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.

High-flow nasal oxygen versus conventional oxygen therapy in patients with COVID-19 pneumonia and mild hypoxaemia: a randomised controlled trial.

RATIONALE: In 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. METHODS: In 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/FiO2 ratio >300 mm Hg). RESULTS: Among 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%)). CONCLUSIONS: Among 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 NUMBER: NCT04655638.

Switching Biological Therapies in Severe Asthma.

Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE (Omalizumab), anti-IL-5/anti-IL-5Rα (Mepolizumab and Benralizumab), and anti-IL-4Rα (Dupilumab). Numerous randomized controlled trials (RCTs) and real-life studies have been conducted to define their efficacy and identify baseline patients' characteristics potentially predictive of favorable outcomes. Switching to another monoclonal antibody is recommended in case of a lack of benefits. The aim of this work is to review the current knowledge on the impact of switching biological therapies in severe asthma as well as on predictors of treatment response or failure. Almost all of the information about switching from a previous monoclonal antibody to another comes from a real-life setting. In the available studies, the most frequent initial biologic was Omalizumab and patients who were switched because of suboptimal control with a previous biologic therapy were more likely to have a higher baseline blood eosinophil count and exacerbation rate despite OCS dependence. The choice of the most suitable treatment may be guided by the patient's clinical history, biomarkers of endotype (mainly blood eosinophils and FeNO), and comorbidities (especially nasal polyposis). Due to overlapping eligibility, larger investigations characterizing the clinical profile of patients benefiting from switching to different monoclonal antibodies are needed.

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.

Use of ketamine in patients with refractory severe asthma exacerbations: systematic review of prospective studies.

PURPOSE: Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring emergency department visits. In addition to conventional strategies for SAEs (inhaled ß-agonists, anticholinergics, and systemic corticosteroids), another pharmacological option is represented by ketamine. We performed a systematic review to explore the role of ketamine in refractory SAEs. METHODS: We performed a systematic search on PubMed and EMBASE up to August 12th, 2021. We selected prospective studies only, and outcomes of interest were oxygenation/respiratory parameters, clinical status, need for invasive ventilation and effects on weaning. RESULTS: We included a total of seven studies, five being randomized controlled trials (RCTs, population range 44-92 patients). The two small prospective studies (n = 10 and n = 11) did not have a control group. Four studies focused on adults, and three enrolled a pediatric population. We found a large heterogeneity regarding sample size, age and gender distribution, inclusion criteria (different severity scores, if any) and ketamine dosing (bolus and/or continuous infusion). Of the five RCTs, three compared ketamine to placebo, while one used fentanyl and the other aminophylline. The outcomes evaluated by the included studies were highly variable. Despite paucity of data and large heterogeneity, an overview of the included studies suggests absence of clear benefit produced by ketamine in patients with refractory SAE, and some signals towards side effects. CONCLUSION: Our systematic review does not support the use of ketamine in refractory SAE. A limited number of prospective studies with large heterogeneity was found. Well-designed multicenter RCTs are desirable.

Impact of asthma on bronchiectasis severity and risk of exacerbations.

OBJECTIVE: Asthma is a frequent comorbidity of bronchiectasis, with possible implications for exacerbation and severity. We investigated the clinical impact of asthma on bronchiectasis in terms of disease severity and exacerbation risk. METHODS: We collected demographic, clinical, and functional characteristics of patients with a confirmed diagnosis of bronchiectasis. All patients were investigated for concomitant diagnosis of asthma. The Bhalla score was used to assess radiological severity of bronchiectasis, and the Bronchiectasis Severity Index (BSI) was used to assess the clinical severity. Blood and sputum samples were collected to assess blood cell count, erythrocyte sedimentation rate, c-reactive protein, immunological status (IgA, IgE, IgM, IgG, and IgG subclasses), and microbiological analysis. RESULTS: A total of 106 patients were enrolled in the study; 30.2% had concomitant asthma and were characterized by higher frequency of bronchiectasis exacerbation, despite higher Bhalla score and lower BSI compared to patients without asthma. Pseudomonas aeruginosa was more frequently isolated from the sputum of bronchiectasis patients without asthma. Total serum IgG, IgG1, and IgG3 were lower in patients with asthma. Blood eosinophils and exhaled nitric oxide were higher in patients with associated asthma. The presence of asthma and presence of Pseudomonas in sputum were the only significant determinants of frequent exacerbations in a binary logistic regression analysis. CONCLUSION: The coexistence of asthma and bronchiectasis is associated with an independent increase in the risk of bronchiectasis exacerbation despite lower radiological and clinical severity indexes. Asthmatic airway inflammation could promote an enhanced "Cole's Cycle" that is responsible for a higher frequency of exacerbations.

