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Non th2 asthma

Luis Pérez de Llano, Borja G Cosío, Amanda Iglesias, Natividad de Las Cuevas, Juan Jose Soler-Cataluña, Jose Luis Izquierdo, Jose Luis López-Campos, Carmen Calero, Vicente Plaza, Marc Miravitlles, Alfons Torrego, Eva Martinez-Moragon, Joan B Soriano, Antolin Lopez Viña, Irina Bobolea
Introduction: The asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of understanding of the underlying mechanisms. Determining systemic mediators may help clarify the nature of inflammation in patients with ACO. Objectives: We aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-α), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO...
2018: International Journal of Chronic Obstructive Pulmonary Disease
Michael D Howell, Carolyn Fitzsimons, Paul Smith
OBJECTIVE: To provide an overview of janus kinase (JAK), chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2), and phosphodiesterase 4 (PDE4) inhibitors in allergic disorders. DATA SOURCES: PubMed literature review. STUDY SELECTIONS: Articles included in this review discuss the emerging mechanism of action of small molecule inhibitors and their utilization in atopic dermatitis (AD), asthma, and allergic rhinitis (AR)...
February 14, 2018: Annals of Allergy, Asthma & Immunology
Tsunahiko Hirano, Kazuto Matsunaga
Because the pathophysiology of asthma has diverse characteristics, to manage the disease effectively, it is important for clinicians to distinguish among the clinical phenotypes. Among them, adult-onset asthma, that is, late-onset asthma (LOA), is increasing because of the aging of the population. The phenotype of LOA is largely divided into two types according to the presence or absence of eosinophilic inflammation, T-helper (Th)2- and non-Th2-associated LOA. Especially in Th2 LOA related to rhinosinusitis, as pulmonary function at onset is poor and asthma exacerbations occur frequently, it is important to detect this phenotype in the early phase by using a biomarker of Th2-type inflammation such as fractional exhaled nitric oxide (FE NO )...
2018: Journal of Asthma and Allergy
Hui Fang Lim, Parameswaran Nair
Severe asthma is a complex disease consisting of different endotypes with different inflammatory and clinicopathological characteristics due to the heterogeneity of immune responses and smooth muscle dysfunction. There is an unmet clinical need to develop and to validate biomarkers that can differentiate between the asthma endotypes and guide clinical management, particularly since the availability of biologicals directed against T2 cytokines. The presence of a "Th2 endotype" is currently assessed in clinical practice using markers, such as eosinophil count in sputum or blood, fraction of exhaled nitric oxide, and immunoglobulin E...
February 2018: Seminars in Respiratory and Critical Care Medicine
Steven F Weinstein, Rohit Katial, Shyamalie Jayawardena, Gianluca Pirozzi, Heribert Staudinger, Laurent Eckert, Vijay N Joish, Nikhil Amin, Jaman Maroni, Paul Rowe, Neil M H Graham, Ariel Teper
BACKGROUND: Dupilumab, an anti-IL-4Rα monoclonal antibody, inhibits IL-4/IL-13 signaling, key drivers of type 2/Th2 immune diseases (e.g. atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting β2-agonists. OBJECTIVE: To examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR)...
January 17, 2018: Journal of Allergy and Clinical Immunology
N Mgaloblishvili, M Gotua
Asthma is a pathologically heterogeneous disease, consisting of several phenotypes. Different types of airway inflammation are the cornerstone feature of this condition. Fraction of nitric oxide in exhaled air (FENO) has been proposed as a noninvasive, specific biomarker for eosinophilic airway inflammation and has been shown to be elevated in patients with allergic asthma phenotype. More recent studies indicate that FeNO identifies T-helper cell type 2 (Th2)-mediated airway inflammation with a high predictive value for identifying inhaled corticosteroid (ICS) responsive airway inflammation...
December 2017: Georgian Medical News
Adelina Orellana, Vicente García-González, Rosa López, Sonia Pascual-Guiral, Estrella Lozoya, Julia Díaz, Daniel Casals, Antolín Barrena, Stephane Paris, Miriam Andrés, Victor Segarra, Dolors Vilella, Rajneesh Malhotra, Paul Eastwood, Anna Planagumà, Montserrat Miralpeix, Arsenio Nueda
Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung epithelium in response to external insult. Considered as a master switch in T helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role in allergic diseases including asthma. The aim of this study was to use a phenotypic approach to identify new biological and chemical starting points for inhibition of TSLP production in human bronchial epithelial cells (NHBE), with the objective of reducing Th2-mediated airway inflammation...
2018: PloS One
Gilda Varricchi, Giancarlo Marone, Giuseppe Spadaro, Michele Russo, Francescopaolo Granata, Arturo Genovese, Gianni Marone
Asthma is a heterogeneous disease characterized by chronic airway inflammation that results in a wide spectrum of clinical manifestations. Patients with severe asthma represent a substantial share of consumption of healthcare resources and hospitalization. Moreover, these patients are at risk of increased morbidity and mortality. Recently, several phenotypes and endotypes of asthma have been identified. The identification of specific subtypes of asthma is fundamental for optimizing the clinical benefit of novel treatments...
