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Summary Background The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. Methods In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT04351152 , and is completed. Findings Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41–137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79–89) participants in the lenzilumab group and in 190 (78%; 72–83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02–2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. Interpretation Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. Funding Humanigen.

Short-acting βIn this cross-sectional study, data on disease characteristics/asthma treatments were collected using electronic case report forms. Patients (aged ≥12 years) were classified by investigator-defined asthma severity (guided by the 2017 Global Initiative for Asthma) and practice type (primary/specialist care). Multivariable regression models analyzed the associations between SABA prescriptions and clinical outcomes.Data from 1096 patients (mean age, 52.0 years) were analyzed. Most patients were female (70%), had moderate-to-severe asthma (79.4%), and were treated by specialists (87.6%). Asthma was partly controlled/uncontrolled in 61.5% of patients; 47.4% experienced ≥1 severe exacerbation in the previous 12 months. Overall, 39.8% of patients were prescribed ≥3 SABA canisters in the preceding 12 months (considered over-prescription). SABA canisters were purchased over the counter (OTC) by 17.2% of patients, of whom 38.8% purchased ≥3 canisters in the 12 months prior. Of patients who purchased SABA OTC, 73.5% were prescribed ≥3 SABA canisters. Higher SABA prescriptions (vs. 1 - 2 canisters) were associated with an increased incidence rate of severe exacerbations (ranging from 1.31 to 3.08) and lower odds ratios of having at least partly controlled asthma (ranging from 0.63 to 0.15).SABA over-prescription was common in Latin America, highlighting the need for urgent collaboration between healthcare providers and policymakers to align clinical practices with the latest evidence-based recommendations to address this public health concern.

Short-acting β2-agonist (SABA) over-reliance is associated with poor asthma outcomes. As part of the SABA Use IN Asthma (SABINA) III study, we assessed SABA prescriptions and clinical outcomes in patients from six Latin American countries. In this cross-sectional study, data on disease characteristics/asthma treatments were collected using electronic case report forms. Patients (aged ≥12 years) were classified by investigator-defined asthma severity (guided by the 2017 Global Initiative for Asthma) and practice type (primary/specialist care). Multivariable regression models analyzed the associations between SABA prescriptions and clinical outcomes. Data from 1096 patients (mean age, 52.0 years) were analyzed. Most patients were female (70%), had moderate-to-severe asthma (79.4%), and were treated by specialists (87.6%). Asthma was partly controlled/uncontrolled in 61.5% of patients; 47.4% experienced ≥1 severe exacerbation in the previous 12 months. Overall, 39.8% of patients were prescribed ≥3 SABA canisters in the preceding 12 months (considered over-prescription). SABA canisters were purchased over the counter (OTC) by 17.2% of patients, of whom 38.8% purchased ≥3 canisters in the 12 months prior. Of patients who purchased SABA OTC, 73.5% were prescribed ≥3 SABA canisters. Higher SABA prescriptions (vs. 1 − 2 canisters) were associated with an increased incidence rate of severe exacerbations (ranging from 1.31 to 3.08) and lower odds ratios of having at least partly controlled asthma (ranging from 0.63 to 0.15). SABA over-prescription was common in Latin America, highlighting the need for urgent collaboration between healthcare providers and policymakers to align clinical practices with the latest evidence-based recommendations to address this public health concern.

Introducao: A septoplastia e a turbinectomia sao as cirurgias funcionais nasais mais comuns realizadas pelos otorrinolaringologistas. Metodos objetivos e subjetivos podem ser aplicados para avaliar os resultados obtidos. Objetivo: Comparar tres metodos subjetivos com um metodo objetivo de avaliacao da obstrucao nasal em pacientes submetidos a cirurgias funcionais nasais e analisar a eficacia dessas cirurgias no pos-operatorio a curto prazo (35 a 45 dias) e em longo prazo (seis meses). Metodos: Trinta pacientes submetidos a cirurgias funcionais do nariz foram avaliados no pre-operatorio, pos-operatorio precoce entre 30 e 45 dias e pos-operatorio tardio de seis meses, por meio do metodo objetivo do Peak Flow , e de escalas subjetivas: Escala Visual Analogica (EVA), Nasal Index Score (NIS) e escala Nasal Obstruction Symptom Evaluation (NOSE scale ). Resultados: Todos os metodos mostraram eficacia significativa das cirurgias em pacientes com obstrucao nasal nos pos-operatorios precoce e tardio. O Peak Flow mostrou uma melhora de 65% do fluxo inspiratorio. As escalas NOSE, NIS e EVA tambem mostraram melhora significativa da obstrucao nasal. Na comparacao entre as escalas NOSE, NIS e EVA com o Peak Flow, nao se encontrou diferenca significativa entre o pre-operatorio e os pos-operatorios inicial e tardio (p≥0,05). Conclusao: Ha grande relacao entre os metodos subjetivos NOSE, NIS e EVA e o objetivo ( Peak Flow) , podendo-se usar qualquer um deles para a avaliacao da obstrucao nasal.

