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Background: Quality of life (QoL) assessment is important in the management of severe asthma, and comorbidities and/or exacerbations may affect longitudinal QoL. However, there are few reports on the longitudinal assessment of QoL in patients with asthma over multiple years and its related factors. This study aimed to clarify the relationship of longitudinal changes in QoL with comorbidities and/or exacerbations during a prolonged observation period in patients with severe asthma. Methods: A total of 105 subjects who participated in the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (Hi-CARAT) with a six-year follow-up were analyzed. QoL was assessed annually, using the Standardized Asthma Quality of Life Questionnaire, and the subjects were divided into three groups: (1) persistently good QoL, (2) persistently poor QoL, and (3) fluctuating QoL. Assessed comorbidities comprised depression, gastroesophageal reflux disease, and excessive daytime sleepiness (EDS), a key symptom of obstructive sleep apnea. Results: Of 105 subjects with severe asthma, 53 (50%) were classified in the persistently good QoL group, 10 (10%) in the persistently poor QoL group, and 42 (40%) in the fluctuating QoL group. The persistently poor QoL group was associated with shorter time to hospitalization due to exacerbation and the presence of multiple comorbidities. In addition, the presence of EDS was an independent contributor to the fluctuating QoL group compared to the persistently good QoL group. Conclusions: The presence of multiple comorbidities and hospitalization due to exacerbation contribute to longitudinal changes in QoL in patients with severe asthma. Copyright (c) 2022, Japanese Society of Allergology. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a “fixed” bronchial obstruction due to structural changes unresponsive to current therapies, from a “reversible” one as demonstrated by lung function normalization during biological therapies not previously obtained even with high dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent tissue-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert “fixed” remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.

Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.

IntroductionClinical remission as a multicomponent treatment goal in severe asthma is being explored in clinical practice. This post hoc analysis used data from the REDES study to assess the proportion of patients with severe eosinophilic asthma achieving our multicomponent definitions of clinical remission after 1 year of mepolizumab treatment.MethodsThe real-world, retrospective observational REDES study enrolled patients with severe eosinophilic asthma who were newly prescribed mepolizumab and with ≥12 months of medical records pre-enrolment. Multicomponent clinical remission was defined as: oral corticosteroid (OCS)-free; exacerbation-free; asthma control test (ACT) score ≥20; and with or without post-bronchodilator forced expiratory volume in 1 second ≥80%. Baseline characteristics were also assessed in those who did/did not achieve clinical remission.Results37% and 30% of patients with severe eosinophilic asthma met our proposed three- and four-component on-treatment clinical remission definitions; an increase from 2% and 3% at baseline. Most frequently achieved individual components of clinical remission were: OCS-free; ACT score ≥20. For patients fulfilling the multicomponent clinical remission definitions, at baseline we observed higher blood eosinophil counts, better ACT scores and lung function, lower maintenance OCS use, and a slightly lower rate of prior exacerbations versus those who did not.DiscussionClinical remission is a realistic target in clinical practice for a subset of patients with severe eosinophilic asthma receiving mepolizumab. Further studies are required to elucidate whether features linked to the underlying endotype can help predict treatment outcomes, increase rates of clinical remission, and potentially modify disease progression.

Background: The most recognizable phenotype of severe asthma comprises people who are blood eosinophil and FeNO-high, driven by type-2 (T2) cytokine biology which responds to targeted biological therapies. However, in many people with severe asthma, these T2 biomarkers are suppressed but poorly controlled asthma persists. The mechanisms driving asthma in the absence of T2 biology are poorly understood. Objectives: To explore airway pathology in T2 biomarker-high and -low severe asthma. Methods: T2 biomarker-high severe asthma (T2-high, n=17) was compared to biomarker-intermediate (T2-intermediate, n=21) and biomarker-low (T2-low, n=20) severe asthma, and healthy controls (n=28). Bronchoscopy samples were processed for immunohistochemistry, and sputum for cytokines, PGD2 and LTE4 measurements. Results: Tissue eosinophil, neutrophil and mast cell counts were similar across severe asthma phenotypes and not increased when compared to healthy controls. In contrast, the remodeling features of airway smooth muscle mass and MUC5AC expression were increased in all asthma groups compared to health, but similar across asthma subgroups. Submucosal glands were increased in T2-intermediate and T2-low asthma. In spite of similar tissue cellular inflammation, sputum IL-4, IL-5, and CCL26 were increased in T2-high versus T2-low asthma, and several further T2-associated cytokines, PGD2 and LTE4, were increased in T2-high and T2-intermediate asthma compared to healthy controls. Conclusions: Eosinophilic tissue inflammation within proximal airways is suppressed in T2 biomarker-high and T2-low severe asthma, but inflammatory and structural cell activation is present, with sputum T2-associated cytokines highest in T2 biomarker-high patients. Airway remodeling persists, and may be important for residual disease expression beyond eosinophilic exacerbations.

