The Role of Galectins in Asthma Pathophysiology: A Comprehensive Review.

Galectins are a group of ß-galactoside-binding proteins with several roles in immune response, cellular adhesion, and inflammation development. Current evidence suggest that these proteins could play a crucial role in many respiratory diseases such as pulmonary fibrosis, lung cancer, and respiratory infections. From this standpoint, an increasing body of evidence have recognized galectins as potential biomarkers involved in several aspects of asthma pathophysiology. Among them, galectin-3 (Gal-3), galectin-9 (Gal-9), and galectin-10 (Gal-10) are the most extensively studied in human and animal asthma models. These galectins can affect T helper 2 (Th2) and non-Th2 inflammation, mucus production, airway responsiveness, and bronchial remodeling. Nevertheless, while higher Gal-3 and Gal-9 concentrations are associated with a stronger degree of Th-2 phlogosis, Gal-10, which forms Charcot-Leyden Crystals (CLCs), correlates with sputum eosinophilic count, interleukin-5 (IL-5) production, and immunoglobulin E (IgE) secretion. Finally, several galectins have shown potential in clinical response monitoring after inhaled corticosteroids (ICS) and biologic therapies, confirming their potential role as reliable biomarkers in patients with asthma.

Successful Benralizumab treatment in acute near-fatal asthma with ECMO support: a case report.

INTRODUCTION: Near-fatal asthma (NFA) is a severe condition that can lead to respiratory arrest or high carbon dioxide levels, often requiring mechanical ventilation. Biologics have revolutionized the management of severe asthma, significantly improving symptom severity, reducing the number of exacerbations and hospitalizations, and decreasing the need for oral corticosteroids. However, their effectiveness in acute settings, particularly for ICU patients experiencing severe respiratory failure, is not well-studied. More research is needed to determine if biologics can improve recovery during severe asthma exacerbations. CASE STUDY: We report a case of NFA in a patient with severe allergic eosinophilic asthma, who experienced global respiratory failure necessitating hospitalization, intubation, and veno-venous extracorporeal membrane oxygenation (VV-ECMO). Given the severity of the clinical condition, compassionate administration of Benralizumab, which targets the IL-5 receptor, was attempted. RESULTS: Five days from anti-IL5 receptor treatment start, the patient was extubated and the ECMO stopped. After the stepdown to the respiratory intensive care unit (RICU), the patient was weaned from oxygen therapy and subsequently discharged from hospital. CONCLUSION: Benralizumab demonstrated rapid effectiveness in improving respiratory failure leading to successful weaning from VV-ECMO and subsequent extubation.

Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis.

BACKGROUND AND OBJECTIVE: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on-treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on-treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Throughout 2 years of treatment with benralizumab, a four-component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function. RESULTS: The present study recruited 164 patients suffering from SEA. After 24 months of add-on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on-treatment (exacerbation rate = 0, OCS dose = 0, pre-bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT-22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post-bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on-treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively). CONCLUSION: Taken together, the results of this real-life clinical investigation indicate that benralizumab can induce a sustained remission on-treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation.

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action-eosinophilic cationic proteins' effects and allergens' proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen-immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients.

Economic impact of a more extensive use of FENO testing on the Italian population with asthma.

