Effects of nasal high flow on nocturnal hypercapnia, sleep, and sympathovagal balance in patients with neuromuscular disorders.

PURPOSE: In neuromuscular disorders (NMD), inspiratory muscle weakness may cause sleep-related hypoventilation requiring non-invasive ventilation (NIV). Alternatively, nasal high flow therapy (NHF) may ameliorate mild nocturnal hypercapnia (NH) through washout of anatomical dead space and generation of positive airway pressure. Ventilatory support by NIV or NHF might have favourable short-term effects on sympathovagal balance (SVB). This study comparatively investigated the effects of NHF and NIV on sleep-related breathing and SVB in NMD patients with evolving NH. METHODS: Transcutaneous CO2 (ptcCO2), peripheral oxygen saturation (SpO2), sleep outcomes and SVB (spectral analysis of heart rate, diastolic blood pressure variability) along with haemodynamic measures (cardiac index, total peripheral resistance index) were evaluated overnight in 17 patients. Polysomnographies (PSG) were randomly split into equal parts with no treatment, NIV and NHF at different flow rates (20 l/min vs. 50 l/min). In-depth analysis of SVB and haemodynamics was performed on 10-min segments of stable N2 sleep taken from each intervention. RESULTS: Compared with no treatment, NHF20 and NHF50 did not significantly change ptcCO2, SpO2 or the apnea hypopnea index (AHI). NHF50 was poorly tolerated. In contrast, NIV significantly improved both gas exchange and AHI without adversely affecting sleep. During daytime, NHF20 and NHF50 had neutral effects on ventilation and oxygenation whereas NIV improved ptcCO2 and SpO2. Effects of NIV and NHF on SVB and haemodynamics were neutral during both night and daytime. CONCLUSIONS: NHF does not correct sleep-disordered breathing in NMD patients with NH. Both NHF and NIV exert no immediate effects on SVB.

Clinical Evidence of Nasal High-Flow Therapy in Chronic Obstructive Pulmonary Disease Patients.

Nasal high-flow therapy (NHFT) is an upcoming treatment for chronic obstructive pulmonary disease (COPD) patients. It supplies heated, humidified, and, desirably, oxygen-enriched air through a nasal cannula at flow rates up to 60 L/min. Several studies examined the effect of NHFT in COPD patients, but a clear overview is lacking. The present review aimed to give an overview of the clinical evidence of NHFT in 3 aspects of COPD care: long-term use in stable COPD patients, use for treatment of COPD exacerbations, and use during exercise therapy in COPD. For each topic, a specific literature search was performed up to December 9, 2019. Studies show promising results, with most evidence for its long-term use in hypoxemic COPD patients that frequently exacerbate, and very limited evidence for its use during COPD exacerbations or as a worthwhile adjunct to exercise training. More evidence is therefore needed to know how to incorporate NHFT in standard clinical practice.

Dose Response to Transnasal Pulmonary Administration of Bronchodilator Aerosols via Nasal High-Flow Therapy in Adults with Stable Chronic Obstructive Pulmonary Disease and Asthma.

BACKGROUND: There has been increasing interest in transnasal pulmonary aerosol administration, but the dose-response relationship has not been reported. OBJECTIVES: To determine the accumulative bronchodilator dose at which patients with stable mild-to-moderate asthma and chronic obstructive pulmonary disease (COPD) achieve similar spirometry responses before and after bronchodilator tests using albuterol via a metered dose inhaler with a valved holding chamber (MDI + VHC). METHOD: Adult patients who met ATS/ERS criteria for bronchodilator responses in pulmonary function laboratory were recruited and consented to participate. After a washout period, patients received escalating doubling dosages (0.5, 1, 2, and 4 mg) of albuterol in a total volume of 2 mL delivered by vibrating mesh nebulizer via a nasal cannula at 37°C with a flow rate of 15-20 L/min using a Venturi air entrainment device. Spirometry was measured at baseline and after each dose. Titration was stopped when an additional forced expiratory volume in 1 second (FEV1) improvement was <5%. RESULTS: 42 patients (16 males) with stable mild-to-moderate asthma (n = 29) and COPD (n = 13) were enrolled. FEV1 increment after a cumulative dose of 1.5 mg of albuterol via nasal cannula at 15-20 L/min was similar to 4 actuations of MDI + VHC (0.34 ± 0.18 vs. 0.34 ± 0.12 L, p = 0.878). Using ATS/ERS criteria of the bronchodilator test, 33.3% (14/42) and 69% (29/42) of patients responded to 0.5 and 1.5 mg of albuterol, respectively. CONCLUSIONS: With a nasal cannula at 15-20 L/min, transnasal pulmonary delivery of 1.5 mg albuterol resulted in similar bronchodilator response as 4 actuations of MDI + VHC.

