Abstract:
RATIONALE:S. aureus is the most common respiratory pathogen isolated from patients with cystic fibrosis (CF) in the US. While modes of acquisition and genetic adaptation have been described for Pseudomonas aeruginosa, resulting in improved diagnosis and treatment, these features remain more poorly defined for S. aureus. OBJECTIVES:To characterize the molecular epidemiology and genetic adaptation of S. aureus during chronic CF airway infection and in response to antibiotic therapy. METHODS:We performed whole genome sequencing of 1,382 S. aureus isolates collected longitudinally over a mean 2.2 years from 246 children with CF at five US centers between 2008-2017. Results were integrated with clinical and demographic data to characterize bacterial population dynamics and identify common genetic targets of in vivo adaptation. MEASUREMENTS AND MAIN RESULTS:45.5% of patients carried multiple, coexisting S. aureus lineages, often having different antibiotic susceptibility profiles. Adaptation during the course of infection commonly occurred in a set of genes related to persistence and antimicrobial resistance. Individual sequence types demonstrated wide geographic distribution, and we identified limited strain sharing among children linked by common household or clinical exposures. Unlike P. aeruginosa, S. aureus genetic diversity was unconstrained, with ongoing flow of new genetic elements into the population of isolates from children with CF. CONCLUSIONS:CF airways are frequently co-infected by multiple, genetically distinct S. aureus lineages, indicating that current clinical procedures for sampling isolates and selecting antibiotics are likely inadequate. Strains can be shared by patients in close domestic or clinical contact and undergo convergent evolution in key persistence and antimicrobial resistance genes, suggesting novel diagnostic and therapeutic approaches for future study.
journal_name
Am J Respir Crit Care Medauthors
Long DR,Wolter DJ,Lee M,Precit M,McLean K,Holmes E,Penewit K,Waalkes A,Hoffman LR,Salipante SJdoi
10.1164/rccm.202003-0735OCsubject
Has Abstractpub_date
2020-12-09 00:00:00eissn
1073-449Xissn
1535-4970pub_type
杂志文章abstract::The gender-and race-specific effects of asthma/wheeze on pulmonary function level and annual growth velocity were studied in a cohort of 10,792 white and 944 black children 6 to 18 yr of age, examined annually between 1974 and 1989 in six U.S. cities. In comparison with white boys who never reported asthma or wheeze, ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.149.5.8173760
更新日期:1994-05-01 00:00:00
abstract::We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5 mg/d for 2 d on the b...
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.162.1.9910039
更新日期:2000-07-01 00:00:00
abstract::Because inflammation stimulates the expression of inducible nitric oxide (NO) synthase (iNOS) with an associated increased local NO production, we hypothesized that patients with pneumonia would have increased excretion of NO into their airways. To test this hypothesis, NO was measured in the exhaled air and from the ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.163.5.9906049
更新日期:2001-04-01 00:00:00
abstract::Rationale: Decisions in medicine are made on the basis of knowledge and reasoning, often in shared conversations with patients and families in consideration of clinical practice guideline recommendations, individual preferences, and individual goals. Observational studies can provide valuable knowledge to inform guide...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.202010-3943ST
更新日期:2021-01-01 00:00:00
abstract::Typical for critical illnesses are substantial alterations within the hypothalamic-anterior pituitary-peripheral hormonal axes that are proportionate to the risk of poor outcome. These neuroendocrine responses to critical illness follow a biphasic pattern. The acute phase (first hours to days) is characterized by an i...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.201607-1516CI
更新日期:2016-12-01 00:00:00
abstract:RATIONALE:Dysregulation of cellular metabolism has been shown to participate in several pathologic processes. However, the role of metabolic reprogramming is not well appreciated in the pathogenesis of organ fibrosis. OBJECTIVES:To determine if glycolytic reprogramming participates in the pathogenesis of lung fibrosis...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201504-0780OC
更新日期:2015-12-15 00:00:00
abstract:RATIONALE:Few studies have examined associations between exposure to air pollution and childhood lung function after implementation of strict air quality regulations in the 1990s. OBJECTIVES:To assess traffic-related pollution exposure and childhood lung function. METHODS:We geocoded addresses for 614 mother-child pa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201506-1058OC
