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Non th2 asthma

Paul C Schröder, Sabina Illi, Vera I Casaca, Anna Lluis, Andreas Böck, Caroline Roduit, Martin Depner, Remo Frei, Jon Genuneit, Petra Ina Pfefferle, Marjut Roponen, Juliane Weber, Charlotte Braun-Fahrländer, Josef Riedler, Jean-Charles Dalphin, Juha Pekkanen, Roger Lauener, Erika von Mutius, Bianca Schaub, Anne Hyvärinen, Anne M Karvonen, Maija-Riitta Hirvonen, Pekka Tiittanen, Sami Remes, Vincent Kaulek, Marie-Laure Dalphin, Markus J Ege, Georg J Loss, Harald Renz, Gert Doekes, Michael Kabesch
BACKGROUND: Farm exposure protects against development of allergies early in life. At 4.5 years, protection against asthma by farm-milk exposure was partially mediated by regulatory T-cells (Tregs). The aim of this study was to investigate the critical time window of the "asthma-protective" farm effect via Tregs during childhood immune maturation. METHODS: Tregs were assessed longitudinally at 4.5 and 6 years in 111 children (56 farm, 55 reference children) from the PASTURE/EFRAIM birth cohort (flow-cytometry)...
October 12, 2016: Allergy
Hussein H Mwanga, Mohamed Aqiel Dalvie, Tanusha S Singh, Kalavati Channa, Mohamed F Jeebhay
The objective of this study was to investigate the relationship between exposure to organophosphate (OP) and pyrethroid (PYR) pesticides with serum cytokine patterns and asthma-related outcomes among rural women workers. A cross-sectional study was conducted among rural women (n = 211), including those working and living on farms and nearby town dwellers. Pesticide exposure was assessed using urinary metabolite concentrations of OP and PYR pesticides. Health outcome assessment was ascertained through the European Community Respiratory Health Survey (ECRHS) questionnaire, fractional exhaled nitric oxide (FeNO), and serum cytokines associated with asthma...
2016: International Journal of Environmental Research and Public Health
Tadahiro Goto, Carlos A Camargo, Kohei Hasegawa
PURPOSE: Recent studies propose TH2-mediated inflammation in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). However, little is known about whether fractional exhaled nitric oxide (FeNO) differs between patients with ACOS and those with COPD alone. To address this knowledge gap, a nationally representative sample was analyzed to determine the difference in FeNO levels between patients with ACOS and those with COPD alone in the US population. PATIENTS AND METHODS: This is a cross-sectional analysis of the National Health and Nutrition Examination Survey from 2007 through 2012...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Hern-Tze Tina Tan, Kazunari Sugita, Cezmi A Akdis
PURPOSE OF REVIEW: The development of biological therapies has rapidly progressed during the last few years, and major advances were reported for the treatment of allergic diseases, such as atopic dermatitis, allergic rhinitis, urticaria, food allergy, and asthma. Here, we review biologicals targeting the type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, natural killer T cells, mast cells, basophils, and epithelial cells, such as IL-4, IL-5, IL-13, IL-31, tumor necrosis factor alpha (TNF-α), and thymic stromal lymphopoietin (TSLP)...
October 2016: Current Allergy and Asthma Reports
Zeneng Wang, Joseph A DiDonato, Jennifer Buffa, Suzy A Comhair, Mark A Aronica, Raed A Dweik, Nancy A Lee, James J Lee, Mary Jane Thomassen, Mani Kavuru, Serpil C Erzurum, Stanley L Hazen
The biochemical mechanisms through which eosinophils contribute to asthma pathogenesis are unclear. Here we show eosinophil peroxidase (EPO), an abundant granule protein released by activated eosinophils, contributes to characteristic asthma-related phenotypes through oxidative posttranslational modification (PTM) of proteins in asthmatic airways through a process called carbamylation. Using a combination of studies we now show EPO uses plasma levels of the pseudohalide thiocyanate (SCN(-)) as substrate to catalyze protein carbamylation, as monitored by PTM of protein lysine residues into N(ϵ)-carbamyllysine (homocitrulline), and contributes to the pathophysiological sequelae of eosinophil activation...