Nocturnal High-Flow Nasal Cannula Therapy and Sinonasal Symptoms During Cystic Fibrosis Exacerbations.

BACKGROUND: Both nasal obstruction and sleep disturbance are common in patients with cystic fibrosis (CF). In patients with obstructive sleep apnea (OSA), studies suggest that these conditions are related and that nasal congestion improves with CPAP therapy. We hypothesized that subjects admitted to hospital for therapy of an exacerbation of CF would have both nasal symptoms and sleep disturbance and that these would improve with the initiation of nocturnal high-flow nasal cannula therapy (HFNC). METHODS: Twenty-five subjects with an exacerbation of CF were enrolled to randomly receive either 5 d of nocturnal HFNC at 20 L/min in the treatment group or 5 L/min of nocturnal nasal cannula air at ambient temperature and humidity in the low-flow group. On the first and last day of the study, the Sino-Nasal Outcome Test (SNOT-20) was administered to evaluate nasal symptoms, and sleep quality was measured using the Actiwatch 2. RESULTS: Fifteen subjects completed the study (6 HFNC, 9 low flow). We confirmed that subjects had significant sleep disturbance that did not improve over the 5 d of the study. Subjects also had disturbing nasal symptoms that significantly improved only in those receiving HFNC (pre 14 [20] vs post 6 [13], P = .027). CONCLUSIONS: Similar to what has been reported in older subjects with OSA, nocturnal HFNC improves sinonasal symptoms in subjects with an exacerbation of CF. There was no measurable effect on sleep quality, which may be due to the short duration of the study, or to subjects being evaluated while being treated in a hospital setting.

Primary tracheal small-cell carcinoma detected 11 months after surgery for pulmonary large-cell neuroendocrine carcinoma: A case report.

Primary tracheal small-cell carcinoma is rare, and is often treated using small-cell lung cancer guidelines given that no standard treatment has been established for it. We report a patient in whom nodules appeared in the trachea and left main bronchus 11 months after surgery for pulmonary large-cell neuroendocrine carcinoma; a biopsy revealed small-cell carcinoma. Given the absence of malignant lesions elsewhere in the body, the lesions were diagnosed as primary tracheal small-cell carcinoma. Respiratory failure progressed rapidly owing to airway stenosis caused by the growing lesion, and the patient required nasal high-flow therapy. However, the lesions shrank a few days after commencing first-line chemotherapy, and his respiratory failure resolved. Accelerated hyperfractionated radiotherapy was administered in conjunction with the third course of chemotherapy, and the patient ultimately achieved a complete response. Although the lesions were initially suspected of being postoperative recurrence of pulmonary large-cell neuroendocrine carcinoma, the fact that the biopsy revealed them to be primary tracheal small-cell carcinoma indicates that intra-airway nodules that appear after lung cancer surgery may possibly be primary tracheal tumors.

Upper airway pressure distribution during nasal high-flow therapy.

Two working mechanisms of Nasal High-Flow Therapy (NHFT) are washout of anatomical dead space and provision of positive end-expiratory pressure (PEEP). The extent of both mechanisms depends on the respiration aerodynamics and the corresponding pressure distribution: at end-expiration the onset of uniform pressure indicates the jet penetration length, and the level of the uniform pressure is the PEEP. The clinical problem is that adequate measurements in patients are presently impossible. In this study, the respiratory pressure distribution is therefore measured in 3D-printed anatomically correct upper-airway models of an adult and an infant. Assuming that elastic fluctuations in airway anatomy are sufficiently small, the aerodynamics in these rigid models will be very similar to the aerodynamics in patients. It appears that, at end-expiration, the jet penetrates into or slightly beyond the nasal cavity, hardly depending on cannula size or NHFT flow rate. PEEP is approximately proportional to the square of the flow rate: it can be doubled by increasing the flow rate by 40%. In the adult model, PEEP is accurately predicted by the dynamic pressure at the prong-exits, but in the infant model this method fails. During respiration, large pressure fluctuations occur when the cannula is relatively large compared to the nostrils.

