Search

Background: Several major sensitization profiles have been described in children with asthma, but it remains unclear how these profiles relate to asthma phenotypes. The aim of this study was to determine allergenic sensitization profiles in a megacity cohort (SAMP). Methods: This was a cross‐sectional analysis performed from 2011 to 2015 including preschool and school‐age children with severe and moderate asthma from the SAMP cohort. We performed ALEX multiplex array and carried out cluster analysis. Results: Data from 367 children were analyzed: 224 of preschool age and 143 of school age, respectively 84 (38%) and 114 (80%) presented at least one allergic sensitization. At preschool age, three clusters were identified: Cluster 1, Few sensitizations to inhaled allergen molecular families and non‐type 2 (T2) inflammation (n = 61); Cluster 2, Predominant sensitization to HDM molecular families (n = 16); Cluster 3, Severe asthma with multiple sensitizations to inhaled and food allergen molecular families (n = 7). At school age, five clusters were identified: Cluster 1, Few sensitizations to inhaled allergen molecular families and non‐T2 inflammation (n = 43); Cluster 2, Predominant sensitization to HDM molecular families (n = 31); Cluster 3, Predominant sensitization to PR‐10 protein family (n = 25); Cluster 4, Severe asthma with predominant sensitization to tropomyosin family (n = 11); Cluster 5, Severe asthma with multiple sensitizations to inhaled and food allergen molecular families (n = 4). Conclusion: These results underline the heterogeneity of sensitization profiles in severe allergic childhood asthma. The most severe asthma phenotypes were associated with multiple sensitizations to both inhaled and food allergen molecular families as expected, and to the tropomyosin molecular family, a novel finding. [ABSTRACT FROM AUTHOR]

(1) Background: Asthma exacerbations represent significant clinical events, however, the underlying inflammatory mechanisms and cytokine profiles in patients with frequent exacerbations remain incompletely understood; (2) Methods: In this prospective, cross-sectional study of 120 stable asthma patients, we compared the serum concentrations of eight key cytokines (IL-4, IL-12, IL-13, IL-17, IFN-α, IFN-γ, TNF-α, and IL-1β) between two groups: 60 patients with frequent exacerbations (≥ 2 events per year) and 60 matched controls with few exacerbations (1 event per year); (3) Results: Patients with frequent exacerbations showed significantly higher serum concentrations of IL-4 and IL-13 (p < 0.05), along with an increased prevalence of allergic history and comorbidities (chronic rhinosinusitis, GERD, OSA; all p < 0.05). The IgE levels correlated positively with IFN-α (rh = 0.26) and TNF-α (rh = 0.29), while the FeNO levels correlated with IL-17 (rh = 0.26) and IL-1β (rh = 0.33) (all p < 0.05); (4) Conclusions: Our findings identify a distinct cytokine signature in frequent exacerbators characterized by elevated IL-4 and IL-13 levels. The correlations between specific cytokines and established biomarkers suggest potential mechanisms underlying exacerbation susceptibility, which may inform targeted therapeutic strategies for this high-risk population.

Background: Asthma is a heterogeneous inflammatory disease with two main clinical endotypes: type 2 (T2) high and low asthma. The plasticity and autophagy in dendritic cells (DCs) influence T helper (Th)2 or Th17 differentiation to regulate asthma endotypes. Enhanced autophagy in DCs fosters Th2 differentiation in allergic environments, while reduced autophagy favors Th17 cell differentiation in sensitized and infected environments. Autophagy regulation in DCs involves interaction with various pathways like G protein‐coupled receptor (GPCR), mammalian target of rapamycin (mTOR), or phosphoinositide 3‐kinase (PI3K) pathway. However, specific molecules within DCs influencing asthma endotypes remain unclear. Methods: Gene expression data series (GSE) 64896, 6858, 2276, and 55247 were obtained from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CD103+ and CD11b+ DCs after induction by ovalbumin (OVA) and lipopolysaccharide (LPS) were analyzed using GEO2R. DEGs were examined through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) analyses. The hub gene network was construct with STRING database and Cytoscape. Autophagy differences in DCs and the selected hub gene in GSE6858, GSE2276, and GSE55247 were evaluated using student t tests. Results: Our analysis identified 635 upregulated and 360 downregulated genes in CD11b+ DCs, compared to CD103+ DCs. These DEGs were associated with "PI3K‐AKT signaling pathway," "Ras signaling pathway," and so forth. Thirty‐five hub genes were identified, in which G protein subunit gamma transduction protein 2 (Gngt2) in CD11b+ DCs exhibited a relatively specific increase in expression associated with autophagy defects under the induction environment similar to T2 low asthma model. No significant difference was found in lung Gngt2 expression between T2 high asthma model and control group. Conclusion: Our analysis suggested Gngt2 acted as an adapter molecule that inhibited autophagy, promoting Th17‐mediated airway inflammation via the GPCR pathway in a T2 low asthma mice model. Targeting this pathway provides new asthma treatment strategies in preclinical research. [ABSTRACT FROM AUTHOR]

Asthma is a common chronic inflammatory disease of the lungs and airway, yet its inflammatory subtypes and potential pathogenesis have not been completely elucidated and require further study. With advances in epigenetic development, methylation has emerged as a new direction for identifying and decoding the occurrence and subtype manifestations of asthma. N6-methyladenosine (m6A), an RNA methylation modification occurring in the N6-position of adenosine, is a prevalent epigenetic modification observed in eukaryotes. It exerts significant control over mRNA metabolism by regulating alternative splicing, stability, export, and translation. The dynamic process of m6A methylation plays a crucial role in the pathogenesis of asthma and is tightly regulated by three types of regulators: writers, readers, and erasers. This article provides a comprehensive review of the association between m6A regulators and the pathogenesis of inflammatory subtypes of asthma, such as involvement of inflammatory cells and related inflammatory response. Furthermore, the findings presented herein provide new insights and a solid foundation for further research on m6A mRNA methylation as biomarkers for the diagnosis and development of personalized treatment for different subtypes of asthma, particularly neutrophilic asthma and eosinophilic asthma. [ABSTRACT FROM AUTHOR]

Abstract Background Since the last guidance was published by the Canadian Thoracic Society, there have been several advances in the clinical management of severe asthma. To gain a better understanding of the current standards of care and treatment patterns of patients, the CASCADE practice reflective program was established to conduct a real-world analysis of severe asthma management among specialists in Canada with a goal of identifying areas of opportunity to enhance patient management and outcomes. Methods The CASCADE program was a two-part practice reflective and assessment program delivered through an on-line portal for selected specialists (Respirologists and Allergists) in Canada. The program consisted of a one-time overview survey of physician practice to establish overall practice parameters, followed by a review of at least 5 severe asthma patients to establish the current landscape of severe asthma management. Results The program collected practice overview surveys from 78 specialists (52 Respirologists, 24 Allergists, and 2 General practice physicians with an interest in respiratory disease) in 8 provinces. Practices included a variety of types in both large metropolitan centres and smaller regional settings. There were 503 patients reviewed and included in the program. Most (65%) patients were currently using a biologic treatment, 30% were biologic naive, and 5% had used a biologic treatment in the past. Most patients (53%) were reported to have mixed allergic and eosinophilic phenotypes, despite a perception that allergic, eosinophilic and mixed phenotypes were evenly balanced in the physician practice. Overall, patients currently treated with biologic agents had parameters suggesting higher control and were more satisfied with treatment. However, there was less than optimal treatment satisfaction for more than half of all patients, particularly for those patients not treated with a biologic agent. Conclusions Phenotyping is hampered by poor availability for several assessments, and the full range of treatments are not currently fully utilized, partly due to physician familiarity with the agents and partly due to prescribing restrictions. Even when treated with biologic agents, patient satisfaction can still be improved.

