Dataset Information

Proteomic profiling of bronchoalveolar lavage fluid in critically ill patients with ventilator-associated pneumonia.

ABSTRACT:

Rationale

Ventilator-associated pneumonia (VAP) is a common complication in patients with acute lung injury (ALI) and can lead to increased morbidity and mortality. Identifying protein profiles specific to VAP in bronchoalveolar lavage fluid (BALF) may aid in earlier diagnosis, elucidate mechanisms of disease, and identify putative targets for therapeutic intervention.

Methods

BALF was obtained from 5 normal subjects and 30 ALI patients: 14 with VAP (VAP(+)) and 16 without VAP (VAP(-)). Each sample underwent shotgun proteomic analysis based on tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation and protein interaction network analysis. Supervised classification algorithms were implemented to discover a proteomic classifier for identifying critically ill patients with VAP.

Results

ALI patients had distinct BALF proteomic profiles compared to normal controls. Within the ALI group, we identified 76 differentially expressed proteins between VAP(+) and VAP(-). Functional analysis of these proteins suggested activation of pro-inflammatory pathways during VAP. We identified and validated a limited proteomic signature that discriminated VAP(+) from VAP(-) patients comprised of three proteins: S100A8, lactotransferrin (LTF), and actinin 1 (ACTN1).

Conclusions

Combining proteomic with computational analyses is a powerful approach to study the BALF proteome during lung injury and development of VAP. This integrative methodology is a promising strategy to differentiate clinically relevant subsets of ALI patients, including those suffering from VAP.

SUBMITTER: Nguyen EV

PROVIDER: S-EPMC3591362 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Proteomic profiling of bronchoalveolar lavage fluid in critically ill patients with ventilator-associated pneumonia.

Nguyen Elizabeth V EV Gharib Sina A SA Palazzo Steven J SJ Chow Yu-hua YH Goodlett David R DR Schnapp Lynn M LM

PloS one 20130307 3

<h4>Rationale</h4>Ventilator-associated pneumonia (VAP) is a common complication in patients with acute lung injury (ALI) and can lead to increased morbidity and mortality. Identifying protein profiles specific to VAP in bronchoalveolar lavage fluid (BALF) may aid in earlier diagnosis, elucidate mechanisms of disease, and identify putative targets for therapeutic intervention.<h4>Methods</h4>BALF was obtained from 5 normal subjects and 30 ALI patients: 14 with VAP (VAP(+)) and 16 without VAP (VA ...[more]

PMID: 23505561

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Project description:BackgroundBacterium/fungus-associated pneumonia (BAP/FAP) is the prominent cause of high mortality and morbidity with important clinical impacts globally. Effective diagnostic methods and proper specimen types hopefully facilitate early diagnosis of pneumonia and prevent spread of drug-resistant bacteria/fungi among critically ill patients.MethodsIn the present study, 342 bronchoalveolar lavage fluid (BALF) samples were collected from critically ill patients with pulmonary infections between November 2020 and March 2021. The BALF materials were comparatively employed to screen BAP/FAP through microscopy, culture, antigenic marker and PCR-based methods. The limit of detection (LOD) of cultures and PCR for bacteria/fungi was determined by serial dilution assays. Specimen slides were prepared with Gram staining for microscopic examinations. Microbial cultures and identifications underwent routine clinical protocols with the aid of mass spectrometry. (1,3)-β-D-glucan and galactomannan tests with BALF were carried out accordingly. Direct detection of pathogens in BALF was achieved through PCR, followed by sequencing and BLAST in GenBank database for pathogenic identification. The subjects' demographic and clinical characteristics were well evaluated.ResultsBAP/FAP was identified in approximately 47% of the subjects by the BALF-based PCR. The PCR-based diagnostic methods showed improved detection performance for fungi with good LOD, but performed similarly for bacteria, when compared to the cultures. There was poor agreement among traditional microscopy, culture and PCR assays for bacterial detections (kappa value, 0.184 to 0.277). For overall bacterial/fungal detections, the microscopy showed the lowest detecting rate, followed by the cultures, which displayed a slightly higher sensitivity than the microscopy did. The sensitivity of PCR was much higher than that of the other means of interest. However, the traditional cultures rather than antigenic marker-based approaches were moderately consistent with the PCR-based methods in fungal species identification, particularly for Candida and Aspergillus spp. Our findings further revealed that the age, length of hospital stay, invasive procedures and cerebral diseases were likely considered as main risk factors for BAP/FAP.ConclusionScreening for BALF in critically ill patients with suspected pneumonia pertaining high risk factors using combined PCR-based molecular detection strategies would hopefully contribute to early diagnosis of BAP/FAP and improved prognosis of the patients.

Dataset Information

Proteomic profiling of bronchoalveolar lavage fluid in critically ill patients with ventilator-associated pneumonia.

Rationale

Methods

Results

Conclusions

Publications

Proteomic profiling of bronchoalveolar lavage fluid in critically ill patients with ventilator-associated pneumonia.

Similar Datasets

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