Abstract:
:Chronic obstructive pulmonary disease (COPD) is a common and progressive disease that is influenced by both genetic and environmental factors. For many years, knowledge of the genetic basis of COPD was limited to Mendelian syndromes, such as alpha-1 antitrypsin deficiency and cutis laxa, caused by rare genetic variants. Over the past decade, the proliferation of genome-wide association studies, the accessibility of whole-genome sequencing, and the development of novel methods for analyzing genetic variation data have led to a substantial increase in the understanding of genetic variants that play a role in COPD susceptibility and COPD-related phenotypes. COPDGene (Genetic Epidemiology of COPD), a multicenter, longitudinal study of over 10,000 current and former cigarette smokers, has been pivotal to these breakthroughs in understanding the genetic basis of COPD. To date, over 20 genetic loci have been convincingly associated with COPD affection status, with additional loci demonstrating association with COPD-related phenotypes such as emphysema, chronic bronchitis, and hypoxemia. In this review, we discuss the contributions of the COPDGene study to the discovery of these genetic associations as well as the ongoing genetic investigations of COPD subtypes, protein biomarkers, and post-genome-wide association study analysis.
journal_name
Am J Respir Crit Care Medauthors
Ragland MF,Benway CJ,Lutz SM,Bowler RP,Hecker J,Hokanson JE,Crapo JD,Castaldi PJ,DeMeo DL,Hersh CP,Hobbs BD,Lange C,Beaty TH,Cho MH,Silverman EKdoi
10.1164/rccm.201808-1455SOsubject
Has Abstractpub_date
2019-09-15 00:00:00pages
677-690issue
6eissn
1073-449Xissn
1535-4970journal_volume
200pub_type
杂志文章,评审abstract::Induced sputum using hypertonic saline (HS) is a useful research tool to study airway inflammation (AI). HS provocation testing can also be used to measure airway hyperresponsiveness (AHR). A combined HS challenge and sputum induction procedure has been developed to permit assessment of AI and AHR in a single test. Th...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.7.2103015
更新日期:2001-10-01 00:00:00
abstract::We reasoned that a prospective assessment of glucocorticoid withdrawal in subjects with asthma would provide insight into the basis for flares of the disease. We therefore enrolled 25 subjects with moderate persistent asthma and treated them for 30 days with inhaled fluticasone propionate (1,760 microg/day) followed b...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200208-960OC
更新日期:2004-04-01 00:00:00
abstract::The present study was designed to examine whether clenbuterol (CLEN) could reduce dexamethasone (DEX)-induced diaphragm dysfunction. We studied four groups of New Zealand white (NZW) rabbits, each receiving one of the following daily injections subcutaneously for 2 wk: saline (control), DEX 3 mg/kg, DEX 3 mg/kg + CLEN...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.6.8970370
更新日期:1996-12-01 00:00:00
abstract::Large pleural effusions are typically associated with dyspnea and potential respiratory compromise. Experimental evidence suggests that with large effusions, increased intrapleural pressure may be transmitted to the pericardial space, resulting in impaired cardiac filling and reduced stroke volume. We report two cases...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm/151.3_Pt_1.904
更新日期:1995-03-01 00:00:00
abstract:RATIONALE:The perception of dyspnea and pain show many similarities. Initial imaging studies suggested an important role of the insular cortex for the perception of both sensations. However, little is known about the cortical processing of dyspnea. OBJECTIVES:This study investigated the influence of lesions of the ins...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200805-731OC
更新日期:2008-12-01 00:00:00
abstract::Pleural disease both before and after organ transplantation has important implications. Pleural effusions are common in candidates for heart, liver, and kidney transplantation. A thoracentesis is not mandatory in these patients, but it should be performed if clinical or radiologic features suggest that the effusion is...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.153.3.8630560
更新日期:1996-03-01 00:00:00
abstract::Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy. To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation, 40 patients with septic shock were randomized in a double-blind crosso...
