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Background/aims: Sensitization to staphylococcal superantigens (SAgs) could contribute to asthma severity. However, its relevance with eosinophilic phenotype has not yet been clarified. This study aimed to investigate associations between serum specific IgE levels to SAg and eosinophilic airway inflammation in adult asthmatics., Methods: The serum specific IgE levels to 3 SAgs, including staphylococcal enterotoxin A (SEA) and B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured by ImmunoCAP in 230 adult asthmatic patients and 50 healthy controls (HCs). Clinical characteristics and laboratory parameters, including serum total/free IgE, and 2 eosinophil-activation markers, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), were analyzed according to blood eosinophil counts (BEC; 150 cells/μL) and serum specific IgE levels to 3 SAgs (0.35 kU/L)., Results: Asthmatic patients showed higher serum specific IgE levels to 3 SAgs than HCs (p < 0.05 for all). The serum total/clinfree IgE levels were significantly higher in asthmatics with positive IgE responses to 3 SAgs than those without (p < 0.05 for all). There were no significant differences in clinical parameters including age, asthma severity, comorbidities, or smoking according to IgE responses to 3 SAgs. Patients with positive IgE responses to SEB (not to SEA/TSST-1) had higher serum specific IgE levels to house dust mites and ECP/EDN as well as higher BEC with positive correlations between serum SEB-specific IgE levels and BEC/ECP/EDN (p < 0.05 for all)., Conclusion: These findings suggest that serum SEB-specific IgE levels could contribute to eosinophil activation as well as IgE production in adult asthma.

Background: Thymic stromal lymphopoietin (TSLP) is released from the airway epithelium in response to various environmental triggers, inducing a type-2 inflammatory response, and is associated with airway inflammation, airway hyperresponsiveness (AHR), and exacerbations. TSLP may also induce AHR via a direct effect on airway smooth muscle and mast cells, independently of type-2 inflammation, although association between airway TSLP and AHR across asthma phenotypes has been described sparsely., Objectives: This study sought to investigate the association between AHR and levels of TSLP in serum, sputum, and bronchoalveolar lavage in patients with asthma with and without type-2 inflammation., Methods: A novel ultrasensitive assay was used to measure levels of TSLP in patients with asthma (serum, n = 182; sputum, n = 81; bronchoalveolar lavage, n = 85) and healthy controls (serum, n = 47). The distribution and association among airway and systemic TSLP, measures of AHR, type-2 inflammation, and severity of disease were assessed., Results: TSLP in sputum was associated with AHR independently of levels of eosinophils and fractional exhaled nitric oxide (ρ = 0.49, P = .005). Serum TSLP was higher in both eosinophil-high and eosinophil-low asthma compared to healthy controls: geometric mean: 1600 fg/mL (95% CI: 1468-1744 fg/mL) and 1294 fg/mL (95% CI: 1167-1435 fg/mL) versus 846 fg/mL (95% CI: 661-1082 fg/mL), but did not correlate with the level of AHR. Increasing age, male sex, and eosinophils in blood were associated with higher levels of TSLP in serum, whereas lung function, inhaled corticosteroid dose, and symptom score were not., Conclusions: The association between TSLP in sputum and AHR to mannitol irrespective of markers of type-2 inflammation further supports a role of TSLP in AHR that is partially independent of eosinophilic inflammation., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Measurement of airway inflammation is an important step to determine phenotype of asthma and allergic rhinitis (AR). Objective: To assess the level of nitric oxide in exhaled air (FeNO), nasal fraction of nitric oxide (nasal NO), their relationship with clinical control and blood eosinophils in patients with steroid-naive mild and moderate asthma and AR. Methods: One hundred forty-seven patients (65 men), ages 26-49.5 years (mean age, 32 years) with AR (n = 81) or AR and concomitant asthma (n = 46) and 20 healthy subjects were included in a single-center cohort study. All the patients underwent spirometry with reversibility test. Control of asthma and AR was assessed by using the Asthma Control Questionnaire and the visual analog scale, respectively. Levels of FeNO and nasal NO were measured by chemiluminescent analyzer, peripheral blood eosinophils were counted by automatic analyzer. Results: The FeNO level was significantly elevated in the patients with asthma and concomitant AR compared with the healthy subjects and was associated with control of both asthma and AR. There was no correlation between nasal NO and control of AR. Receiver operating characteristic analysis revealed that the level of eosinophils of 150 cells/μL may be a cutoff for lower airway eosinophilic inflammation. Blood eosinophils count was unable to distinguish eosinophilic and non-eosinophilic upper airway inflammation. Conclusion: We confirm that FeNO but not nasal NO is a marker of eosinophilic airway inflammation in patients with mild-moderate steroid-naive AR and concomitant asthma. A blood eosinophil level of ≥150 cells/µL may be a simple marker of eosinophilic airway inflammation in patients with asthma. However, its low specificity requires repeated measurements and use in combination with other biomarkers.

