Abstract:
BACKGROUND:Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function. This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting beta2-agonists, formoterol and salmeterol. METHODS:This was a randomized, double-blind, double-dummy, two-way crossover, multicenter study. Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 microg) and salmeterol/fluticasone (50/500 microg), separated by a 4-14-day washout period. ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients. The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects. RESULTS:Mean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 microM x hr versus 6.21 microM x hr) and fluticasone (0.84 microM x hr versus 1.50 microM x hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point). In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 microM versus 0.09 microM). The amount of expectorated fluticasone (percentage of estimated lung-deposited dose) in sputum over 6 hours was significantly higher versus budesonide (ratio 5.21; p = 0.006). Both treatments were well tolerated. CONCLUSION:The relative systemic availabilities of budesonide and fluticasone between patients with severe COPD and healthy subjects were similar. In patients with COPD, a larger fraction of fluticasone was expectorated in the sputum as compared with budesonide. TRIAL REGISTRATION:Trial registration number NCT00379028.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Dalby C,Polanowski T,Larsson T,Borgström L,Edsbäcker S,Harrison TWdoi
10.1186/1465-9921-10-104subject
Has Abstractpub_date
2009-10-31 00:00:00pages
104eissn
1465-9921issn
1465-993Xpii
1465-9921-10-104journal_volume
10pub_type
杂志文章,多中心研究,随机对照试验abstract:BACKGROUND:Influenza virus binds to cell receptors via sialic acid (SA) linked glycoproteins. They recognize SA on host cells through their haemagglutinins (H). The distribution of SA on cell surfaces is one determinant of host tropism and understanding its expression on human cells and tissues is important for underst...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-73
更新日期:2007-10-25 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:OBJECTIVE:To investigate the differences in the proportions of BMPR2 mutations in familial hereditary pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH) between males and females and the relationship between BMPR2 mutation and PAH severity. METHODS:A computer was used to searc...
journal_title:Respiratory research
pub_type: 杂志文章,meta分析
doi:10.1186/s12931-020-1309-2
更新日期:2020-02-06 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::Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD. Our understanding of the key molecular mechanisms which drive the pathologi...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-019-1017-y
更新日期:2019-03-04 00:00:00
abstract:STUDY OBJECTIVE:The primary aim of this study was to investigate whether IMA levels are helpful in the diagnosis of pulmonary embolism (PE). The secondary aim was to determine whether IMA was more effective alone or in combination with clinical probability scores in the diagnosis of PE. Thirdly, the sensitivity and spe...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-49
更新日期:2008-05-30 00:00:00
abstract:BACKGROUND:Extended culture of monocytes and fibroblasts in three-dimensional collagen gels leads to degradation of the gels (see linked study in this issue, "Fibroblasts and monocytes contract and degrade three-dimensional collagen gels in extended co-culture"). The current study, therefore, was designed to evaluate p...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/rr73
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Although T cells, especially CD8+, have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, their role during acute exacerbations (AE-COPD) is uncertain. METHODS:We recruited subjects with COPD and a history of previous AE-COPD and studied them quarterly to collect blood and sponta...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章
doi:10.1186/s12931-015-0251-1
更新日期:2015-08-05 00:00:00
abstract:BACKGROUND:Mutations in the eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4) gene have recently been identified in recessively inherited veno-occlusive disease. In this study we assessed if EIF2AK4 mutations occur also in a family with autosomal dominantly inherited pulmonary arterial hypertension (HPAH) ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0457-x
更新日期:2016-11-04 00:00:00
abstract:BACKGROUND:WNT/β-catenin signaling plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, the role of WNT10A via transforming growth factor (TGF)-β signaling remains unclear. METHODS:We evaluated the expression of WNT10A and TGF-β in bleomycin (BLM)-treated mice and the interactio...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0357-0
更新日期:2016-04-12 00:00:00
abstract:BACKGROUND:The study of small airway diseases such as post-transplant bronchiolitis obliterans syndrome (BOS) is hampered by the difficulty in assessing peripheral airway function either physiologically or directly. Our aims were to develop robust methods for sampling small airway epithelial cells (SAEC) and to establi...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-10-99
更新日期:2009-10-26 00:00:00
abstract:BACKGROUND:Gas exchange represents the key physiological function of the lung, and is dependent upon proper formation of the delicate alveolar structure. Malformation or destruction of the alveolar gas-exchange regions are key histopathological hallmarks of diseases such as bronchopulmonary dysplasia (BPD), chronic obs...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-018-0837-5
更新日期:2018-08-06 00:00:00
abstract:BACKGROUND:Myofibroblasts play a major role in the synthesis of extracellular matrix (ECM) and the stimulation of these cells is thought to play an important role in the development of silicosis. The present study was undertaken to investigate the anti-fibrotic effects of dibutyryl-cAMP (db-cAMP) on rats induced by sil...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0523-z
更新日期:2017-02-21 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:Allergic asthma is characterized by airway inflammation in response to antigen exposure, leading to airway remodeling and lung dysfunction. Epithelial-mesenchymal transition (EMT) may play a role in airway remodeling through the acquisition of a mesenchymal phenotype in airway epithelial cells. TGF-β1 is kno...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-14-118
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Surfactant protein D (SP-D) can regulate both innate and adaptive immunity. Recently, SP-D has been shown to contribute to the pathogenesis of airway allergic inflammation and bleomycin-induced pulmonary fibrosis. However, in allergic airways disease, the role of SP-D in airway remodeling remains unknown. Th...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-014-0143-9
更新日期:2014-11-29 00:00:00
abstract:BACKGROUND:Few longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships. METHODS:Children underwent home collections of nasal lavage during scheduled surveillance periods and...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0922-9
更新日期:2018-11-21 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: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:Heightened inflammation, including expression of COX-2, is associated with COPD pathogenesis. RelB is an NF-κB family member that attenuates COX-2 in response to cigarette smoke by a mechanism that may involve the miRNA miR-146a. There is no information on the expression of RelB in COPD or if RelB prevents C...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-015-0214-6
更新日期:2015-05-06 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::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: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::In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-alpha R1KO) to understand the roles of TNF-alpha on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-alpha, we ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-75
更新日期:2007-10-30 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:Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV1-decline in male heavy smokers. M...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/1465-9921-14-55
更新日期:2013-05-20 00:00:00
abstract::The role of the ATP binding cassette transporter A1 (ABCA1) in maintaining cellular lipid homeostasis in cardiovascular disease is well established. More recently, the important beneficial role played by ABCA1 in modulating pathogenic disease mechanisms, such as inflammation, in a broad range of chronic conditions has...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-020-01515-9
更新日期:2020-09-25 00:00:00
abstract:BACKGROUND:The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma. METHODS:We performed a cross-sectional study comparing subjects with COPD and asthma to subjects ...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/1465-9921-12-127
更新日期:2011-09-27 00:00:00
abstract:BACKGROUND:It is unclear whether the responses of refractory and common Mycoplasma pneumoniae (MP) pneumonia to macrolides differ. Hence, this study aimed to identify biomarkers that may be used to distinguish refractory and common pneumonias caused by MP in children at hospital admission. METHODS:The study included 1...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1152-5
更新日期:2019-08-23 00:00:00
abstract:BACKGROUND:The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). METHODS:In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomis...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/1465-9921-12-55
更新日期:2011-04-26 00:00:00