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/rccm.200205-446OC
更新日期:2003-02-15 00:00:00
abstract::To investigate whether the magnitude of blood flow contributes to ventilator-induced lung injury, 14 sets of isolated rabbit lungs were randomized for perfusion at either 300 (Group A: n = 7) or 900 ml/ min (Group B: n = 7) while ventilated with 30 cm H2O peak static pressure. Control lungs (Group C: n = 7) were venti...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.6.9612006
更新日期:1998-06-01 00:00:00
abstract::Pneumonectomized rats develop pulmonary hypertension (PH) and pulmonary vascular neointimal formation 4 wk after monocrotaline (MCT) administration. Male Sprague-Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Three groups (n = 5) received 40-O-(2-hydroxyethyl)-rapamycin (RAD, 2.5 mg/k...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.163.2.2006093
更新日期:2001-02-01 00:00:00
abstract::Previous studies have shown that the allergic late airway response (LR) is dependent on the leukotriene (LT) pathway in Brown Norway (BN) rats. In this same model, interleukin-2 (IL-2) has been shown to increase allergic airway responses without increasing LT production. This study examined the relationship between th...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2109012
更新日期:2002-06-01 00:00:00
abstract::We developed a bronchial provocation test (BPT) with a dry powder preparation of mannitol. The mannitol was inhaled from gelatin capsules containing 5, 10, 20, or 40 mg to a cumulative dose of 635 mg, and was delivered via an inhalator, Halermatic, or Dinkihaler device. We studied the airway sensitivity to inhaled man...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/ajrccm.156.3.9701113
更新日期:1997-09-01 00:00:00
abstract:RATIONALE:As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. OBJECTIVES:Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. METHODS:A total of 4,104 parti...
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.201505-1040OC
更新日期:2016-03-01 00:00:00
abstract::Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the N...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.201505-0963WS
更新日期:2015-12-01 00:00:00
abstract:RATIONALE:The majority of patients with sarcoidosis resolve their condition; however 5-10% of patients with sarcoidosis develop pulmonary fibrosis with poor prognosis. Prostaglandin-endoperoxide synthase 2 (PTGS2) is a key regulatory enzyme in the synthesis of the antifibrotic agent prostaglandin E(2) and is reduced in...
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.200512-1839OC
更新日期:2006-10-15 00:00:00
abstract::To be most effective, noninvasive ventilation (NIV) ventilators should synchronize well with patients' breathing. However, the speed with which different ventilators can respond to the transitions between inspiration and expiration may vary, and abnormal respiratory mechanics and mask leaks may exacerbate this problem...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.11.2011147
更新日期:2001-12-01 00:00:00
abstract:RATIONALE:Outcome measures that integrate mortality and morbidity, like quality-adjusted life years (QALYs), have been proposed for critical care clinical trials. OBJECTIVES:We sought to describe the distribution of QALYs in critically ill patients and estimate sample size requirements for a hypothetical trial using Q...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201206-1057OC
更新日期:2013-02-01 00:00:00
abstract::We investigated 116 Italian atopic families (560 individuals) for linkage with 13 DNA markers on chromosome 12. All the subjects were phenotyped for asthma, total serum IgE, bronchial hyperresponsiveness, skin-prick positivity to common aeroallergens, and atopy. A relative location map of the markers was prepared from...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.4.9909031
更新日期:2000-10-01 00:00:00
abstract::Prior data indicate positive effects of long-term exercise interventions for cognitive functioning among patients with chronic obstructive pulmonary disease (COPD), but no prior studies have examined acute effects of individual bouts of exercise among patients with COPD. This study evaluated acute effects of exercise ...
