Home respiratory strategies in COPD patients with chronic hypercapnic respiratory failure: a systematic review and network meta-analysis.

Background: Home non-invasive positive pressure ventilation (NPPV) may improve chronic hypercarbia in COPD and patient important outcomes. The efficacy of home high flow nasal cannula (HFNC) as an alternative is unclear.Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL, SCOPUS, and Clinicaltrials.gov for randomized trials of patients from inception to March 31st and updated the search on July 14, 2023. We performed a frequentist network meta-analysis and assessed the certainty of the evidence using the GRADE approach. We analyzed randomized trials (RCTs) comparing NPPV, HFNC, or standard care in adult COPD patients with chronic hypercapnic respiratory failure. Outcomes included mortality, COPD exacerbations, hospitalizations, and quality of life (SGRQ).Results: We analyzed twenty-four RCTs (1850 patients). We found that NPPV may reduce death risk compared to standard care (relative risk [RR] 0.82 [95% CI 0.66 to 1.00]) and probably reduces acute exacerbations (RR 0.71 [95% CI 0.58 to 0.87]). HFNC probably reduces acute exacerbations compared to standard care (RR 0.77 [0.68 to 0.88]) but its effect on mortality is uncertain (RR 1.20 [95% CI 0.63 to 2.28]). HFNC probably improves SGRQ scores (mean difference [MD] -7.01 [95% CI -12.27 to -1.77]) and may reduce hospitalizations (RR 0.87 [0.69 to 1.09]) compared to standard care. No significant difference was observed between HFNC and NPPV in reducing exacerbations.Conclusion: Both NPPV and HFNC reduce exacerbation risks in COPD patients compared to standard care. HFNC may offer advantages in improving quality of life.

Diagnostic delay in bronchiectasis: an Italian perspective.

It takes ∼3.5 years to reach a diagnosis of bronchiectasis from onset of symptoms: the long patient's journey in Italy https://bit.ly/46XMWAz.

Effects of inhaled beclomethasone dipropionate/formoterol fumarate/glycopyrronium on diaphragmatic workload and lung function in uncontrolled asthma: a case report.

Beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) single inhaler extrafine triple therapy is effective for the treatment of uncontrolled asthma. Nevertheless, there is a lack of data about the use of diaphragmatic ultrasonography to monitor adult asthmatics while they are receiving inhaled treatment. We took into consideration a 78-year-old woman complaining of asthma, treated with inhaled corticosteroid/long-acting ß2-adrenergic agonist (ICS/LABA), characterized by an asthma control questionnaire-5 (ACQ-5) score and a lung function test suggestive of uncontrolled asthma. Moreover, a diaphragmatic ultrasound showed signs of high diaphragm workload. Because of these findings, we proposed to our patient a shift toward triple inhaled therapy with BDP/FF/G, and she underwent a second evaluation after 7 days of treatment. Improvements in the diaphragmatic ultrasound parameters, lung function test, and ACQ-5 score were found. In particular, we detected a reduction of thickening fraction (TF), and a normalization of the other diaphragmatic measures, indicative of a decrease in diaphragmatic workload. To our knowledge, this is the first literature report showing concomitant improvements of both lung function tests and diaphragmatic ultrasonography parameters, observed in an adult patient with uncontrolled asthma after short-term treatment with the single inhaler triple therapy BDP/FF/G.

Features of severe asthma response to anti-IL5/IL5r therapies: identikit of clinical remission.

