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16 June 2020 Inhalation increased focus and push for innovation from what has classically been a "me-too" space. Trans-nasal pulmonary administration remains in its infancy but is poised to grow as evidenced by its rapid adoption to routine use in many intensive care units worldwide. As we better understand the relationships of particle size, delivered gas, patient anatomy, and inspiratory patterns across patient populations, we expect more optimized pulmonary delivery efficiency, expanding trans-nasal methods in treatment of neo- nates, infants, toddlers and older adults with a variety of agents. is could replace use of poorly tolerated ill-fitting masks and again enable new therapies. For toddlers who fight use of a mask for aerosol deliv- ery at home, trans-nasal pulmonary delivery could greatly reduce drama while increasing efficacy and prescription compliance. With nasal and trans-nasal pulmonary delivery, we are at the cusp of an inflection point in two intrinsi- cally connected, but very different fields of research and product development. We believe the next decade should see significant advances in both, further increas- ing the quality of life for patients, as well as offering sig- nificant value and opportunity for those groups willing to focus on them now. References 1. Hermens WA, Hooymans PM, Verhoef JC, Merkus FW. Effects of absorption enhancers on human nasal tissue ciliary movement in vitro. Pharmaceutical Research. 1990;7(2):144-146. 2. Djupesland PG. Nasal drug delivery devices: Characteristics and performance in a clinical per- spective—A review. Drug Delivery and Translational Research. 2013;3(1):42-62. 3. Hampel FC, Ratner PH, Van Bavel J, Amar N, Daftary P, Wheeler W, et al. Double-blind, placebo- controlled study of azelastine and fluticasone in a single nasal spray delivery device. Annals of Allergy, Asthma & Immunology. 2010;105(2):168-173. 4. Landis MS, Boyden T, Pegg S. Nasal-to-CNS drug delivery: Where are we now and where are we head- ing? An industrial perspective. erapeutic Delivery. 2012;3(2):195-208. 5. Laube BL. Devices for aerosol delivery to treat sinus- itis. Journal of Aerosol Medicine. 2007;20(s1):S5-S18. 6. Warnken ZN, Smyth HD, Watts AB, Weitman S, Kuhn JG, Williams III RO. Formulation and device design to increase nose to brain drug delivery. Journal of Drug Delivery Science and Technology. 2016;35:213-222. 7. Graff CL, Pollack GM. Nasal drug administra- tion: Potential for targeted central nervous sys- tem delivery. Journal of Pharmaceutical Sciences. 2005;94(6):1187-1195. Fugitive aerosols One often-overlooked aspect of aerosol delivery, whether it be by nebulizer, pressurized metered dose inhaler, soft mist inhaler or dry powder inhaler, is the risk of aerosols being released to the environment on exhalation or simply because they bypass the patient. HFNT is a candidate for large fugitive drug aerosol emissions (as opposed to patient-derived bioaerosol emissions) considering that the gas flow carrying the aerosol is unidirectional and continuous throughout the breath maneuver. One study in the literature has quantified these emissions. In the study, emissions across combinations of nasal cannula, tracheostomy and gas flow rate were assessed. The main findings suggest fugitive aerosol are emitted to the local envi- ronment however, at the higher gas flow rates, they are lower than those recorded at the lower gas flow rates. Again, this is likely due to higher levels of inertial impaction losses within the nasal passages, and thus, less is available to escape. 34 Evidence suggests that cov- ering the nasal cannula with a simple surgical mask can greatly reduce the dispersion of fugitive emissions. 35 Future possibilities With the use of HFNT increasing across the critical care and home care settings, the importance of opti- mized concurrent aerosol delivery will be critical. In order to facilitate that, custom-designed adapters or integrated nebulizer controls will be required and need to be designed through collaboration between partners, i.e., nebulizer and HFNT equipment manufacturers. We already see jet nebulizers being contraindicated by some systems, but often HFNT companies pay scant regard to the potential pitfalls of mismatched systems. It is proposed that more HFNT companies look to include provisions for nebulizer usage or, ideally, design specific adapters that facilitate optimal aerosol delivery. Concluding remarks: Where do we go next? Administration of aerosol to the nose is common and well accepted for a variety of local as well as systemic targets. Most therapeutic nasal sprays use relatively large particles to minimize pulmonary delivery, with seem- ingly little change in technology or approach over the last 40 years. However, with recent advances in the state of the art in both device and formulation, many more conditions are expected to be treatable with nasal deliv- ery. Additionally, we can expect to see further innova- tions in the delivery device arena, with devices capable of greater control over reliability and reproducibility of dosing, as well as increased accuracy in targeting. Now, more than ever, healthcare economics are pro- viding the impetus for innovation in this space and consequently we will see some non-obvious disease states being treated using the nasal route, for example autism and narcolepsy. Brain, central nervous system and systemic system therapies will all benefit from this