BACKGROUND: Asthma is a common chronic inflammatory airway affecting over 260 million people worldwide, and characterized, in the large majority of cases, by the so-called "type 2 inflammation". Fractional exhaled nitric oxide (FENO) testing is noninvasive point-of-care tool to assess type 2 inflammation and therefore improve asthma management. It has been suggested to determine eligibility for a specific biologic therapy and predict likelihood to respond. The aim of this study was to estimate the overall economic impact of an extensive use of FENO testing on the Italian population with asthma, including extra costs of testing and savings generated by more appropriate prescriptions, increased adherence and lower frequency of exacerbations. METHODS: A cost of illness analysis was firstly performed to estimate the yearly economic burden from the National Healthcare Service (NHS) perspective in Italy of the management of asthmatic patients with standard of care (SOC) according to the application of GINA (Global Initiative for Asthma) guidelines; then, we evaluated the changes in the economic burden in patient management by introducing FENO testing into clinical practice. The cost items considered were: visits/exams, exacerbations, drugs, management of adverse events caused by short-term oral corticosteroids use. Efficacy of FeNO test and SOC is based on literature evidence. Costs refer to published data or Diagnosis Related Group/outpatient tariffs. RESULTS: Considering one asthma visit every 6 months, the total yearly cost for the management of patients with asthma in Italy is 1,599,217,876€ (409.07€ per patient), while for FENO testing strategy this figure is 1,395,029,747€ (356.84€ per patient). An increased utilization rate of FENO testing from 50 to 100% of patients may lead to savings for the NHS from about 102 to 204 million € compared to SOC. CONCLUSIONS: Our study showed that FeNO testing strategy may improve the management of asthmatic patients leading to significant savings for the NHS.

Can single-inhaler Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium therapy postpone or save biologics for severe asthma?

Inhaled corticosteroids, along with beta2-agonists and anti-muscarinics, represent the cornerstone of asthma treatment. Although the advent of monoclonal antibodies has dramatically changed severe asthma management, there are still patients ineligible or with poor response to biologics. Moreover, high costs associated with monoclonal antibodies prescription are still an open issue, leading clinicians to carefully assess cost-benefit ratio before their administration. From this perspective, the use of single-inhaler Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium in patients with severe asthma could not only improve their clinical and functional performance, but also postpone biologic prescription, with positive repercussions on healthcare costs.

The Comorbid Patient in the Spotlight: Efficacy of Benralizumab on Chronic Rhinosinusitis with Nasal Polyp Outcomes in Presence of Severe Asthma.

PURPOSE OF REVIEW: The present review aims to systematically assess published data to elucidate benralizumab efficacy on nasal outcomes in comorbid patients. RECENT FINDINGS: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease of the nasal cavity often associated with severe asthma (SA), contributing to a global disease burden in asthmatics. The two pathologies share common underlying mechanisms (e.g., type-2 inflammation), which sustain symptoms and poor comorbid patient quality of life. Therefore, it is of primary importance to identify the correct therapeutic option in order to achieve the optimal management of patients affected by both pathologies. Benralizumab is a humanized monoclonal antibody directed at the α subunit of the interleukin-5 receptor (IL-5Rα) approved for the treatment of severe eosinophilic asthma. Increasing body of literature provides data on its efficacy also on CRSwNP in the comorbid SA patient. Based on the data described in this review, when benralizumab is administered to comorbid patients, it does not only control severe asthma but also improves CRSwNP clinical outcomes, although we need further studies to add stronger evidence and to improve the correct pheno-endotyping of the comorbid patient.

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.

Effect of Food Intake on Exhaled Volatile Organic Compounds Profile Analyzed by an Electronic Nose.

Exhaled breath analysis using an e-nose is a groundbreaking tool for exhaled volatile organic compound (VOC) analysis, which has already shown its applicability in several respiratory and systemic diseases. It is still unclear whether food intake can be considered a confounder when analyzing the VOC-profile. We aimed to assess whether an e-nose can discriminate exhaled breath before and after predefined food intake at different time periods. We enrolled 28 healthy non-smoking adults and collected their exhaled breath as follows: (a) before food intake, (b) within 5 min after food consumption, (c) within 1 h after eating, and (d) within 2 h after eating. Exhaled breath was collected by a formerly validated method and analyzed by an e-nose (Cyranose 320). By principal component analysis, significant variations in the exhaled VOC-profile were shown for principal component 1 (capturing 63.4% of total variance) when comparing baseline vs. 5 min and vs. 1 h after food intake (both p < 0.05). No significance was shown in the comparison between baseline and 2 h after food intake. Therefore, the exhaled VOC-profile seems to be influenced by very recent food intake. Interestingly, two hours might be sufficient to avoid food induced alterations of exhaled VOC-spectrum when sampling for research protocols.

