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.

Background: Inspired air is heated and humidified in the nose before it reaches lower airways. This mechanism is bypassed during tracheostomy, directly exposing the airways to colder and drier air from the environment, known to negatively affect mucociliary transport; however, little is known about how quickly mucociliary transport deteriorates. This study determines the short-term effect of flowing room air and nebulized hypertonic saline and mannitol on mucociliary transport in the trachea. In an ovine perfused in vitro tracheal model (N = 9) the epithelium was exposed to 25 L/min of flow, heated to lamb body temperature (38 °C) and fully saturated with water vapor as the control, followed by either room air (22 °C and 50% relative humidity) or nebulized solutions of NaCl 7% and mannitol 20% up to 1 min for a short duration, until mucociliary transport had visually changed. Mucus transport velocity (MTV) and cilia beat frequency (CBF) were continuously measured with video-microscopy. Results: Exposing the tracheal epithelium to air heated to body temperature and fully humidified had stable MTV 9.5 ± 1.1 mm/min and CBF 13.4 ± 0.6 Hz. When exposed to flow of room air, MTV slowed down to 0.1 ± 0.1 mm/min in 2.0 ± 0.4 s followed by a decrease in CBF to 6.7 ± 1.9 Hz, after 2.3 ± 0.8 s. Both MTV and CBF recovered to their initial state when heated and humidified air-flow was re-introduced. Exposing the tracheal epithelium to nebulized hypertonic saline and nebulized mannitol for 1 min increased MTV without a subsequent increase in CBF. Conclusions: This study demonstrates mucociliary transport can deteriorate within seconds of exposing the tracheal epithelium to flowing room air and increase rapidly when exposed to nebulized hypertonic solutions. The reduction in MTV precedes slowing of CBF with room air and MTV increases without a subsequent increase in CBF during the nebulization. Their relationship is non-linear and a minimum CBF of approximately 6 Hz is required for MTV > 0, while MTV can reach 10.9 mm/min without CBF increasing. Clinically these findings indicate a potential rapid detrimental effect of breathing with non-humidified air via bypassed upper airways and the short-term effects of nebulized osmotic agents that increase MTV.

In newborns, it is unclear how nasal high flow (NHF) generates positive airway pressure. In addition, the reported benefits of NHF such as reduction in work of breathing may be independent of airway pressure. The authors hypothesized that during NHF the area of leak and the flow determine airway pressure and that NHF can reduce the required minute ventilation to maintain gas exchange. In response to NHF, pressure was measured in the upper airways of 9 newborns and ventilation was measured in another group of 17 newborns. In a bench model, airway pressures were measured during NHF with different prong sizes, nare sizes, and flows. The airway pressures during 8 L/min NHF were greater when a larger cannula versus a smaller cannula was used ( P < 0.05). NHF reduced minute ventilation in 16 of 17 neonates, with a mean decrease of 24% from a baseline of 0.66 L/min (SD 0.21) ( P < 0.001), and was unrelated to changes in airway pressure; arterial oxygen saturation by pulse oximetry ([ ]) and tissue CO₂were unchanged. In the bench model, the airway pressure remained <2 cmH₂O when <50% of the “nare” was occluded by the prongs. As the leak area decreased, because of a smaller nare or a larger cannula, the airway pressure increased exponentially and was dependent on flow. In newborns NHF using room air substantially reduced minute ventilation without affecting gas exchange irrespective of a decrease or an increase of respiratory rate. NHF generates low positive airway pressure that exponentially increases with flow and occlusion of the nares.NEW & NOTEWORTHY In healthy newborns, nasal high flow (NHF) with room air reduced minute ventilation by one-fourth without affecting gas exchange but, in contrast to adults, produced variable response in respiratory rate during sleep. During NHF, pressure in the upper airways did not exceed 2 cmH₂O at 8 L/min (3.4 L·min⁻¹·kg⁻¹) and was unaffected by opening of the mouth. NHF can generate higher pressure with larger prongs that decrease the leak around the cannula or by increasing the flow rate.

Mucociliary transport in the respiratory epithelium depends on beating of cilia to move a mucus layer containing trapped inhaled particles toward the mouth. Little is known about the relationship between cilia beat frequency (CBF) and mucus transport velocity (MTV) in vivo under normal physiological conditions and when inspired air is dry or not fully humidified. This study was designed to use video-microscopy to simultaneously measure CBF and MTV in the tracheal epithelium through an implanted optical window in mechanically ventilated lambs. The inspired air in 6 animals was heated to body temperature and fully saturated with water for 4 hours as a baseline. In another series of experiments, 5 lambs were ventilated with air at different temperatures and humidities and the mucosal surface temperature was monitored with infrared macro-imaging. In the baseline experiments, during ventilation with fully humidified air at body temperature, CBF remained constant, mean 13.9 ± 1.6 Hz but MTV varied considerably between 0.1 and 26.1 mm/min with mean 11.0 ± 3.9 mm/min, resulting in a maximum mucus displacement of 34.2 µm/cilia beat. Fully humidified air at body temperature prevented fluctuations in the surface temperature during breathing indicating a thermodynamic balance in the airways. When lambs were ventilated with dryer air, the mucosal surface temperature and MTV dropped without a significant change in CBF. When inspired air was dry, mainly latent heat (92%) was transferred to air in the trachea, reducing the surface temperature by 5 °C. Reduced humidity of the inspired air lowered the surface temperature and reduced MTV in the epithelium during ventilation.