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| References | Study designs | Countries | Total (n) HFNC/NIV | Participants | HFNC device | NIV device | Age (HFNC/NIV) | Setting of HFNC and NIV | Duration of HFNC or NIV | Outcomes |
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| Mckinstry et al. 2019 [8] | Single-center crossover RCT | New Zealand | 24 | Eligible participants were aged at least 40 years, had a doctor’s diagnosis of COPD and had a capillary partial pressure of carbon dioxide of ˃45 mmHg | AIRVO 2 device (PT101AZ, fisher and paykel healthcare, Auckland, New Zealand) | Philips respironics BiPAP AVAPS-ST 60 series (Philips Respironics, Eindhoven, Netherlands) | 68 ± 9.0 | All participants received an AB/BA crossover design. HFNC was delivered at a flow rate of 45 L/min and a temperature of 37°C. NIV settings were delivered at an inspiratory pressure of 15 cm H2O and expiratory pressure of 4 cm H2O | Participants received both HFNC and NIV for 60 min each, while seated, followed by a 15 min to allow the PtCO2 to return to within 2 mm Hg of the baseline measurement | The transcutaneous partial pressure of carbon dioxide (PtCO2), respiratory rate, oxygen saturation, heart rate, borg dyspnea scores, tolerability questionnaires |
| Jing et al. 2019 [9] | Single-centre RCT | China | 22/20 | COPD patients who were intubated for exacerbation, with hypercapnia (PaCO2 ˃45 mmHg) at the time of extubation and met the pulmonary infection control window” criteria were recruited | Optiflow or AIRVOTM 2 device (PT101AZ, fisher and paykel healthcare, Auckland, New Zealand) | Noninvasive ventilator (VPAP III ST; ResMed, Bella Vista, NSW, Australia | 77.4 ± 6.8/73.9 ± 6.9 | HFNC was utilized with the humidifier temperature set at 37°C and the fraction of inspired oxygen adjusted to maintain oxygen saturation recorded by pulse oximetry (SpO2) at 88–92%. For NIV, its standard oral-nasal mask was used. Inspiratory positive airway pressure was initiated at 10−12 cm H2O, and subsequent adjustments were based on the patients’ ABGs. Oxygen was blended via the port on the mask and adjusted to maintain SpO2 88–92% | Both HFNC and NIV were used at least 8 hr/day | The primary outcome parameters were ABGs (PH, PaCO2, partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaCO2/FiO2) and vital signs (heart rate), mean arterial pressure (MAP), respiratory rate (RR) at 3, 24, and 48 hr after extubation. Secondary outcomes included the duration of respiratory support, length of ICU stay, the patient’s comfort score, the incidence of adverse events, and the number of patients who needed bronchoscopy for secretion removal within 48 hr after extubation |
| Papachatzakis et al. 2020 [10] | Single-centre RCT | Greece | 20/20 | We enrolled patients who were admitted to the hospital because of acute respiratory failure type 2 (PaCO2 ˃45 mmHg) | HFNC: optiflow nasal interface connected to the PT101AZ (Airvo2) humidifier fisher and paykel healthcare, Auckland, New Zealand) | NIV: synchrony, respironics, inc, Murrysville, Pennsylvania | 76.0 ± 13.4/78.1 ± 8.1 | HFNC therapy typically was initiated at a flow of 35 L/min, titrating flow upward if tolerated to 45−50 L/min, to maintain SaO2 > 90% or according to specific clinical orders. NIV was initiated by bilevel positive airway pressure (BiPAP) supplied with an identical set of modes. Expiratory and inspiratory pressures were gradually increased to the maximum tolerated over 1 h, to maintain Sao2 > 90%, or according to specific clinical orders | Both HFNC and NIV were used during hospitalization (days) 11.5 ± 8.5 | We measured and recorded vital signs, arterial blood gases (ABGs), and comfort. Endpoints to evaluate after HFNC or NIV therapy were intubation and mortality rate, length of hospitalization, duration of therapy, and possible differences between vital signs, ABGs, and comfort |
| Cortegiani et al. 2020 [11] | Multicentre RCT | Italy | 24/29 | Patients with a diagnosis of COPD exacerbation according to GOLD criteria were admitted for mild-to-moderate acute hypercapnic respiratory failure, with an arterial PH between 7.25 and 7.35 and a PaCO2 ≥ 55 mmHg | Optiflow and MR850 or AIRVOTM 2, Fisher and Paykel Healthcare, Auckland, New Zealand | | 74 ± 13/77 ± 12 | HFNC: initially set at 60 L/min and at a temperature of 37°C. In case of discomfort, flow and/or temperature were down-regulated to the most tolerated setting. NIV: the ventilation was set in pressure support ventilation (PSV) mode, with a PEEP titrated between 3 and 5 cm H2O. The inspiratory pressure was titrated to achieve a measured or estimated expiratory tidal volume equal to 6–8 mL kg−1 of the ideal body weight | All patients received the assigned treatment after randomization. By 2 h, six patients in the HFNC group had switched to NIV and one to IMV in the HFNC group. Due to the