Stanislav Tatkov

Background: Aerosol delivery during nasal high-flow (NHF) therapy occurs within a heated and humidified environment where formulation composition, NHF rate, and Next Generation Impactor (NGI)/system temperature may jointly influence aerosol behavior. However, their combined effects following NHF-conditioned transport remain incompletely characterized. Methods: A balanced 4 × 2 × 2 full-factorial design evaluated NGI/system temperature (5, 21, 37, and 40 °C), formulation (isotonic and 3% hypertonic salbutamol formulations), and NHF rate (30 and 50 L·min⁻¹). Aerosols generated using a vibrating mesh nebulizer integrated within an NHF system were transported through an adult nasal replica coupled to an NGI. Particle-size, fine-particle, delivery-efficiency, and regional-deposition metrics were analyzed using factorial ANOVA. Results: NHF rate exerted the greatest influence on downstream aerosol delivery, with increasing NHF rate reducing delivery efficiency, Fine Particle Dose (FPD), and NGI deposition while increasing NHF circuit retention. Significant Temperature × Formulation × Flow interactions were observed for MMAD (p = 0.0055), D16 (p < 0.0001), GSD (p = 0.0009), Fine Particle Fraction (FPF) (p = 0.0042), and dose-normalized FPD (p = 0.0149). The hypertonic formulation exhibited greater thermal sensitivity across several particle metrics. Although increasing NGI/system temperature generally reduced MMAD, D16, and D84, similar reductions in MMAD frequently produced markedly different responses in FPF, FPD, delivery efficiency, and regional deposition. All aerosols remained within ranges commonly associated with pulmonary deposition. Conclusions: Aerosol characteristics during NHF are governed by interacting effects of flow, formulation, and NGI/system temperature. Measurements conducted at NGI/system temperatures approaching body temperature provide additional mechanistic insight, particularly for hypertonic aerosols, and support integrated assessment of particle-size, delivery, and deposition outcomes rather than APSD metrics alone.

Background: During non-invasive respiratory support with nasal high flow (NHF), an asymmetrical interface (AI) featuring nasal prongs of different sizes has been shown to reduce re-breathing and improve gas exchange in hypoxemic and COPD patients. The objective of this study was to investigate the mechanisms of expired gas clearance during NHF in the presence of a nasogastric (NG) tube, which is commonly used post extubation and causes partial upper-airway occlusion. Methods: A computational fluid dynamics study was conducted using an averaged adult upper-airway model with breathing patterns representative of both healthy adults and patients with respiratory failure. Gas flow containing an end-tidal CO ₂ concentration of 5% was numerically simulated using Ansys Fluent (Ansys Inc., USA) during NHF at rates of 20 L/min and 60 L/min. The computational domain included the nasopharynx and the distal portions of commercially available nasal cannula interfaces. Results: During NHF, the AI splits the flow both inside and outside the prongs, resulting in differential pressure across the nasal cavities. At an NHF rate of 60 L/min this generated reverse flow through the choanae and increased gas clearance by more than 65%, with up to 91% of expired CO ₂ expelled through the less occluded naris, compared with a symmetrical cannula interface with similarly-sized nasal prongs. The position of the NG tube on the side of either the large or small prong had only a marginal effect on the almost complete clearance (100% vs. 98.6%) observed at an NHF rate of 60 L/min. However, at a lower NHF rate of 20 L/min, clearance increased from 29.6% to 53.1% when the NG tube was positioned on the side of the large prong. Conclusion: In the computational experiments, asymmetry in the upper-airway cross-sectional area produced by differences in nasal prong size and the presence of an NG tube during NHF alters the gas kinetics and may accelerate anatomical dead-space clearance, thereby reducing re-breathing of expired gas.

The asymmetrical cannula interface used during nasal high flow (NHF) causes unequal occlusion of the nares. This study demonstrates that physiological changes of nasal patency at the internal nasal valve, known as the nasal cycle, do not affect ventilation during NHF. In contrast, anatomical variability, such as differences in the cross-sectional area of the nares or severe nasal septum deviation, may substantially influence the generated pressure and could produce physiologically relevant effects during therapy.

