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Asthma AND gene expression

Minji Jeon, Sunkyu Kim, Sungjoon Park, Heewon Lee, Jaewoo Kang
BACKGROUND: Drug combination therapy, which is considered as an alternative to single drug therapy, can potentially reduce resistance and toxicity, and have synergistic efficacy. As drug combination therapies are widely used in the clinic for hypertension, asthma, and AIDS, they have also been proposed for the treatment of cancer. However, it is difficult to select and experimentally evaluate effective combinations because not only is the number of cancer drug combinations extremely large but also the effectiveness of drug combinations varies depending on the genetic variation of cancer patients...
March 19, 2018: BMC Systems Biology
Erika M Manczak, Bryn Dougherty, Edith Chen
Depressive symptoms in parents and in youths have been found to relate to disease comorbidity processes in children, including greater disease-related impairment and poorer clinical outcomes. The current study sought to assess whether coming from a family characterized by more depressive symptoms on average would potentiate the effects of changes in youths' own negative mood on the expression of two receptor genes relevant to asthma that are the primary targets of asthma medication, such that the combination of low child negative mood in the context of greater parental depressive symptoms would relate to the lowest levels of gene expression...
March 20, 2018: Journal of Abnormal Child Psychology
Salman Siddiqui, Aarti Shikotra, Matthew Richardson, Emma Doran, David Choy, Alex Bell, Cary D Austin, Jeffrey Eastham-Anderson, Beverley Hargadon, Joseph R Arron, Andrew Wardlaw, Christopher E Brightling, Liam G Heaney, Peter Bradding
BACKGROUND: Asthma is a complex chronic disease underpinned by pathological changes within the airway wall. How variations in structural airway pathology and cellular inflammation contribute to the expression and severity of asthma are poorly understood. OBJECTIVES: Therefore we evaluated pathological heterogeneity using topological data analysis (TDA) with the aim of visualizing disease clusters and microclusters. METHODS: A discovery population of 202 adult patients (142 asthmatic patients and 60 healthy subjects) and an external replication population (59 patients with severe asthma) were evaluated...
March 7, 2018: Journal of Allergy and Clinical Immunology
Mei Mei, Haojun Song, Lina Chen, Bin Hu, Ru Bai, Diandou Xu, Ying Liu, Yuliang Zhao, Chunying Chen
BACKGROUND: Epidemiological studies have suggested that elevated levels of air pollution contribute to an increased incidence or severity of asthma. Although late-onset adult asthma seems to be more attributable to environmental risk factors, limited data is available on the impact of early-life exposure to size-fractionated ambient particulate matter (PM) on asthma in adults. We aimed to determine the effect on the development and exacerbation of asthma in the adult after the mice were exposed as juveniles to three size-fractionated ambient particulates collected from Beijing...
March 14, 2018: Particle and Fibre Toxicology
Allison K Farrell, Richard B Slatcher, Erin T Tobin, Ledina Imami, Derek E Wildman, Francesca Luca, Samuele Zilioli
The glucocorticoid receptor gene NR3C1 is an important down-regulator of inflammation and is typically under-expressed in individuals with low socioeconomic status (SES). Negative emotionality has been suggested as a potential mediator of SES disparities in health outcomes. In this study, we expand this literature by naturalistically assessing negative emotionality in a key emotional environment: the family. In a sample of 104 youth with asthma (10-17 years) and their primary caregiver, we assessed SES via caregiver report, emotional expression by youth and parents in the home over four days using the electronically activated recorder (EAR), and NR3C1 expression via blood collected from youth...
February 15, 2018: Psychoneuroendocrinology
Gregory E Miller, Edith Chen, Madeleine U Shalowitz, Rachel E Story, Adam K K Leigh, Paula Ham, Jesusa M G Arevalo, Steve W Cole
AIM: There are marked socioeconomic disparities in pediatric asthma control, but the molecular origins of these disparities are not well understood. To fill this gap, we performed genome-wide expression profiling of monocytes and T-helper cells from pediatric asthma patients of lower and higher socioeconomic status (SES). METHOD: Ninety-nine children with asthma participated in a cross-sectional assessment. Out of which 87% were atopic, and most had disease of mild (54%) or moderate (29%) severity...