Acute and long-term management of severe bronchiectasis with high flow nasal therapy: A case report.

Bronchiectasis (BE) is a long-term, chronic lung condition featured by widened and scarred airways. These can alter the physiological mucociliary clearance, making it difficult to clear mucus and microorganisms, leading to frequent exacerbations. High flow nasal therapy (HFNT) is a noninvasive respiratory support that delivers heated and humidified gas eventually enriched with oxygen, through a nasal cannula.  Humidification is crucial for adequate airways mucociliary clearance, improving ciliary function and consequently reducing airways inflammation and recurrent infections. HFNT has been mostly used in patients with acute hypoxemic respiratory failure and in selected patients with chronic respiratory failure due to COPD. Still, evidence about its use in acute and long-term home setting in patients with clinically relevant BE are lacking. We report a case of severe widespread BE, already on top medical therapy and pulmonary rehabilitation, still suffering from difficult mucus expectoration and recurrent exacerbations, who has been additionally treated with HFNT, both in hospital and domiciliary, reporting significant improvements on relevant clinical and patient-centered outcomes. Thus, HFNT may confer additional benefits as an add-on treatment of patients with severe BE and respiratory failure.

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.

Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma.

Thymic stromal lymphopoietin (TSLP) is an innate cytokine, belonging to the group of alarmins, which plays a key pathogenic role in asthma by acting as an upstream activator of cellular and molecular pathways leading to type 2 (T2-high) airway inflammation. Released from airway epithelial cells upon tissue damage induced by several noxious agents including allergens, viruses, bacteria, and airborne pollutants, TSLP activates dendritic cells and group 2 innate lymphoid cells involved in the pathobiology of T2-high asthma. Tezepelumab is a fully human monoclonal antibody that binds to TSLP, thereby preventing its interaction with the TSLP receptor complex. Preliminary results of randomized clinical trials suggest that tezepelumab is characterized by a good safety and efficacy profile in patients with severe, uncontrolled asthma.

Secretion management in patients with ineffective airway clearance with non-invasive mechanical ventilation use: Expert guidance for clinical practice.

Non-invasive ventilation (NIV) is a mainstay of management of chronic respiratory failure in many disorders which are known to cause abnormal airway secretion clearance. Currently, there is no guidance regarding either the secretion handling during NIV use or the role of NIV in secretion management in these patients. The aim of this document was to provide an overview of the various techniques available in the management of respiratory secretions and their use in conjunction with NIV. Literature search was performed using the keywords, "(secretion OR secretions) AND (noninvasive ventilation OR NIV)" on PubMed and EMBASE. The search yielded 1681 and 509 titles from PubMed and EMBASE, respectively. After screening, 19 articles were included in this review. Suggestions of the expert panel were formulated by mutual consensus after reviewing the relevant literature. The draft of the expert panel's suggestions was circulated among all authors via electronic mail for comments. Any conflicts were resolved by mutual discussion to achieve agreement. The final document was approved by all. This document by the International Network for Airway Secretions Management in NIV describes various airway secretion clearance techniques. It provides the expert panel's suggestions for the use of these techniques in conjunction with NIV for patients with muco-obstructive and neuromuscular disorders.

Real-life evaluation of mepolizumab efficacy in patients with severe eosinophilic asthma, according to atopic trait and allergic phenotype.

