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Francesco Menzella,1 Matteo Fontana,1 Carla Galeone,1 Maria D’Amato,2 Giorgio Walter Canonica,3 Giulia Ghidoni,1 Silvia Capobelli,1 Chiara Scelfo,1 Anna Simonazzi,1 Chiara Catellani,1 Patrizia Ruggiero,1 Nicola Facciolongo1 1Pulmonology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia- IRCCS, Reggio Emilia, 42123, Italy; 2Department of Pulmonology, AO “Dei Colli” Federico II University, Naples, 80131, Italy; 3Personalized Medicine, Asthma and Allergy - Humanitas Clinical and Research Center, IRCCS - Rozzano, Milan, ItalyCorrespondence: Francesco MenzellaPulmonology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia- IRCCS, Reggio Emilia, 42123, ItalyEmail francesco.menzella@ausl.re.itBackground: The important progress made on asthma phenotyping encouraged the development of new therapeutic strategies, such as monoclonal antibodies (mAbs) and bronchial thermoplasty (BT). The aim of this study is to compare patients diagnosed with severe refractory asthma (SRA) who are currently being treated with omalizumab, mepolizumab, benralizumab or BT and to evaluate the efficacy of these treatments over a 12-month observation period.Methods: Overall, 199 consecutive patients with SRA were included. The cohort was selected referring to the eligibility criteria for all available biologics and BT.Results: Among 32 patients treated with benralizumab, we found a 16.7% reduction in hospitalizations, a 66.6% reduction in exacerbations (p = 0.0001) and the greater improvement in FEV1 (+ 37.4%, p < 0.0001). Among omalizumab group (54 patients), there was a 85.7% (p = 0.012) reduction in hospitalizations and a 88.8% (p < 0.0001) reduction in exacerbations. In the mepolizumab group (83 patients), we found a 89.5% (p = 0.02) reduction in hospitalizations and a 92.1% (p < 0.0001) reduction in exacerbations. BT subgroup (30 patients) showed a 93.7% (p = 0.001) reduction in hospitalizations and a 73.5% (p < 0.0001) reduction in exacerbations. The best results in terms of OCS sparing effect were obtained by BT (- 76%, p < 0.0001) and mepolizumab (- 90.2%, p = 0.002). Omalizumab showed the highest percentage of super responder patients.Conclusion: To our knowledge, this is the first study to compare all marketed mAbs with BT, ending in more comprehensive and applicable results to clinical practice. All biologics, to varying degrees, reduced hospitalizations, exacerbations, and OCS use. The starting point for patients in the BT group was worse regarding hospitalizations, exacerbations and OCS, but despite this, even this non-pharmacological option obtained positive results, comparable to biologics.Keywords: severe asthma, biologics, bronchial thermoplasty, oral corticosteroids, exacerbations

