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asthma endotypes or phenotypes

Tomotaka Kawayama, Takashi Kinoshita, Kazuko Matsunaga, Yoshiko Naito, Jun Sasaki, Yoshikazu Tominaga, Tomoaki Hoshino
Asthma is an allergic disease characterized by chronic airway inflammation, airway hyperresponsiveness (AHR), reversibility and remodeling. Inhaled corticosteroids (ICS) are effective in many patients with asthma. However, ICS are a controlling, but not but curative treatment, and there are still many patients with refractory and difficult-to-treat asthma. The evaluation of airway inflammation by induced sputum, non-specific AHR by methacholine, and asthmatic reactions by specific allergen challenge techniques are useful not only to investigate the pathogenesis of asthma but also to help develop new drugs for asthma management...
March 16, 2018: Kurume Medical Journal
C Incorvaia, C Cavaliere, F Frati, S Masieri
Allergic rhinitis (AR) was long considered a quite trivial disease, but the advance in epidemiological and clinical knowledge, with a major role for Allergic rhinitis and its Impact on Asthma (ARIA) initiative, substantially changed the scene. Now we know that AR has significant effects on patients’ quality of life and also has a relevant economic burden. The ARIA phenotypes related to the duration of symptoms and to the severity of AR are very useful in establishing the optimal strategy in each patient with AR, also according to the kind of allergens that cause rhinitis...
January 2018: Journal of Biological Regulators and Homeostatic Agents
Baptiste Couvy-Duchesne, Victoria O'Callaghan, Richard Parker, Natalie Mills, Katherine M Kirk, Jan Scott, Anna Vinkhuyzen, Daniel F Hermens, Penelope A Lind, Tracey A Davenport, Jane M Burns, Melissa Connell, Brendan P Zietsch, James Scott, Margaret J Wright, Sarah E Medland, John McGrath, Nicholas G Martin, Ian B Hickie, Nathan A Gillespie
PURPOSE: The Nineteen and Up study (19Up) assessed a range of mental health and behavioural problems and associated risk factors in a genetically informative Australian cohort of young adult twins and their non-twin siblings. As such, 19Up enables detailed investigation of genetic and environmental pathways to mental illness and substance misuse within the Brisbane Longitudinal Twin Sample (BLTS). PARTICIPANTS: Twins and their non-twin siblings from Queensland, Australia; mostly from European ancestry...
March 17, 2018: BMJ Open
Mari Hikichi, Shu Hashimoto, Yasuhiro Gon
Asthma and COPD appear as a result of different mechanisms triggered by different pathogeneses and although they present different features and symptoms of airway inflammation and airway obstruction, there are also cases that present the features of both asthma and COPD. This type of pathology is known as asthma-COPD overlap syndrome (ACOS). Asthma-COPD overlap is identified in clinical practice by the features that it shares with both asthma and COPD. This is not a definition, but a description for clinical use, as asthma-COPD overlap includes several different clinical phenotypes and there are likely to be several different underlying mechanisms"...
March 14, 2018: Allergology International: Official Journal of the Japanese Society of Allergology
Giuseppe Brescia, Claudia Zanotti, Daniela Parrino, Umberto Barion, Gino Marioni
PURPOSE: Endotyping chronic rhinosinusitis with nasal polyps (CRSwNP) poses a challenge for rhinologists nowadays. Phenotyping CRSwNP proved inappropriate as an approach to their classification because of their common clinical features. Endotyping, being based on the pathogenic mechanism, provides a precise picture more appropriate for use in clinical practice. Patients' treatment and follow-up can thus be tailored to cope with the degree of aggressiveness of a specific CRSwNP endotype...
March 7, 2018: American Journal of Otolaryngology
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
Nuria Farré, Ramon Farré, David Gozal
Obstructive Sleep Apnea (OSA) has emerged as a highly prevalent public health problem that imposes important mid-term and long-term consequences, namely cardiovascular, metabolic, cognitive and cancer-related alterations. OSA is characterized by increased upper airway resistance, alveolar hypoventilation, and recurrent upper airway obstruction during sleep. Recurrent collapse of the upper airway develops with sleep onset, and is associated with both intermittent hypoxemia and sleep fragmentation. The microbiome is a vast and complex polymicrobial ecosystem that coexists with the human organism, and has been identified as playing significant roles in the development of host immunological phenotypes...
