@article{kolanjiyil_kleinstreuer_kleinstreuer_pham_sadikot_2019, title={Mice-to-men comparison of inhaled drug-aerosol deposition and clearance}, volume={260}, ISSN={["1878-1519"]}, DOI={10.1016/j.resp.2018.11.003}, abstractNote={Part of the effective prediction of the pharmacokinetics of drugs (or toxic particles) requires extrapolation of experimental data sets from animal studies to humans. As the respiratory tracts of rodents and humans are anatomically very different, there is a need to study airflow and drug-aerosol deposition patterns in lung airways of these laboratory animals and compare them to those of human lungs. As a first step, interspecies computational comparison modeling of inhaled nano-to-micron size drugs (50 nm < d< 15μm) was performed using mouse and human upper airway models under realistic breathing conditions. Critical species-specific differences in lung physiology of the upper airways and subsequently in local drug deposition were simulated and analyzed. In addition, a hybrid modeling methodology, combining Computational Fluid-Particle Dynamics (CF-PD) simulations with deterministic lung deposition models, was developed and predicted total and regional drug-aerosol depositions in lung airways of both mouse and man were compared, accounting for the geometric, kinematic and dynamic differences. Interestingly, our results indicate that the total particle deposition fractions, especially for submicron particles, are comparable in rodent and human respiratory models for corresponding breathing conditions. However, care must be taken when extrapolating a given dosage as considerable differences were noted in the regional particle deposition pattern. Combined with the deposition model, the particle retention and clearance kinetics of deposited nanoparticles indicates that the clearance rate from the mouse lung is higher than that in the human lung. In summary, the presented computer simulation models provide detailed fluid-particle dynamics results for upper lung airways of representative human and mouse models with a comparative analysis of particle lung deposition data, including a novel mice-to-men correlation as well as a particle-clearance analysis both useful for pharmacokinetic and toxicokinetic studies.}, journal={RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement and Kleinstreuer, Nicole C. and Pham, Wellington and Sadikot, Ruxana T.}, year={2019}, month={Feb}, pages={82–94} }
 @article{kolanjiyil_kleinstreuer_2019, title={Modeling Airflow and Particle Deposition in a Human Acinar Region}, volume={2019}, ISSN={["1748-6718"]}, DOI={10.1155/2019/5952941}, abstractNote={The alveolar region, encompassing millions of alveoli, is the most vital part of the lung. However, airflow behavior and particle deposition in that region are not fully understood because of the complex geometrical structure and intricate wall movement. Although recent investigations using 3D computer simulations have provided some valuable information, a realistic analysis of the air-particle dynamics in the acinar region is still lacking. So, to gain better physical insight, a physiologically inspired whole acinar model has been developed. Specifically, air sacs (i.e., alveoli) were attached as partial spheroids to the bifurcating airway ducts, while breathing-related wall deformation was included to simulate actual alveolar expansion and contraction. Current model predictions confirm previous notions that the location of the alveoli greatly influences the alveolar flow pattern, with recirculating flow dominant in the proximal lung region. In the midalveolar lung generations, the intensity of the recirculating flow inside alveoli decreases while radial flow increases. In the distal alveolar region, the flow pattern is completely radial. The micron/submicron particle simulation results, employing the Euler–Lagrange modeling approach, indicate that deposition depends on the inhalation conditions and particle size. Specifically, the particle deposition rate in the alveolar region increases with higher inhalation tidal volume and particle diameter. Compared to previous acinar models, the present system takes into account the entire acinar region, including both partially alveolated respiratory bronchioles as well the fully alveolated distal airways and alveolar sacs. In addition, the alveolar expansion and contraction have been calculated based on physiological breathing conditions which make it easy to compare and validate model results with in vivo lung deposition measurements. Thus, the current work can be readily incorporated into human whole-lung airway models to simulate/predict the flow dynamics of toxic or therapeutic aerosols.}, journal={COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement}, year={2019} }
 @article{calmet_kleinstreuer_houzeaux_kolanjiyil_lehmkuhl_olivares_vazquez_2018, title={Subject-variability effects on micron particle deposition in human nasal cavities}, volume={115}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2017.10.008}, abstractNote={Validated computer simulations of the airflow and particle dynamics in human nasal cavities are important for local, segmental and total deposition predictions of both inhaled toxic and therapeutic particles. Considering three, quite different subject-specific nasal airway configurations, micron-particle transport and deposition for low-to-medium flow rates have been analyzed. Of special interest was the olfactory region from which deposited drugs could readily migrate to the central nervous system for effective treatment. A secondary objective was the development of a new dimensionless group with which total particle deposition efficiency curves are very similar for all airway models, i.e., greatly