Sputum Proteomics in Inflammatory and Suppurative Respiratory Diseases

Gray, Robert D.; MacGregor, Gordon; Noble, Donald; Imrie, M.; Dewar, Maria H; Boyd, A. Christopher; Innes, J A; Porteous, David J.; Greening, A P

doi:10.1164/rccm.200703-409oc

Cited by 174 publications

(159 citation statements)

References 51 publications

Supporting

Mentioning

154

Contrasting

Order By: Relevance

“…Selection criteria for the 15 candidate proteins included detection in blood, biologic plausibility, publications suggesting a role for these proteins in CF or other chronic inflammatory lung diseases (including proteomic investigations [24][25][26]), and availability and subsequent validation of commercial assays (ELISA or other) for these proteins. Although airway inflammation has long been recognized as a hallmark feature of CF lung disease, the role of systemic inflammation in CF has In fact, based on preliminary findings from this study, serum CRP, SAA, and calprotectin were measured and used to demonstrate immunomodulatory effects of azithromycin in a CF interventional trial (27).…”

Section: O2 Saturationmentioning

confidence: 99%

Effect of Treatment of Cystic Fibrosis Pulmonary Exacerbations on Systemic Inflammation

et al. 2015

View full text Add to dashboard Cite

Rationale: In cystic fibrosis (CF), pulmonary exacerbations present an opportunity to define the effect of antibiotic therapy on systemic measures of inflammation.Objectives: Investigate whether plasma inflammatory proteins demonstrate and predict a clinical response to antibiotic therapy and determine which proteins are associated with measures of clinical improvement.Methods: In this multicenter study, a panel of 15 plasma proteins was measured at the onset and end of treatment for pulmonary exacerbation and at a clinically stable visit in patients with CF who were 10 years of age or older.Measurements and Main Results: Significant reductions in 10 plasma proteins were observed in 103 patients who had paired blood collections during antibiotic treatment for pulmonary exacerbations. Plasma C-reactive protein, serum amyloid A, calprotectin, and neutrophil elastase antiprotease complexes correlated most strongly with clinical measures at exacerbation onset. Reductions in C-reactive protein, serum amyloid A, IL-1ra, and haptoglobin were most associated with improvements in lung function with antibiotic therapy. Having higher IL-6, IL-8, and a 1 -antitrypsin (a1AT) levels at exacerbation onset were associated with an increased risk of being a nonresponder (i.e., failing to recover to baseline FEV 1 ). Baseline IL-8, neutrophil elastase antiprotease complexes, and a1AT along with changes in several plasma proteins with antibiotic treatment, in combination with FEV 1 at exacerbation onset, were predictive of being a treatment responder. Conclusions:Circulating inflammatory proteins demonstrate and predict a response to treatment of CF pulmonary exacerbations. A systemic biomarker panel could speed up drug discovery, leading to a quicker, more efficient drug development process for the CF community.

show abstract

Section: O2 Saturationmentioning

confidence: 99%

Effect of Treatment of Cystic Fibrosis Pulmonary Exacerbations on Systemic Inflammation

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Intense proteomics research to unveil protein markers has resulted in fi nding associations between myeloperoxidase, interleukin (IL)-8, cleaved ␣ -antitrypsin, and S100A8 (CF antigen) in sputum and the frequency of pulmonary exacerbations ( 7 ) or directly in the presence of CFTR mutations ( 8,9 ), in addition to proteomic signatures in serum or corresponding to known infl ammation markers ( 10 ) or other proteins differentially expressed in target tissues of CF before the appearance of any sign of the disease, like annexin-1 ( 11 ), cytosolic phospholipase A2 ␣ ( 11 ), cytokeratins 8 and 18 ( 12 ), and peroxiredoxin 6 ( 13,14 ). More recently, sputum proteomics has revealed that a prolineglycine-proline (PGP) peptide, an extracellular matrixderived neutrophil attractant, is a marker of infl ammatory clinical parameters at both time points.…”

mentioning

confidence: 99%

Plasma lipidomics reveals potential prognostic signatures within a cohort of cystic fibrosis patients