BACKGROUND: Anti-interleukin-5 (IL-5) monoclonal antibodies can be used as add-on biological therapies in allergic and non-allergic patients with severe eosinophilic asthma. However, within such a therapeutic context real-life investigations are lacking. OBJECTIVE: Therefore, the aim of the present observational study was to evaluate the effects of mepolizumab in allergic and non-allergic subjects with severe eosinophilic asthma. METHODS: Relevant clinical, functional, laboratory, and pharmacotherapeutic parameters were assessed in the above patient subgroups. RESULTS: After one year of add-on biological treatment with mepolizumab, our 88 patients experienced a remarkable improvement of their severe asthma, documented by a better symptom control, expressed by a significant improvement in asthma control test (ACT) score. Indeed, the mean value (±standard deviation) of ACT score increased from 12.55 (±3.724) to 21.08 (±3.358). Moreover, significant improvements were also detected with regard to the median values (interquartile range) of forced expiratory volume in one second (FEV1 ), blood eosinophil numbers, annual rate of disease exacerbations, and daily intake of oral corticosteroids (OCS). In particular, FEV1 enhanced from 1640 mL (1110-2275) to 1920 mL (1525-2615), blood eosinophil count dropped from 711.0 cells/µL (500.0-1022) to 90.00 cells/µL (50.00-117.5), the annual rate of asthma exacerbations decreased from 3.000 (2.000-6.000) to 0.000 (0.000-1.000), and the daily prednisone intake fell from 6.250 mg (0.000-25.00) to 0.000 mg (0.000-0.000). After one year of mepolizumab treatment, the improvements in clinical, functional, and haematological parameters were quite similar in patient subgroups characterized by skin prick test (SPT) negativity or positivity, respectively. A significant correlation was observed between serum IgE levels and OCS intake decrease (r = -0.2257; P < .05). CONCLUSION AND CLINICAL RELEVANCE: Hence, our real-life data suggest that mepolizumab can represent a valid add-on therapeutic option for patients with severe eosinophilic asthma, irrespective of IgE serum concentrations, and allergic sensitization.

New treatments for asthma: From the pathogenic role of prostaglandin D2 to the therapeutic effects of fevipiprant.

Prostaglandin D2 (PGD2) is a pleiotropic mediator, significantly involved in the pathogenesis of type 2 (T2) asthma because of its biologic actions exerted on both immune/inflammatory and airway structural cells. In particular, the pro-inflammatory and pro-remodelling effects of PGD2 are mainly mediated by stimulation of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). This receptor is the target of the oral competitive antagonist fevipiprant, which on the basis of recent phase II studies is emerging as a potential very promising anti-asthma drug. Indeed, fevipiprant appears to be safe and effective, especially in consideration of its ability to inhibit eosinophilic bronchial inflammation and improve forced expiratory volume in one second (FEV1). Further ongoing phase III trials will definitely clarify if fevipiprant can prospectively become a valid option for an efficacious add-on treatment of moderate-to-severe T2-high asthma.

High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial.

BACKGROUND: The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO2 clearance after 2 h of treatment. METHODS: We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25-7.35, PaCO2 ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. RESULTS: Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO2 reduction from baseline to 2 h were - 6.8 mmHg (± 8.7) in the HFNT and - 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. CONCLUSIONS: HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. TRIAL REGISTRATION: The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

The Link between Asthma and Bronchiectasis: State of the Art.

The nonrecognition of asthma-associated comorbidities is often responsible for the therapeutic failure and the worsening of symptoms, and it is associated with frequent exacerbations, higher disease severity, and increased health costs. Bronchiectasis, one of the most frequent asthma-associated comorbidities, can increase airways inflammation and exacerbation rates and cause respiratory functional impairment. The aim of this article is to review the interactions between bronchiectasis and asthma, in order to better identify patients in the overlap between the 2 diseases and to select an "ad hoc" therapy. A literature search on PubMed/MEDLINE was performed using the following search terms: bronchiectasis in asthma, the association between asthma and bronchiectasis, comorbidities in asthma, and severe asthma. This review analyzed the following items: incorrect or underestimated diagnosis of asthma and bronchiectasis, prevalence of bronchiectasis in asthma, the impact of bronchiectasis in asthma, radiological imaging features of the 2 diseases, etiopathogenesis, and common causes (such as gastroesophageal reflux disease, immune deficits, chronic rhinosinusitis and allergic bronchopulmonary aspergillosis, and treatment of asthma and bronchiectasis). The concomitant presence of bronchiectasis and asthma should be suspected and investigated in patients with severe asthma, frequent exacerbations, and not responding to standard therapy. This clinical phenotype, characterized by a more severe disease, worse outcomes, and functional decline, must be readily recognized in order to choose the most appropriate therapeutic approach, able to potentially improve the management of bronchial asthma, to prevent the onset of exacerbations as well the functional decline, and to reduce health costs.