The use of biologic agents has enabled control of severe asthma, but there is a risk that eosinophilic granulomatosis with polyangiitis (EGPA) may be masked in some cases. We herein report a 71-year-old man who was administered dupilumab for 2 years to stabilize his asthma symptoms. A few months after discontinuation of dupilumab administration, an increase in the eosinophil count in peripheral blood, leg pain, and a rash appeared. Based on pathology, he was diagnosed with EGPA. EGPA in this case was considered to have become apparent due to the discontinuation of dupilumab administration.

Introduction: The clinical phenotype of severe acute asthma at the pediatric intensive care unit (PICU) is highly heterogeneous. However, current treatment is still based on a ‘one-size-fits-all approach’. Areas covered: We aim to give a comprehensive description of the clinical characteristics of pediatric patients with severe acute asthma admitted to the PICU and available immunological biomarkers, providing the first steps toward precision medicine for this patient population. A literature search was performed using PubMed for relevant studies on severe acute (pediatric) asthma. Expert opinion: Omics technologies should be used to investigate the relationship between cellular molecules and pathways, and their clinical phenotypes. Inflammatory phenotypes might guide bedside decisions regarding the use of corticosteroids, neutrophil modifiers and/or type of beta-agonist. A next step toward precision medicine should be inclusion of these patients in clinical trials on biologics.

Little is known about adult asthma patients' perspective of their disease burden. This study aimed to obtain a comprehensive picture of patient needs, evaluate their knowledge, source of information, and perception of the severity of their asthma, and compare these variables between severe (SA) and non-severe (NSA) asthma patients.We conducted an online cross-sectional survey in Spain among asthma patients aged ≥18 years. A bespoke questionnaire was used to collect sociodemographic data, asthma characteristics, treatments, disease burden, patient's perception of disease severity, and asthma information sources. Patients were classified as SA and NSA according to GINA 2020 treatment steps recommendations. To compare populations, 600 participants (200 SA and 400 NSA) were randomly selected to complete the survey.Participants were mostly women, mean age38 years. SA patients underestimated the severity of their asthma; 52% judged it as mild, and only 2% considered their asthma severe. Overall, 50% of NSA and 96% of SA patients had experienced ≥1 exacerbation the previous year (p 0.001). Fewer asthma exacerbations (SA) and improved quality of life (QoL) (NSA) were the most frequently expected therapy outcomes. NSA patients believe that asthma impacts their daily life (37%) and worsens QoL (34%) to a lesser degree than SA (67% and 59%, respectively; p 0.001). Patient-preferred sources of information were specialists (NSA:42%; SA: 38%) and primary care physicians (NSA: 41%; SA: 33%).Despite the effective therapies currently available, the results of this study still show a significant emotional burden and QoL impairment in patients with severe asthma.

Introduction Based on the latest literature evidence, between 30% and 60% of adults with severe refractory asthma (SRA) are systemic corticosteroid (SCS) dependent. There are numerous therapeutic options in asthma, which are often not effective in severe forms. In these cases, SCS should be considered but it is increasingly recognized that their regular use is often associated with significant and potentially serious adverse events. Areas covered The aim of this article is to provide an update about the recent and significant literature on SCS and to establish their role in the management of SRA. We summarized the most important and recent evidence and we provided useful indications for clinicians. Expert opinion There is now strong evidence supporting the increased risk of comorbidities and complications with long-term SCS therapies, regardless of the dose. New evidence on SCS tapering and withdrawal will allow to define protocols to address SCS management with greater safety and effectiveness, after starting efficient steroid-sparing strategies. In the next 5 years, it will be necessary to implement corrective actions to address these unmet needs, to reduce the inappropriate use of SCS by maximizing the application of more innovative and effective therapies.