March 12, 2018: Pediatric Pulmonology
Michael C Peters, Sheena Kerr, Eleanor M Dunican, Prescott G Woodruff, Merritt L Fajt, Bruce D Levy, Elliot Israel, Brenda R Phillips, David T Mauger, Suzy A Comhair, Serpil C Erzurum, Mats W Johansson, Nizar N Jarjour, Andrea M Coverstone, Mario Castro, Annette T Hastie, Eugene R Bleecker, Sally E Wenzel, John V Fahy
BACKGROUND: Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients on high dose inhaled corticosteroids (ICS) is uncertain. OBJECTIVE: To determine if airway type 2 inflammation persists in patients treated with ICS and to evaluate the clinical features of patients with steroid resistant airway type-2 inflammation. METHODS: We used qPCR to generate a composite metric of type-2 cytokine gene expression (type 2 Gene Mean, "T2GM") in induced sputum cells from healthy controls, severe asthma patients on ICS (n=174), and non-severe asthma patients on ICS (n=85)...
March 7, 2018: Journal of Allergy and Clinical Immunology
Charu Rajput, Megan P Walsh, Breanna N Eder, Ediri E Metitiri, Antonia P Popova, Marc B Hershenson
Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit discrete phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out using IFN-y and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2...
March 9, 2018: Physiological Genomics
Yu-Li Liu, Li-de Zhang, Tie-Ming Ma, Si-Tong Song, Hai-Tao Liu, Xu Wang, Ning Li, Chang Yang, Song Yu
Acupuncture was proven beneficial in treating allergic inflammation. We aimed to explore the regulation underlying the effects of acupuncture on Feishu, an acupoint most commonly used in the acupuncture therapy for respiratory diseases, with respect to the system of sympathetic nerve neurotransmitter acetylcholine (Ach). Male Wistar rats were randomly grouping. No treatment was taken in the normal group. Allergic asthma was induced using ovalbumin on the model, Feishu acupuncture, and sham acupuncture groups; then control or acupuncture treatment lasting for 3 weeks was performed...
March 8, 2018: Inflammation
F Nicole Dijk, Chengjian Xu, Erik Melén, Anne-Elie Carsin, Asish Kumar, Ilja M Nolte, Olena Gruzieva, Goran Pershagen, Neomi S Grotenboer, Olga E M Savenije, Josep Maria Antó, Iris Lavi, Carlota Dobaño, Jean Bousquet, Pieter van der Vlies, Ralf J P van der Valk, Johan C de Jongste, Martijn C Nawijn, Stefano Guerra, Dirkje S Postma, Gerard H Koppelman
Interleukin-1 receptor-like 1 ( IL1RL1 ) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of IL1RL1 SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study...
March 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Matthew C Altman, Elizabeth Whalen, Alkis Togias, George T O'Connor, Leonard B Bacharier, Gordon R Bloomberg, Meyer Kattan, Robert A Wood, Scott Presnell, Petra LeBeau, Katy Jaffee, Cynthia M Visness, William W Busse, James E Gern
BACKGROUND: Childhood asthma in inner city populations is a major public health burden and understanding early life immune mechanisms that promote asthma onset is key to disease prevention. Children who develop asthma demonstrate a high prevalence of aeroallergen sensitization and T helper 2 (Th2)-type inflammation, however the early life immune events that lead to Th2 skewing and disease development are unknown. OBJECTIVE: We sought to use RNA sequencing of peripheral blood mononuclear cells (PBMCs) collected at age 2 to determine networks of immune responses that occur in children who develop allergy and asthma...
