Low-intensity rehabilitation in persistent post COVID-19 dyspnoea: the value of Spa health resort as appropriate setting.

Background: Post COVID-19 syndrome is a frequent disabling outcome, leading to a delay in social reintegration and return to working life. Study design: This was a prospective observational cohort study. The main objective was to explore the effectiveness of a Spa rehabilitation treatment on the improvement of post COVID-19 dyspnoea and fatigue, also analyzing the relationship between such symptoms. Additionally, it was assessed if different clinical characteristics could predispose patients in experiencing post COVID-19 symptoms or could influence the effectiveness of a Spa intervention. Methods: From July to November 2021, 187 post COVID-19 patients were enrolled in the study. All the patients complained persisting dyspnoea, whose impact on daily activities was assessed using the modified Medical Research Council dyspnoea scale. 144 patients (77.0%) reported also fatigue. The Spa treatment was started at least 3 months after COVID-19 acute phase. At the end of the treatment, patients were asked to rate the improvement in the dyspnoea and fatigue sensation. 118 patients also underwent the modified Borg Dyspnoea Scale for severity estimation of Exertion Dyspnoea and the Barthel index for severity estimation of Physical Limitation. Results: 165 out of 187 patients (88.2%) reported an improvement in dyspnoea, while 116 out 144 patients (80.6%) reported an improvement in both dyspnoea and fatigue. On a total of 118 subjects, a clinically significant improvement in the modified Borg Dyspnoea Scale (i.e. Delta Borg equal or more than -2.0 points) was reached by the 50.8% of patients, while a clinically significant improvement in the Barthel index (i.e. Delta Barthel equal or more than +10.0 points) was reached by the 51.7% of them. The 31.4% of patients reached a minimal clinically important improvement in both the modified Borg Dyspnoea Scale and the Barthel index. No risk factors were associated to a clinically impacting dyspnoea at entry, while a BMI>30 Kg/m2 was the main risk factor for chronic fatigue. Presence of respiratory comorbidities, obesity and severe acute COVID-19 (phenotype 4) configured risk factors for the lack of improvement of dyspnoea after the treatment, while no risk factors were associated to a lack of improvement for fatigue. Older age, obesity and comorbidities seemed to make more difficult to reach a clinically meaningful improvement in the modified Borg Dyspnoea Scale and the Barthel index after treatment. Female gender may imply more physical limitation at entry, while male patients seem to show less improvement in the Barthel index after treatment. Conclusions: Dyspnoea and fatigue were confirmed to be important post COVID-19 symptoms even in younger subjects of working age and subjects with absent or modest pulmonary alterations at distance from acute COVID-19. A Spa health resort seems to be an effective "low-intensity" setting for a rehabilitation program of such patients. There is a strong relationship in terms of improvement between dyspnoea and fatigue, even if risk factors for their occurrence appear to be different. The improvement in exertion dyspnoea and physical limitation seemed to be less mutually related, probably due to a greater complexity in the assessment questionnaires. Some risk factors may predict a lack of improvement in symptoms after treatment.

Predictive tools for nocturnal respiratory failure in patients with moderate and severe OSAS.

PURPOSE: The impact of obstructive sleep apnea syndrome (OSAS) in terms of mortality, morbidity, and quality of life has been well established. Phenotyping OSAS is essential in order to make the best therapeutic choice. A particular subset of patients with OSAS shows nocturnal respiratory failure, defined by a nighttime oxygen saturation <90% in more than 30% of the total sleep time (TST90). The aim of this study was to identify possible predictive factors for nighttime respiratory failure (NRF) in patients with OSAS. METHODS: In this retrospective study, patients with suspected OSAS who underwent a sleep study were enrolled. Of 116 patients with moderate/severe OSAS who met the inclusion criteria, 67 also had nocturnal respiratory failure. We compared clinical, anthropometric, and laboratory data in patients with OSAS vs. OSAS and nocturnal respiratory failure. RESULTS: Patients with OSAS and nocturnal respiratory failure were more frequently female, had a higher BMI, lower daytime oxygen partial pressure (PaO2) in arterial blood, higher Apnea Hypopnea Index (AHI), and a lower number of sleep hours per night. Chronic obstructive pulmonary disease (COPD) was more diagnosed in the group of patients with nocturnal respiratory failure. A lower number of total sleep hours, lower daytime PaO2, lower AHI, increased oxygen desaturation index (ODI), and the presence of a diagnosed COPD were all found to increase the risk of having nocturnal respiratory failure. CONCLUSION: COPD, AHI, ODI, daytime PaO2, and total sleep hours are the main predictors for NRF in patients with moderate and severe OSAS.