High Flow Nasal Therapy Use in Patients with Acute Exacerbation of COPD and Bronchiectasis: A Feasibility Study.

The efficacy and feasibility of high flow nasal therapy (HFNT) use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and bronchiectasis is unknown. We performed a single-center, single-arm prospective observational study in patients with AECOPD, documented bronchiectasis, pH ≥ 7.35, respiratory rate (RR) ≥ 26 breaths/minute despite receiving maximal medical treatment and oxygen via face mask up to 10 L/m. Patients received HFNT (Airvo 2, Fisher & Paykel) at a gas flow of 50 L/min and FIO2 adjusted to maintain SpO2 ≥92%. Dyspnea, rated by Borg scale, RR, arterial blood gases and mucus production (ranging from 1 to 3) were collected before and 1 h after starting HFNT and then every 24 h for 3 days. Tolerance was measured using a visual analogic scale (VAS). Fifteen patients were enrolled. After 24 h, patients showed a significant improvement in dyspnea score [Borg scale from 6.7 ± 1.4 to 4.1 ± 1.3 (p<.001)]; RR decreased from 29.6 ± 2.7 breaths/min to 23.2 ± 2.9 breaths/min (p<.001); pCO2 significantly decreased after 24 h [58.4 ± 13 vs. 51.7 ± 8.2 (p=.003)] while quantity of mucus production increased [(1.1 ± 0,6 vs. 2.4 ± 0.7, p<.001)]. No patient received invasive or noninvasive mechanical ventilation. Overall VAS score for HFNT tolerance was 6.5. HFNT was effective in improving dyspnea score, decreasing RR, improving gas exchange, and increasing mucus production in patients with AECOPD and coexisting bronchiectasis. Moreover, no safety concerns on its use were detected. Nevertheless, due to the single-arm design, the effect of HFNT could not be isolated from standard pharmacological treatment due to the study design.

Real-life rapidity of benralizumab effects in patients with severe allergic eosinophilic asthma: Assessment of blood eosinophils, symptom control, lung function and oral corticosteroid intake after the first drug dose.

Benralizumab is a humanized monoclonal antibody which binds to the α subunit of the interleukin-5 (IL-5) receptor and to the FcγRIIIa receptor expressed by natural killer cells, thus suppressing the pro-eosinophil actions of IL-5 and triggering eosinophil apoptosis via the very effective mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC). Because of its recent approval and introduction in clinical practice for the add-on biological therapy of severe eosinophilic asthma, real-life investigations are still lacking. In this regard, our present real-life study refers to 13 patients with severe allergic eosinophilic asthma, currently under treatment with benralizumab at the Respiratory Unit of "Magna Græcia" University Hospital located in Catanzaro, Italy. Already 4 weeks after the first subcutaneous injection of benralizumab at the dosage of 30 mg, blood eosinophil count rapidly dropped down from 814.7 ±â€¯292.3 cells/µL to 51.3 ±â€¯97.5 cells/µL (p < 0.0001). This relevant hematologic change was associated with quick and significant increases in asthma control test (ACT) score (from 15.31 ±â€¯2.78 to 21.15 ±â€¯3.58; p < 0.0001), pre-bronchodilator forced expiratory volume in 1 s (FEV1) (from 1441 ±â€¯757.9 mL to 1887 ±â€¯837.3 mL; p < 0.001), and morning peak expiratory flow (PEF) (from 4.21 ±â€¯2.20 to 5.33 ±â€¯1.99 L/sec; p < 0.01). Furthermore, the marked improvement in global health status experienced by our patients allowed them to progressively lower and then completely interrupt, within 4 weeks, their daily intake of oral corticosteroids (OCS), which thereby fell from 15.58 ±â€¯8.30 to 0 mg (p < 0.0001) of prednisone. Therefore, such preliminary results suggest that in patients with severe allergic eosinophilic asthma benralizumab can exert, within a real-life context, a very rapid and effective therapeutic action, already detectable 4 weeks after the first drug administration.

