Abstract
Chronic obstructive pulmonary disease (COPD) is an imminent public health catastrophe. A proper severity marker is desperately needed to reflect the progress of the disease in a stage-specific manner (GOLD I–IV/A–D). The aim of the study was testing the applicability of thermodynamic analysis of blood, identifying different stages of COPD patients against each other and healthy controls. Sera from 63 COPD patients were investigated using differential scanning calorimetry (DSC). Patients formed four groups according to their GOLD severity stages, and smoking or ex-smoking subgroups were further analysed. In total, 18 GOLD A, 17 GOLD B, 16 GOLD C and 12 GOLD D patients’ DSC characteristics were investigated. Nine healthy sera (smoker and non-smoker controls) were evaluated using the same methodology. Enthalpy and melting parameters of severe COPD patients are significantly different from those in the early stages and from healthy subjects. There are clearly visible trends in both features in all stages as COPD progresses. The thermal denaturation parameters are significantly different between the smokers and non-smokers in advanced COPD stages (C&D). Healthy controls do not differ significantly according to their smoking status. The new thermophysical method described here has a potential to be applicable as a stage and/or symptom score of the individual COPD patients. Longitudinal studies are needed to monitor DSC changes of the same patients during progression and/or stagnation.
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References
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Revised 2011, Updated 2015. www.goldcopd.com.
Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3:e442.
Stokley RA. Biomarkers in COPD: time for a deep breath. Chest. 2008;133(6):1296–8.
Turino GM. COPD and biomarkers: the search goes on. Thorax. 2008;63:1032–4.
Bucher HC, Guyatt GH, Cook DJ, Holbrook A, McAlister FA. Users’ guides to the medical literature: XIX. Applying clinical trial results: A. How to use an article measuring the effect of an intervention on surrogate end points: Evidence-Based Medicine Working Group. JAMA. 1999;282:771–8.
Tashkin D. COPD progression and individual rates of change of FEV1 and the BODE index. Am J Respir Crit Care Med. 2011;184(9):988–90.
Singh D, Edwards L, Tal-Singer R, Rennard S. Sputum neutrophils as a biomarker in COPD: findings from the ECLIPSE study. Respir Res. 2010;11:77. doi:10.1186/1465-9921-11-77.
Barnes PJ, Chowdhury B, Kharitonov SA, Magnussen H, Page CP, Postma D, et al. Pulmonary biomarkers in COPD. Am J Respir Crit Care Med. 2006;174:6–14.
Antus B, Kullmann T, Barta I. Assessment of exhaled breath condensate pH. Am J Respir Crit Care Med. 2011;183:952–3.
Augusti AG, Sauleda J, Miralles C, Gomez C, Togores B, Sala E, et al. Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002;166:485–9.
Stokley RA. Neutrophils and protease/antiprotease imbalance. Am J Respir Crit Care Med. 1999;160:49–52.
De Torres JP, Pinto-Plata V, Casanova C, Mullerova H, Córdoba-Lanús E, Muros de Fuentes M, et al. C-reactive protein levels and survival in patients with moderate to very severe COPD. Chest. 2008;133:1336–43.
Man SFP, Connett JE, Anthonisen NR, Wise RA, Tashkin DP, Sin DD. C-reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease. Thorax. 2006;61:849–53.
Dickens JA, Miller BE, Edwards LD, Silverman EK, Lomas DA, Tal-Singer R. COPD association and repeatability of blood biomarkers in the ECLIPSE cohort. Respir Res. 2011;12:146. doi:10.1186/1465-9921-12-146.
Plasma Fibrinogen receives FDA approval for use in COPD trials, 9 Jul 2015 http://www.fdanews.com/articles/172062-fda-issues-guidance-on-plasma-fibrinogen-as-biomarker-in-copd-trials.
Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir Med. 2015;3(6):435–42.
Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy L. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009;34:648–54.
