Background: The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO₂ clearance after 2 h of treatment. Methods: We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25–7.35, PaCO₂ ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO₂ from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO₂ at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. Results: Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO₂ reduction from baseline to 2 h were − 6.8 mmHg (± 8.7) in the HFNT and − 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO₂ reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO₂ reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. Conclusions: HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO₂ after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. Trial registration: The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

Noninvasive ventilation (NIV) is indicated to treat respiratory acidosis due to exacerbation of chronic obstructive pulmonary disease (COPD). Recent nonrandomized studies also demonstrated some physiological effects of high-flow nasal therapy (HFNT) in COPD patients. We designed a prospective, unblinded, multicenter, randomized controlled trial to assess the noninferiority of HFNT compared to NIV with respect to the reduction of arterial partial pressure of carbon dioxide (PaCO2) in patients with hypercapnic acute respiratory failure with mild-to-moderate respiratory acidosis. We will enroll adult patients with acute hypercapnic respiratory failure, as defined by arterial pH between 7.25 and 7.35 and PaCO2 ≥ 55 mmHg. Patients will be randomly assigned 1:1 to receive NIV or HFNT. NIV will be applied through a mask with a dedicated ventilator in pressure support mode. Positive end-expiratory pressure will be set at 3–5 cmH2O with inspiratory support to obtain a tidal volume between 6 and 8 ml/kg of ideal body weight. HFNT will be initially set at a temperature of 37 °C and a flow of 60 L/min. At 2 and 6 h we will assess arterial blood gases, vital parameters, respiratory rate, treatment intolerance and failure, need for endotracheal intubation, time spent under mechanical ventilation (both invasive and NIV), intensive care unit and hospital length of stay, and hospital mortality. Based on an α error of 5% and a β error of 80%, with a standard deviation for PaCO2 equal to 15 mmHg and a noninferiority limit of 10 mmHg, we computed a sample size of 56 patients. Considering potential drop-outs and nonparametric analysis, the final computed sample size was 80 patients (40 per group). HFNT is more comfortable than NIV in COPD patients recovering from an episode of exacerbation. If HFNT would not be inferior to NIV, HFNT could be considered as an alternative to NIV to treat COPD patients with mild-to-moderate respiratory acidosis. ClinicalTrials.gov, NCT03370666 . Registered on December 12, 2017.

Respiratory failure in SARS-CoV-2 patients is characterized by the presence of hypoxemia and hypocapnia without relevant dyspnea. To date, the use of respiratory parameters other than PaO2/FiO2 ratio to stratify the risk of worsening of these patients has not been sufficiently studied. Aim of this work was to evaluate whether the ratio between partial pressure levels of carbon dioxide (PaCO2) and the fraction of inspired oxygen (FiO2) measured at emergency department (ED) admission is predictive of the clinical course of patients suffering from SARS-CoV-2 pneumonia. We retrospectively studied 236 patients with SARS-CoV-2 pneumonia evaluated at the ED of the Perugia Hospital. The end-points were: in-hospital mortality, need for invasive mechanical ventilation (IMV) and length of in-hospital stay (LOS). Clinical, blood gas and laboratory data were collected at ED admission. Of the 236 patients 157 were male, the mean age was 64 ± 16. Thirtythree patients (14%) needed IMV, 49 died (21%). In the univariate analysis, the PaCO2/FiO2 ratio was inversely associated with the need for IMV (p <0.001), mortality (p <0.001) and LOS (p = 0.005). At the multivariate analysis the PaCO2/FiO2 ratio was found to be predictive of the need for IMV, independently from age, gender, number of comorbidities, neutrophils, lymphocytes, glomerular filtrate, d-dimer, LDH and CRP. the PaCO2/FiO2 ratio is predictive of the risk of respiratory failure worsening in patients with SARS-CoV-2 pneumonia, independently from other several confounding factors.

Patients who present to an Emergency Department (ED) and leave without being seen by a physician represent a safety concern because they may become severely ill and experience adverse events as a result of lacking or delayed ED treatment. Prior to the COVID-19 outbreak, the increasing number of patients accessing care through the ED in Italy and throughout the world has had implications for health policies. A retrospective cohort study that included all ED visits from 1st January 2013 to 31st December 2018 in the Perugia University Hospital has been carried out. During the 5 years investigated 26,344 out of 300,372 (8.77%) patients who attended the ED left the triage area before being seen with an average of 439 patients per month. The same phenomenon has been analysed from February to October 2020. During these 9 months there were a total of 1,824 out of 30,990 (5.88%) patients who left the ED without being seen with an average of 202 per month. The latter value is one third lower than the one related to the period investigated prior to the COVID-19 outbreak. Such investigation could help to differentiate actual essential demand from non-essential demand within the ED, which could inform quality-improvement policies. Several strategies could be implemented to lower the proportion of patients who leave the department without being seen. Reorganising the activities in the ED with different paths should be implemented with the aim of reducing waiting times and in turn patients' satisfaction.