Abstract:
RATIONALE:FVC has emerged as a standard primary endpoint in clinical trials evaluating novel therapies for patients with idiopathic pulmonary fibrosis (IPF). However, it has recently been proposed that all-cause mortality or a composite comprised of all-cause mortality and all-cause nonelective hospitalization be adopted as the standard primary endpoint for IPF clinical trials. OBJECTIVES:To conduct a comprehensive evaluation of mortality in three phase 3 clinical trials and evaluate the feasibility of mortality trials in patients with IPF. METHODS:The study population included 622 patients randomized to placebo in the CAPACITY studies evaluating pirfenidone (n = 347) or the INSPIRE study evaluating interferon-γ1b (n = 275). The Kaplan-Meier estimate of 2-year survival was fit to the exponential distribution and used to calculate sample size requirements for a mortality study with 90% power to detect a 25% reduction in all-cause mortality with a two-sided α of 0.05. Modeling analyses were used to assess the effects of selected variables on sample size and study design. MEASUREMENTS AND MAIN RESULTS:A total of 73 deaths occurred during the period of observation (mean duration of follow-up, 80.1 wk). The all-cause mortality rate was 6.6% at 1 year and 13.7% at 2 years. Based on the observed 2-year mortality rate, a total of 508 events would be required to detect a significant treatment benefit in a two-arm trial with 90% power to detect a 25% reduction in all-cause mortality. The estimated sample size for a trial enrolled over 3 years with a maximum follow-up period of 5 years is 2,582 patients. CONCLUSIONS:The all-cause mortality rate is relatively low in patients with IPF with mild to moderate impairment in lung function. Accordingly, the necessary size, duration, and cost of all-cause mortality trials in this population are substantial and likely prohibitive.
journal_name
Am J Respir Crit Care Medauthors
King TE Jr,Albera C,Bradford WZ,Costabel U,du Bois RM,Leff JA,Nathan SD,Sahn SA,Valeyre D,Noble PWdoi
10.1164/rccm.201311-1951OCsubject
Has Abstractpub_date
2014-04-01 00:00:00pages
825-31issue
7eissn
1073-449Xissn
1535-4970journal_volume
189pub_type
杂志文章abstract:RATIONALE:Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between children's phthalate exposures and fractional exhaled nitric oxide (Fe(NO)), a biomarker of airway inflammation, have not been examine...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201203-0398OC
更新日期:2012-11-01 00:00:00
abstract::Two distinct types of tumor necrosis factor receptors (TNF-R) have been identified (TNF-R55 and TNF-R75). Both TNF-R also exist in soluble forms (TNF-sR), resulting from the release of the extracellular domains (TNF-sR55 and TNF-sR75). TNF-sR may play an important role in vivo as they can bind to TNF alpha and prevent...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.149.6.8004330
更新日期:1994-06-01 00:00:00
abstract::The effects of exposure to environmental tobacco smoke (ETS) on pulmonary function were investigated in a random sample of 1,033 adults aged 40 to 69 yr from a residential area in Beijing. Compared with those not exposed, those exposed to ETS either at home or at work were associated with a 102-ml (SE = 40 ml) reducti...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.1.7812570
更新日期:1995-01-01 00:00:00
abstract::We examined endotoxin exposure and wheezing episodes during the first year of life in a birth cohort of 499 infants with one or both parents having a history of asthma or allergy. We measured endotoxin in settled dust from the baby's bed, bedroom floor, family room, and kitchen floor within the first 3 mo after birth....
