BackgroundAcute exacerbations of chronic obstructive pulmonary disease (COPD) in the emergency department (ED) involve dyspnea, cough, and chest discomfort; frequent exacerbations are associated with increased mortality and reduced quality of life. Noninvasive positive pressure ventilation (NiPPV) is commonly used to help relieve symptoms but is limited due to patient intolerance. We aimed to determine whether high‐velocity nasal insufflation (HVNI) is noninferior to NiPPV in relieving dyspnea within 4 h in ED patients with acute hypercapnic respiratory failure.MethodsThis randomized control trial was conducted in seven EDs in the United States. Symptomatic patients with suspected COPD, partial pressure of carbon dioxide (pCO2) ≥ 60 mm Hg, and venous pH 7.0–7.35 were randomized to receive HVNI (n = 36) or NiPPV (n = 32). The primary outcome was dyspnea severity 4 h after the initiation of study intervention, as measured by the Borg score. Secondary outcomes included vital signs, oxygen saturation, venous pCO2, venous pH, patient discomfort level, and need for endotracheal intubation.ResultsSixty‐eight patients were randomized between November 5, 2020, and May 10, 2023 (mean age 65.6 years; 47% women). The initial pCO2 was 77.7 ± 13.6 mm Hg versus 76.5 ± 13.6 mm Hg and the initial venous pH was 7.27 ± 0.063 versus 7.27 ± 0.043 in the HVNI and NiPPV groups, respectively. Dyspnea was similar in the HVNI and NiPPV groups at baseline (dyspnea scale score 5.4 ± 2.93 and 5.6 ± 2.41) and HVNI was noninferior to NiPPV at the following time points: 30 min (3.97 ± 2.82 and 4.54 ± 1.65, p = 0.006), 60 min (3.09 ± 2.70 and 4.07 ± 1.77, p < 0.001), and 4 h (3.17 ± 2.59 and 3.34 ± 2.04, p = 0.03). At 4 h, there was no difference between the groups in the pCO2 mm Hg (68.76 and 67.29, p = 0.63). Patients reported better overall comfort levels in the HVNI group at 30 min, 60 min, and 4 h (p = 0.003).ConclusionsIn participants with symptomatic COPD, HVNI was noninferior to NiPPV in relieving dyspnea 4 h after therapy initiation. HVNI may be a reasonable treatment option for some patients experiencing moderate acute exacerbations of COPD in the ED.