Abstract Background DEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are “non-atopic”, lacking a clear etiology. Methods In a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman’s rank correlation coefficients, multiple logistic regression, and multinomial logistic regression. Results Asthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified. Conclusion The current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies.

Background: Since the last guidance was published by the Canadian Thoracic Society, there have been several advances in the clinical management of severe asthma. To gain a better understanding of the current standards of care and treatment patterns of patients, the CASCADE practice reflective program was established to conduct a real-world analysis of severe asthma management among specialists in Canada with a goal of identifying areas of opportunity to enhance patient management and outcomes. Methods: The CASCADE program was a two-part practice reflective and assessment program delivered through an on-line portal for selected specialists (Respirologists and Allergists) in Canada. The program consisted of a one-time overview survey of physician practice to establish overall practice parameters, followed by a review of at least 5 severe asthma patients to establish the current landscape of severe asthma management. Results: The program collected practice overview surveys from 78 specialists (52 Respirologists, 24 Allergists, and 2 General practice physicians with an interest in respiratory disease) in 8 provinces. Practices included a variety of types in both large metropolitan centres and smaller regional settings. There were 503 patients reviewed and included in the program. Most (65%) patients were currently using a biologic treatment, 30% were biologic naive, and 5% had used a biologic treatment in the past. Most patients (53%) were reported to have mixed allergic and eosinophilic phenotypes, despite a perception that allergic, eosinophilic and mixed phenotypes were evenly balanced in the physician practice. Overall, patients currently treated with biologic agents had parameters suggesting higher control and were more satisfied with treatment. However, there was less than optimal treatment satisfaction for more than half of all patients, particularly for those patients not treated with a biologic agent. Conclusions: Phenotyping is hampered by poor availability for several assessments, and the full range of treatments are not currently fully utilized, partly due to physician familiarity with the agents and partly due to prescribing restrictions. Even when treated with biologic agents, patient satisfaction can still be improved. [ABSTRACT FROM AUTHOR]

Background: DEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are "non-atopic", lacking a clear etiology. Methods: In a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman's rank correlation coefficients, multiple logistic regression, and multinomial logistic regression. Results: Asthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified. Conclusion: The current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies. [ABSTRACT FROM AUTHOR]

Asthma is a common chronic heterogeneous disease. Outdoor air pollutants are an important cause of acute asthma. Until now, the association between the risk of acute asthma and outdoor air pollutants is unclear. And the relationship between the different phenotypes of asthma and outdoor air pollutants has not been reported. Thus, an analysis of the association between outdoor air pollutants and daily acute asthma inpatient and outpatient visits in Xi'an, China, from January 1 to December 31, 2018, was conducted. A total of 3395 people were included in the study. The statistical analysis and relational analysis based on the logistic regression were used for illustrating the relatedness of the acute asthma risk factor and phenotype with outdoor air pollutants, while the age, gender, pollen peak and non-pollen peak periods, high type 2 (T2) asthma and non-high T2 asthma were also stratified. Results showed that particulate matter with particle size below 10 μm and 2.5 μm (PM10 and PM2.5), sulfur dioxide(SO2), nitrogen dioxide(NO2), and carbon monoxide(CO) increase the risk of acute asthma and that air pollutants have a lagged effect on asthma patients. PM10, NO2, CO, and Ozone (O3) are associated with an increased risk of acute attacks of high T2 asthma. PM10, PM2.5, SO2, NO2 and CO are associated with an increased risk of acute asthma in males of 0–16 years old. PM10 and PM2.5 are more harmful to asthma patients with abnormal lung function. [ABSTRACT FROM AUTHOR]

Asthma is a common chronic inflammatory disease of the lungs and airway, yet its inflammatory subtypes and potential pathogenesis have not been completely elucidated and require further study. With advances in epigenetic development, methylation has emerged as a new direction for identifying and decoding the occurrence and subtype manifestations of asthma. N6-methyladenosine (m6A), an RNA methylation modification occurring in the N6-position of adenosine, is a prevalent epigenetic modification observed in eukaryotes. It exerts significant control over mRNA metabolism by regulating alternative splicing, stability, export, and translation. The dynamic process of m6A methylation plays a crucial role in the pathogenesis of asthma and is tightly regulated by three types of regulators: writers, readers, and erasers. This article provides a comprehensive review of the association between m6A regulators and the pathogenesis of inflammatory subtypes of asthma, such as involvement of inflammatory cells and related inflammatory response. Furthermore, the findings presented herein provide new insights and a solid foundation for further research on m6A mRNA methylation as biomarkers for the diagnosis and development of personalized treatment for different subtypes of asthma, particularly neutrophilic asthma and eosinophilic asthma.

The astounding number of genetic variants revealed in the 15 years of genome-wide association studies of asthma has not kept pace with the goals of translational genomics. Moving asthma diagnosis from a nonspecific umbrella term to specific phenotypes/endotypes and related traits may provide insights into features that may be prevented or alleviated by therapeutical intervention. This review provides an overview of the different asthma endotypes and phenotypes and the genomic findings from asthma studies using patient stratification strategies and asthma-related traits. Asthma genomic research for treatable traits has uncovered novel and previously reported asthma loci, primarily through studies in Europeans. Novel genomic findings for asthma phenotypes and related traits may arise from multi-trait and specific phenotyping strategies in diverse populations. [ABSTRACT FROM AUTHOR]

Background: Multidisciplinary systematic assessment improves outcomes in difficult‐to‐treat asthma, but without clear response predictors. Using a treatable‐traits framework, we stratified patients by trait profile, examining clinical impact and treatment responsiveness to systematic assessment. Methods: We performed latent class analysis using 12 traits on difficult‐to‐treat asthma patients undergoing systematic assessment at our institution. We examined Asthma Control Questionnaire (ACQ‐6) and Asthma Quality of Life Questionnaire (AQLQ) scores, FEV1, exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment. Results: Among 241 patients, two airway‐centric profiles were characterized by early‐onset with allergic rhinitis (n = 46) and adult onset with eosinophilia/chronic rhinosinusitis (n = 60), respectively, with minimal comorbid or psychosocial traits; three non‐airway‐centric profiles exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance (n = 51), psychosocial (anxiety, depression, smoking, unemployment) dominance (n = 72), or multi‐domain impairment (n = 12). Compared to airway‐centric profiles, non‐airway‐centric profiles had worse baseline ACQ‐6 (2.7 vs. 2.2, p <.001) and AQLQ (3.8 vs. 4.5, p <.001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway‐centric profiles had more FEV1 improvement (5.6% vs. 2.2% predicted, p <.05) while non‐airway‐centric profiles trended to greater exacerbation reduction (1.7 vs. 1.0, p =.07); mOCS dose reduction was similar (3.1 mg vs. 3.5 mg, p =.782). Conclusion: Distinct trait profiles in difficult‐to‐treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult‐to‐treat asthma, offer a conceptual framework to address disease heterogeneity, and highlight areas responsive to targeted intervention. [ABSTRACT FROM AUTHOR]