Francesco Menzella,1 Matteo Fontana,1 Marco Contoli,2 Patrizia Ruggiero,1 Carla Galeone,1 Silvia Capobelli,1 Anna Simonazzi,1 Chiara Catellani,1 Chiara Scelfo,1 Claudia Castagnetti,1 Francesco Livrieri,1 Nicola Facciolongo1 1Pulmonology Unit, Arcispedale Santa Maria Nuova, Azienda USL – IRCCS di Reggio Emilia, Reggio Emilia, Italy; 2Respiratory Section, Department of Translational Medicine, University of Ferrara, Ferrara, ItalyCorrespondence: Francesco Menzella, Pulmonology Unit, Arcispedale Santa Maria Nuova, Azienda USL – IRCCS di Reggio Emilia, Reggio Emilia, Italy, Tel +39 0522 296073, Email fmenzella@gmail.comPurpose: Treatment of severe asthma has made great strides thanks to rapid progress in understanding immune response and inflammatory pathways. This led to the advent of the first biologic for severe allergic asthma (SAA), omalizumab. Although the long-term efficacy and safety of omalizumab has been confirmed, increasingly longer follow-up data can further reinforce this evidence and potentially provide new ones, for example on any loss of efficacy or the appearance of unexpected side effects. This study reports omalizumab treatment-related outcomes after 16 years of follow-up.Patients and Methods: In this real-life retrospective study, an extension of a previous 9-year follow-up study on patients initially recruited in a clinical trial, we enrolled 8 adult patients with SAA followed-up from November 2005 to December 2021. Study subjects were selected based on omalizumab eligibility criteria.Results: Exacerbation rate significantly decreased from 3.6 ± 2.1 events in year before index date to 0.1 ± 0.4 after 32 weeks of treatment (p < 0.0001). Mean annual number of mild-to-moderate exacerbations at 16 years was 0.88 compared with 1.8 in the year before the index date and 1.1 at 32 weeks. No hospitalizations were documented during the 16-year follow-up compared to 0.3 hospitalizations/patient in the year before the index date. Respiratory function also progressively and significantly improved. Regarding patient-reported outcomes (PROs), The AQLQ and ACT significantly improved from baseline throughout the follow-up, particularly up to 9 years of follow-up. During the study, an overall reduction in doses of asthma medications was observed, with a significant OCS-sparing effect.Conclusion: Our study, the longest clinical follow-up on patients treated with anti-IgE, confirms and amplifies the results of the studies carried out so far, as they are maintained over a very long interval of time without drops in efficacy without any type of side effect.Keywords: severe allergic asthma, biologics, omalizumab, exacerbations, side effects, oral corticosteroids

Background: Biological drugs have been recognized as a breakthrough in the treatment of severe refractory asthma. This retrospective real-life observational study aims to evaluate the effect of add-on benralizumab on lung function, exacerbation rate, oral corticosteroids (OCS) reduction and asthma control questionnaire (ACQ) score after 52 weeks.Methods: In this observational study, a cohort of 18 patients with severe eosinophilic asthma (SEA) according to the ERS / ATS and GINA 2020 classifications, with reference to the Pulmonology Unit of the Azienda USL - IRCCS, Reggio Emilia, Italy, were enrolled from 1 September 2019 to 31 August 2020. For each patient, the following data were collected: demographic data (age, sex, age of onset of asthma, history of smoking and atopy); comorbidity; clinical data (lung function, exacerbations, emergency room visits and hospitalizations); asthma control questionnaire (ACQ); biomarkers (blood eosinophil count and total serum IgE); asthma control drugs as high-dose inhaled corticosteroids / long-acting beta-adrenoceptor agonists (ICS / LABA), long-acting muscarinic antagonists (LAMA), leukotriene receptor antagonists (LTRA), theophylline, OCS. The benralizumab 30 mg treatment schedule was based on the currently recommended dosing regimen.Results: After end-of-treatment (EOT), a complete weaning of all patients from OCS was confirmed. After 26 weeks, the number of exacerbations decreased from 2.90 to 0.05 (p

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by necrotizing eosinophilic granulomatous inflammation that frequently involves the respiratory tract (90% of cases). Asthma in EGPA is systematically severe and often refractory to common treatment, it is corticosteroid resistant and can often anticipate the onset of systemic vasculitis by many years. A release of cytokines necessary for the activation, maturation and survival of eosinophils, such as IL-4, IL-5 and IL-13 occurs in the activated Th-2 phenotype. In particular, IL-5 level is high in active EGPA and its inhibition has become a key therapeutic target. Oral glucocorticoids (OCS) are effective treatment options but unfortunately, frequent relapses occur in many patients and they lead to frequent side effects. As for now, there are currently no official recommendations on doses and treatment schedules in the management of EGPA.Case presentation: In this article, we describe the case of a man with EGPA, severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), with poor asthma and CRSwNP control despite OCS and mepolizumab treatment. Respiratory and vasculitis symptoms improved markedly after therapeutic switch to benralizumab. During the treatment, in addition to clinical effects, we witnessed a depletion of blood eosinophils, as well as an improvement in both pulmonary function tests, CT scan and skin lesions present initially. Conclusions: While there are many studies confirming the efficacy of benralizumab in EGPA, the most interesting aspect of our report is that efficacy was confirmed in a patient previously unresponsive to mepolizumab, known to be effective in EGPA.

