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14 June 2020 Inhalation the lungs and delivers administered gas flow rates of typically between 5 and 60 liters per minute of heated, humidified air. Gas flows are set to match or exceed peak inspiratory flow rates in an effort to purge the upper airways of CO 2 , at the same time as delivering oxygen to the airways. HFNT is commonly adminis- tered via nasal cannula but it can also be administered by tracheostomy or a nose mask. In the current climate of the worldwide spread of COVID-19, patients are becoming hypoxic, and the World Health Organi- zation estimates that as many as 85% of patients will require some form of oxygen therapy. Many of those patients will likely be prescribed HFNT. 17 e clinical HFNT literature has focused on exam- ining patient outcomes when compared to the tradi- tional and more invasive means of ventilatory support, such as invasive mechanical ventilation. HFNT finds application across emergency ward and critical care settings, and consequently is used in the treatment of a wide variety of disease states, and patient types, infant through adult. us far, the number of reported therapeutics deliv- ered concurrently during HFNT is quite low, with the most common being bronchodilators in the treatment of acute asthma exacerbations, saline for hydration of the airways, prostacylins for treatment of pulmonary arterial hypertension and maintenance of normal mucociliary function during extended treatment. 18-23 High flow nasal therapy devices HFNT devices are generally classified as systems rely- ing on compressed oxygen and air supplied through the hospital wall or cylinders, systems generating their own flow by means of an integrated turbine, or systems whose primary function is mechanical ventilation, which includes HFNT functionality. Importantly, only some of these systems have approved accesso- ries for nebulizer attachment and few were designed to optimize aerosol delivery efficiency. is remains a significant opportunity for future improvement in HFNT system design. For example, those systems with integrated turbines may benefit from integrated nebu- lizer control, where such controls act to mitigate drug losses resulting from the various influencing factors discussed in the following sections. Aerosol delivery Concurrent aerosol delivery during HFNT is com- monplace. As previously mentioned, a relatively nar- row range of therapeutics are delivered. A review of the literature would suggest that these therapeutics are mainly aerosolized using nebulizers and predominately vibrating mesh nebulizers (VMNs). is is likely due to the VMN mode of action, and the fact that they do not add flow or pressure to the HFNT circuit, a par- ticularly important consideration in pediatric patients who have flows less than 20 liters per minute. A single bench model report on the use of pressurized metered dose inhalers (pMDIs) during HFNT indicated that and also to avoid exposure of the lower respiratory tract. Of note, there are no guidelines or international consensus regarding the relationship between aerosol characteristics and the precise deposition site within the nasal cavities. However, international regulatory guidance and requirements state that droplet or parti- cle size does need to be tightly controlled and validated through appropriate means, typically laser diffraction methods. Ultimately, the resultant efficacy of the prod- uct is very much reliant on clinical outcome studies, which in turn somewhat validate the appropriateness of the droplet or particles being generated. Much research is underway in this area; and indeed some of it is funded by agencies such as the United States Food and Drug Administration (FDA). erefore, we can expect fur- ther guidance and insight as the relevant bodies become more informed. Devices Depending on the type of formulation, a variety of devices have been used to deliver drugs intranasally. Devices for liquid formulations include instillation catheters, droppers, unit-dose containers, squeeze bottles, pump sprays, airless and preservative-free sprays, compressed air nebulizers and metered dose inhalers (MDIs). Devices for powder dosage forms include insufflators, single-dose and multi-dose powder inhalers and pres- surized MDIs. A comprehensive review of nasal drug delivery devices is provided by Djupesland. 2 Future possibilities Considering the massive potential for nasal admin- istration as a route for drug administration, there is a real need for improvements in the state of the art. We foresee that those improvements will center around formulations and devices and, most importantly, combinations of them. To facilitate this, Forbes, et al have recently published an expert consensus setting out the roadmap for future focus and developments in this field. 10 e relatively nascent field of targeting the CNS/brain is likely to see biggest strides. Non-obvious drivers such as healthcare economics and social drivers will probably provide the impetus. For example, in migraine treatment. Migraines are neurological disor- ders, often inherited, and affect patients ranging in age from adolescence to adulthood. is debilitating con- dition can have a direct impact on school performance, professional or work performance, social interactions and family life, and therefore is considered a high- value target. Treatment modalities today include oral, injection and, just recently, nasal. As described here, the ability to deliver a therapeutic API locally for fast action is a key advantage to be exploited. Trans-nasal lung deposition Trans-nasal lung deposition is typically achieved during concurrent high-flow nasal therapy (HFNT). HFNT is an increasingly common method of oxygenation of