Eosinophilic granulomatous polyangiitis is a systemic vasculitis associated with bronchial asthma and eosinophilic sinusitis. Here, we describe an unusual presentation of eosinophilic granulomatous polyangiitis that initially manifested as swelling of the oral cavity floor and cervical soft tissue. A 58 year-old Japanese man was diagnosed with bronchial asthma during childhood but did not receive regular medication. Prior to this presentation, he had a persistent cough for over 1 month, and a local physician diagnosed him with bronchial asthma. However, 6 months later, his cough worsened, and a blood test revealed elevated eosinophil levels. Immediately afterward, swelling of the floor of the oral cavity and cervical soft tissue developed. Cellulitis was suspected and antimicrobial treatment was initiated; however, the symptoms persisted and abdominal pain developed. An endoscopic examination revealed duodenitis and a duodenal ulcer. The patient was diagnosed with eosinophilic granulomatous polyangiitis based on three items of the 2022 American College of Rheumatology/European College of Rheumatology classification criteria: obstructive airway disease, blood eosinophil count ≥1 × 109 cells/L, and extravascular eosinophilic infiltration with a score of 10. Oral prednisolone (70 mg/day), intravenous cyclophosphamide (500 mg/m2), and subcutaneous mepolizumab (300 mg every 4 weeks) were administered. The patient's symptoms improved after these treatments, and the eosinophil count and inflammatory marker levels declined. When swelling of the oral cavity floor and cervical soft tissue following an increase in eosinophilia and allergic symptoms occurs, it is crucial to consider the likelihood of eosinophilic granulomatous polyangiitis and collaborate with otolaryngologists and dentists to ensure its prompt identification., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Eosinophilic otitis media (EOM) is an intractable otitis media with highly viscous middle ear effusion and is usually associated with bronchial asthma. Since the diagnostic criteria of EOM were established in 2011, the concept of EOM has been known worldwide. EOM is caused by Type 2 inflammation in the respiratory tract, similar to bronchial asthma and eosinophilic rhinosinusitis. With the appreciation of Type 2 inflammatory diseases, EOM is no longer considered to be a rare disease and should be specifically treated to improve quality of life. The diagnosis of EOM needs to be reconsidered because many reports have described varying pathogenesis and mechanisms of rare middle ear conditions. Systemic and topical administration of corticosteroids is presently the most effective treatment to control EOM. However, EOM treatments are developing because various biologics have been used to treat patients with bronchial asthma with and without eosinophilic rhinosinusitis and EOM. Surgical intervention is also no longer contraindicated with the use of biologics. These advances represent the beginning of a new stage of basic and clinical research for EOM. This review focuses on the diagnosis and treatment of EOM based on the most recent advances regarding EOM., Competing Interests: Disclosure Statement We have no conflicts of interest to disclose in connection with this review., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: To determine the average serum periostin level in children with asthma between 6 and 16 y of age, and to find out if the levels correlated with markers of eosinophilic inflammation, asthma control, and severity., Methods: Children under follow-up at a tertiary care centre were enrolled. Children with conditions causing elevated serum periostin other than asthma, or history of systemic steroid use in the past 6 mo were excluded. Serum total IgE and periostin were estimated by ELISA., Results: The median (IQR) serum periostin level was 52.6 (45.4, 58.3) ng/mL. Levels did not vary with age, gender, duration of symptoms, positive family history, or history of exacerbations in the last 6 mo. There was no significant correlation with anthropometric parameters or their z scores, or markers of eosinophilic inflammation in blood including serum total IgE, eosinophil percentage or absolute eosinophil count. There was no difference in median periostin levels of children with different asthma symptom control or asthma severity., Conclusions: In a group of 26 Indian children with physician-diagnosed asthma, serum periostin showed no significant correlation to markers of eosinophilic inflammation., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of systemic vasculitis with eosinophilic inflammation. However, existing classification criteria are all designed to classify EGPA among vasculitis and there is no established method distinguishing EGPA from other eosinophilic disorders. The aim of the present study was to propose a scoring system to differentiate EGPA among eosinophilic disorders., Methods: Non-supervised hierarchical clustering using Ward's method and principal component analysis (PCA) were performed for 19 clinical parameters of 58 patients with eosinophilia-related diseases at a tertiary university hospital. The newly proposed scoring system was externally validated in 40 patients at another tertiary institution., Results: Two distinct clusters were identified, and clinical features including peripheral neuropathy, asthma, skin involvement, lung involvement, rheumatoid factor (RF) positivity, myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) positivity, IgE elevation, C-reactive protein (CRP) elevation, and vasculitis pathological findings were predominantly observed in one of these clusters (p < 0.05). Ten features defining the cluster with a high rate of vasculitis were weighted by PCA to create the E-CASE (EGPA classification among systemic eosinophilia) scoring system, on a 16-point scale. Based on the distribution of scores in the primary cohort, we defined an E-CASE score ≥12 as positive, ≤ 8 as negative, and 9-11 as undeterminable. The sensitivity and specificity of the E-CASE score in the validation cohort were 93.3% and 100%, respectively., Conclusions: We developed and verified a novel scoring system for differentiating EGPA from other types of eosinophilic disorders., (Copyright © 2022 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis of small and medium sized blood vessels., Case Description: Thirteen-year-old male, with history of rhinitis and asthma, who presented to the emergency room with one week of asthenia, arthralgias and myalgias and two days of fever. A diffuse petechial rash, palpable purpura and polyarthritis were detected on examination. Leukocytosis (34990/μL) with eosinophilia (66%) and elevated C-reactive protein were identified. The patient was admitted and ceftriaxone and doxycycline were started. The clinical status deteriorated in the following days. The patient developed myopericarditis, bilateral pulmonary infiltrates and pleural effusion, requiring mechanical ventilation and aminergic support. Non-clonal eosinophils were detected on the bone marrow aspiration and the skin biopsy showed leukocytoclastic vasculitis with eosinophils. Antineutrophil cytoplasmic antibodies and genetic analysis for hypereosinophilic syndrome mutations were negative. After treatment with methylprednisolone for three days a fast clinical, laboratory and radiological improvement occurred. The patient started azatiophrine and reduced steroids progressively. No relapses occurred since diagnosis five years ago., Discussion: Clinical suspicion and early treatment of EGPA are crucial to improve prognosis.

BACKGROUND Eosinophilic gastroenteritis (EG) can be associated with parasitic infections, atopic drug reactions, or atopic diseases, such as asthma. This report describes 25-year-old and 27-year-old sisters with a family history of asthma who presented with abdominal pain due to EG. CASE REPORT Case 1: A 25-year-old woman presented with a 4-month history of chronic left upper quadrant abdominal pain that did not improve with proton pump inhibitor and sucralfate therapy. She has a history of asthma and allergic rhinitis. Endoscopic pathology revealed pangastritis, with eosinophilic infiltration >25 per 1 high power field. Case 2: Her 27-year-old sister was admitted with chronic abdominal discomfort in the form of vomiting and recurrent abdominal pain for the past 2 years. Treatment with proton pump inhibitors and sucralfate did not lead to improvement. She also had intermittent asthma. Pathological findings on her endoscopy showed chronic inflammation of the fundus and antrum, with eosinophilic infiltration >40 per 1 high power field. Association of eosinophilic gastrointestinal diseases in siblings has not been reported previously. CONCLUSIONS This report has highlighted that atopic disease, such as asthma, is often familial, and can be associated with generalized eosinophilia, including EG. In these 2 sisters, the clinical history and histological findings on colonic biopsy were important to confirm the diagnosis.

Recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) with a predominant Th2 endotype of inflammation, including associated with bronchial asthma and/or allergic rhinitis, aspirin triad, refers to diseases with an insufficient level of control, despite the use of a wide range of options for conservative and surgical treatment., Objective: To analyze our own experience, clinical and organizational features of the application of the method of biological therapy in patients with severe forms of recurrent CRSwNP., Material and Methods: 25 patients with severe and moderate forms of CRSwNP were examined, who, in a round-the-clock hospital (model CSG 36.018) was treated with Dupilumab, in the form of subcutaneous injections of 300 mg/2 ml 1 every two weeks. The diagnosis was confirmed on the basis of anamnestic data, SNOT-22 quality of life questionnaires, visual endoscopic examination, evaluation of CT data (Lund-Mackay scale), laboratory data. The effectiveness of treatment was monitored after 16 weeks, based on endoscopic examination data, evaluation of CT and SNOT-22 data. In 3 observations, a study of pathomorphological material for tissue eosinophilia was performed., Results: The duration of the course of treatment ranged from 10 to 56 weeks. The most striking clinical effect was observed for signs such as sense of smell and nasal breathing (in some cases-after the first injection). The degree of regression of polyps according to CT and endoscopic examination was more prolonged in time, the same dynamics was observed in the level of total IgE. In a number of patients, the phenomenon of eosinophilia growth was observed against the background of treatment (with regression of clinical symptoms). Pathomorphological examination confirmed a high level of tissue eosinophilia as one of the fundamental signs of Th2 inflammation. One patient with concomitant chronic tubar dysfunction had an improvement in hearing. All patients with AD noted a subjective improvement in disease control (a decrease in the frequency and severity of choking attacks). The cancellation (break in treatment) of treatment was accompanied by a gradual return of symptoms in all patients at various times., Conclusions: Patients who have not achieved an acceptable level of control of CRSwNP,that meets the criteria of Th2 inflammation can be considered as candidates for the use of targeted biological therapy. With strict compliance with the selection criteria, there is a good clinical effect, primarily in relation to nasal symptoms (sense of smell and nasal breathing) and improved control of asthma symptoms.

Chronic cough is a debilitating condition affecting 10-12% of the general population and is one of the leading causes for referral to secondary care. Many conditions have been associated with chronic cough, including asthma, gastro-esophageal reflux disease and upper airways cough syndrome. Inflammatory airway conditions including cough variant asthma (CVA) and non-asthmatic eosinophilic bronchitis (NAEB) contribute to a significant proportion of presentations with chronic cough, with differing diagnostic criteria and different responses to commonly used asthma therapy for their respective diagnoses. Mechanistic studies in both animal models and humans have identified increased neuronal sensitivity and subsequent central sensitization. These mechanisms include inflammatory-mediated nociceptor sensitization and alterations of afferent nerve terminal excitability, phenotypic changes in the vagal afferent neurons over time, and central neuroplasticity resulting from increased synaptic signalling from peripheral afferents. The aim of this review is to discuss the mechanisms, neurophysiology, and management approaches currently available for patients presenting with chronic cough with underlying asthma, CVA, and NAEB and to shed a light on areas of further research required to elucidate the mechanisms of cough in this patient population., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We present a case report of nivolumab-aggravated treatment-resistant chronic rhinosinusitis with nasal polyposis with asthma, suggestive of aspirin-exacerbated respiratory disease, normalized with the IL-5R antagonist benralizumab. For patients experiencing symptomatic complications of immunotherapy-associated eosinophilia, this case suggests anti-IL-5(R) biologics may durably resolve nasal polyposis and asthma symptoms, permitting continuity of checkpoint inhibitor therapy and sparing of systemic corticosteroids. Postulated mechanisms of checkpoint inhibition favoring eosinophilia and polyposis, and the uncertain effect of eosinophil reduction upon malignancy progression, are reviewed.

Background: Asthma is a significant comorbidity of eosinophilic chronic rhinosinusitis (CRS). Type2-driven biomarkers such as sinus tissue eosinophilia and fractional nitric oxide (FeNO) may be utilized to detect high risk patients who develop asthma symptoms after endoscopic sinus surgery (ESS) in CRS patients., Methods: Thirty-six CRS patients without asthma who agreed to undergo ESS between October 2015 and December 2017 were prospectively observed for 12 months following ESS. They were monitored for the development of typical asthma symptoms including dyspnea, wheezes, and cough which responded to anti-asthma medication. Biomarkers were compared between patients who developed asthma symptoms after ESS (asthma symptoms group) and those who did not (non-asthma group). Biomarker changes following ESS intervention were also evaluated., Results: Six patients were lost to follow after ESS. Thus, 30 CRS patients [16 with nasal polyps (NPs) proved by surgery] were followed. Seven (23%) newly complained of asthma symptoms during follow-up. Levels of FeNO and the prevalence of eosinophilic NPs (eosinophils ≥ 70/high power fields) were significantly higher in the asthma symptom group than in non-asthma group [50.7 ppb vs 22.4 ppb for FeNO levels, and 100% ( n  = 3) vs 23% ( n  = 3) for eosinophilic NP prevalence, both p  < 0.05]. Levels of sputum periostin decreased significantly by ESS in the non-asthma group. However, changes of biomarkers after ESS were comparable between the two groups., Conclusions: Eosinophils in NPs (≥70/high power fields) and preoperative FeNO may be significant biomarkers for predicting the development of asthma symptoms after ESS.