Significant burden of post-COVID exertional dyspnoea in a South-Italy region: knowledge of risk factors might prevent further critical overload on the healthcare system.

Background: Exertional dyspnoea in post-COVID syndrome is a debilitating manifestation, requiring appropriate comprehensive management. However, limited-resources healthcare systems might be unable to expand their healthcare-providing capacity and are expected to be overwhelmed by increasing healthcare demand. Furthermore, since post-COVID exertional dyspnoea is regarded to represent an umbrella term, encompassing several clinical conditions, stratification of patients with post-COVID exertional dyspnoea, depending on risk factors and underlying aetiologies might provide useful for healthcare optimization and potentially help relieve healthcare service from overload. Hence, we aimed to investigate the frequency, functional characterization, and predictors of post-COVID exertional dyspnoea in a large cohort of post-COVID patients in Apulia, Italy, at 3-month post-acute SARS-CoV-2 infection. Methods: A cohort of laboratory-confirmed 318 patients, both domiciliary or hospitalized, was evaluated in a post-COVID Unit outpatient setting. Post-COVID exertional dyspnoea and other post-COVID syndrome manifestations were collected by medical history. Functional characterization of post-COVID exertional dyspnoea was performed through a 6-min walking test (6-mwt). The association of post-COVID exertional dyspnoea with possible risk factors was investigated through univariate and multivariate logistic regression analysis. Results: At medical evaluation, post-COVID exertional dyspnoea was reported by as many as 190/318 patients (59.7%), showing relatively high prevalence also in domiciliary-course patients. However, functional characterization disclosed a 6-mwt-based desaturation walking drop in only 24.1% of instrumental post-COVID exertional dyspnoea patients. Multivariate analysis identified five independent predictors significantly contributing to PCED, namely post-COVID-fatigue, pre-existing respiratory co-morbidities, non-asthmatic allergy history, age, and acute-phase-dyspnoea. Sex-restricted multivariate analysis identified a differential risk pattern for males (pre-existing respiratory co-morbidities, age, acute-phase-dyspnoea) and females (post-COVID-fatigue and acute-phase-dyspnoea). Conclusion: Our findings revealed that post-COVID exertional dyspnoea is characterized by relevant clinical burden, with potential further strain on healthcare systems, already weakened by pandemic waves. Sex-based subgroup analysis reveals sex-specific dyspnoea-underlying risk profiles and pathogenic mechanisms. Knowledge of sex-specific risk-determining factors might help optimize personalized care management and healthcare resources.

Economic impact of implementing prescription of single-inhaler triple therapies versus current multiple-inhaler triple therapies for COPD in the Apulia Region.

