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Published in: BMC Pulmonary Medicine 1/2016

Open Access 01-12-2016 | Research article

Analysis of mitochondrial DNA alteration in new phenotype ACOS

Authors: G. E. Carpagnano, D. Lacedonia, M. Malerba, G. A. Palmiotti, G. Cotugno, M. Carone, M. P. Foschino-Barbaro

Published in: BMC Pulmonary Medicine | Issue 1/2016

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Abstract

Background

Mitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress and as a consequence could be damaged in quantity. Oxidative stress is largely recognized to play a key role in the pathogenesis of asthma and COPD and might have a role in the new intermediate phenotype ACOS (asthma-COPD overlap syndrome). The aim of this study was to investigate MtDNA alterations, as an expression of mitochondrial dysfunction, in ACOS and to verify whether they might help in the identification of this new phenotype and in its differentiation from asthma and COPD.

Methods

Ten (10) ACOS according to Spanish guidelines, 13 ACOS according to GINA guidelines, 13 COPD, 14 asthmatic patients and ten normal subjects were enrolled. They further underwent a blood, induced sputum and exhaled nitric oxide collection. Content of MtDNA and nuclear DNA (nDNA) were measured in the blood cells of patients by Real Time PCR.

Results

ACOS patients showed an increase of MtDNA/nDNA ratio. Dividing ACOS according to guidelines, those from the Spanish showed a higher value of MtDNA/nDNA compared to those from GINA/GOLD (92.69 ± 7.31 vs 80.68 ± 4.16). Spanish ACOS presented MtDNA/nDNA ratio closer to COPD than asthma. MtDNA was higher in asthmatic, COPD, GINA and Spanish ACOS patients compared to healthy subjects (73.30 ± 4.47–137.0 ± 19.45–80.68 ± 4.16–92.69 ± 7.31 vs 65.97 ± 20.56).

