Abstract:
BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the antifibrotic drug pirfenidone. METHODS:We conducted a post-hoc analysis of the prospective, multicenter, randomized, placebo-controlled, phase 3 trial of pirfenidone in Japan (total, n = 267; pirfenidone, n = 163; placebo, n = 104). Logistic regression analysis was performed to extract parameters that predicted disease progression, defined by a ≥ 10% relative decline in vital capacity (VC) from baseline and/or death, at week 52. For assessment of serum surfactant protein (SP)-D, SP-A and Krebs von den Lungen (KL)-6, all patients were dichotomized by the median concentration of each biomarker at baseline to the high and low biomarker subgroups. Associations of these concentrations were examined with changes in VC at each time point from baseline up to week 52, along with progression-free survival (PFS). Additionally, the effect of pirfenidone treatment on serial longitudinal concentrations of these biomarkers were evaluated. RESULTS:In the multivariate logistic regression analysis, body mass index (BMI), %VC and SP-D in the pirfenidone group, and BMI and %VC in the placebo group were indicated as predictors of disease progression. Pirfenidone treatment reduced the decline in VC with statistical significance in the low SP-D and low SP-A subgroups over most of the treatment period, and also prolonged PFS in the low SP-D and low KL-6 subgroups. Furthermore, SP-D levels over time course were reduced in the pirfenidone group from as early as week 8 until the 52-week treatment period compared with the placebo group. CONCLUSIONS:Serum SP-D was the most consistent biomarker for the efficacy of pirfenidone in the cohort trial of IPF. Serial measurements of SP-D might have a potential for application as a pharmacodynamic biomarker. Trial registration The clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13, 2005 (registration No. JapicCTI-050121; http://Clinicaltrials.jp ).
journal_name
Respir Resjournal_title
Respiratory researchauthors
Ikeda K,Chiba H,Nishikiori H,Azuma A,Kondoh Y,Ogura T,Taguchi Y,Ebina M,Sakaguchi H,Miyazawa S,Suga M,Sugiyama Y,Nukiwa T,Kudoh S,Takahashi H,Pirfenidone Clinical Study Group in Japan.doi
10.1186/s12931-020-01582-ysubject
Has Abstractpub_date
2020-11-30 00:00:00pages
316issue
1eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-020-01582-yjournal_volume
21pub_type
杂志文章abstract::The novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been co...
journal_title:Respiratory research
pub_type: 信件
doi:10.1186/s12931-020-01363-7
更新日期:2020-04-22 00:00:00
abstract:BACKGROUND:Accumulation of profibrotic myofibroblasts in fibroblastic foci (FF) is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis (IPF) pathogenesis, and transforming growth factor (TGF)-β plays a key regulatory role in myofibroblast differentiation. Reactive oxygen species (ROS) has...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0420-x
更新日期:2016-08-30 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: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:While adverse effects of exposure to air pollutants on respiratory health are well studied, little is known about the effect of a reduction in air pollutants on chronic respiratory symptoms and diseases. We investigated whether different declines in air pollution levels in industrialised and rural areas in G...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-11-113
更新日期:2010-08-22 00:00:00
abstract:BACKGROUND:Prior microrheologic assessments of selected, microlitre plugs of cystic fibrosis (CF) sputum suggest no intrinsic rheologic abnormality. However, such analyses may not be representative of CF sputum as a whole. We therefore reassessed this question using whole sputum macrorheology. Additionally, we wished t...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-10-63
更新日期:2009-07-06 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:There are limited series concerning Dieulafoy disease of the bronchus. We describe the clinical presentation of a series of 7 patients diagnosed with Dieulafoy disease of the bronchus and provide information about the pathological diagnosis approach. PATIENTS AND METHODS:A retrospective review of patients w...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-58
更新日期:2008-08-05 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: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:BACKBROUND:COPD is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease caused, in part, by the aberrant function of airway smooth muscle (ASM). We have previously demonstrated that hydrogen sulfi...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0788-x
更新日期:2018-05-09 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::Asthma is a complex inflammatory disorder controlled by both genetic and environmental influences. Multiple genetic analyses have identified the T helper type 2 (Th2) cytokine gene cluster on chromosome 5q as a susceptibility locus for asthma. Recently, the Th2 cytokine interleukin-13 has been shown to be a critical m...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/rr7
