Abstract:
RATIONALE:Tumor-infiltrating immune cells affect lung cancer outcome. However, the factors that influence the composition and function of the tumor immune environment remain poorly defined and need investigation, particularly in the era of immunotherapy. OBJECTIVES:To determine whether the tumoral immune environment is related to lung adenocarcinoma mutations. METHODS:This retrospective cohort included 316 consecutive patients with lung adenocarcinoma (225 men; 258 smokers) studied from 2001 to 2005 in a single center. We investigated the association of densities of intratumoral mature dendritic cells (mDCs), CD8+ T cells, neutrophils, and macrophages with clinical and pathological variables and tumor cell mutation profiles obtained by next-generation sequencing. MEASUREMENTS AND MAIN RESULTS:In 282 tumors, we found 460 mutations, mainly in TP53 (59%), KRAS (40%), STK11 (24%), and EGFR (14%). Intratumoral CD8+ T-cell density was high in smokers (P = 0.02) and TP53-mutated tumors (P = 0.02) and low in BRAF-mutated tumors (P = 0.005). Intratumoral mDC density was high with low pathological tumor stage (P = 0.01) and low with STK11 mutation (P = 0.004). Intratumoral neutrophil density was high and low with BRAF mutation (P = 0.04) and EGFR mutation (P = 0.02), respectively. Intratumoral macrophage density was low with EGFR mutation (P = 0.01). Intratumoral CD8+ T-cell and mDC densities remained strong independent markers of overall survival (P = 0.001 and P = 0.02, respectively). CONCLUSIONS:Intratumoral immune cell densities (mDCs, CD8+ T cells, neutrophils, macrophages) were significantly associated with molecular alterations in adenocarcinoma underlying the interactions between cancer cells and their microenvironment.
journal_name
Am J Respir Crit Care Medauthors
Mansuet-Lupo A,Alifano M,Pécuchet N,Biton J,Becht E,Goc J,Germain C,Ouakrim H,Régnard JF,Cremer I,Laurent-Puig P,Dieu-Nosjean MC,Blons H,Damotte Ddoi
10.1164/rccm.201510-2031OCsubject
Has Abstractpub_date
2016-12-01 00:00:00pages
1403-1412issue
11eissn
1073-449Xissn
1535-4970journal_volume
194pub_type
杂志文章abstract:RATIONALE:Inhaled corticosteroids are commonly prescribed to patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES:To examine whether these medications might be associated with an excess risk of pneumonia. METHODS:We conducted a nested case-control study within a cohort of patients with COPD from Que...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200611-1630OC
更新日期:2007-07-15 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::Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200407-895OC
更新日期:2005-02-01 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::Airway remodeling may lead to irreversible loss of lung function in asthma. The impact of childhood asthma, airway responsiveness, atopy, and smoking on airway remodeling was investigated in a birth cohort studied longitudinally to age 26. A low postbronchodilator ratio of forced exhaled volume in 1 second (FEV1) to v...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2108009
更新日期:2002-06-01 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
abstract::Obstructive apneas and hypopneas during sleep are a well recognized cause of excessive daytime sleepiness. Snoring is also associated with excess sleepiness, although it is not known whether this reflects an independent effect of snoring or whether snoring is simply a marker for obstructive sleep apnea. To further exp...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/ajrccm.162.4.9911073
更新日期:2000-10-01 00:00:00
abstract::Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension in which the vascular changes originate in the small pulmonary veins and venules. The pathogenesis is unknown and any link with primary pulmonary hypertension (PPH) has been speculative. Mutations in the bone morphogenetic protein recepto...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200208-861OC
更新日期:2003-03-15 00:00:00
abstract::Phosphodiesterase (PDE)-5 degrades guanosine 3',5'cyclic monophosphate (cGMP) and its inhibitor sildenafil citrate (Viagra) treats erectile dysfunction by smooth muscle relaxation through elevated cGMP. Sildenafil was examined in two guinea pig models of airways disease: guinea pigs exposed to LPS or sensitized guinea...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200211-1372OC
更新日期:2004-01-15 00:00:00
abstract::The predisposing factors and complications of unplanned extubation (UEX) in mechanically ventilated adult patients are not well recognized. We designed a prospective multicenter observational study to identify risk factors and describe the complications of UEX. We followed 426 ventilated patients over a 2-mo period. C...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/ajrccm.157.4.9702083
更新日期:1998-04-01 00:00:00
abstract::Muscle nerve sympathetic activity (MSA), the interval between two R-waves in the ECG, or the interbeat interval (RR-interval), and blood pressure (BP) were recorded in 10 awake patients with obstructive sleep apnea (OSA) and in nine sex- and age-matched controls. Changes in RR-interval and MSA, evoked by sodium nitrop...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/ajrccm.154.5.8912770
更新日期:1996-11-01 00:00:00
abstract:RATIONALE:The temporal stability of adult asthma phenotypes identified using clustering methods has never been addressed. Longitudinal cluster-based methods may provide novel insights in the study of the natural history of asthma. OBJECTIVES:To compare the stability of cluster-based asthma phenotype structures a decad...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201301-0156OC
更新日期:2013-09-01 00:00:00
abstract::Obstructive sleep apnea (OSA) is traditionally diagnosed using overnight polysomnography. Decision rules may provide an alternative to polysomnography. A consecutive series of patients referred to a tertiary sleep center underwent prospective evaluation with the upper airway physical examination protocol, followed by ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200112-110OC
更新日期:2003-05-15 00:00:00