Conclusion

We found an increase of MtDNA/nDNA ratio in ACOS subjects that led us to conclude that there is presence of mitochondrial dysfunction in this disease, that makes it closer to COPD than to asthma. Although the MtDNA/nDNA ratio results are a useful marker for differential diagnosis from asthma, COPD and ACOS, further studies are needed to confirm the potentiality of MtDNA/nDNA ratio and to a better characterization of ACOS.
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Literature
1.
go back to reference Barrecheguren M, Esquinas C, Miravitlles M. The asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): opportunities and challenges. Curr Opin Pulm Med. 2015;21(1):74–9.CrossRefPubMed Barrecheguren M, Esquinas C, Miravitlles M. The asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): opportunities and challenges. Curr Opin Pulm Med. 2015;21(1):74–9.CrossRefPubMed
2.
go back to reference Soler-Cataluña JJ, Cosío B, Izquierdo JL, López-Campos JL, Marín JM, Agüero R, et al. Consensus document on the overlap phenotype COPD-asthma in COPD. Arch Bronconeumol. 2012;48(9):331–7.CrossRefPubMed Soler-Cataluña JJ, Cosío B, Izquierdo JL, López-Campos JL, Marín JM, Agüero R, et al. Consensus document on the overlap phenotype COPD-asthma in COPD. Arch Bronconeumol. 2012;48(9):331–7.CrossRefPubMed
3.
go back to reference Montuschi P, Malerba M, Santini G, Miravitlles M. Pharmacological treatment of chronic obstructive pulmonary disease: from evidence-based medicine to phenotyping. Drug Discov Today. 2014;19(12):1928–35.CrossRefPubMed Montuschi P, Malerba M, Santini G, Miravitlles M. Pharmacological treatment of chronic obstructive pulmonary disease: from evidence-based medicine to phenotyping. Drug Discov Today. 2014;19(12):1928–35.CrossRefPubMed
4.
go back to reference Bujarski S, Parulekar AD, Sharafkhaneh A, Hanania NA. The asthma COPD overlap syndrome (ACOS). Curr Allergy Asthma Rep. 2015;15(3):509.CrossRefPubMed Bujarski S, Parulekar AD, Sharafkhaneh A, Hanania NA. The asthma COPD overlap syndrome (ACOS). Curr Allergy Asthma Rep. 2015;15(3):509.CrossRefPubMed
5.
go back to reference Wojtczak L, Zabłocki K. Mitochondria in cell life, death and disease. Postepy Biochem. 2008;54(2):129–41.PubMed Wojtczak L, Zabłocki K. Mitochondria in cell life, death and disease. Postepy Biochem. 2008;54(2):129–41.PubMed
6.
go back to reference Andreu AL, Martinez R, Marti R, García-Arumí E. Quantification of mitochondrial DNA copy number: pre-analytical factors. Mitochondrion. 2009;9(4):242–6.CrossRefPubMed Andreu AL, Martinez R, Marti R, García-Arumí E. Quantification of mitochondrial DNA copy number: pre-analytical factors. Mitochondrion. 2009;9(4):242–6.CrossRefPubMed
7.
go back to reference Yang Ai SS, Hsu K, Herbert C, Cheng Z, Hunt J, Lewis CR, et al. Mitochondrial DNA mutations in exhaled breath condensate of patients with lung cancer. Respir Med. 2013;107(6):911–8.CrossRefPubMed Yang Ai SS, Hsu K, Herbert C, Cheng Z, Hunt J, Lewis CR, et al. Mitochondrial DNA mutations in exhaled breath condensate of patients with lung cancer. Respir Med. 2013;107(6):911–8.CrossRefPubMed
8.
go back to reference Dai JG, Zhang ZY, Liu QX, Min JX. Mitochondrial genome microsatellite instability and copy number alteration in lung carcinomas. Asian Pac J Cancer Prev. 2013;14(4):2393–9.CrossRefPubMed Dai JG, Zhang ZY, Liu QX, Min JX. Mitochondrial genome microsatellite instability and copy number alteration in lung carcinomas. Asian Pac J Cancer Prev. 2013;14(4):2393–9.CrossRefPubMed
9.
10.
go back to reference Zifa E, Daniil Z, Skoumi E, et al. Mitochondrial genetic background plays a role in increasing risk to asthma. Mol Biol Rep. 2012;39(4):4697–708.CrossRefPubMed Zifa E, Daniil Z, Skoumi E, et al. Mitochondrial genetic background plays a role in increasing risk to asthma. Mol Biol Rep. 2012;39(4):4697–708.CrossRefPubMed