Background: Small population group-based cohorts have found that perinatal factors may contribute to the development of asthma in children. We aimed to investigate maternal and neonatal risk factors for the asthma phenotypes using two databases from the Taiwan's Maternal and Child Health Database (TMCHD) and the National Health Insurance Research Database (NHIRD). Methods: Perinatal data was obtained from 2004 to 2008 in the TMCHD and linked the NHIRD to obtain relevant medical information regarding maternal and neonatal risk factors of three asthma phenotypes which were identified as transient early asthma, persistent asthma, and late-onset asthma. A multivariate logistic regression analysis was conducted to adjust for covariates. Results: The percentage of non-asthmatic patients was 77.02% and asthmatic (transient early asthma, late onset asthma, and persistent asthma) patients were 8.96%, 11.64%, and 2.42%, respectively. Maternal risk factors—including Cesarean section, maternal asthma, maternal allergic rhinitis (AR), and premature rupture of membranes—and neonatal risk factors, such as male gender, gestational age 29–37 weeks, ventilator use, antibiotics use, AR, and atopic dermatitis, were associated with the development of these three asthma phenotypes. Twins and a gestational age of 28 weeks or less premature were associated with the development of transient early asthma and persistent asthma, but not late onset asthma. Triplets and above were associated with the development of transient early asthma, but not late onset or persistent asthma. Conclusion: Various asthma phenotypes have different risk factors; therefore, their distinct risk factors should be identified in order to early diagnosis and treatment.

Rationale: Corticosteroids (CSs) are the most effective asthma therapy, but responses are heterogeneous and systemic CSs lead to long-term side effects. Therefore, an improved understanding of the contributing factors in CS responses could enhance precision management. Although several factors have been associated with CS responsiveness, no integrated/cluster approach has yet been undertaken to identify differential CS responses. Objectives: To identify asthma subphenotypes with differential responses to CS treatment using an unsupervised multiview learning approach. Methods: Multiple-kernel k-means clustering was applied to 100 clinical, physiological, inflammatory, and demographic variables from 346 adult participants with asthma in the Severe Asthma Research Program with paired (before and 2-3 weeks after triamcinolone administration) sputum data. Machine-learning techniques were used to select the top baseline variables that predicted cluster assignment for a new patient. Measurements and Main Results: Multiple-kernel clustering revealed four clusters of individuals with asthma and different CS responses. Clusters 1 and 2 consisted of young, modestly CS-responsive individuals with allergic asthma and relatively normal lung function, separated by contrasting sputum neutrophil and macrophage percentages after CS treatment. The subjects in cluster 3 had late-onset asthma and low lung function, high baseline eosinophilia, and the greatest CS responsiveness. Cluster 4 consisted primarily of young, obese females with severe airflow limitation, little eosinophilic inflammation, and the least CS responsiveness. The top 12 baseline variables were identified, and the clusters were validated using an independent Severe Asthma Research Program test set. Conclusions: Our machine learning-based approaches provide new insights into the mechanisms of CS responsiveness in asthma, with the potential to improve disease treatment.

Objective: Childhood bronchial asthma (BA) is a globally significant chronic disease with major health consequences. Recently, focus on the role of the innate immune system has been highlighted. Therefore, this study explores the role of circulating monocytes and natural killer (NK) clusters in childhood asthma. Methods: This case-control study enrolled 50 children with asthma divided equally into severe and mild groups and 26 healthy children. Flow-cytometry analysis was used to identify circulating blood monocytes and natural killers' subsets. In addition, pulmonary function test (spirometry) for children with asthma was performed. Results: This study showed significant negative correlations between frequency of total circulating, classical, intermediate, and nonclassical monocytes with ratio of forced expiratory volume/forced vital capacity (FEV1/FVC) (r = −0.637, P < 0.001; r = −0.575, P < 0.001; r = −0.657, P < 0.001; r = −0.329, P = 0.004, respectively). Also, there was significant negative correlations between frequency of total NKs and CD56dim CD16+ NK with FEV1/FVC (r = −0.584, P < 0.001) and (r = −0.579, P < 0.001). Significant predictors of childhood asthma severity were frequencies of total monocytes, total NKs, intermediate monocytes, and CD56dimCD16+ NK. Conclusion: Finally, we concluded that the FEV1/FVC is linked to aberrations of monocytes' and natural killers' immunophenotypic subsets in children with asthma. The frequencies of total monocytes and NK are significant predictors of severity of childhood asthma. The frequencies of CD14high CD16+ intermediate monocytes and CD56dim CD16+ NK cells are the best independent predictors of severity in children with asthma. [ABSTRACT FROM AUTHOR]

Alicia Habernau Mena,1,&ast; Ismael García-Moguel,2,3,&ast; María Vazquez de la Torre Gaspar,4 Victoria Mugica,5 Maria Isabel Alvarado Izquierdo,6 Maria Aranzazu Jimenez Blanco,7 Mar Gandolfo-Cano,8 Mar Jiménez Lara,9 Ana Gonzalez Moreno,10 Pilar Saura Foix,11 Ana Navarro-Pulido,12 Cristina Martin-Arriscado Arroba,13 Julio Delgado Romero,14 Javier Dominguez-Ortega15 On behalf of Asthma Committee of SOCIEDAD ESPAÑOLA DE ALERGOLOGÍA E INMUNOLOGÍA CLÍNICA (SEAIC)1Department of Allergy. Complejo Hospitalario de Mérida, Mérida, Spain; 2Department of Allergy, Hospital Universitario 12 de Octubre, Madrid, Spain; 3Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas 12), Madrid, Spain; 4Department of Allergy, Hospital Universitario Infanta Leonor, Madrid, Spain; 5Department of Allergy, Hospital de la Princesa, Madrid, Spain; 6Department of Allergy, Hospital Universitario de Cáceres, Cáceres, Spain; 7Department of Allergy, Hospital Cruz Roja, Madrid, Spain; 8Department of Allergy, Hospital Universitario de Fuenlabrada, Madrid, Spain; 9Department of Allergy, Hospital de Toledo, Toledo, Spain; 10Department of Allergy, Fundación Hospital Alcorcón, Madrid, Spain; 11Department of Allergy, Consorci Sanitari de Terrassa, Terrassa, Spain; 12Allergology Clinical Management Unit (UGC), El Tomillar Hospital, Sevilla, Spain; 13Research and Science Support Unit, Instituto de investigación Biomédica del Hospital Universitario 12 de Octubre I+12, Madrid, Spain; 14Department of Allergy, Hospital Universitario Virgen Macarena, Sevilla, Spain; 15Department of Allergy, Hospital Universitario La Paz. Instituto de Investigación (idiPaz), Madrid, Spain&ast;These authors contributed equally to this workCorrespondence: Ismael García-Moguel, Department of Allergy, Hospital Universitario 12 de Octubre, Av de Córdoba s/n, Zip code 28005, Madrid, Spain, Tel +34-645852229, Email Ismaelgmoguel@gmail.comPurpose: The acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a high impact on patients with chronic diseases. In the literature, there are different perspectives on asthma as comorbidity or risk factor on COVID-19 severity.Patients and Methods: The aim of this retrospective study across 13 allergy departments in Spain was to determine the severity of COVID-19 in asthmatic adults followed in allergy departments and its relationship with atopy, clinical and demographic characteristics, phenotypes and laboratory data. In addition, lung function test and asthma control test (ACT) before and after COVID-19 were analyzed. Data was obtained from electronic medical records from March 2020 to April 2021.Results: Two hundred one asthmatic patients were diagnosed with COVID-19 infection by validated detection test. About 30% of the patients were admitted for bilateral pneumonia. Advanced age, elevated D-dimer, lower numbers of lymphocytes and eosinophils, heart diseases and hypertension were associated with severe COVID-19. Allergic and mixed allergic/eosinophilic phenotype and their biomarkers (total IgE, aeroallergens sensitizations, allergic rhinitis, and blood eosinophilia) were related to fewer hospital admissions. Poor control and lower forced expiratory volume in the first second (FEV1) were related to worse prognosis of COVID-19.Conclusion: Asthmatic patients with allergic and eosinophilic phenotype have a better evolution of COVID-19 and lower risk of admissions. Older patients, cardiovascular comorbidities, AERD and eosinopenia are related to severity COVID-19.Keywords: COVID-19, allergic asthma, eosinophils, asthma phenotype, SARS-CoV-2