reducing the impact of intersubject variability. Assuming dilute particle suspensions with inhalation flow rates ranging from 7.5 to 20 L/min, the airflow and particle-trajectory equations were solved in parallel with the in-house, multi-purpose Alya program at the Barcelona Supercomputing Center. The geometrically complex nasal airways generated intriguing airflow fields where the three subject models exhibit among them both similar as well as diverse flow structures and wall shear stress distributions, all related to the coupled particle transport and deposition. Nevertheless, with the new Stokes-Reynolds-number group, Stk1.23Re1.28, the total deposition-efficiency curves for all three subjects and flow rates almost collapsed to a single function. However, local particle deposition efficiencies differed significantly for the three subjects when using particle diameters dp = 2, 10, and 20μm. Only one of the three subject-specific olfactory regions received, at relatively high values of the inertial parameter dp2Q, some inhaled microspheres. Clearly, for drug delivery to the brain via the olfactory region, a new method of directional inhalation of nanoparticles would have to be implemented.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Calmet, H. and Kleinstreuer, C. and Houzeaux, G. and Kolanjiyil, A. V. and Lehmkuhl, O. and Olivares, E. and Vazquez, M.}, year={2018}, month={Jan}, pages={12–28} }
 @article{kolanjiyil_kleinstreuer_2017, title={Computational analysis of aerosol-dynamics in a human whole-lung airway model}, volume={114}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2017.10.001}, abstractNote={Prediction of the air-particle dynamics in human lungs can reveal critical deposition sites of toxins or can determine best physical parameters for direct drug delivery and associated inhaler devices. However, the sheer complexity of the human lung, featuring a total of 16 million airways, prohibits a full-scale study. So, as an alternative, a physiologically realistic and computationally efficient computer simulation model has been developed. The configuration of the new whole-lung airway model (WLAM) consists of subject-specific upper airways from nose/mouth to, say, generation 3, which are then connected to adjustable triple bifurcation units (TBUs). These TBUs are in series and parallel to cover the remaining generations, based on morphometric measurements of human lung casts. Actual transient airflow, fluid-particle dynamics and alveolar tissue dynamics have been implemented to evaluate the impact of all respiratory airways under realistic inlet conditions. Specifically, the expanding and contracting motion of the alveoli mimic inhalation and exhalation in the alveolar region. Particle transport and deposition depend on the lung-airway geometry, particle characteristics, and inhalation flow frequency. Considering inhalation/exhalation in form of a square-wave breathing profile at 15 L/min with different tidal volumes and 3 μm-size microspheres as a WLAM test case, significantly higher deposition was observed in the alveolar region than in the upper airways. For short and light breathing conditions, multiple breathing cycles are required to exhale all the suspended particles. Particle deposition patterns differ for inhalation vs. exhalation, as well as in subsequent breathing cycles. During later cycles, the suspended particles tend to travel to distal airways. The model predictions agree well with in vivo results. The new WLAM can be used for local, segmental and total deposition predictions of inhaled toxic or therapeutic aerosols, and for providing inhaler-design guidelines to improve drug-aerosol targeting.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement}, year={2017}, month={Dec}, pages={301–316} }
 @article{kolanjiyil_kleinstreuer_2016, title={Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part I: Theory and model validation}, volume={79}, ISSN={["1879-0534"]}, DOI={10.1016/j.compbiomed.2016.10.020}, abstractNote={Computational predictions of aerosol transport and deposition in the human respiratory tract can assist in evaluating detrimental or therapeutic health effects when inhaling toxic particles or administering drugs. However, the sheer complexity of the human lung, featuring a total of 16 million tubular airways, prohibits detailed computer simulations of the fluid-particle dynamics for the entire respiratory system. Thus, in order to obtain useful and efficient particle deposition results, an alternative modeling approach is necessary where the whole-lung geometry is approximated and physiological boundary conditions are implemented to simulate breathing. In Part I, the present new whole-lung-airway model (WLAM) represents the actual lung geometry via a basic 3-D mouth-to-trachea configuration while all subsequent airways are lumped together, i.e., reduced to an exponentially expanding 1-D conduit. The diameter for each generation of the 1-D extension can be obtained on a subject-specific basis from the calculated total volume which represents each generation of the individual. The alveolar volume was added based on the approximate number of alveoli per generation. A wall-displacement boundary condition was applied at the bottom surface of the first-generation WLAM, so that any breathing pattern due to the negative alveolar pressure can be reproduced. Specifically, different inhalation/exhalation scenarios (rest, exercise, etc.) were implemented by controlling the wall/mesh displacements to simulate realistic breathing cycles in the WLAM. Total and regional particle deposition results agree with experimental lung deposition results. The outcomes provide critical insight to and quantitative results of aerosol deposition in human whole-lung airways with modest computational resources. Hence, the WLAM can be used in analyzing human exposure to toxic particulate matter or it can assist in estimating pharmacological effects of administered drug-aerosols. As a practical WLAM application, the transport and deposition of asthma drugs from a commercial dry-powder inhaler is discussed in Part II.}, journal={COMPUTERS IN BIOLOGY AND MEDICINE}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement}, year={2016}, month={Dec}, pages={193–204} }
