be a major mechanism of deposition in the upper respiratory tract (URT). Because turbulence levels are a function of gas density, the use of a low-density carrier gas should reduce deposition in the URT allowing the aerosol to reach more peripheral airways of the lung. We performed aerosol...

Aerosol mixing resulting from turbulent flows is thought to be a major mechanism of deposition in the upper respiratory tract (URT). Because turbulence levels are a function of gas density, the use of a low-density carrier gas should reduce deposition in the URT allowing the aerosol to reach more peripheral airways of the lung. We performed aerosol...

Verifying numerical predictions with experimental data is an important aspect of any modeling studies. In the case of the lung, the absence of direct in vivo flow measurements makes such verification almost impossible. We performed computational fluid dynamics (CFD) simulations in a 3D scaled-up model of an alveolated bend with rigid walls that inc...

Verifying numerical predictions with experimental data is an important aspect of any modeling studies. In the case of the lung, the absence of direct in vivo flow measurements makes such verification almost impossible. We performed computational fluid dynamics (CFD) simulations in a 3D scaled-up model of an alveolated bend with rigid walls that inc...

We developed two new three-dimensional models of aerosol transport and deposition representative of two generations in the alveolar zone of the human lung, one with the bifurcation area, and one without. The models were used to simulate particle trajectories of 1–5μm particles in generations 18–22 of the human lung in different orientations with re...

Studies related to aerosol deposition in the alveolar pulmonary airways have been mostly restricted to numerical studies, which require further experimental validation. Few experimental studies have been performed extracting quantitative data due to the involved complexity accompanying the extremely low Reynolds-numbers (in the order of 0.01) encou...

Recent single breath washout (SBW) studies in microgravity and on the ground have suggested an important effect of airway closure on gas mixing in the human lung, reflected particularly in the phase III slope of vital capacity SBW and bolus tests. In order to explore this effect, we designed a SBW in which subjects inspired 2-l from residual volume...

Convective mixing (CM) refers to the different transport mechanisms except Brownian diffusion that irreversibly transfer inspired air into resident air and can be studied using aerosol bolus inhalations. This paper provides a review of the present understanding of how each of these mechanisms contributes to CM. Original data of the combined effect...

It has been suggested that irreversibility of alveolar flow combined with a stretched and folded pattern of streamlines can lead to a sudden increase in mixing in the lung. To determine whether this phenomenon is operative in the human lung in vivo, we performed a series of bolus studies with a protocol designed to induce complex folding patterns....

Aerosol mixing resulting from turbulent flows is thought to be an important mechanism of deposition in the upper respiratory tract (URT). Since turbulence levels are a function of gas density, the use of a low density carrier gas would be expected to reduce deposition in the URT. We measured aerosol deposition in the respiratory tract of 8 healthy...