Skip to main content
Erschienen in: Lung 6/2018

14.09.2018 | COPD

Free Desmosine is a Sensitive Marker of Smoke-Induced Emphysema

verfasst von: Jerome Cantor, Arnulfo Ochoa, Shuren Ma, Xingjian Liu, Gerard Turino

Erschienen in: Lung | Ausgabe 6/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

While the elastin-specific crosslinks, desmosine and isodesmosine (DID), are increased in blood, urine, and sputum of patients with clinically documented pulmonary emphysema, the usefulness of DID in detecting early lung injury remains untested. To this end, our laboratory has measured DID in a hamster model of smoke-induced emphysema, involving only minimal alveolar wall damage.

Methods

Animals were either treated with cigarette smoke for 2 h/day, 5 days/week, or exposed only to room air (controls) for a period of 3 months. DID levels in bronchoalveolar lavage fluid (BALF) and whole lungs were determined at monthly intervals, using liquid chromatography and tandem mass spectrometry. Lung surface area was also determined, as a measure of airspace enlargement.

Results

The portion of BALF DID not bound to peptides (free DID) was significantly higher in smoke-exposed animals at 2 months (9.2 vs 4.4 pg/mg protein; p < 0.05), whereas total BALF DID showed no significant increases over the course of the study, and total lung DID remained unchanged. There was a mild, but significant, loss of lung surface area in the smoke-exposed group at 2 months (28.8% vs 25.2%, p < 0.05), which showed no further progression, consistent with the return of free DID to control levels at 3 months.

