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Non th2 asthma

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https://www.readbyqxmd.com/read/29328030/modern-approaches-to-fractional-exhaled-nitric-oxide-as-a-useful-biomarker-for-allergic-asthma-phenotyping-and-management
#1
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
https://www.readbyqxmd.com/read/29320511/application-of-a-phenotypic-drug-discovery-strategy-to-identify-biological-and-chemical-starting-points-for-inhibition-of-tslp-production-in-lung-epithelial-cells
#2
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
https://www.readbyqxmd.com/read/29318959/novel-biological-therapies-in-severe-asthma-targeting-the-right-trait
#3
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
https://www.readbyqxmd.com/read/29313707/sputum-eosinophilia-and-mri-ventilation-heterogeneity-in-severe-asthma
#4
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
https://www.readbyqxmd.com/read/29306759/il-4-and-serum-amyloid-p-inversely-regulate-fibrocyte-differentiation-by-targeting-store-operated-ca2-channels
#5
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
https://www.readbyqxmd.com/read/29305916/pkc-%C3%AE-%C3%AE-regulates-th17-differentiation-and-house-dust-mite-induced-allergic-airway-inflammation
#6
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
https://www.readbyqxmd.com/read/29279262/inkt-cells-are-increased-in-children-with-severe-therapy-resistant-asthma
#7
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
https://www.readbyqxmd.com/read/29274414/lrp-1-attenuates-house-dust-mite-induced-eosinophilic-airway-inflammation-by-suppressing-dendritic-cell-mediated-adaptive-immune-responses
#8
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
https://www.readbyqxmd.com/read/29221262/differences-in-airway-remodeling-and-airway-inflammation-among-moderate-severe-asthma-clinical-phenotypes
#9
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
https://www.readbyqxmd.com/read/28992358/role-of-galectin-3-in-the-pathophysiology-underlying-allergic-lung-inflammation-in-a-timp-1-knockout-model-of-murine-asthma
#10
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
https://www.readbyqxmd.com/read/28982074/autophagy-regulates-duox1-localization-and-superoxide-production-in-airway-epithelial-cells-during-chronic-il-13-stimulation
#11
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...
September 22, 2017: Redox Biology
https://www.readbyqxmd.com/read/28955341/chimeric-antigen-receptor-redirected-regulatory-t-cells-suppress-experimental-allergic-airway-inflammation-a-model-of-asthma
#12
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
https://www.readbyqxmd.com/read/28939412/th1-signatures-are-present-in-the-lower-airways-of-children-with-severe-asthma-regardless-of-allergic-status
#13
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: To construct the immunological landscape in the airways of children with severe asthma. METHODS: Comprehensive analysis of multiple cell types and mediators was performed by flow cytometry and multiplex assay using bronchoalveolar lavage (BAL) specimens (n=68) from 52 highly characterized allergic and non-allergic children (0.5-17 years) with severe treatment-refractory asthma...
September 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28912020/intestinal-dysbiosis-featuring-abundance-of-ruminococcus-gnavus-associates-with-allergic-diseases-in-infants
#14
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
https://www.readbyqxmd.com/read/28863927/the-role-of-non-invasive-modalities-for-assessing-inflammation-in-patients-with-non-cystic-fibrosis-bronchiectasis
#15
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...
August 29, 2017: Cytokine
https://www.readbyqxmd.com/read/28756630/dna-methylation-of-th2-lineage-determination-genes-at-birth-is-associated-with-allergic-outcomes-in-childhood
#16
S J Barton, S Ngo, P Costello, E Garratt, S El-Heis, E Antoun, R Clarke-Harris, R Murray, T Bhatt, G Burdge, C Cooper, H Inskip, E M van der Beek, A Sheppard, K M Godfrey, K A Lillycrop
BACKGROUND: There is now increasing evidence that asthma and atopy originate in part in utero, with disease risk being associated with the altered epigenetic regulation of genes. OBJECTIVE AND METHODS: To determine the relationship between variations in DNA methylation at birth and the development of allergic disease, we examined the methylation status of CpG loci within the promoter regions of Th1/2 lineage commitment genes (GATA3, IL-4, IL-4R, STAT4 and TBET) in umbilical cord DNA at birth in a cohort of infants from the Southampton Women's Survey (n = 696) who were later assessed for asthma, atopic eczema and atopy...