Nasal High-Flow Therapy during Exercise in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Background: Several studies have evaluated the effect of nasal high-flow (NHF) therapy to enhance exercise performance and tolerance in patients with chronic obstructive pulmonary disease (COPD); however, results are disparate. Objective: The aim of this systematic review and meta-analysis was to assess the effect of NHF therapy as an adjuvant to exercise training on functional exercise capacity in patients with COPD. Data Sources: An electronic search was performed in the following databases: PubMed, the Cochrane Central Register of Controlled Trials, the Physiotherapy Evidence Database, ScienceDirect, the Web of Science, OpenGrey, ClinicalTrials.gov, and European Respiratory Society and American Thoracic Society databases. Data Extraction: Two authors independently selected relevant randomized trials (parallel-group or crossover design), extracted data, assessed the risk of bias, and rated the quality of the evidence. Synthesis: Eleven studies were included, involving 408 participants (eight full papers and three conference abstracts). Most studies had a high risk of bias or other methodological limitations. The use of NHF therapy during a single session increased functional exercise capacity (standardized mean difference, 0.36 [95% confidence interval (CI), 0.03 to 0.69]; P = 0.03, heterogeneity [I2 = 83%]). When conference abstracts were included in the pooled analysis, the estimated effect did not change (P = 0.006). The use of NHF therapy throughout a pulmonary rehabilitation program (parallel-group randomized controlled trials) increased functional exercise capacity at 4-12 weeks compared with training without NHF therapy (standardized mean difference, 0.34 [95% CI, 0.00-0.68]; P = 0.05, heterogeneity [I2 = 18%]). Conclusions: There is very-low-quality to low-quality evidence that NHF therapy improves functional exercise capacity. Patient responses to NHF therapy were highly variable and heterogeneous, with benefits ranging from clinically trivial to worthwhile.

Successful management of a patient with preoperative respiratory failure due to a solid giant retroperitoneal tumor: a case report.

BACKGROUND: We report the successful preoperative management of respiratory failure in a patient with a solid giant retroperitoneal tumor with a hemodynamic monitoring system and nasal high-flow therapy (NHFT). CASE PRESENTATION: Twenty days before his scheduled resection of a giant retroperitoneal liposarcoma, a 64-year-old man presented with dyspnea. After admission to our intensive care unit, he received NHFT and hemodynamic therapy using a LiDCOrapid V3™ monitor (Masimo Japan, Tokyo). NHFT and intense diuresis improved his respiratory condition. The tumor resection was performed on the 5th day. He was discharged to the general ward with an oxygen nasal cannula on the second postoperative day. Although preoperative transthoracic echography showed mild aortic regurgitation and moderate mitral regurgitation, the degree of regurgitation had become trivial about 1-month post-surgery. CONCLUSIONS: A cause of preoperative respiratory failure associated with a giant retroperitoneal tumor might be not only diaphragmatic compression but also heart failure and excess fluid volume.

Nasal High Flow Therapy For Symptom Management in People Receiving Palliative Care.

For patients with chronic non-malignant lung disease, severe chronic breathlessness can significantly impact quality of life, causing significant disability, distress, social isolation, and recurrent hospital admissions. Caregivers for people with challenging symptoms, such as severe breathlessness, are also profoundly impacted. Despite increasing research focused on breathlessness over recent years, this symptom remains extremely difficult to manage, with no effective treatment that completely relieves breathlessness. A new potential treatment for relieving breathlessness in patients at home is nasal high flow (NHF) therapy. NHF therapy is a respiratory support system that delivers heated, humidified air (together with oxygen if required) with flows of up to 60 L/min. This case describes a patient with very severe chronic obstructive pulmonary disease who received domiciliary NHF therapy (approximately 8 hours/day, flow rate of 20 L/min) over twelve months with good effect for the relief of severe chronic breathlessness. We discuss the management principles for severe chronic breathlessness, the physiological effects of NHF therapy and the evidence for long-term use in the community setting. With the support of respiratory and palliative care clinicians together, domiciliary NHF therapy has great potential for improving current symptom management approaches in people with life-limiting illnesses.