Conclusions

These findings support the hypothesis that free DID are sensitive indicators of smoke-induced lung injury. Measurement of free DID in smokers with minimally decreased lung mass may help determine the utility of this parameter as a test for incipient pulmonary emphysema.
Literatur
1.
Zurück zum Zitat Hogg JC, Timens W (2009) The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol 4:435–459CrossRef Hogg JC, Timens W (2009) The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol 4:435–459CrossRef
2.
Zurück zum Zitat Tuder RM, Petrache I (2012) Pathogenesis of chronic obstructive pulmonary disease. J Clin Invest 122:2749–2755CrossRef Tuder RM, Petrache I (2012) Pathogenesis of chronic obstructive pulmonary disease. J Clin Invest 122:2749–2755CrossRef
3.
Zurück zum Zitat Shifren A, Mecham RP (2006) The stumbling block in lung repair of emphysema: elastic fiber assembly. Proc Am Thorac Soc 3:428–433CrossRef Shifren A, Mecham RP (2006) The stumbling block in lung repair of emphysema: elastic fiber assembly. Proc Am Thorac Soc 3:428–433CrossRef
4.
Zurück zum Zitat Li B, Daggett V (2002) Molecular basis for the extensibility of elastin. J Muscle Res Cell Motil 23:561–573CrossRef Li B, Daggett V (2002) Molecular basis for the extensibility of elastin. J Muscle Res Cell Motil 23:561–573CrossRef
5.
Zurück zum Zitat Kielty CM, Sherratt MJ, Shuttleworth CA (2002) Elastic fibres. J Cell Sci 115:2817–2828PubMed Kielty CM, Sherratt MJ, Shuttleworth CA (2002) Elastic fibres. J Cell Sci 115:2817–2828PubMed
6.
Zurück zum Zitat Iadarola P, Luisetti M (2013) The role of desmosines as biomarkers for chronic obstructive pulmonary disease. Expert Rev Respir Med 7:137–144CrossRef Iadarola P, Luisetti M (2013) The role of desmosines as biomarkers for chronic obstructive pulmonary disease. Expert Rev Respir Med 7:137–144CrossRef
7.
Zurück zum Zitat Turino GM, Ma S, Lin YY, Cantor JO, Luisetti M (2011) Matrix elastin: a promising biomarker for chronic obstructive pulmonary disease. Am J Respir Crit Care Med 184:637–641CrossRef Turino GM, Ma S, Lin YY, Cantor JO, Luisetti M (2011) Matrix elastin: a promising biomarker for chronic obstructive pulmonary disease. Am J Respir Crit Care Med 184:637–641CrossRef
8.
Zurück zum Zitat Turino GM, Lin YY, He J, Cantor JO, Ma S (2012) Elastin degradation: an effective biomarker in COPD. COPD 9:435–438CrossRef Turino GM, Lin YY, He J, Cantor JO, Ma S (2012) Elastin degradation: an effective biomarker in COPD. COPD 9:435–438CrossRef
9.
Zurück zum Zitat Lindberg CA, Engstrom G, de Verdier MG, Nihlén U, Anderson M, Forsman-Semb K, Svartengren M (2012) Total desmosines in plasma and urine correlate with lung function. Eur Respir J 39:839–845CrossRef Lindberg CA, Engstrom G, de Verdier MG, Nihlén U, Anderson M, Forsman-Semb K, Svartengren M (2012) Total desmosines in plasma and urine correlate with lung function. Eur Respir J 39:839–845CrossRef
10.
Zurück zum Zitat Ma S, Turino GM, Lin YY (2011) Quantitation of desmosine and isodesmosine in urine, plasma, and sputum by LC-MS/MS as biomarkers for elastin degradation. J Chromatogr B 879:1893–1898CrossRef Ma S, Turino GM, Lin YY (2011) Quantitation of desmosine and isodesmosine in urine, plasma, and sputum by LC-MS/MS as biomarkers for elastin degradation. J Chromatogr B 879:1893–1898CrossRef
11.
Zurück zum Zitat Fregonese L, Ferrari F, Fumagalli M, Luisetti M, Stolk J, Iadarola P (2011) Long-term variability of desmosine/isodesmosine as biomarker in alpha-1-antitrypsin deficiency-related COPD. COPD 8:329–333CrossRef Fregonese L, Ferrari F, Fumagalli M, Luisetti M, Stolk J, Iadarola P (2011) Long-term variability of desmosine/isodesmosine as biomarker in alpha-1-antitrypsin deficiency-related COPD. COPD 8:329–333CrossRef
12.
Zurück zum Zitat Luisetti M, Ma S, Iadarola P, Stone PJ, Viglio S, Casado B, Lin YY, Snider GL, Turino GM (2008) Desmosine as a biomarker of elastin degradation in COPD: current status and future directions. Eur Respir J 32:1146–1157CrossRef Luisetti M, Ma S, Iadarola P, Stone PJ, Viglio S, Casado B, Lin YY, Snider GL, Turino GM (2008) Desmosine as a biomarker of elastin degradation in COPD: current status and future directions. Eur Respir J 32:1146–1157CrossRef
13.
Zurück zum Zitat Ma S, Lin YY, Turino GM (2007) Measurements of desmosine and isodesmosine by mass spectrometry in COPD. Chest 131:1363–1371CrossRef Ma S, Lin YY, Turino GM (2007) Measurements of desmosine and isodesmosine by mass spectrometry in COPD. Chest 131:1363–1371CrossRef
14.