Luis Pérez de Llano, David Dacal Rivas, Nagore Blanco Cid, Irene Martin Robles Head of the Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Monforte, Cervo. C/ Doctor Ulises Romero, nº 1, Lugo, 27003, SpainCorrespondence: Luis Pérez de LlanoHead of the Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Monforte, Cervo, C/Doctor Ulises Romero, nº 1, Lugo, 27003, SpainTel +34 982296000Email eremos262@hotmail.comAbstract: Despite recent advances in therapy, a substantial proportion of asthmatics remain not well controlled. The classical stepwise approach to pharmacological therapy in adult asthma recommends that treatment is progressively stepped up by increasing the inhaled corticosteroid (ICS) dose or by adding another controller medication- to achieve symptom control and reduce the risk of exacerbations, and stepped down after a period of control. In general, asthma guideline recommendations do not reflect that there are significant differences between ICS in terms of potency. Moreover, they do not consider efficacy and safety separately, incorrectly assuming that “low” and “high” dose categories inevitably correspond with low and high risk of systemic effects. Another point of criticism is the fact that guidelines do not take into account the inflammatory profile of the patient, although substantial groups of patients with mild and moderate asthma have little evidence of “T2-high” inflammation, and by extension are likely to show a poor response to ICS treatment. On the other hand, the latest version of the Global Initiative for Asthma (GINA) equally recommends regular ICS and ICS/formoterol as needed to prevent exacerbations in step 2 patients, without taking into consideration that the therapeutic objectives (exacerbations, symptoms) may differ between individual patients and that different goals may warrant distinct treatment strategies. In this review, we bring to the table several controversial issues concerning asthma treatment and suggest an alternative proposal that takes into consideration the potential side effects of high ICS doses, the patient’s inflammatory profile and the therapeutic goals to be achieved.Keywords: asthma, asthma treatment, asthma phenotype, asthma endotype, personalized medicine

BackgroundPhenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications.MethodsThe Individualized Therapy for Asthma in Toddlers study was a multicenter, randomized, double-blind, double-dummy clinical trial in children aged 12 to 59 months (n = 300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2- to 8-week run-in period followed by 3 crossover periods with daily inhaled corticosteroids (ICSs), daily leukotriene receptor antagonists, and as-needed ICS treatment coadministered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved 2 stages: determination of differential response and assessment of whether 3 prespecified features (aeroallergen sensitization, previous exacerbations, and sex) predicted a differential response.ResultsSeventy-four percent (170/230) of children with analyzable data had a differential response to the 3 treatment strategies. Within differential responders, the probability of best response was highest for a daily ICS and was predicted by aeroallergen sensitization but not exacerbation history or sex. The probability of best response to daily ICS was further increased in children with both aeroallergen sensitization and blood eosinophil counts of 300/μL or greater. In these children daily ICS use was associated with more asthma control days and fewer exacerbations compared with the other treatments.ConclusionsIn young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophil counts is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with a daily ICS is beneficial despite possible risks of growth suppression.

Background: An orosomucoid-like 3 (ORMDL3)/gasdermin B (GSDMB) gene locus on chromosome 17q is consistently associated with childhood-onset asthma, which is highly atopic. As some evidence suggests the relationship between asthma and allergic sensitization reflects asthma patient susceptibility to augmented IgE responses driven by common environmental allergens rather than an increased asthma risk after allergen exposure, we aimed to determine any relationships between this locus region and childhood-onset adult asthma with regard to serum total IgE levels or allergic sensitization. Methods: We conducted a case–control association study using three independent Japanese populations (3869 total adults) and analyzed the ORs for association of rs7216389, an expression quantitative trait locus for ORMDL3/GSDMB, with adult asthma according to onset age. Additionally, associations between the rs7216389 genotype and total serum IgE levels or allergic sensitization was examined. Results: Rs7216389 was associated with both childhood-onset adult asthma (OR for asthmatic patients afflicted at the age of 10 years or younger = 1.61, p = 0.00021) and asthmatic patients with higher levels of total serum IgE (OR for asthmatic patients with IgE ≥1000IU/mL = 1.55, p = 0.0033). In both healthy controls and in the combined healthy and asthmatic individuals, rs7216389 was correlated with increased total serum IgE levels (p 0.1). Conclusions: ORMDL3/GSDMB is an important susceptibility gene for childhood-onset adult asthma in Japanese populations and this association is linked to elevated total serum IgE levels but not to allergic sensitization.

Background: Asthma exacerbation (AE) leads to social and economic costs and long‐term adverse outcomes. We aimed to predict exacerbation‐prone asthma (EPA) in children. Methods: The Korean childhood Asthma Study (KAS) is a prospective nationwide pediatric asthma cohort of children aged 5–15 years followed every 6 months. Patients with AE during the 6 months prior to all three visits, with AE prior to one or two visits, and without AE prior to any visit were defined as having EPA, exacerbation‐intermittent asthma (EIA), and exacerbation‐resistant asthma (ERA), respectively. Risk factors and prediction models of EPA were explored. Results: Of the 497 patients who completed three visits, 42%, 18%, and 15% had exacerbations prior to visits 1, 2, and 3 and 5%, 47%, and 48% had EPA, EIA, and ERA, respectively. Univariate and multivariable logistic regression revealed forced expiratory volume in 1 s (FEV1) z‐score, forced vital capacity (FVC) z‐score, white blood cell (WBC) count, and asthma control test (ACT) score as relevant EPA risk factors. The EPA prediction model comprised FVC z‐score, WBC count, ACT score, sex, and parental education level (area under the receiver operating characteristic curve [AUROC] 0.841 [95% confidence interval (CI): 0.728–0.954]). Conclusion: With appropriate management, AE decreases over time, but persistent AEs may occur. Apart from asthma control level, baseline lung function and WBC count predicted EPA. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to investigate the frequency and sociodemographic and clinical distinguishing features of asthmatic patients in whom long-acting muscarinic antagonists (LAMA) were added to maintenance therapy in our clinic., Methods: In this cross-sectional study, data on sociodemographic, phenotypic, and clinical characteristics of patients with asthma using Steps 4 and 5 medications, who were followed up in our center for at least 1 year, were obtained from file records. Whether the patients received add-on LAMA for at least 6 months was also noted., Results: A total of 279 patients with asthma using Steps 4 and 5 medications (female/male: 215/64) with a mean age of 50.84 ± 12.42 years were included in the study. Seventy-nine (28.3%) patients (female/male: 60/19) with a mean age of 52.45 ± 11.61 years used LAMA as an add-on treatment; 28 (37.8%) at Step 4 and 51 (24.8%) at Step 5. In Steps 4 and 5, there was no difference in terms of age, sex, body mass index, smoking status, being allergic or eosinophilic, phenotype, and asthma onset between patients with and without add-on LAMA. Asthma control in the previous year was better, and minimum forced expiratory volume in 1s (FEV1) was lower in patients with LAMA than in those without in Step 4 (P = 0.001 and P = 0.030, respectively). In Step 5, the rate of being well-controlled was higher in those without add-on LAMA (P < 0.001). The number of exacerbations in the previous year was higher, and minimum and maximum FEV1 were lower in patients with add-on LAMA (P < 0.001 and P < 0.001, respectively)., Conclusion: Our study showed that add-on LAMA treatment was effective in increasing asthma control in patients using Step 4 medication independent of baseline characteristics and asthma phenotype., Competing Interests: The authors have no conflicts of interest to declare.