abstract::Acute sustained hypoxia causes an early rise in ventilation, followed by a reduction in ventilation ("roll off") after several minutes to levels below the peak but above baseline. The underlying mechanism(s) of this biphasic response is unclear. Hypoxia induces changes in the release and metabolic turnover of glutamat...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm/151.4.1113
更新日期:1995-04-01 00:00:00
abstract:RATIONALE:Data regarding the influence of ambient air pollution on infant bronchiolitis are few. OBJECTIVES:We evaluated the impact of several air pollutants and their sources on infant bronchiolitis. METHODS:Infants in the Georgia Air Basin of British Columbia with an inpatient or outpatient clinical encounter for b...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200901-0117OC
更新日期:2009-11-15 00:00:00
abstract::Colony-forming units of Mycobacterium tuberculosis in sputum were counted at 2-day intervals in 100 patients treated with 22 regimens of isoniazid, rifampin, pyrazinamide, ethambutol, or streptomycin, given alone or in combinations. The exponential fall in colony-forming units was measured by linear regression coeffic...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200210-1125OC
更新日期:2003-05-15 00:00:00
abstract::The present prospective study was designed to determine the prevalence of pleural effusion at approximately 28 days after cardiac surgery and their subsequent course. This consecutive case study included 389 patients; 312 had only coronary artery bypass graft surgery (CABG) surgery, 37 had both valve and CABG surgery,...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200203-184OC
更新日期:2002-12-15 00:00:00
abstract::If lipid peroxidation (LP) contributes to organ dysfunction in sepsis rather than simply reflecting established injury, it should occur soon after the onset of the septic insult, and it may not progress uniformly in all organs. We assessed whether LP occurs within 90 min after onset of continuous intravenous endotoxin...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.3.7881670
更新日期:1995-03-01 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::The aim of this study was to determine the effects of maturation on crossbridge properties and myosin isoform composition in hamster diaphragm muscle. Diaphragm strips were obtained at postnatal Days 1 and 8 and in adults (10 to 12 wk). Peak isometric tension and maximum unloaded shortening velocity (Vmax) increased w...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.3.9701051
更新日期:1997-09-01 00:00:00
abstract:RATIONALE:Acute lung injury is a common complication after severe trauma, which predisposes patients to multiple organ failure. This syndrome largely accounts for the late mortality that arises and despite many theories, the pathological mechanism is not fully understood. Discovery of histone-induced toxicity in mice p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201206-1037OC
更新日期:2013-01-15 00:00:00
abstract:RATIONALE:Chronic hypoxia induces pulmonary vascular remodeling, pulmonary hypertension, and right ventricular hypertrophy. At present, little is known about mechanisms driving these responses. Hypoxia-inducible factor-1α (HIF-1α) is a master regulator of transcription in hypoxic cells, up-regulating genes involved in ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201302-0302OC
更新日期:2014-02-01 00:00:00
abstract::Airway hyperresponsiveness in asthma has been attributed to impaired ability of deep inspiration (DI) to stretch airway smooth muscle. We have retested this hypothesis by comparing the responses to methacholine of 10 asthmatic and 10 control subjects. After each dose subjects breathed tidally without deep inspiration ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.1.9707125
更新日期:1998-07-01 00:00:00
abstract::The pathophysiology of impaired exercise tolerance in patients with cystic fibrosis (CF) is not completely understood. The objective of this study was to compare exercise ability (at clinical and cellular levels) and resting energy expenditure in female athletes with CF compared with matched control subjects. Sixteen ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.200303-363OC
更新日期:2003-12-15 00:00:00
abstract::The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS)....
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.1.8542150
更新日期:1996-01-01 00:00:00
abstract:RATIONALE:Human metapneumovirus is a newly described virus isolated in 2001 from children with acute respiratory viral infection. It has subsequently been reported globally, although there are limited data in lung transplant recipients. OBJECTIVES:To prospectively analyze whether human metapneumovirus was circulating ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200711-1657OC
更新日期:2008-10-15 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA) has been associated with kidney function loss, which may be related to changes in the renin-angiotensin system (RAS). OBJECTIVES:We sought to determine the effect of continuous positive airway pressure (CPAP) of patients with OSA on renal hemodynamics at baseline and in response...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.201403-0526OC
更新日期:2014-09-01 00:00:00
abstract:RATIONALE:Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. OBJECTIVES:To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. METHODS:We conducted a randomized, double-blind, placebo-controlled ...
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.200804-567OC
更新日期:2009-05-01 00:00:00
abstract:RATIONALE:In San Francisco, 70% of the tuberculosis cases occur among foreign-born persons, mainly from China, the Philippines, and Mexico. We postulate that there are differences in the characteristics and risk factors for tuberculosis among these populations. OBJECTIVES:To determine the clinical, epidemiological and...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201212-2239OC
更新日期:2013-05-01 00:00:00
abstract::Long-term effects of high doses of inhaled corticosteroids (ICS) on bone density and metabolism are still uncertain. Fifty-one patients (37 male, 14 female) using beclomethasone or budesonide at a daily dose > 800 microgram/d (high-dose group [Group HD] mean: 983 microgram/d [prescribed dose x estimated compliance]) o...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.3.9802096
更新日期:1999-03-01 00:00:00