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Objective: To investigate the role of arterial blood gas (ABG) analysis parameters (blood carbon dioxide, pCO2; oxygen, pO2; carbonate, HCO3−; standard base excess, SBE) in monitoring respiratory f...

The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies.To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle.180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57-73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively.Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020.

RationaleIn patients with COVID-19 pneumonia and mild hypoxaemia, the clinical benefit of high-flow nasal oxygen (HFNO) remains unclear. We aimed to examine whether HFNO compared with conventional oxygen therapy (COT) could prevent escalation of respiratory support in this patient population.MethodsIn this multicentre, randomised, parallel-group, open-label trial, patients with COVID-19 pneumonia and peripheral oxygen saturation (SpO2) ≤92% who required oxygen therapy were randomised to HFNO or COT. The primary outcome was the rate of escalation of respiratory support (ie, continuous positive airway pressure, non-invasive ventilation or invasive mechanical ventilation) within 28 days. Among secondary outcomes, clinical recovery was defined as the improvement in oxygenation (SpO2≥96% with fractional inspired oxygen (FiO2) ≤30% or partial pressure of arterial carbon dioxide/FiO2ratio >300 mm Hg).ResultsAmong 364 randomised patients, 55 (30.3%) of 181 patients assigned to HFNO and 70 (38.6%) of 181 patients assigned to COT underwent escalation of respiratory support, with no significant difference between groups (absolute risk difference −8.2% (95% CI −18% to +1.4%); RR 0.79 (95% CI 0.59 to 1.05); p=0.09). There was no significant difference in clinical recovery (69.1% vs 60.8%; absolute risk difference 8.2% (95% CI −1.5% to +18.0%), RR 1.14 (95% CI 0.98 to 1.32)), intensive care unit admission (7.7% vs 11.0%, absolute risk difference −3.3% (95% CI −9.3% to +2.6%)), and in hospital length of stay (11 (IQR 8–17) vs 11 (IQR 7–20) days, absolute risk difference −1.0% (95% CI −3.1% to +1.1%)).ConclusionsAmong patients with COVID-19 pneumonia and mild hypoxaemia, the use of HFNO did not significantly reduce the likelihood of escalation of respiratory support.Trial registration numberNCT04655638.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has changed bronchoscopy practices worldwide. Bronchoscopy is a high-risk aerosol-generating procedure with a potential for direct SARS-CoV-2 exposure and hospital-acquired infection. Current guidelines about personal protective equipment and environment considerations represent key competencies to minimize droplets dispersion and reduce the risk of transmission. Different measures should be put in field based on setting, patient's clinical characteristics, urgency and indications of bronchoscopy. The use of this technique in SARS-CoV-2 patients is reported primarily for removal of airway plugs and for obtaining microbiological culture samples. In mechanically ventilated patients with SARS-CoV-2, bronchoscopy is commonly used to manage complications such as hemoptysis, atelectasis or lung collapse when prone positioning, physiotherapy or recruitment maneuvers have failed. Further indications are represented by assistance during percutaneous tracheostomy. Continuous positive airway pressure, non-invasive ventilation support and high flow nasal cannula oxygen are frequently used in patient affected by Coronavirus Disease-2019 (COVID-19): management of patients' airways and ventilation strategies differs from bronchoscopy indications, patient's clinical status and in course or required ventilatory support. Sedation is usually administered by the pulmonologist (performing the bronchoscopy) or by the anesthetist depending on the complexity of the procedure and the level of sedation required. Finally, elective bronchoscopy for diagnostic indications during COVID-19 pandemic should be carried on respecting rigid standards which allow to minimize potential viral transmission, independently from patient's COVID-19 status. This narrative review aims to evaluate the indications, procedural measures and ventilatory strategies of bronchoscopy performed in different settings during COVID-19 pandemic.

Background High generated tidal volumes (Vt) have been correlated with higher risk of self-induced lung injury and worse clinical outcome. This study aimed to evaluate the effectiveness and safety of a new helmet continuous positive airway pressure delivered (h-CPAP) configuration allowing Vt monitoring in patients affected by COVID-19. Methods This prospective observational study was performed in the respiratory intermediate care unit of University Hospital in Turin, Italy, between March 24th, and June 15th, 2020. Included patients were treated with CPAP via a single-limb intentional leak configuration by a turbine-driven ventilator, provided with a dedicated patch. Effectiveness and safety of the configuration and healthcare workers safety were the outcomes of the study. Main findings Thirty-five patients were included in this study. Median age was 67 years (IQR 57–76 years), and 30 patients (85.7%) were men. Median value of overall leaks (intentional plus unintentional) was 68 L/min (IQR 63–75). Reliability of Vt measurements was 100%. An out of scale of Vt (above 50% compared to the previous values) was never recorded. Six patients (17.1%) needed more than two helmet replacements, due to leak test >10 l/min. Arm oedema and skin breakdowns were reported in sixteen (45.7%) and seven (20%) patients respectively. Among the 63 healthcare workers involved in the care of COVID-19 patients during the study only one was positive at RT-PCR nasopharyngeal swab testing. Conclusions The use of h-CPAP for treating COVID-19 in this configuration allowed for reliable Vt monitoring. Further studies evaluating this configuration in larger patients’ cohorts are needed.