January 9, 2018: Current Medicinal Chemistry
Sarah Svenningsen, Rachel L Eddy, Hui Fang Lim, P Gerard Cox, Parameswaran Nair, Grace Parraga
RATIONALE: Inflammation and smooth muscle dysfunction are integral components of severe asthma that contribute to luminal obstruction causing airflow limitation, ventilation heterogeneity and symptoms. This is important for guiding treatment decisions directed at inflammatory (eg. anti-Th2 monoclonal antibodies) and non-inflammatory, smooth muscle-mediated (eg. bronchial thermoplasty) components of severe asthma. OBJECTIVE: To investigate the contribution of eosinophilic-bronchitis and smooth muscle dysfunction to magnetic-resonance-imaging (MRI) ventilation heterogeneity in severe asthmatics...
January 9, 2018: American Journal of Respiratory and Critical Care Medicine
Jin-Nan Zhong, Lan Lan, Yi-Fei Chen, Ge Huang, Guang-Zhen He, Jiong Yang, Ya-Dong Gao
BACKGROUND: Circulating fibrocytes (CFs) have been shown to participate in subepithelial fibrosis of asthma with chronic airflow limitation by acting as an important source of fibroblasts deposited beneath airway epithelia. Serum amyloid P (SAP) is an innate inhibitor of fibrocytes differentiation. Store-operated Ca2+ entry (SOCE) is the major Ca2+ influx of non-excitable cells. In this study, the role of SOCE in the regulation of fibrocytes differentiation and the effects of Th2 cytokine IL-4 and SAP on SOCE of fibrocytes were investigated...
July 12, 2017: Pharmacological Reports: PR
Yingying Yang, Panpan Dong, Jing Zhao, Wei Zhou, Yonghua Zhou, Yongliang Xu, Congjin Mei, Fukun Guo, Yi Zheng, Jun-Qi Yang
Asthma is a chronic airway inflammation in which Th2 and Th17 cells play critical roles in its pathogenesis. We have reported that atypical protein kinase (PKC) λ/ι is a new regulator for Th2 differentiation and function. However, the role of PKCλ/ι for Th17 cells remains elusive. In this study, we explored the effect of PKCλ/ι on Th17 cells in the context of ex vivo cell culture systems and an in vivo murine model of allergic airway inflammation with the use of activated T cell-specific conditional PKCλ/ι-deficient mice...
January 3, 2018: Biochimica et Biophysica Acta
L Antunes, A P Duarte de Souza, P D de Araújo, L A Pinto, M H Jones, R T Stein, P M Pitrez
BACKGROUND: Invariant natural killer T (iNKT) cells play complex functions in the immune system, releasing both Th1 and Th2 cytokines. The role of iNKT cells in human asthma is still controversial and never described in severe therapy-resistant asthma in children. The objective of this work was to analyse iNKT frequency in peripheral blood of children with severe therapy-resistant asthma (STRA), compared to children with milder asthma and healthy controls. METHODS: Children with asthma (n=136) (non-severe and STRA) from a referral centre and healthy controls (n=40) were recruited...
December 23, 2017: Allergologia et Immunopathologia
Amarjit Mishra, Xianglan Yao, Ankit Saxena, Elizabeth M Gordon, Maryann Kaler, Rosemarie A Cuento, Amisha V Barochia, Pradeep K Dagur, J Philip McCoy, Karen J Keeran, Kenneth R Jeffries, Xuan Qu, Zu-Xi Yu, Stewart J Levine
BACKGROUND: The LDL-receptor related protein 1 (LRP-1) is a scavenger receptor that regulates adaptive immunity and inflammation. LRP-1 is not known to modulate the pathogenesis of allergic asthma. OBJECTIVE: To assess whether LRP-1 expression by dendritic cells (DCs) modulates adaptive immune responses in house dust mite (HDM)-induced airways disease. METHODS: LRP-1 expression on peripheral blood DCs was quantified by flow cytometry. The role of LRP-1 in modulating HDM-induced airways disease was assessed in mice with a deletion of LRP-1 in CD11c+ cells (Lrp1fl/fl; CD11c-Cre) and by the adoptive transfer of HDM-pulsed CD11b+ DCs from Lrp1fl/fl; CD11c-Cre mice to wild-type mice...
December 20, 2017: Journal of Allergy and Clinical Immunology
Wen-Jing Ye, Wei-Guo Xu, Xue-Jun Guo, Feng-Feng Han, Juan Peng, Xiao-Ming Li, Wen-Bin Guan, Li-Wei Yu, Jin-Yuan Sun, Zhi-Lei Cui, Lin Song, Yue Zhang, Yan-Min Wang, Tian-Yun Yang, Xia-Hui Ge, Di Yao, Song Liu
Background: To identify asthma clinical phenotypes using cluster analysis and improve our understanding of heterogeneity in asthma. Methods: Clustering approaches were applied to 203 patients who were diagnosed with asthma in XinHua Hospital (January 2012 to December 2015). One hundred and twenty patients underwent multi-slice spiral computed tomography (MSCT) examination and 30 underwent bronchial mucosal biopsy for evaluation of airway remodeling and airway inflammation among the phenotypes...