Introduction: Clinical remission (CliR) achievement has been recognized as a new potential outcome in severe asthma. Nevertheless, we still lack a detailed profile of what features could better identify patients undergoing clinical remission. In this study, we aim to address this issue, tracing a possible identikit of patients fulfilling remission criteria. Methods: We enrolled 266 patients with severe eosinophilic asthma (SEA) treated with a 12-month course of anti-IL5/IL5 receptor (IL5r) monoclonal antibodies. Patients with no exacerbation, OCS withdrawal, ACT ≥ 20 and FEV1 ≥ 80% after 1 year of biologic treatment were classified as in clinical remission. Results: 30.5% of the enrolled patients achieved remission after biologic administration. CliR group showed a lower number of baseline asthma exacerbations and better lung function parameters, with a trend for higher ACT scores and a less frequent history of a positive skin prick test. CliR achievement was unlikely in presence of a higher BMI, a positive skin prick test, an increased number of asthma exacerbations before biologic treatment, anti-muscarinic administration, and a previous diagnosis of EGPA, bronchiectasis or osteoporosis. In contrast, a better lung function, an increased blood eosinophilic count, the presence of chronic rhinosinusitis with nasal polyps and a more frequent use of reliever therapy predicts remission development. Changes in exacerbations number, OCS use, ACT scores and FEV1% between remittent and non-remittent patients arise at specific follow up timepoints and are positively associated with CliR achievement. Discussion: anti-IL5/IL5r biologics can induce CliR in a proportion of patients with SEA. Patients achieving remission demonstrate specific clinical, functional and inflammatory features, as well as a specific moment of improvement in all the CliR items.

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective.

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.

Effect of high flow nasal oxygen on inspiratory effort of patients with acute hypoxic respiratory failure and do not intubate orders.

High flow nasal oxygen (HFNO) is recommended as a first-line respiratory support during acute hypoxic respiratory failure (AHRF) and represents a proportionate treatment option for patients with do not intubate (DNI) orders. The aim of the study is to assess the effect of HFNO on inspiratory effort as assessed by esophageal manometry in a population of DNI patients suffering from AHRF. Patients with AHRF and DNI orders admitted to Respiratory intermediate Care Unit between January 1st, 2018 and May 31st, 2023 to receive HFNO and subjected to esophageal manometry were enrolled. Esophageal pressure swing (ΔPes), clinical variables before and after 2 h of HFNO and clinical outcome (including HFNO failure) were collected and compared as appropriate. The change in physiological and clinical parameters according to the intensity of baseline breathing effort was assessed and the correlation between baseline ΔPes values and the relative change in breathing effort and clinical variables after 2 h of HFNO was explored. Eighty-two consecutive patients were enrolled according to sample size calculation. Two hours after HFNO start, patients presented significant improvement in ΔPes (12 VS 16 cmH2O, p < 0.0001), respiratory rate (RR) (22 VS 28 bpm, p < 0.0001), PaO2/FiO2 (133 VS 126 mmHg, p < 0.0001), Heart rate, Acidosis, Consciousness, Oxygenation and respiratory rate (HACOR) score, (4 VS 6, p < 0.0001), Respiratory rate Oxygenation (ROX) index (8.5 VS 6.1, p < 0.0001) and BORG (1 VS 4, p < 000.1). Patients with baseline ΔPes below 20 cmH2O where those who improved all the explored variables, while patients with baseline ΔPes above 30 cmH2O did not report significant changes in physiological or clinical features. A significant correlation was found between baseline ΔPes values and after 2 h of HFNO (R2 = 0.9, p < 0.0001). ΔPes change 2 h after HFNO significantly correlated with change in BORG (p < 0.0001), ROX index (p < 0.0001), HACOR score (p < 0.001) and RR (p < 0.001). In DNI patients with AHRF, HFNO was effective in reducing breathing effort and improving respiratory and clinical variables only for those patients with not excessive inspiratory effort.

Real-world characteristics of "super-responders" to mepolizumab and benralizumab in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis.

Background: The current definition of severe eosinophilic asthma (SEA) super-responders to biologic treatment does not include patients with other eosinophil-based comorbidities. Although eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with SEA, we lack data on a possible super-response to biologic treatments in patients suffering from these two diseases. We aim to assess super-responder features in real-life patients with SEA and EGPA treated with mepolizumab and benralizumab. Methods: We enrolled 39 patients with SEA and EGPA eligible for treatment with mepolizumab or benralizumab. Super-responder assessment was performed considering oral corticosteroid (OCS) cessation, lack of exacerbations, forced expiratory volume in 1 s and Asthma Control Test (ACT) improvement. Results: Super-responders showed worse clinical baseline characteristics than non-super-responder patients, with a greater improvement in severe asthma exacerbations, OCS dose reduction and ACT score increase. Definition of super-responders was consistent only considering a 12-month course of monoclonal antibody, lacking sensitivity in earlier evaluations. Conclusion: Mepolizumab and benralizumab are safe and effective in patients with EGPA and SEA, since a consistent proportion of patients show a super-response after 12 months of treatment. Further studies will address specific criteria for super-responder assessment in these patients.