October 14, 2016: Journal of Biological Chemistry
Zhihong Chen, Jue Pan, Yi Jia, Dandan Li, Zhihui Min, Xiaoqiong Su, Honglei Yuan, Geng Shen, Shengxuan Cao, Lei Zhu, Xiangdong Wang
BACKGROUND: Recent data have demonstrated that long-lived memory T cells are present in the human lung and can play significant roles in the pathogenesis of specific allergic and autoimmune diseases. However, most evidence has been obtained from mouse studies, and the potential roles of memory T cells in human allergic diseases, such as asthma, remain largely unknown. METHODS: Thirty-three asthmatics, 26 chronic obstructive pulmonary disease (COPD) patients, and 22 healthy volunteers were enrolled in this study...
August 31, 2016: Cell Biology and Toxicology
Chih-Hsi Scott Kuo, Stelios Pavlidis, Matthew Loza, Fred Baribaud, Anthony Rowe, Ioannis Pandis, Uruj Hoda, Christos Rossios, Ana Sousa, Susan J Wilson, Peter Howarth, Barbro Dahlen, Sven-Erik Dahlen, Pascal Chanez, Dominick Shaw, Norbert Krug, Thomas Sandström, Bertrand De Meulder, Diane Lefaudeux, Stephen Fowler, Louise Fleming, Julie Corfield, Charles Auffray, Peter J Sterk, Ratko Djukanovic, Yike Guo, Ian M Adcock, Kian Fan Chung
RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes. METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement...
August 31, 2016: American Journal of Respiratory and Critical Care Medicine
Cynthia Kanagaratham, Danuta Radzioch
Asthma is a disease that currently affects approximately 300 million people worldwide. It is generally viewed as an allergic disease and can manifest itself in a variety of phenotypes. Two of its main phenotypes routinely assessed at the clinic include airway hyperresponsiveness and IgE production. They can be measured in a non-invasive manner and have been used for genetic studies. However, the genetic complexity of asthma and its phenotypes makes it difficult to map their genetic contributors. Though human studies have been successful at mapping candidate genes for asthma phenotypes, they require large sample sizes and proper segregation of the population to control for potential confounding factors...
August 29, 2016: Current Pharmaceutical Design
Magdalena Muc, Anabela Mota-Pinto, Cristina Padez
Obesity is a risk factor for asthma, and obese asthmatics have lower disease control and increased symptom severity. Several putative links have been proposed, including genetics, mechanical restriction of the chest and the intake of corticosteroids. The most consistent evidence, however, comes from studies of cytokines produced by the adipose tissue called adipokines. Adipokine imbalance is associated with both proinflammatory status and asthma. Although reverse causation has been proposed, it is now acknowledged that obesity precedes asthma symptoms...
August 12, 2016: Nutrition Research Reviews
Bo Lund Krogsgaard Chawes
Asthma and allergies are today the most common chronic diseases in children and the leading causes of school absences, chronic medication usage, emergency department visits and hospitalizations, which affect all members of the family and represent a significant societal and scientific challenge. These highly prevalent disorders are thought to originate from immune distortion in early childhood, but the etiology and heterogeneity of the disease mechanisms are not understood, which hampers preventive initiatives and makes treatment inadequate...
August 2016: Danish Medical Journal
T A Smith-Norowitz, S Carvajal-Raga, J Weedon, R Joks, K B Norowitz, D Weaver, H G Durkin, M R Hammerschlag, S Kohlhoff
BACKGROUND: Asthma is a common pediatric chronic inflammatory airway disease. Respiratory viral infections are frequent infectious triggers for exacerbations of asthma. OBJECTIVE: We sought to determine whether Enterovirus 71 (EV71), a ubiquitous virus that causes systemic inflammatory responses in children but is not a known respiratory pathogen, can also serve as an infectious trigger for asthma. METHODS: Specific EV71 IgE and IgM antibodies (Abs), total serum IgE, and IL-2 and IL-4 cytokine levels in serum of asthmatic and non-asthmatic children (N = 42, ages 5-19; N = 35, ages 1-20, respectively) were measured (ELISA)...
