Abstract:
BACKGROUND:Current therapy for relieving bronchoconstriction may be ineffective in severe asthma, particularly in the small airways. The aim of this study was to further characterise responses to the recently identified novel bronchodilators rosiglitazone (RGZ) and chloroquine (CQ) under conditions where β-adrenoceptor agonist efficacy was limited or impaired in mouse small airways within lung slices. METHODS:Relaxation to RGZ and CQ was assessed following submaximal methacholine (MCh) pre-contraction, in slices treated overnight with either RGZ, CQ or albuterol (ALB) (to induce β-adrenoceptor desensitization), and in slices treated with caffeine/ryanodine in which contraction is associated with increases in Ca2+ sensitivity in the absence of contractile agonist-induced Ca2+ oscillations. Furthermore, the effects of RGZ, CQ, ALB and isoproterenol (ISO) on the initiation and development of methacholine-induced contraction were also compared. RESULTS:RGZ and CQ, but not ALB or ISO, elicited complete relaxation with increasing MCh pre-contraction and maintained their potency and efficacy following β-adrenoceptor desensitization. RGZ, CQ and ALB maintained efficacy following overnight incubation with RGZ or CQ. Relaxation responses to all dilators were generally maintained but delayed after caffeine/ryanodine. Pre-treatment with RGZ, but not CQ, ALB or ISO, reduced MCh potency. CONCLUSIONS:This study demonstrates the superior effectiveness of RGZ in comparison to CQ and β-adrenoceptor agonists as a dilator of mouse small airways. Further investigation of the mechanisms underlying the relatively greater efficacy of RGZ under these conditions are warranted and should be extended to include studies in human asthmatic airways.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Donovan C,Simoons M,Esposito J,Ni Cheong J,Fitzpatrick M,Bourke JEdoi
10.1186/1465-9921-15-29subject
Has Abstractpub_date
2014-03-12 00:00:00pages
29eissn
1465-9921issn
1465-993Xpii
1465-9921-15-29journal_volume
15pub_type
杂志文章abstract:BACKGROUND:Myofibroblasts, proposed as being derived from circulating fibrocytes, are considered to be important cells in thickening of the basement membrane in patients with asthma. We have studied the correlation of tissue fibrocyte levels to basement membrane thickness and the presence of fibrocytes in bronchoalveol...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-50
更新日期:2006-03-29 00:00:00
abstract::Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs) do in tissues. The catalytic activity of these enzymes has been implicated to function in normal lung biology by participating in branching morphogenesis, homeostasis, and r...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/rr33
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:The variability in the inflammatory burden of the lung in cystic fibrosis (CF) patients together with the variable effect of glucocorticoid treatment led us to hypothesize that glucocorticoid receptor (GR) gene polymorphisms may affect glucocorticoid sensitivity in CF and, consequently, may contribute to var...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究
doi:10.1186/1465-9921-8-88
更新日期:2007-11-29 00:00:00
abstract:BACKGROUND:Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine wh...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0462-0
更新日期:2016-11-16 00:00:00
abstract:BACKGROUND:Cysteine-containing leukotrienes (cysteinyl-LTs) are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smoot...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-42
更新日期:2006-03-22 00:00:00
abstract:BACKGROUND:In utero exposure to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) has been linked to child lung function. Overlapping evidence suggests that child sex and exposure timing may modify effects and associations may be mediated through glutathione S-transferase P1 (GSTP1) methylatio...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0774-3
更新日期:2018-04-27 00:00:00
abstract:BACKGROUND:Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown tha...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章
doi:10.1186/1465-9921-6-81
更新日期:2005-07-24 00:00:00
abstract:BACKGROUND:Previously we showed that reduced availability of the essential amino acid tryptophan per se attenuates post-transcriptional control of interleukin (IL)-6 and IL-8 leading to hyperresponsive production of these inflammatory mediators by airway epithelial cells. Availability of the non-essential amino acid ar...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-10-62
更新日期:2009-07-03 00:00:00
abstract:BACKGROUND:Deep inspirations (DI) have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic air...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-23
更新日期:2008-02-28 00:00:00
abstract:BACKGROUND:Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies. This study investigated subjec...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-52
更新日期:2008-07-11 00:00:00
abstract:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a rapid progressive fibro-proliferative disorder with poor prognosis similar to lung cancer. The pathogenesis of IPF is uncertain, but loss of epithelial cells and fibroblast proliferation are thought to be central processes. Previous reports have shown that BARD1 expre...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-015-0278-3
更新日期:2015-09-29 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-38
更新日期:2006-03-10 00:00:00
abstract:BACKGROUND:The effects of corticosteroid-based therapy in patients with idiopathic nonspecific interstitial pneumonia (iNSIP), and factors affecting treatment outcome, are not fully understood. We aimed to investigate the long-term treatment response and factors affecting the treatment outcome in iNSIP patients from a ...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究
doi:10.1186/s12931-017-0686-7
更新日期:2017-12-06 00:00:00