Patient and physician perspectives on biological treatment in severe asthma: a Severe Asthma Network Italy survey.

Patients with severe asthma perceive beneficial effects of biologics and good self-reported adherence to treatment, even when self-administered at home https://bit.ly/48vP70w.

Personalized Medicine in Asthma: Current Approach and Future Perspectives.

Asthma is one of the most common chronic respiratory diseases, affecting over 300 million people worldwide [...].

Effects of High-Flow Nasal Cannula on Right Heart Dysfunction in Patients with Acute-on-Chronic Respiratory Failure and Pulmonary Hypertension.

High-flow nasal cannula (HFNC) has several benefits in patients affected by different forms of acute respiratory failure, based on its own mechanisms. We postulated that HFNC may have some advantages over conventional oxygen therapy (COT) on the heart function in patients with acute-on-chronic respiratory failure with concomitant pulmonary hypertension (PH). We therefore designed this retrospective observational study to assess if HFNC improves the right and left ventricle functions and morphologies, arterial blood gases (ABGs), and patients' dyspnea, compared to COT. We enrolled 17 hospitalized patients receiving HFNC, matched with 17 patients receiving COT. Echocardiographic evaluation was performed at the time of admission (baseline) and 10 days after (T10). HFNC showed significant improvements in right ventricular morphology and function, and a reduction in sPAP. However, there were no significant changes in the left heart measurements with HFNC application. Conversely, COT did not lead to any modifications in echocardiographic measurements. In both groups, oxygenation significantly improved from baseline to T10 (in the HFNC group, from 155 ± 47 to 204 ± 61 mmHg while in the COT group, from 157 ± 27 to 207 ± 27 mmHg; p < 0.0001 for both comparisons). In conclusion, these data suggest an improvement of oxygenation with both treatments; however, only HFNC was able to improve the right ventricular morphology and function after 10 days from the beginning of treatment in a small cohort of patients with acute-on-chronic respiratory failure with PH.

A pragmatic, open-label, multi-center, randomized controlled clinical trial on the rotational use of interfaces vs standard of care in patients treated with noninvasive positive pressure ventilation for acute hypercapnic respiratory failure: the ROTAtional-USE of interface STUDY (ROTA-USE STUDY).

BACKGROUND: In the last decades, noninvasive ventilation (NIV) has been increasingly used to support patients with hypercapnic and hypoxemic acute respiratory failure. Pressure ulcers are a frequently observed NIV-related adverse effect, directly related to interface type and exposure time. Switching to a different interface has been proposed as a solution to improve patient comfort. However, large studies investigating the benefit of this strategy are not available. Thus, the aim of the ROTAtional-USE of interface STUDY (ROTA-USE STUDY) is to investigate whether a protocolized rotational use of interfaces during NIV is effective in reducing the incidence of pressure ulcers. METHODS: The ROTA-USE STUDY is a pragmatic, parallel arm, open-label, multicenter, spontaneous, non-profit, randomized controlled trial requiring non-significant risk medical devices, with the aim to determine whether a rotational strategy of NIV interfaces is associated with a lower incidence of pressure ulcers compared to the standard of care. In the intervention group, NIV mask will be randomly chosen and rotated every 6 h. In the control group, mask will be chosen according to the standard of care of the participating centers and changed in case of discomfort or in the presence of new pressure sores. In both groups, the skin underneath the mask will be inspected every 12 h for any possible damage by blinded assessors. The primary outcome is the proportion of patients developing new pressure sores at 36 h from randomization. The secondary outcomes are (i) onset of pressure sores measured at different time points, i.e., 12, 24, 36, 48, 60, 72, 84, and 96 h; (ii) number and stage of pressure sores and comfort measured at 12, 24, 36, 48, 60, 72, 84, and 96 h; and (iii) the economic impact of the protocolized rotational use of interfaces. A sample size of 239 subjects per group (intervention and control) is estimated to detect a 10% absolute difference in the proportion of patients developing pressure sores at 36 h. DISCUSSION: The development of pressure ulcers is a common side effect of NIV that negatively affects the patients' comfort and tolerance, often leading to NIV failure and adverse outcomes. The ROTA-USE STUDY will determine whether a protocolized rotational approach can reduce the incidence, number, and severity of pressure ulcers in NIV-treated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05513508. Registered on August 24, 2022.