Several endotypes of severe asthma with predominantly type 2 inflammation can be distinguished by the immune pathways driving the inflammatory processes. However, in the absence of type 2 inflammation, asthma is less clearly defined and is generally associated with poor responses to conventional anti-asthmatic therapies. Studies have shown that disruption of the epithelial barrier triggers inflammatory responses and increases epithelial permeability. A key aspect of this process is that epithelial cells release alarmin cytokines, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), in response to allergens and infections. Among these cytokines, TSLP has been identified as a potential therapeutic target for severe asthma, leading to the development of a new biologic, tezepelumab (TZP). By blocking TSLP, TZP may produce wide-ranging effects. Based on positive clinical trial results, TZP appears to offer a promising, safe, and effective treatment approach. This narrative review examines the evidence for treating severe asthma with TZP, analyses clinical trial findings, and provides clinicians with practical insights into identifying patients who may respond best to this novel biologic therapy., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Purpose: The acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a high impact on patients with chronic diseases. In the literature, there are different perspectives on asthma as comorbidity or risk factor on COVID-19 severity. Patients and Methods: The aim of this retrospective study across 13 allergy departments in Spain was to determine the severity of COVID-19 in asthmatic adults followed in allergy departments and its relationship with atopy, clinical and demographic characteristics, phenotypes and laboratory data. In addition, lung function test and asthma control test (ACT) before and after COVID-19 were analyzed. Data was obtained from electronic medical records from March 2020 to April 2021. Results: Two hundred one asthmatic patients were diagnosed with COVID-19 infection by validated detection test. About 30% of the patients were admitted for bilateral pneumonia. Advanced age, elevated D-dimer, lower numbers of lymphocytes and eosinophils, heart diseases and hypertension were associated with severe COVID-19. Allergic and mixed allergic/eosinophilic phenotype and their biomarkers (total IgE, aeroallergens sensitizations, allergic rhinitis, and blood eosinophilia) were related to fewer hospital admissions. Poor control and lower forced expiratory volume in the first second (FEV1) were related to worse prognosis of COVID-19. Conclusion: Asthmatic patients with allergic and eosinophilic phenotype have a better evolution of COVID-19 and lower risk of admissions. Older patients, cardiovascular comorbidities, AERD and eosinopenia are related to severity COVID-19. [ABSTRACT FROM AUTHOR]

Background: Traffic-related pollution is associated with the onset of asthma and the development of different phenotypes of asthma. Few studies have investigated the association between traffic proximity and late-onset of asthma (LOA) and early-onset asthma (EOA). This study was conducted to investigate the associations of LOA phenotypes with a function of the distance between residence and heavy traffic roads (HTRs).Methods: The study group consisted of 280 patients who were (LOA: 78.4%) recruited consecutively from a pay-for-performance asthma program to clarify the patient characteristics and proximity to HTRs within 1,000 m from their residences between EOA and LOA in three urban centers in Taiwan. The subsequent analysis focused on patients with LOA (n = 210) linking phenotypes and distance to HTRs.Results: Subjects with LOA tended to be older than those with EOA and had shorter asthma duration, poorer lung function, lower atopy, and less exposure to fumes or dust at home. Patients with LOA were more likely than those with EOA to live within 900 m of two or more HTRs (14.3 vs. 3.4%, p = 0.02). Among patients with LOA, minimum distance to an HTR was negatively associated with numbers of specific IgE as well as positively associated with the age of onset and body weight significantly. A higher proportion of patients with atopy (26.3 vs. 20.6%, p = 0.001. odds ratio [OR]: 2.82) and anxiety/depression (21.0 vs. 18.1%, p = 0.047. OR: 1.81) and a trend of lower proportion of patients with obese (5.7 vs. 12.4%, p = 0.075) were found to be living within 900 m from HTRs.Conclusions: Late-onset of asthma (LOA) tended to live in areas of higher HTR density compared to EOAs. Among patients with LOA living close to HTRs, the interaction between traffic-related pollution, allergy sensitization, and mood status were the factors associated with asthma onset early. Obesity may be the factor for later onset who live far from HTRs.

Background: Asthma is a heterogeneous disease in which the interaction between genetic and environmental factors plays a major role. The significance of blood eosinophil is unclear. The aim of the study was to determine the significance of blood eosinophil count in moderate‐to‐severe asthmatic children of preschool age and school age. Methods: This was a prospective cross‐sectional study performed from 2011 to 2015 including children from the severe asthma molecular phenotype (SAMP) cohort at Trousseau Hospital (Paris, France). We included children with severe and moderate asthma, or severe and moderate recurrent wheeze, aged from 1 to 15 years at the time of exploration. Results: We analyzed data from 402 children: 248 of preschool age and 154 of school age. Blood eosinophil count third quartile thresholds were 322 and 600 cells/μL for the preschool‐ and school‐age groups, respectively. In multivariate analysis, a blood eosinophil count over this threshold was associated with elevated total IgE (OR = 5.33, P <.01), multiple hospitalizations for asthma attacks (OR = 4.96, P =.03), and a maternal history of asthma (OR = 4.91, P =.01) in preschool children; and with staphylococcal toxin–specific IgE (OR = 2.75, P =.03) in children of school age. Random forest analysis reinforced these results. Conclusion: High blood eosinophil count is linked to both atopic features and control of asthma with different parameters associated with these features depending on age. [ABSTRACT FROM AUTHOR]

Despite recent advances in therapy, a substantial proportion of asthmatics remain not well controlled. The classical stepwise approach to pharmacological therapy in adult asthma recommends that treatment is progressively stepped up by increasing the inhaled corticosteroid (ICS) dose or by adding another controller medication- to achieve symptom control and reduce the risk of exacerbations, and stepped down after a period of control. In general, asthma guideline recommendations do not reflect that there are significant differences between ICS in terms of potency. Moreover, they do not consider efficacy and safety separately, incorrectly assuming that "low" and "high" dose categories inevitably correspond with low and high risk of systemic effects. Another point of criticism is the fact that guidelines do not take into account the inflammatory profile of the patient, although substantial groups of patients with mild and moderate asthma have little evidence of "T2-high" inflammation, and by extension are likely to show a poor response to ICS treatment. On the other hand, the latest version of the Global Initiative for Asthma (GINA) equally recommends regular ICS and ICS/formoterol as needed to prevent exacerbations in step 2 patients, without taking into consideration that the therapeutic objectives (exacerbations, symptoms) may differ between individual patients and that different goals may warrant distinct treatment strategies. In this review, we bring to the table several controversial issues concerning asthma treatment and suggest an alternative proposal that takes into consideration the potential side effects of high ICS doses, the patient's inflammatory profile and the therapeutic goals to be achieved. [ABSTRACT FROM AUTHOR]