July 30, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28737932/ins-and-outs-in-environmental-and-occupational-safety-studies-of-asthma-and-engineered-nanomaterials
#17
Marina A Dobrovolskaia, Michael R Shurin, Valerian E Kagan, Anna A Shvedova
According to the Centers for Disease Control and Prevention, approximately 25 million Americans suffer from asthma. The disease total annual cost is about $56 billion and includes both the direct and indirect costs of medications, hospital stays, missed work, and decreased productivity. Air pollution with xenobiotics, bacterial agents, and industrial nanomaterials, such as carbon nanotubes, contribute to the exacerbation of this condition and are a point of particular attention in environmental toxicology as well as in occupational health and safety research...
August 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28668505/regulation-of-allergic-airway-inflammation-by-adoptive-transfer-of-cd4-t-cells-preferentially-producing-il-10
#18
Masaya Matsuda, Kana Doi, Tatsuya Tsutsumi, Shinya Fujii, Maki Kishima, Kazuma Nishimura, Ikue Kuroda, Yu Tanahashi, Rino Yuasa, Toshihiko Kinjo, Nobuyuki Kuramoto, Nobuaki Mizutani, Takeshi Nabe
Anti-inflammatory pharmacotherapy for asthma has mainly depended on the inhalation of glucocorticoids, which non-specifically suppress immune responses. If the anti-inflammatory cytokine interleukin (IL)-10 can be induced by a specific antigen, asthmatic airway inflammation could be suppressed when individuals are exposed to the antigen. The purpose of this study was to develop cellular immunotherapeutics for atopic diseases using IL-10-producing CD4(+) T cells. Spleen cells isolated from ovalbumin (OVA)-sensitized mice were cultured with the antigen, OVA and growth factors, IL-21, IL-27 and TGF-β for 7 days...
June 29, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28658564/a-clustering-approach-to-identify-and-characterize-the-asthma-and-chronic-obstructive-pulmonary-disease-overlap-phenotype
#19
K Hirai, T Shirai, M Suzuki, T Akamatsu, T Suzuki, I Hayashi, A Yamamoto, T Akita, S Morita, K Asada, D Tsuji, K Inoue, K Itoh
BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. The phenotypes that have clinical features of both asthma and COPD are still incompletely understood. OBJECTIVE: To clarify the best discriminators of the asthma-COPD overlap phenotype from asthma and COPD subgroups using a clustering approach. METHODS: This study assessed pathophysiological parameters, including mRNA expression levels of T helper cell-related transcription factors, namely TBX21 (Th1), GATA3 (Th2), RORC (Th17) and FOXP3 (Treg), in peripheral blood mononuclear cells in asthma patients (n=152) and in COPD patients (n=50)...
November 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28658559/innate-and-adaptive-type-2-immunity-in-lung-allergic-inflammation
#20
REVIEW
Masato Kubo
Allergic inflammation is a type 2 immune disorder classically characterized by high levels of immunoglobulin E (IgE) and the development of Th2 cells. Asthma is a pulmonary allergic inflammatory disease resulting in bronchial hyper-reactivity. Atopic asthma is defined by IgE antibody-mediated mast cell degranulation, while in non-atopic asthma there is no allergen-specific IgE and more involvement of innate immune cells, such as basophils, group 2 innate lymphoid cells (ILC2), and eosinophils. Recently, protease allergens were shown to cause asthmatic responses in the absence of Th2 cells, suggesting that an innate cell network (IL-33/TSLP-basophil-ILC2-IL-5/IL-13 axis) can facilitate the sensitization phase of type 2 inflammatory responses...
July 2017: Immunological Reviews
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