Abstract:
BACKGROUND:Early life impairments leading to lower lung function by adulthood are considered as risk factors for chronic obstructive pulmonary disease (COPD). Recently, we compared the lung transcriptomic profile between two mouse strains with extreme total lung capacities to identify plausible pulmonary function determining genes using microarray analysis (GSE80078). Advancement of high-throughput techniques like deep sequencing (eg. RNA-seq) and microarray have resulted in an explosion of genomic data in the online public repositories which however remains under-exploited. Strategic curation of publicly available genomic data with a mouse-human translational approach can effectively implement "3R- Tenet" by reducing screening experiments with animals and performing mechanistic studies using physiologically relevant in vitro model systems. Therefore, we sought to analyze the association of functional variations within human orthologs of mouse lung function candidate genes in a publicly available COPD lung RNA-seq data-set. METHODS:Association of missense single nucleotide polymorphisms, insertions, deletions, and splice junction variants were analyzed for susceptibility to COPD using RNA-seq data of a Korean population (GSE57148). Expression of the associated genes were studied using the Gene Paint (mouse embryo) and Human Protein Atlas (normal adult human lung) databases. The genes were also assessed for replication of the associations and expression in COPD-/mouse cigarette smoke exposed lung tissues using other datasets. RESULTS:Significant association (p < 0.05) of variations in 20 genes to higher COPD susceptibility have been detected within the investigated cohort. Association of HJURP, MCRS1 and TLR8 are novel in relation to COPD. The associated ADAM19 and KIT loci have been reported earlier. The remaining 15 genes have also been previously associated to COPD. Differential transcript expression levels of the associated genes in COPD- and/ or mouse emphysematous lung tissues have been detected. CONCLUSION:Our findings suggest strategic mouse-human datamining approaches can identify novel COPD candidate genes using existing datasets in the online repositories. The candidates can be further evaluated for mechanistic role through in vitro studies using appropriate primary cells/cell lines. Functional studies can be limited to transgenic animal models of only well supported candidate genes. This approach will lead to a significant reduction of animal experimentation in respiratory research.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Vishweswaraiah S,George L,Purushothaman N,Ganguly Kdoi
10.1186/s12931-018-0795-ysubject
Has Abstractpub_date
2018-06-06 00:00:00pages
92issue
1eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-018-0795-yjournal_volume
19pub_type
杂志文章abstract::Reports regarding gender-related differences in COPD expression have provided conflicting results. In the French Initiatives BPCO real-world cohort, which contained 688 patients (146 women) when data were extracted, women were matched with men (1:3 ratio: n = 107:275) on age (5-year intervals) and FEV1 (5% predicted i...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-15-20
更新日期:2014-02-17 00:00:00
abstract:BACKGROUND:Pulmonary arterial hypertension (PAH) is associated with inflammatory response but it is unknown whether it is associated with alterations in NNMT activity and MNA plasma concentration. Here we examined changes in NNMT-MNA pathway in PAH in rats and humans. METHODS:PAH in rats was induced by a single subcut...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0423-7
更新日期:2016-08-31 00:00:00
abstract:BACKGROUND:Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile ...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12931-018-0950-5
更新日期:2018-12-07 00:00:00
abstract:BACKGROUND:Generally, structural destruction of lung parenchyma, such as pulmonary emphysema, is considered to be related to the low diagnostic yields and high complication rates of lung biopsies of peripheral lung lesions. Currently, little is known about the clinical outcomes of using endobronchial ultrasound with a ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1149-0
更新日期:2019-08-06 00:00:00
abstract:BACKGROUND:Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC) nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO) production--due to competition with neuronal NO-synthase (nNOS) for the comm...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-6
更新日期:2006-01-12 00:00:00
abstract:BACKGROUND:A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by activated leukocytes, and fibroblasts in vitro. Whether ADAM15 expression is increased in the lungs of COPD patients is not known. METHODS:ADAM15 gene expression and/or protein levels were measured in whole lung and bronchoalveolar lavag...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01446-5
更新日期:2020-07-16 00:00:00
abstract::By airway surface liquid, we mean a thin fluid continuum consisting of the airway lining layer and the alveolar lining layer, which not only serves as a protective barrier against foreign particles but also contributes to maintaining normal respiratory mechanics. In recent years, measurements of the rheological proper...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-019-1229-1
更新日期:2019-12-04 00:00:00
abstract:RATIONALE:We had shown that COPD women expressed more dyspnea than men for the same degree of airway obstruction. OBJECTIVES:Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients. METHODS:In a FEV1 % matched population of 100 men and women with COPD we measured: age, MMRC, FEV1, ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-18
更新日期:2007-03-06 00:00:00
abstract:BACKGROUND:Human beta-defensin-4 (hBD-4), a new member of the beta-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrob...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-130
更新日期:2005-11-04 00:00:00
abstract:BACKGROUND:The common cold is the most widespread viral infection in humans. Iota-carrageenan has previously shown antiviral effectiveness against cold viruses in clinical trials. This study investigated the efficacy of a carrageenan-containing nasal spray on the duration of the common cold and nasal fluid viral load i...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/1465-9921-14-124
更新日期:2013-11-13 00:00:00
abstract:BACKGROUND:Neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human Enterovirus 71 (EV71) strain MP4. However, the hallmark of severe human EV71 infection, pulmonary edema (PE), was not evident. METHODS:To test whether EV71-induced PE required a proinflammato...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-147
