Skip to main content
Erschienen in: Lung 3/2012

01.06.2012

Serum Cystatin C and Emphysema: Results from the National Health and Nutrition Examination Survey (NHANES)

verfasst von: Haala K. Rokadia, Shikhar Agarwal

Erschienen in: Lung | Ausgabe 3/2012

Einloggen, um Zugang zu erhalten

Abstract

Background

Cystatin C (CysC) is a potent nonorgan-specific cysteine protease inhibitor and may contribute to elastolysis and tissue destruction by a mechanism of protease–antiprotease imbalance. Given the prevalence of CysC in the serum of smokers and its role in tissue destruction, we aimed to evaluate the association between CysC and emphysema.

Methods

Pooled cross-sectional data from the National Health and Nutrition Examination Survey 1999–2002 were used. Emphysema and chronic bronchitis were defined by a self-reported history ascertained using standardized questionnaires. Active smokers were defined as self-reported current smokers or measured serum cotinine ≥10 ng/mL. Nonactive smokers with a serum cotinine level >0.05 ng/mL were defined as environmental tobacco smoke (ETS)-exposed.

Results

The prevalence (95% CI) of emphysema was 1.3% (range = 0.9–1.8%). The mean (SE) CysC level in the emphysema group was significantly higher than in normal controls [1,139 (22) vs. 883 (8) μg/L; p = 0.001]. Upon stratification of the study population by C-reactive protein (CRP) concentrations, we demonstrated a progressive increase in the mean serum CysC level with serially increasing CRP concentrations. Active smokers with emphysema had 115.4 (46.5) μg/L higher mean (SE) CysC levels than the normal controls (p < 0.001). Upon adjusted analysis, we observed that nonactive smokers with significant ETS exposure had 31.2 (15.2) μg/L higher mean (SE) serum CysC levels as compared to ETS unexposed nonactive smokers (p = 0.04).