Ignacio Esteban-Gorgojo,1 Darío Antolín-Amérigo,2 Javier Domínguez-Ortega,3,4 Santiago Quirce3,4 1Department of Allergy, Hospital General de Villalba, Madrid, Spain; 2Department of Allergy, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain; 3Department of Allergy, Hospital La Paz Institute for Health Research (IdiPAZ), 4CIBER de Enfermedades Respiratorias, CIBERES, Madrid, Spain Abstract: Although non-eosinophilic asthma (NEA) is not the best known and most prevalent asthma phenotype, its importance cannot be underestimated. NEA is characterized by airway inflammation with the absence of eosinophils, subsequent to activation of non-predominant type 2 immunologic pathways. This phenotype, which possibly includes several not well-defined subphenotypes, is defined by an eosinophil count

Introduction: The serum periostin level is a promising biomarker of type 2- high inflammation pattern of bronchial asthma. It has been proven that serum periostin levels decrease in response to systemic and inhaled corticosteroid (ICS) therapy. However, we have only limited knowledge about changes in serum periostin levels reflecting omalizumab (OMA) treatment and other variables, such as chronic rhinosinusitis with nasal polyps (CRSwNP). Aim: To critically appraise clinically relevant parameters influencing periostin levels in asthma patients. Material and methods: A pilot, cross-sectional, observational study to assess serum periostin levels of 48 asthma patients (38 treated by conventional therapy comprising ICS and 10 treated by ICS and OMA as an add-on therapy) with respect to asthma clinical traits, comorbidities and to other biomarkers of type 2-high asthma phenotype (total IgE, absolute and relative eosinophil count, eosinophilic cationic protein (ECP) and a fraction of exhaled NO (FeNO)). Results: Serum periostin correlates with total IgE levels (Spearman rho = 0.364, p = 0.025) in a subgroup of conventionally treated patients, and with eosinophil count (Spearman rho = 0.401, p = 0.021) in a subgroup of patients with concurrent CRSwNP. Serum periostin levels were decreased in omalizumab-treated patients in comparison to conventionally treated patients (p = 0.025). This effect was remarkably apparent only if CRSwNP was not present (p = 0.005). Conversely, we measured elevated periostin levels in OMA-treated patients with concurrent CRSwNP (p = 0.017). Conclusions: Serum periostin production is significantly associated with treatment modality (omalizumab vs. conventional) and presence of CRSwNP. These variables need to be taken into account to interpret periostin levels accurately. [ABSTRACT FROM AUTHOR]

Asthma guidelines provide clinicians with evidence-based management strategies for this chronic condition. The preferred therapy for patient with persistent asthma is inhaled corticosteroids. However, ∼40% of the patients with persistent asthma continue to present with symptoms while treated according to the guidelines. Multiple factors are being explored to explain the variability in response to inhaled corticosteroids including asthma phenotype and genetic predisposition among others. The nonatopic asthma phenotype has been described in the literature. These patients tend to have milder symptoms of asthma and typically outgrow their asthma by adolescence. They present with chronic asthma symptoms in the absence of a positive allergy test, either skin prick test or specific immunoglobulin E blood test. Although patients with nonatopic asthma share many characteristics with patients with atopic asthma, there are several studies that suggest a different inflammatory pathway may be involved in their pathophysiology. Therefore, it is possible that children with nonatopic asthma could respond differently to inhaled corticosteroids compared with those with atopic asthma. Currently there is a variable definition of this phenotype. Furthermore, there is a paucity of therapeutic trial directed toward the patients with nonatopic asthma specifically. Future research should be guided toward identifying the inflammatory pathways in nonatopic asthma and potential phenotype-guided therapies. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated that a coding SNP (rs6967330, Cys529→Tyr) in cadherin-related family member 3 (CDHR3), which was previously associated with wheezing illness and hospitalizations in infancy, could support efficient human rhinovirus C (RV-C) entry and replication. Here, we sought to examine the genetic contribution of this variant to the development of adult asthma. Methods: We performed a candidate gene case–control association study of 2 independent Japanese populations (a total of 3366 adults). The odds ratios (ORs) for association of the A allele at rs6967330 with adult asthma were calculated according to age at onset of asthma. In addition, the effect of the CDHR3 genotype on the development of specific asthma phenotypes was examined. Results: The A allele was associated with asthma (OR = 1.56; Mantel–Haenszel p = 0.0040) when the analysis was limited to patients with early-onset adult asthma. In addition, when the analysis was limited to atopic individuals, a stronger association of the CDHR3 variant with early-onset asthma was found, and interaction of the CDHR3 genotype with atopy was demonstrated. Finally, a significant association of this variant was specifically found with a phenotype of asthma characterized by atopy, early-onset, and lower lung function. Conclusions: Our study supports the concept that the CDHR3 variant is an important susceptibility factor for severe adult asthma in individuals who develop the disease in early life. The interaction between the CDHR3 variant and atopy indicates that genetic predisposition to early respiratory viral infection is combined with atopy in promoting asthma.

The aim of this study is to measure the level of the endothelin-1 in blood samples and to assess vasoactive function of the endothelial in asthma patients with different phenotypes and to develop the methods of the objective assess of the ongoing treatment. Materials and methods. 119 asthma patients were separated into several phenotypes: patients with atopic asthma (60 pat); patients with ACOS (35 pat); asthma with obesity (24 pat). In all patients endothelium-dependent vasodilation and plasma level of endothelin-1 were assessed. Results. Endothelial dysfunction revealed in all asthma phenotypes. The highest level of the endothelin-1 shown in ACOS patients. In patients which achieved asthma control during three month of the anti-inflammatory therapy showed decreasing of the endothelin-1 level by 1,5 times in comparison with basic level (0,35 ± 0,06 fmol/ml and 0,64 ± 0,15 fmol/ml respectively, р < 0,01). But in patients with persistent symptoms and/or without lung function improvement the level of the endothelin-1 was not decreased significantly. Conclusions. Change of the functional conditions of the endothelial depend on the time and severity and phenotype of the asthma. The endothelin-1 level and the endothelium-dependent vasodilatation assess on the course of the treatment allow to reveal success of this anti- inflammatory therapy.

Asthma is a complex, heterogenous medical condition which is very common in children and adults. The transition process from pediatric to adult health care services can be a challenge for young people with chronic medical conditions. The significant changes in physical and mental health during this time, as well as the many unique developmental and psychosocial challenges that occur during adolescence can complicate and impede transition if not adequately addressed and managed. The transition period can also be a challenging time for health professionals to assess readiness for transition and manage some of the complications which are particularly common during this time, including poor adherence to therapy, smoking, drug use, and emerging mental health conditions. The natural history, presentation, symptoms, and management of asthma is often significantly different when comparing pediatric and adult practice. In addition, management in infants, toddlers, school aged children, and adolescents differs significantly, offering an additional challenge to pediatric physicians managing asthmatic children and young people. Despite these challenges, if the transition process for young people with asthma is planned and performed in a formalized manner, many of these issues can be addressed, allowing the transition to occur smoothly despite changes that may occur in medical and psychosocial domains.