improvement of respiratory failure, one patient switched to no support in the HFNC group while two patients switched to HFNC, and six to no support in the NIV group | The primary endpoint was the mean difference of PaCO2. (2) Treatment change rates. (3) Dyspnea score and proportion of patients who did not improve the dyspnea score. (4) Discomfort score and proportion of patients showing poor tolerance to treatment. (5) The proportion of patients who had PaCO2 worsening or reduction <10 mmHg from baseline assessment, or worsening or no improvement of the dyspnea. (6) Respiratory rate. (7) Change in arterial blood gases. (8) Time spent under mechanical ventilation (both IMV and NIV). (9) Hospital length of stay. (10) Hospital mortality |
| Tan et al. 2020 [12] | Multicentre RCT | China | 44/42 | COPD patients with hypercapnic respiratory failure who received invasive ventilation were screened for enrollment. Other inclusion criteria included patients who were ≤85 years of age, able to care for themselves, and met the criteria of the pulmonary infection control window | AIRVOTM 2, Fisher and Paykel Healthcare, Auckland, New Zealand | Philips V60 or BiPap vision | 68.4 ± 9.3/71.4 ± 7.8 | HFNC: the initial airflow was set at 50 L/min and adjusted according to patient tolerance. The HFNC was set to an absolute humidity of 44 mg H2O/L, the temperature was set to 37°C, and FiO2 was adjusted to maintain a SpO2 of 88–92%. NIV: all subjects receiving NIV were set in S/T mode with a standard oral-nasal (full-face) mask (RT040). The initial expiratory pressure airway pressure was set to 4 cm H2O, and the pressure level was gradually increased to ensure that the patient could trigger the NIV device with each inhalation. The inspiratory airway pressure was initially set to 8 cm H2O and gradually increased to achieve a satisfactory tidal volume with acceptable tolerance | The patient’s initial respiratory support was targeted to last at least 2 h and then continued as needed. NIV or HFNC were discontinued when the total daily treatment duration was less than 4 h and could be reused if needed. Treatment success was defined as no need for respiratory support within 72 h after stopping NIV or HFNC | The primary outcome was treatment failure. Secondary outcomes included arterial blood gas analysis and vital signs such as the respiratory rate, heart rate, and blood pressure, the daily number of nursing airway care interventions, the patient’s comfort score, the patient dyspnea score, the incidence of nasofacial skin breakdown, 28-day mortality, and total ICU and hospital lengths of stay |
| Cong et al. 2019 [7] | Single-centre RCT | China | 84/84 | The patients were aged 40 to 76 years and the duration of COPD was 2 to 18 years. Patients were included if they were diagnosed with AECOPD according to the national guideline. Admitted to ICU due to severe illness and given ventilation therapy | Patients were ventilated using OH–60°C high-flow noninvasive breathing therapeutic apparatus (Micomme, Hunan, China) | Patients were ventilated by mouth and nose using a ventilator Hamilton G5 (Hamilton medical AG; Bonaduz, Switzerland | The patients were aged 40 to 76 years with an average of 67.51 ± 7.13 years | HFNC: the air temperature was set at 37°C at a flow rate of 30–35 L/min. For NIV, the inspiratory positive airway pressure (IPPV) was set at 10 cm H2O, and expiration pressure was set at 5 cm H2O at the beginning, and gradually increased after the patient adapted | Both HFNC and NIV were used during hospitalization | The primary endpoint was blood gases as a measure of systemic inflammation during AECOPD and was measured before, 12 h, and 5 days after treatments. Secondary clinical endpoints included ventilation support time, hospitalization days and complications, comfort, and nursing satisfaction. Comfort and nursing satisfaction were investigated using hospital-designed questionnaires |
| Fang et al. 2021 [13] | Single-centre RCT | China | 20/24 | Patients with a diagnosis of COPD exacerbation according to GOLD criteria were admitted for mild-to-moderate acute hypercapnic respiratory failure, with an arterial pH < 7.30 and a PaCO2 ≥50 mmHg | AIRVOTM 2, Fisher and Paykel Healthcare, Auckland, New Zealand | Philips V60 | 67.9 ± 6.9/72.3 ± 7.8 | HFNC: the air temperature was set at 37°C at a flow rate of 30–55 L/min. For NIV, the inspiratory positive airway pressure (IPPV) was set at 10 cm H2O, and expiration pressure was set at 5 cm H2O | Both HFNC and NIV were used for three days after extubation | The primary endpoint was the rate of reintubation within 7 days of extubation. Secondary clinical endpoints included: Blood gases, complications, duration of endotracheal intubation mechanical ventilation, length of RICU stay, length of hospital stay, and mortality |
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