Effectiveness and safety of anti-IL-5/Rα biologics in eosinophilic granulomatosis with polyangiitis: a two-year multicenter observational study.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia. Objective: To assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in EGPA for 24 months. Methods: We conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/Rα biologics in 9 Italian specialized facilities. Systemic disease activity, remission and relapse rate were evaluated from 3 to 24 months after treatment initiation. Respiratory outcomes, hematological parameters, corticosteroid (OCS) and immunosuppressants consumption were also assessed. Results: 49 patients with relapsing-refractory EGPA were included [26 (53.1%) benralizumab 30mg, 20 (40.8%) mepolizumab 100mg, 3 (6.1%) mepolizumab 300mg]. Overall, 38.8% and 57.1% achieved remission after 12 and 24 months, respectively (69.2% benralizumab and 43.5% mepolizumab). Lower OCS intake and higher blood eosinophil count at baseline were associated with remission at 24 months. Both biologics exerted beneficial effects on severe asthma outcomes. Indeed, 61.2% (61.5% benralizumab and 60.8% mepolizumab) remained exacerbation-free during treatment. Lung function parameters showed improvements in the overall cohort (all p<0.05), but began to decline from month 12, especially with mepolizumab. Marked reduction in blood eosinophils was registered with mepolizumab (p<0.0001), while benralizumab depleted both eosinophils (p<0.0001) and basophils (p<0.0001). In general, 69.6% (76% benralizumab and 61.9% mepolizumab) of OCS-dependent patients lowered their daily dose by 75%, while 28.3% discontinued these drugs. Immunosuppressants were suspended in 88.2% of cases. Adverse events were reported in 8.2% of patients. Conclusions: These real-world data suggest that anti-IL-5/Rα biologics are effective and safe in the long-term as add-on treatments for patients with EGPA.

Benralizumab in Patients with Severe Eosinophilic Asthma: A Multicentre Real-Life Experience.

BACKGROUND: Mepolizumab and benralizumab are monoclonal antibodies directed against anti-IL-5 and anti-IL5R, respectively, and their use reduces the exacerbation rate and maintains oral corticosteroid requirements in severe eosinophilic asthma. Previous studies have tested the therapeutic switch between two biologics with excellent results, further demonstrating the heterogeneity of asthmatic disease and the complexity of the therapeutic choice. It remains unclear if such patients may improve following a switch from mepolizumab to benralizumab. AIMS: Within a multicentre real-life setting, we decided to evaluate the potential effectiveness of a therapeutic switch to benralizumab in patients with severe eosinophilic asthma initially treated with mepolizumab, who experienced sub-optimal responses. The secondary aim was to identify the clinical factors associated with a better response to benralizumab. METHODS: We retrospectively assessed patients with severe eosinophilic asthma treated at six Italian specialist centres, who were switched from mepolizumab to benralizumab following a sub-optimal response, defined as a partial or total lack of clinical remission (i.e., frequent severe exacerbations and/or poorly controlled symptoms and/or higher OCS daily use in patients with a poor or moderate response in the global evaluation of treatment effectiveness scale), after at least 12 months of treatment. RESULTS: Twenty-five patients were included in the analysis (mean age 56.76 ± 11.97 years, 65% female). At 6 months of treatment with benralizumab, the ACT score was significantly higher than the ACT score with mepolizumab (20.24 ± 3.38 vs. 16.77 ± 3.48, p < 0.0001); the mean number of daily SABA inhalations was significantly lower after 6 months and 12 months of treatment with benralizumab than that after treatment with mepolizumab; OCS intake and the prednisone median dosage at 6 months of treatment with benralizumab were significantly lower than those with mepolizumab. Benralizumab treatment resulted in a marked improvement in asthma control, suppressed blood eosinophil levels and reduction in the number of exacerbations in the subgroup of patients with severe eosinophilic asthma and nasal polyposis. CONCLUSIONS: Patients diagnosed with severe eosinophilic asthma who experience a partial response to mepolizumab could benefit from switching to benralizumab, and even more those who have nasal polyposis.