13.
go back to reference Lacedonia D, Carpagnano GE, Crisetti E, Cotugno G, Palladino GP, Patricelli G, et al. Mitochondrial DNA alteration in obstructive sleep apnea. Respir Res. 2015;16(1):47.PubMedCentralCrossRefPubMed Lacedonia D, Carpagnano GE, Crisetti E, Cotugno G, Palladino GP, Patricelli G, et al. Mitochondrial DNA alteration in obstructive sleep apnea. Respir Res. 2015;16(1):47.PubMedCentralCrossRefPubMed
14.
go back to reference Pieters N, Koppen G, Smeets K, Napierska D, Plusquin M, De Prins S, et al. Decreased mitochondrial DNA content in association with exposure to polycyclic aromatic hydrocarbons in house dust during wintertime: from a population enquiry to cell culture. PLoS One. 2013;8(5):e63208.PubMedCentralCrossRefPubMed Pieters N, Koppen G, Smeets K, Napierska D, Plusquin M, De Prins S, et al. Decreased mitochondrial DNA content in association with exposure to polycyclic aromatic hydrocarbons in house dust during wintertime: from a population enquiry to cell culture. PLoS One. 2013;8(5):e63208.PubMedCentralCrossRefPubMed
15.
go back to reference Ajaz S, Czajka A. Malik. Accurate measurement of circulating mitochondrial DNA content from human blood samples using real-time quantitative PCR. A Methods Mol Biol. 2015;1264:117–31.CrossRefPubMed Ajaz S, Czajka A. Malik. Accurate measurement of circulating mitochondrial DNA content from human blood samples using real-time quantitative PCR. A Methods Mol Biol. 2015;1264:117–31.CrossRefPubMed
16.
go back to reference Di Donato S, Marmolino D, Taroni F. Mitochondrial disorders. In: Manto M, Gruol D, Schmahmann J, Koibuchi N, Rossi F, editors. Handbook of the cerebellum and cerebellar disorders. 2013. p. 2269–311.CrossRef Di Donato S, Marmolino D, Taroni F. Mitochondrial disorders. In: Manto M, Gruol D, Schmahmann J, Koibuchi N, Rossi F, editors. Handbook of the cerebellum and cerebellar disorders. 2013. p. 2269–311.CrossRef
17.
go back to reference Bogenhagen DF. Mitochondrial DNA, nucleoid structure. Biochim Biophys Acta. 2012;1819(9–10):914–20.CrossRefPubMed Bogenhagen DF. Mitochondrial DNA, nucleoid structure. Biochim Biophys Acta. 2012;1819(9–10):914–20.CrossRefPubMed
18.
go back to reference Lee HC, Lu CY, Fahn HJ, Wei YH. Aging- and smoking-associated alteration in the relative content of mitochondrial DNA in human lung. FEBS Lett. 1998;441(2):292–6.CrossRefPubMed Lee HC, Lu CY, Fahn HJ, Wei YH. Aging- and smoking-associated alteration in the relative content of mitochondrial DNA in human lung. FEBS Lett. 1998;441(2):292–6.CrossRefPubMed
19.
go back to reference Malik AN, Shahni R, Iqbal MM. Increased peripheral blood mitochondrial DNA in type 2 diabetic patients with nephropathy. Diabetes Res Clin Pract. 2009;86(2):e22–4.CrossRefPubMed Malik AN, Shahni R, Iqbal MM. Increased peripheral blood mitochondrial DNA in type 2 diabetic patients with nephropathy. Diabetes Res Clin Pract. 2009;86(2):e22–4.CrossRefPubMed
20.
go back to reference Malik AN, Shahni R, Rodriguez-de-Ledesma A, Laftah A, Cunningham P. Mitochondrial DNA as a non-invasive biomarker: accurate quantification using real time quantitative PCR without co-amplification of pseudogenes and dilution bias. Biochem Biophys Res Commun. 2011;412(1):1–7.CrossRefPubMed Malik AN, Shahni R, Rodriguez-de-Ledesma A, Laftah A, Cunningham P. Mitochondrial DNA as a non-invasive biomarker: accurate quantification using real time quantitative PCR without co-amplification of pseudogenes and dilution bias. Biochem Biophys Res Commun. 2011;412(1):1–7.CrossRefPubMed
21.
go back to reference Lucie H, Adriano M, Karl-Christian B, Megon B, Guido B, Ulf D, et al. The skin prick test – European standards. Clin Transl Allergy. 2013;3:3.CrossRef Lucie H, Adriano M, Karl-Christian B, Megon B, Guido B, Ulf D, et al. The skin prick test – European standards. Clin Transl Allergy. 2013;3:3.CrossRef