BACKGROUND: The most impacting direct costs associated to COPD for the National Health Systems (NHS) are those related to accesses to the emergency room and hospital admissions, due to the onset of one or more COPD exacerbations. At the same time, severe COPD treatment, that often require a combination of medicaments, represents a substantial economic burden for the National Health Systems (NHS). This study aimed to evaluate the potential saving deriving from the implementation in the prescription of the two currently available single-inhaler triple therapies (SITTs) versus the currently used multiple-inhaler triple therapies (MITTs) in an eligible COPD population residing in the Apulia Region. METHODS: A budget impact model was developed hypothesizing the progressive replacement of the different MITTs on the reference market (Scenario A) with the pre-established SITTs, assuming a degree of penetration of 30%, 50% and 100% (Scenario B). Drug costs were based on prices published on the Official Gazette and therapy durations were based on prescribing information over the year 2019 (IQVIA™ prescription dataset). RESULTS: Our analysis showed that the extemporaneous MITT with the highest prevalence on the reference market was the inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) combination plus a long-acting muscarinic antagonists (LAMA). This association of medicaments was paradoxically also the one associated to the highest expense value. The expanded use of a pre-established ICS/LAMA/LABA SITT was associated to a significant economic saving, ranging from a minimum of -€ 1,108,814 (SITT use: 30%) to a maximum of -€ 3,658,950 (SITT use: 100%). The cheapest pre-established SITT contained the fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) combination. CONCLUSION: A pre-fixed ICS/LAMA/LABA SITT is cost-saving, compared to the different currently used extemporaneous MITTs. Clinicians should consider the potential benefits of finding less expensive regimens while maintaining adequate efficacy in the prescriptive decision making process of COPD patients.

Early effectiveness of type-2 severe asthma treatment with dupilumab in a real-life setting; a FeNO-driven choice that leads to winning management.

Background: Dupilumab is a humanized monoclonal antibody targeting the IL4/IL13 signaling pathway, already used for atopic dermatitis and chronic rhinitis with nasal polyps, recently approved for severe type-2 asthma. Its efficacy has been demonstrated in randomized control trials. The aim of our study is to evaluate possible early clinical improvement and type 2 biomarkers modifications in severe asthmatic patients treated with dupilumab in a real-life setting. Methods: We included 12 patients with severe, uncontrolled asthma and dupilumab was chosen if there was at least one evidence of blood eosinophils> 150 cells/ml and/or FeNO>25 ppb during last year. Recent blood eosinophil count report, assessment through ACT, FeNO test and spirometry were performed at baseline and after 3 months of treatment. We calculated also the number of patients achieving a minimal, yet clinically relevant difference in FEV1 and ACT. Results: After three months of treatment with dupilumab, ACT had a significant improvement (mean ACT pre 13.25±4.65 vs mean ACT post 19.17±4.45; p<0.01), so as FEV1% (mean FEV1% pre 62.58±15.73 vs mean FEV1% post 71.00±13.11; p<0.01). FeNO had a significant reduction (median FeNO 32 pre, IQR 19-48.5 vs median FeNO19 post, IQR 16.5-26), differently from eosinophils blood count (median eosinophils pre 280, IQR 193.8-647.3 vs median eosinophils post 349.5, IQR 103-836.8; p=0.52). Four patients (33%) had a positive MCID for FEV1, and eight patients (67%) had a positive MCID for ACT. Conclusions: In RCTs performed during clinical development program dupilumab showed an early efficacy in increasing FEV1, reducing FeNO and improving asthma control. Our study demonstrates early improvement in asthmatic symptoms, lung function and FeNO in severe type-2 asthma patients after only 3 months of dupilumab biologic therapy. The introduction of FeNO levels evaluation in the selection criteria for dupilumab, further helps the identification of eligible patients among type-2 severe asthma patients and allows a complete outpatient assessment. Further real-life studies with a longer follow up time will be useful to confirm dupilumab efficacy and to promote its use in clinical practice.

The association between dysphagia and OSA.