Zurück zum Zitat Ma S, Lin YY, Cantor JO, Chapman KR, Sandhaus RA, Fries M, Edelman JM, McElvaney MG, Turino GM (2017) The effect of alpha-1 proteinase inhibitor on biomarkers of elastin degradation in alpha-1 antitrypsin deficiency: an analysis of the rapid/rapid extension trials. J Chronic Obstr Pulm Dis 4:34–44 Ma S, Lin YY, Cantor JO, Chapman KR, Sandhaus RA, Fries M, Edelman JM, McElvaney MG, Turino GM (2017) The effect of alpha-1 proteinase inhibitor on biomarkers of elastin degradation in alpha-1 antitrypsin deficiency: an analysis of the rapid/rapid extension trials. J Chronic Obstr Pulm Dis 4:34–44
15.
Zurück zum Zitat Liu X, Ma S, Liu S, Liu M, Turino G, Cantor J (2015) The ratio of free to bound desmosine and isodesmosine may reflect emphysematous changes in COPD. Lung 193:329–334CrossRef Liu X, Ma S, Liu S, Liu M, Turino G, Cantor J (2015) The ratio of free to bound desmosine and isodesmosine may reflect emphysematous changes in COPD. Lung 193:329–334CrossRef
16.
Zurück zum Zitat Slowik N, Ma S, He J, Lin YY, Soldin OP, Robbins RA, Turino GM (2011) The effect of secondhand smoke exposure on markers of elastin degradation. Chest 140:946–953CrossRef Slowik N, Ma S, He J, Lin YY, Soldin OP, Robbins RA, Turino GM (2011) The effect of secondhand smoke exposure on markers of elastin degradation. Chest 140:946–953CrossRef
17.
Zurück zum Zitat Winkler T, Suki B (2011) Emergent structure-function relations in emphysema and asthma. Crit Rev Biomed Eng 39:263–280CrossRef Winkler T, Suki B (2011) Emergent structure-function relations in emphysema and asthma. Crit Rev Biomed Eng 39:263–280CrossRef
18.
Zurück zum Zitat Rucker RB, Dubick MA (1984) Elastin metabolism and chemistry: potential roles in lung development and structure. Environ Health Perspect 55:179–191CrossRef Rucker RB, Dubick MA (1984) Elastin metabolism and chemistry: potential roles in lung development and structure. Environ Health Perspect 55:179–191CrossRef
19.
20.
Zurück zum Zitat Osman M, Cantor JO, Roffman S, Keller S, Turino GM, Mandl I (1985) Cigarette smoke impairs elastin resynthesis in lungs of hamsters with elastase-induced emphysema. Am Rev Respir Dis 132:640–643PubMed Osman M, Cantor JO, Roffman S, Keller S, Turino GM, Mandl I (1985) Cigarette smoke impairs elastin resynthesis in lungs of hamsters with elastase-induced emphysema. Am Rev Respir Dis 132:640–643PubMed
21.
Zurück zum Zitat Cantor JO, Ma S, Turino GM (2013) What percolation theory can tell us about COPD. Med Hypotheses 81:152–155CrossRef Cantor JO, Ma S, Turino GM (2013) What percolation theory can tell us about COPD. Med Hypotheses 81:152–155CrossRef
22.
Zurück zum Zitat Anwar RA, Gerber GE, Baig KH (1977) Studies on cross-linked regions of elastin. In: Friedman M (ed) Protein crosslinking. Advances in experimental medicine and biology, vol 86. Springer, Boston, pp 709–727CrossRef Anwar RA, Gerber GE, Baig KH (1977) Studies on cross-linked regions of elastin. In: Friedman M (ed) Protein crosslinking. Advances in experimental medicine and biology, vol 86. Springer, Boston, pp 709–727CrossRef
23.
Zurück zum Zitat Doyle TJ, Pinto-Plata V, Morse D, Celli BR, Rosas IO (2012) The expanding role of biomarkers in the assessment of smoking-related parenchymal lung diseases. Chest 142:1027–1034CrossRef Doyle TJ, Pinto-Plata V, Morse D, Celli BR, Rosas IO (2012) The expanding role of biomarkers in the assessment of smoking-related parenchymal lung diseases. Chest 142:1027–1034CrossRef
24.
Zurück zum Zitat Rosenberg SR, Kalhan R (2012) Biomarkers in chronic obstructive pulmonary disease. Transl Res 159:228–237CrossRef Rosenberg SR, Kalhan R (2012) Biomarkers in chronic obstructive pulmonary disease. Transl Res 159:228–237CrossRef
25.
Zurück zum Zitat Bates JH, Davis GS, Majumdar A, Butnor KJ, Suki B (2007) Linking parenchymal disease progression to changes in lung mechanical function by percolation. Am J Respir Crit Care Med 176:617–623CrossRef Bates JH, Davis GS, Majumdar A, Butnor KJ, Suki B (2007) Linking parenchymal disease progression to changes in lung mechanical function by percolation. Am J Respir Crit Care Med 176:617–623CrossRef
26.
Zurück zum Zitat Suki B, Bates JH (2011) Lung tissue mechanics as an emergent phenomenon. J Appl Physiol 110:1111–1118CrossRef Suki B, Bates JH (2011) Lung tissue mechanics as an emergent phenomenon. J Appl Physiol 110:1111–1118CrossRef
Metadaten
Titel
Free Desmosine is a Sensitive Marker of Smoke-Induced Emphysema
verfasst von
Jerome Cantor
Arnulfo Ochoa
Shuren Ma
Xingjian Liu
Gerard Turino
Publikationsdatum
14.09.2018
Verlag
Springer US
Erschienen in
Lung / Ausgabe 6/2018
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-018-0163-1

Weitere Artikel der Ausgabe 6/2018

Lung 6/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.