更新日期:2016-04-15 00:00:00
abstract::The forced oscillation technique (FOT) and interrupter technique are particularly attractive for pediatric use as they require only passive cooperation from the patient. We compared the sensitivity and specificity of these methods for detecting airway obstruction and its reversibility in 118 children (3-16 yr) with as...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.6.2010153
更新日期:2001-09-15 00:00:00
abstract::Numerous in vitro and in vivo studies in both animals and patients with asthma have shown that interleukin (IL)-9 is an important inflammatory mediator in asthma. To examine the effects of IL-9 antagonism on airway inflammation, ovalbumin-sensitized BALB/c mice were intravenously given anti-IL-9 antibody or an isotype...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2105079
更新日期:2002-08-01 00:00:00
abstract::The potential role of nitric oxide synthase-2 (NOS2) in acute lung injury (ALI) has gained increasing attention. This study evaluates the effects of hypoxia, an important feature of ALI, on NOS2 expression in a rat model of ALI caused by exposure to hypoxia and LPS. Exposure to hypoxia alone had no effect on the expre...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200209-1027OC
更新日期:2003-08-01 00:00:00
abstract::The aim of this study was to clarify the influence of gastroesophageal reflux (GER) on cough threshold in patients with digestive symptoms but free from respiratory involvement. Of 57 consecutive subjects referred for 24-h esophageal pH monitoring because of digestive reflux symptoms, 29 patients free from respiratory...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.2.7842220
更新日期:1995-02-01 00:00:00
abstract:RATIONALE:The association between aging and idiopathic pulmonary fibrosis is established. The associations between aging-related biomarkers and interstitial lung abnormalities (ILA) have not been comprehensively evaluated. OBJECTIVE:Evaluate associations between aging biomarkers, ILA, and all-cause mortality. METHODS...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.202007-2993OC
更新日期:2020-10-20 00:00:00
abstract::Wheezing in childhood is not a single disorder and different wheezing-associated respiratory illnesses have been recently described. We investigated the association between wheezing conditions and familial, pre-, peri-, and postnatal risk factors. We studied 16,333 children, 6 to 7 yr old, enrolled in a population-bas...
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.160.5.9811002
更新日期:1999-11-01 00:00:00
abstract:RATIONALE:Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress. OBJECTIVES:Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidativ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1164/rccm.201801-0105OC
更新日期:2018-09-01 00:00:00
abstract::Segmental bronchoprovocation (SBP) with allergen was used in an attempt to study eosinophils recruited to the airway 24 h after challenge. Unexpectedly, in the first four patients, neutrophils (rather than eosinophils) were recruited in the bronchoalveolar lavage (BAL) fluids, and we hypothesized that the allergen ext...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.149.6.8004300
更新日期:1994-06-01 00:00:00
abstract::The blood beryllium lymphocyte proliferation test is used in medical surveillance to identify both beryllium sensitization and chronic beryllium disease. Approximately 50% of individuals with beryllium sensitization have chronic beryllium disease at the time of their initial clinical evaluation; however, the rate of p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200402-190OC
更新日期:2005-01-01 00:00:00
abstract:RATIONALE:Identification of patients with drug-resistant pathogens at initial diagnosis is essential for treatment of pneumonia. OBJECTIVES:To elucidate clinical features of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), and to clarify risk factors for drug-resistant pathogens in patien...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201301-0079OC
更新日期:2013-10-15 00:00:00
abstract::We found that continuous eosinophilic inflammation after repeated antigen instillation into the nose was observed only in A/J mice, not in three other strains. Histologic analysis of tissues from A/J mice revealed features typical of airway remodeling, i.e., airway wall thickening and increased collagen depositions we...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200210-1188OC
更新日期:2003-10-15 00:00:00
abstract:RATIONALE:Roflumilast is a therapeutic agent in the treatment of chronic obstructive pulmonary disease (COPD). It has antiinflammatory effects; however, it is not known whether it can affect a biologic pathway implicated in COPD pathogenesis and progression. The self-propagating acetyl-proline-glycine-proline (AcPGP) p...