SARS-CoV-2 pneumonia and Eisenmenger's Syndrome: doubling the challenge.

Eisenmenger's syndrome (ES) is the most severe phenotype of pulmonary arterial hypertension (PAH) secondary to congenital heart disease. In these cases, a significant systemic-to-pulmonary (left-to-right) shunting triggers the development of pulmonary vascular disease (PVD) and pulmonary hypertension. In cases of acute hypoxemic respiratory failure in patients with ES, high flow nasal cannula (HFNC) oxygen therapy should be considered as a first-line approach in order to avoid pulmonary complications and right ventricular overload related to positive pressure ventilation. Here, we report a case of HFNC use in a patient with COVID-19 infection and ES.

Assessment of Five Questionnaires for Chronic Obstructive Pulmonary Disease in a Southern Italian Population: A Proof-of-Concept Study.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a growing burden to society, and remains underdiagnosed in Italy. This study aimed at evaluating five validated screening questionnaires to consider which one was the most accurate, and the optimal cut-off score for each to be considered for the Southern Italian population. Materials and Methods: A total of 144 patients were recruited in the study. The age range was 46-85 years. All subjects underwent spirometry, and completed the five questionnaires: CDQ, LFQ, COPD-PS, COPD-SQ, and CAPTURE. Receiver-operator curves (ROC) were drawn for each questionnaire. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), values for the optimal cut-off score and previously recommended score were calculated and compared. Results: Of the questionnaires, the CDQ, LFQ, and COPD-SQ had significant differences between COPD (n = 86) and non-COPD (n = 52) groups. The AUCs for each questionnaire with (95%CI) were: CAPTURE, 0.602 (0.431-0.773); CDQ, 0.714 (0.555-0.872); LFQ, 0.331 (0.183-0.479; COPD-PS, 0.652 (0.497-0.807); and COPD-SQ, 0.679 (0.520-0.837). Only the CDQ and COPD-SQ had significant AUC screening characteristics. The optimal cut-off values for the CDQ, LFQ, and COPD-PS were modified to 22, 10, and 4, respectively. The COPD-SQ remained at 17. Conclusion: The CDQ and COPD-SQ can discriminate between individuals with and without COPD in the Italian population. The CDQ has a moderate screening accuracy, and the COPD-PS and COPD-SQ have low accuracy, when the optimal cut-off scores are used. Of the five questionnaires assessed, the CDQ and COPD-SQ questionnaires could be used for screening for COPD in the Southern Italian population.

[Inclusion of vaccination into clinical pathways for COPD and asthma: current challenges and future perspectives in Italy]. / La vaccinazione dei pazienti con BPCO e Asma nei PDTA in Italia: gap da colmare e prospettive future.

OBJECTIVES: to describe the importance given to vaccination as a preventive measure in the clinical pathways (CPWs) of patients affected by chronic obstructive pulmonary disease (COPD) and asthma in the Italian regional healthcare services. DESIGN: a comparative analysis was conducted to assess the presence/absence of vaccination recommendations among the available regional CPWs for the management of COPD and asthma. SETTING AND PARTICIPANTS: all the regional CPWs for COPD and asthma available in the "Fondazione ReS" database between 2008 and 2019 have been analysed. MAIN OUTCOME MEASURES: the role attributed to vaccination was assessed in terms of type of recommended vaccinations, management step indicated for administration, vaccination schedules, healthcare professionals involved in the vaccination pathway, potential contraindications, use of indicators for the monitoring of the offer. RESULTS: thirteen CPWs for COPD and only 3 for asthma were published between 2008 and 2019. Twelve of the CPWs for COPD included recommendation for influenza vaccination, 11 of which including also pneumococcal vaccination. The most recent CPW also contained recommendations for measles-mumps-rubella, varicella, Herpes Zoster, and tetanus-diphtheria-acellular pertussis vaccinations. Two of the CPWs related to asthma in adults recommended influenza vaccination. All CPWs provided for the vaccination recommendations during the patient follow-up step. CONCLUSIONS: Italian CPWs still pay little attention to the topic of vaccinations in patients with COPD and asthma. CPWs are required to be updated in the future being compliant with the national immunization schedule recommendations.

