Calprotectin — A Marker of Mortality in COPD? Results from a Prospective Cohort Study

Holmgaard, Dennis Back; Mygind, Lone Hagens; Titlestad, Ingrid Louise; Madsen, Hanne; Pedersen, Susanne Juhl; Mortensen, Ole Hartvig; Pedersen, Court

doi:10.3109/15412555.2013.781580

Cited by 16 publications

(16 citation statements)

References 47 publications

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“…In patients suffering from cystic fibrosis, serum levels of calprotectin decreased in patients treated with antibiotics, and calprotectin levels measured at baseline and after treatment were inversely correlated with FEV 1 and predicted time to next exacerbation [ 19 ]. Recently, we have shown that plasma calprotectin predicts all-cause mortality in patients with moderate to very severe COPD in stable phase [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Neutrophil-to-lymphocyte ratio, calprotectin and YKL-40 in patients with chronic obstructive pulmonary disease: correlations and 5-year mortality – a cohort study

et al. 2015

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BackgroundChronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and progressive decline in pulmonary function. Neutrophil-to-lymphocyte ratio (NLR), YKL-40 and calprotectin are biomarkers of inflammation and predict mortality in patients with different inflammatory diseases. We aimed to investigate the correlation between levels of these three biomarkers and neutrophil granulocyte and lymphocyte count in patients with moderate to very severe COPD stratified by use of systemic glucocorticoids. Furthermore, we studied the ability of these biomarkers to predict all-cause mortality.Methods386 patients with moderate to very severe COPD were followed prospectively for 10 years. Patients were divided into two groups according to systemic glucocorticoid use at baseline. Correlations between biomarkers were assessed by Spearman’s Rho, and mortality was evaluated in uni- and multivariate Cox regression analyses with hazard ratios (HR) and 95% confidence intervals (CI).ResultsPlasma calprotectin was positively correlated with neutrophil granulocyte count and NLR. No significant association was found between plasma YKL-40 and the cellular biomarkers, irrespective of glucocorticoid treatment. In the group not treated with systemic glucocorticoids, plasma calprotectin [HR 1.002 (95% CI 1.000 – 1.004)], NLR [HR 1.090 (1.036 – 1.148)] and lymphocyte count [HR 0.667 (0.522 – 0.851)] were significantly associated with higher mortality. In the group treated with systemic glucocorticoids, higher plasma YKL-40 was significantly associated with mortality in univariate Cox regression analysis [HR 1.006 (1.003 – 1.008)].ConclusionsCalprotectin was related to neutrophil granulocyte count and NLR in patients with moderate to very severe COPD in stable phase and not in treatment with systemic glucocorticoids. Lymphopenia, higher plasma calprotectin and higher NLR were independent predictors of increased all-cause mortality in this group. Our data also suggests that treatment with systemic glucocorticoids has a significant impact on the ability of inflammatory biomarkers to predict all-cause mortality.Trial registrationClinicalTrials.gov NCT00132860.

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Section: Introductionmentioning

confidence: 99%

Neutrophil-to-lymphocyte ratio, calprotectin and YKL-40 in patients with chronic obstructive pulmonary disease: correlations and 5-year mortality – a cohort study

et al. 2015

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“…The total cell concentration was considerably higher in BALf samples from the endotoxin-exposed segments than from the vehicle-exposed ones at both 12 4 cells/mL; p < 0.01), giving, on average, a 19-fold-higher concentration on the endotoxin-exposed side at 12 h. At the same time point, the concentration of neutrophils was (on average) 66-fold, that of alveolar macrophages 7-fold, and that of lymphocytes 9-fold-higher on the endotoxin-exposed side. This effect of endotoxin largely remained at 24 h after exposure ( Fig.…”

Section: Influx Of Leukocytesmentioning

confidence: 94%

“…This AMP has been detected in the sputa, bronchoalveolar lavage fluid (BALf), and blood of patients with chronic obstructive pulmonary disease [10][11][12] as well as in induced sputum from patients with exacerbations of cystic fibrosis [10] . Calprotectin has also been detected in induced sputum after the inhalation of endotoxin [13] .…”

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confidence: 99%

Endotoxin Exposure Increases LL-37 - but Not Calprotectin - in Healthy Human Airways