Background: Dental treatment often requires prolonged mouth opening. This may compromise comfort during spontaneous nasal breathing and saliva swallowing, leading to stress or anxiety. A high-flow nasal cannula (HFNC) delivers warmed and humidified air at high flow rates and may improve breathing comfort; however, the feasibility of its routine use during dental treatment has not been established. Objectives: The primary objective of this pilot study is to evaluate the feasibility of conducting a definitive clinical trial to investigate the use of a HFNC during dental treatment. The secondary objective is to explore preliminary patient-centered outcomes related to stress and comfort to inform the design of future clinical trials. Methods: This single-center, open-label pilot feasibility study will be conducted at Nagasaki University Hospital, with adult patients undergoing routine full-mouth periodontal treatment participating in two treatment sessions, one without a HFNC and one with a HFNC, separated by at least four weeks. The primary feasibility outcomes include recruitment and retention rates, patient tolerance and acceptability of the HFNC, completeness of data collection, and device-related adverse events. The secondary outcomes are exploratory and include physiological stress-related parameters (pulse rate, respiratory rate, autonomic nervous system indices, and electroencephalographic alpha wave activity) and patient-reported comfort assessed using a questionnaire. Conclusions: This pilot study was designed to assess the feasibility and safety of HFNC use during full-mouth periodontal treatment and to inform the design of future definitive clinical trials. In particular, the resultant exploratory patient-centered outcomes and preliminary data may be used to guide outcome selection and sample size estimation.

Introduction: Dexmedetomidine is used for the sedation method in the case of endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of relieving patient anxiety. It has been reported that CO₂ accumulated during sedation causes an arousal reaction, so how to normalize CO₂ during sedation can be improved by administration of the minimum necessary sedative. Nasal High Flow oxygen therapy (NHF) uses a mild positive pressure load that improves carbon dioxide washout and reduces rebreathing to improve respiratory function and therefore is widely used to prevent hypoxemia and hypercapnia. In this study, we will investigate whether the upper airway patency would be maintained and the hypercapnia and hypoxemia during sedation would be prevented, by applying NHF as a respiratory management method to patients undergoing ERCP under sedation. Methods/design: In a randomized comparative study of 2 groups, the NHF device use group and the nasal cannula use group, for adult patients who visited the Nagasaki University Hospital and underwent ERCP examination under sedation. For sedation, Dexmedetomidine will be used in combination with and Midazolam and evaluation by anesthesiologist. In addition, as an analgesic, pethidine hydrochloride was administered intravenously. The total dose of the analgesic pethidine hydrochloride used in combination is used as the primary endpoint. As a secondary evaluation item, the percutaneous CO₂ concentration is evaluated with a TCO₂ monitor to examine whether it is effective in preventing hypercapnia. Furthermore, we will evaluate the incidence of hypoxemia with a percutaneous oxygen saturation value of 90% or less, and examine whether the use of equipment is effective in preventing the occurrence of hypercapnia and hypoxemia. Discussion: The purpose of this study was to obtain evidence for the utility of NHF as a potential therapeutic device for patients undergoing an ERCP under sedation, assessed by determining if the incidence rates of hypercapnia and hypoxemia decreased in the NHF device group, compared to the control group that did not use of this device.

Background: Nebulised drugs, including osmotic agents and saline, are increasingly used during noninvasive respiratory support, including nasal high-flow therapy. The authors conducted anin vitrostudy to compare the hydration effect of nebulised isotonic 0.9% and hypertonic 7.0% saline on mucociliary transport.Methods: In a perfused organ bath, 10 sheep tracheas were exposed to 7.5 mL nebulised 0.9% and 7.0% saline entrained into heated (38°C) and humidified air delivered at high and low flow (20 and 7 L·min⁻¹, respectively). Simultaneous measurements of the airway surface liquid height, mucus transport velocity, cilia beat frequency and surface temperature were made over time. The data are presented as mean±sd.Results: The airway surface liquid height increased significantly with both 0.9% and 7.0% saline: at low-flow by 37.2±10.0 µm and 152.7±10.9 µm, respectively, and at high-flow by 62.3±5.6 µm and 163.4±25.4 µm, respectively (p−1to 8.8±0.7 mm·min⁻¹and 17.1±0.5 mm·min⁻¹, respectively, with low-flow and at high-flow to 9.8±0.02 mm·min⁻¹(p=0.04) and 16.9±0.5 mm·min⁻¹(p<0.05), respectively. Ciliary beating did not change with 0.9% saline, but declined from 13.1±0.6 Hz to 10.2±0.6 Hz and 11.1±0.6 Hz (p<0.05) with 7.0% saline at low- and high-flow, respectively.Conclusions: The findings demonstrate that nebulised isotonic 0.9% saline, like hypertonic 7.0% saline, significantly stimulates basal mucociliary transport, and the use of high-flow delivery had no significantly different hydration effects compared with low-flow delivery. Hypertonic 7.0% saline suppressed ciliary beating, indicating an increase in airway surface liquid osmolarity, which may have negative effects on the airway surface with frequent use.