Background A double-blind, placebo-controlled, phase III study (200622) showed that mepolizumab reduces disease flares for patients with uncontrolled FIP1-like-1-platelet-derived growth factor receptor α–negative hypereosinophilic syndrome (HES) and two or more flares in the previous year. Objective To further characterize the safety, clinical benefit, and pharmacodynamics of mepolizumab. Methods Eligible patients from both treatment arms of the double-blind study could enter an open-label extension study (205203; NCT03306043) to receive 4-weekly mepolizumab (300 mg subcutaneously) plus background therapy for 20 weeks. Primary end points were safety-based; other end points included flare rates and changes from baseline in mean daily oral corticosteroid (OCS) dose and blood eosinophil count. Results Of 104 patients who completed the double-blind study, 98% (previous placebo, n = 52; previous mepolizumab, n = 50) enrolled in the open-label extension. Overall, 66 of patients reported adverse events (AEs) (65%), 15 reported treatment-related AEs (15%), and nine reported serious AEs (9%). No events were fatal. The annualized flare rate (95% confidence interval) in the previous placebo and previous mepolizumab groups was 0.37 (0.16-0.86) and 0.14 (0.04-0.49) events/y, respectively. Of 72 patients receiving OCS during weeks 0 to 4, 20 (28%; previous placebo, n = 14; previous mepolizumab, n = 6) achieved 50% or greater reductions in mean daily dose during weeks 16 to 20. At week 20, blood eosinophil count was reduced by 89% in patients previously receiving placebo and remained reduced for those previously receiving mepolizumab. Conclusions Extended mepolizumab treatment was associated with a positive benefit–risk profile. Continued control of disease flares and blood eosinophil counts, plus reductions in OCS use, were observed with mepolizumab in patients with FIP1-like-1-platelet-derived growth factor receptor α–negative HES.

Introduction: Patients with severe asthma may present with different phenotypes. Severe eosinophilic asthma patients require frequent use of health care resources and have impaired health-related quality of life. Objective: We sought to determine the prevalence of an eosinophilic phenotype, defined as blood eosinophil counts >300 cells/mm3, for patients with severe asthma in Brazil. Methods: This was a cross-sectional, observational study of adult patients with severe asthma (high dose inhaled corticosteroid [GINA 2018] plus second controller) in routine clinical practice in Brazil. Allergic phenotype was defined as serum IgE>100 IU/mL plus clinical features of allergy. Results: A total of 385 patients were enrolled from 10 Brazilian centers. Most were female (78.4%) and white (57.4%), with a mean age of 53±13 years old. Prevalence of patients with eosinophilic phenotype was 40.0% [95% CI: 35.1–44.9%]. Those were mainly female (76.0%), white (62.3%), with mean age 50±14 years old. Eosinophilic patients presented lower BMI, with no other relevant clinical or demographics differences compared with non-eosinophilic phenotype patients. A high prevalence of allergic phenotype of 62.6% [95% CI: 57.8%-67.4%] was also identified. There was a high overlap between phenotypes as 79.9% [95% CI: 73.5–86.2%] of eosinophilic patients were also allergic. Conclusions: The prevalence of an eosinophilic phenotype for patients with severe asthma in Brazil is high, and these patients present with clinical and demographic characteristics similar to other worldwide populations. The overlap between allergic and eosinophilic phenotypes was common.

Tang, Mimi/0000-0002-3839-5293; Romano, Antonino/0000-0001-9742-9898; Zuberbier, Torsten/0000-0002-1466-8875; Thong, Bernard/0000-0002-6338-8482; EBO, Didier/0000-0003-0672-7529; Scala, Enrico/0000-0002-9391-9168; Monge Ortega, Olga Patricia/0000-0002-6195-417X WOS:000523267300003 PubMed: 32128023 Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen. WAO Board of Directors The authors wish to thank the allergy societies from the membership of the World Allergy Organization who provided critical review of the draft and the WAO Board of Directors for supporting this work.