March 5, 2018: Journal of Allergy and Clinical Immunology
Junfei Wang, Alen Faiz, Qi Ge, Cornelis J Vermeulen, Joanne Van der Velden, Kenneth J Snibson, Rob van de Velde, Sonia Sawant, Dikaia Xenaki, Brian Oliver, Wim Timens, Nick Ten Hacken, Maarten van den Berge, Alan James, John G Elliot, Liang Dong, Janette K Burgess, Anthony W Ashton
Neovascularization, increased basal membrane thickness and increased airway smooth muscle (ASM) bulk are hallmarks of airway remodelling in asthma. In this study, we examined connective tissue growth factor (CTGF) dysregulation in human lung tissue and animal models of allergic airway disease. Immunohistochemistry revealed that ASM cells from patients with severe asthma (A) exhibited high expression of CTGF, compared to mild and non-asthmatic (NA) tissues. This finding was replicated in a sheep model of allergic airways disease...
March 7, 2018: Journal of Cellular and Molecular Medicine
Angel Cy Mak, Marquitta J White, Walter L Eckalbar, Zachary A Szpiech, Sam S Oh, Maria Pino-Yanes, Donglei Hu, Pagé Goddard, Scott Huntsman, Joshua Galanter, Ann Chen Wu, Blanca E Himes, Soren Germer, Julia M Vogel, Karen L Bunting, Celeste Eng, Sandra Salazar, Kevin L Keys, Jennifer Liberto, Thomas J Nuckton, Thomas A Nguyen, Dara G Torgerson, Pui-Yan Kwok, Albert M Levin, Juan C Celedón, Erick Forno, Hakon Hakonarson, Patrick M Sleiman, Amber Dahlin, Kelan G Tantisira, Scott T Weiss, Denise Serebrisky, Emerita Brigino-Buenaventura, Harold J Farber, Kelley Meade, Michael A Lenoir, Pedro C Avila, Saunak Sen, Shannon M Thyne, William Rodriguez-Cintron, Cheryl A Winkler, Andrés Moreno-Estrada, Karla Sandoval, Jose R Rodriguez-Santana, Rajesh Kumar, L Keoki Williams, Nadav Ahituv, Elad Ziv, Max A Seibold, Robert B Darnell, Noah Zaitlen, Ryan D Hernandez, Esteban G Burchard
Rationale Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. Objective To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. Methods We performed the first whole genome sequencing (WGS) pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. Measurements and Main Results We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (p < 3...
March 6, 2018: American Journal of Respiratory and Critical Care Medicine
Yali Huang, Shengding Zhang, Xiaoyu Fang, Lu Qin, Yu Fan, Dandan Ding, Xiansheng Liu, Min Xie
OBJECTIVE: We investigated the relationship between plasma miRNAs levels and inflammatory characteristics in asthmatic patients. METHODS: Eligible adults with untreated asthma (n = 35) underwent a clinical assessment, sputum induction, and assessment of pulmonary function test and Asthma Control Test (ACT) scores. Asthma phenotypes were defined using the sputum cell count. miR-199a-5p expression was measured using quantitative real-time polymerase chain reaction (qPCR)...
2018: PloS One
Bo Sun, Linnan Zhu, Yaling Tao, Hai-Xi Sun, Yang Li, Peng Wang, Yuzhu Hou, Yang Zhao, Xiaodong Zhang, Lianfeng Zhang, Ning Na, Yong Zhao
Neutrophils are involved in the pathogenesis of allergy. However, the contribution of the different functionally polarized neutrophils in allergy needs to be clarified. We sought to define the characteristics of interleukin (IL)-33-induced neutrophils and the involvement of this subset of polarized neutrophils in allergic pathogenesis. Freshly isolated neutrophils were treated with different cytokines and the cytokine expression levels were detected by real-time PCR. The gene expression profile of IL-33-induced neutrophils was determined by microarray assay...
March 5, 2018: Cellular & Molecular Immunology
Oussama Lahmar, Mariem Salhi, Wajih Kaabachi, Anissa Berraies, Jamel Ammar, Munawar Hussain Soomro, Martin Larsen, Isabella Annesi-Maesano, Kamel Hamzaoui, Agnes Hamzaoui
INTRODUCTION: Several studies have shown a strong correlation between the serum vitamin D level and asthma severity and deficits in lung function. OBJECTIVE: Study the relationship between vitamin D and the severity of asthma by targeting five SNPs of vitamin D metabolism gene pathway in a Tunisian adult asthmatics population. METHODS: Our case-control study includes 154 adult asthmatic patients and 154 healthy Tunisian subjects. We genotyped many variants in three human genes encoding key components of the vitamin D metabolism, CYP2R1, CYP27B1, GC...