Smith

Stockfelt²,

Tengvall³

et al. 2017

J Innate Immun

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Rationale: The antimicrobial peptides (AMPs) LL-37 and calprotectin are important players in the innate immunity of human airways. In patients with diseases characterized by bacterial colonization, the airway concentrations of these AMPs are increased. Less is known about their presence and release patterns in healthy humans. Our aim was to determine whether LL-37 and calprotectin are released after the activation of the innate immune response in the peripheral airways. Methods: Healthy volunteers underwent exposure to endotoxin and vehicle in contralateral segment bronchi. After 12 or 24 h, samples of bronchoalveolar lavage fluid (BALf) were collected bilaterally from exposed segments. Cell and AMP concentrations were assessed, as were the pro-form and active form of LL-37. Results: Both LL-37 and calprotectin were detected in cell-free BALf from both endotoxin- and vehicle-exposed segments. The concentrations of precursor and active LL-37 and neutrophils were significantly higher in endotoxin-exposed segments after 12 and 24 h, and the concentrations of LL-37 and neutrophils correlated positively. The concentrations of calprotectin were not markedly affected by exposure to endotoxin. Conclusions: Local endotoxin exposure elicits the release and activation of LL-37 but not calprotectin in healthy human peripheral airways, suggesting an inducible involvement of LL-37 in the local innate immune response.

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“…EC-LIPSE is a 3-year longitudinal study with four specific aims: (i) definition of clinically relevant COPD subtypes, (ii) identification of parameters that predict disease progression in these subtypes, (iii) examination of biomarkers that correlate with COPD subtypes and may predict disease progression, and (iv) identification of novel genetic factors and/or biomarkers that both correlate with clinically relevant COPD subtypes and predict disease progression [33] . Furthermore, our systematic search identified interventional case-control studies in which different COPD treatments (neutrophil elastase inhibitors, long acting beta agonists, prophylactic antibiotic treatments, cholesterol lowering medication, or corticoidsteroids) were evaluated (NCT-00949975 [34] , NCT01110200 [35] , NCT00132860 [36,37] , NCT01061671 [38] , NCT00325897 [39] , EUROSCOP [40] ). In this category, the Lung Health Study (LHS) is a representative example.…”

Section: Copd Cohortsmentioning

confidence: 99%

“…Accumulating evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD [60,61] . In this respect, most of the potential biomarkers included in our list are proteins involved in inflammation or the immune response such as CRP, IL-6, beta defensin 2, among many others [25][26][27]29,36,37,54,[62][63][64][65][66][67][68][69][70][71][72][73][74] . One of the main causes leading to COPD is chronic smoking which exposes the respiratory tract to reactive oxygen species, resulting in oxidative stress and injury (which in the last instance leads also to inflammation) [59,75] .…”

Section: Copd Protein Biomarkersmentioning

confidence: 99%

Prioritization of COPD protein biomarkers, based on a systematic study of the literature

Camacho¹,

Klont²,

Horvatovich³

et al. 2016

Adv Precis Med

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Chronic Obstructive Pulmonary Disease (COPD) is a chronic lung disease mostly due to smoking and until now diagnosed by spirometry (post bronchodilator FEV 1 /FVC <70%). However, in spite of the usefulness of FEV 1 as diagnostic and prognostic tool, it has proven to be a weak indicator of future exacerbations, unable to predict lung function decline within COPD patients, as well as unable to identify the smokers "susceptible" to developing COPD at an early stage. Thus, there is an urgent need for biomarkers that address these questions and support clinical decision making in the diagnosis and treatment of (early) COPD. In this respect, considerable efforts have been devoted to identifying protein biomarkers that enable a better understanding of this complex disease and leading to better diagnostic and prognostic tools. However, in spite of the wide range of candidates that have been suggested as potentially useful COPD biomarkers, most remained at the level of the initial discovery, and only fibrinogen has been approved by the Food and Drug Administration (FDA) as predictor for all-cause mortality and COPD exacerbations. There is thus a need for future investigations of these biomarkers in large-scale and well characterized studies in order to prove their usefulness as surrogate endpoints. Based on this, the aim of the present review is to advance COPD biomarker development by providing a comprehensive overview of protein biomarker candidates which have been evaluated in clinical studies and prioritize them according to their potential of becoming valid, clinically useful COPD biomarkers.

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Calprotectin — A Marker of Mortality in COPD? Results from a Prospective Cohort Study

Cited by 16 publications

References 47 publications

Neutrophil-to-lymphocyte ratio, calprotectin and YKL-40 in patients with chronic obstructive pulmonary disease: correlations and 5-year mortality – a cohort study

Neutrophil-to-lymphocyte ratio, calprotectin and YKL-40 in patients with chronic obstructive pulmonary disease: correlations and 5-year mortality – a cohort study

Endotoxin Exposure Increases LL-37 - but Not Calprotectin - in Healthy Human Airways

Prioritization of COPD protein biomarkers, based on a systematic study of the literature

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