Conclusion

In a large representative noninstitutionalized US population, we demonstrated an association between emphysema and serum CysC. Active smokers with emphysema had significantly higher CysC levels. These findings suggest that CysC may play a role in the pathogenesis of smoking-related emphysema.
Literatur
1.
Zurück zum Zitat Jannoff A, Sloan B, Weinbaum G et al (1977) Experimental emphysema induced with purified human neutrophil elastase: tissue localization of the instilled protease. Am Rev Respir Dis 115:461–478 Jannoff A, Sloan B, Weinbaum G et al (1977) Experimental emphysema induced with purified human neutrophil elastase: tissue localization of the instilled protease. Am Rev Respir Dis 115:461–478
2.
Zurück zum Zitat Owen CA, Campbell EJ (1999) The cell biology of leukocyte-mediated proteolysis. J Leukoc Biol 65:137–150PubMed Owen CA, Campbell EJ (1999) The cell biology of leukocyte-mediated proteolysis. J Leukoc Biol 65:137–150PubMed
3.
Zurück zum Zitat Lesser M, Padilla ML, Cardozo C (1992) Induction of emphysema in hamsters by intratracheal instillation of cathepsin B. Am Rev Respir Dis 145:661–668PubMed Lesser M, Padilla ML, Cardozo C (1992) Induction of emphysema in hamsters by intratracheal instillation of cathepsin B. Am Rev Respir Dis 145:661–668PubMed
4.
Zurück zum Zitat Chughtai B, O’Riordan TG (2004) Potential role of inhibitors of neutrophil elastase in treating diseases of the airway. J Aerosol Med 17:289–298PubMedCrossRef Chughtai B, O’Riordan TG (2004) Potential role of inhibitors of neutrophil elastase in treating diseases of the airway. J Aerosol Med 17:289–298PubMedCrossRef
5.
Zurück zum Zitat Chua F, Laurent GJ (2006) Neutrophil elastase: mediator of extracellular matrix destruction and accumulation. Proc Am Thorac Soc 3:424–427PubMedCrossRef Chua F, Laurent GJ (2006) Neutrophil elastase: mediator of extracellular matrix destruction and accumulation. Proc Am Thorac Soc 3:424–427PubMedCrossRef
6.
Zurück zum Zitat Lungarella G, Cavarra E, Lucattelli M, Martorana PA (2008) The dual role of neutrophil elastase in lung destruction and repair. Int J Biochem Cell Biol 40:1287–1296PubMedCrossRef Lungarella G, Cavarra E, Lucattelli M, Martorana PA (2008) The dual role of neutrophil elastase in lung destruction and repair. Int J Biochem Cell Biol 40:1287–1296PubMedCrossRef
7.
Zurück zum Zitat Owen CA (2008) Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease. Int J Chronic Obstr Pulm Dis 3:253–268 Owen CA (2008) Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease. Int J Chronic Obstr Pulm Dis 3:253–268
8.
Zurück zum Zitat Abboud RT, Vimalanathan S (2008) Pathogenesis of COPD. Part 1. The role of protease–antiprotease imbalance in emphysema. Int J Tuberc Lung Dis 12:361–367PubMed Abboud RT, Vimalanathan S (2008) Pathogenesis of COPD. Part 1. The role of protease–antiprotease imbalance in emphysema. Int J Tuberc Lung Dis 12:361–367PubMed
9.
Zurück zum Zitat Kos J, Lah TT (1998) Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis, and therapy in cancer. Oncol Rep 5:1349–1361PubMed Kos J, Lah TT (1998) Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis, and therapy in cancer. Oncol Rep 5:1349–1361PubMed
10.
Zurück zum Zitat Chapman HA, Stone OL (1984) Comparison of live human neutrophils and alveolar macrophage elastolytic activity in vitro. Relative resistance of macrophage elastolytic activity to serum and alveolar proteinase inhibitors. J Clin Invest 74:1693–1700PubMedCrossRef Chapman HA, Stone OL (1984) Comparison of live human neutrophils and alveolar macrophage elastolytic activity in vitro. Relative resistance of macrophage elastolytic activity to serum and alveolar proteinase inhibitors. J Clin Invest 74:1693–1700PubMedCrossRef
11.
Zurück zum Zitat Abbott DE, Margaryan NV, Jeruss JS et al (2010) Reevaluating cathepsin D as a biomarker for breast cancer: serum activity levels versus histopathology. Cancer Biol Ther 9:23–30PubMedCrossRef Abbott DE, Margaryan NV, Jeruss JS et al (2010) Reevaluating cathepsin D as a biomarker for breast cancer: serum activity levels versus histopathology. Cancer Biol Ther 9:23–30PubMedCrossRef
12.
Zurück zum Zitat Meng L, Yang Y, Qi LT, Wang XJ, Xu GB, Zhang BW (2011) Elevated serum cystatin C is an independent predictor of cardiovascular events in people with relatively normal renal function. J Nephrol. doi:10.5301/jn.5000020 PubMed Meng L, Yang Y, Qi LT, Wang XJ, Xu GB, Zhang BW (2011) Elevated serum cystatin C is an independent predictor of cardiovascular events in people with relatively normal renal function. J Nephrol. doi:10.​5301/​jn.​5000020 PubMed
13.
Zurück zum Zitat Bevc S, Hojs R, Ekart R, Gorenjak M, Puklavec L (2011) Simple cystatin C formula compared to sophisticated CKD-EPI formulas for estimation of glomerular filtration rate in the elderly. Ther Apher Dial 15:261–268PubMedCrossRef Bevc S, Hojs R, Ekart R, Gorenjak M, Puklavec L (2011) Simple cystatin C formula compared to sophisticated CKD-EPI formulas for estimation of glomerular filtration rate in the elderly. Ther Apher Dial 15:261–268PubMedCrossRef
14.
Zurück zum Zitat Kottgen A, Selvin E, Stevens LA et al (2008) Serum cystatin C in the United States: the third National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis 51:385–394PubMedCrossRef Kottgen A, Selvin E, Stevens LA et al (2008) Serum cystatin C in the United States: the third National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis 51:385–394PubMedCrossRef
15.
Zurück zum Zitat Kyhse-Andersen J, Schmidt C, Nordin G et al (1994) Serum cystatin C, determined by a rapid, automated particle-enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate. Clin Chem 40:1921–1926PubMed Kyhse-Andersen J, Schmidt C, Nordin G et al (1994) Serum cystatin C, determined by a rapid, automated particle-enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate. Clin Chem 40:1921–1926PubMed