March 3, 2018: Lung
Tetsuo Miyake, Takashi Miyake, Makoto Sakaguchi, Hirokazu Nankai, Takahiro Nakazawa, Ryuichi Morishita
Transactivation of inflammatory and immune mediators in asthma is tightly regulated by nuclear factor κB (NF-κB) and signal transducer and activator of transcription 6 (STAT6). Therefore, we investigated the efficacy of simultaneous inhibition of NF-κB and STAT6 using a chimeric decoy strategy to prevent asthma exacerbation. The effects of decoy oligodeoxynucleotides were evaluated using an ovalbumin-induced mouse asthma model. Ovalbumin-sensitized mice received intratracheal administration of decoy oligodeoxynucleotides 3 days before ovalbumin challenge...
March 2, 2018: Molecular Therapy. Nucleic Acids
Cheng-Jian Xu, Cilla Söderhäll, Mariona Bustamante, Nour Baïz, Olena Gruzieva, Ulrike Gehring, Dan Mason, Leda Chatzi, Mikel Basterrechea, Sabrina Llop, Maties Torrent, Francesco Forastiere, Maria Pia Fantini, Karin C Lødrup Carlsen, Tari Haahtela, Andréanne Morin, Marjan Kerkhof, Simon Kebede Merid, Bianca van Rijkom, Soesma A Jankipersadsing, Marc Jan Bonder, Stephane Ballereau, Cornelis J Vermeulen, Raul Aguirre-Gamboa, Johan C de Jongste, Henriette A Smit, Ashish Kumar, Göran Pershagen, Stefano Guerra, Judith Garcia-Aymerich, Dario Greco, Lovisa Reinius, Rosemary R C McEachan, Raf Azad, Vegard Hovland, Petter Mowinckel, Harri Alenius, Nanna Fyhrquist, Nathanaël Lemonnier, Johann Pellet, Charles Auffray, Pieter van der Vlies, Cleo C van Diemen, Yang Li, Cisca Wijmenga, Mihai G Netea, Miriam F Moffatt, William O C M Cookson, Josep M Anto, Jean Bousquet, Tiina Laatikainen, Catherine Laprise, Kai-Håkon Carlsen, Davide Gori, Daniela Porta, Carmen Iñiguez, Jose Ramon Bilbao, Manolis Kogevinas, John Wright, Bert Brunekreef, Juha Kere, Martijn C Nawijn, Isabella Annesi-Maesano, Jordi Sunyer, Erik Melén, Gerard H Koppelman
BACKGROUND: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. METHODS: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design...
February 26, 2018: Lancet Respiratory Medicine
Niloufar Farzan, Susanne J Vijverberg, Michael Kabesch, Peter J Sterk, Anke H Maitland-van der Zee
Asthma is a complex multifactorial disease and it is the most common chronic disease in children. There is a high variability in response to asthma treatment, even in patients with good adherence to maintenance treatment, and a correct inhalation technique. Distinct underlying disease mechanisms in childhood asthma might be the reason of this heterogeneity. A deeper knowledge of the underlying molecular mechanisms of asthma has led to the recent development of advanced and mechanism-based treatments such as biologicals...
March 1, 2018: Pediatric Pulmonology
Jose L Gomez, Maria P Diaz, Gustavo Nino, Clemente J Britto
BACKGROUND: Asthma exacerbations are an important cause of morbidity in asthma. Respiratory infections are often involved in asthma exacerbations in both children and adults. Some individuals with asthma have increased susceptibility to viral infections and as a result increased rates of asthma exacerbations. We sought to identify a transcriptomic signature in the blood associated with asthma exacerbations triggered by respiratory infections (AETRI) and determine its association with increased risk for asthma exacerbations...
February 27, 2018: BMC Medical Genomics
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