Effectiveness of benralizumab in severe eosinophilic asthma: Distinct sub-phenotypes of response identified by cluster analysis.

BACKGROUND: Benralizumab is effective in severe eosinophilic asthma (SEA), but suboptimal responses are observed in some patients. Although several factors have been associated with benralizumab response, no cluster analysis has yet been undertaken to identify different responsiveness sub-phenotypes. OBJECTIVE: To identify SEA sub-phenotypes with differential responsiveness to benralizumab. METHODS: One hundred and five patients diagnosed with SEA who had completed 6 months of benralizumab treatment were included in a hierarchical cluster analysis based on a set of clinical variables that can be easily collected in routine practice (age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV1 % predicted, nasal polyposis, bronchiectasis). RESULTS: Four clusters were identified: Clusters 2 and 3 included patients with high levels of both IgE and eosinophils (type-2 biomarkers high), whereas Clusters 1 and 4 included patients with only one type-2 biomarker at a high level: IgE in Cluster 1 and eosinophils in Cluster 4. Clusters 2 and 3 (both type-2 biomarkers high) showed the highest response rate to benralizumab in terms of elimination of exacerbations (79% and 80% respectively) compared to Clusters 1 and 4 (52% and 60% respectively). When super-response (the absence of exacerbation without oral corticosteroid use) was assessed, Cluster 2, including patients with more preserved lung function than the other clusters, but comparable exacerbation rate, oral corticosteroid use and symptom severity, was the most responsive cluster (87.5% of patients). CONCLUSIONS: Our cluster analysis identified benralizumab differential response sub-phenotypes in SEA, with the potential of improving disease treatment and precision management.

Could transthoracic ultrasound be useful to suggest a small airways disease in severe uncontrolled asthma?

BACKGROUND: Transthoracic ultrasound (TUS) is an accepted complementary tool in the diagnostic process of several pleuro-pulmonary diseases. However, to the best of our knowledge, TUS findings in patients with severe asthma have never been systematically described. OBJECTIVE: To explore if TUS examination is a useful imaging method in suggesting the presence of a "small airways disease" in patients with severe uncontrolled asthma. METHODS: Seventy-two consecutive subjects with a diagnosis of severe uncontrolled asthma were enrolled. The presence of a "small airways disease" was assessed through the execution of pulmonary function tests. All the patients underwent a complete TUS examination and a chest high resolution computed tomography (HRCT), which was regarded as the reference standard for comparison with TUS findings. RESULTS: Pulmonary function tests results have confirmed a reduction in expiratory flows relative to the small airways and a condition of hyperinflation in 78% and 82% of our patients, respectively. The main signs observed in the TUS examination were a thickened and/or irregular pleural line and the lack or reduction of the "gliding sign." TUS showed high sensitivity and specificity in suggesting the presence of hyperinflation and distal airways inflammation according to the HRCT scan. K Cohen's coefficients showed substantial agreement between the 2 diagnostic tests. CONCLUSION: TUS in patients with severe uncontrolled asthma can provide useful information on the state of the peripheral lung, suggesting the execution of a second-line HRCT scan for better assessment of eventual alterations that may represent the underlying causes of nonresponse to treatment.

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.

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.

The Role of a Polymer-Based E-Nose in the Detection of Head and Neck Cancer from Exhaled Breath.

