Genetic Advances in Chronic Obstructive Pulmonary Disease. Insights from COPDGene.

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.

authors

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 EK

doi

10.1164/rccm.201808-1455SO

subject

Has Abstract

pub_date

2019-09-15 00:00:00

pages

677-690

issue

6

eissn

1073-449X

issn

1535-4970

journal_volume

200

pub_type

杂志文章,评审
  • The tolerability, safety, and success of sputum induction and combined hypertonic saline challenge in children.

    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

    authors: Jones PD,Hankin R,Simpson J,Gibson PG,Henry RL

    更新日期:2001-10-01 00:00:00

  • Asthma exacerbations after glucocorticoid withdrawal reflects T cell recruitment to the airway.

    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

    authors: Castro M,Bloch SR,Jenkerson MV,DeMartino S,Hamilos DL,Cochran RB,Zhang XE,Wang H,Bradley JP,Schechtman KB,Holtzman MJ

    更新日期:2004-04-01 00:00:00

  • Effect of the beta-agonist clenbuterol on dexamethasone-induced diaphragm dysfunction in rabbits.

    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

    authors: Jiang TX,Cairns A,Road JD,Wilcox PG

    更新日期:1996-12-01 00:00:00

  • Clinical, echocardiographic, and hemodynamic evidence of cardiac tamponade caused by large pleural effusions.

    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

    authors: Kaplan LM,Epstein SK,Schwartz SL,Cao QL,Pandian NG

    更新日期:1995-03-01 00:00:00

  • Reduced perception of dyspnea and pain after right insular cortex lesions.

    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

    authors: Schön D,Rosenkranz M,Regelsberger J,Dahme B,Büchel C,von Leupoldt A

    更新日期:2008-12-01 00:00:00

  • The pleural space and organ transplantation.

    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

    authors: Judson MA,Sahn SA

    更新日期:1996-03-01 00:00:00

  • Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study.

    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

    authors: Keh D,Boehnke T,Weber-Cartens S,Schulz C,Ahlers O,Bercker S,Volk HD,Doecke WD,Falke KJ,Gerlach H

    更新日期:2003-02-15 00:00:00

  • Consequences of vascular flow on lung injury induced by mechanical ventilation.

    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

    authors: Broccard AF,Hotchkiss JR,Kuwayama N,Olson DA,Jamal S,Wangensteen DO,Marini JJ

    更新日期:1998-06-01 00:00:00

  • 40-O-(2-hydroxyethyl)-rapamycin attenuates pulmonary arterial hypertension and neointimal formation in rats.

    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

    authors: Nishimura T,Faul JL,Berry GJ,Veve I,Pearl RG,Kao PN

    更新日期:2001-02-01 00:00:00

  • Interleukin-2-induced increased airway responsiveness and lung Th2 cytokine expression occur after antigen challenge through the leukotriene pathway.

    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

    authors: Nag S,Lamkhioued B,Renzi PM

    更新日期:2002-06-01 00:00:00

  • A new method for bronchial-provocation testing in asthmatic subjects using a dry powder of mannitol.

    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

    authors: Anderson SD,Brannan J,Spring J,Spalding N,Rodwell LT,Chan K,Gonda I,Walsh A,Clark AR

    更新日期:1997-09-01 00:00:00

  • Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling.

    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

    authors: Wille MM,Dirksen A,Ashraf H,Saghir Z,Bach KS,Brodersen J,Clementsen PF,Hansen H,Larsen KR,Mortensen J,Rasmussen JF,Seersholm N,Skov BG,Thomsen LH,Tønnesen P,Pedersen JH

    更新日期:2016-03-01 00:00:00

  • Future Research Directions in Asthma. An NHLBI Working Group Report.

    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

    authors: Levy BD,Noel PJ,Freemer MM,Cloutier MM,Georas SN,Jarjour NN,Ober C,Woodruff PG,Barnes KC,Bender BG,Camargo CA Jr,Chupp GL,Denlinger LC,Fahy JV,Fitzpatrick AM,Fuhlbrigge A,Gaston BM,Hartert TV,Kolls JK,Lynch SV,Moo

    更新日期:2015-12-01 00:00:00

  • Functional prostaglandin-endoperoxide synthase 2 polymorphism predicts poor outcome in sarcoidosis.

    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

    authors: Hill MR,Papafili A,Booth H,Lawson P,Hubner M,Beynon H,Read C,Lindahl G,Marshall RP,McAnulty RJ,Laurent GJ

    更新日期:2006-10-15 00:00:00

  • Noninvasive ventilator triggering in chronic obstructive pulmonary disease. A test lung comparison.