July 20, 2016: Irish Journal of Medical Science
Rob G J A Zuiker, Catherine Tribouley, Zuzana Diamant, J Diderik Boot, Adam F Cohen, K Van Dyck, I De Lepeleire, Veronica M Rivas, Vladislav A Malkov, Jacobus Burggraaf, Marcella K Ruddy
BACKGROUND: Inhaled allergen challenge is a validated disease model of allergic asthma offering useful pharmacodynamic assessment of pharmacotherapeutic effects in a limited number of subjects. OBJECTIVES: To evaluate whether an RNA signature can be identified from induced sputum following an inhaled allergen challenge, whether a RNA signature could be modulated by limited doses of inhaled fluticasone, and whether these gene expression profiles would correlate with the clinical endpoints measured in this study...
2016: European Clinical Respiratory Journal
Chin-Kan Chan, Ting-Chun Lin, Yung-An Huang, Ya-Shan Chen, Chia-Ling Wu, Huei-Yu Lo, Ming-Ling Kuo, Kang-Hsi Wu, Jing-Long Huang
BACKGROUND: Asthma is a chronic airway inflammatory disease that has a high prevalence nowadays, and seeking the means of relieving asthmatic symptoms is now an issue with increased importance. While mesenchymal stem cells have been demonstrated to display immunomodulatory effects, the effect of fetus-type mesenchymal stem cells (MSCs) on asthmatic symptoms in vivo have not been reported to date. METHODS: Female BALB/c mice at 8 weeks of age were sensitized by ovalbumin, and MSCs derived from Wharton's jelly of human umbilical cord mesenchymal stem cells (hUCMSCs) were injected into the asthmatic mice...
October 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Magdy Mohamed Zedan, Amal Mohamed Osman, Wafaa Nabil Laimon, Mohamed Magdy Zedan, Nermin Youssef Abo-Elkheir, Ahmed Zaki
Asthma is a heterogeneous disease, in which asthmatic patients present with different clinical phenotypes, variable endotypes, and different response to asthma medicines. Thus, we are faced with an asthma paradox; asthma is diagnosed subjectively by clinical history and treated with biologically active drugs. To solve this paradox, we need objective airway biomarkers to tailor the proper medications to the proper patient. Biomarkers should have one or more of the following characteristics:1) A biomarker that could differentiate poor symptoms perceivers from over perceivers, 2) A biomarker that could predict disease activity and hence disease outcome, 3) A biomarker that could clarify responders from non-responders asthma phenotypes, and finally 4) A biomarker that could characterize different clinical asthma phenotypes...
June 2016: Iranian Journal of Immunology: IJI
M C Matheson, J C Reece, R K Kandane-Rathnayake, M L K Tang, J A Simpson, I H Feather, M C Southey, H Tsimiklis, J L Hopper, S C Morrison, G G Giles, E H Walters, S C Dharmage
BACKGROUND: Evidence suggests that specific allergen sensitizations are associated with different allergic diseases which may reflect different underlying immune profiles. We aimed to examine the cytokine profiles of individuals sensitized to eight common aeroallergens. METHODS: We used data from the Tasmanian Longitudinal Health Study a population-based cohort study of 45-year-olds. Serum cytokines (IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α) were measured in 1157 subjects using the LINCOplex assays...