OBJECTIVE: The aim of our study was to investigate the presence of dysphagia in patients with Obstructive Sleep Apnoea (OSA) and to correlate swallowing impairment with hypnologic and anatomic parameters. METHODS: The study population includes 36 patients suffering from OSA. Patients were divided into two groups using the presence of dysphagia as a distinctive parameter. Group 1 included 27 OSA patients without signs of dysphagia and Group 2 included 9 OSA patients with signs of dysphagia. RESULTS: The age of patients in Group 2 was higher compared with the age of patients in Group 1. Analysis of Continuous Positive Airway Pressure (CPAP), obtained in the titration phase, showed that OSA patients with signs of dysphagia required a higher level of CPAP pressure than those who were not affected by swallowing abnormalities (12.6 ± 1 vs 10.5 ± 1.9 p = 0.003). No other differences in anthropometric, hypnologic, or arterial blood gas values were found between the two groups. CONCLUSIONS: In clinical practice, all OSA patients should undergo a complete ENT exam, including assessment of swallowing, before CPAP therapy is started. This may predict the need for higher CPAP pressure settings to resolve apnoea episodes in the presence of dysphagia as well as guide the choice of CPAP interfaces (orofacial vs. nasal) in these patients.

Mild/Moderate Asthma Network in Italy (MANI): a long-term observational study.

OBJECTIVE: The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences. METHODS: This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844). RESULTS AND CONCLUSION: Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease. ABBREVIATIONS: MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting ß2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

Relationships between Obstructive Sleep Apnea Syndrome and cardiovascular risk in a naïve population of southern Italy.

BACKGROUND: Obstructive sleep apnea (OSA) is a worldwide increasing syndrome, which, by promoting endothelial dysfunction, contributes to extend the cardiovascular risk. We evaluated the cardiovascular risk in a group of OSA patients. METHODS: A total of 185 OSA subjects (19 normal weight, 57 overweight, 109 obese), who entered the Ambulatory of Sleep Disorders of the Institute of Respiratory Diseases of the University of Bari, during 1 year, were enrolled in the study. We assessed anthropometric features, polysomnographic findings, cardiovascular risk factors, smoking habit, Pulmonary Function Test, Arterial Blood Gas Analysis, Epworth Questionnaire, and Charlson Co-morbidities Index (CCI). Subjects were divided into three groups, according to their BMI: individuals with BMI ≥30 kg/m2 (Group 1 n = 109, mean age 61 ± 1; 74.3% men), individuals with BMI ranging from 25.0 to 29.9 kg/m2 defined as overweight subjects (Group 2 n = 57, mean age 58.8 ± 1.4; 77% men), and subjects with a BMI ranging from 18.5 to 24.9 kg/m2 defined as normal weight subjects (Group 3 n = 19, mean age 54.2 ± 2.3; 64,2% men). RESULTS: In the whole population, the percentage cardiovascular risk was weakly related with BMI (r = 0.33; P < .001), but not with AHI. The cardiovascular risk was strictly related to the obesity (P < .00002), while the Epworth Questionnaire score and the Charlson Co-morbidity Index were respectively statistically higher in the group of obese individuals (P = .004, P = .0002) than in the other two sub-groups. When AHI values were stratified in tertiles, the percentage cardiovascular risk did not vary with increasing AHI values (Figure 2). CONCLUSIONS: Further studies are required to investigate the pivotal role of inflammation resulting from obesity, and underlying increased cardiovascular risk in OSA patients.

Impact of smoking, COPD and comorbidities on the mortality of COVID-19 patients.

The prognosis of the coronavirus disease 2019 (COVID-19) patients is variable and depends on several factors. Current data about the impact of chronic obstructive pulmonary disease (COPD) and smoking on the clinical course of COVID-19 are still controversial. This study evaluated the prevalence and the prognosis of COPD patients and smokers in a cohort of 521 patients admitted to four intermediate Respiratory Intensive Care Units (Puglia, Italy) with respiratory failure due to COVID-19 pneumonia. The prevalence of COPD and current smokers was 14% and 13%, respectively. COPD patients had a higher 30-day all-cause mortality than non-COPD patients. Former smokers compared to never smokers and current smokers had higher 30-day all-cause mortality. COPD patients and former smokers had more comorbidities. This study described the prevalence and the outcomes of COPD patients and smokers in a homogenous cohort of COVID-19 patients. The study showed that the prevalence of COPD and current smokers was not high, suggesting that they were not at increased risk of getting the infection. However, when SARS-CoV-2 infection occurred, COPD patients and former smokers were those with the highest all-cause mortality, which seemed to be mainly related to the presence of comorbidities and not to COPD and smoking itself.