Asthma is a complex, heterogeneous chronic airway disease with high prevalence of uncontrolled disease. New therapies, including biologics, are now available to treat T2 high asthma. Treatment of T2 low asthma remains a challenge. Asthma guidelines need be to updated to incorporate new therapeutics.

Basic science has enriched our understanding of the pathophysiology of severe asthma. Clinical translation of these discoveries has resulted in biologic therapies that target key components of asth...

Interleukin-23 has been implicated in airway inflammation that is mediated by type 2 and type 17 cytokines. Whether targeting interleukin-23 in the treatment of asthma improves disease control and reduces airway inflammation is unclear.We conducted a phase 2a, multicenter, randomized, double-blind, placebo-controlled, 24-week, parallel-group trial to assess the efficacy and safety of risankizumab, an anti-interleukin-23p19 monoclonal antibody, in adults with severe asthma. Patients were assigned to receive 90 mg of risankizumab or placebo, administered subcutaneously once every 4 weeks. The primary end point was the time to the first asthma worsening. Asthma worsening was defined as deterioration from baseline on 2 or more consecutive days; deterioration was considered to be a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in the number of puffs of rescue medication in a 24-hour period (equating to at least four additional puffs), a severe asthma exacerbation, or an increase of 0.75 or more points on the 5-item Asthma Control Questionnaire (ACQ-5; scores range from 0 to 6, with higher scores indicating less control). Secondary end points were the annualized rate of asthma worsening, the annualized rate of severe exacerbations, the ACQ-5 score, and the forced expiratory volume in 1 second. Exploratory end points were assessed with the use of sputum cytologic analysis and gene expression analysis, and safety was assessed.A total of 105 patients received risankizumab and 109 received placebo. The clinical characteristics of the patients were similar in the two groups. The time to the first asthma worsening was shorter with risankizumab than with placebo (median, 40 days vs. 86 days; hazard ratio, 1.46; 95% confidence interval [CI], 1.05 to 2.04; P = 0.03). The rate ratio for annualized asthma worsening with risankizumab as compared with placebo was 1.49 (95% CI, 1.12 to 1.99), and the rate ratio for severe exacerbations was 1.13 (95% CI, 0.75 to 1.70). Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of the type 1 helper T and type 17 helper T transcription factors were down-regulated by risankizumab. No safety concerns were associated with risankizumab therapy.Risankizumab treatment was not beneficial in severe asthma. The time to the first asthma worsening was shorter and the annualized rate of asthma worsening was higher with risankizumab than with placebo. (Funded by AbbVie and Boehringer Ingelheim; ClinicalTrials.gov number, NCT02443298.).

Asthma as a clinical entity manifests with a broad spectrum of disease severity. Unlike milder asthma, severe disease is poorly controlled by inhaled corticosteroids, the current standard of care. Transcriptomic data, along with patient characteristics and response to biologics show that though Type 2 (T2) immune response remains an integral feature of asthma, additional molecular and immunologic factors may play important roles in pathogenesis. Mechanisms of T2 development, cellular sources of T2 cytokines and their relationship to additional immune pathways concurrently activated may distinguish several different sub-phenotypes, and perhaps endotypes of asthma, with differential response to non-specific and targeted anti-inflammatory therapies. Recent data have also associated non-T2 cytokines derived from T cells, particularly IFN-γ, and epithelial mediators with severe asthma. These topics and their relationships to acute asthma exacerbations are discussed in this review.

Asthma is the most common life-threatening chronic disease in children. Although guidelines exist for the diagnosis and treatment of asthma, treatment of severe, pediatric asthma remains difficult. Limited studies in the pediatric population on new asthma therapies, complex issues with adolescence and adherence, health disparities, and unequal access to guideline-based care complicate the care of children with severe, persistent asthma. The purpose of this review is to provide an overview of asthma, including asthma subtypes, comorbidities, and risk factors, to discuss diagnostic considerations and pitfalls and existing treatments, and then present existing and emerging therapeutic approaches to asthma management. An improved understanding of asthma heterogeneity, clinical characteristics, inflammatory patterns, and pathobiology can help further guide the management of severe asthma in children. More studies are needed in the pediatric population to understand emerging therapeutics application in children. Effective multimodal strategies tailored to individual characteristics and a commitment to address risk factors, modifiers, and health disparities may help reduce the burden of asthma in the USA.