Long-Term Ventilation in Neuromuscular Patients: Review of Concerns, Beliefs, and Ethical Dilemmas.

BACKGROUND: Noninvasive mechanical ventilation (NIV) is an effective treatment in patients with neuromuscular diseases (NMD) to improve symptoms, quality of life, and survival. SUMMARY: NIV should be used early in the course of respiratory muscle involvement in NMD patients and its requirements may increase over time. Therefore, training on technical equipment at home and advice on problem solving are warranted. Remote monitoring of ventilator parameters using built-in ventilator software is recommended. Telemedicine may be helpful in reducing hospital admissions. Anticipatory planning and palliative care should be carried out to lessen the burden of care, to maintain or withdraw from NIV, and to guarantee the most respectful management in the last days of NMD patients' life. Key Message: Long-term NIV is effective but challenging in NMD patients. Efforts should be made by health care providers in arranging a planned transition to home and end-of-life discussions for ventilator-assisted individuals and their families.

Noninvasive continuous arterial pressure monitoring with Clearsight during awake carotid endarterectomy: A prospective observational study.

BACKGROUND: Continuous noninvasive blood pressure (CNBP) measurement using the volume-clamp method is a less invasive alternative compared with invasive intra-arterial monitoring for awake patients during carotid endarterectomy (CEA) under regional anaesthesia. OBJECTIVE: We investigated the agreement of blood pressure (BP) recorded with invasive and CNBP methods during awake CEA. DESIGN: A prospective observational study for assessing agreement with Bland-Altman plots, agreement-tolerability indices (ATI), concordance and interchangeability. SETTING: Azienda Ospedaliera Universitaria G. Martino, Messina, a University tertiary referral centre in Italy. PATIENTS: In 30 consecutive patients, we recorded continuously ipsilateral invasive and noninvasive BPs, from 3 min before carotid cross-clamping to 5 min after unclamping. MAIN OUTCOME MEASURES: Primary outcome was bias, 95% limits of agreement, ATI, concordance and interchangeability for mean arterial pressure (MAP). Secondary outcomes were agreements for systolic arterial pressure and diastolic arterial pressure. Tracking of changes was assessed with four-quadrant polar plots and the trend interchangeability method. Optimal bias was defined as 5 mmHg or less. RESULTS: A total of 2672 invasive and CNBP paired measurements (93% of overall data) were analysed, with a median of 92 readings per patient [IQR 76 to 100]. Mean (SD) bias for MAP, systolic arterial pressure and DAP were -6.8 (6.7), -3.0 (9.7) and -9.0 (5.4) mmHg, respectively. The ATIs were 0.88, 0.95 and 0.71, respectively, where ATI of 1.0 or less and at least 2.0 defined acceptable, marginal and unacceptable agreements. The four-quadrant plot analysis for beat-to-beat differences showed concordance rates of 97.3%, 99.98% and 96.4%, respectively. Polar plot analysis showed 95% limits of agreement of -3 to 3, -2 to 2 and -2 to 2 mmHg respectively. Trend interchangeability method showed an interchangeability rate of 95% for MAP. CONCLUSION: During CEA performed under regional anaesthesia, CNBP offers a less invasive approach for BP monitoring. We found acceptable agreement for MAP defined by an ATI of 0.88 and an excellent 95% global interchangeability rate. A suboptimal bias of 7 mmHg was found with CNBP for MAP.

Inhalation therapy in the next decade: Determinants of adherence to treatment in asthma and COPD.

Proceedings of the European Seminars in Respiratory Medicine course, Inhalation therapy in the next decade: Determinants of adherence to treatment in asthma and COPD, held in Taormina, Italy, on 3-4 March, 2017.