March 13, 2018: Chest
Karina Jahnz-Różyk, Joanna Lis, Marta Warchoł, Aleksandra Kucharczyk
BACKGROUND: Allergic asthma is the most prevalent phenotype of severe asthma where treatment with omalizumab (OMB) has been proven to be particularly beneficial. In Poland, OMB therapy is available and reimbursed within a drug programme where strict inclusion and exclusion criteria are defined. The objective of this study was to present a descriptive analysis regarding the trends in outcomes (clinical, quality of life, costs) among a cohort of patients who satisfy inclusion criteria for the initiation of OMB treatment and who successfully responded to OMB according to a set of objective criteria...
March 16, 2018: BMC Pulmonary Medicine
Tao Wei, Lei Liu, Xiaoying Zhou
Airway smooth muscle (ASM) is a prominent effecter in maintaining bronchial muscle contraction and responsible for airway hyper-responsiveness (AHR); the phenotype change and over-proliferation of airway smooth muscle cells (ASMCs) play key roles in the pathogenesis of asthma. The aim of this study was to investigate the anti-proliferation effects of Cortex Dictamni aqueous extract (CDAE) and ethanol extract (CDE) on ASMCs and the possible underline mechanisms. Cell proliferation rates were determined by MTT assay; matrix metalloproteinases-2 (MMP-2) activity was examined by gelatin zymography; cell proliferation and migration were appraised by in-vitro cell-gap closure assessment; protein expressions of p38, Bcl-2 and FAK of ASMCs were evaluated by western blotting and Ca2+ influx of cells was measured by confocal laser microscope...
March 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Dimity H Ball, Lamyaa Al-Riyami, William Harnett, Margaret M Harnett
ES-62 is a secreted parasitic worm-derived immunomodulator that exhibits therapeutic potential in allergy by downregulating aberrant MyD88 signalling to normalise the inflammatory phenotype and mast cell responses. IL-33 plays an important role in driving mast cell responses and promoting type-2 allergic inflammation, particularly with respect to asthma, via MyD88-integrated crosstalk amongst the IL-33 receptor (ST2), TLR4 and FcεRI. We have now investigated whether ES-62 targets this pathogenic network by subverting ST2-signalling, specifically by characterising how the functional outcomes of crosstalk amongst ST2, TLR4 and FcεRI are modulated by the worm product in wild type and ST2-deficient mast cells...
March 14, 2018: Scientific Reports
Sean A McGhee
PURPOSE OF REVIEW: Although biologic therapies can provide outstanding efficacy in the management of lung disease, especially asthma, most of these agents have been approved only for adults. Recent findings provide new strategies for using these agents in children. RECENT FINDINGS: Extensive evidence has consistently demonstrated the efficacy and safety of biologic therapy for asthma. In addition, some studies have documented potentially important secondary effects, such as improving response to respiratory virus infection in asthmatic patients...
March 13, 2018: Current Opinion in Pediatrics
Cynthia Kanagaratham, Victoria Chiwara, Bianca Ho, Sanny Moussette, Mina Youssef, David Venuto, Lucie Jeannotte, Guillaume Bourque, Juan Bautista de Sanctis, Danuta Radzioch, Anna K Naumova
The human chromosomal region 17q12-q21 is one of the best replicated genome-wide association study loci for childhood asthma. The associated SNPs span a large genomic interval that includes several protein-coding genes. Here, we tested the hypothesis that the zona pellucida-binding protein 2 (ZPBP2) gene residing in this region contributes to asthma pathogenesis using a mouse model. We tested the lung phenotypes of knock-out (KO) mice that carry a deletion of the Zpbp2 gene. The deletion attenuated airway hypersensitivity (AHR) in female, but not male, mice in the absence of allergic sensitization...
March 13, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Yrina Rochman, Krista Dienger-Stambaugh, Phoebe K Richgels, Ian P Lewkowich, Andrey V Kartashov, Artem Barski, Gurjit K Khurana Hershey, Warren J Leonard, Harinder Singh
Pathogenic T helper 2 (TH 2) cells, which produce increased amounts of the cytokines interleukin-5 (IL-5) and IL-13, promote allergic disorders, including asthma. Thymic stromal lymphopoietin (TSLP), a cytokine secreted by epithelial and innate immune cells, stimulates such pathogenic TH 2 cell responses. We found that TSLP signaling in mouse CD4+ T cells initiated transcriptional changes associated with TH 2 cell programming. IL-4 signaling amplified and stabilized the genomic response of T cells to TSLP, which increased the frequency of T cells producing IL-4, IL-5, and IL-13...
