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.

Normative ranges of nasal airflow variables in healthy adults.

PURPOSE: Virtual surgery planning based on computational fluid dynamics (CFD) simulations of nasal airflow has the potential to improve surgical outcomes for patients with nasal airway obstruction (NAO). Virtual surgery planning requires normative ranges of airflow variables, but few studies to date have quantified inter-individual variability of nasal airflow among healthy subjects. This study reports CFD simulations of nasal airflow in 47 healthy adults. METHODS: Anatomically accurate three-dimensional nasal models were reconstructed from cone beam computed tomography scans and used for steady-state inspiratory airflow simulations with a bilateral flowrate of 250 ml/s. Normal subjective sensation of nasal patency was confirmed using the nasal obstruction symptom evaluation and visual analog scale. Healthy ranges for several CFD variables known to correlate with subjective nasal patency were computed, including unilateral airflow, nasal resistance, airspace minimal cross-sectional area (mCSA), heat flux (HF), and surface area stimulated by mucosal cooling (defined as the area where HF > 50 W/m2). The normative ranges were targeted to contain 95% of the healthy population and computed using a nonparametric method based on order statistics. RESULTS: A wide range of inter-individual variability in nasal airflow was observed among healthy subjects. Unilateral airflow varied from 60 to 191 ml/s, airflow partitioning ranged from 23.8 to 76.2%, and unilateral mCSA varied from 0.24 to 1.21 cm2. These ranges are in good agreement with rhinomanometry and acoustic rhinometry data from the literature. A key innovation of this study are the normative ranges of flow variables associated with mucosal cooling, which recent research suggests is the primary physiological mechanism of nasal airflow sensation. Unilateral HF ranged from 94 to 281 W/m2, while the surface area stimulated by cooling ranged from 27.4 to 64.3 cm2. CONCLUSIONS: These normative ranges may serve as targets in future virtual surgery planning for patients with NAO.

A hierarchical stepwise approach to evaluate nasal patency after virtual surgery for nasal airway obstruction.

BACKGROUND: Despite advances in medicine and expenditures associated in treatment of nasal airway obstruction, 25-50% of patients undergoing nasal surgeries complain of persistent obstructive symptoms. Our objective is to develop a "stepwise virtual surgery" method that optimizes surgical outcomes for treatment of nasal airway obstruction. METHODS: Pre-surgery radiographic images of two subjects with nasal airway obstruction were imported into Mimics imaging software package for three-dimension reconstruction of the airway. A hierarchical stepwise approach was used to create seven virtual surgery nasal models comprising individual (inferior turbinectomy or septoplasty) procedures and combined inferior turbinectomy and septoplasty procedures via digital modifications of each subject's pre-surgery nasal model. To evaluate the effects of these procedures on nasal patency, computational fluid dynamics modeling was used to perform steady-state laminar inspiratory airflow and heat transfer simulations in every model, at resting breathing. Airflow-related variables were calculated for virtual surgery models and compared with dataset containing results of healthy subjects with no symptoms of nasal obstruction. FINDINGS: For Subject 1, nasal models with virtual septoplasty only and virtual septoplasty plus inferior turbinectomy on less obstructed side were within the healthy reference thresholds on both sides of the nasal cavity and across all three computed variables. For Subject 2, virtual septoplasty plus inferior turbinectomy on less obstructed side model produced the best result. INTERPRETATION: The hierarchical stepwise approach implemented in this preliminary report demonstrates computational fluid dynamics modeling ability to evaluate the efficiency of different surgical procedures for nasal obstruction in restoring nasal patency to normative level.

Virtual Surgery for the Nasal Airway: A Preliminary Report on Decision Support and Technology Acceptance.