Chronic cough, defined as a cough lasting for greater than 8 weeks, accounts for a substantial number of primary care and specialist consultations in the United States. Although cough can arise from a myriad number of serious respiratory diseases, attention has traditionally focused on diagnosing and treating gastroesophageal reflux, upper airway cough syndrome, and eosinophilic airway inflammation (asthma and nonasthmatic eosinophilic bronchitis) in patients with normal chest imaging. The newly described paradigm and entity of cough hypersensitivity syndrome (CHS) becomes useful when the etiology of cough remains elusive or when the cough remains refractory despite appropriate therapy for underlying causes. We present an update on the evolving understanding of refractory chronic cough and/or unexplained chronic cough as manifestations of laryngeal hypersensitivity and CHS. This includes a focus on understanding the pathophysiology underlying current and novel therapeutics for CHS, while also ensuring that common causes of chronic cough continue to be evaluated and treated in a systematic multidisciplinary manner., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is rare vasculitis syndrome that involves the skin and other organ systems manifesting as asthma, eosinophilia, and pulmonary infiltrates. The understanding of EGPA, previously known as Churg-Strauss Syndrome, has continued to evolve from its earliest documentation in the literature in 1951. Herein, we review key historical advances in the diagnosis, classification, and nomenclature of EGPA that have shaped our understanding of this protean disorder over time., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

A very detailed differential diagnosis is necessary to investigate the causes of blood hypereosinophilia. In the differential diagnosis of hypereosinophilia with pulmonary involvement, primary and secondary eosinophilic lung diseases should be kept in mind, and more specific diagnoses should be considered in those with a history of nasal polyposis and asthma. Here, it was aimed to present a case of organ-limited hypereosinophilia with asthma and nasal polyposis.

Background: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts., Research Question: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables?, Study Design and Methods: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC)., Results: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV 1 , 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy., Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In France, data regarding epidemiology and management of severe asthma are scarce. The objective of this study was to describe asthma phenotypes using a cluster analysis in severe asthmatics recruited in a real world setting., Methods: The study design was prospective, observational and multicentric. The patients included were adults with severe asthma (GINA 4-5) followed-up in French Non Academic Hospital between May 2016 and June 2017. One hundred and seven physicians included 1502 patients. Both sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis on a population of 1424 patients., Results: Five clusters were identified: cluster 1 (n = 690, 47%) called early onset allergic asthma (47.5% with asthma before 12 years), cluster 2 (n = 153, 10.5%): obese asthma (63.5% with BMI > 30 kg/m 2 ), cluster 3 (n = 299, 20.4%): late-onset asthma with severe obstructive syndrome (89% without atopy), cluster 4 (n = 143, 9.8%): eosinophilic asthma (51.7% had more than 500 eosinophils/mm 3 ), and cluster 5 (n = 139, 9.5%): aspirin sensitivity asthma (63% had severe asthma attacks)., Conclusions: In our population of adults with severe asthma followed by pulmonologists, five distinct phenotypes were identified and are quite different from those mentioned in previous studies.

A 47-year-old male presented with dyspnoea and pulmonary nodules. He had longstanding asthma, chronic rhinosinusitis and a history of seizures, having been treated with valproic acid for years. A transbronchial biopsy and a bronchoalveolar lavage yielded a eosinophilic bronchitis and alveolitis without any malignant cells. The patient was then treated with oral corticosteroids for a few months, and the antiepileptic medication was switched to levetiracetam. Within a few months the dyspnoea improved and both the pulmonary nodules and the eosinophilia in the full blood count resolved. Eosinophilic lung diseases warrant a thorough investigation. Most likely, our patient suffers from eosinophilic granulomatosis with polyangiitis. As well, the eosinophilic lung disease might have been caused by valproic acid. Similar cases have been described in the literature., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilic asthma. Objective: This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to compare the superiority of one over the other, especially in asthma with an eosinophilic phenotype. Methods: The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants, and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E values were examined. Results: TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups (p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group (p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis. The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. The present study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore, when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostin in serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively. Conclusion: Serum and sputum TARC and periostin may contribute for monitoring the improvement of patients, particularly those with asthma. Furthermore, TARC was a more reliable biomarker than periostin for patients with eosinophilic asthma.

Background: Eosinophilic chronic rhinosinusitis (ECRS) is often complicated by asthma and can be difficult to diagnose. This study aimed to clarify the usefulness of the self-administered odor questionnaire (SAOQ) and visual analog scale (VAS) to identify olfactory disorders in patients with asthma., Methods: This retrospective study was conducted on patients with asthma who were referred to the Otolaryngology clinic between May and September 2018. The treatment step of asthma, asthma control test (ACT), pulmonary function test, peripheral blood eosinophils, and fractional exhaled nitric oxide (FeNO) were analyzed. ECRS was diagnosed based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study score. Olfactory dysfunction was evaluated using the SAOQ and VAS for olfactory disorders., Results: The study included 56 patients (18 males and 38 females), who were divided into two groups; those with ECRS (n = 18) and those without ECRS (n = 38). Age, sex, treatment step, ACT score, and pulmonary function were not significantly different between the groups. The ECRS group had a significantly higher FeNO value (89.1 ppb vs. 39.1 ppb) and a significantly lower SAOQ score (40.1% vs. 96.1%). The area under the receiver operating characteristic curve for the efficacy of ECRS diagnosis was 0.88, 0.889, 0.799, and 0.757 for SAOQ, VAS, blood eosinophil count, and FeNO, respectively., Conclusion: The SAOQ and VAS scores were useful tools that presented similar results to the blood eosinophil count and FeNO, and may help to improve the diagnosis of ECRS in patients with asthma., Competing Interests: Conflict of interest The authors have no conflicts of interest., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: It is widely acknowledged that food sensitization is related to atopic dermatitis in infants and young children. Objective: To investigate the association of aeroallergen sensitization with increased rates and severity of atopic dermatitis in school children. Methods: We enrolled 576 children (mean age, 9.4 ± 1.8 years) from six elementary schools. Atopic dermatitis was diagnosed by questionnaires, and severity was rated by physical examinations graded by using the Scoring Atopic Dermatitis (SCORAD) index. Skin-prick tests to 22 common allergens (6 aeroallergens and 16 food allergens) were conducted. Logistic and linear regression analyses were performed by using two models: model I adjusted for age, sex, and body mass index z score; and model II adjusted for all model I factors plus asthma and allergic rhinitis. Results: We diagnosed atopic dermatitis in 22.4% (n = 129) of the children, sensitization to foods in 48.3% (n = 278), and sensitization to aeroallergens in 11.3% (n = 65). A total of 26.2% of the children (n = 149) had mild and 6.5% had moderate-to-severe symptoms and signs of atopic dermatitis (n = 37). Atopic dermatitis was associated with sensitization to aeroallergens and eosinophilia (model I), but this risk was no longer significant after additional adjustment for current allergic status (model II). However, the relationship of the total SCORAD score with aeroallergen sensitization and eosinophilia was significant in model I and model II. Conclusion: The severity of atopic dermatitis correlated with the extent of allergic sensitization and eosinophilia. Analysis of our results suggests that more sensitization to dust mites and eosinophilia are related to increased rates and high severity scores of atopic dermatitis.