Nasal high-flow therapy as an adjunct to exercise in patients with cystic fibrosis: A pilot feasibility trial.

BACKGROUND: Exercise tolerance in people with CF and advanced lung disease is often reduced. While supplemental oxygen can improve oxygenation, it does not affect dyspnoea, fatigue or comfort. Nasal high-flow therapy (NHFT), thanks to its pathophysiological mechanisms, could improve exercise tolerance, saturation and dyspnoea. This study explores the feasibility of conducting a clinical trial of using NHFT in patients with CF during exercise. METHODS: A pilot, open-label, randomized crossover trial was performed, enroling 23 participants with CF and severe lung disease. Participants completed two treadmill walking test (TWT) with and without NHFT at 24-48 h interval. Primary outcome was trial feasibility, and exploratory outcomes were TWT distance (TWTD), SpO2, transcutaneous CO2, dyspnoea and comfort. RESULTS: Recruitment rate was 2.4 subjects/month with 1.3:1 screening-to-randomization ratio. No adverse events caused by NHFT were observed. Tolerability was good and data completion rate was 100%. Twenty subjects (91%) were included in the exploratory study. Mean difference in TWTD on NHFT was 19 m (95% CI [4.8 - 33.1]). SpO2 was similar, but respiratory rate and mean tcCO2 were lower on NHFT (mean difference = -3.9 breaths/min 95% CI [-5.9 - -1.9] and -0.22 kPa 95% CI [-0.4 - 0.04]). NHFT reduced exercise-induced dyspnoea and discomfort. CONCLUSION: Trials using NHFT in patients with CF during exercise are feasible. NHFT appears to improve walking distance, control respiratory rate, CO2, dyspnoea and improve comfort. A larger trial with a longer intervention is feasible and warranted to confirm the impact of NHFT in training programmes for patients with CF.

DUAL-energy computed tomography findings in a case of COVID-19.

BACKGROUND: COVID-19 pneumonia has lesions with a decreased blood flow. Dual-energy computed tomography is suitable to elucidate the pathogenesis of COVID-19 pneumonia because it highlights the blood flow changes in organs. We report the dual-energy computed tomography findings of a successfully treated case of COVID-19 pneumonia. CASE PRESENTATION: An obese 49-year-old man with COVID-19 pneumonia was transferred from another hospital on day 11 after onset of illness. Although he was hypoxemic (PaO2/FiO2 = 100), tracheal intubation was not performed after anticipating difficulty in weaning from mechanical ventilation. Prone position therapy and nasal high flow therapy were administered, and the patient was discharged after his condition improved. Dual-energy computed tomography was performed three times during hospitalization, and it revealed improvement in the blood flow defect, unlike plain computed tomography that did not show much improvement. CONCLUSION: Dual-energy computed tomography can assess perfusion in COVID-19 pneumonia in real time and may be able to predict its severity.

Implementation of a protocol-based strategy for weaning nasal high flow therapy in preterm infants.

OBJECTIVE: We compared protocolized weaning versus nonprotocolized weaning practice from nasal high flow therapy (nHFT) in preterm infants. STUDY DESIGN: A before-and- after observational study. METHODS: The study was conducted in three phases; Phase 1: infants were weaned according to usual practice for 6 months (nonprotocolized), Phase 2: education and training physicians and nursing staff for the protocol for 1 month, and Phase 3: protocol of weaning from nHFT was applied for the following 6 months with specified criteria for readiness to wean, weaning failure and weaning technique. The primary outcome was failure to wean off nHFT. RESULTS: One hundred and four preterm infants were enrolled, 51 preterm infants in the protocol group and 53 in the nonprotocol group. The groups were similar in demographic and clinical characteristics at baseline. There were significantly lower number of patients who failed weaning from nHFT in the protocol group compared to nonprotocol group (4 [7.8%] versus 15 [28.3%], p = .007]. There was shorter time to reach full enteral feeding in the protocol group compared with nonprotocol group (p = .03). There were no significant differences between groups regarding other outcomes including total durations of respiratory support, nHFT and oxygen therapy, duration of nHFT after decision of weaning, and neonatal mortality and morbidity. CONCLUSION: Implementation of a standardized protocol for weaning from nHFT in preterm infants reduced weaning failure and reduced the time to full feeds. Larger trials are recommended to detect the impact of weaning protocols on other outcomes.