22.
go back to reference Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948–68.CrossRefPubMed Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948–68.CrossRefPubMed
23.
go back to reference Spanevello A, Confalonieri M, Sulotto F. Induced sputum cellularity. Reference values and distribution in normal volunteers. Am J Respir Crit Care Med. 2000;1:1172–4.CrossRef Spanevello A, Confalonieri M, Sulotto F. Induced sputum cellularity. Reference values and distribution in normal volunteers. Am J Respir Crit Care Med. 2000;1:1172–4.CrossRef
24.
go back to reference American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med. 2005;171:912–30.CrossRef American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med. 2005;171:912–30.CrossRef
25.
go back to reference Kharitonov SA, Gonio F, Kelly C, Meah S, Barnes PJ. Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children. Eur Respir J. 2003;21:433–8.CrossRefPubMed Kharitonov SA, Gonio F, Kelly C, Meah S, Barnes PJ. Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children. Eur Respir J. 2003;21:433–8.CrossRefPubMed
26.
go back to reference Papaiwannou A, Zarogoulidis P, Porpodis K, Spyratos D, Kioumis I, Pitsiou G, et al. Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): current literature review. J Thorac Dis. 2014;6 Suppl 1:S146–51.PubMedCentralPubMed Papaiwannou A, Zarogoulidis P, Porpodis K, Spyratos D, Kioumis I, Pitsiou G, et al. Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): current literature review. J Thorac Dis. 2014;6 Suppl 1:S146–51.PubMedCentralPubMed
27.
go back to reference Fu JJ, McDonald VM, Gibson PG, Simpson JL. Systemic inflammation in older adults with asthma-COPD overlap syndrome. Allergy Asthma Immunol Res. 2014;6(4):316–24.PubMedCentralCrossRefPubMed Fu JJ, McDonald VM, Gibson PG, Simpson JL. Systemic inflammation in older adults with asthma-COPD overlap syndrome. Allergy Asthma Immunol Res. 2014;6(4):316–24.PubMedCentralCrossRefPubMed
28.
go back to reference Iwamoto H, Gao J, Koskela J, Kinnula V, Kobayashi H, Laitinen T, et al. Differences in plasma and sputum biomarkers between COPD and COPD-asthma overlap. Eur Respir J. 2014;43(2):421–9.CrossRefPubMed Iwamoto H, Gao J, Koskela J, Kinnula V, Kobayashi H, Laitinen T, et al. Differences in plasma and sputum biomarkers between COPD and COPD-asthma overlap. Eur Respir J. 2014;43(2):421–9.CrossRefPubMed
29.
go back to reference Kirkham P, Rahman I. Oxidative stress in asthma and COPD: antioxidants as a therapeutic strategy. Pharmacol Ther. 2006;111(2):476–94.CrossRefPubMed Kirkham P, Rahman I. Oxidative stress in asthma and COPD: antioxidants as a therapeutic strategy. Pharmacol Ther. 2006;111(2):476–94.CrossRefPubMed
30.
go back to reference Hardin M, Silverman EK, Barr RG, Hansel NN, Schroeder JD, Make BJ, et al. The clinical features of the overlap between COPD and asthma. Respir Res. 2011;12:127.PubMedCentralCrossRefPubMed Hardin M, Silverman EK, Barr RG, Hansel NN, Schroeder JD, Make BJ, et al. The clinical features of the overlap between COPD and asthma. Respir Res. 2011;12:127.PubMedCentralCrossRefPubMed
31.
go back to reference Miravitlles M, Soriano JB, Ancochea J, Muñoz L, Duran-Tauleria E, Sánchez G, et al. Characterisation of the overlap COPD-asthma phenotype. Focus on physical activity and health status. Respir Med. 2013;107(7):1053–60.CrossRefPubMed Miravitlles M, Soriano JB, Ancochea J, Muñoz L, Duran-Tauleria E, Sánchez G, et al. Characterisation of the overlap COPD-asthma phenotype. Focus on physical activity and health status. Respir Med. 2013;107(7):1053–60.CrossRefPubMed
32.