Objective: To evaluate how Amyotrophic Lateral Sclerosis (ALS) patients��� mortality rates change, based on different levels of forced vital capacity (FVC) and disease duration, providing a scheme of mortality rates of a real population of ALS patients to improve the design of future RCTs. Methods: One random spirometry for each ALS patient was selected during four time intervals from disease onset: (1) ���12 months; (2) ���18 months; (3) ���24 months; (4) ���36 months. Date of spirometry corresponded to date of trial entry, while time interval onset-spirometry to disease duration at enrollment. Mortality rates from inclusion were computed at different time intervals. Based on progression rates, patients were stratified in slow, intermediate and fast progressors. Survival from recruitment was calculated depending on FVC, disease duration and progression rate. Results: We included 659 patients in group 1, 888 in group 2, 1019 in group 3 and 1102 in group 4. Mortality rates were higher in each group at reducing the FVC cutoff used for recruitment (p p Conclusions: This is a simple model for setting eligibility criteria, based on mortality rates of patients depending on FVC and disease duration, to select the best population for RCTs, tailored to trials��� primary endpoints and duration.

The respiratory failure management in NMD is complex. A correct choice of NIV initiation with a correct evaluation of lung function, sleep disorders, and symptoms is very important, besides a selection of appropriate interfaces and ventilator settings. With the progression of NMD, there is an increase of NIV dependence with the evaluation of multiple interface exchanges and different ventilation profiles for daytime and nocturnal ventilation, and for this reason, a key role is played by a proper follow-up. Adequate NIV management and mucus clearance therapy reduce morbidity and mortality.

In late December 2019, clusters of patients with interstitial pneumonia of unknown cause were reported by some local health facilities in Wuhan (China). The Chinese Centre for Disease Control conducted an epidemiologic and etiologic investigation, leading to the identification of a novel coronavirus (SARS-CoV-2).1, 2 On March 11th, the World Health Organization (WHO) declared the novel coronavirus disease (COVID-19) a pandemic. In the area of Wuhan, COVID-19 mainly affected male patients (around 60%), with a median age of about 50 years; 40% of patients developed Acute Respiratory Distress Syndrome (ARDS) 5% requiring intensive care. The mortality rate was around 2%.3, 4 However, Grasselli et al. found that the mortality was 26% in ICU. The death rate was higher among those who were older.5. The hypothesis is that in case of a pandemic, selected COVID-19 patients may benefit from the combination of early hCPAP and prone position sessions, in order to reduce the need for intubation and invasive mechanical ventilation, “buying time” for the disease to heal.

There is still a lack of consensus among different guidelines about the right timing for starting non-invasive mechanical ventilation (NIMV) in amyotrophic lateral sclerosis (ALS).1–3 The importance of spirometry as a reliable prognostic factor in ALS has been widely recognised; conversely, very few studies investigated the role of arterial blood gas analysis (ABG). With respiratory failure being the main cause of death in ALS, we aimed at investigating the role of ABG as proxy for pulmonary function tests (PFTs) in a large cohort of patients with ALS, identifying the best cut-off values for forced vital capacity (FVC%), carbon dioxide (pCO2), carbonate (HCO3-) and standard base excess (SBE) to predict NIMV starting and survival. We included 488 patients with concomitant ABGs, PFTs and Amyotrophic Lateral Sclerosis Functional Rating Scale - revised (ALSFRS-r) score, followed up in the Turin ALS Center, resident in Piemonte and Valle d’Aosta, diagnosed between 2000 and 2015, excluding patients with severe pulmonary and kidney comorbidities. Descriptive statistic of the population is shown in the online supplementary material 1. Two-hundred and seventy-four patients (56.1%) underwent NIMV. Median time between ABG/PFT and NIMV initiation was 5.0 months (IQR 1.0–12.0). NIMV was started at a median FVC% value of 57.4% (IQR 44.2–73.6). Median overall survival after NIMV initiation was 225 days (IQR 104–491). Patients who did not undergo NIMV (n=214) were significantly older (68.6 years vs 64.9 years, p