Reduction of Sniff Nasal Inspiratory Pressure (SNIP) as an Early Indicator of the Need of Enteral Nutrition in Patients with Amyotrophic Lateral Sclerosis.

Percutaneous endoscopic gastrostomy (PEG) is the standard procedure for feeding severely dysphagic patients with amyotrophic lateral sclerosis (ALS). It is associated with prolonged survival and improvement in quality of life. Nasal inspiratory pressure during a sniff (SNIP) is a respiratory test used extensively in ALS for the assessment of inspiratory muscle strength. In this study, we aimed to investigate the role of SNIP at baseline to predict PEG placement in ALS. Data from a clinical incident cohort of 179 ALS cases attending the multidisciplinary ALS unit of the University of Bari between April 2006 and December 2012 were retrospectively analysed. At baseline, patients underwent detailed neurological, nutritional and respiratory assessments, including measurements of SNIP and forced vital capacity (FVC). Patients were therefore followed up approximately every three to six months until they were able to attend the centre. The censoring date for the survival analysis was 15 April 2014, with PEG placement as the main outcome. Cox proportional hazard regression models were used to examine the association between SNIP and PEG placement, adjusted for possible confounders. During the follow-up period, 75 participants (42%) received PEG implant. PEG placement was more frequent (57% vs. 31%; p = 0.001) and earlier (after 11.6 ± 14.0 months from the first visit, vs. 23.3 ± 15.5 months; p < 0.0001) in the group of patients with baseline SNIP ≤ 40 cm H2O. Baseline SNIP was a predictor of PEG placement even after correction for multiple potential confounders (HR 0.98; 95% CI: 0.96-0.99; p = 0.02). To conclude, the present study showed that SNIP at baseline is an early indicator of disease progression and therefore of the need for enteral nutrition in ALS.

Prolonged Active Prone Positioning in Spontaneously Breathing Non-intubated Patients With COVID-19-Associated Hypoxemic Acute Respiratory Failure With PaO2/FiO2 >150.

Background: The COVID-19 pandemic has led to new approaches to manage patients outside the ICU, including prone positioning in non-intubated patients. Objectives: To report the use of prolonged active prone positioning in spontaneously breathing patients with COVID-19-associated acute respiratory failure. Spontaneously breathing vs non-invasive respiratory support for COVID19 associated acute respiratory failure. Methods: Patients with PaO2/FiO2 > 150, with lung posterior consolidations as assessed by means of lung ultrasound, and chest x-ray were studied. Under continuous pulse oximetry (SpO2) monitoring, patients maintained active prone position. A PaO2/FiO2 < 150 was considered as treatment failure and patients had to be switched to non-invasive respiratory support. Retrospectively, data of 16 patients undergoing who refused proning and underwent non-invasive respiratory support were used as controls. The primary outcome was the proportion of patients maintaining prolonged prone position and discharged home. Secondary outcomes included improvement in oxygenation, hospital length of stay, and 6-month survival. Results: Three out of 16 (18.7%) patients did not tolerate the procedure. Three more patients showed a worsening in PaO2/FiO2 to <150 and required non-invasive support, two of whom finally needing endotracheal intubation. After 72 h, 10 out of 16 (62.5%) patients improved oxygenation [PaO2/FiO2: from 194.6 (42.1) to 304.7 (79.3.2) (p < 0.001)] and were discharged home. In the control group, three out of 16 failed, required invasive ventilatory support, and died within 1 month in ICU. Thirteen were successful and discharged home. Conclusion: In non-intubated spontaneously breathing COVID-19 patients with PaO2/FiO2 >150, active prolonged prone positioning was feasible and tolerated with significant improvement in oxygenation.

Incidence of deep venous thrombosis in patients with both Pulmonary Embolism and COPD.