Nasal High Flow in Room Air for Hypoxemic Bronchiolitis Infants.

Background: Bronchiolitis is the most common reason for hospital admission in infants, with one third requiring oxygen therapy due to hypoxemia. It is unknown what proportion of hypoxemic infants with bronchiolitis can be managed with nasal high-flow in room air and their resulting outcomes. Objectives and Settings: To assess the effect of nasal high-flow in room air in a subgroup of infants with bronchiolitis allocated to high-flow therapy in a recent multicenter randomized controlled trial. Patients and Interventions: Infants allocated to the high-flow arm of the trial were initially treated with room air high-flow if saturations were ≥85%. Subsequently, if oxygen saturations did not increase to ≥92%, oxygen was added and FiO2 was titrated to increase the oxygen saturations. In this planned sub-study, infants treated during their entire hospital stay with high-flow room air only were compared to infants receiving either standard-oxygen or high-flow with oxygen. Baseline characteristics, hospital length of stay and length of oxygen therapy were compared. Findings: In the per protocol analysis 64 (10%) of 630 infants commenced on high-flow room air remained in room air only during the entire stay in hospital. These infants on high-flow room air were on average older and presented with moderate hypoxemia at presentation to hospital. Their length of respiratory support and length of stay was also significantly shorter. No pre-enrolment factors could be identified in a multivariable analysis. Conclusions: In a small sub-group of hypoxemic infants with bronchiolitis hypoxemia can be reversed with the application of high-flow in room air only. Trial registration: ACTRN12615001305516.

Nasal High-Flow Therapy as Primary Respiratory Support for Preterm Infants without the Need for Rescue with Nasal Continuous Positive Airway Pressure.

AIM: To evaluate the effectiveness of nasal high-flow therapy (nHFT) as primary respiratory support for preterm infants with respiratory distress syndrome (RDS) in two tertiary neonatal units. METHODS: A retrospective outcome analysis of initial respiratory support strategies was performed in two tertiary neonatal units in the UK: John Radcliffe Hospital (JRH), Oxford and St Peter's Hospital (SPH), Chertsey. Infants born between 28+0 and 36+6 weeks gestational age (GA) between May 2013 and June 2015 were included. RESULTS: A total of 381 infants, 191 from JRH and 190 from SPH, were analysed. Infants were stabilised in the delivery room using mask continuous positive airway pressure followed by nHFT. Endotracheal intubation was performed according to local protocols, depending on the severity of RDS. There were significant differences in initial intubation rates according to GA (26% JRH vs. 16.9% SPH, p < 0.001 for babies < 32 weeks GA, and 8.2% JRH vs. 6.5% SPH, p < 0.001 for babies > 32 weeks GA); however, most infants were successfully transitioned to nHFT. Intubation rates during the first 72 h were comparable between centres (14.7% JRH vs. 11.1% SPH, p = 0.29). There were no differences in neonatal morbidities, including air leak, duration of oxygen supplementation, bronchopulmonary dysplasia, sepsis, retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, or median time to full-suck feeds. CONCLUSION: Use of nHFT for primary respiratory support, without use of nasal continuous positive airway pressure as "rescue" treatment, resulted in intubation rates lower or comparable to published data from randomised controlled trials.

Modelling nasal high flow therapy effects on upper airway resistance and resistive work of breathing.