Benralizumab and mepolizumab are new therapies for severe eosinophilic asthma. They are both humanized IgG antibodies, targeting the IL-5 receptor and IL-5, respectively, suppressing the corresponding pathways. No specific biomarkers have been proposed to evaluate treatment response to benralizumab or mepolizumab. The aim of this proteomic study was to compare serum protein profiles of patients with severe eosinophilic asthma before and after anti-IL5 or anti-IL5R therapies. Proteomic analysis highlighted 22 differently abundant spots. Among the proteins identified, CAYP1, A1AT and A2M expression was significantly modified in both groups of patients after therapies while ceruloplasmin showed a significant modification in the group of benralizumab treatment. These differentially expressed proteins could be potential biomarkers of response to mepolizumab and benralizumab treatments and need further evaluation.

Cough is an important symptom of asthma. The objective assessment of chronic cough has been enhanced by the development of ambulatory cough monitoring systems. Mepolizumab has been demonstrated to reduce exacerbations in eosinophilic asthmatics long-term. We evaluate the utility of objective cough count as an outcome measure in severe eosinophilic asthma treated with mepolizumab. Consecutive, consenting patients initiated on treatment with mepolizumab had a 24-h cough count recorded at baseline; this was repeated at 1, 3 and 6 months. Asthma control questionnaire (ACQ) scores and exacerbation frequency were also recorded. The mean 24-h cough count in 11 subjects (8 females, mean age 53.6 years) was 172.4 at baseline; at 1, 3 and 6 months following initiation of treatment this decreased to 101.4, 92 and 70.8, respectively (p < 0.02). Significant improvements were also observed in mean ACQ score (3-1.6, p < 0.01) and exacerbation frequency (5.5 per year - 1.3, p < 0.01). Objective cough measurement could be used as an early, precise and clinically relevant endpoint in assessing response to asthma therapy.

Objective: To assess the effect of asthma exacerbations and mepolizumab treatment on health status of patients with severe asthma using the St George's Respiratory Questionnaire (SGRQ). Methods: Post hoc analyses were conducted using data from two randomized controlled trials in patients ≥12 years old with severe eosinophilic asthma randomized to receive placebo or mepolizumab 75 mg intravenously (32-week MENSA study) or 100 mg subcutaneously (MENSA/24-week MUSCA studies), and an observational single-visit study in patients with severe asthma (IDEAL). Linear regression models assessed the impact of historical exacerbations on baseline SGRQ total and domain scores (using data from each of the three studies), and within-study severe exacerbations and mepolizumab treatment on end-of-study SGRQ scores (using data from MENSA/MUSCA). Results: Overall, 1755 patients were included (MENSA, N  = 540; MUSCA, N = 551; IDEAL, N  = 664). In all studies, higher numbers of historical exacerbations were associated with worse baseline SGRQ total scores. Each additional historical exacerbation (beyond the second [MENSA/MUSCA]) or first [IDEAL] was associated with worsening mean total SGRQ scores of +1.5, +1.1 at baseline and +2.3 within the year prior to study enrollment. During MENSA and MUSCA, each within-study severe exacerbation was associated with a worsening in total SGRQ score of +2.4 and +3.4 points at study end. Independent of exacerbation reduction, mepolizumab accounted for an improvement in total SGRQ score of -5.3 points (MENSA) and -6.2 points (MUSCA). Conclusions: These findings support an association between a higher number of exacerbations and worse health status in patients with severe (eosinophilic) asthma.

Background: The humanized monoclonal antibody benralizumab targets the α subunit of the interleukin-5 (IL-5) receptor and the FcγRIIIa receptor expressed by natural killer cells. Through this dual mechanism of action, benralizumab neutralizes the pro-eosinophil functions of IL-5 and promotes eosinophil apoptosis., Objectives and Methods: The present real-life study aimed to evaluate, in 22 allergic patients with severe eosinophilic asthma, the effects of benralizumab on asthma exacerbations and lung hyperinflation., Results: In this regard here we show that, after 24 weeks of add-on treatment, benralizumab completely depleted peripheral blood eosinophils (from 810 to 0 cells/μL; p < 0.0001), and significantly decreased both asthma exacerbation number (from 4 to 0; p < 0.0001) and residual volume (from 2720 to 2300 mL; p < 0.01). Moreover, at the same time point (24 weeks) benralizumab also increased pre-bronchodilator FEV 1 (from 1295 to 1985 mL; p < 0.0001), FVC (from 2390 to 2974 mL; p < 0.0001), FEF 25-75 (from 0.6 to 1.42 L/sec; p < 0.0001), IC (from 1940 to 2460 mL; not significant), and ACT score (from 14.73 to 22.95; p < 0.0001), as well as reduced prednisone intake (from 25 to 0 mg; p < 0.0001)., Conclusion: In conclusion, our results suggest that via its anti-eosinophil actions benralizumab improved airflow limitation, lung hyperinflation, and respiratory symptoms, as well as lowered asthma exacerbation rate and abrogated OCS consumption in most patients., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Severe asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment., Methods: In a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile., Results: At enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5-10]) mg prednisone equivalent). BEC was high (> 400/mm 3 ) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients., Conclusion: These data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.