 @article{vaish_kleinstreuer_kolanjiyil_saini_pillalamarri_2016, title={Laminar/turbulent airflow and microsphere deposition in a patient-specific airway geometry using an open-source solver}, volume={22}, ISSN={["1752-6426"]}, DOI={10.1504/ijbet.2016.079145}, abstractNote={Using the open-source software OpenFOAM as the solver, airflow and microsphere transport have been simulated in a patient-specific lung-airway model. A suitable transitional turbulence model was validated and implemented to accurately simulate airflow fields, as the laryngeal jet occurring in the throat region may induce turbulence immediately downstream. Furthermore, a modified eddy interaction model with a generalised near-wall correction factor is presented that more accurately simulates the particle trajectories and subsequent deposition phenomena which are especially affected by near-wall velocity fluctuations. Particle depositions in the realistic lung-airway configuration are compared with those in an idealised upper airway model. The results indicate that for microsphere deposition in turbulent airflow regions, selection of an appropriate near-wall correction factor can reduce the problem of subject variability for different lung-airway configurations. Open-source solvers for lung-aerosol dynamics simulations, such as OpenFOAM, are predictive tools which are basically cost-free, flexible, largely user-friendly, and portable.}, number={2}, journal={INTERNATIONAL JOURNAL OF BIOMEDICAL ENGINEERING AND TECHNOLOGY}, author={Vaish, Mayank and Kleinstreuer, Clement and Kolanjiyil, Arun V. and Saini, Nadish and Pillalamarri, Narasimha R.}, year={2016}, pages={145–161} }
 @article{kolanjiyil_kleinstreuer_2013, title={Nanoparticle Mass Transfer From Lung Airways to Systemic Regions-Part I: Whole-Lung Aerosol Dynamics}, volume={135}, ISSN={["1528-8951"]}, DOI={10.1115/1.4025332}, abstractNote={This is a two-part paper describing inhaled nanoparticle (NP) transport and deposition in a model of a human respiratory tract (Part I) as well as NP-mass transfer across barriers into systemic regions (Part II). Specifically, combining high-resolution computer simulation results of inhaled NP deposition in the human airways (Part I) with a multicompartmental model for NP-mass transfer (Part II) allows for the prediction of temporal NP accumulation in the blood and lymphatic systems as well as in organs. An understanding of nanoparticle transport and deposition in human respiratory airways is of great importance, as exposure to nanomaterial has been found to cause serious lung diseases, while the use of nanodrugs may have superior therapeutic effects. In Part I, the fluid-particle dynamics of a dilute NP suspension was simulated for the entire respiratory tract, assuming steady inhalation and planar airways. Thus, a realistic airway configuration was considered from nose/mouth to generation 3, and then an idealized triple-bifurcation unit was repeated in series and parallel to cover the remaining generations. Using the current model, the deposition of NPs in distinct regions of the lung, namely extrathoracic, bronchial, bronchiolar, and alveolar, was calculated. The region-specific NP-deposition results for the human lung model were used in Part II to determine the multicompartmental model parameters from experimental retention and clearance data in human lungs. The quantitative, experimentally validated results are useful in diverse fields, such as toxicology for exposure-risk analysis of ubiquitous nanomaterial as well as in pharmacology for nanodrug development and targeting.}, number={12}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement}, year={2013}, month={Dec} }
 @article{kolanjiyil_kleinstreuer_2013, title={Nanoparticle Mass Transfer From Lung Airways to Systemic Regions-Part II: Multi-Compartmental Modeling}, volume={135}, ISSN={["1528-8951"]}, DOI={10.1115/1.4025333}, abstractNote={This is the second article of a two-part paper, combining high-resolution computer simulation results of inhaled nanoparticle deposition in a human airway model (Kolanjiyil and Kleinstreuer, 2013, “Nanoparticle Mass Transfer From Lung Airways to Systemic Regions—Part I: Whole-Lung Aerosol Dynamics,” ASME J. Biomech. Eng., 135(12), p. 121003) with a new multicompartmental model for insoluble nanoparticle barrier mass transfer into systemic regions. Specifically, it allows for the prediction of temporal nanoparticle accumulation in the blood and lymphatic systems and in organs. The multicompartmental model parameters were determined from experimental retention and clearance data in rat lungs and then the validated model was applied to humans based on pharmacokinetic cross-species extrapolation. This hybrid simulator is a computationally efficient tool to predict the nanoparticle kinetics in the human body. The study provides critical insight into nanomaterial deposition and distribution from the lungs to systemic regions. The quantitative results are useful in diverse fields such as toxicology for exposure-risk analysis of ubiquitous nanomaterial and pharmacology for nanodrug development and targeting.}, number={12}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement}, year={2013}, month={Dec} }