Morphological and Molecular Characteristics of “Difficult” Asthma

Селиванова, П. А.; Куликов, Е. С.; Козина, О. В.; Gereng, E. A.; Freidin, Maxim B.; Огородова, Л. М.

doi:10.3109/02770900903584001

Cited by 14 publications

(12 citation statements)

References 12 publications

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“…In leukocytes and the bronchi of patients with cystic fibrosis it was shown that the content of acetylcholine is substantially reduced, leading to reduced vesicle storage and transport of nonneuronal acetylcholine [33]. With respect to gene expression of muscarinic receptors, bronchoscopic evaluation of the mucosa in asthma patients revealed an increased expression of M 3 receptor mRNA in severe asthmatics compared to patients with mild-to-moderate asthma and significantly higher levels of M 3 receptor mRNA in patients with brittle asthma [45]. A similar investigation revealed that there are significantly lower levels of the M 3 receptor mRNA in patients with COPD as compared to asthma patients, and that M 3 receptor mRNA gene expression was significantly elevated in COPD patients with bronchial hyperresponsiveness as compared with patients without bronchial hyperresponsiveness [46], indicating that different molecular mechanisms underlie the clinical heterogeneity of bronchoconstriction in severe asthma and COPD.…”

Section: Muscarinic Receptors In Obstructive Pulmonary Diseasesmentioning

confidence: 99%

Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects

Karakiulakis

Roth

2012

Mediators of Inflammation

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Muscarinic receptors are expressed by most cell types and mediate cellular signaling of their natural ligand acetylcholine. Thereby, they control numerous central and peripheral physiological organ responses to neuronal activity. In the human lung, muscarinic receptors are predominantly expressed by smooth muscle cells, epithelial cells, and fibroblasts. Antimuscarinic agents are used for the treatment of chronic obstructive pulmonary disease and to a lesser extent for asthma. They are primarily used as bronchodilators, but it is now accepted that they are also associated with anti-inflammatory, antiproliferative, and antiremodeling effects. Remodeling of the small airways is a major pathology in COPD and impairs lung function through changes of the extracellular matrix. Glycosaminoglycans, particularly hyaluronic acid, and matrix metalloproteases are among extracellular matrix molecules that have been associated with tissue inflammation and remodeling in lung diseases, including chronic obstructive pulmonary disease and asthma. Since muscarinic receptors have been shown to influence the homeostasis of glycosaminoglycans and matrix metalloproteases, these molecules may be proved valuable endpoint targets in clinical studies for the pharmacological exploitation of the anti-inflammatory and antiremodeling effects of muscarinic inhibitors in the treatment of chronic obstructive pulmonary disease and asthma.

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Section: Muscarinic Receptors In Obstructive Pulmonary Diseasesmentioning

confidence: 99%

Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects

Karakiulakis

Roth

2012

Mediators of Inflammation

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“…We have previously shown that HRH1 mRNA expression was significantly up-regulated in adults (p=0.04) with asthma compared to those without asthma (10) . Selivanova et al also found that HRH1 mRNA expression is significantly higher in patients with “brittle” asthma compared to those with mild to moderate asthma suggesting a possible “dose response” (39) . Therefore in our study we wanted to determine if the difference in mRNA expression between those with and without asthma could be explained by genetic variation in genes that directly involve histamine.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation within the histamine pathway among patients with asthma – a pilot study

et al. 2014

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Objective Histamine is an important mediator in the pathophysiology of asthma. We have previously reported that HRH1 is differentially expressed among those with asthma compared to those without asthma. Single histamine related genes have also been associated with asthma. We aimed to evaluate known single nucleotide polymorphisms (SNPs) in genes along the histamine biotransformation and response pathway and determine their association with asthma and HRH1 mRNA expression. Methods We enrolled children and adults (n=93) with/without asthma who met inclusion/exclusion criteria. Genotyping was performed for 9 known SNPs in the HDC, HRH1, HRH4, HNMT, and ABP1 genes. HRH1 mRNA expression was determined on RNA from buccal tissue. General linear model, Fisher's exact test, and Chi-square test were used to determine differences in allele, genotype, and haplotype frequency between subjects with and without asthma and differential HRH1 mRNA expression relative to genotype. Statistical significance was determined by p<0.05. Results No difference was observed in genotype/allele frequency for the 9 SNPs between subjects with and without asthma. The HNMT-1639C/ −464C/ 314C/ 3’UTRA haplotype was more frequently observed in those without asthma than those with asthma (p=0.03). We also observed genetic differences relative to race and gender. HNMT 314 genotype CT was more frequent in males with asthma compared to those without asthma (p=0.04). Conclusions Histamine pathway haplotype was associated with a diagnosis of asthma in our cohort but allele and genotype were not. Subgroup evaluations may also be important. Further studies are needed to determine the potential biological/clinical significance of our findings.

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“…Ранее нами были описаны морфологические и мо лекулярные особенности фенотипов тяжелой резис тентной к терапии БА [24][25][26]. В данном исследо вании мы дополнили группы пациентов с БА и сравнили показатели с больными ХОБЛ.…”

Section: Discussionunclassified

Genetic aspects of different phenotypes of COPD and asthma

Огородова¹,

Черняк²,

Козина³

et al. 2013

Pulʹmonologiâ (Mosk.)

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Morphological and Molecular Characteristics of “Difficult” Asthma

Abstract: There is evidence of significantly different morphological characteristics and molecular mechanisms of inflammation and bronchoconstriction underlying the clinical heterogeneity of severe asthma.

Cited by 14 publications

References 12 publications

Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects

Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects

Genetic variation within the histamine pathway among patients with asthma – a pilot study

Genetic aspects of different phenotypes of COPD and asthma

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