COPD Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry

Leung, Janice M.; Chen, Virginia; Hollander, Zsuzsanna; Dai, Darlene; Tebbutt, Scott J.; Aaron, Shawn D.; Vandemheen, Kathy L.; Rennard, Stephen I.; FitzGerald, J. Mark; Woodruff, Prescott G.; Lazarus, Stephen C.; Connett, John E.; Miller, Bruce E.; Borchers, Christoph H.; McManus, Bruce M.; Ng, Raymond T.; Sin, Don D.

doi:10.1371/journal.pone.0161129

Cited by 21 publications

(16 citation statements)

References 42 publications

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“…The increased level of serum biomarkers during AE could help clinicians to identify AECOPD early in the clinical course to enable intervention. In recent years, biomarker candidates have been reported for AECOPD 16–19. Chen et al conducted a systematic review.…”

Section: Discussionmentioning

confidence: 99%

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Serum levels of IGFBP7 are elevated during acute exacerbation in COPD patients

Ruan¹,

Wu²,

Shi³

et al. 2017

COPD

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ObjectiveThe purpose of this study was to explore the insulin-like growth factor binding protein 7 (IGFBP7) level in the serum of chronic obstructive pulmonary disease (COPD) patients during acute exacerbation (AE).MethodsThe study population consisted of 47 AECOPD patients, including 25 patients enrolled between January 2011 and February 2011 (the first group) and 22 patients enrolled from December 2011 to August 2012 (the second group) and 29 healthy controls. Chemiluminescence–linked immunoassay was used to detect serum IGFBP7 levels. For the second group patients, IGFBP7 and C-reactive protein (CRP) levels were measured both on the admission day and on the discharge day.ResultsAmong the first group AECOPD patients, serum IGFBP7 levels were significantly elevated in AECOPD patients in the intensive care unit (ICU; 52.92±16.32 ng/mL), and in hospitalized AECOPD patients not in ICU (40.66±13.9), compared to healthy subjects (30.3±7.09 ng/mL; P<0.01). For the second group AECOPD patients, the increased IGFBP7 levels reduced after the patients had recovered (34.42±11.88 vs 27.24±7.2 ng/mL; P<0.01). During AE, the correlation coefficient between IGFBP7 and CRP was 0.357. In receiver operating characteristic analysis, the area under the curve was 0.799 for CRP, and 0.663 for IGFBP7 in distinguishing patients with AECOPD on the admission day from the discharge day.ConclusionSerum IGFBP7 levels were raised during AECOPD. Similar to the expression pattern of CRP, the IGFBP7 levels reduced after convalescence, suggesting that IGFBP7 might have a candidate role as a biomarker of AECOPD. No significant linear correlation was detected between IGFBP7 and CRP, indicating the probable different role for the two molecules in assessing AECOPD. Further study is needed to explore the value of IGFBP7 in differentiating phenotypes of AECOPD.

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Section: Discussionmentioning

confidence: 99%

“…In recent years, biomarker candidates have been reported for AECOPD. 16 – 19 Chen et al conducted a systematic review. CRP, interleukin-6, and tumor necrosis factor-alpha were the most frequently studied biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of IGFBP7 are elevated during acute exacerbation in COPD patients

Ruan¹,

Wu²,

Shi³

et al. 2017

COPD

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“…Smoking may result in chronic inflammation, such as COPD, with great morbidity and mortality [24]. The search for alternative anti-inflammatory treatments through medicinal plants is important and can be effective in the prevention and recovery of diseases caused by smoking [14].…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory actions of herbal medicines in a model of chronic obstructive pulmonary disease induced by cigarette smoke

Possebon

Lebron

Silva

et al. 2018

Biomedicine & Pharmacotherapy

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The effects of four medicinal herbs (Arctium lappa, Plantago major, Mikania glomerata Spreng and Equisetum arvense) with anti-inflammatory properties were evaluated in a chronic obstructive pulmonary disease (COPD) model. Wistar rats were exposed to cigarette smoke during 8 weeks and one of the groups was orally given a solution containing 4% of each alcoholic herbal extracts during the exposure period. Control group was not exposed to smoke or treated. Histopathological, immunohistochemical and biochemical analyzes were performed. Normal blood plasma levels of gamma glutamyl transferase indicated no toxicity of the administered herbal extracts. The treatment reduced leukocytes influx in bronchoalveolar lavage, mast cell and macrophages numbers in lungs, as well as prevented pulmonary congestion and tracheal metaplasia. Herbal mixture also decreased plasma inflammatory mediator levels and pulmonary expression of annexin A1 and nuclear factor-k?. Our data indicate synergistic and protective effects of the used herbal medicines in animals exposed to cigarette smoke as a potential therapeutic strategy.

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“…To determine which if any of the steroid-responsive genes discovered in study 1 could be replicated and which of these replicated genes related to 1-year mortality among patients who experienced a severe AECOPD, requiring hospitalisation, we used data from the Rapid Transition Program (RTP) cohort. The details of the RTP cohort have been previously reported [7]. Briefly, RTP included patients admitted for AECOPD as the Principal (or Most Responsible) Diagnosis at Vancouver General Hospital (VGH) or St. Paul’s Hospital (SPH) in Vancouver, Canada.…”

Section: Methodsmentioning

confidence: 99%

Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial

et al. 2019

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Background Effects of systemic corticosteroids on blood gene expression are largely unknown. This study determined gene expression signature associated with short-term oral prednisone therapy in patients with chronic obstructive pulmonary disease (COPD) and its relationship to 1-year mortality following an acute exacerbation of COPD (AECOPD). Methods Gene expression in whole blood was profiled using the Affymetrix Human Gene 1.1 ST microarray chips from two cohorts: 1) a prednisone cohort with 37 stable COPD patients randomly assigned to prednisone 30 mg/d + standard therapy for 4 days or standard therapy alone and 2) the Rapid Transition Program (RTP) cohort with 218 COPD patients who experienced AECOPD and were treated with systemic corticosteroids. All gene expression data were adjusted for the total number of white blood cells and their differential cell counts. Results In the prednisone cohort, 51 genes were differentially expressed between prednisone and standard therapy group at a false discovery rate of < 0.05. The top 3 genes with the largest fold-changes were KLRF1, GZMH and ADGRG1; and 21 genes were significantly enriched in immune system pathways including the natural killer cell mediated cytotoxicity. In the RTP cohort, 27 patients (12.4%) died within 1 year after hospitalisation of AECOPD; 32 of 51 genes differentially expressed in the prednisone cohort significantly changed from AECOPD to the convalescent state and were enriched in similar cellular immune pathways to that in the prednisone cohort. Of these, 10 genes including CX3CR1, KLRD1, S1PR5 and PRF1 were significantly associated with 1-year mortality. Conclusions Short-term daily prednisone therapy produces a distinct blood gene signature that may be used to determine and monitor treatment responses to prednisone in COPD patients during AECOPD. Trial registration The prednisone cohort was registered at clinicalTrials.gov ( NCT02534402 ) and the RTP cohort was registered at ClinicalTrials.gov ( NCT02050022 ). Electronic supplementary material The online version of this article (10.1186/s12931-019-1147-2) contains supplementary material, which is available to authorized users.

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COPD Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry

Cited by 21 publications

References 42 publications

Serum levels of IGFBP7 are elevated during acute exacerbation in COPD patients

Serum levels of IGFBP7 are elevated during acute exacerbation in COPD patients

Anti-inflammatory actions of herbal medicines in a model of chronic obstructive pulmonary disease induced by cigarette smoke

Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial

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