September 2017: Journal of Thoracic Disease
Manoj J Mammen, Mark F Sands, Elaine Abou-Jaoude, Ravikumar Aalinkeel, Jessica L Reynolds, Neil U Parikh, Umesh Sharma, Stanley A Schwartz, Supriya D Mahajan
Asthma is a chronic inflammatory respiratory disease characterized by airway inflammation, airway hyper-responsiveness and reversible airway obstruction. Understanding the mechanisms that underlie the various endotypes of asthma could lead to novel and more personalized therapies for individuals with asthma. Utilizing a Tissue inhibitors of metalloproteinase-1 (TIMP-1) knockout murine allergic asthma model, we previously showed that Tissue inhibitors of metalloproteinase-1 deficiency results in an asthma phenotype, exhibiting airway hyperreactivity, enhanced eosinophilic inflammation, and TH2 cytokine gene and protein expression following sensitization with ovalbumin...
October 9, 2017: Immunology
John D Dickinson, Jenea M Sweeter, Kristi J Warren, Iman M Ahmad, Xavier De Deken, Matthew C Zimmerman, Steven L Brody
The airway epithelium is a broad interface with the environment, mandating well-orchestrated responses to properly modulate inflammation. Classically, autophagy is a homeostatic pathway triggered in response to external cellular stresses, and is elevated in chronic airway diseases. Recent findings highlight the additional role of autophagy in vesicle trafficking and protein secretion, implicating autophagy pathways in complex cellular responses in disease. Th2 cytokines, IL-13 and IL-4, are increased in asthma and other airway diseases contributing to chronic inflammation...
April 2018: Redox Biology
Jelena Skuljec, Markus Chmielewski, Christine Happle, Anika Habener, Mandy Busse, Hinrich Abken, Gesine Hansen
Cellular therapy with chimeric antigen receptor (CAR)-redirected cytotoxic T cells has shown impressive efficacy in the treatment of hematologic malignancies. We explored a regulatory T cell (Treg)-based therapy in the treatment of allergic airway inflammation, a model for asthma, which is characterized by an airway hyper-reactivity (AHR) and a chronic, T helper-2 (Th2) cell-dominated immune response to allergen. To restore the immune balance in the lung, we redirected Tregs by a CAR toward lung epithelia in mice upon experimentally induced allergic asthma, closely mimicking the clinical situation...
2017: Frontiers in Immunology
Julia A Wisniewski, Lyndsey M Muehling, Jacob D Eccles, Brian J Capaldo, Rachana Agrawal, Debbie-Ann Shirley, James T Patrie, Lisa J Workman, Alexander J Schuyler, Monica G Lawrence, W Gerald Teague, Judith A Woodfolk
BACKGROUND: The pathogenesis of severe asthma in childhood remains poorly understood. OBJECTIVE: We sought to construct the immunologic landscape in the airways of children with severe asthma. METHODS: Comprehensive analysis of multiple cell types and mediators was performed by using flow cytometry and a multiplex assay with bronchoalveolar lavage (BAL) specimens (n = 68) from 52 highly characterized allergic and nonallergic children (0...
September 20, 2017: Journal of Allergy and Clinical Immunology
Huey-Huey Chua, Hung-Chieh Chou, Ya-Ling Tung, Bor-Luen Chiang, Chien-Chia Liao, Hong-Hsing Liu, Yen-Hsuan Ni
BACKGROUND & AIMS: Dysbiosis of the intestinal microbiota has been associated with development of allergies in infants. However, it is not clear what microbes might contribute to this process. We investigated what microbe(s) might be involved in analyses of infant twins and mice. METHODS: We studied fecal specimens prospectively in a twin cohort (n=30) and age-matched singletons (n=14) born at National Taiwan University Children's Hospital, Taipei, Taiwan, from April 2011 to March 2013...
September 11, 2017: Gastroenterology
Stamatoula Tsikrika, Katerina Dimakou, Andriana I Papaioannou, Georgios Hillas, Loukas Thanos, Kostantinos Kostikas, Stelios Loukides, Spyros Papiris, Nickolaos Koulouris, Petros Bakakos
INTRODUCTION: Bronchiectasis is a heterogeneous entity, taking into account clinical characteristics, inflammatory response, effectiveness of treatment and frequency of exacerbations. In stable state non-cystic fibrosis (non-CF) bronchiectasis, little is known about non-invasive techniques used for evaluating airway inflammation in obstructive airway diseases. OBJECTIVES: We sought to evaluate the associations between induced sputum and clinical/radiologic characteristics, and the differences between biomarkers expressing Th1 and Th2 response in patients with non-CF bronchiectasis and to compare our findings with a previously studied population of patients with asthma and COPD...
November 2017: Cytokine
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