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).

During the coronavirus disease 2019 (COVID-19) pandemic, noninvasive respiratory support has played a central role in managing patients affected by moderate-to-severe acute hypoxemic respiratory failure, despite inadequate scientific evidence to support its usage. High-flow nasal cannula (HFNC) treatment has gained popularity because of its effectiveness in delivering a high fraction of humidified oxygen, which improves ventilatory efficiency and the respiratory pattern, as well as its reported high tolerability, ease of use, and application outside of ICUs. Nevertheless, the risk of infection transmission to health-care workers has raised some concerns about its use in the first wave of the pandemic outbreak, with controversial recommendations provided by different scientific societies. This narrative review provides an overview of the recent evidence on the physiologic rationale, risks, and benefits of using HFNC instead of conventional oxygen therapy and other types of noninvasive respiratory support devices, such as continuous positive airway pressure and noninvasive ventilation in patients affected by COVID-19 pneumonia with associated acute hypoxemic respiratory failure. It also summarizes the available evidence with regard to the clinical use of HFNC during the current pandemic and its reported outcomes, and highlights the risks of bioaerosol dispersion associated with HFNC use.

Thymic stromal lymphopoietin (TSLP) is an innate cytokine, belonging to the group of alarmins, which plays a key pathogenic role in asthma by acting as an upstream activator of cellular and molecular pathways leading to type 2 (T2-high) airway inflammation. Released from airway epithelial cells upon tissue damage induced by several noxious agents including allergens, viruses, bacteria, and airborne pollutants, TSLP activates dendritic cells and group 2 innate lymphoid cells involved in the pathobiology of T2-high asthma. Tezepelumab is a fully human monoclonal antibody that binds to TSLP, thereby preventing its interaction with the TSLP receptor complex. Preliminary results of randomized clinical trials suggest that tezepelumab is characterized by a good safety and efficacy profile in patients with severe, uncontrolled asthma.

Background: Pulmonary rehabilitation (PR) may improve respiratory symptoms and skeletal muscle strength in patients with COPD. We aimed to evaluate changes in ultrasound (US) measurements of diaphragmatic mobility and thickness after PR in COPD patients and to test its correlation with PR outcomes. Methods: Twenty-five COPD patients were enrolled and underwent a diaphragm US assessment before and after a 12-week PR program. Results: We found a correlation between the intraindividual percentage of change in the diaphragmatic length of zone of apposition at functional residual capacity (ΔLzapp%) and the change in 6-minute walking distance (6MWD) after PR (rho=0.49, P=0.02). ΔLzapp% was significantly higher in patients with improved 6MWD and COPD Assessment Test (CAT) score (mean rank=12.03±2.57 vs 6.88±4.37; P=0.02). A ΔLzapp% of ≥10% was able to discriminate among patients with improved 6MWD, with a sensitivity of 83% and a specificity of 74%. The area under the receiver operating characteristic curve for ΔLzapp% was 0.83. A cutoff value of ≥9% of ΔLzapp% had a positive predictive value in discriminating a reduction in ≥2 points of CAT score after PR, with a sensitivity and a specificity of 80% and 62%, respectively. Conclusion: Diaphragm US assessment represents a useful prognostic marker of PR outcomes in COPD patients.

Introduction: Dupilumab is a monoclonal antibody targeting IL-4Rα recently licensed for severe asthma (SA). A Named Patients Program (NPP) was created in Italy before its commercial availability for SA patients with no other available therapeutic options. We aimed to assess the real-world effectiveness of dupilumab in patients with SA and unmet needs. Methods: We performed a multicentre retrospective study, including SA patients admitted to the NPP treated with dupilumab for 12 months. Data on the number of exacerbations, Asthma Control Test (ACT), pre-bronchodilator FEV₁%, oral corticosteroids (OCSs) use, FeNO and eosinophils count in peripheral blood were recorded at baseline and after 3, 6, and 12 months. Results: We included 18 SA patients (mean age 53.3± 12.4 years, 66.7% female). Eleven (61.1%) were OCSs dependent. Five patients (27.8%) received previous anti-IgE and/or anti-IL-5 agents. A significant improvement in ACT score (from 15.7± 5.1 to 18.8± 4.8, p=0.023), OCSs intake [10 (5– 25) mg/day to 0 (0– 5) mg/day, p=0.0333] and FeNO [from 25 (20– 80) ppb to 21 (10.9– 55.3) ppb, p=0.0190] was already detected after 3 months of treatment. After 12 months, a statistically significant decrease in the number of exacerbations from 2 (0– 3) to 0 (0– 1) (p< 0.0068) and increase in FEV₁% from 73.5± 19.5% to 87.1± 19.2% (p=0.0407) and ACT to a mean value of 22.4± 1.7 (p< 0.0001) and the interruption of OCSs in all the patients (p< 0.0001) was observed. A transient increase in the eosinophil count was observed in five patients (above 1000 cells/μL in 2 cases) after 3 months, without any clinical effect. Conclusion: Dupilumab improved all the explored clinical outcomes after 12 months, and the transient hypereosinophilia did not modify treatment response. These real-world data confirm the results reported in randomized controlled trials and provide an important opportunity to characterize the clinical impact of the treatment in a non-trial setting. Further real-world studies with a larger cohort of patients are needed to confirm these findings.