Acute dyspnea in the emergency department: a clinical review.

Acute dyspnea represents one of the most frequent symptoms leading to emergency room evaluation. Its significant prognostic value warrants a careful evaluation. The differential diagnosis of dyspnea is complex due to the lack of specificity and the loose association between its intensity and the severity of the underlying pathological condition. The initial assessment of dyspnea calls for prompt diagnostic evaluation and identification of optimal monitoring strategy and provides information useful to allocate the patient to the most appropriate setting of care. In recent years, accumulating evidence indicated that lung ultrasound, along with echocardiography, represents the first rapid and non-invasive line of assessment that accurately differentiates heart, lung or extra-pulmonary involvement in patients with dyspnea. Moreover, non-invasive respiratory support modalities such as high-flow nasal oxygen and continuous positive airway pressure have aroused major clinical interest, in light of their efficacy and practicality to treat patients with dyspnea requiring ventilatory support, without using invasive mechanical ventilation. This clinical review is focused on the pathophysiology of acute dyspnea, on its clinical presentation and evaluation, including ultrasound-based diagnostic workup, and on available non-invasive modalities of respiratory support that may be required in patients with acute dyspnea secondary or associated with respiratory failure.

Acute Improvements of Oxygenation with Cpap and Clinical Outcomes in Severe COVID-19 Pneumonia: A Multicenter, Retrospective Study.

It is not known if the degrees of improvement in oxygenation obtained by CPAP can predict clinical outcomes in patients with COVID-19 pneumonia. This was a retrospective study conducted on patients with severe COVID-19 pneumonia treated with CPAP in three University hospitals in Milan, Italy, from March 2020 to March 2021. Arterial gas analysis was obtained before and 1 h after starting CPAP. CPAP failure included either death in the respiratory units while on CPAP or the need for intubation. Two hundred and eleven patients (mean age 64 years, 74% males) were included. Baseline median PaO2, PaO2/FiO2 ratio (P/F), and the alveolar-arterial (A-a) O2 gradient were 68 (57−83) mmHg, 129 (91−179) mmHg and 310 (177−559) mmHg, respectively. Forty-two (19.9%) patients died in the respiratory units and 51 (24.2%) were intubated. After starting CPAP, PaO2/FiO2 increased by 57 (12−113; p < 0.001) mmHg, and (A-a) O2 was reduced by 68 (−25−250; p < 0.001) mmHg. A substantial overlap of PaO2, P/F, and A-a gradient at baseline and during CPAP was observed in CPAP failures and successes; CPAP-associated improvements in oxygenation in both groups were similar. In conclusion, CPAP-associated improvements in oxygenation do not predict clinical outcomes in patients with severe COVID-19 pneumonia.

Predictors of Helmet CPAP Failure in COVID-19 Pneumonia: A Prospective, Multicenter, and Observational Cohort Study.

Background: Continuous positive airway pressure (CPAP) can be beneficial in acute respiratory failure (ARF) due to coronavirus (COVID-19) pneumonia, but delaying endotracheal intubation (ETI) in nonresponders may increase mortality. We aimed at investigating the performance of composite respiratory indexes as possible predictors of CPAP failure in ARF due to COVID-19. Methods: This was a multicenter, prospective, observational, and cohort study conducted in the respiratory units of three University hospitals in Milan and in a secondary care hospital in Codogno (Italy), on consecutive adult patients with ARF due to COVID-19 pneumonia that underwent CPAP between March 2020 and March 2021. ETI transfer to the intensive care unit or death is defined CPAP failure. Predictors of CPAP failure were assessed before T0 and 1 hour after T1 CPAP initiation and included mROX index (ratio of PaO2/FiO2 to respiratory rate), alveolar-to-arterial (A-a) O2 gradient, and the HACOR (heart rate, acidosis, consciousness, oxygenation, and respiratory rate) score. Results: Three hundred and fifty four patients (mean age 64 years, 73% males) were included in the study; 136 (38.4%) satisfied criteria for CPAP failure. A-a O2 gradient, mROX, and HACOR scores were worse in patients who failed CPAP, both at T0 and T1 (p < 0.001 for all parameters). The HACOR score was associated with CPAP failure (odds ratio-OR-for every unit increase in HACOR = 1.361; 95%CI: 1.103-1.680; p=0.004; AUROC = 0.742; p < 0.001). CPAP failure was best predicted by a threshold of 4.50 (sensitivity = 53% and specificity = 87%). Conclusions: The HACOR score may be a reliable and early predictor of CPAP failure in patients treated for ARF in COVID-19 pneumonia.