IMPORTANCE: Nasal airway obstruction (NAO) is a common problem that affects patient quality of life. Surgical success for NAO correction is variable. Virtual surgery planning via computational fluid dynamics (CFD) has the potential to improve the success rates of NAO surgery. OBJECTIVE: To elicit surgeon feedback of a virtual surgery planning tool for NAO and to determine if this tool affects surgeon decision making. DESIGN, SETTING, AND PARTICIPANTS: For this cross-sectional study, 60-minute face-to-face interviews with board-certified otolaryngologists were conducted at a single academic otolaryngology department from September 16, 2016, through October 7, 2016. Virtual surgery methods were introduced, and surgeons were able to interact with the virtual surgery planning tool interface. Surgeons were provided with a patient case of NAO, and open feedback of the platform was obtained, with emphasis on surgical decision making. MAIN OUTCOMES AND MEASURES: Likert scale responses and qualitative feedback were collected for the virtual surgery planning tool and its influence on surgeon decision making. RESULTS: Our 9 study participants were all male, board-certified otolaryngologists with a mean (range) 15 (4-28) number of years in practice and a mean (range) number of nasal surgeries per month at 2.2 (0.0-6.0). When examined on a scale of 1 (not at all) to 5 (completely), surgeon mean (SD) score was 3.4 (0.5) for how realistic the virtual models were compared with actual surgery. On the same scale, when asked how much the virtual surgery planning tool changed surgeon decision making, mean (SD) score was 2.6 (1.6). On a scale of 1 (strongly disagree) to 7 (strongly agree), surgeon scores for perceived usefulness of the technology and attitude toward using it were 5.1 (1.1) and 5.7 (0.9), respectively. CONCLUSIONS AND RELEVANCE: Our study shows positive surgeon experience with a virtual surgery planning tool for NAO based on CFD simulations. Surgeons felt that future applications and areas of study of the virtual surgery planning tool include its potential role for patient counseling, selecting appropriate surgical candidates, and identifying which anatomical structures should be targeted for surgical correction. LEVEL OF EVIDENCE: NA.

Correlation between Subjective Nasal Patency and Intranasal Airflow Distribution.

Objectives (1) Analyze the relationship between intranasal airflow distribution and subjective nasal patency in healthy and nasal airway obstruction (NAO) cohorts using computational fluid dynamics (CFD). (2) Determine whether intranasal airflow distribution is an important objective measure of airflow sensation that should be considered in future NAO virtual surgery planning. Study Design Cross-sectional. Setting Academic tertiary medical center and academic dental clinic. Subjects and Methods Three-dimensional models of nasal anatomy were created based on computed tomography scans of 15 patients with NAO and 15 healthy subjects and used to run CFD simulations of nasal airflow and mucosal cooling. Subjective nasal patency was quantified with a visual analog scale (VAS) and the Nasal Obstruction Symptom Evaluation (NOSE). Regional distribution of nasal airflow (inferior, middle, and superior) was quantified in coronal cross sections in the narrowest nasal cavity. The Pearson correlation coefficient was used to quantify the correlation between subjective scores and regional airflows. Results Healthy subjects had significantly higher middle airflow than patients with NAO. Subjective nasal patency had no correlation with inferior and superior airflows but a high correlation with middle airflow (| r| = 0.64 and | r| = 0.76 for VAS and NOSE, respectively). Anterior septal deviations tended to shift airflow inferiorly, reducing middle airflow and reducing mucosal cooling in some patients with NAO. Conclusion Reduced middle airflow correlates with the sensation of nasal obstruction, possibly due to a reduction in mucosal cooling in this region. Further research is needed to elucidate the role of intranasal airflow distribution in the sensation of nasal airflow.

Low re-inhalation of the exhaled flow during normal nasal breathing in a pediatric airway replica.