BACKGROUND: There are no studies investigating populations of patients with both pulmonary embolism and chronic obstructive pulmonary disease (PE-COPD) with and without deep venous thrombosis (DVT). AIM OF THE STUDY: To define prevalence of DVT in COPD with PE and to compare characteristics of COPD patients who develop PE, with and without DVT. Secondly, we aimed to assess differences in the localization of PE among study groups.  METHODS. 116 patients with PE were enrolled in a retrospective study. Clinical data as well as echocardiographic and lower limb ultrasonography records were collected for all subjects. Subjects were divided into two groups according to the presence of COPD: Group 1, 54 patients with diagnosis of PE without COPD and Group 2, 66 patients diagnosed of PE with  COPD. Then, individuals of Group 2 were subdivided in two subgroups according to the presence (n=21) or absence (n=45) of DVT. RESULTS: 33% of patients with COPD and PE showed DVT.  These subjects had higher PaCO2 and ejection fraction (p<0.05 for all) and higher percentage of chronic renal failure and diabetes mellitus compared to those without DVT (p<0.05 for all). Moreover, in COPD-PE patients with DVT, the most frequent localization was proximal (54% of total), whereas COPD-PE patients without DVT showed a more frequent segmental localization (60% of total). No difference was found in clinical presentation and blood-chemistry tests. CONCLUSIONS: DVT was non-common in PE-COPD patients. Chronic renal failure, and type 2 diabetes mellitus are more frequent in PE-COPD patients with DVT, that showed a higher frequency of proximal localization, thereby indicating a greater risk of more severe clinical implications. Conversely, PE- COPD subjects without DVT showed a more frequent segmental localization and were less hypercapnic. PE should be taken into account in COPD with worsening of respiratory symptoms, also in absence of DVT.

Criteria of prescription of antibiotics and systemic corticosteroids among pulmonologists and general practictioners during asthma and COPD exacerbations: a southern Italian survey.

To date, there is still a lack of unanimity regarding the definition of exacerbation of asthma and COPD and about objective measurements in the currently used criteria. The aim of our study was to conduct a survey among general practitioners (GPs) and pulmonologists regarding the clinical criteria arbitrarily considered as important to start a course of systemic corticoids and/or antibiotics in asthma and COPD. We conducted a survey enrolling 50 general practitioners (GPs) and 50 pulmonologists, that evaluated the clinical criteria arbitrated as essential to start a course of systemic corticosteroids or antibiotics during asthma and/or COPD exacerbations. Our results demonstrated incongruities between GPs and pulmonologist and within the same professional category concerning systemic corticosteroids. Conversely, we showed higher consensus between and within the groups about criteria to prescribe antibiotics.

COVID-19 clinical phenotypes and short-term outcomes: differences between the first and the second wave of pandemic in Italy.

Objectives: There are no comparative studies between patients belonging to the first and second waves of the SARS-CoV-2 pandemic, the virus triggering coronavirus disease 2019 (COVID-19). In this retrospective observational study, we analyzed the clinical characteristics and the short-term outcomes of two groups of laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS) belonging to two different waves of the pandemic. Methods: We analyzed 97 consecutive patients from 11 March 2020 to 31 May 2020 and 52 consecutive patients from 28 August 2020 to 15 October 2020. Results: Patients belonging to the second wave were younger, had a lower number of concomitant chronic conditions (multimorbidity), and had a milder clinical phenotype. Medical treatments and respiratory support use have changed during the COVID-19 pandemic, based on different laboratory results and disease clinical features. Patients in the second wave had better short-term clinical outcomes, with lower death rates and more step-down transfers to a general ward. Conclusion: The present findings show a clear phenotypic difference in patients hospitalized at different stages of the COVID-19 pandemic in Italy. These results can help to stratify clinical risk and to better tailor medical treatments and respiratory support for patients with ARDS and COVID-19 pneumonia.

Noninvasive respiratory support outside the intensive care unit for acute respiratory failure related to coronavirus-19 disease: a systematic review and meta-analysis.