更新日期:2011-11-06 00:00:00
abstract::Small airway and vessels play a critical role in chronic airway and pulmonary vascular diseases, but their pharmacology has not been well characterised. We have studied airway and vascular responses in rat lung slices and separately in vitro using myography. In lung slices, under basal conditions, acetylcholine contra...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-111
更新日期:2006-08-21 00:00:00
abstract:OBJECTIVES:Swimming is one of the most popular forms of physical activity. Pool water is cleaned with chlorine, which - in combination with compounds contained in water - could form chloramines and trichloromethane in the swimmer's lungs. The aim of the present study was to examine the effect of swimming training in an...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01350-y
更新日期:2020-04-15 00:00:00
abstract:BACKGROUND:Acute respiratory distress syndrome (ARDS) is a life-threatening critical illness, characterised by qualitative and quantitative surfactant compositional changes associated with premature airway collapse, gas-exchange abnormalities and acute hypoxic respiratory failure. The underlying mechanisms for this dys...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-014-0128-8
更新日期:2014-11-07 00:00:00
abstract::The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The pas...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/1465-9921-6-78
更新日期:2005-07-21 00:00:00
abstract:BACKGROUND:Recent studies have indicated the presence of multipotent mesenchymal stromal cells (MSCs) in human lung diseases. Excess airway smooth muscle, myofibroblasts and activated fibroblasts have each been noted in asthma, suggesting that mesenchymal progenitor cells play a role in asthma pathogenesis. We therefor...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-11-127
更新日期:2010-09-21 00:00:00
abstract:BACKGROUND:Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popula...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0611-0
更新日期:2017-06-30 00:00:00
abstract:BACKGROUND:Patients with severe, uncontrolled asthma, particularly those with a non-eosinophilic phenotype, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01513-x
更新日期:2020-10-13 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc) is a rare connective tissue disease with a heterogeneous clinical course. Interstitial lung disease (ILD) is a common manifestation of SSc and a leading cause of death. MAIN BODY:All patients newly diagnosed with SSc should receive a comprehensive clinical evaluation, including asse...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-019-0980-7
更新日期:2019-01-18 00:00:00
abstract:BACKGROUND:Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity. METHODS:We selected 31 phenotypic variables and 12 ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-11-30
更新日期:2010-03-16 00:00:00
abstract:BACKGROUND:Dual bronchodilator therapy is recommended for symptomatic patients with chronic obstructive pulmonary disease (COPD). There are limited data on effects of a combination of two long-acting bronchodilators on lung function including body plethysmography. METHODS:This multicentre, randomised, double-blind, si...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/s12931-016-0498-1
更新日期:2017-01-11 00:00:00
abstract:BACKGROUND:An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene B4 (LTB4), and lipoxin A4 (LXA4) production by alveolar macrophages (AMs) and studied the impact of corticosteroids. METHODS:AMs obtained by fiberoptic bronch...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-11-71
更新日期:2010-06-07 00:00:00
abstract:BACKGROUND:Stress of the endoplasmic reticulum (ER) leading to activation of the unfolded protein response (UPR) and alveolar epithelial cell (AEC) apoptosis may play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our objectives were to determine whether circulating caspase-cleaved cytokeratin-18 (c...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-13-105
更新日期:2012-11-20 00:00:00
abstract::Healthy individuals have few goblet cells in their airways, but in patients with hypersecretory diseases goblet-cell upregulation results in mucus hypersecretion, airway plugging, and death. Multiple stimuli produce hypersecretion via epidermal growth factor receptor (EGFR) expression and activation, causing goblet-ce...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/rr43
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:The patterns of mandibular movements (MM) during sleep can be used to identify increased respiratory effort periodic large-amplitude MM (LPM), and cortical arousals associated with "sharp" large-amplitude MM (SPM). We hypothesized that Cheyne Stokes breathing (CSB) may be identified by periodic abnormal MM p...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0551-8
更新日期:2017-04-20 00:00:00
abstract::Important paradigms of pulmonary disease with nontuberculous mycobacteria (NTM) are currently shifting based on an increasing attention within the field of cystic fibrosis (CF). These shifts are likely to benefit the management of all patients with pulmonary NTM, regardless of underlying pathology. Currently several k...
journal_title:Respiratory research
pub_type: 社论
doi:10.1186/1465-9921-15-41
更新日期:2014-04-11 00:00:00
abstract:BACKGROUND:Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD) evening and twice-daily (BD) regimens of the novel inhaled corticosteroid fluticasone furoate (FF) in ast...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/1465-9921-12-160
更新日期:2011-12-21 00:00:00
abstract:BACKGROUND:Pulmonary neuroendocrine cells (PNEC) are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribut...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-115
更新日期:2005-10-10 00:00:00
abstract:BACKGROUND:Obesity augments pulmonary responses to ozone. We have reported that IL-33 contributes to these effects of obesity in db/db mice. The purpose of this study was to determine whether IL-33 also contributes to obesity-related changes in the response to ozone in mice with diet-induced obesity. METHODS:Male wild...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01361-9
更新日期:2020-04-23 00:00:00
abstract:BACKGROUND:Impaired regulatory T cell (Treg) function is thought to contribute to ongoing inflammatory responses in sarcoidosis, but underlying mechanisms remain unclear. Moreover, it is not known if increased apoptotic susceptibility of Tregs may contribute to an impaired immunosuppressive function in sarcoidosis. The...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-015-0265-8
更新日期:2015-09-16 00:00:00