Positive airway pressure that dynamically changes with breathing, and clearance of anatomical dead space are the key mechanisms of noninvasive respiratory support with nasal high flow (NHF). Pressure mainly depends on flow rate and nare occlusion. The hypothesis is that an increase in asymmetrical occlusion of the nares leads to an improvement in dead-space clearance resulting in a reduction in re-breathing. Clearance was investigated with volumetric capnography in an adult upper-airway model, which was ventilated by a lung simulator with entrained carbon dioxide (CO₂) at respiratory rates (RR) of 15-45min^-1, and at 18min^-1 with COPD breathing patterns. Clearance was assessed at NHF of 20-60L/min with a symmetrical interface (SI) and an asymmetrical interface (AI). CO₂ kinetics visualized by infrared spectroscopy and mathematical modeling were used to study the mechanisms of clearance. At a higher RR(35 min^-1) and NHF of 60L/min clearance in the upper airway was significantly higher with the AI when compared to the SI(29.64±9.96%,p < 0.001), as opposed to at a lower RR (15min^-1) (1.40±6.25%,p > 0.05), (mean±SD). With COPD breathing, clearance by NHF was reduced, but significantly improved with the AI by 45.93% relative to the SI at NHF 20L/min (p < 0.0001). The maximum pressure achieved with the AI was 6.6cmH₂O and NHF 60L/min at the end of expiration. Pressure differences between nasal cavities led to the reverse flow observed in the optical model. Asymmetrical NHF increases dead-space clearance by reverse flow through the choanae and accelerates purging of expired gas via the less occluded nare.

Nasal high flow (NHF) is an efficient oxygenation tool for the treatment of respiratory failure. The study investigated the effect of breathing pattern on positive airway pressure and dead-space clearance by NHF. The breathing cycle during NHF was characterized in 26 patients with acute respiratory failure (ARF) and stable COPD and after mechanical ventilation (post-MV) via tracheostomy where also pressure was measured in the trachea. Dead-space clearance was measured in airway models during different breathing patterns. NHF reduced the respiratory rate (RR) and T_I/T_E through prolonging the T_E; the T_I/T_E ranged between ≤0.5 observed in the COPD patients and ∼1.0 in the ARF patients. NHF via a standard medium-sized cannula interface generated a low-level expiratory pressure proportional to NHF rate and breathing flow; the median generated positive end-expiratory pressure was only 1.71 cmH₂O at NHF 45 L/min. The dilution and purging of expired gas from a nasal cavity model were observed to occur at the end of expiration as expiratory flow slowed and the dynamic pressure decreased. The higher RR with shorter end-expiratory period resulted in reduced dead-space clearance by NHF; 20 L/min cleared 43 ± 2 mL at RR 15 min⁻¹ vs. 9 ± 5 mL at RR 45 min⁻¹, P < 0.001, which was increased at higher NHF rate. At lower RR, the clearance was similar between NHF rates 20 and 60 L/min. Higher NHF rates elevate positive airway pressure, and at the increased RR can improve the clearance. This may enhance gas exchange and lead to a reduction in the work of breathing. NEW & NOTEWORTHY During nasal high flow (NHF) an increased breathing frequency, which is commonly observed in acute respiratory failure, can lead to decreased dead-space clearance. Higher NHF rates increase the clearance and reduce the rebreathing which may eventually lower the respiratory rate and the work of breathing. Monitoring of the respiratory rate could be an important indicator of not only the respiratory function but also the NHF rate selection and the therapy efficacy.