June 22, 2016: Allergy
Yi Jia, Xu Fang, Xuehua Zhu, Chunxue Bai, Lei Zhu, Meiling Jin, Xiangdong Wang, Min Hu, Renhong Tang, Zhihong Chen
RATIONALE: Type 2 innate lymphoid cells (ILC2s) have been shown to produce large amounts of type 2 cytokines in a non-antigen specific manner. These cytokines act upstream and downstream of ILC2 and are increasingly popular in asthma drug development, thus warranting a closer investigation of the mechanism-related clinical manifestations of ILC2 from asthma patient selection perspective. OBJECTIVES: We hypothesized that IL-13+ ILC2s in the circulation might correlate with asthma control status as a result of persistent Th2 inflammation in the lung...
June 17, 2016: American Journal of Respiratory Cell and Molecular Biology
Alison N Thorburn, Hsin-Yi Tseng, Chantal Donovan, Nicole G Hansbro, Andrew G Jarnicki, Paul S Foster, Peter G Gibson, Philip M Hansbro
BACKGROUND: Exposure to non-pathogenic Streptococcus pneumoniae and vaccination are inversely associated with asthma. Studies in animal models demonstrate that airway administration of S. pneumoniae (live or killed), or its vaccines or components, suppresses the characteristic features of asthma in mouse models of allergic airway disease (AAD). These components could be developed into immunoregulatory therapies. S. pneumoniae components are recognized by Toll-like receptors (TLR) 2 and TLR4, and both induce inflammatory cell responses through the adaptor protein myeloid differentiation primary response gene 88 (MyD88)...
2016: PloS One
A C Gavino, K Nahmod, U Bharadwaj, G Makedonas, D J Tweardy
BACKGROUND: STAT3 drives development of Th17 cells and cytokine production by Th2 and Th17 cells, which contribute to asthma. Alternative asthma treatments are needed, especially for the Th17 phenotype. We sought to determine whether C188-9, a small-molecule STAT3 inhibitor, can block Th2 and Th17 cell expansion and cytokine production to prevent house dust mite (HDM)-induced airway inflammation and remodeling. METHODS: Three groups of C57BL/6 mice were treated intranasally (IN) and intraperitoneally (IP) daily for 3 weeks with the following: (i) vehicle 1 IN and vehicle 2 IP, (ii) HDM IN and vehicle 2 IP, or (iii) HDM IN and C188-9 IP...
May 26, 2016: Allergy
C C de Araújo, P S Marques, J D Silva, C S Samary, A L da Silva, I Henriques, M A Antunes, M V de Oliveira, R C Goldenberg, M M Morales, I Abreu, B L Diaz, N N Rocha, V L Capelozzi, P R M Rocco
Experimental studies have reported that aerobic exercise after asthma induction reduces lung inflammation and remodeling. Nevertheless, no experimental study has analyzed whether regular/moderate aerobic training before the induction of allergic asthma may prevent these inflammatory and remodeling processes. For this purpose, BALB/c mice (n = 96) were assigned into non-trained and trained groups. Trained animals ran on a motorized treadmill at moderate intensity, 30 min/day, 3 times/week, for 8 weeks, and were further randomized into subgroups to undergo ovalbumin sensitization and challenge or receive saline using the same protocol...
January 6, 2016: Scandinavian Journal of Medicine & Science in Sports
Shanru Li, Cynthia Koziol-White, Joseph Jude, Meiqi Jiang, Hengjiang Zhao, Gaoyuan Cao, Edwin Yoo, William Jester, Michael P Morley, Su Zhou, Yi Wang, Min Min Lu, Reynold A Panettieri, Edward E Morrisey
Asthma is one of the most common chronic diseases globally and can be divided into presenting with or without an immune response. Current therapies have little effect on nonimmune disease, and the mechanisms that drive this type of asthma are poorly understood. Here, we have shown that loss of the transcription factors forkhead box P1 (Foxp1) and Foxp4, which are critical for lung epithelial development, in the adult airway epithelium evokes a non-Th2 asthma phenotype that is characterized by airway hyperresponsiveness (AHR) without eosinophilic inflammation...
May 2, 2016: Journal of Clinical Investigation
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