<i>Pseudomonas aeruginosa</i>in children with cystic fibrosis diagnosed through newborn screening: Assessment of clinic exposures and microbial genotypes

Hayes, Don; West, Susan E. H.; Rock, Michael J.; Li, Zhanhai; Splaingard, Mark; Farrell, Philip M.

doi:10.1002/ppul.21263

Cited by 15 publications

(12 citation statements)

References 35 publications

(64 reference statements)

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“…We did not evaluate the effects of cohorting practices on risk of Pa acquisition, as this has previously been evaluated [37,38]. There is no evidence that the risk of patient-to-patient transmission is less among those with residual CFTR function, so we would not recommend that patients with residual CFTR function be managed differently from an infection control standpoint or that clinics should be segregated by CFTR function.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort

Rosenfeld

Emerson

McNamara

et al. 2012

Journal of Cystic Fibrosis

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Background Risk factors for initial Pseudomonas aeruginosa (Pa) acquisition, particularly environmental exposures, are poorly understood. We aimed to identify such risk factors in order to inform prevention strategies and identify high-risk populations. Methods The study cohort included all participants in the U.S. EPIC Observational Study who had no prior Pa-positive respiratory cultures (N=889). Cox proportional hazard models were used to test the effects of factors on age at first Pa-positive respiratory culture. Results Cystic fibrosis (CF) genotype functional class had an important effect on age at initial Pa acquisition (hazard ratio (HR) comparing minimal to residual CFTR function 2.87 (95% CI 1.88, 4.39)). None of the modifiable risk factors evaluated, including cigarette smoke, hot tub use, breastfeeding, or daycare, was associated with age at Pa acquisition. Similarly, newborn screening was not associated with age at Pa acquisition (HR 0.85, 95% CI 0.66, 1.09). Key associations were validated in a CF Foundation National Patient Registry replication cohort. Conclusions Given the ubiquitous presence of Pa in the environment, it may be that many imposed lifestyle changes will have less impact on age at initial Pa acquisition than genetic determinants.

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Section: Discussionmentioning

confidence: 99%

Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort

Rosenfeld

Emerson

McNamara

et al. 2012

Journal of Cystic Fibrosis

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“…New P. aeruginosa strains can appear after eradication therapies. [3] With chronicity of infection and prolonged administration of drugs, P. aeruginosa strains become resistant against antibiotics, diversifies its colony morphology, acquires mucoidity and shows multiple genotypes. [4] There are six different colony morphotypes of P. aeruginosa , type 5 (mucoid Type) was found to be the most common morphotype in chronic patients.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic characterization and PCR-Ribotypic profile of Pseudomonas aeruginosa isolated from cystic fibrosis patients in Iran

et al. 2013

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Background:Pseudomonas aeruginosa, is the most common pathogen in patients with cystic fibrosis (CF) that shows various resistance to antibiotics, acquires mucoidity and multiple genotypes. This survey was performed to study phenotypic and genotypic variations among P. aeruginosa isolates in CF patients at Alzahra Hospital in Isfahan, Iran.Materials and Methods:The isolates of Pseudomonas aeruginosa from CF patients at Alzahra Hospital was identified by appropriate biochemical and microscopic tests, then performed antibiotic resistance tests and mucoid colony morphotyping. The genum of isolates extracted and confirmed on 16S rDNA-based PCR assay and typed on 16S rDNA-23SrDNA spacer, restricted with Hinf1 restriction enzyme.Results:P. aeruginosa was isolated from 21 of the 59 CF patients (35.5%), Out of 21 isolates 9 (42.8%) strains were revealed mucoid morphotype. 81.8% isolates of mucoid strains were resistance to at least one of four antibiotics (GM, AN, PIP and CP). Most of the isolates (86%) showed resistance to ceftazidime. Ribotyping revealed two patterns (P1, P5).Conclusion:The isolates of P. aeruginosa showed meaningful difference between drug resistance to antibiotics. The majority of P. aeruginosa isolated from CF patients showed pattern1 of PCR-Ribotyping.

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“…Regardless of the initial cause, hyperinflammation in the CF lung occurs early and continues throughout life (5). This inflammatory state is further amplified by bacterial infections, in particular, Pseudomonas aeruginosa (6,7). The presence of bacteria promotes the airway epithelium to release proinflammatory cytokines such as the potent neutrophil chemoattractant IL-8 (8).…”

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confidence: 99%

Dysregulation of TIM-3–Galectin-9 Pathway in the Cystic Fibrosis Airways

Vega-Carrascal

Reeves

Niki

et al. 2011

The Journal of Immunology

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The T-cell Ig and mucin domain-containing molecules (TIMs) have emerged as promising therapeutic targets to correct abnormal immune function in several autoimmune and chronic inflammatory conditions. It has been reported that proinflammatory cytokine dysregulation and neutrophil-dominated inflammation are the main causes of morbidity in cystic fibrosis (CF). However, the role of TIM receptors in CF has not been investigated. In this study, we demonstrated that TIM-3 is constitutively overexpressed in the human CF airway, suggesting a link between CF transmembrane conductance regulator (CFTR) function and TIM-3 expression. Blockade of CFTR function with the CFTR inhibitor-172 induced an upregulation of TIM-3 and its ligand galectin-9 in normal bronchial epithelial cells. We also established that TIM-3 serves as a functional receptor in bronchial epithelial cells, and physiologically relevant concentrations of galectin-9 induced TIM-3 phosphorylation, resulting in increased IL-8 production. In addition, we have demonstrated that both TIM-3 and galectin-9 undergo rapid proteolytic degradation in the CF lung, primarily because of neutrophil elastase and proteinase-3 activity. Our results suggest a novel intrinsic defect that may contribute to the neutrophil-dominated immune response in the CF airways.

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Pseudomonas aeruginosain children with cystic fibrosis diagnosed through newborn screening: Assessment of clinic exposures and microbial genotypes

Cited by 15 publications

References 35 publications

Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort

Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort

Phenotypic characterization and PCR-Ribotypic profile of Pseudomonas aeruginosa isolated from cystic fibrosis patients in Iran

Dysregulation of TIM-3–Galectin-9 Pathway in the Cystic Fibrosis Airways

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