An important proportion of asthma patients remain uncontrolled despite the use of inhaled corticosteroids and long-acting beta-agonists. Some add-on therapies, like azithromycin, have been recommended for this subgroup of patients. The purpose of this study was to assess the cost-effectiveness of azithromycin as an add-on therapy to ICS + LABA for patients with severe asthma.A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. The total costs and QALYS of two interventions, including standard therapy (ICS + LABA), and add-on therapy with azithromycin, were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.The model suggests a potential gain of 0.037 QALYs per patient per year on azithromycin, with a difference of US $718 in favor of azithromycin, showing dominance with respect to SOC. A position of dominance negates the need to calculate an incremental cost-effectiveness ratio. In the deterministic sensitivity analyses, our base-case results were robust to variations in all assumptions and parameters.Add-on therapy with azithromycin was found to be cost-effective when added to usual care in patients who remain uncontrolled despite treatment with medium or high-dose ICS/LABA.

Objectives Although the efficacy of the addition of ipratropium bromide (IB) to short-acting β2-agonists (SABAs) for treating children with moderate to severe asthma exacerbations has been demonstrated, evidence of its cost-effectiveness is scarce. The aim of the present study was to evaluate the cost-effectiveness of treatment with a combination of SABAs and IB compared with SABAs alone for the treatment of children with moderate to severe asthma exacerbations. Methods To achieve the objectives of the study, a decision-analysis model was adapted. Effectiveness parameters were obtained from a systematic review of the literature with meta-analysis. Cost data were obtained from hospital bills and from the national manual of drug prices in Colombia. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome of the model was avoidance of hospital admission. Results In children with moderate to severe asthma exacerbations, the base-case analysis showed that compared to SABAs alone, treatment with a combination of SABAs and IB was associated with lower overall treatment costs (US$126.24 vs. US$170.69 mean cost per patient) and a higher probability of hospital admission avoided (0.7999 vs. 0.7100), thus leading to dominance. For children with severe asthma exacerbations, these values were US$132.99 versus US$170.69 and 0.7883 versus 0.7100, respectively. Conclusions In Colombia, when compared to therapy with SABAs alone, therapy with a combination of SABAs and IB for treating pediatric patients with moderate to severe asthma exacerbations involves a lower probability of hospital admission at lower treatment costs.

Last year brought a significant advance in asthma management, unyielding to the pressure of the pandemics. Novel key findings in asthma pathogenesis focus on the resident cell compartment, epigenetics and the innate immune system. The precision immunology unbiased approach was supplemented with novel tools and greatly facilitated by the use of artificial intelligence. Several randomised clinical trials and good quality real-world evidence shed new light on asthma treatment and supported the revision of several asthma guidelines (GINA, Expert Panel Report 3, ERS/ATS guidelines on severe asthma) and the conception of new ones (EAACI Guidelines for the use of biologicals in severe asthma). Integrating asthma management within the broader context of Planetary Health has been put forward. In this review, recently published articles and clinical trials are summarised and discussed with the goal to provide clinicians and researchers with a concise update on asthma research from a translational perspective.

Background Food allergen immunotherapy (FA-AIT) practice is known to vary globally. This project aims to identify and characterize European centres performing FA-AIT. Methods An EAACI task force conducted an online survey to gather relevant information regarding FA-AIT practice and setting-specific resources after reviewing the published literature and congress abstracts throughout Europe. Results We identified 102 FA-AIT centres in 18 countries; only Spain (n = 39) and France (n = 16) had ≥10 such centres. Overall, most facilities were hospital-based (77.5%), publicly funded (80.4%) and delivered FA-AIT as routine clinical care (80.4%). On average, departments had 3 allergists/paediatric allergists and 2 nurses. Surveyed centres had provided FA-AIT for a median of 9 years [1-24] to a median of 105 [5-2415] patients. The estimated total number of treated patients was 24875, of whom 41.3% received AIT for milk, 34.2% egg, 12.8% peanut and 11.7% other foods. Anaphylaxis to AIT doses requiring over 4-6 h of observation was reported by 70.6% of centres, ICU admissions by 10.8% and eosinophilic esophagitis by 45.1%. Quality of life and sustained unresponsiveness were evaluated in 20.6% and 54.9% of centres, respectively. The main contraindications for food AIT were severe asthma (57%-63%), eosinophilic esophagitis (56%-48%) and age below 5 years (47%-41%). Conclusions In Europe, FA-AIT is provided mostly in clinical practice. Significant variation is seen in the number of centres per country, facility characteristics and inclusion/exclusion criteria, and in certain aspects of protocols. Potential inequality in access to AIT has been identified as well as the need for education and guidance for treatment standardization.