Introduction During this long COVID‐19 pandemic outbreak, continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) are being widely used to treat patients with moderate to severe acute respiratory failure (ARF). As for now, data on the efficacy of NIV in COVID‐19 acute respiratory distress syndrome (ARDS) are lacking, and for this reason it is extremely important to accurately determine the outcomes of this strategy. This study aimed to evaluate clinical data and outcomes of NIV in patients with COVID‐19 ARDS. Matherials and methods Seventy‐nine consecutive patients with sudden worsening of respiratory failure were evaluated. All patients (71% male) had a confirmed SARS‐CoV‐2 infection and signs, symptoms and radiological findings compatible with COVID‐19 pneumonia and all of them underwent a trial of NIV. Primary outcomes were NIV success and failure defined by intubation and mortality rate. Secondary outcome was the duration of NIV. Results NIV was successful in 38 (48.1%) patients (Table 1). EOT was necessary in 21 patients (26.6%). Death occurred in 20 patients (25.3%). In the group of patients having failed a trial with NIV and then being intubated, compared to those who continued NIV, there was no higher mortality rate. By evaluating the ICU survival outcome of the subgroup of patients intubated after NIV, 57% of the patients were discharged and 43% died. Conclusion Previous studies conducted on patients undergoing invasive mechanical ventilation showed higher mortality rate than the present study. Our data showed that NIV can avoid intubation in almost half of the patients. Therefore, this data could reassure clinicians who would consider using NIV in COVID‐19 ARDS‐related treatment.

The increasing knowledge on immuno-inflammatory pathways allowed the development of new therapeutic options in the field of severe refractory asthma (SRA). It is therefore very important to accurately identify phenotypes and endotypes of patients potentially eligible for innovative treatments. The aim of this study was to describe a cohort of patients affected by SRA referring to the Pneumology Unit of Azienda USL di Reggio Emilia/IRCCS in Reggio Emilia, Italy. It is an observational cross-sectional study, investigating the proportion of subjects with eligibility criteria for biological treatments (omalizumab, mepolizumab, benralizumab) and non-pharmacological treatment (bronchial thermoplasty, BT). We enrolled 137 patients with SRA referring to the centre from June 1st, 2017 to June 30th, 2019. The results of this study showed that 125 (91%) of patients were eligible for at least one biologic and 94 (69%) were eligible for BT. Only 6 (4%) of patients had no criteria for any available SRA treatments. Among biologics, there were only 11 (8%) patients resulting in overlap between omalizumab, mepolizumab and benralizumab, and 22 (16%) overlap of patients when BT was included. Considering eligibility criteria for BT, only 6 (4%) patients had inclusion criteria for BT, instead in real life 28% of patients were treated with BT. The major comorbidities were: bronchiectasis, chronic rhinosinusitis with nasal polyps (CRSwNP), gastro-esophageal reflux disease (GERD), and eosinophilic granulomatosis with polyangiitis (EGPA). The prevalence of bronchiectasis was much higher in the mepolizumab (45%) and benralizumab (43%) groups than in omalizumab (1%) and BT (7%), p 0,001; CRSwNP and GERD were equally present and EGPA was only present in the mepolizumab group. Overall, our population was eligible for biologicals in almost all cases, and a significant percentage of patients showed the presence of an overlap of allergic and eosinophilic endotypes. This implies the possibility of different therapeutic options and reiterates the need for a correct characterization of patients. This study confirmed how the identification of inflammatory endotypes and phenotypes represent a key role in the selection of the right therapy for the right patient.