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.163.2.2002088
更新日期:2001-02-01 00:00:00
abstract::We prospectively investigated the mechanism of airflow limitation before and after targeted emphysematous resection in 12 consecutively studied adult patients 68 +/- 4 yr of age (mean +/- SD) with very severe COPD undergoing bilateral thoracoscopic stapling techniques. Lung function, static lung elastic recoil, and ai...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.4.8887590
更新日期:1996-10-01 00:00:00
abstract::Sepsis and cancer share a number of pathophysiological features, and both result from the inability of the host's immune system to cope with the initial insult (tissue invasion by pathogens and malignant cell transformation, respectively). The common coexistence of both disorders and the profound related alterations i...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.202004-1116TR
更新日期:2020-12-15 00:00:00
abstract::This study describes the natural history of atopic and wheezy disorders from birth to adult life in a cohort at risk of atopy. One hundred subjects born in Poole, England, were selected at birth in 1976 on the basis that at least one parent was atopic. Subjects were examined annually in the preschool years, and at the...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.2.2104032
更新日期:2002-01-15 00:00:00
abstract:RATIONALE:Inhibition of pharyngeal motoneurons accompanies REM sleep and is a cause of hypoventilation and obstructive sleep apnea in humans. One explanation posits that the neurotransmitters glycine and γ-aminobutyric acid are responsible for REM sleep motor inhibition. However, blockade of that mechanism at cranial m...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201209-1654OC
更新日期:2013-02-01 00:00:00
abstract:RATIONALE:Bronchiolitis is the most common lower respiratory infection in infants; however, it remains unclear which infants with bronchiolitis will develop severe illness. In addition, although emerging evidence indicates associations of the upper-airway microbiome with bronchiolitis severity, little is known about th...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.201701-0071OC
更新日期:2017-10-01 00:00:00
abstract::In 35 patients fulfilling the criteria of systemic inflammatory response syndrome (SIRS) of infectious origin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), tumor necrosis factor-soluble receptor (TNF-sR), and interleukin-12 (IL-12), C-reactive protein (CRP) levels and the Acute Physiology, and Chroni...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.3.9607131
更新日期:1997-09-01 00:00:00
abstract:RATIONALE:Neutrophils are usually the first circulating leukocytes to respond during bacterial pneumonia. Their expression of oxidants, proteases, and other mediators present in granules is well documented, but their ability to produce mediators through transcription and translation after migration to an inflammatory s...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201004-0592OC
更新日期:2011-05-15 00:00:00
abstract::We addressed the hypothesis that noncholinergic parasympathetic nerves modulate airway smooth-muscle (ASM) tone in guinea pigs. The NO synthase inhibitor L-N(G)-nitro-arginine (L-NNA) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) potentiated cholinergic contractions and partly i...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.4.2004005
更新日期:2002-02-15 00:00:00
abstract::To determine the incidence and 90-d mortality of acute respiratory failure (ARF), acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS), we carried out an 8-wk prospective cohort study in Sweden, Denmark, and Iceland. All intensive care unit (ICU) admissions (n = 13,346) >/= 15 yr of age were ass...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.6.9808136
更新日期:1999-06-01 00:00:00
abstract::In anaphylactic shock (AS), the relative effects of the autacoids including histamine, prostaglandins, and leukotrienes on causing cardiovascular collapse and the extent to which receptor blocking agents and pathway inhibitors may prevent this collapse are not clear. In a ragweed model of anaphylaxis, we examined whet...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.160.4.9901021
更新日期:1999-10-01 00:00:00
abstract::The role of ventilatory-control abnormalities in predisposing to familial sleep-disordered breathing (SDB) was assessed in 31 subjects 28 +/- 10 yr of age (mean +/- SD). Subjects with (n = 10) and without SDB (n = 12) were recruited from 13 families having two or more members with SDB. Nine age- and gender-matched con...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.1.9610016
更新日期:1997-07-01 00:00:00
abstract::Mechanical ventilation may promote overdistension-induced pulmonary lesions in patients with acute respiratory distress syndrome (ARDS). The static pressure-volume (P-V) curve of the respiratory system can be used to determine the lung volume and corresponding static airway pressure at which lung compliance begins to ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.1.7599810
更新日期:1995-07-01 00:00:00
abstract::In addition to its central role in hemostasis, thrombin may play a role in inflammation and remodeling. To investigate the contribution of thrombin to allergic airway inflammation in asthma, we used an enzymatic assay to determine thrombin activity in bronchoalveolar lavage fluid obtained from 19 subjects with atopic ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200308-1156OC
更新日期:2004-02-01 00:00:00