Equine asthma syndrome (EAS) is a common problem that affects horses of any age. Severe EAS is reported to affect 10–20% of adult horses in the northern hemisphere, while mild/moderate EAS is reported to affect 60–100% of adult horses, depending on the population and geographic region. For both severe and mild/moderate EAS, the presence of lower airway inflammation is attributed to airborne “triggers” such as dust, mold, and bacterial components that horses encounter in hay and stable-environments; and treatment recommendations for horses with EAS often include full-time pasture turnout. The caveat to this recommendation is horses with summer-pasture associated EAS (SP-EAS), who experience allergic lower airway inflammation when exposed to summer pasture. The prevalence of EAS in horses on pasture that do not have SP-EAS has not been reported. The purpose of this study was to use bronchoalveolar lavage (BAL) cytology to determine the prevalence of EAS in a herd of pastured, adult research horses with no history of respiratory disease. The horses were members of a teaching animal herd housed on pasture in the southeastern United States and fed round-bale Bermuda-grass hay. BAL fluid (BALF) cytology was analyzed in both summer (May–August 2017) and winter (November 2017–February 2018). Similar to previous reports, the prevalence of severe EAS in our study population was 10% in summer and 4.3% in winter. The prevalence of mild/moderate EAS was 60% in summer and 87% in winter. The high prevalence of mild/moderate EAS in this population was unexpected, given the 24-h, year-round pasture environment and the lack of history of respiratory disease. Additionally, 61.1% of horses with both summer and winter data had a different BALF cytology profile between the two seasons. To the authors' knowledge, this is the first study to use BAL cytology to diagnose, and monitor changes in, EAS phenotype in pastured adult horses. These results help to inform discussions regarding prevalence of EAS in pastured, adult horses in the southeastern region of North America.

Background: Asthma patients present with distinct immunological profiles, with a predominance of type 2 endotype. The aim of this study was to investigate the impact of high‐altitude treatment on the clinical and immunological response in asthma. Methods: Twenty‐six hospitalized asthma patients (nine eosinophilic allergic; EA, nine noneosinophilic allergic; NEA and eight noneosinophilic nonallergic; NN) and nine healthy controls in high altitude for 21 days were enrolled in the study. We assessed eosinophils, T cells, Tregs, and innate lymphoid cells (ILC) from peripheral blood using flow cytometry. Results: The number of eosinophils (both resting and activated) and chemoattractant receptor homolog expressed on Th2 cells (CRTH2)‐expressing CD4+ and CD8+ T cells decreased significantly in EA patients after altitude treatment. The frequency of CRTH2+ Tregs as decreased significantly in all the asthma phenotypes as well as the frequency of ILC2 was significantly reduced in EA after altitude treatment. After 21 days of altitude therapy, CRTH2‐expressing ILC2, CD4+ and CD8+ T cells and Treg cells showed attenuated responses to exogenous PGD2. Furthermore, PGD2 signaling via CRTH2 was found to diminish the suppressive function of CRTH2+ Tregs which partially normalized during high‐altitude treatment. Improved asthma control was particularly evident in allergic asthma patients and correlated with decreased frequencies of CRTH2+ Treg cells in EA patients. Serum IL‐5 and IL‐13 decreased during climate treatment in asthma patients with high baseline levels. Conclusions: Asthma treatment in high altitude reduced the type 2 immune response, corrected the increased CRTH2 expression and its dysregulated functions. [ABSTRACT FROM AUTHOR]

Several biomarkers have been studied to diagnose or to detect the phenotype of asthma. Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammatory diseases. We aimed to study serum clusterin level in atopic versus non-atopic childhood asthma and its relation to disease severity. This case-control study included 160 children; 120 stable asthmatic children and 40 apparently healthy children. Asthmatic children were further subdivided into atopic and non-atopic. All children were subjected to medical history taking, clinical examination, and laboratory investigations including complete blood count, serum IgE, serum clusterin level and spirometry before and after bronchodilator therapy. In comparison to controls, patients had significantly higher eosinophils count which was higher in atopic than non-atopic group, also serum IgE level was higher in the atopic asthmatics (118.1 ± 16.2 U/ml) than in both the non-atopic asthmatics (81.2 ± 6.1 U/ml) and the controls (76.3 ± 11.6 U/ml). There was statistical significant difference in serum levels of Clusterin which were highest in the atopic group (182.5 ± 33.5 ng/l), followed by the non-atopic patients (127.5 ± 32.5 ng/l) and lowest in the controls (46.09 ± 7.01 ng/l). Moreover, the higher the severity of asthma, the higher was the level of serum clusterin. In conclusion serum level of clusterin was higher in atopic than non-atopic asthmatic children and it increases significantly with increased severity of the disease. [ABSTRACT FROM AUTHOR]

The management of asthma has largely stagnated over the last 25 years, but we are at the dawning of a new age wherein -omics technology can help us manage the disease objectively and rationally. Even in this new scientific age, getting the basics of asthma management right remains essential. The new technologies which can be applied to multiple biological samples include genomics (study of the genome), transcriptomics (gene transcription), lipidomics, proteomics and metabolomics (lipids, proteins and metabolites, respectively) and breathomics, using exhaled breath as a source of biomarkers, which is of particular interest in view of its non-invasive nature in pediatrics. Important applications will include the diagnosis of airways disease, including its components; the pathways driving airway pathology; monitoring the response to treatment; and measuring future risk (asthma attacks, poor lung growth trajectory). With the advent of a wide range of novel biologicals to treat asthma, -omics technology to personalize therapy will be especially important. The U-BIOPRED (Europe) and SARP (USA) groups have been most active in this field, especially using bronchoscopically obtained samples to perform cluster analyses to define new asthma endotypes. However, stability over time and consistency between investigators is imperfect. This is perhaps unsurprising; results of biomarker studies in asthma will be a composite of the underlying disease, the (variable) effects of adverse drivers such as allergen exposure and pollution, the effects of treatment, and the effects of adherence or otherwise to treatment. Ultimately, the aim should be an exhaled breath based tool with a rapid result that can be used as a routine in the clinic. However, at the moment, there are as yet no clinical applications in children of -omics technology. [ABSTRACT FROM AUTHOR]

Background Interferons play an important role in innate immunity. Previous studies report deficiency in virus induction of interferon ( IFN)-α, IFN-β and IFN-λ in bronchial epithelial and bronchial lavage cells in atopic asthmatics. It is now recognized that asthma is a heterogeneous disease comprising different inflammatory phenotypes, some of which may involve innate immune activation in the absence of overt infection. Objective The aim of this study was to investigate whether the severity of asthma or a specific cellular sputum pattern may be linked to evidence of innate immune activation. Methods Here we investigate the expression of IFN-β, IFN-λ1 ( IL-29), IFN-λ2/3 ( IL-28A/B) and the interferon-stimulated genes ( ISGs) such as myxovirus resistance 1 (Mx1), oligoadenylate synthetase ( OAS) and viperin in unstimulated sputum cells in 57 asthmatics (including 16 mild, 19 moderate and 22 severe asthma patients) and compared them with 19 healthy subjects. Results We observed increased expression of IFN-β, IFN-λ1/ IL-29, OAS and viperin in asthmatics compared with healthy subjects, while IL-28 was not expressed in any group. The overexpression was restricted to neutrophilic asthmatics (sputum neutrophils ≥ 76%), while eosinophilic asthmatics (sputum eosinophils ≥ 3%) did not differ from healthy subjects or even showed a lower expression of Mx1. No difference in interferon or ISG expression was observed according to clinical asthma severity. Conclusion and Clinical Relevance Neutrophilic, but not eosinophilic, asthmatics display overexpression of IFN-β, IFN-λ1/ IL-29 and ISGs in their sputum cells that may reflect ongoing innate immune activation. [ABSTRACT FROM AUTHOR]