Mortality and clinical outcomes in patients with COVID-19 pneumonia treated with non-invasive respiratory support: A rapid review.

INTRODUCTION AND AIM: Non-invasive ventilation (NIV) and continuous positive airway pressure (CPAP) have been widely employed to treat acute respiratory failure secondary to COVID-19 pneumonia, but their role in terms of efficacy and safety are still debated. The aim of this review was to analyse mortality and intubation rates in COVID-19 patients treated with NIV/CPAP. METHODS: Rapid review methodology was applied to include all the studies published since December-2019 until November-2020 with available data on in-hospital mortality in COVID-19 patients treated with NIV or CPAP. RESULTS: 23 manuscripts were included (4776 patients, 66% males, 46% with hypertension). 46% of patients received non-invasive respiratory support, of which 48.4% with CPAP, 46% with NIV, and 4% with either CPAP or NIV. Non-invasive respiratory support failed in 47.7% of patients, of which 26.5% were intubated and 40.9% died. In-hospital mortality was higher in patients treated with NIV compared with CPAP (35.1% vs. 22.2%). Complications were under-reported, but mostly not related to CPAP/NIV treatment. CONCLUSION: CPAP and NIV appear equally and frequently applied in patients with COVID-19 pneumonia, but associated with high mortality. Robust evidence is urgently needed to confirm the clinical efficacy of non-invasive respiratory support in COVID-19-related ARDS.

Feasibility and Clinical Outcomes of a Step Up Noninvasive Respiratory Support Strategy in Patients with Severe COVID-19 Pneumonia.

The best noninvasive respiratory strategy in patients with Coronavirus Disease 2019 (COVID-19) pneumonia is still discussed. We aimed at assessing the rate of endotracheal intubation (ETI) in patients treated with continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) if CPAP failed. Secondary outcomes were in-hospital mortality and in-hospital length of stay (LOS). A retrospective, observational, multicenter study was conducted in intermediate-high dependency respiratory units of two Italian university hospitals. Consecutive patients with COVID-19 treated with CPAP were enrolled. Thoraco-abdominal asynchrony or hemodynamic instability led to ETI. Patients showing SpO2 ≤ 94%, respiratory rate ≥ 30 bpm or accessory muscle activation on CPAP received NIV. Respiratory distress and desaturation despite NIV eventually led to ETI. 156 patients were included. The overall rate of ETI was 30%, mortality 18% and median LOS 24 (17-32) days. Among patients that failed CPAP (n = 63), 28% were intubated, while the remaining 72% received NIV, of which 65% were intubated. Patients intubated after CPAP showed lower baseline PaO2/FiO2, lower lymphocyte counts and higher D-dimer values compared with patients intubated after CPAP + NIV. Mortality was 22% with CPAP + ETI, and 20% with CPAP + NIV + ETI. In the case of CPAP failure, a NIV trial appears feasible, does not deteriorate respiratory status and may reduce the need for ETI in COVID-19 patients.

Differential Redox State and Iron Regulation in Chronic Obstructive Pulmonary Disease, Acute Respiratory Distress Syndrome and Coronavirus Disease 2019.