Benralizumab Effectiveness in Severe Eosinophilic Asthma with Co-Presence of Bronchiectasis: A Real-World Multicentre Observational Study.

Introduction: The co-presence of bronchiectasis (BE) in severe eosinophilic asthma (SEA) is common. Data about the effectiveness of benralizumab in patients with SEA and BE (SEA + BE) are lacking. Aim: The aim of this study was to evaluate the effectiveness of benralizumab and remission rates in patients with SEA compared to SEA + BE, also according to BE severity. Methods: We conducted a multicentre observational study, including patients with SEA who underwent chest high-resolution computed tomography at baseline. The Bronchiectasis Severity Index (BSI) was used to assess BE severity. Clinical and functional characteristics were collected at baseline and after 6 and 12 months of treatment. Results: We included 74 patients with SEA treated with benralizumab, of which 35 (47.2%) showed the co-presence of bronchiectasis (SEA + BE) with a median BSI of 9 (7-11). Overall, benralizumab significantly improved the annual exacerbation rate (p < 0.0001), oral corticosteroids (OCS) consumption (p < 0.0001) and lung function (p < 0.01). After 12 months, significant differences were found between SEA and SEA + BE cohorts in the number of exacerbation-free patients [64.1% vs. 20%, OR 0.14 (95% CI 0.05-0.40), p < 0.0001], the proportion of OCS withdrawal [-92.6% vs. -48.6, p = 0.0003], and the daily dose of OCS [-5 mg (0 to -12.5) vs. -12.5 mg (-7.5 to -20), p = 0.0112]. Remission (zero exacerbations + zero OCS) was achieved more frequently in the SEA cohort [66.7% vs. 14.3%, OR 0.08 (95% CI 0.03-0.27), p < 0.0001]. Changes in FEV1% and FEF25-75% were inversely correlated with BSI (r = -0.36, p = 0.0448 and r = -0.41, p = 0.0191, respectively). Conclusions: These data suggest that benralizumab exerts beneficial effects in SEA with or without BE, although the former achieved less OCS sparing and fewer respiratory-function improvements.

Lessons from COVID-19 in the management of acute respiratory failure.

Accumulated evidence supports the efficacy of noninvasive respiratory support therapies in coronavirus disease 2019 (COVID-19)-related acute hypoxaemic respiratory failure, alleviating admissions to intensive care units. Noninvasive respiratory support strategies, including high-flow oxygen therapy, continuous positive airway pressure via mask or helmet and noninvasive ventilation, can be alternatives that may avoid the need for invasive ventilation. Alternating different noninvasive respiratory support therapies and introducing complementary interventions, like self-proning, may improve outcomes. Proper monitoring is warranted to ensure the efficacy of the techniques and to avoid complications while supporting transfer to the intensive care unit. This article reviews the latest evidence on noninvasive respiratory support therapies in COVID-19-related acute hypoxaemic respiratory failure.

Intermittent abdominal pressure ventilation management in neuromuscular diseases: a Delphi panel Consensus.

BACKGROUND: Intermittent abdominal pressure ventilator (IAPV) use started in the 1930s for ventilatory assistance with muscular dystrophy patients. Later, the device was perfected and expanded for other neuromuscular disorders (NMD). In recent years, the morbidity and mortality tracheotomies and trach tubes related renewed the interest around IAPV. However, there are no guidelines for its use. This study aimed to establish a consensus among physicians involved in its practice to provide IAPV suggestions for the treatment of patients with NMD. METHOD: A 3-step modified Delphi method was used to establish consensus. Fourteen respiratory physicians and one psychiatrist with strong experience in IAPV use and/or who published manuscripts on the topic participated in the panel. A systematic review of the literature was carried out according to the PRISMA to identify existing evidence on IAPV for patients with neuromuscular disorders. RESULTS: In the first round, 34 statements were circulated. Panel members marked 'agree' or 'disagree' for each statement and provided comments. The agreement was reached after the second voting session for all 34 statements. CONCLUSIONS: Panel members agreed and IAPV indications, parameter settings (including procedure protocol), potential limitations, contraindications, complications, monitoring, and follow-up are described. This is the first expert consensus on IAPV.