AIM: The goal of this paper is to quantify upper airway resistance with and without nasal high flow (NHF) therapy. For adults, NHF therapy feeds 30-60 L/min of warm humidified air into the nose through short cannulas which do not seal the nostril. NHF therapy has been reported to increase airway pressure, increase tidal volume (Vt) and decrease respiratory rate (RR), but it is unclear how these findings affect the work done to overcome airway resistance to air flow during expiration. Also, there is little information on how the choice of nasal cannula size may affect work of breathing. In this paper, estimates of airway resistance without and with different NHF flow (applied via different cannula sizes) were made. The breathing efforts required to overcome airway resistance under these conditions were quantified. METHOD: NHF was applied via three different cannula sizes to a 3-D printed human upper airway. Pressure drop and flow rate were measured and used to estimate inspiratory and expiratory upper airway resistances. The resistance information was used to compute the muscular work required to overcome the resistance of the upper airway to flow. RESULTS: NHF raises expiratory resistance relative to spontaneous breathing if the breathing pattern does not change but reduces work of breathing if peak expiratory flow falls. Of the cannula sizes used, the large cannula produced the greatest resistance and the small cannula produced the least. The work required to cause tracheal flow through the upper airway was reduced if the RR and minute volume are reduced by NHF. NHF has been observed to do so in COPD patients (Bräunlich et al., 2013). A reduction in I:E ratio due to therapy was found to reduce work of breathing if the peak inspiratory flow is less than the flow below which no inspiratory effort is required to overcome upper airway resistance. CONCLUSION: NHF raises expiratory resistance but it can reduce the work required to overcome upper airway resistance via a fall in inspiratory work of breathing, RR and minute volume.

Powder aerosol delivery through nasal high-flow system: In vitro feasibility and influence of process conditions.

We aimed to obtain fundamental information for potential pulmonary delivery of powder aerosols using a clinically-approved nasal high-flow system (AIRVO), with spray-dried mannitol (SD-Man) being a model powder. Compressed air exiting the AIRVO at set 'dispersion' air flow rates dispersed SD-Man loaded in an Osmohaler® into a human nasal airway replica (NAR) coupled downstream to a Next Generation Impactor (NGI) running at specific 'inspiratory' flow rates. Increasing the dispersion flow rate from 30 to 60L/min increased powder deposition in the NAR from 50 to 70% of the emitted dose, while decreased the NGI deposition from 50 to 30% of the emitted dose. The inspiratory flow rate did not affect powder deposition in the NAR and NGI. In contrast, as the inspiratory flow rate was increased from 15 to 40L/min, powder recovery, emitted fraction, and fine particle fraction below 5µm (as aerosol performance indices) were increased from 90, 30 and 5% to 97, 45 and 8% of the loaded dose, respectively. The dispersion flow rate did not change the performance indices. Importantly, heating and humidification of dispersion airflow, loaded doses, and nasal cannula sizes did not greatly affect the aerosol characteristics.

Nasal high flow therapy in very low birth weight infants with mild respiratory distress syndrome: a single center experience.

BACKGROUND: Pulmonary disorders and respiratory failure represent one of the most common morbidities of preterm newborns admitted to neonatal intensive care units (NICUs). The use of nasal high-flow therapy (nHFT) has been more recently introduced into the NICUs as a non-invasive respiratory (NIV) support. METHODS: We performed a retrospective study to evaluate safety and effectiveness of nHFT as primary support for infants born < 29 weeks of gestation and/or VLBW presenting with mild Respiratory Distress Syndrome (RDS). The main outcome was the percentage of patients that did not need mechanical ventilation. Secondary outcomes were rate of bronchopulmonary dysplasia (BDP), air leaks, nasal injury, late onset sepsis (LOS), intraventricular hemorrhage (IVH), retinopathy (ROP), necrotizing enterocolitis (NEC), hemodynamically-significant patent ductus arteriosus (PDA) and death. RESULTS: Sixty-four preterm newborns were enrolled. Overall, 93% of enrolled patients did not need mechanical ventilation. In a subgroup analysis, 88.5% of infants < 29 weeks and 86.7% of infants ELBW (< 1000 g BW) did not need mechanical ventilation. BPD was diagnosed in 26.6% of preterms enrolled (Mild 20%, Moderate 4.5%, Severe 1.5%). In subgroup analysis, BPD was diagnosed in 53.9% of newborns with GA < 29 weeks, in 53.3% of ELBW newborns and in 11.1% of small for gestational age (SGA) newborns. Neither air leaks nor nasal injury were recorded as well as no exitus occurred. LOS, IVH, ROP, NEC and PDA occurred respectively in 16.1%, 0%, 7.8%, and 1.6% of newborns. CONCLUSIONS: According to our results, n-HFT seems to be effective as first respiratory support in preterm newborns with mild RDS. Further studies in a larger number of preterm newborns are required to confirm nHFT effectiveness in the acute phase of RDS.