Asthma therapy and airway remodeling

Mauad, Thaís; Bel, Elisabeth H.; Sterk, Peter J.

doi:10.1016/j.jaci.2007.06.031

Cited by 170 publications

(126 citation statements)

References 161 publications

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“…ICS decrease airway vascularity, abnormal vascular permeability, basal membrane thickness, and airway hyperresponsiveness and increase forced expiratory volume in the first second (FEV1) [3]. Despite ICS treatment efficacy, it is known that treatment response is highly variable between patients.…”

Section: Introductionmentioning

confidence: 99%

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids

Rijavec¹,

Žavbi²,

Lopert³

et al. 2018

J Investig Allergol Clin Immunol

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Background. Asthma treatment response is highly variable and pharmacogenetic markers that predict treatment response would be one step closer to personalized treatment. GWAS studies have shown that polymorphisms GLCCI1 could be associated with asthma treatment response to inhaled corticosteroids (ICS).Materials and methods. We genotyped rs37973 of GLCCI1 in 208 adult asthma patients treated with ICS. Change in % predicted FEV1 was analysed after short-term (3 months) and after long-term (at least 3 years) treatment. Treatment success was defined as good when FEV1 decreased less than 30 ml/year.Results. After 3 months of treatment, change of % predicted FEV1 was higher in patients with GG genotype than in patients with AG+AA genotype, and this genotype dependent difference was only evident in non-smokers. Similar results were found after at least 3 years of treatment when all patients were analysed, in non-smokers and patients with atopy. Even though, no differences in treatment success (good vs. poor response) were observed when analysing the entire group of patients, genotype dependent treatment success was highly influenced by smoking and atopy. GG genotype was overrepresented in non-smokers and patients with atopy with good response.Conclusions. Rs37973 was associated with short-and long-term treatment response; however, there was a great influence of smoking and atopy on pharmacogenetic association. Furthermore, we found GG genotype to be associated with better treatment response, what is contrary to results found in GWAS.Keywords: pharmacogenetics, rs37973, GLCCI1, FEV1, smoking, atopy ResumenIntroducción: La respuesta al tratamiento del asma es muy variable y los marcadores farmacogenéticos que predicen esta respuesta nos sitúan más cerca del tratamiento personalizado. Los estudios de asociación de genoma completo (GWAS) han demostrado que los polimorfismos GLCCI1 podrían estar asociados con la respuesta al tratamiento con corticosteroides inhalados (ICS).Material y métodos. Se genotipó el polimorfismo de un solo nucleótico (SNP) rs37973 de GLCCI1 en 208 pacientes adultos con asma tratados con ICS. El cambio en el porcentual de lFEV1 predicho se analizó después de un tratamiento a corto plazo (3 meses) y después de un tratamiento a largo plazo (al menos 3 años). El éxito del tratamiento se definió como bueno cuando el FEV1 disminuyó menos de 30 ml / año.Resultados. Después de 3 meses de tratamiento, el cambio en el porcentual del FEV1 predicho fue mayor en pacientes con genotipo GG que en pacientes con genotipo AG + AA, y esta diferencia asociada al genotipo solo fue evidente en los no fumadores. Se encontraron resultados similares, en el análisis de la muestra completa de pacientes, después de al menos 3 años de tratamiento, tanto en no fumadores y como en pacientes atópicos. A pesar de que no se observaron diferencias en el éxito del tratamiento (buena frente a mala respuesta) al analizar todo el grupo de pacientes, el éxito del tratamiento dependiente del genotipo estuvo muy influenciado por el...

