Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov , NCT04327388 ; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 1...

Interleukin-5 (IL-5) exerts a central pathogenic role in differentiation, recruitment, survival, and degranulation of eosinophils. Indeed, during the last years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the powerful actions of IL-5 finalized to the induction, maintenance, and amplification of eosinophilic inflammation. Therefore, IL-5 is a suitable target for add-on biological therapies based on either IL-5 inhibition (mepolizumab, reslizumab) or blockade of its receptor (benralizumab). These modern treatments can result in being definitely beneficial for patients with severe type 2 (T2)-high eosinophilic asthma, refractory to conventional antiinflammatory drugs such as inhaled and even systemic corticosteroids.

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To the Editor, Since the end of February 2020, Italy, first non-Asian Country, has reported an ever increasing number of COronaVIrus Disease 19 (COVID-19) patients, which has reached over 200 000 confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected subjects, resulting in more than 34 000 deaths (data updated to June 19th, 2020 1). Patients with asthma are potentially more severely affected by SARS-CoV-2 infection and respiratory viruses are known to be associated with severe adverse asthma outcomes, including increased risk of asthma exacerbation episodes. 2 Nonetheless, according to the epidemiological studies published so far, asthma is not among the most common clinical conditions in COVID-19 patients. 3 About 5%-10% of asthmatics are severe, 4 and one would expect increased vulnerability to SARS-CoV-2 infection, but no data are so far available to confirm this hypothesis. We investigated the incidence of COVID-19, describing its clinical course, in the population of the Severe Asthma Network in Italy (SANI), one of the largest registry for severe asthma worldwide, 5 and in an additional Center (Azienda Ospedaliero Univeristaria di Ferrara, Ferrara, Italy). All centres have been contacted and inquired to report confirmed or highly suspect cases of COVID-19 (ie, patients with symptoms, laboratory findings and lung imaging typical of COVID-19 but without access to nasopharyngeal or oropharyngeal swab specimens because of clinical contingencies/emergency) among their cohorts of severe asthma. Demographic and clinical have been obtained from the

Background: Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT, and consequently, a lack of information on how AIT effectively works in real life. Methods:To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will use the RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic "real-world" database using systematic data collection. Based on the current RWE base, and perspectives and recommendations of authorities and scientific societies, aGlobally, SLIT appears to be the most common route of administration of AIT, as demonstrated by an analysis of the worldwide market hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence. Key Results:There is a need to establish more AIT registries that collect data in a cohesive way, using standardized protocols.Conclusions: This will provide an essential source of real-world data that can be easily shared, promoting evidence-based research and quality improvement in study design and clinical decision-making.

Asthma prevalence in Italy is on the rise and is estimated to be over 6% of the general population. The diagnosis of asthma can be challenging and elusive, especially in children and the last two decades has brought evidences that asthma is not a single disease but consists of various phenotypes. Symptoms can be underestimated by the patient or underreported to the clinician and physical signs can be scanty. Usual objective measures, like spirometry, are necessary but sometimes not significant. Despite proper treatment asthma can be a very severe condition (even leading to death) however new drugs have recently become available which can be very effective in its control. Since asthma is currently thought to be caused by inflammation, a direct measure of the latter can be of paramount importance.  For this purpose, the measurement of Fractional Exhaled Nitric Oxide (FENO) has been used since the early years of the current century as a non-invasive, easy-to-assess tool useful for diagnosing and managing asthma. This SIP-IRS/SIAAIC Position Paper is a narrative review which summarizes the evidence behind the usefulness of FENO in the diagnosis, management and phenotypization of asthma.

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