The publisher regrets we have been made aware of the below errors: 1) In Table 15, row NOVEOS chemiluminescent assay is written “utilizes 40 μL (0.04 ml) of sample per result”. The correct value would be “4 μL (0.004 ml)" of sample per result.2) In Table 16, is written “NOVEOS menu has 79 available allergens, consisting of 69 extracts and 10 molecular allergens”. It should say “NOVEOS menu continues to increase and it has 152 total allergens with 108 extracts and 44 components".3) In Table 15, row “Euroimmun”, column “Patient's serum”, is written “1000 ml”. The correct value would be “0.1 ml (-0.4 ml)”.The publisher would like to apologise for any inconvenience caused.

INTRODUCTION: Allergic rhinitis is considered the most prevalent respiratory disease in Brazil and worldwide, with great impact on quality of life, affecting social life, sleep, and also performance at school and at work. OBJECTIVE: To compare the efficacy and safety of two formulations containing mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis after four weeks of treatment. METHODS: Phase III, randomized, non-inferiority, national, open study comparing mometasone furoate in two presentations (control drug and investigational drug). The primary endpoint was the percentage of patients with reduction of at least 0.55 in nasal index score (NIS) after four weeks of treatment. Secondary outcomes included total nasal index score score after four and 12 weeks of treatment; individual scores for symptoms of nasal obstruction, rhinorrhea, sneezing, and nasal pruritus; as well as score for pruritus, lacrimation, and ocular redness after four and 12 weeks of treatment. The study was registered at clinicaltrials.gov with the reference number NCT01372865. RESULTS: The efficacy primary analysis demonstrated non-inferiority of the investigational drug in relation to the control drug, since the upper limit of the confidence interval (CI) of 95% for the difference between the success rates after four weeks of treatment (12.6%) was below the non-inferiority margin provided during the determination of the sample size (13.7%). Adverse events were infrequent and with mild intensity in most cases. CONCLUSION: The efficacy and safety of investigational drug in the treatment of persistent allergic rhinitis were similar to the reference product, demonstrating its non-inferiority. Resumo Introdução: A rinite alérgica é considerada a doença respiratória mais prevalente no Brasil e em todo o mundo, com grande impacto na qualidade de vida; além de, afetar a vida social, o sono e também o desempenho na escola e no trabalho. Objetivo: Comparar a eficácia e segurança de duas formulações contendo furoato de mometasona no tratamento da rinite alérgica persistente leve, moderada ou grave por um período de quatro semanas. Método: Trata-se de um estudo nacional aberto de fase III, randomizado, de não inferioridade de comparação do furoato de mometasona em duas apresentações (medicação de controle e fármaco sob investigação). O ponto final primário foi o percentual de pacientes com redução mínima de 0,55 no escore de índice nasal (EIN) após quatro semanas de tratamento. Os desfechos secundários foram: escore NIS total após 4 e 12 semanas de tratamento; escores individuais para sintomas de obstrução nasal, rinorréia, espirros e prurido nasal, bem como escores para prurido, lacrimejamento e hiperemia conjuntival após 4 e 12 semanas de tratamento. O estudo foi registrado em clinicaltrials.gov com o número de referência NCT01372865. Resultados: A análise de eficácia primária demonstrou não inferioridade do fármaco sob investigação em relação à medicação de controle, visto que o limite superior do intervalo de confiança (IC) de 95% para a diferença entre os percentuais de sucesso após quatro semanas de tratamento (12,6%) situava-se abaixo da margem de não inferioridade proporcionada durante a determinação do tamanho da amostra (13,7%). Eventos adversos foram pouco frequentes e de leve intensidade na maioria dos casos. Conclusão: A eficácia e a segurança de um fármaco experimental no tratamento da rinite alérgica persistente foram similares às do produto de referência, o que demonstrou sua não inferioridade.

Background Allergen immunotherapy (IT) is widely used to treat patients with allergic diseases, proven effective and recommended by national and international guidelines. Its efficacy and safety depend on the correct indication, use of relevant allergens and good quality extracts, as well as prescription and supervision by a trained professional. Our aims were to evaluate the frequency of use of IT in Brazil and to investigate whether this practice meets recommendations of the Brazilian Association of Allergy and Immunology (ASBAI) and Brazilian Medical Association.