People with severe and difficult to control asthma can be a complex and heterogenous group of patients often with multiple comorbidities. Living with this disease imposes a huge physical and psychological burden upon the patient which requires a comprehensive, systematic and patient-focused assessment, using a wide range of clinical expertise from within the multidisciplinary team. This article describes a severe asthma systematic and multidimensional day case assessment, and the positive benefits that the authors perceive it offers for patient care. These benefits include a confirmed diagnosis, consideration of alternative diagnosis, enhanced adherence, medication optimisation, access to and gatekeeping of high-cost specialist medications, improved patient self-management skills and signposting to appropriate therapies. As a consequence, they believe that this facilitates better patient outcomes through a reduction in corticosteroid exposure, exacerbations and hospitalisation. This severe asthma multidisciplinary team day case approach offers more than just physical benefits when compared with the traditional medical model. Patient feedback reports an excellent patient experience, feeling listened to, understood, empowered and hopeful for the future.

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including metaanalyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force’s questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations:• suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes;• suggest using a blood eosinophil cut-point ≥150 μL−1 to guide anti-IL-5 initiation in adult patients with severe asthma;• suggest considering specific eosinophil (≥260 μL−1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy;• suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4 – 5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies;• suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype;• suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels.These recommendations should be reconsidered as new evidence becomes available.

Asthma is a heterogenous respiratory disease, usually associated with chronic airway inflammation and hyper-responsiveness, which affects an estimated 339 million people worldwide. Severe asthma affects approximately 5–10% of patients with asthma, approximately 17–34 million people globally, more than half of whom have uncontrolled disease. Severe asthma carries a substantial burden of disease, including unpredictable symptoms and potentially life-threatening flare-ups. Furthermore, severe asthma has a substantial burden on health care systems and economies worldwide. In 2018, a group of experts from the clinical community, patient support groups, and professional organisations joined together to develop the Severe Asthma Patient Charter, which set out six principles to define what patients should expect for the management of their severe asthma and what should constitute a basic standard of care. Since the publication of that original Charter in 2018, several important changes have occurred, including an improved understanding of asthma and effective asthma management; several new therapies have become available; and finally, the COVID-19 pandemic has placed a spotlight on respiratory conditions, the workforces that treat them, and the fundamental importance of health care system resilience. With those developments in mind, we, representatives of the academic, clinical, and patient advocacy group communities, have updated the Charter to Improve Patient Care in Severe Asthma with a focus on six principles: (1) I deserve a timely, comprehensive assessment of my asthma and its severity; (2) I deserve a timely, straightforward referral to an appropriate specialist for my asthma when it is not well controlled; (3) I deserve to understand what makes my asthma worse; (4) I deserve access to treatment and care that reduces the impact of asthma on my daily life; (5) I deserve not to be reliant on systemic corticosteroids; (6) I deserve to be involved in decisions about my treatment and care.