The association between primary aldosteronism (PA) and obstructive sleep apnea (OSA) has been a matter of debate. 2016 Endocrine Society guideline recommends screening for PA all hypertensive patients with OSA. We designed a multicenter, multiethnic, cross-sectional study to evaluate the prevalence of PA in patients with OSA and the prevalence of OSA in unselected patients with PA. Two hundred and three patients with OSA (102 whites and 101 Chinese) were screened for PA, and 207 patients with PA (104 whites, 100 Chinese, and 3 of African descent) were screened for OSA by cardiorespiratory polygraphy. Eighteen patients with OSA (8.9%) had PA (11.8% of white and 5.9% of Chinese ethnicity). In patients without other indications for PA screening, the prevalence of PA dropped to 1.5%. The prevalence of OSA in patients with PA was 67.6%, consistent in both white and Chinese patients. A correlation between aldosterone levels and apnea/hypopnea index was observed in white patients with PA ( R 2 =0.225, P =0.016) but not in Chinese patients. Multinomial logistic regression confirmed a significant and independent association between plasma aldosterone levels and moderate to severe OSA diagnosis in white patients (odds ratio, 1.002; P =0.002). In conclusion, aldosterone levels may contribute to the severity of OSA in white patients with hyperaldosteronism, but patients with OSA are not at high risk of PA. Results of the present study challenge the current recommendation of the Endocrine Society guideline that all patients with OSA should be screened for PA, irrespective of the grade of hypertension.

To compare the prognostic role of FVC and SVC at diagnosis in amyotrophic lateral sclerosis (ALS) patients. We included all patients from the Piemonte and Valle D’Aosta ALS register (PARALS) who had been diagnosed with ALS between 1995 and 2015 and underwent spirometry at diagnosis. Survival was considered as time to death/tracheostomy; to assess the prognostic value in typical trial timeframes, survival at 12 and 18 months was calculated too. Cox proportional hazard regression models adjusted by sex, age at diagnosis, diagnostic delay, onset site, and ALSFRS-R total score at the moment of diagnosis were used to assess the prognostic role of FVC and SVC. A total of 795 ALS patients underwent spirometry at diagnosis during the study period. Four hundred and sixteen (52.3%) performed both FVC and SVC, whereas the others performed FVC only. FVC and SVC values were highly correlated (r = 0.92, p

BACKGROUND: A recent study found that activation of disconnection and low-pressure alarms is common during mouthpiece ventilation and may represent a major limitation to its use. The aim of this bench study was: (1) to investigate the technical aspects that can influence the setting of the ventilator during mouthpiece ventilation and (2) to provide a practical setting strategy to avoid the alarm activation. METHODS: Eight life-support ventilators able to deliver volume controlled ventilation were tested in a bench study using a single-limb non-vented circuit configuration connected to a standard mouthpiece. Disconnection and apnea alarm were turned off or set at the least sensitive setting. The backup frequency was set at the lowest available level. Different tidal volumes (VT) (from 500 to 1,200 mL) were tested with the rectangular and descending flow shape. For each VT, we reported the maximum set inspiratory time (TI) that allowed preventing activation of the low-pressure alarm. The presence of auto-triggering was also surveyed. RESULTS: We found that a correct combination of VT and TI avoided the activation of disconnection and low-pressure alarms in all but 3 ventilators. One ventilator did not allow mouthpiece ventilation independently from the settings used. The inability to turn off the apnea alarm in two other ventilators led to the alarm going off in any tested conditions after 120 s without triggered breaths. Auto-triggering was seldom found and easily worked out, except for in one ventilator. CONCLUSIONS: An appropriate alarm setting and combination of VT and TI would allow the majority of the tested ventilators to be used for mouthpiece ventilation without alarm activation.

