Abstract:
BACKGROUND:Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF. METHODS:Using pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI (< 25; ≥25 to < 30; ≥30 kg/m2) and by weight loss over 52 weeks (≤5; > 5%) using random coefficient regression. RESULTS:In the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (- 283.3 [SE 22.4], - 207.9 [20.9] and - 104.5 [21.4] in patients with BMI < 25 kg/m2, ≥25 to < 30 kg/m2 and ≥ 30 kg/m2, respectively). Nintedanib reduced the rate of FVC decline versus placebo in all subgroups by BMI, with a consistent treatment effect across subgroups (interaction p = 0.31). In the placebo group, the mean rate of FVC decline was numerically greater in patients with > 5% than ≤5% weight loss over 52 weeks (- 312.7 [SE 32.2] versus - 199.5 [SE 14.4] mL/year). Nintedanib reduced the rate of FVC decline versus placebo in both subgroups by weight loss, with a greater treatment effect in patients with > 5% weight loss (interaction p = 0.0008). The adverse event profile of nintedanib was similar across subgroups. CONCLUSIONS:In patients with IPF, lower BMI and weight loss may be associated with faster decline in FVC. Nintedanib reduces the rate of FVC decline both in patients who lose weight on treatment and those who do not. TRIAL REGISTRATION:ClinicalTrials.gov ; Nos. NCT01335464 and NCT01335477 ; URL: www.clinicaltrials.gov .
journal_name
Respir Resjournal_title
Respiratory researchauthors
Jouneau S,Crestani B,Thibault R,Lederlin M,Vernhet L,Valenzuela C,Wijsenbeek M,Kreuter M,Stansen W,Quaresma M,Cottin Vdoi
10.1186/s12931-020-01528-4subject
Has Abstractpub_date
2020-11-25 00:00:00pages
312issue
1eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-020-01528-4journal_volume
21pub_type
杂志文章abstract:BACKGROUND:Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associat...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-014-0089-y
更新日期:2014-08-06 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: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::MMP28 is constitutively expressed by epithelial cells in many tissues, including the respiratory epithelium in the lung and keratinocytes in the skin. This constitutive expression suggests that MMP28 may serve a role in epithelial cell homeostasis. In an effort to determine its function in epithelial cell biology, we ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-144
更新日期:2011-10-31 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: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: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::The transcription factors nuclear factor interleukin-6 (NF-IL6), early growth response-1 (EGR-1) and hypoxia-inducible factor-1 (HIF-1) have important roles in the molecular pathophysiology of hypoxia-associated pulmonary disease. NF-IL6 controls the production of interleukin (IL)-6 in vascular endothelial cells, whic...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/rr27
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. METHODS:In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 alpha1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplant...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-14
更新日期:2005-02-10 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::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
abstract:BACKGROUND:Adolescence is a period of change, which coincides with disease remission in a significant proportion of subjects with childhood asthma. There is incomplete understanding of the changing characteristics underlying different adolescent asthma transitions. We undertook pathophysiological characterization of tr...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-014-0153-7
更新日期:2014-11-29 00:00:00
abstract::COVID-19 is a complex and heterogeneous disease. The pathogenesis and the complications of the disease are not fully elucidated, and increasing evidence shows that SARS-CoV-2 causes a systemic inflammatory disease rather than a pulmonary disease. The management of hospitalized patients in COVID-19 dedicated units is a...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-020-01516-8
更新日期:2020-10-09 00:00:00
abstract:BACKGROUND:Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investig...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-13-103
更新日期:2012-11-17 00:00:00
abstract:BACKGROUND:An important goal of chronic obstructive pulmonary disease (COPD) treatment is to reduce the frequency of exacerbations. Some observations suggest a decline in exacerbation rates in clinical trials over time. A more systematic understanding would help to improve the design and interpretation of COPD trials. ...
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
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::Pulmonary surfactant is a complex fluid that comprises phospholipids and four proteins (SP-A, SP-B, SP-C, and SP-D) with different biological functions. SP-B, SP-C, and SP-D are essential for the lungs' surface tension function and for the organization, stability and metabolism of lung parenchyma. SP-A and SP-D, which...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-016-0385-9
更新日期:2016-06-01 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:BACKGROUND:Lung cancer is one of the leading cause of cancer-related death in the world. Recently, many clinical researches have reported that COL6A3 had strong role in many diseases. The aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) in COL6A3 and lung cancer susceptib...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1114-y
更新日期:2019-07-08 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:RESEARCH QUESTION:There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and functional characteristics as well as outcomes of patients with severe physiologic impairment. PATIENTS A...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01600-z
更新日期:2021-01-06 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
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:Lung inflammation in COPD is poorly controlled by inhaled corticosteroids (ICS). Strategies to improve ICS efficacy or the search of biomarkers who may select those patients candidates to receive ICS in COPD are needed. Recent data indicate that MUC1 cytoplasmic tail (CT) membrane mucin can mediate corticost...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0927-4
更新日期:2018-11-20 00:00:00
abstract:BACKGROUND:The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH) in rats. METHODS:CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-128
更新日期:2005-11-01 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:Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) a...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0452-2
更新日期:2016-10-27 00:00:00
abstract:BACKGROUND:IL-10 is a cytokine mainly produced by macrophages that plays key roles in tolerance to inhaled antigens and in lung homeostasis. Its regulation in alveolar macrophages (HAM), the resident lung phagocytes, remains however unknown. METHODS:The present study investigated the role of intracellular signalling a...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-71
更新日期:2007-10-04 00:00:00
abstract:BACKGROUND:Progestins as respiratory stimulants in chronic obstructive pulmonary disease (COPD) have been investigated in males and during wakefulness. However, sleep and gender may influence therapeutic responses. We investigated the effects of a 2-week medroxyprogesterone acetate (MPA) therapy on sleep and nocturnal ...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章
doi:10.1186/1465-9921-6-28
更新日期:2005-04-04 00:00:00
abstract:BACKGROUND:Radiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predi...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究
doi:10.1186/s12931-018-0775-2
更新日期:2018-04-24 00:00:00