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Section: Introductionmentioning

confidence: 99%

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids

Rijavec¹,

Žavbi²,

Lopert³

et al. 2018

J Investig Allergol Clin Immunol

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“…This includes an increase in airway smooth muscle (ASM) mass, altered deposition of extracellular matrix proteins in-and outside the ASM layer, goblet cell and glandular hyperplasia and angiogenesis [4]. Therefore, the functional and structural characteristics of the airways in asthma are highly complex, which impedes the development of novel targeted therapy [5].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome sequencing (RNA-Seq) of human endobronchial biopsies: asthmaversuscontrols

Yick

Zwinderman²,

Kunst

et al. 2013

Eur Respir J

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The cellular and molecular pathways in asthma are highly complex. Increased understanding can be obtained by unbiased transcriptomic analysis (RNA-Seq). We hypothesised that the transcriptomic profile of whole human endobronchial biopsies differs between asthma patients and controls.First, we investigated the feasibility of obtaining RNA from whole endobronchial biopsies suitable for RNA-Seq. Secondly, we examined the difference in transcriptomic profiles between asthma and controls. This cross-sectional study compared four steroid-free atopic asthma patients and five healthy nonatopic controls. Total RNA from four biopsies per subject was prepared for RNA-Seq. Comparison of the numbers of reads per gene in asthma and controls was based on the Poisson distribution.46 genes were differentially expressed between asthma and controls, including pendrin, periostin and BCL2. 10 gene networks were found to be involved in cellular morphology, movement and development.RNA isolated from whole human endobronchial biopsies is suitable for RNA-Seq, showing different transcriptomic profiles between asthma and controls. Novel and confirmative genes were found to be linked to asthma. These results indicate that biological processes in the airways of asthma patients are regulated differently when compared to controls, which may be relevant for the pathogenesis and treatment of the disease. @ERSpublications Transcriptome sequencing shows processes in the airways of asthmatics are differently regulated at transcriptomic level

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“…Goblet cell hyperplasia and increased mucus production is commonly described within the airways of asthmatics along with an alteration in the composition of the released mucus (Rogers, 2002;Fahy, 2002;Mauad et al, 2007). Under asthmatic conditions, mucin protein expression appears to be altered, with the mucus itself being found to be more adhesive and less fluid in nature (Fahy; Gordon; Mauad et al; Sumi & Hamid; Warner & Knight).…”

Section: Introductionmentioning

confidence: 99%

The Morphological Effects of Asthma, As Well As Conventional and Alternative Asthma Therapies on Parietal and Chief Cells in the Stomach of BALB/c Mice

2011

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VIEIRA, W. A.; OBERHOLZER, H. M. & PRETORIUS, E.The morphological effects of asthma, as well as conventional and alternative asthma therapies on parietal and chief cells in the stomach of BALB/c mice. Int. J. Morphol., 29(4):1341-1350, 2011. SUMMARY:Scientific literature, although limited in this area, supports the hypothesis that asthma, by means of selective leukocyte trafficking between the various mucosal and glandular sites of the body, can have the same pathophysiological effects on the stomach as the airways. This study aimed to determine if asthma, in the absence and presence of various asthma therapies (Hydrocortisone and Modul8 TM ), imparted any morphological alteration on the stomach parietal and chief cells. The BALB/c murine asthmatic mouse model was the model of choice in this study. The asthma induction protocol as well as the asthma therapies were proved to be effective with the aid of bronchial lavage fluid leukocyte quantification. Fundic and pyloric biopsies were extracted at termination and assessed by means of transmission electron, scanning electron and light microscopy. The extracted fundic and pyloric biopsies revealed asthma alone induced parietal cell hypertrophy (increase in parietal cell size P < 0.000100 in both stomach regions) and chief cell hyper functioning. The use of Hydrocortisone and Modul8 TM , as a therapy to correct the perceived gastric alterations were dismal; only in the case of fundic parietal cells were both treatments able to compensate for the hypertrophic effect caused by asthma, while in the pylorus parietal cell asthma-induced hypertrophy was only compensated for by Modul8 TM .

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Asthma therapy and airway remodeling

Cited by 170 publications

References 161 publications

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids

Transcriptome sequencing (RNA-Seq) of human endobronchial biopsies: asthmaversuscontrols

The Morphological Effects of Asthma, As Well As Conventional and Alternative Asthma Therapies on Parietal and Chief Cells in the Stomach of BALB/c Mice

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