Background: Cluster analyses were previously performed to identify asthma phenotypes underlying asthma syndrome. Although a large number of patients with asthma develop the disease later in life, these previous cluster analyses focused mainly patients with younger-onset asthma. Methods: Cluster analysis examined the existence of distinct phenotypes of late-onset asthma in Japanese patients with adult asthma. We then associated genotypes at the CCL5, TSLP, IL4, and ADRB2 genes with the clusters of asthma identified. Results: Using the 8 variables of age, sex, age at onset of the disease, smoking status, total serum IgE, %FEV1, FEV1/FVC, and specific IgE responsiveness to common inhaled allergens, two-step cluster analysis of 880 Japanese adult asthma patients identified 6 phenotypes: cluster A (n = 155): older age at onset, no airflow obstruction; cluster B (n = 170): childhood onset, normal-to-mild airflow obstruction; cluster C (n = 119): childhood onset, the longest disease duration, and moderate-to-severe airflow obstruction; cluster D (n = 108): older age at onset, severe airflow obstruction; cluster E (n = 130): middle-age at onset, no airflow obstruction; and cluster F (n = 198): older age at onset, mild-to-moderate airflow obstruction. The CCL5-28C>G genotype was significantly associated with clusters A, B and D (OR 1.65, p = 0.0021; 1.67, 0.018; and 1.74, 0.011, respectively). The ADRB2 Arg16Gly genotype was also associated with clusters B and D (OR 0.47, p = 0.0004; and 0.63, 0.034, respectively). Conclusions: The current cluster analysis identified meaningful adult asthma phenotypes linked to the functional CCL5 and ADRB2 genotypes. Genetic and phenotypic data have the potential to elucidate the pheno- typic heterogeneity and pathophysiology of asthma.

Background Treatment levels required to control asthma vary greatly across a population with asthma. The factors that contribute to variability in treatment requirements of inner-city children have not been fully elucidated. Objective We sought to identify the clinical characteristics that distinguish difficult-to-control asthma from easy-to-control asthma. Methods Asthmatic children aged 6 to 17 years underwent baseline assessment and bimonthly guideline-based management visits over 1 year. Difficult-to-control and easy-to-control asthma were defined as daily therapy with 500 μg of fluticasone or greater with or without a long-acting β-agonist versus 100 μg or less assigned on at least 4 visits. Forty-four baseline variables were used to compare the 2 groups by using univariate analyses and to identify the most relevant features of difficult-to-control asthma by using a variable selection algorithm. Nonlinear seasonal variation in longitudinal measures (symptoms, pulmonary physiology, and exacerbations) was examined by using generalized additive mixed-effects models. Results Among 619 recruited participants, 40.9% had difficult-to-control asthma, 37.5% had easy-to-control asthma, and 21.6% fell into neither group. At baseline, FEV 1 bronchodilator responsiveness was the most important characteristic distinguishing difficult-to-control asthma from easy-to-control asthma. Markers of rhinitis severity and atopy were among the other major discriminating features. Over time, difficult-to-control asthma was characterized by high exacerbation rates, particularly in spring and fall; greater daytime and nighttime symptoms, especially in fall and winter; and compromised pulmonary physiology despite ongoing high-dose controller therapy. Conclusions Despite good adherence, difficult-to-control asthma showed little improvement in symptoms, exacerbations, or pulmonary physiology over the year. In addition to pulmonary physiology measures, rhinitis severity and atopy were associated with high-dose asthma controller therapy requirement. [ABSTRACT FROM AUTHOR]

Background: Measurement of the fractional exhaled nitric oxide (FeNO) and eosinophils in induced sputum are noninvasive markers for assessing airway inflammation in asthma. The clinical usefulness of the correlation between raised FeNO and sputum eosinophilia is controversial. We aimed to examine dissociation between FeNO and sputum eosinophils in a clinical series of asthma patients and to determine whether dissociation between these noninvasive markers was associated with clinical and inflammatory differences in these patients.Methods and findings: A total of 110 patients with asthma were included in a cross-sectional study. All of them were on maintenance treatment for asthma. All patients underwent the following on the same day: FeNO, induced sputum, spirometry, serum total IgE levels and skin prick test. The level of asthma control was determined by the Asthma control Test Questionnaire. In 46 (41.8%) patients, a discrepancy between FeNO and sputum eosinophil count was observed, of those, 34 (73.9%) had a FeNO <50 ppb and high eosinophil count, and were characterized by having a predominance of nonallergic asthma with bronchial eosinophilic inflammatory phenotype. Also, 12 (26.1%) patients had FeNO ≥50 ppb and sputum eosinophilia within the normal reference values, and were characterized by having a predominance of atopy with a paucigranulocytic inflammatory phenotype.Conclusions: A high percentage of patients with dissociation between results of FeNO and sputum eosinophils was observed. These patients showed differential clinical and inflammatory features. [ABSTRACT FROM AUTHOR]

The eosinophil is a fully delineated granulocyte that disseminates throughout the bloodstream to end-organs after complete maturation in the bone marrow. While the presence of eosinophils is not uncommon even in healthy individuals, these granulocytes play a central role in inflammation and allergic processes. Normally appearing in smaller numbers, higher levels of eosinophils in the peripheral blood or certain tissues typically signal a pathologic process. Eosinophils confer a beneficial effect on the host by enhancing immunity against molds and viruses. However, tissue-specific elevation of eosinophils, particularly in the respiratory system, can cause a variety of short-term symptoms and may lead to long-term sequelae. Eosinophils often play a role in more commonly encountered disease processes, such as asthma and allergic responses in the upper respiratory tract. They are also integral in the pathology of less common diseases including eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and drug reaction with eosinophilia and systemic symptoms. They can be seen in neoplastic disorders or occupational exposures as well. The involvement of eosinophils in pulmonary disease processes can affect the method of diagnosis and the selection of treatment modalities. By analyzing the complex interaction between the eosinophil and its environment, which includes signaling molecules and tissues, different therapies have been discovered and created in order to target disease processes at a cellular level. Innovative treatments such as mepolizumab and benralizumab will be discussed. The purpose of this article is to further explore the topic of eosinophilic presence, activity, and pathology in the respiratory tract, as well as discuss current and future treatment options through a detailed literature review. [ABSTRACT FROM AUTHOR]

Three concomitant phenomena occur in the later years of childhood: increases in the incidence of asthma, obesity and early menarche. This article is an overview of the current epidemiologic, basic, genetic and epigenetic evidence about this relationship. As a consequence we propose that obese girls who have an early menarche (≤ 11 years of age) constitute a new asthma phenotype in childhood. Future studies need to be carried out in order to find the best control and treatment of this new asthma phenotype. [ABSTRACT FROM AUTHOR]