Background: Intervention studies with vitamin D in asthma are inconclusive for several reasons, such as inadequate dosing or duration of supplementation or uncontrolled baseline vitamin D status. Our aim was to evaluate the benefit of long term vitamin D add-on in asthmatic patients with actual vitamin D deficiency, that is a serum 25-hydroxy vitamin D (25-OHD ) below 20 ng/mL. Methods: Serum 25-OHD, asthma exacerbations, spirometry and inhaled corticosteroids (CS) dose were evaluated in a cohort of 119 asthmatic patients. Patients with deficiency were evaluated again after one year vitamin supplementation. Results: 25-OHD was low in 111 patients and was negatively related to exacerbations (p < 0.001), inhaled CS dose (p = 0.008) and asthma severity (p = 0.001). Deficiency was found in 90 patients, 55 of whom took the supplement regularly for one year, while 24 discontinued the study and 11 were not adherent. Patients with vitamin D deficiency after 12 months supplementation showed significant decrease of exacerbations (from 2.6 ± 1.2 to 1.6 ± 1.1, p < 0.001), circulating eosinophils (from 395 ± 330 to 272 ± 212 106/L, p < 0.001), and need of oral CS courses (from 35 to 20, p = 0.007) and improvement of airway obstruction. Conclusions: Asthma exacerbations are favored by vitamin D deficiency and decrease after long-term vitamin D replacement. Patients who are vitamin D deficient benefit from vitamin D supplementation.

Body: We evaluated the long term effect (four years) of omalizumab on severe asthma (SA), in terms of symptoms (ACT), exacerbations (AE), airway obstruction, FENO, circulating eosinophils (EOS). Methods: In 29 patients with allergic SA and FEV1 Results: In the 29 overall patients, omalizumab treatment was followed by significant improvement in FEV1, ACT, AE and EOS. In baseline, G1 had higher FEV1 (67 vs 57 %), FENO (75.8 vs 26.6 ppb), EOS (738 vs 339 10^6/L), while total IgE (434 vs 343 UI/L), ACT (16 vs 16) and AE (4.6 vs 4.2) were similar to G2. In G1 all the variables improved during treatment, while in G2 improved only ACT and AE, see figure. Conclusions: Our findings support the long term efficacy of omalizumab on exacerbations and symptoms in patients with SA. In a subgroup of patients, identifiable with higher EOS and FENO, omalizumab attenuates airway inflammation and reverses airway obstruction, suggesting an effect on airway remodeling.

Background: We recently found that in COPD patients severe vitamin D (25-OHD) deficiency is associated with disease exacerbations (AECOPD) and hospitalizations (HCOPD). We evaluated if vitamin D supplementation may decrease the number of AECOPD and HCOPD in 45 COPD patients with 25-OHD deficiency (25-OHD Methods: The patients were 16 men and 28 women, age range 50-84 years, 30 active smokers. The number of AECOPD and HCOPD in the year preceding 25-OHD assessment were compared to those recorded the following year, during vitamin supplementation (1000 IU daily). Results: GOLD class distribution was : 1 = 7 pt, 2 = 24, 3 = 7, 4 = 6. In baseline, 20 pts had severe 25-OHD deficiency ( Conclusion: Our findings suggest that in COPD patients, 25-OHD deficiency is frequent and favors exacerbations and hospitalization for the disease. This hypothesis is supported by the significant decrease in AECOPD and HCOPD observed after vitamin D replenishment.

Background: Amyotrophic Lateral Sclerosis (ALS) is a progressive fatal neurodegenerative disease with respiratory impairment (RI). ASL patients (pts) with RI are home-treated with non-invasive ventilation (NIV), only a minor percentage with invasive tracheostomy ventilation (IVt). Telemonitoring can be useful to improve home-treating clinical problems and optimize home ventilation. Methods: From April 2013 to October 2014, ALS pts have been telemonitored with financial support of Piemonte Region; the project consisted of dedicated pneumologist for home visits, call center, patient-dedicated tablet, oximeter for real time data, monthly monitoring of nocturnal oximetry and data base. Each patient had to answer on the tablet to daily and fortnight questions about symptoms and mechanical ventilation parameters; the answers could determine telephone or video call with pneumologist, home medical visit or hospitalization. Results: 41 (30 NIV, 11 IVt) ALS pts have been enrolled; 6081 daily clinical questionnaires (total adherence 58%, 65% IVt, 51% NIV) and 510 fortnight questionnaires (total adherence 76%, 77% IVt, 80% NIV) have been answered. Based on the answers, 15 unscheduled home visits and 113 telephone contacts with pneumologist have been performed. 8 NIV pts needed hospitalization for 99 days (3.1 day/pt/yr). Mortality in NIV was 10 pts (33%). In a similar group of 24 NIV-ALS pts without telemonitoring in 2012, 8 pts needed hospitalization for 132 days (5,5 day/pt/yr) and mortality was 8 pts (33%). Conclusion: In our experience, telemonitoring ALS patients in NIV doesn9t change mortality but reduces the need for hospitalization and costs for patient.