To estimate the fraction of the exhaled airflow that is re-inhaled during normal nasal breathing, experiments were carried out in a water tank with an anatomically accurate respiratory tract model of a 4-year-old child. The velocity of respiratory flow was scaled using similarity laws between air and water. Breath simulation was performed via a computer-controlled piston-cylinder system. Food-dye visualization allows a qualitative analysis of the re-inhaled fraction of this exhaled flow. For the quantitative analysis, neutrally buoyant particles were added to the water medium, and illuminated by the laser which illuminates the whole breathing region of the respiratory model, such that the trajectory and quantity of the re-inhaled particles can be recorded and counted. The experimental results in the pediatric airway replica show that a negligible fraction (<0.06%) of the exhaled airflow is re-inhaled during normal nasal breathing in the absence of the rising thermal plume. The artificial plume generated by a heated aluminium brick at the tank bottom increases the re-inhalation ratio by 4 times under the investigated case (albeit still at a very low value of 0.15%). Our results thus reveal that during normal nasal breathing in the present pediatric subject, the vast majority of human exhaled airflow escapes from the inhalation zone and is not re-inhaled.

Validation of airway resistance models for predicting pressure loss through anatomically realistic conducting airway replicas of adults and children.

This work describes in vitro measurement of the total pressure loss at varying flow rate through anatomically realistic conducting airway replicas of 10 children, 4 to 8 years old, and 5 adults. Experimental results were compared with analytical predictions made using published airway resistance models. For the adult replicas, the model proposed by van Ertbruggen et al. (2005. J. Appl. Physiol. 98, 970-980) most accurately predicted central conducting airway resistance for inspiratory flow rates ranging from 15 to 90 L/min. Models proposed by Pedley et al. (1970. J. Respir. Physiol. 9, 371-386) and by Katz et al. (2011. J. Biomech. 44, 1137-1143) also provided reasonable estimates, but with a tendency to over predict measured pressure loss for both models. For child replicas, the Pedley and Katz models both provided good estimation of measured pressure loss at flow rates representative of resting tidal breathing, but under predicted measured values at high inspiratory flow rate (60 L/min). The van Ertbruggen model, developed based on flow simulations performed in an adult airway model, tended to under predict measured pressure loss through the child replicas across the range of flow rates studied (2 to 60 L/min). These results are intended to provide guidance for selection of analytical pressure loss models for use in predicting airway resistance and ventilation distribution in adults and children.

Nasal versus oral aerosol delivery to the "lungs" in infants and toddlers.

OBJECTIVES: The oral route has been considered superior to the nasal route for aerosol delivery to the lower respiratory tract (LRT) in adults and children. However, there are no data comparing aerosol delivery via the oral and nasal routes in infants. The aim of this study was to compare nasal and oral delivery of aerosol in anatomically correct replicas of infants' faces containing both nasal and oral upper airways. METHODS: Three CT-derived upper respiratory tract ("URT") replicas representing infants/toddlers aged 5, 14 and 20 months were studied and aerosol delivery to the "lower respiratory tract" (LRT) by either the oral or nasal route for each of the replicas was measured at the "tracheal" opening. A radio-labeled (99mDTPA) normal saline solution aerosol was generated by a soft-mist inhaler (SMIRespimat® Boehringer Ingelheim, Germany) and aerosol was delivered via a valved holding chamber (Respichamber® TMI, London, Canada) and an air-tight mask (Unomedical, Inc., McAllen, TX). A breath simulator was connected to the replicas and an absolute filter at the "tracheal" opening captured the aerosol representing "LRT" dose. Age-appropriate mask dimensions and breathing patterns were employed for each of the airway replicas. Two different tidal volumes (Vt ) were used for comparing the nasal versus oral routes. RESULTS: Nasal delivery to the LRT exceeded that of oral delivery in the 5- and 14-month models and was equivalent in the 20-month model. Differences between nasal and oral delivery diminished with "age"/size. Similar findings were observed with lower and higher tidal volumes (Vt ). CONCLUSION: Nasal breathing for aerosol delivery to the "LRT" is similar to, or more efficient than, mouth breathing in infant/toddler models, contrary to what is observed in older children and adults. Pediatr Pulmonol. 2015; 50:276-283. © 2014 Wiley Periodicals, Inc.