This review will outline an evidence-based approach for diagnosing and managing children with problematic severe asthma (PSA). Children with PSA have uncontrolled asthma symptoms, despite maximal prescribed asthma treatment. These children have high morbidity and mortality and should be referred for specialist respiratory assessment and management. The first step in the assessment of a child with PSA is confirming the diagnosis of asthma using objective evidence. Following this, an assessment of inhaled corticosteroid adherence and a multi-disciplinary team approach is essential for separating difficult asthma (DA) from severe therapy resistant asthma (STRA). The majority of children have DA which entails uncontrolled asthma symptoms due to underlying modifiable factors including poor treatment adherence, poor inhaler technique, exposure to environmental allergens, co-morbid conditions and psycho-social factors. Approximately 20% of children with PSA have STRA, and have persistent asthma symptoms despite good treatment adherence and correction of modifiable factors. Children with STRA typically have multiple and severe aeroallergen sensitization, eosinophilic airway inflammation and high fraction exhaled nitric oxide (FeNO). Further investigation of children with STRA includes an assessment of systemic steroid responsiveness, this is important for confirming the diagnosis of STRA and guiding the choice of additional treatment. Biologics are an add on (immune targeted) therapy for STRA. The current biologics used in children target the T2 helper (Th2) pathway mediating eosinophilic, allergic asthma. CONCLUSION: Future clinical trials of biologics in children will be essential to help identify childhood specific biomarkers and to decide which biologic is best for which individual child., (Copyright © 2020 by Academy of Sciences and Arts of Bosnia and Herzegovina.)

The aim of this manuscript is to outline an approach to severe asthma, which is among the most challenging problems faced by paediatric pulmonologists. A logical, protocolised approach is essential. The first step is to rule out alternative diagnoses. The next step is a multidisciplinary assessment. Severe, therapy resistant asthma (STRA) is rare, and most of those referred will improve if basic management is corrected, especially adherence to treatment. However some are unable or unwilling to make necessary changes (refractory asthma plus or refractory difficult asthma). Some, especially asthma in the obese, and those thought to have STRA, progress to bronchoscopic airway phenotyping and a parenteral steroid trial to determine an individualised treatment plan. Those with persistent eosinophilc airway inflammation should be considered for omalizumab, and mepolizumab. Pauci-inflammatory asthma remains a therapeutic challenge, with a paucity of evidence; increasing steroid therapy seems neither logical nor efficacious, but options include tiotropium and azithromycin. However the most important message to the paediatrician looking after a child with apprently severe asthma is that the answer is not uncritically escalating treatment, but finding the answer to the question, what is it about this child, and his/her environment, which means there is no response to what should be easily treated airway pathology? The answer usually requires input from a skilled and experienced multi-disciplinary team, without which management is unlikely to be succesful. CONCLUSION: When managing a child with severe asthma, a detailed multi-disciplinary is essential to get the basic management right, before prescribing biologicals., (Copyright © 2020 by Academy of Sciences and Arts of Bosnia and Herzegovina.)

Background: Asthma and non-asthmatic eosinophilic bronchitis (NAEB) are among the commonest causes of chronic cough in adults. We sought to determine the role of non-invasive measurements of airway inflammation, including induced sputum and fractional exhaled nitric oxide, in the evaluation of cough associated with asthma, and what the best treatment is for cough due to asthma or NAEB., Methods: We undertook three systematic reviews of randomized controlled trials and observational trials of adults and adolescents > 12 years of age with a chronic cough due to asthma or NAEB. Eligible studies were identified in MEDLINE, CENTRAL, and SCOPUS and assessed for relevance and quality. Guidelines were developed and voted upon using CHEST guideline methodology., Results: Of the citations reviewed, 3/1,175, 53/656, and 6/134 were identified as being eligible for inclusion in the three systematic reviews, respectively. In contrast to established guidelines for asthma therapies in general and the inclusion in some guidelines for a role of biomarkers of airway inflammation to guide treatment in severe disease, the evidence of specific benefit related to the use of non-invasive biomarkers in patients with chronic cough due to asthma was weak. The best therapeutic option for cough in asthma or NAEB is inhaled corticosteroids followed by leukotriene receptor antagonism., Conclusions: This guideline offers recommendations on the role of non-invasive measurements of airway inflammation and treatment for cough due to asthma or NAEB based on the available literature, and identifies gaps in knowledge and areas for future research., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Eosinophilia is frequently a feature of asthma. Sputum analysis can help with the diagnosis and phenotyping of asthma. The current gold standard method is unsuitable for samples <100 mg. However, children frequently produce samples below this threshold. Aim: To compare and validate our modified, small sample (>10 mg and <100 mg) sputum processing method (which omits sample filtering), with the current gold standard. Method: Prospective study of 32 adults with severe asthma providing sputum samples of sufficient size for dual processing. Results: The median (IQR) sample weight was 211.0 (162.4-185.5) mg and 57.5 (22.0-61.6) mg for standard, and small sputum sample processing respectively. There was no statistically significant difference in the median (IQR) cell counts between Method A and B, respectively: eosinophils 3.8% (1.5-14.0) versus 4.9% (1.3-15.5); neutrophils 78.1% (46.5-92.4) versus 65.0% (48.3-86.6). Conclusion: The small sputum sample processing is feasible and reliable, and yields similar results to standard processing.

The aim of this study has been to evaluate the efficacy of the IL-5 receptor blocker benralizumab on chronic rhinosinusitis with nasal polyposis (CRSwNP), associated with severe eosinophilic allergic asthma. Ten patients with severe eosinophilic allergic asthma and CRSwNP were enrolled. Sino-nasal outcome test (SNOT-22), numerical rating scale (NRS), endoscopic nasal polyp score, Lund Mackey CT (computed tomography) score, and blood eosinophil count were measured at baseline and after 24 weeks of treatment with benralizumab. All the above clinical, endoscopic, imaging, and hematological parameters significantly improved after 24 weeks of treatment with benralizumab. In particular, SNOT-22 decreased from 61.10 ± 17.20 to 26.30 ± 19.74 ( P < 0.001), NRS decreased from 7.20 ± 1.55 to 3.40 ± 2.22 ( P < 0.001), the endoscopic polyp nasal score decreased from 4.20 ± 1.32 to 2.50 ± 1.78 ( P < 0.001), the Lund-Mackay CT score decreased from 16.60 ± 5.50 to 6.90 ± 5.99 ( P < 0.001), and blood eosinophil count decreased from 807.3 ± 271.1 cells/μL to 0 cells/μL ( P < 0.0001). These results strongly suggest that benralizumab exerted a very effective therapeutic action on CRSwNP associated with severe asthma, thus improving nasal symptoms and decreasing polyp size.

