Studies employing noninvasive pressure support ventilation in cardiogenic pulmonary edema have been performed in the intensive care unit when overt respiratory failure is already present and in small groups of patients. In this multicenter study, performed in emergency departments, 130 patients with acute respiratory failure were randomized to receive medical therapy plus O2 (65 patients) or noninvasive pressure support ventilation (65 patients). The primary end point was the need for intubation; secondary end points were in-hospital mortality and changes in some physiological variables. Noninvasive pressure support ventilation improved PaO2/FIO2, respiratory rate, and dyspnea significantly faster. Intubation rate, hospital mortality, and duration of hospital stay were similar in the two groups. In the subgroup of hypercapnic patients noninvasive pressure support ventilation improved PaCO2 significantly faster and reduced the intubation rate compared with medical therapy (2 of 33 versus 9 of 31; p=0.015). Adverse events, including myocardial infarction, were evenly distributed in the two groups. We conclude that during acute respiratory failure due to cardiogenic pulmonary edema the early use of noninvasive pressure support ventilation accelerates the improvement in PaO2/FIO2, PaCO2, dyspnea, and respiratory rate, but does not affect the overall clinical outcome. Noninvasive pressure support ventilation does, however, reduce the intubation rate in the subgroup of hypercapnic patients.

Background: As the novel SARS-CoV-2 pandemic occurred, no specific treatment was yet available. Inflammatory response secondary to viral infection might be the driver of severe diseases. We report the safety and efficacy (in terms of overall survival and hospital discharge) of the anti-IL6 tocilizumab (TCZ) in subjects with COVID-19. Methods: This retrospective, single-center analysis included all the patients consecutively admitted to our Hospital with severe or critical COVID-19 who started TCZ treatment from March 13th to April 03rd, 2020. A 1:2 matching to patients not treated with TCZ was performed according to age, sex, severity of disease, P/F, Charlson Comorbidity Index and length of time between symptoms onset and hospital admittance. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and Cox regression models for survival, hospital discharge and orotracheal intubation were used. Results: Seventy-four patients treated with TCZ were matched with 148 matched controls. They were mainly males (81.5%), Caucasian (82.0%) and with a median age of 59 years. The majority (69.8%) showed critical stage COVID-19 disease. TCZ use was associated with a better overall survival (HR 0.499 [95% CI 0.262-0.952], p = 0.035) compared to controls but with a longer hospital stay (HR 1.658 [95% CI 1.088-2.524], p = 0.019) mainly due to biochemical, respiratory and infectious adverse events. Discussion: TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events. Financial support: Some of the tocilizumab doses used in the subjects included in this analysis were provided by the "Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia" (EudraCT Number: 2020-001110-38) supported by the Italian National Agency for Drugs (AIFA). No specific funding support was planned for study design, data collection and analysis and manuscript writing of this paper.

Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

The choice of the interface for noninvasive ventilation (NIV) is a key factor in NIV success. We hypothesised that a new helmet specifically design to improve performance in hypercapnic patients would be clinically equivalent to a standard oronasal mask.In a multicentre, short-term, physiological, randomised trial in chronic obstructive pulmonary disease patients facing an acute hypercapnic respiratory failure episode, we compared the changes in arterial blood gases (ABGs) and tolerance score obtained using the helmet or mask, and, as secondary end-points, dyspnoea, vital signs, early NIV discontinuation and rate of intubation. 80 patients were randomly assigned to receive NIV either with the helmet (n=39) or mask (n=41), using an intensive care unit ventilator.Compared with baseline, in the first 6 h, NIV improved ABGs, dyspnoea and respiratory rate ( p<0.05) in both groups. Changes in ABGs and discomfort were similar with the two groups, while dyspnoea decreased more ( p<0.005) using the mask. The rate of intubation and the need for interface change during the whole period of NIV were very low and not different between groups.The new helmet may be a valid alternative to a mask in improving ABGs and achieving a good tolerance during an episode of acute hypercapnic respiratory failure. @ERSpublications In COPD patients undergoing NIV, an oronasal mask and a helmet equally improved ABGs and tolerance score

Expiration under positive pressure was effective in acutely removing secretions in patients with exacerbation of COPD and mild acidosis requiring NIPPV. In conclusion, we suggest that this chest physiotherapy technique represents a useful therapeutic option for such patients and it should often be performed in addition to NIPPV.