abstract:BACKGROUND:A multitude of epidemiological studies have shown that ambient fine particulate matter 2.5 (diameter < 2.5um; PM2.5) was associated with increased morbidity and mortality of chronic obstructive pulmonary disease (COPD). However, the underlying associated mechanisms have not yet been elucidated. We conducted ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1081-3
更新日期:2019-06-13 00:00:00
abstract:BACKGROUND:Possible variation in bronchodilator response (BDR) according to age at the diagnosis of adult-onset asthma is unknown. Our aim was to assess if BDR in FEV1 is related to age at diagnosis of adult-onset asthma and how many subjects fulfill the 400 mL criterion of BDR, the suggested cut-off for asthma-like re...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01441-w
更新日期:2020-07-13 00:00:00
abstract::There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages. Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-019-1108-9
更新日期:2019-07-08 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-21
更新日期:2011-02-04 00:00:00
abstract:BACKGROUND:Inhaled furosemide offers a potentially novel treatment for dyspnoea, which may reflect modulation of pulmonary stretch receptor feedback to the brain. Specificity of relief is unclear because different neural pathways may account for different components of clinical dyspnoea. Our objective was to evaluate i...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12931-018-0886-9
更新日期:2018-09-20 00:00:00
abstract:BACKGROUND:Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients. Bacterial infection causes increased airway neutrophilic inflammation. The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain. We tested the hypothesis that bacterial load and eosinophi...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0570-5
更新日期:2017-05-08 00:00:00
abstract:BACKGROUND:The aim of this study was to develop and validate a model for pulmonary fibrosis, using ex vivo tissue cultures of lungs from bleomycin treated animals, enabling the investigation of fibrosis remodeling using novel biomarkers for the detection of ECM protein fragments. The combination of in vivo and ex vivo ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0394-8
更新日期:2016-07-05 00:00:00
abstract:BACKGROUND:ATP-regulated potassium channels (KATP) regulate pulmonary vascular tone and are involved in hypoxic pulmonary vasoconstriction (HPV). In patients with inflammation like sepsis or ARDS, HPV is impaired, resulting in a ventilation-perfusion mismatch and hypoxia. Since increase of vascular KATP channel Kir6.1 ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0735-x
更新日期:2018-02-13 00:00:00
abstract:BACKGROUND:Smoking cessation following lung cancer diagnosis has been found to improve several patient outcomes. Electronic cigarette (e-cigarette) use is now prevalent within Great Britain, however, use and practice among patients with lung cancer has not as yet been explored. The current study aims to explore e-cigar...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0367-y
更新日期:2016-05-17 00:00:00
abstract:BACKGROUND:Pentraxin 3 (PTX3) regulates multiple aspects of innate immunity and tissue inflammation. Recently, it has been reported that PTX3 deficiency enhances interleukin (IL)-17A-dominant pulmonary inflammation in an ovalbumin (OVA)-induced mouse asthma model. However, whether PTX3 treatment would provide protectio...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01499-6
更新日期:2020-09-16 00:00:00
abstract:BACKGROUND:Mechanical ventilation can cause ventilator-induced lung injury (VILI) and lung fibrosis; however, the underlying mechanisms are still not fully understood. RNA sequencing is a powerful means for detecting vitally important protein-coding transcripts and long non-coding RNAs (lncRNAs) on a genome-wide scale,...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0822-z
更新日期:2018-06-22 00:00:00
abstract:BACKGROUND:Aim of this prospective study was to compare clinical and genetic findings in children with idiopathic or heritable pulmonary arterial hypertension (I/HPAH) with children affected with congenital heart defects associated PAH (CHD-APAH). METHODS:Prospectively included were 40 consecutive children with invasi...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-14-3
更新日期:2013-01-09 00:00:00
abstract::A proportion of patients with certain types of interstitial lung disease (ILD), including chronic hypersensitivity pneumonitis and ILDs associated with autoimmune diseases, develop a progressive fibrosing phenotype that shows similarities in clinical course to idiopathic pulmonary fibrosis. Irrespective of the clinica...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-019-1022-1
更新日期:2019-03-14 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0451-3
更新日期:2016-10-24 00:00:00
abstract:BACKGROUND:Emphysema is a crucial pathological characteristic of chronic obstructive pulmonary disease (COPD). Oxidative stress, apoptosis and epigenetic mechanisms contribute to the pathogenesis of emphysema. However, an attempt to accurately identify whether these mechanisms interact with each other and how they are ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01495-w
更新日期:2020-09-03 00:00:00
abstract:RATIONALE:Smoking-induced chronic obstructive pulmonary disease (COPD) is associated with acquired systemic cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Recently, sweat evaporimetry has been shown to efficiently measure β-adrenergic sweat rate and specifically quantify CFTR function in the se...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-15-25
更新日期:2014-02-25 00:00:00
abstract::There is an increasing interest in the potential of exhaled biomarkers, such as volatile organic compounds (VOCs), to improve accurate diagnoses and management decisions in pulmonary diseases. The objective of this manuscript is to systematically review the current knowledge on exhaled VOCs with respect to their poten...
journal_title:Respiratory research
pub_type: 杂志文章,meta分析,评审
doi:10.1186/1465-9921-13-117
更新日期:2012-12-21 00:00:00