    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

    authors: Stell IM,Paul G,Lee KC,Ponte J,Moxham J

    更新日期:2001-12-01 00:00:00

  • Integrating mortality and morbidity outcomes: using quality-adjusted life years in critical care trials.

    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

    authors: Ferguson ND,Scales DC,Pinto R,Wilcox ME,Cook DJ,Guyatt GH,Schünemann HJ,Marshall JC,Herridge MS,Meade MO,Canadian Critical Care Trials Group.

    更新日期:2013-02-01 00:00:00

  • Linkage analysis of chromosome 12 markers in Italian families with atopic asthmatic children.

    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

    authors: Malerba G,Lauciello MC,Scherpbier T,Trabetti E,Galavotti R,Cusin V,Pescollderungg L,Zanoni G,Martinati LC,Boner AL,Levitt RC,Pignatti PF

    更新日期:2000-10-01 00:00:00

  • Acute effects of exercise on cognition in patients with chronic obstructive pulmonary disease.

    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

    authors: Emery CF,Honn VJ,Frid DJ,Lebowitz KR,Diaz PT

    更新日期:2001-11-01 00:00:00

  • DNA fingerprinting with two probes decreases clustering of Mycobacterium tuberculosis.

    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

    authors: Burman WJ,Reves RR,Hawkes AP,Rietmeijer CA,Yang Z,el-Hajj H,Bates JH,Cave MD

    更新日期:1997-03-01 00:00:00

  • Human airway narrowing measured using high resolution computed tomography.

    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

    authors: Okazawa M,Müller N,McNamara AE,Child S,Verburgt L,Paré PD

    更新日期:1996-11-01 00:00:00

  • Noninvasive Ventilation Use in Critically Ill Patients with Acute Asthma Exacerbations.

    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

    authors: Althoff MD,Holguin F,Yang F,Grunwald GK,Moss M,Vandivier RW,Ho PM,Kiser TH,Burnham EL

    更新日期:2020-12-01 00:00:00

  • Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia.

    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

    authors: Baddour LM,Yu VL,Klugman KP,Feldman C,Ortqvist A,Rello J,Morris AJ,Luna CM,Snydman DR,Ko WC,Chedid MB,Hui DS,Andremont A,Chiou CC,International Pneumococcal Study Group.

    更新日期:2004-08-15 00:00:00

  • Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection.

    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

    authors: Gregson AL,Hoji A,Injean P,Poynter ST,Briones C,Palchevskiy V,Weigt SS,Shino MY,Derhovanessian A,Sayah D,Saggar R,Ross D,Ardehali A,Lynch JP 3rd,Belperio JA

    更新日期:2015-12-15 00:00:00

  • Lung microvascular and arterial endothelial cells differ in their responses to intercellular adhesion molecule-1 ligation.

    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

    authors: Wang Q,Pfeiffer GR 2nd,Stevens T,Doerschuk CM

    更新日期:2002-09-15 00:00:00

  • Risk factors for nosocomial pneumonia: comparing adult critical-care populations.

    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

    authors: Cunnion KM,Weber DJ,Broadhead WE,Hanson LC,Pieper CF,Rutala WA

    更新日期:1996-01-01 00:00:00

  • Optimization and Interpretation of Serial QuantiFERON Testing to Measure Acquisition of Mycobacterium tuberculosis Infection.

    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

    authors: Nemes E,Rozot V,Geldenhuys H,Bilek N,Mabwe S,Abrahams D,Makhethe L,Erasmus M,Keyser A,Toefy A,Cloete Y,Ratangee F,Blauenfeldt T,Ruhwald M,Walzl G,Smith B,Loxton AG,Hanekom WA,Andrews JR,Lempicki MD,Ellis R,Ginsb

    更新日期:2017-09-01 00:00:00

  • Impaired vasodilator responses in obstructive sleep apnea are improved with continuous positive airway pressure therapy.

    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

    authors: Imadojemu VA,Gleeson K,Quraishi SA,Kunselman AR,Sinoway LI,Leuenberger UA

    更新日期:2002-04-01 00:00:00

  • Lavage administration of dilute surfactants after acute lung injury in neonatal piglets.

    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

    authors: Balaraman V,Meister J,Ku TL,Sood SL,Tam E,Killeen J,Uyehara CF,Egan E,Easa D

    更新日期:1998-07-01 00:00:00

  • Transforming growth factor-beta (TGF-beta) in silicosis.

    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

    authors: Jagirdar J,Begin R,Dufresne A,Goswami S,Lee TC,Rom WN

    更新日期:1996-10-01 00:00:00

  • Intravenous lidocaine and oral mexiletine block reflex bronchoconstriction in asthmatic subjects.

    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

    authors: Groeben H,Foster WM,Brown RH

    更新日期:1996-10-01 00:00:00