March 13, 2018: Science Signaling
Giuseppe Brescia, Daniela Parrino, Lorenzo Nicolè, Claudia Zanotti, Cristiano Lanza, Umberto Barion, Filippo Marino, Gino Marioni
PURPOSE: The term aspirin-exacerbated respiratory disease (AERD) refers to a combination of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and acute respiratory tract reactions to nonsteroidal anti-inflammatory drugs. AERD has now been included among the CRSwNP endotypes, and is considered one of the most aggressive in terms of disease recurrence. Cortactin is a multi-domain protein with a part in several cellular mechanisms involving actin assembly and cytoskeleton arrangement...
March 5, 2018: American Journal of Otolaryngology
Eleftherios Zervas, Konstantinos Samitas, Andriana I Papaioannou, Petros Bakakos, Stelios Loukides, Mina Gaga
A small subgroup of patients with asthma suffers from severe disease that is either partially controlled or uncontrolled despite intensive, guideline-based treatment. These patients have significantly impaired quality of life and although they constitute <5% of all asthma patients, they are responsible for more than half of asthma-related healthcare costs. Here, we review a definition for severe asthma and present all therapeutic options currently available for these severe asthma patients. Moreover, we suggest a specific algorithmic treatment approach for the management of severe, difficult-to-treat asthma based on specific phenotype characteristics and biomarkers...
January 2018: ERJ Open Research
Ross Arena, Amy McNeil, Steven Street, Samantha Bond, Deepika R Laddu, Carl J Lavie, Andrew P Hills
Noncommunicable and chronic disease are interchangeable terms. According to the World Health Organization, "they are of long duration and generally slow progression. The 4 main types of chronic diseases are cardiovascular diseases (ie, heart attacks and stroke), cancers, chronic respiratory diseases (such as chronic obstructive pulmonary disease and asthma), and diabetes." We have known about the benefits of physical activity (PA) for thousands of years. Perhaps our approach, from public health messaging to the individual clinical encounter, as to how PA and exercise are discussed and prescribed can be improved upon, with the ultimate goal of increasing the likelihood that an individual moves more; ultimately moving more should be the goal...
April 2018: Current Problems in Cardiology
Cynthia C Jose, Lakshmanan Jagannathan, Vinay Singh Tanwar, Xiaoru Zhang, Chongzhi Zang, Suresh Cuddapah
Nickel (Ni) is an environmental and occupational carcinogen, and exposure to Ni is associated with lung and nasal cancers in humans. Furthermore, Ni exposure is implicated in several lung diseases including chronic inflammatory airway diseases, asthma and fibrosis. However, the mutagenic potential of Ni is low and does not correlate with its potent toxicity and carcinogenicity. Therefore, mechanisms underlying Ni exposure-associated diseases remain poorly understood. Since the health risks of environmental exposures often continue post exposure, understanding the exposure effects that persist after the termination of exposure could provide mechanistic insights into diseases...
March 12, 2018: Molecular Carcinogenesis
Jisoo Park, Eun Kyung Kim, Mi Ae Kim, Tae Hyung Kim, Jung Hyun Chang, Yon Ju Ryu, Sei Won Lee, Yeon Mok Oh, Suk Joong Yong, Won Il Choi, Kwang Ha Yoo, Ji Hyun Lee
BACKGROUND: Obstructive airway disease patients with increased variability of airflow and incompletely reversible airflow obstruction are often categorized as having asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). ACOS is heterogeneous with two sub-phenotypes: asthma-ACOS and COPD-ACOS. The objective of this study was to determine the difference in risk of exacerbation between the two sub-phenotypes of ACOS. METHODS: A total of 223 patients exhibiting incompletely reversible airflow obstruction with increased variability (spirometrically defined ACOS) were enrolled...
March 7, 2018: Tuberculosis and Respiratory Diseases
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
Fang Gong, Hua-Yan Zhu, Jie Zhu, Qiao-Jing Dong, Xuan Huang, Dong-Jin Jiang
The pathogenesis of allergic asthma is primarily characterized by abnormality in immunoglobin(Ig)E pathway, suggesting a possible role for follicular helper T cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR)5+ CD4+ T cells, known as "circulating" Tfh, share common functional characteristics with Tfh cells from germinal centers. The aim of this study was to determine the phenotypes and functions of circulating CXCR5+ CD4+ T cells in allergic asthmatics...
March 5, 2018: Immunology Letters
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