Introduction: The SARS-CoV-2 pandemic has deeply revolutionized our lives and consequently the management of patients, specifically ones with severe asthma.Objective: A survey was conducted to evaluate the effects on adherence, exacerbations and quality of life in patients with severe asthma during the COVID-19 pandemic period.Methods: 100 severe asthma patients, who accepted to participate to the survey, were asked to respond to different questionnaires in order to assess asthma symptoms (Asthma Control Test - ACT, and Asthma Control Quality - ACQ) and rino-sinusal ones (Sino-nasal outcome test - SNOT-22).Results: 31 out of 100 patients reported worsening of respiratory symptoms requiring a step-up in therapy dosage or frequency during the observational period; however, exacerbation rate was very low. Only 17 (17%) of the 100 participants experienced a severe asthma exacerbation. Moreover, there was no confirmed diagnosis of COVID-19 in this population.Conclusion: Patients with severe asthma did not show higher rates of exacerbations during the pandemic outbreak as well as no increased risk of contracting COVID-19 infection or developing the disease. Self-administration of biological drugs could be useful to maintain high rates of adherence to therapy, and, at the same time, to decrease the risk of exacerbations or Intensive Care Unit (ICU) room access.

Rationale: Some reports indicate longitudinal variability in sputum differential cell counts, whereas others describe stability. Highly variable sputum eosinophil percentages are associated with greater lung function loss than persistently elevated eosinophil percentages, but elevated neutrophils are linked to more severe asthma.Objectives: To examine sputum granulocyte stability or variability longitudinally and associations with important clinical characteristics.Methods: The SARP III (Severe Asthma Research Program III) cohort underwent comprehensive phenotype characterization at baseline and annually over 3 years. Adult subjects with acceptable sputum levels were assigned to one of three longitudinal sputum groups: eosinophils predominantly 2 SDs determined from independent, repeated baseline eosinophil percentages). Subjects were similarly assigned to one of three longitudinal neutrophil groups with a 50% cut point.Measurements and Main Results: The group with predominantly

Background: To determine the lung function of children admitted to the intensive care unit (ICU) for a severe asthma exacerbation in the medium- to long-term following hospital discharge. Methods: We performed a retrospective chart review of children ≥6 years of age admitted to the ICU for a severe asthma exacerbation at a tertiary care center from January 1, 2000, to December 31, 2013. Lung function was ascertained during outpatient follow-up visits at 3–12 months and 12–24 months postdischarge. A total of 72 subjects met the inclusion criteria. Results: Subjects were predominantly boys (56.9%) and had a mean (standard deviation [SD]) age at admission of 10.3 years (3.4 years). The median (interquartile range) length of stay in the ICU was 1 day (1–3 days). Thirty-eight and 28 subjects performed pulmonary function tests with acceptable technique at the 3–12 months and 12–24 months postdischarge visits, respectively. At 3–12 months, the mean (SD) predicted forced expiratory volume in 1 s (FEV(1)) and forced expiratory flow between 25% and 75% of vital capacity (FEF(25–75)) percent were 95.9 (16.7) and 76.7 (25.8), respectively, and 97.4 (17.6) and 70.5 (24.9), respectively, at 12–24 months. FEV(1)/forced vital capacity (FEV(1)/FVC) was 81.7 (8.3) at 3–12 months and 79.3 (7.7) at 12–24 months. A paired t-test on 20 subjects who performed acceptable spirometry at both visits showed a significant intraindividual decrease in FEV(1) (P = 0.008), FEF(25–75) (P = 0.02), and FEV(1)/FVC (P = 0.01) between the 2 time points. Conclusion: Although prospective studies are required to confirm our findings, our study suggests that children admitted to the ICU for severe asthma exacerbations may be at risk for declining pulmonary function in the medium- to long-term postdischarge.

Funding Information: In the preparation of this article, the authors received collaboration from the medical writer Duarte Oliveira (W4Research) financially supported by Sanofi. Sanofi had no role in the preparation of the manuscript or in the decision to submit the manuscript for publication. All authors declare collaborating and receiving fees from Sanofi and other pharmaceutical companies either through participation in advisory boards or consultancy, congress symposia, conducting clinical trials, investigator-initiated trials or grants. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

