Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic.

How human respiratory physiology and the transport phenomena associated with inhaled airflow in the upper airway proceed to impact transmission of SARS-CoV-2, leading to the initial infection, stays an open question. An answer can help determine the susceptibility of an individual on exposure to a COVID-2019 carrier and can also provide a preliminary projection of the still-unknown infectious dose for the disease. Computational fluid mechanics enabled tracking of respiratory transport in medical imaging-based anatomic domains shows that the regional deposition of virus-laden inhaled droplets at the initial nasopharyngeal infection site peaks for the droplet size range of approximately 2.5–19 $$\upmu $$μ . Through integrating the numerical findings on inhaled transmission with sputum assessment data from hospitalized COVID-19 patients and earlier measurements of ejecta size distribution generated during regular speech, this study further reveals that the number of virions that may go on to establish the SARS-CoV-2 infection in a subject could merely be in the order of hundreds.

Importance: Nasal valve compromise is a major cause of nasal obstruction, and multiple methods have been developed to address it. Objective: To compare nasal airflow resistance, airflow partitioning, and mucosal cooling (heat flux) before and after 2 surgical interventions, butterfly and spreader graft placement, used to treat nasal valve compromise. Design, Setting, and Participants: In this cadaveric tissue study, 4 fresh cadaveric heads underwent both spreader graft and butterfly graft surgical procedures in alternating sequence in March 2016. Preoperative and postoperative computed tomographic scans were used to generate 3-dimensional (3-D) models of the nasal airway. These models were then used in steady state computational fluid dynamics simulations of airflow and heat transfer during inspiration. Intervention: Butterfly and spreader graft techniques. Main Outcomes and Measures: Nasal airflow resistance, airflow partitioning, and heat flux. Results: Donors 1, 2, and 3 were white males; donor 4, a white female. Computational fluid dynamics simulations during inspiration in 3-D models generated from preoperative and postoperative computed tomographic scans of the 4 cadaveric heads indicated reductions from preoperative values in nasal airflow resistance associated with both butterfly grafts (range, 20%-51%) and spreader grafts (range, 2%-29%). Butterfly grafts were associated with a greater reduction in nasal airflow resistance in models of all 4 cadaveric heads. Changes from preoperative values for heat flux, a biophysical variable that correlates with the subjective sensation of nasal patency, were more variable, ranging from −11% to 4% following butterfly grafts and −9% to 10% following spreader grafts. The preoperative airflow allocation in the left and right nostrils improved consistently with the butterfly graft. With the spreader graft, there were improvements for donors 1 and 4, but the allocations were worse for donors 2 and 3. Conclusions and Relevance: The results of this study suggest that the more recently developed butterfly graft technique may be associated with a similar level of improved nasal airflow as that observed with the use of a spreader graft in nasal valve compromise. Both interventions were associated with comparable changes in heat flux. Because this study addressed only static internal nasal valve stenosis, even greater differences in air flow and heat flux between the 2 techniques may be anticipated in a dynamic model. Further investigation in patients is warranted. Level of Evidence: NA .