Abstract:
BACKGROUND:Proteomic studies of respiratory disorders have the potential to identify protein biomarkers for diagnosis and disease monitoring. Utilisation of sensitive quantitative proteomic methods creates opportunities to determine individual patient proteomes. The aim of the current study was to determine if quantitative proteomics of bronchial biopsies from asthmatics can distinguish relevant biological functions and whether inhaled glucocorticoid treatment affects these functions. METHODS:Endobronchial biopsies were taken from untreated asthmatic patients (n = 12) and healthy controls (n = 3). Asthmatic patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months) and new biopsies were obtained. Proteins extracted from the biopsies were digested and analysed using isobaric tags for relative and absolute quantitation combined with a nanoLC-LTQ Orbitrap mass spectrometer. Spectra obtained were used to identify and quantify proteins. Pathways analysis was performed using Ingenuity Pathway Analysis to identify significant biological pathways in asthma and determine how the expression of these pathways was changed by treatment. RESULTS:More than 1800 proteins were identified and quantified in the bronchial biopsies of subjects. The pathway analysis revealed acute phase response signalling, cell-to-cell signalling and tissue development associations with proteins expressed in asthmatics compared to controls. The functions and pathways associated with placebo and budesonide treatment showed distinct differences, including the decreased association with acute phase proteins as a result of budesonide treatment compared to placebo. CONCLUSIONS:Proteomic analysis of bronchial biopsy material can be used to identify and quantify proteins using highly sensitive technologies, without the need for pooling of samples from several patients. Distinct pathophysiological features of asthma can be identified using this approach and the expression of these features is changed by inhaled glucocorticoid treatment. Quantitative proteomics may be applied to identify mechanisms of disease that may assist in the accurate and timely diagnosis of asthma. TRIAL REGISTRATION:ClinicalTrials.gov registration NCT01378039.
journal_name
Respir Resjournal_title
Respiratory researchauthors
O'Neil SE,Sitkauskiene B,Babusyte A,Krisiukeniene A,Stravinskaite-Bieksiene K,Sakalauskas R,Sihlbom C,Ekerljung L,Carlsohn E,Lötvall Jdoi
10.1186/1465-9921-12-124subject
Has Abstractpub_date
2011-09-22 00:00:00pages
124eissn
1465-9921issn
1465-993Xpii
1465-9921-12-124journal_volume
12pub_type
杂志文章,随机对照试验abstract:BACKGROUND:During 2007-2010, the National Health and Nutrition Examination Survey (NHANES) conducted a spirometry component which obtained pre-bronchodilator pulmonary lung function data on a nationally representative sample of US adults aged 6-79 years and post-bronchodilator pulmonary lung function data for the subse...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-14-103
更新日期:2013-10-09 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::The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive. Transforming Growth Factor beta 1(TGF-beta1) is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar ep...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-114
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known. ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-25
更新日期:2005-03-05 00:00:00
abstract::Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised ...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-017-0578-x
更新日期:2017-05-17 00:00:00
abstract::The Global Initiative for Asthma (GINA) guidelines do not specify a bronchodilator range for bronchodilator response (BDR) testing and simply recommend a salbutamol dose of 200 to 400 μg. We determined the oscillometric BDR results of children given low-dose (2 puffs, 200 μg) and standard-dose (4 puffs, 400 μg) salbut...
journal_title:Respiratory research
pub_type: 信件,随机对照试验
doi:10.1186/s12931-017-0632-8
更新日期:2017-08-03 00:00:00
abstract:BACKGROUND:The home is the predominant environment for exposure to many environmental irritants such as air pollutants and allergens. Exposure to common indoor irritants including volatile organic compounds, formaldehyde and nitrogen dioxide, may increase the risk of snoring for children. The aim of this study was to i...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/1465-9921-5-19
更新日期:2004-11-04 00:00:00
abstract:BACKGROUND:Long-term lung allograft survival is limited by bronchiolitis obliterans syndrome (BOS). Mannose binding lectin (MBL) belongs to the innate immune system, participates in complement activation, and may predispose to graft rejection. We investigated mannose binding (MBL) during cold ischemia and in tissue sam...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-13-56
更新日期:2012-07-04 00:00:00
abstract:BACKGROUND:High-tidal-volume mechanical ventilation and hyperoxia used in patients with acute lung injury (ALI) can induce the release of cytokines, including high-mobility group box-1 (HMGB1), oxygen radicals, neutrophil infiltration, and the disruption of epithelial and endothelial barriers. Hyperoxia has been shown ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-90
更新日期:2011-07-05 00:00:00
abstract:BACKGROUND:Several previously healthy young adults have developed Coronavirus Disease 2019 (COVID-19), and a few of them progressed to the severe stage. However, the factors are not yet determined. METHOD:We retrospectively analyzed 123 previously healthy young adults diagnosed with COVID-19 from January to March 2020...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01412-1
更新日期:2020-06-22 00:00:00