In patients affected by Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Coronavirus Disease 2019 (COVID-19), unclear mechanisms negatively interfere with the hematopoietic response to hypoxia. Although stimulated by physiological hypoxia, pulmonary hypoxic patients usually develop anemia, which may ultimately complicate the outcome. To characterize this non-adaptive response, we dissected the interplay among the redox state, iron regulation, and inflammation in patients challenged by either acute (ARDS and COVID-19) or chronic (COPD) hypoxia. To this purpose, we evaluated a panel of redox state biomarkers that may integrate the routine iron metabolism assays to monitor the patients' inflammatory and oxidative state. We measured redox and hematopoietic regulators in 20 ARDS patients, 20 ambulatory COPD patients, 9 COVID-19 ARDS-like patients, and 10 age-matched non-hypoxic healthy volunteers (controls). All the examined pathological conditions induced hypoxia, with ARDS and COVID-19 depressing the hematopoietic response without remarkable effects on erythropoietin. Free iron was higher than the controls in all patients, with higher levels of hepcidin and soluble transferrin receptor in ARDS and COVID-19. All markers of the redox state and antioxidant barrier were overexpressed in ARDS and COVID-19. However, glutathionyl hemoglobin, a candidate marker for the redox imbalance, was especially low in ARDS, despite depressed levels of glutathione being present in all patients. Although iron regulation was dysfunctional in all groups, the depressed antioxidant barrier in ARDS, and to a lesser extent in COVID-19, might induce greater inflammatory responses with consequent anemia.

Helmet CPAP to Treat Acute Hypoxemic Respiratory Failure in Patients with COVID-19: A Management Strategy Proposal.

Since the beginning of March 2020, the coronavirus disease 2019 (COVID-19) pandemic has caused more than 13,000 deaths in Europe, almost 54% of which has occurred in Italy. The Italian healthcare system is experiencing a stressful burden, especially in terms of intensive care assistance. In fact, the main clinical manifestation of COVID-19 patients is represented by an acute hypoxic respiratory failure secondary to bilateral pulmonary infiltrates, that in many cases, results in an acute respiratory distress syndrome and requires an invasive ventilator support. A precocious respiratory support with non-invasive ventilation or high flow oxygen should be avoided to limit the droplets' air-dispersion and the healthcare workers' contamination. The application of a continuous positive airway pressure (CPAP) by means of a helmet can represent an effective alternative to recruit diseased alveolar units and improve hypoxemia. It can also limit the room contamination, improve comfort for the patients, and allow for better clinical assistance with long-term tolerability. However, the initiation of a CPAP is not free from pitfalls. It requires a careful titration and monitoring to avoid a delayed intubation. Here, we discuss the rationale and some important considerations about timing, criteria, and monitoring requirements for patients with COVID-19 respiratory failure requiring a CPAP treatment.

Mobile Extracorporeal Membrane Oxygenation Teams for Organ Donation After Circulatory Death.

The shortage of available organ donors is a significant problem worldwide, and various efforts have been carried out to avoid the loss of potential organ donors. Among them, organ donation from cardiocirculatory deceased donors (DCD), in which withdrawal of life-sustaining therapies is ongoing (Maastricht type III donors), is one emerging strategy. Thanks to the latest advances in transplantation and organ preservation, such as normothermic regional perfusion (NRP), ex vivo perfusion techniques, and good organization and communication among prehospital care providers, emergency departments, intensive care units, and transplantation units, DCD is rapidly increasing; it's estimated that it will increase the number of donations of lungs and splanchnic organs by more than 40%. Although Maastricht type II DCD requires a 24/7 available experienced extra corporeal membrane oxygenation (ECMO) team in the institution, Maastricht DCD type III could be organized in secondary care and spoke hospitals without in loco ECMO facilities for NRP. This article analyses a potential mobile team organization based on the hub-and-spoke model, which already exists and functions in Italy, by estimating the dimension of the controlled DCD phenomenon in Italy, coordination requirements, costs, personnel training, and education, and reporting a single center experience in Milan, Italy.

Mucins and Asthma: Are We Headed to the Revolutionary Road?

Mucus represents the first line of defense of our respiratory tract and mucociliary clearance is essential for maintaining the homeostasis of airway epithelium. The latter mechanisms are altered in asthma and mucus plugging of proximal and distal airways is the main cause of death in cases of fatal asthma. Starting from the influential review performed by Luke R. Bonser and David J. Erle in 2017, we discuss the latest evidence in terms of mucins regulation and potential treatment of mucus hypersecretion and tissue remodeling in severe asthma.