__Objective:__ In order to provide concrete context to research on biologicals for severe asthma we explore the everyday experiences of patients living with severe asthma and using biologicals. __Methods:__ We use a multi-method qualitative research-design including existing patient narratives, ten life-history interviews with patients mainly usingusing benralizumab (_N_ = 8), dupilumab (_N_ = 1), no biologicals (_N_ = 1), and two interviews with healthcare professionals (_N_ = 2) in the Netherlands. Our analysis focuses on patients’ experiences with the burden of disease and the burden of treatment regarding severe asthma. __Results:__ Findings show how our respondents experience a high burden of disease (breathlessness, fatigue, exacerbations, loss of family, friends and employment) and treatment (oral corticosteroids’ side-effects, dependency, life-style changes). Treatment with biologicals is relatively new for respondents. They mention to be cautious in their embrace of biologicals and in expressing hope for the future. Respondents who react to treatment with biologicals experience relief of both the burden of disease and and of treatment. They aim to regain their social life and societal participation, a striking contrast to those for whom biologicals proof prove ineffective. Biologicals’ Bburden of treatment is experienced as low and minor side-effects are mentioned by only few three respondents. Respondents appear relatively unconcerned about the lack of knowledge concerning the long-term effects and safety of biologicals. __Conclusions:__ Effective treatment with biologicals is generally experienced as a cautiously optimistic next step in a much longer and complex process of living with severe asthma. The practical lessons we draw point to managing patients’ expectations and the need to pay attention to patients not eligible for treatment with biologicals.

Obesity is associated with increased severity of asthma. Bariatric surgery can be effective in weight loss and improvement in asthma. Two reviewers conducted a systematic review using search terms: 'weight loss', 'bariatric surgery', and 'asthma'. Adult studies including all bariatric procedures and nonsurgical weight loss regimes were included. Thirty-nine studies, including twenty-six bariatric studies and thirteen nonsurgical studies, were found. No study directly compared bariatric surgery to nonsurgical techniques. Bariatric surgery offered greater weight loss (22-36%) than nonsurgical programmes (4.1-14.2%) and more consistently improved medication use, airway hyperresponsiveness, hospitalisation rate or ED attendance and lung function, while change in inflammatory markers were variable. Bariatric surgery appears to be superior in treating asthma; however, further study on surgery for both mild and severe asthma is required.

Introduction: Omalizumab is used to treat severe uncontrolled allergic asthma and chronic spontaneous urticaria (CSU), and is approved for self-administration in prefilled syringes. It is thus important to understand the advantages, critical issues, and indications for home administration.Areas covered: The present review summarizes the available evidence on home administration of omalizumab in asthma and CSU to illustrate the advantages derived from self-administration of patients in this setting.Expert opinion: The available data suggest that patients can safely administer biologics at home with suitable training, and that home administration is time saving and cost-effective. The majority of patients with severe asthma or CSU treated with omalizumab are likely to be suitable candidates for self-administration, which can be proposed to anyone that the clinician deems suitable. In addition to clinicians, pharmacists can also play a key role in managing patients who are prescribed home administration. A practical flow chart is proposed on selection of patients and their management during home administration. Self-administration of biologics can be considered as a valid alternative to traditional injections in a clinical setting, and the evidence has shown that no major issues need to be overcome in terms of safety or efficacy.

Background: We recently reported that severe asthma patients with frequent exacerbations showed high blood eosinophil counts (Eo) and fractions of exhaled nitric oxide (FeNO) compared with non-exacerbators. However, we did not determine exact cutoff values related to exacerbation. The aim of this study was to determine the cutoff values of Eo and FeNO that could be related to the exacerbation of severe asthma. We also aimed to confirm the clinical utility of Th2 markers related to exacerbation. Methods: This study included 105 severe asthma patients who completed a three-year follow-up of a severe asthma cohort study, including smokers. Three Th2 markers were selected, viz., Eo, FeNO, and positive atopic status. Regarding Eo and FeNO, we determined the cutoff values for the definition of "positive" Th2 features using receiver operating characteristic curve analyses, based on the comparisons between frequent exacerbators and other patients. Results: The cutoff values for positive Th2 features were Eo >= 250 cells/mL and FeNO >= 31 ppb. Sixteen patients (15.2%) had no Th2 features, 40 (38.1%) had one, 25 ( 23.8%) had two, and 24 (22.9%) had three. A high number of positive Th2 features was significantly associated with exacerbation frequencies over three years (p < 0.05). Similarly, compared to patients with one or no Th2 features, those with three Th2 features had a significantly higher probability of having more than one exacerbation (p < 0.05). Conclusions: The cutoff values determined in the current analysis were good predictors of future exacerbations in severe asthma patients. Copyright (C) 2020, Japanese Society of Allergology. Production and hosting by Elsevier B.V.

Background Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.