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.164.9.2104137
更新日期:2001-11-01 00:00:00
abstract::DNA fingerprinting of Mycobacterium tuberculosis is used to study the epidemiology of tuberculosis, but the specificity of the widely used IS6110 technique has not been validated. Isolates from Denver, Colorado from December 1988 through June 1994 were fingerprinted with the IS6110 technique. Available records were re...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.3.9117000
更新日期:1997-03-01 00:00:00
abstract::Exaggerated airway narrowing in response to bronchoconstricting stimuli is a characteristic feature of asthmatic subjects. It is unknown whether the site of airway narrowing differs in asthmatic subjects from that observed in normal subjects. Increased airway wall thickness has been suggested as a contributing cause f...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/ajrccm.154.5.8912780
更新日期:1996-11-01 00:00:00
abstract::Rationale: Noninvasive ventilation decreases the need for invasive mechanical ventilation and mortality among patients with chronic obstructive pulmonary disease but has not been well studied in asthma.Objectives: To assess the association between noninvasive ventilation and subsequent need for invasive mechanical ven...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201910-2021OC
更新日期:2020-12-01 00:00:00
abstract::Retrospective studies have suggested that combination antibiotic therapy for severe bacteremic pneumococcal pneumonia may reduce mortality. We assessed this issue in a prospective, multicenter, international observational study of 844 adult patients with bacteremia due to Streptococcus pneumoniae. The effect of combin...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1164/rccm.200311-1578OC
更新日期:2004-08-15 00:00:00
abstract:RATIONALE:The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201503-0558OC
更新日期:2015-12-15 00:00:00
abstract::Neutrophil adherence to tumor necrosis factor-alpha (TNF-alpha)-treated human pulmonary microvascular endothelial cells (PMECs) induces cytoskeletal changes in endothelial cells that require intercellular adhesion molecule-1 (ICAM-1)-dependent signaling events. This study determined whether similar changes occurred in...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2201007
更新日期:2002-09-15 00:00:00
abstract::The purpose of the study was to examine risk factors for nosocomial pneumonia in the surgical and medical/respiratory intensive care unit (ICU) populations. In a public teaching hospital, all cases of nosocomial pneumonia in the surgical and medical/respiratory ICUs (n = 20, respectively) were identified by prospectiv...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.1.8542110
更新日期:1996-01-01 00:00:00
abstract:RATIONALE:Conversion from a negative to positive QuantiFERON-TB test is indicative of Mycobacterium tuberculosis (Mtb) infection, which predisposes individuals to tuberculosis disease. Interpretation of serial tests is confounded by immunological and technical variability. OBJECTIVES:To improve the consistency of seri...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201704-0817OC
更新日期:2017-09-01 00:00:00
abstract::Obstructive sleep apnea causes cardiovascular morbidity and premature death. Potential links between sleep apnea and cardiovascular complications are chronically elevated activity of the sympathetic nervous system and abnormal vascular function. To explore vascular function, we determined the reactive hyperemic blood ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.7.2102003
更新日期:2002-04-01 00:00:00
abstract::Exogenous surfactant therapy is not standard in the acute respiratory distress syndrome (ARDS) because of a lack of proven benefit. Nonuniform surfactant distribution after either bolus or aerosol administration may be an important factor limiting response. In a previous study of acute lung injury, we demonstrated tha...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.1.9704119
更新日期:1998-07-01 00:00:00
abstract::Silicosis is characterized by fibrosing nodular lesions that may eventually develop into progressive massive fibrosis (PMF). Cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor-alpha [TNF-alpha] and growth factors insulin-like growth factor-1 [IGF-1] platelet-derived growth factor [PDGF]) have been implicat...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.4.8887610
更新日期:1996-10-01 00:00:00
abstract::Stimulation of the airways of asthmatic individuals causes severe bronchoconstriction, which is in part neurally mediated via the vagus nerve. Local anesthetics are commonly administered to prevent this reflex-induced bronchoconstriction. Therefore, in a double-blind, placebo-controlled prospective study, we tested th...
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.154.4.8887580
更新日期:1996-10-01 00:00:00