Elevated Peptides in Lung Lavage Fluid Associated with Bronchiolitis Obliterans Syndrome

Stone, Matthew D.; Harvey, Stephen B.; Nelsestuen, Gary L.; Reilly, Cavan; Hertz, Marshall I.; Wendt, Chris H.

doi:10.1371/journal.pone.0084471

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…Each fraction was submitted for MS/MS analysis in the orbitrap mass spectrometer for peptide identification. Sample loading, HPLC, and mass spectrometry were performed as previously described [ 8 ] with a few exceptions. Electrospray mass spectrometry was performed using a LTQ-Orbitrap XL (ThermoScientific) with spray voltage set to 1.95 kV.…”

Section: Methodsmentioning

confidence: 99%

Peptides in Bronchoalveolar Lavage in Chronic Obstructive Pulmonary Disease

et al. 2016

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BackgroundChronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease with a significant public health burden. Currently there is no biomarker that identifies those at risk of developing COPD, progression of disease or disease phenotypes. We performed metabolomic profiling of bronchoalveolar lavage fluid (BALF) from COPD patients to determine if metabolites correlated with clinical measurements such as lung function, functional status and degree of emphysema.MethodsMetabolomic components of BALF from 59 subjects with COPD and 20 healthy controls were separated by reversed-phase UPLC and analyzed by ESI-ToF mass spectrometry. We used univariate analysis and multiple regression models to investigate associations between metabolomic features and various clinical variables, such as lung function, functional status as measured by the St. George Respiratory Quotient Score and emphysema as measured by the CT density mask score.ResultsWe identified over 3900 features by mass spectrometry, many consistent with peptides. Subjects with severe COPD had increased concentration of peptides compared to controls (p < 9.526e-05). The peptide concentration correlated with spirometry, specifically pulmonary function tests associated with airflow obstruction. There was no correlation with CT density, i.e. emphysema, or functional status.ConclusionsMetabolomic profiling of BALF in COPD patients demonstrated a significant increase in peptides compared to healthy controls that associated strongly to lung function, but not emphysema or functional status.

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Section: Methodsmentioning

confidence: 99%

Peptides in Bronchoalveolar Lavage in Chronic Obstructive Pulmonary Disease

et al. 2016

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“…Treatment is limited to immunosuppressant augmentation to which response is poor and five-year survival after diagnosis is only 30-40% [2]. While single proteins, such as human neutrophil defensin, MMP-9, surfactant protein A, and unique peptides have previously been identified that correlate with the development of BOS, the global longitudinal changes in proteins and their associated biological processes in the development of BOS have not been described [3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal protein expression patterns in bronchiolitis obliterans syndrome

Roark¹,

Sandri²,

Dey³

et al. 2015

Pulmonol Respir Res

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Background: Lung transplant is an effective therapy, however, long-term survival is currently limited due to the high rate of bronchiolitis obliterans syndrome (BOS). The longitudinal biological changes that occur as a patient progresses to BOS are not well understood. The objective of this study was to evaluate the bronchoalveolar lavage fluid (BALF) proteome, seeking to identify proteins and their representative biological functions that have coherent changes in the development of BOS. Methods: Isobaric tag for relative and absolute quantification(iTRAQ ® ) with LC MS/MS were performed on BALF enriched for medium and low abundance proteins from three time points (range 699 days pre-BOS to 83 days post-BOS) taken from four patients that developed BOS. Controls consisted of pooled samples from nine patients who did not develop BOS within five years of sample acquisition. We investigated how the protein profiles changed longitudinally as the patient progressed towards BOS using Short Time-series Expression Miner, (STEM), analysis and identified gene ontology terms associated with these protein clusters. Results: We identified 871 unique proteins at a 5% FDR. STEM analysis revealed three models that met statistical significance.Gene ontology revealed three biological processes that associated with these models and included: sequestering of actin monomers, cytoskeletal organization and an inflammatory or defense response. Conclusion: Longitudinal and gene cluster models reveal coherent changes in BALF proteins as patients approach BOS.

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A review of metabolomics approaches and their application in identifying causal pathways of childhood asthma

Turi

Romick-Rosendale

Ryckman

et al. 2018

Journal of Allergy and Clinical Immunology

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Because asthma is a disease that results from host-environment interactions, an approach that allows assessment of the effect of the environment on the host is needed to understand the disease. Metabolomics has appealing potential as an application to study pathways to childhood asthma development. The objective of this review is to provide an overview of metabolomics methods and their application to understanding host-environment pathways in asthma development. We reviewed recent literature on advances in metabolomics and their application to study pathways to childhood asthma development. We highlight the (1) potential of metabolomics in understanding the pathogenesis of disease and the discovery of biomarkers; (2) choice of metabolomics techniques, biospecimen handling, and data analysis; (3) application to studying the role of the environment on asthma development; (4) review of metabolomics applied to the outcome of asthma; (5) recommendations for application of metabolomics-based -omics data integration in understanding disease pathogenesis; and (6) limitations. In conclusion, metabolomics allows use of biospecimens to identify useful biomarkers and pathways involved in disease development and subsequently to inform a greater understanding of disease pathogenesis and endotypes and prediction of the clinical course of childhood asthma phenotypes.

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Elevated Peptides in Lung Lavage Fluid Associated with Bronchiolitis Obliterans Syndrome

Cited by 3 publications

References 21 publications

Peptides in Bronchoalveolar Lavage in Chronic Obstructive Pulmonary Disease

Peptides in Bronchoalveolar Lavage in Chronic Obstructive Pulmonary Disease

Longitudinal protein expression patterns in bronchiolitis obliterans syndrome

A review of metabolomics approaches and their application in identifying causal pathways of childhood asthma

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