abstract::It is known that the ventilatory response to carbon dioxide (CO2) is increased in asthmatics with airway obstruction. Increased vagal afferent activity as well as increased airway resistance have been postulated as the causative mechanisms. However, whether increased vagal afferent activity without bronchoconstriction...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.6.7952620
更新日期:1994-12-01 00:00:00
abstract::Pulmonary emphysema and periodontal disease are each characterized by the uncontrolled proteolysis of connective tissue proteins by proteinases derived from human neutrophils. Although these diseases would not appear to be related in terms of the initial insult to individual tissues, the ultimate result in each diseas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm/150.6_Pt_2.S143
更新日期:1994-12-01 00:00:00
abstract:RATIONALE:Secondhand smoke exposure (SHSe) is a significant modifiable risk for respiratory health in children. Although SHSe is declining overall, it has increased for low-income and minority populations. Implementation of effective SHSe interventions within community organizations has the potential for significant pu...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1164/rccm.201404-0618OC
更新日期:2014-06-15 00:00:00
abstract::Sarcoidosis is a systemic granulomatous disease of unknown etiology that primarily affects the lungs. The etiology remains unclear; however, environmental, genetic, ethnic, and familial factors probably modify expression of the disease. As an example, African Americans are at greater risk of mortality and morbidity th...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.200308-1073WS
更新日期:2004-09-01 00:00:00
abstract::Measurement of respiratory compliance is advocated for assessing the severity of acute respiratory failure (ARF). Recently, the administration of an automated constant flow of 15 L/min was proposed as a method easier to implement at the bedside than supersyringe or inspiratory occlusions methods. However, pressure-vol...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.1.9802082
更新日期:1999-01-01 00:00:00
abstract:RATIONALE:Secondhand tobacco smoke (SHS) and traffic-related air pollutants are associated with asthma and allergy. Diesel exhaust particles (DEPs) and SHS can interact with allergens in exacerbating allergic airway diseases through generation of reactive oxygen species. Glutathione S-transferases (GSTs) metabolize rea...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1164/rccm.200509-1424OC
更新日期:2006-12-15 00:00:00
abstract::The etiology of sleep disruption in patients in intensive care units (ICUs) is poorly understood, but is thought to be related to environmental stimuli, especially noise. We sampled 203 patients (121 males and 82 females) from different ICUs (cardiac [CCU], cardiac stepdown [CICU], medical [MICU], and surgical [SICU])...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.4.9806141
更新日期:1999-04-01 00:00:00
abstract::Bronchial overproduction of leukotrienes and inhibition of prostaglandin synthesis are involved in the pathogenesis of aspirin-induced asthma. We investigated whether inhaled prostaglandin E2 (PGE2) attenuates the response to bronchial challenge with lysine acetylsalicylate (LASA) and the associated increase in urinar...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.153.2.8564100
更新日期:1996-02-01 00:00:00
abstract:RATIONALE:Exhaled carbon monoxide (CO) and arterial blood carboxyhemoglobin concentrations (Hb-CO) increase in inflammatory pulmonary diseases. OBJECTIVES:To study whether arterial Hb-CO is useful to monitor disease activity in patients with chronic obstructive pulmonary disease (COPD) who had stopped smoking. METHOD...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.200407-914OC
更新日期:2005-06-01 00:00:00
abstract::Many patients who develop incapacitating illness have not expressed clear treatment preferences. Therefore, surrogate decision makers are asked to make judgments about what treatment pathway is most consistent with the patient's values. Surrogates often struggle with such decisions. The difficulty arises because answe...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.201204-0710CP
更新日期:2012-09-15 00:00:00
abstract::We present a case of a pulmonary nodular lesion in an immunocompetent patient documented at open lung biopsy to be due to Mycobacterium haemophilum. This organism has recently been recognized as a cause of disease in immunocompromised patients, presenting predominantly as skin lesions, arthritis, and rarely pneumonia....
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.160.4.9904003
更新日期:1999-10-01 00:00:00
abstract::The bactericidal activities of several once-weekly rifapentine (P)-containing combination regimens against Mycobacterium tuberculosis, and their ability to prevent the selection of rifampin (R)-resistant mutants, were compared with those of the standard six-times-weekly regimen consisting of R, isoniazid (H), and pyra...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.5.9709072
更新日期:1998-05-01 00:00:00
abstract::The lungs of newborn rats exposed to 60% oxygen for 14 days develop an injury that shares morphologic similarities to human bronchopulmonary dysplasia (BPD). Neutrophil influx into the lung, as part of an inflammatory response, may play a pivotal role in the development of BPD. A neutrophil chemokine, cytokine-induced...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200402-215OC
更新日期:2004-12-01 00:00:00