Whereas most studies demonstrate a marked improvement in oxygenation with increasing air-flow rates, inconsistencies exist with regard to the respiratory pattern response to NHF. The majority of studies tested responses to NHF during wakefulness. Although some patients may have stayed awake throughout the protocols, others may have dozed off, given the comfort and relief of respiratory stress with NHF. In particular, several studies indicate that patients reduce their respiratory rates when using NHF, but this response was not consistent across individuals and between studies [4]. One study demonstrated that respiratory rate responses to NHF were markedly dependent on the sleep/wake state [4]. During wakefulness, respiratory rate slowed and tidal volume increased in response to NHF, whereas during sleep there was no change in respiratory rate but a reduction in tidal volume. Of note, the respiratory rate response during wakefulness preserved minute ventilation, whereas NHF during sleep was associated with an approximately 20 % decrease in minute ventilation. The physiologic mechanisms for the wakefulness ventilatory responses observed with NHF are unclear. Nevertheless, if these responses are present in patients with cardiorespiratory diseases, it may help to treat patients with COPD. These patients often adopt pursed-lip breathing to lower their respiratory rate and prolong expiratory time to alleviate expiratory and dynamic hyperinflation. Pursed-lip breathing is, however, associated with an increased work of breathing and patients cannot maintain this pattern over a longer time period. NHF responses, in fact, resemble the breathing pattern of pursed-lip breathing. Thus, NHF may provide a therapeutic benefit for patients who cannot or will not adopt a slow and deep breathing pattern. NHF may also be beneficial for subjects who have high dead space ventilation due to tachypnea or a rapid, shallow breathing pattern, particularly during sleep. NHF may help to prevent development of respiratory failure in patients who suffer from increased ventilatory loads during sleep.

Although nasal high flow increases pharyngeal pressure (see Fig. 80.2), it differs from CPAP during the expiratory phase [5]. The contribution of the cannula size/nasal valve area and nasal cannula flow rate determine expiratory pressure. There are two main explanations for the difference in expiratory resistance responses between NHF and CPAP. NHF exerts a jet-flow effect that creates a pressure gradient across the flow-restricted nose segment, whereas CPAP increases the pressure at the nares without creating a further pressure gradient across the valve area. Furthermore, CPAP only minimally increases pressure during expiration, indicating that air-flow resistance during expiration remained relatively constant with CPAP. Stiffening of the nasal passage may also contribute to a greater expiratory resistance with increasing expiratory air flow. Regardless of the mechanism, NHF is not like minimal CPAP; rather, it serves as a means to increase resistance to expiratory air. When NHF is present, the pressure at onset of inspiration remains above atmosphere for most of the inspiratory phase, raising the driving pressure for inspiration. Despite similar patient acceptance [6], improvements in inspiratory air-flow dynamics and increases in expiratory resistance make NHF a distinctly different form of ventilatory assistance compared with CPAP.

Several studies have examined the effect of NIV or CPAP on ventilation and gas exchanges in patients with COPD. Increasing levels of CPAP increases minute ventilation without a change in arterial blood gases, indicating that patients’ ventilatory responses to CPAP would differ from responses to NHF. Likewise, NHF would also differ from responses to NIV. During NIV, nasal or facial masks impose added dead-space volume. Improvements in alveolar ventilation must first overcome this added dead-space volume, which often requires the application of either high tidal volumes or high transpulmonary pressures, both of which are rarely well tolerated. In vitro imaging methods utilizing flow-dependent tracer-gas clearance models demonstrated increasing dead-space washout with increasing NHF rates. An anatomically based model established complete tracer-gas removal from the nasal cavities within 1.0 s. The level of clearance in the nasal cavities increased by 1.8 m /s for every 1.0 /min increase in the rate of NHF, which is capable of reducing dead-space re-breathing [7].

A reduction in dead-space volume to assist breathing has been used in patients with tracheotomies by insufflating fresh air into the tracheal tube. In these studies, reductions in dead-space volumes as low as 40 ml have been shown either to decrease arterial CO₂ from 46 to 40 mmHg, if tidal volume remained unchanged, or to reduce minute ventilation and work of breathing with no or only minimal reductions in arterial CO₂ [8]. The ventilatory responses to nasal NHF, therefore, resemble more those of tracheal gas insufflation. Thus, the principles of tracheal gas insufflation appear more suitable to explaining physiologic and clinical responses of nasal NHF than CPAP and NIV.