Ollero

Astarita

Guerrera

et al. 2011

Journal of Lipid Research

View full text Add to dashboard Cite

Cystic fi brosis (CF) is associated with abnormal lipid metabolism. We have recently shown variations in plasma levels of several phosphatidylcholine (PC) and lysophopshatidylcholine (LPC) species related to disease severity in CF patients. Here our goal was to search for blood plasma lipid signatures characteristic of CF patients bearing the same mutation (F508del) and different phenotypes, and to study their correlation with forced expiratory volume in 1 s (FEV1) and Pseudomonas aeruginosa chronic infection, evaluated at the time of testing (t = 0) and three years later (t = 3). Samples from 44 F508del homozygotes were subjected to a lipidomic approach based on LC-ESI-MS. Twelve free fatty acids were positively correlated with FEV1 at t = 0 (n = 29). Four of them (C20:3n-9, C20:5n-3, C22:5n-3, and C22:6n-3) were also positively correlated with FEV1 three years later, along with PC(32:2) and PC(36:4) (n = 31). Oleoylethanolamide (OEA) was negatively correlated with FEV1 progression (n = 17). Chronically infected patients at t = 0 showed lower PC(32:2), PC(38:5), and C18:3n-3 and higher cholesterol, cholesterol esters, and triacylglycerols (TAG). Chronically infected patients at t = 3 showed significantly lower levels of LPC(18:0). These results suggest a potential prognostic value for some lipid signatures in, to our knowledge, the fi rst longitudinal study aimed at identifying lipid biomarkers for CF. -Ollero, M., G. Astarita, I. C. Guerrera, I. Sermet-Gaudelus, S.

show abstract

“…However, the present study is a preliminary research, further studies, increasing the sample size and including other airway obstructive diseases such as asthma into control group, are needed to confirm these results and especially to identify and subsequently validate the discovered protein peaks. In addition, samples from airway locality such as sputum can provide information about both inflammatory cells and mediators present in the airways [29,30]. Sputum reflects the microenvironment of the lung whereas serum reflects a processed proteome; combining data on these samples may provide the necessary means to understand, diagnose and treat COPD [31].…”

Section: Discussionmentioning

confidence: 99%

SELDI-TOF-MS in chronic obstructive pulmonary disease

Xia

Zhang

et al. 2012

Chin. Sci. Bull.

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) has a profound impact on daily life, yet remains underdiagnosed and undertreated. This study aims to discover potential protein biomarkers for diagnosis and classification of COPD. Fifty-seven COPD patients and 40 controls were divided into a training set (30 COPD patients, 20 healthy controls) and a test set (27 COPD patients, 20 healthy controls). Serum proteomic profiles were measured using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). A classification tree was established using Biomarker Pattern Software (BPS). Next we screened distinct proteins present in patients with acute exacerbations of COPD (AECOPD), stable COPD and healthy controls, in order to establish diagnostic models for classification of COPD. Twenty peaks showed statistically significant differences between COPD patients and healthy controls (P < 0.05). Two proteomic peaks (3167 and 5477 m/z) were chosen by BPS to establish a classification tree in the training set. The sensitivity and specificity of this classification tree were 92.59% and 90.00% respectively in the testing set. Furthermore, differently expressed proteins were detected among the patients with AECOPD, stable COPD, and healthy controls. Two protein profiles (3167 and 4645 m/z) could distinguish between stable COPD patients and healthy controls. Three protein profiles (3167, 2963 and 2973 m/z) could distinguish between AECOPD patients and healthy controls. Three protein profiles (5476, 14039 and 2831 m/z) could distinguish between stable COPD patients and AECOPD patients. SELDI-TOF-MS Proteinchip technology is a quick, easy and practical, high throughput analytic method. It shows the diagnostic models established by distinguished proteomic peaks can discriminate COPD patients from healthy control and can identify different stages of COPD. It will provide a highly accurate approach for diagnosis and clinical staging of COPD. chronic obstructive pulmonary disease, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, proteomics Citation:Zhang X, Zhang J, Li Q, et al. SELDI-TOF-MS in chronic obstructive pulmonary disease.

show abstract

Sputum Proteomics in Inflammatory and Suppurative Respiratory Diseases

Cited by 174 publications

References 51 publications

Effect of Treatment of Cystic Fibrosis Pulmonary Exacerbations on Systemic Inflammation

Effect of Treatment of Cystic Fibrosis Pulmonary Exacerbations on Systemic Inflammation

Plasma lipidomics reveals potential prognostic signatures within a cohort of cystic fibrosis patients

SELDI-TOF-MS in chronic obstructive pulmonary disease

Contact Info

Product

Resources

About