Nishimura K, Izumi T, Tsukino M, Oga T. Dyspnoea is a better predictor of 5-year survival than airway obstruction in patients with COPD. Chest. 2002;121:1434–40.
Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363:1128–38.
Celli BR, Locantore N, Yates J, Tal-Singer R, Miller BE, Bakke B, et al. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary. Am J Respir Crit Care Med. 2012;185:1065–72.
Szalai Z, Molnár FT, Lőrinczy D. Differential scanning calorimetry (DSC) of blood serum in chronic obstructive pulmonary disease. J Therm Anal Calorim. 2013;113:259–64.
Michnik A, Michalik K, Kluczewska A, Drzazga Z. Comparative DSC study of human and bovine serum albumin. J Therm Anal Calorim. 2006;84:113–7.
Lőrinczy D, Belagyi J. Intermediate states of myosin head during ATP hydrolysis cycle in psoas muscle fibres by EPR and DSC (a review). J Therm Anal Calorim. 2007;90:611–21.
Lőrinczy D, Vértes Z, Könczöl F, Belagyi J. Thermal transitions of actin. J Therm Anal Calorim. 2009;95:713–9.
Könczöl F, Lőrinczy D, Vértes Z, Hegyi G, Belagyi J. Inter-monomer cross-linking affects the thermal transitions in F-actin. J Therm Anal Calorim. 2010;101:549–53.
Garbett NC, Mekmaysy CS, Helm CW, Jenson AB, Chaires JB. Differential scanning calorimetry of blood plasma for clinical diagnosis and monitoring. Exp Mol Pathol. 2009;86:186–91.
Fish DJ, Brewood GP, Kim JS, Garbett NC, Chaires JB, Benight AS. Statistical analysis of plasma thermograms measured by differential scanning calorimetry. Biophys Chem. 2010;152:184–90.
Michnik A, Drzazga Z. Thermal denaturation of mixtures of human serum proteins. J Therm Anal Calorim. 2010;101:513–8.
Zapf I, Fekecs T, Ferencz A, Lőrinczy D. DSC analysis of human plasma in breast cancer patients. Thermochim Acta. 2011;524:88–91.
Ferencz A, Fekecs T, Lőrinczy D. Differential scanning calorimetry, as a new method to monitor human plasma in melanoma patients with regional lymph node or distal metastases, chapter 6. In: Yaguang X, editor. Skin Cancer—Book 2, Intech Publisher, Rijeka, Croatia; 2011. p. 141–151. ISBN 979-953-307-661-3.
Mehdi M, Ferencz A, Lőrinczy D. Evaluation of blood plasma changes by differential scanning calorimetry in psoriatic patients treated with drugs. J Therm Anal Calorim. 2014;116:557–62.
Könczöl F, Wiegand N, Nöt LG, Lőrinczy D. Examination of the cyclophosphamide induced polyneuropathy on Guinea pig sciatic nerve and gastrocnemius muscle with differential scanning calorimetry. J Therm Anal Calorim. 2014;115:2239–43.
Todinova S, Krumova S, Radoeva R, Gartcheva L, Taneva S. Calorimetric markers of bone jones and nonsecretory multiple myeloma serum proteome. Anal Chem. 2014;86(24):12355–61.
Read J. The lungs and circulation in chronic pulmonary disease. J R Coll Physicians Lond. 1971;5(3):221–31.
Boussuges A, Rossi P, Gouitaa M, Nussbaum E. Alterations in the peripheral circulation in COPD patients. Clin Physiol Funct Imaging. 2007;27(5):284–90.
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SETARAM (France) Micro DSC-II calorimeter was supported by OTKA (Hungarian Scientific Research Found) CO-272 (for D. Lőrinczy).
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Szalai, Z., Molnár, T.F. & Lőrinczy, D. Role of differential scanning calorimetry (DSC) in the staging of COPD. J Therm Anal Calorim 127, 1231–1238 (2017). https://doi.org/10.1007/s10973-016-5495-6
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DOI: https://doi.org/10.1007/s10973-016-5495-6