Noninvasive ventilation (NIV) refers to the noninvasive delivery of mechanical ventilation or continuous positive airway pressure (CPAP) through the patient’s mouth, nose, or both via different external interfaces. Noninvasive ventilation (NIV) has found a wide application both in home care and in the hospital setting. However, most of the studies on the acute application of NIV were carried out in the intensive care unit (ICU), emergency room, or in step-down units. These locations represent an “ideal” environment for the safe treatment of patients with moderate to severe acute respiratory failure (potentially with need of airway intubation) for the expertise of the staff and careful monitoring. This article will review the use of NIV outside the critical care area.

Background Acute exacerbations of COPD (AECOPD) are common and strongly influence disease severity and relative healthcare costs. Vitamin D deficiency is frequent among COPD patients and its contributory role in disease exacerbations is widely debated. Our aim was to assess the relationship of serum vitamin D levels with COPD severity and AECOPD. Methods Serum vitamin D (25-hydroxyvitamin D) levels were measured in 97 COPD patients and related to lung function, comorbidities, FEV1 decline, AECOPD and hospital admission during the previous year. Results Most patients (96%) had vitamin D deficiency, which was severe in 35 (36%). No significant relationship was found between vitamin D and FEV1 or annual FEV1 decline. No difference between patients with and without severe vitamin D deficiency was found in age, gender, BMI, smoking history, lung function, and comorbidities, apart from osteoporosis (60.9% in severe deficiency vs 22.7%, p = 0.001). In multiple logistic regression models, severe deficiency was independently associated with AECOPD [adjusted odds ratios (aOR) of 30.5 (95% CI 5.55, 168), p

Adherence to medical therapies is a growing issue, so much so that the World Health Organization defined it as “a new pharmacological problem”. The main factors affecting compliance are: frequency of administration, rapid onset of action, role of device. The most severe consequence of non-adherence is the increased risk of poor clinical outcome, associated with worsening of the quality of life and increase in health-care expenditure. It appears crucial to identify those COPD patients who are “poorly or not at all compliant with their treatment”. In order to evaluate adherence to the medical therapy, several methods were proposed, the most effective of which turned out to be self-reports, i.e. simple, brief questionnaires (e.g. Morisky test). To increase the likelihood of quickly identifying non-compliant patients, it may be useful to administer a simple questionnaire to naïve subjects (for example, in the waiting room before an examination) including six specific items allowing to identify the patient’s key characteristics. Depending on the answers, patients who do not comply with their pharmacological treatment may be classified as belonging to 6 phenotypes. For patients who are already under treatment it might be useful to administer another short questionnaire during follow up examination. Once the risk of non-compliance is identified, four possible types of measures can be taken: prescription-related, educational, behavioral and complex combined measures (combination of two or more actions). Therefore, while it is clear that adherence in COPD is a critical issue, it is also obvious that raising awareness on the disease and improving cooperation among specialists, general practitioners, health-care professionals, and patients is the starting point at which this evolution should immediately begin. Each medication is able to foster good compliance with the therapy, and consequently to maximize the efficacy, by virtue of its specific inhaler and its own active ingredient. Electronic supplementary material The online version of this article (doi:10.1186/2049-6958-9-60) contains supplementary material, which is available to authorized users.

To assess the behaviour of a pressure-preset volume-guaranteed (V(TG)) mode of ventilation in the presence of non-intentional leaks in single-limb circuit (SLC) home ventilators.All SLC home ventilators commercially available in Italy can be used in a V(TG) mode with an intentional leak ("vented") or a true expiratory valve ("non-vented") configuration were selected. Using an experimental model consisting of a mannequin connected to an active lung simulator, for each level of leak (15, 25 and 37 l/min) three different conditions of respiratory mechanics (normal, restrictive and obstructive) were simulated using the ventilators in either a "vented" or "non-vented" configuration.Three home ventilators were tested: Vivo50 (Breas), PB560 (Covidien) and Ventilogic LS (Weimann). In a "vented" circuit configuration all three ventilators kept constant or increased inspiratory pressure in all leak conditions to guarantee the V(TG). Conversely, in a "non-vented" circuit configuration, all tested ventilators showed a drop in inspiratory pressure in all leak conditions, resulting in a concomitant reduction in delivered tidal volume. The same behaviour was found in all conditions of respiratory mechanics. In the absence of leaks, all the ventilators, independently of circuit configuration, were able to maintain the set V(TG) in the presence of modifications of the respiratory mechanics.The ability of the V(TG) mode to compensate for non-intentional leaks depends strictly on whether a "vented" or "non-vented" circuit configuration is used. This difference must be taken into account as a possible risk when a V(TG) mode is used in the presence of non-intentional leaks.