go back to reference Chung JW, Kong KA, Lee JH, Lee SJ, Ryu YJ, Chang JH. Characteristics and self-rated health of overlap syndrome. Int J Chron Obstruct Pulmon Dis. 2014;9:795–804.PubMedCentralPubMed Chung JW, Kong KA, Lee JH, Lee SJ, Ryu YJ, Chang JH. Characteristics and self-rated health of overlap syndrome. Int J Chron Obstruct Pulmon Dis. 2014;9:795–804.PubMedCentralPubMed
33.
go back to reference Shaya FT, Maneval MS, Gbarayor CM, Sohn K, Dalal AA, Du D, et al. Burden of COPD, asthma, and concomitant COPD and asthma among adults: racial disparities in a medicaid population. Chest. 2009;136(2):405–11.PubMedCentralCrossRefPubMed Shaya FT, Maneval MS, Gbarayor CM, Sohn K, Dalal AA, Du D, et al. Burden of COPD, asthma, and concomitant COPD and asthma among adults: racial disparities in a medicaid population. Chest. 2009;136(2):405–11.PubMedCentralCrossRefPubMed
34.
go back to reference Malik AN, Czajka A. Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction? Mitochondrion. 2013;13(5):481–92.CrossRefPubMed Malik AN, Czajka A. Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction? Mitochondrion. 2013;13(5):481–92.CrossRefPubMed
35.
go back to reference Girodet PO, Allard B, Thumerel M, Begueret H, Dupin I, Ousova O, et al. Bronchial Smooth Muscle Remodeling in Non-severe Asthma. Am J Respir Crit Care Med. 2015. [Epub ahead of print]. Girodet PO, Allard B, Thumerel M, Begueret H, Dupin I, Ousova O, et al. Bronchial Smooth Muscle Remodeling in Non-severe Asthma. Am J Respir Crit Care Med. 2015. [Epub ahead of print].
36.
go back to reference Flaquer A, Heinzmann A, Rospleszcz S, Mailaparambil B, Dietrich H, Strauch K, et al. Association study of mitochondrial genetic polymorphisms in asthmatic children. Mitochondrion. 2014;14(1):49–53.CrossRefPubMed Flaquer A, Heinzmann A, Rospleszcz S, Mailaparambil B, Dietrich H, Strauch K, et al. Association study of mitochondrial genetic polymorphisms in asthmatic children. Mitochondrion. 2014;14(1):49–53.CrossRefPubMed
37.
go back to reference Pastukh VM, Zhang L, Ruchko MV, Gorodnya O, Bardwell GC, Tuder RM, et al. Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences. Int J Chron Obstruct Pulmon Dis. 2011;6:209–17.PubMedCentralPubMed Pastukh VM, Zhang L, Ruchko MV, Gorodnya O, Bardwell GC, Tuder RM, et al. Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences. Int J Chron Obstruct Pulmon Dis. 2011;6:209–17.PubMedCentralPubMed
38.
go back to reference Ahmad T, Sundar IK, Lerner CA, Gerloff J, Tormos AM, Yao H, et al. Impaired mitophagy leads to cigarette smoke stress-induced cellular senescence: Implications for chronic obstructive pulmonary disease. FASEB J. 2015;29(7):2912–29.CrossRefPubMed Ahmad T, Sundar IK, Lerner CA, Gerloff J, Tormos AM, Yao H, et al. Impaired mitophagy leads to cigarette smoke stress-induced cellular senescence: Implications for chronic obstructive pulmonary disease. FASEB J. 2015;29(7):2912–29.CrossRefPubMed
39.
go back to reference Aravamudan B, Kiel A, Freeman M, Delmotte P, Thompson M, Vassallo R, et al. Cigarette smoke-induced mitochondrial fragmentation and dysfunction in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2014;306(9):L840–54.PubMedCentralCrossRefPubMed Aravamudan B, Kiel A, Freeman M, Delmotte P, Thompson M, Vassallo R, et al. Cigarette smoke-induced mitochondrial fragmentation and dysfunction in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2014;306(9):L840–54.PubMedCentralCrossRefPubMed
Metadata
Title
Analysis of mitochondrial DNA alteration in new phenotype ACOS
Authors
G. E. Carpagnano
D. Lacedonia
M. Malerba
G. A. Palmiotti
G. Cotugno
M. Carone
M. P. Foschino-Barbaro
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2016
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-016-0192-6

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