The aim of our study was to assess whether a polymer-based e-nose can distinguish head and neck cancer subjects from healthy controls, as well as from patients with allergic rhinitis. A total number of 45 subjects participated in this study. The first group was composed of 15 patients with histology confirmed diagnosis of head and neck cancer. The second group was made up of 15 patients with diagnoses of allergic rhinitis. The control group consisted of 15 subjects with a negative history of upper airways and/or chest symptoms. Exhaled breath was collected from all participants and sampled by a polymer-based e-nose (Cyranose 320, Sensigent, Pasadena, CA, USA). In the Principal Component Analysis plot, patients with head and neck cancer clustered distinctly from the controls as well as from patients with allergic rhinitis. Using canonical discriminant analysis, the three groups were discriminated, with a cross validated accuracy% of 75.1, p < 0.01. The area under the curve of the receiver operating characteristic curve for the discrimination between head and neck cancer patients and the other groups was 0.87. To conclude, e-nose technology has the potential for application in the diagnosis of head and neck cancer, being an easy, quick, non-invasive and cost-effective tool.

Authors' response to the Letter to the Editor regarding: Post severe COVID-19 infection lung damages study. The experience of early three months multidisciplinary follow-up.

To the Editor, we thank Dr Ruggeri et al. for their interest in our previously published manuscript focused on lung damages after severe respiratory COVID-19 infection...

Long-term home noninvasive ventilation (LTHNIV) in restrictive thoracic diseases: the Italian snapshot.

Long-term home noninvasive ventilation (LTHNIV) in restrictive thoracic diseases was explored via the recently published international REINVENT ERS survey. The Italian subset of respondents (ITA-r), the highest above all participating nations, was analyzed and compared to non-Italian respondents (NO-ITA-r). The ITA-r represented 20% of the total answers examined. Ninety-four percent were physicians, whose half worked in a respiratory ICU (RICU). ITA-r mainly worked in community hospitals vs NO-ITA-r who are largely affiliated with university hospitals (p<0.0001). Amyotrophic lateral sclerosis (ALS) was considered the most common medical condition leading to NIV indication by both ITA-r and NO-ITA-r (93% vs 78%, p>0.5). A greater proportion of ITA-r considered MIP/MEP the most important test for NIV initiation as compared to NO-ITA-r (p<0.05). There was no significant difference for both ITA-r and NO-ITA-r as regards the other questions. This study illustrates Italian LTHNIV practices in patients with NMD and it shows some important differences with the other countries' practices but agreement in terms of goals to achieve, reasons to initiate NIV, and practices among the two communities.

Post severe COVID-19 infection lung damages study. The experience of early three months multidisciplinary follow-up.

The correct type and time of follow-up for patients affected by COVID19 ARDS is still unclear. The aim of this study was to evaluate at the survivors to COVID19 ARDS requiring non-invasive respiratory support (NRS) admitted to a Respiratory Intensive care unit (RICU) from March 8th till May 31th 2020 looking at all sequelae via a comprehensive follow up. All patients underwent a multi-disciplinary instrumental and clinical assessment within three months form admission to evaluate all infection related sequelae. Thirty-eight patients were enrolled Lung-Ultrasound (LUS) showed an outstanding discrimination ability (ROC AUC: 0.95) and a substantial agreement rate (Cohen's K: 0.74) compared to chest CT-scan detecting improvement of lung consolidations. Youden's test showed a cut-off pressure of 11 cmH2O ExpiratoryPAP-Continuous-PAP-max (EPAP-CPAP) applied at the airways during hospitalization to be significantly correlated (p value: 0.026) to the increased pulmonary artery common trunk diameter. A total of 8/38 patients (21.8%), 2 of whom during follow-up, were diagnosed with Pulmonary Emboli (PE) and started anticoagulant treatment. Patients with PE had a statistically significant shorter length of time of hospitalization, time to negative swab, CPAP/NIV duration, P/F ratio and D-dimers at follow-up compared to non PE. A comprehensive approach to patients with ARDS COVID19 requiring NRS is necessary. This study highlighted cardiopulmonary impairment related to the ARDS and to the high-EPAP-CPAP-max greater than 11mmHg provided during admission, the usefulness of LUS in monitoring post-infection recovery and the correct identification and  treatment of patients with PE during follow up.