BACKGROUND: Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU. METHODS: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with 'do-not-intubate' (DNI) orders. RESULTS: Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30-41%]. 26% [21-30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36-54%]. 23% [15-32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65-78%]. Oxygenation on admission was the main source of between-study heterogeneity. CONCLUSIONS: During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020.

Risk factors for transfer from Respiratory Intermediate Care Unit to Intensive Care Unit in COVID-19.

BACKGROUND: Patients hospitalized for COVID-19-related pneumonia often need several degrees of ventilatory support, which are performed between Respiratory Intermediate Care Units (RICUs) and Intensive Care Units (ICUs), and which depend on the severity of acute respiratory distress syndrome. There is no firm consensus on transfer predictors from the RICU to the ICU. METHODS: In this retrospective observational single center study, we evaluated 96 COVID-19 patients referred to the RICU for acute respiratory failure (ARF) according to their transferal to the ICU or their stay at the RICU. We compared demographic data, baseline laboratory profile, and final clinical outcomes to identify early risk factors for transfer. RESULTS: The best predictors for transfer to the ICU were elevated C-reactive protein and lymphopenia. The mortality rate was lower in the RICU than in the ICU, where transferred patients who died were mostly younger men and with less comorbidities than those in the RICU. CONCLUSIONS: Few inflammatory markers can predict the need for transfer from the RICU to the ICU. Due to the ongoing COVID-19 pandemic, we urge better clinical stratification by early and meaningful profiles in patients admitted to the RICU who are at risk of transferal to the ICU.

Galectin-3 and neutrophil-to-lymphocyte ratio are indicative of heart remodelling and disease severity in patients with obstructive sleep apnoea.

BACKGROUND: Galectin-3, considered as a new inflammatory marker; it is increased in cardiovascular disease. We investigated Galectin-3 in relation to heart damage in patients with OSA and its role in inflammation, based on the Neutrophil-to-Lymphocyte Ratio (NLR). METHODS: Sixty-three consecutive patients (45 males, 18 females, 58.60 ± 12.28 years old) were studied. According to the Apnoea-Hypopnoea Index (AHI) patients were divided into Group 1 - non-severe (AHI <30) (17 males and 10 females, 59.89 ± 10.62 years old) and Group 2 - severe (AHI ≥30) (29 males and 6 females, aged 57.53 ± 13.30 years old) OSA. All patients underwent morning blood gas analysis, laboratory tests, nocturnal polygraphy, and echocardiography. RESULTS: Galectin-3 was significantly increased in Group 2 (p = 0.027) patients. Moreover, it was directly related to left ventricle (LV) mass, left ventricle hypertrophy and LV posterior wall diameter. Tissue Doppler septal velocity (e'), that measures wall motion, was inversely correlated to Galectin-3. Furthermore, a direct association to diastolic dysfunction, evaluated as E/e' ratio, was observed. In line with these data, a direct correlation between Galectin-3 and left atrium volume was also found. Galectin-3 and percentage of total registration time with nocturnal oxygen saturation <90% (TST90) were directly correlated (p = 0.0003), while Galectin-3 and mean nocturnal SpO2 were negatively correlated (p = 0.0045). We found a direct correlation between Galectin-3 and NLR (p = 0.011). Finally, Galectin-3 was able to predict 3-yr mortality with a specificity of 83.33% and a sensitivity of 91.84%. CONCLUSION: Galectin-3 showed a direct association to nocturnal respiratory indices and to cardiac remodelling in patients with OSA. OSA-induced inflammation may play an important role in the pathogenesis of heart damage.

Clinical and economic consequences of switching from omalizumab to mepolizumab in uncontrolled severe eosinophilic asthma.

Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS), which worsen patients' health and increase healthcare spending. The aim of this study was to assess the clinical and economic impact of switching from omalizumab (OMA) to mepolizumab (MEP) in patients eligible for both biologics, but not optimally controlled by omalizumab. We retrospectively enrolled uncontrolled severe asthmatic patients who switched from OMA to MEP during the last two years. Information included blood eosinophil count, asthma control test (ACT), spirometry, serum IgE, fractional exhaled nitric oxide (FeNO), OCS intake, drugs, exacerbations/hospitalizations, visits and diagnostic exams. Within the perspective of Italian National Health System, a pre- and post-MEP 12-month standardized total cost per patient was calculated. 33 patients were enrolled: five males, mean age 57 years, disease onset 24 years. At OMA discontinuation, 88% were OCS-dependent with annual mean rate of 4.0 clinically significant exacerbations, 0.30 exacerbations needing emergency room visits or hospitalization; absenteeism due to disease was 10.4 days per patient. Switch to MEP improved all clinical outcomes, reducing total exacerbation rate (RR = 0.06, 95% CI 0.03-0.14), OCS-dependent patients (OR = 0.02, 95% CI 0.005-0.08), and number of lost working days (Δ = - 7.9, 95% CI - 11.2 to - 4.6). Pulmonary function improved, serum IgE, FeNO and eosinophils decreased. Mean annual costs were €12,239 for OMA and €12,639 for MEP (Δ = €400, 95% CI - 1588-2389); the increment due to drug therapy (+ €1,581) was almost offset by savings regarding all other cost items (- €1,181). Patients with severe eosinophilic asthma, not controlled by OMA, experienced comprehensive benefits by switching to MEP with only slight increases in economic costs.

More skilled clinical management of COVID-19 patients modified mortality in an intermediate respiratory intensive care unit in Italy.

BACKGROUND: Some studies investigated epidemiological and clinical features of laboratory-confirmed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the virus causing coronavirus disease 2019 (COVID-19), but limited attention has been paid to the follow-up of hospitalized patients on the basis of clinical setting and the expertise of clinical management. METHODS: In the present single-centered, retrospective, observational study, we reported findings from 87 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory syndrome hospitalized in an intermediate Respiratory Intensive Care Unit (RICU), subdividing the patients in two groups according to the admission date (before and after March 29, 2020). RESULTS: With improved skills in the clinical management of COVID-19, we observed a significant lower mortality in the T2 group compared with the T1 group and a significantly difference in terms of mortality among the patients transferred in Intensive Care Unit (ICU) from our intermediate RICU (100% in T1 group vs. 33.3% in T2 group). The average length of stay in intermediate RICU of ICU-transferred patients who survived in T1 and T2 was significantly longer than those who died (who died 3.3 ± 2.8 days vs. who survived 6.4 ± 3.3 days). T CONCLUSIONS: The present findings suggested that an intermediate level of hospital care may have the potential to modify survival in COVID-19 patients, particularly in the present phase of a more skilled clinical management of the pandemic.

Bilevel and continuous positive airway pressure and factors linked to all-cause mortality in COVID-19 patients in an intermediate respiratory intensive care unit in Italy.

Objectives: In the present single-centered, retrospective, observational study, we reported findings from 78 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS) hospitalized in an intermediate Respiratory Intensive Care Unit, subdividing the patients into two groups according to their clinical outcome, dead patients and discharged patients.Methods: We further subdivided patients depending on the noninvasive respiratory support used during hospitalization.Results: In those patients who died, we found significant older age and higher multimorbidity and higher values of serum lactate dehydrogenase, C-reactive protein, and D-dimer. Among patients who were submitted to bilevel positive airway pressure (BPAP), those who died had a significant shorter number of days in overall length of stay and lower values of arterial oxygen partial pressure to fractional inspired oxygen ratio (PaO2/FiO2 ratio) compared to those who survived. No difference in all-cause mortality was observed between the two different noninvasive respiratory support groups [48% for continuous positive airway pressure (CPAP) and 52% for BPAP].Conclusion: In COVID-19 patients with moderate-to-severe ARDS using BPAP in an intermediate level of hospital care had more factors associated to all-cause mortality (shorter length of stay and lower baseline PaO2/FiO2 ratio) compared to those who underwent CPAP.