Zinc oxide nanoparticles (ZnONPs) are widely used in the manufacturing of many commercial products. Workers exposed to ZnO particles may develop metal fume fever. Our previous study suggested that the oropharyngeal aspiration of ZnONPs could cause eosinophilic airway inflammation and increase T helper 2 (Th2) cytokine expression in the absence of allergens in mice. ZnO has been used topically as a sunscreen and a therapeutic agent for dermatological conditions. To understand whether inhalation and topically applied ZnONPs might cause or exert an adjuvant effect on the development of allergic airway inflammation in mice, C57BL/6 J mice were exposed to filtered air or 2.5 mg/m 3 ZnONPs via whole-body inhalation for 5 h a day over 5 days, and BALB/c mice were topically exposed to ZnONPs using modified mouse models of atopic dermatitis (AD) and asthma. Ovalbumin (OVA) solution was used as an allergen in the topical exposure experiments. A significantly increased eosinophil count and mixed Th1/Th2 cytokine expression were detected in the bronchoalveolar lavage fluid (BALF) after ZnONP inhalation. However, only mild eosinophilia and low Th2 cytokine expression were detected in the BALF after oropharyngeal OVA aspiration in the high-dose ZnONP topical treatment group. These results suggest that ZnONP inhalation might play a role in the development of allergic airway inflammation in mice. However, topically applied ZnONPs only play a limited role in the development of allergic airway inflammation in mice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To identify and characterize asthma with blood eosinophilia in adults. Methods : This cross-sectional study consisted of 164 asthma patients, aged 18 years or older. Multivariate analyses by logistic regression were performed to identify clinical characteristics and biomarkers associated with asthma with blood eosinophilia (defined as asthma and a peripheral blood eosinophil count ≥400 cells/mm 3 ). To evaluate the diagnostic accuracy of these biomarkers, the sensitivity, specificity and predictive values were calculated. Additionally, the area under the receiver operating characteristic (ROC) curve (AUC) was estimated for each biomarker. Results : Overall, 37.8% (95%CI: 30.7-45.4%) of asthma patients had blood eosinophilia. The following factors were associated with this characteristic: patient age <50 years (OR 3.25; 95% CI: 1.33-7.94), a serum level of IgE ≥300 UI/mL (OR 2.32; 95%CI: 1.14-4.75), and an Asthma Control Test (ACT) score <20 points (OR 3.10; 95%CI: 1.35-4.75); asthma with blood eosinophilia was also associated with a baseline FEV 1 /FVC <70% (OR 2.68; 95%CI: 1.28-5.59). On the other hand, age <50 years and ACT score <20 showed the highest sensitivity (above 80% each). Serum IgE level ≥300 UI/mL had the highest specificity (almost 68%). Finally, those with an ACT score <20 had the highest AUC (68%). Conclusions : In our study population, one-third of asthmatic adults had asthma with blood eosinophilia. Furthermore, the prevalence was greater in those ≤50 years of age; these patients experienced more severe, more poorly controlled asthma and had higher total serum IgE levels.

Case Presentation: A previously healthy 45-year-old man was admitted to our ED with a 3-week history of progressive dyspnea on exertion. He also presented with orthopnea, paroxysmal nocturnal dyspnea, and mild ankle swelling, but he showed no fever, wheezing, coughing, or sputum production. Outpatient laboratory studies, performed 1 week after symptom onset, revealed hypereosinophilia (4.100/μL). He was diagnosed with asthma and prescribed inhaled corticosteroids and low-dose prednisone, but he showed no symptomatic improvement. Over the last 48 h, he experienced rapid progression of dyspnea that made it difficult to speak with accompanying resting, substernal, nonradiating chest pain that became worse on inspiration. He had no allergies and reported no recent travels. Before symptom onset, he had not been taking any medication. He denied eating raw fish or meat and had not been exposed to mildew. His only exposure to animals was from his two indoor cats., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Eosinophilic asthma is the most common phenotype of severe asthma. It is characterized by abnormal production and release of type 2 cytokines from T helper type 2 (TH2) lymphocytes and type 2 innate lymphoid cells, such as IL-5. This leads to a persistent increase and activation of eosinophils in blood and the airways despite treatment with high-dose inhaled corticosteroids. Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma. Benralizumab is a monoclonal antibody that binds to IL-5R via its Fab domain, blocking the binding of IL-5 to its receptor and resulting in inhibition of eosinophil differentiation and maturation in bone marrow. In addition, this antibody is able to bind through its afucosylated Fc domain to the RIIIa region of the Fcy receptor on NK cells, macrophages, and neutrophils, thus strongly inducing antibody-dependent, cell-mediated cytotoxicity in both circulating and tissue-resident eosinophils. This double function of benralizumab induces almost complete fast and maintained depletion of eosinophils that is much greater than that induced by other monoclonal antibodies targeting the IL-5 pathway, such as mepolizumab and reslizumab. This review focuses on benralizumab as an alternative to other agents targeting the IL-5 pathway in the treatment of eosinophilic asthma.

Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild-moderate asthma into a T2-high phenotype. We examined whether currently available clinical biomarkers can predict AEC-defined T2-high phenotype within the U-BIOPRED cohort.The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from interleukin (IL)-13-exposed AECs.37% of asthmatics (45% nonsmoking severe asthma, n=49; 33% of smoking or ex-smoking severe asthma, n=18; and 28% mild-moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher exhaled nitric oxide fraction ( F eNO ) and blood and sputum eosinophils, but not serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. F ) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression.T2-high severe asthma can be predicted to some extent from raised levels of eNO (≥30 ppb) and blood eosinophils (≥300 cells·µL -1 ) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression.T2-high severe asthma can be predicted to some extent from raised levels of F eNO , blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors. Better bedside biomarkers are needed to detect T2-high., Competing Interests: Conflict of interest: S. Pavlidis has nothing to disclose. Conflict of interest: K. Takahashi reports personal fees from Asahi General Hospital, during the conduct of the study. Conflict of interest: F. Ng Kee Kwong has nothing to disclose. Conflict of interest: J. Xie has nothing to disclose. Conflict of interest: U. Hoda has nothing to disclose. Conflict of interest: K. Sun has nothing to disclose. Conflict of interest: V. Elyasigomari has nothing to disclose. Conflict of interest: P. Agapow has nothing to disclose. Conflict of interest: M. Loza is employed by Janssen R&D and owns stock in parent company Johnson & Johnson, outside the submitted work. Conflict of interest: F. Baribaud reports being an employee of Janssen R&D and being a share holder of Johnson & Johnson. Conflict of interest: P. Chanez has provided consultancy services for Boehringer Ingelheim, Johnson & Johnson, GlaxoSmithKline, Merck Sharp & Dohme, AstraZeneca, Novartis, Teva, Chiesi, Sanofi and SNCF; served on advisory boards for Almirall, Boehringer Ingelheim, Johnson & Johnson, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi and Sanofi; received lecture fees from Boehringer Ingelheim, Centocor, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, Boston Scientific and ALK; and received industry-sponsored grants from Roche, Boston Scientific, Boehringer Ingelheim, Centocor, GlaxoSmithKline, AstraZeneca, ALK, Novartis, Teva, ABscience and Chiesi. Conflict of interest: S.J. Fowler reports grants from IMI, during the conduct of the study; personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim and Novartis, outside the submitted work. Conflict of interest: D.E. Shaw reports personal fees for advisory board work from GSK, AZ, Teva and Boehringer Ingelheim, outside the submitted work. Conflict of interest: L.J. Fleming reports personal fees for advisory board work from Novartis, Vectura and Boehringer Ingelheim, grants from Asthma UK and BLF, and personal fees for speaking engagements from Novartis, outside the submitted work. Conflict of interest: P.H. Howarth reports grants from IMI, during the conduct of the study; part-time employment by GSK as Global Medical Expert, outside the submitted work. Conflict of interest: A.R. Sousa has nothing to disclose. Conflict of interest: J. Corfield has nothing to disclose. Conflict of interest: C. Auffray reports grants (U-BIOPRED Consortium IMI number 115010) from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: B. De Meulder reports grants (U-BIOPRED Consortium IMI number 115010) from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: R. Knowles is an employee of Knowles Consulting Ltd, outside the submitted work; and is a former employee (to 2011) and current shareholder in GlaxoSmithKline Ltd, and drug discovery consultant for Knowles Consulting Ltd, Peptinnovate Ltd and Imperial College London. Conflict of interest: P.J. Sterk reports grants from Innovative Medicines Initiative (IMI), during the conduct of the study. Conflict of interest: Y. Guo has nothing to disclose. Conflict of interest: I.M. Adcock reports personal fees for advisory board work from GSK, A-Z, Novartis, Boehringer Ingelheim and Vectura, grants from Pfizer, GSK, MRC, EU, BI and IMI, and personal fees for speaking from AZ and BI, outside the submitted work. Conflict of interest: R. Djukanovic reports personal fees for lectures at company sponsored symposia and consulting on advisory boards from TEVA, grants and personal fees for lectures at company sponsored symposia and consulting on advisory boards from Novartis, and personal fees for consultancy from and hold shares in Synairgen, outside the submitted work. Conflict of interest: K.F. Chung reports grants and personal fees for advisory board work from GlaxoSmithKline, personal fees for advisory board work and speaking from AstraZeneca and Novartis, grants and personal fees for advisory board work and speaking from Merck, and personal fees for advisory board work from Boehringer Ingelheim, TEVA and Menlo Therapeutics, outside the submitted work., (Copyright ©ERS 2019.)

Objective: Asthma is a heterogeneous disease composed of multiple disease subtypes. Obesity may worsen asthma, although the mechanism is poorly understood and its effects on different subtypes are not well characterized. We sought to determine whether obesity affects eosinophilic asthma differently from non-eosinophilic asthma., Methods: Charts of 196 persistent asthmatics were reviewed. Subjects were categorized according to BMI (obese ≥ 30 kg/m 2 ) and blood eosinophilia based on two different cutoffs (≥200 or ≥400 cells/µl): eosinophilic, non-obese (E-NO), eosinophilic, obese (E-O), non-eosinophilic, non-obese (NE-NO), and non-eosinophilic, obese (NE-O). We analyzed clinical parameters across these groups to determine associations with obesity and/or eosinophilia., Results: Obesity was highly prevalent in our population (50.5%, 99/196). The majority of asthmatics were female (75.5%), though the ratio was lower in the E-NO group (56%). The NE-NO group was associated with lowest asthma severity, lower atopy, and less medication use. Regardless of eosinophilia, obesity was associated with higher inhaled corticosteroid doses and lower FVC% predicted than their non-obese counterparts. Obesity was associated with reduced FEV1% only in the non-eosinophilic group. Eosinophilia was also associated with reduced FEV1% in the non-obese subjects, but FEV1% was not further reduced in the E-O group compared to the E-NO and NE-O groups. Similar findings were observed regardless of whether the blood eosinophil cutoff was 200 or 400 cells/ µl., Conclusion: Multiple clinical features of asthma are adversely affected by obesity, which may affect eosinophilic and non-eosinophilic subtypes differently.

Most patients with asthma are managed by primary care providers. Severe asthma is associated with substantial morbidity and health care resource use, and long-term sequelae of severe asthma include airway remodeling and a greater risk of developing chronic obstructive pulmonary disease. These consequences highlight the importance of early identification and improved management of patients with severe asthma. Although treatment guidelines can be confusing and it can be difficult to keep abreast of updates, routine assessments of lung function, frequency and severity of exacerbations, symptom control, and medication adherence in the primary care setting provide the necessary information for identifying severe asthma and determining appropriate management strategies. An increased understanding of asthma pathophysiology and its relationship to disease activity has identified therapeutic targets and associated biomarkers. Biologic therapies directed at these targets offer individualized targeted treatment of severe asthma. We review evidence-based guidelines for identification and management of severe asthma, clarify the relationship of asthma control and asthma severity, and provide an overview of new biologic therapies offering additional treatment options for patients with severe asthma., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)