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:To assess the symptomatic and cost burden among patients initiating long-acting bronchodilator (LABD) therapy and impact of adherence on healthcare resource use and costs. METHODS:This retrospective cohort study identified patients with COPD who were newly prescribed a LABD (long-acting muscarinic antagonis...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-015-0295-2
更新日期:2015-11-16 00:00:00
abstract:BACKGROUND:MIF is a critical mediator of the host defense, and is involved in both acute and chronic responses in the lung. Neutralization of MIF reduces neutrophil accumulation into the lung in animal models. We hypothesized that MIF, in the alveolar space, promotes neutrophil accumulation via activation of the CD74 r...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-10-33
更新日期:2009-05-04 00:00:00
abstract:BACKGROUND:Colonization of the airways with potential pathogenic bacteria is observed in a number of chronic respiratory diseases, such as COPD or cystic fibrosis. Infections with respiratory viruses are known triggers of exacerbations of these diseases. We here investigated if pre-exposure to bacteria alters the respo...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0382-z
更新日期:2016-06-03 00:00:00
abstract::A new international statement defines usual interstitial pneumonia (UIP) which is a histological and radiological form of idiopathic pulmonary fibrosis (IPF) more precisely than previously. In the diagnosis of IPF, either in high resolution computed tomography (HRCT) a UIP pattern must be present or alternatively spec...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/1465-9921-14-43
更新日期:2013-04-15 00:00:00
abstract:BACKGROUND:Cigarette smoke (CS) is the main cause in the development of chronic obstructive pulmonary disease (COPD), the pathogenesis of which is related to an extended inflammatory response. In this study, we investigated the effect of low and high doses of gas phase cigarette smoke (GPS) on cultured lymphocyte proge...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-10-82
更新日期:2009-09-10 00:00:00
abstract:BACKGROUND:ABCA3 transporter (ATP-binding cassette transporter of the A subfamily) is localized to the limiting membrane of lamellar bodies, organelles for assembly and storage of pulmonary surfactant in alveolar epithelial type II cells (AECII). It transports surfactant phospholipids into lamellar bodies and absence o...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-4
更新日期:2011-01-07 00:00:00
abstract:BACKGROUND:The aim of the study is to examine the effect of limited and prolonged hyperoxia on neonatal rat lung. This is done by examining the morphologic changes of apoptosis, the expression of ceramide, an important mediator of apoptosis, the expression of inflammatory mediators represented by IL-1beta and the expre...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-100
更新日期:2006-07-26 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0410-z
更新日期:2016-07-29 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章,meta分析
doi:10.1186/s12931-019-1163-2
更新日期:2019-08-16 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-89
更新日期:2007-12-04 00:00:00
abstract:BACKGROUND:The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction receptor that can initiate and perpetuate inflammation. Its soluble isoform (sRAGE) acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation. With the present study, we aime...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-37
更新日期:2011-03-30 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::Signaling through G protein-coupled receptors (GPCRs) mediates numerous airway smooth muscle (ASM) functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that ...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:
更新日期:2003-01-01 00:00:00
abstract::Mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a protein with anti-inflammatory properties and the archetypal member of the dual-specificity phosphatases (DUSPs) family that have emerged over the past decade as playing an instrumental role in the regulation of airway inflammation. Not only does MKP-1...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-017-0637-3
更新日期:2017-08-10 00:00:00
abstract:BACKGROUND:Induced and spontaneous sputum are used to evaluate the airways microbiota. Whether the sputum types can be used interchangeably in microbiota research is unknown. Our aim was to compare microbiota in induced and spontaneous sputum from COPD patients sampled during the same consultation. METHODS:COPD patien...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0645-3
更新日期:2017-08-29 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01442-9
更新日期:2020-07-29 00:00:00
abstract:BACKGROUND:The prevalence of pneumocystis pneumonia (PCP) and associated hypoxic respiratory failure is increasing in human immunodeficiency virus (HIV)-negative patients. However, no prior studies have evaluated the effect of early anti-PCP treatment on clinical outcomes in HIV-negative patient with severe PCP. Theref...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1188-6
更新日期:2019-09-26 00:00:00