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.201503-0543OC
更新日期:2015-10-15 00:00:00
abstract::We have studied intrasubject variability with respect to counts of immunostained inflammatory cells in snap frozen endobronchial biopsies from a group of patients with clinically mild to moderate stable asthma. Fiberoptic bronchoscopy was used to obtain endobronchial biopsies from the upper and lower lobes in 12 volun...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.3.8630570
更新日期:1996-03-01 00:00:00
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 adopt...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201311-1951OC
更新日期:2014-04-01 00:00:00
abstract::Short-term increases in particulate air pollution are associated with increased incidence of cardiovascular events. Previously, we showed that intratracheally instilled diesel exhaust particles (DEPs) are prothrombotic. Here, we investigated the time course and the mechanisms. At 1, 6, and 24 hours after instillation ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200306-801OC
更新日期:2003-12-01 00:00:00
abstract::There is a need for quick, reliable, and noninvasive lung function tests to assess airway obstruction in preschool children both for pediatric pulmonary care as well as for research purposes. We studied feasibility, reproducibility, and validity of measurements of the respiratory system using the interrupter technique...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.163.6.2005076
更新日期:2001-05-01 00:00:00
abstract::Respiratory syncytial virus (RSV) is the major pathogen responsible for acute bronchiolitis in infancy. However, evaluation of the relative importance of rhinovirus or multiple viral infections has been hampered by the lack of sensitive diagnostic methodologies. Therefore, in this study we used the reverse transcripti...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200112-118BC
更新日期:2002-05-01 00:00:00
abstract::A major cause of morbidity and mortality following lung transplantation is posttransplant lymphoproliferative disease (PTLD). In a retrospective cohort analysis of pediatric patients, we evaluated the risk factors associated with PTLD in 128 first-time lung transplant recipients from 1990 to 1997. The greatest risk fa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.4.9901013
更新日期:2000-04-01 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::Long-term cognitive impairment is common among ICU survivors, but its natural history remains unclear. In this systematic review, we report the frequency of cognitive impairment in ICU survivors across various time points after ICU discharge that were extracted from 46 of the 3,350 screened records. Prior studies used...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201904-0816CI
更新日期:2020-07-15 00:00:00
abstract::Reduced bronchodilatation in response to deep inspiration (DI) has been demonstrated in asthmatics. We have previously shown that inhibition of DI for 10 min or more during methacholine inhalation increases airway narrowing in normals. We tested the hypothesis that inhibition of DIs during methacholine inhalation in a...
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.164.2.2006101
更新日期:2001-07-15 00:00:00
abstract::To elucidate which cells are synthesizing tenascin in usual interstitial pneumonia (UIP) we have analyzed thoracoscopic or open lung biopsies from 30 patients with UIP by mRNA in situ hybridization, using (35)S-labeled tenascin RNA probes. The phenotype of the cells expressing tenascin mRNA was confirmed by immunohist...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.3.9809115
更新日期:2000-03-01 00:00:00
abstract::The effect of suplatast tosilate, which has been proven to inhibit T-cell synthesis of IL-4 and IL-5, on the response to antigen inhalation challenge was investigated in sensitized guinea pigs. The animals were given an oral dose of 30 or 100 mg/kg of suplatast or vehicle (distilled water) daily for 1 wk before antige...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.160.1.9809059
更新日期:1999-07-01 00:00:00