abstract:BACKGROUND:Little is known about the association between cigarette smoking and asthma severity. We assessed smoking as a determinant of disease severity and control in a cohort of clinic-referred allergic subjects who developed new onset asthma. METHODS:Allergic rhinitis subjects with no asthma (n = 371) were followed...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-16
更新日期:2011-01-24 00:00:00
abstract:BACKGROUND:Adherence to tuberculosis (TB) treatment is troublesome, due to long therapy duration, quick therapeutic response which allows the patient to disregard about the rest of their treatment and the lack of motivation on behalf of the patient for improved. The objective of this study was to develop and validate a...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究
doi:10.1186/1465-9921-13-75
更新日期:2012-09-02 00:00:00
abstract:BACKGROUND:In vivo, the airways are constantly subjected to oscillatory strain (due to tidal breathing during spontaneous respiration) and (in the event of mechanical ventilation) positive pressure. This exposure is especially problematic for the cartilage-free bronchial tree. The effects of cyclic stretching (other th...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0464-y
更新日期:2016-11-14 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
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:The burden of symptoms and risk of exacerbations are the main drivers of the overall assessment of the Chronic Obstructive Pulmonary Disease (COPD) and the adequate treatment approaches per current Global Initiative for Chronic Obstructive Lung Disease (GOLD). Physical activity has emerged as both functional...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/s12931-019-1053-7
更新日期:2019-05-14 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:Diesel exhaust particles (DEPs) are deposited into the respiratory tract and are thought to be a risk factor for the development of diseases of the respiratory system. In healthy individuals, the timing and mechanisms of respiratory tract injuries caused by chronic exposure to air pollution remain to be clar...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-015-0172-z
更新日期:2015-02-07 00:00:00
abstract:BACKGROUND:Tobacco smoke and genetic susceptibility are risk factors for asthma and wheezing. The aim of this study was to investigate whether there is a combined effect of interleukin-13 gene (IL13) polymorphisms and tobacco smoke on persistent childhood wheezing and asthma. METHODS:In the Isle of Wight birth cohort ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-2
更新日期:2008-01-10 00:00:00
abstract:BACKGROUND:We have previously shown that vitamin D deficiency has a detrimental impact on lung development. In this study, we aimed to identify the mechanisms linking vitamin D with lung development using a mouse model of dietary manipulation. METHODS:Female offspring were euthanized at different time-points; embryoni...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0362-3
更新日期:2016-04-27 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:BACKGROUND:Hepcidin serves as a major regulator of systemic iron metabolism and immune function. Airway epithelial cells have an extensive interface with the environment, and so must be able to respond locally to the presence of particulates, infection, and inflammation. Therefore, we hypothesized that hepcidin is expr...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-100
更新日期:2011-08-02 00:00:00
abstract:BACKGROUND:Obstructive sleep apnea syndrome (OSAS) is a common disorder with significant morbidity and mortality. We aimed to evaluate the predictive accuracy of the Berlin questionnaire in patients with suspected OSAS undergoing PSG in the sleep laboratory setting against those going through the Embletta™ portable dia...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12931-019-1009-y
更新日期:2019-02-22 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: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:Although phosphodiesterase-4 (PDE4) inhibitors have been shown to reduce COPD exacerbation rate, their biological mechanism of action is not completely elucidated at the molecular level. We aimed to characterise the whole genome gene expression profile of the inhaled PDE4-inhibitor CHF6001 on top of triple t...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/s12931-020-1329-y
更新日期:2020-03-20 00:00:00
abstract:BACKGROUND:The relative contributions of the cytotoxic phenotype of P. aeruginosa expressing type III secretory toxins and an immunocompromised condition lacking normal Toll-like receptor 4 (TLR4) signaling in the pathogenesis of acute lung injury and sepsis were evaluated in a mouse model for Pseudomonas aeruginosa pn...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-5-1
更新日期:2004-02-12 00:00:00
abstract:BACKGROUND:Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and ...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究
doi:10.1186/1465-9921-15-27
更新日期:2014-03-04 00:00:00
abstract:BACKGROUND:Cognitive impairment has been found in chronic obstructive pulmonary disease (COPD) patients. However, the structural alteration of the brain and underlying mechanisms are poorly understood. METHODS:Thirty-seven mild-to-moderate COPD patients, forty-eight severe COPD patients, and thirty-one control subject...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-14-140
更新日期:2013-12-21 00:00:00
abstract:BACKGROUND:Although protective mechanical ventilation (MV) has been used in a variety of applications, lung injury may occur in both patients with and without acute respiratory distress syndrome (ARDS). The purpose of this study is to use machine learning to identify clinical phenotypes for critically ill patients with...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01588-6
更新日期:2020-12-10 00:00:00