16.
Zurück zum Zitat Dharnidharka VR, Kwon C, Stevens G (2002) Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 40:221–226PubMedCrossRef Dharnidharka VR, Kwon C, Stevens G (2002) Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 40:221–226PubMedCrossRef
17.
Zurück zum Zitat Zore I, Krasovec M, Cimerman N et al (2001) Cathepsin B/Cystatin C complex levels in sera from patients with lung and colorectal cancer. Biol Chem 382:805–810PubMedCrossRef Zore I, Krasovec M, Cimerman N et al (2001) Cathepsin B/Cystatin C complex levels in sera from patients with lung and colorectal cancer. Biol Chem 382:805–810PubMedCrossRef
18.
Zurück zum Zitat Poteryaeva ON, Falameyeva OV, Korolenko TA et al (2000) Cysteine proteinase inhibitor level in tumor and normal tissues in control and cured mice. Drugs Exp Clin Res 26:301–306PubMed Poteryaeva ON, Falameyeva OV, Korolenko TA et al (2000) Cysteine proteinase inhibitor level in tumor and normal tissues in control and cured mice. Drugs Exp Clin Res 26:301–306PubMed
19.
Zurück zum Zitat Krepela E, Prochazka J, Karova B, Cermak J, Roubkova H (1998) Cysteine proteases and cysteine protease inhibitors in non-small cell lung cancer. Neoplasma 45:318–331PubMed Krepela E, Prochazka J, Karova B, Cermak J, Roubkova H (1998) Cysteine proteases and cysteine protease inhibitors in non-small cell lung cancer. Neoplasma 45:318–331PubMed
20.
Zurück zum Zitat Kos J, Werle B, Lah T, Brunner N (2000) Cysteine proteinases and their inhibitors in extracellular fluids: markers for diagnosis and prognosis in cancer. Int J Biol Markers 15:84–89PubMed Kos J, Werle B, Lah T, Brunner N (2000) Cysteine proteinases and their inhibitors in extracellular fluids: markers for diagnosis and prognosis in cancer. Int J Biol Markers 15:84–89PubMed
21.
Zurück zum Zitat Werle B, Schanzenbacher U, Lah TT et al (2006) Cystatins in non-small cell lung cancer: tissue levels, localization and relation to prognosis. Oncol Rep 16:647–655PubMed Werle B, Schanzenbacher U, Lah TT et al (2006) Cystatins in non-small cell lung cancer: tissue levels, localization and relation to prognosis. Oncol Rep 16:647–655PubMed
22.
Zurück zum Zitat Buttle DJ, Burnett D, Abrahamson M (1990) Levels of neutrophil elastase and cathepsin B activities, and cystatins in human sputum: relationship to inflammation. Scand J Clin Lab Invest 50:509–516PubMedCrossRef Buttle DJ, Burnett D, Abrahamson M (1990) Levels of neutrophil elastase and cathepsin B activities, and cystatins in human sputum: relationship to inflammation. Scand J Clin Lab Invest 50:509–516PubMedCrossRef
23.
Zurück zum Zitat Luthgens K, Ebert W, Trefz G, Gabrijelcic D, Turk V, Lah T (1993) Cathepsin B and cysteine proteinase inhibitors in bronchoalveolar lavage fluid of lung cancer patients. Cancer Detect Prev 17:387–397PubMed Luthgens K, Ebert W, Trefz G, Gabrijelcic D, Turk V, Lah T (1993) Cathepsin B and cysteine proteinase inhibitors in bronchoalveolar lavage fluid of lung cancer patients. Cancer Detect Prev 17:387–397PubMed
24.
Zurück zum Zitat Werle B, Sauckel K, Nathanson CM et al (2003) Cystatins C, E/M, and F in human pleural fluids of patients with neoplastic and inflammatory lung disorders. Biol Chem 382:281–287CrossRef Werle B, Sauckel K, Nathanson CM et al (2003) Cystatins C, E/M, and F in human pleural fluids of patients with neoplastic and inflammatory lung disorders. Biol Chem 382:281–287CrossRef
25.
Zurück zum Zitat Warfel AH, Cardozo C, Yoo OH, Zucker-Franklin D (1991) Cystatin C and cathepsin B production by alveolar macrophages from smokers and nonsmokers. J Leukoc Biol 49:41–47PubMed Warfel AH, Cardozo C, Yoo OH, Zucker-Franklin D (1991) Cystatin C and cathepsin B production by alveolar macrophages from smokers and nonsmokers. J Leukoc Biol 49:41–47PubMed
26.
Zurück zum Zitat Altiok O, Yasumatsu R, Bingol-Karakoc G et al (2006) Imbalance between cysteine proteases and inhibitors in a baboon model of bronchopulmonary dysplasia. Am J Respir Crit Care Med 173:318–326PubMedCrossRef Altiok O, Yasumatsu R, Bingol-Karakoc G et al (2006) Imbalance between cysteine proteases and inhibitors in a baboon model of bronchopulmonary dysplasia. Am J Respir Crit Care Med 173:318–326PubMedCrossRef
28.
Zurück zum Zitat Levey AS, Coresh J, Balk E et al (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation classification and stratification. Ann Intern Med 139:137–147PubMed Levey AS, Coresh J, Balk E et al (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation classification and stratification. Ann Intern Med 139:137–147PubMed
29.
Zurück zum Zitat Coresh J, Selvin E, Stevens LA et al (2007) Prevalence of chronic kidney disease in the United States. JAMA 298:2038–2047PubMedCrossRef Coresh J, Selvin E, Stevens LA et al (2007) Prevalence of chronic kidney disease in the United States. JAMA 298:2038–2047PubMedCrossRef
30.
Zurück zum Zitat Selvin S, Manzi J, Stevens LA et al (2007) Calibration of serum creatinine in the National Health and Nutrition Examination Surveys (NHANES) 1988–1994, 1999–2004. Am J Kidney Dis 50:918–926PubMedCrossRef Selvin S, Manzi J, Stevens LA et al (2007) Calibration of serum creatinine in the National Health and Nutrition Examination Surveys (NHANES) 1988–1994, 1999–2004. Am J Kidney Dis 50:918–926PubMedCrossRef
31.
Zurück zum Zitat Korkmaz B, Horwitz MS, Jenne DE, Gauthier F (2010) Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human disease. Pharmacol Rev 62:726–759PubMedCrossRef Korkmaz B, Horwitz MS, Jenne DE, Gauthier F (2010) Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human disease. Pharmacol Rev 62:726–759PubMedCrossRef
33.
Zurück zum Zitat Salgado JV, Neves FA, Bastos MG et al (2010) Monitoring renal function: measured and estimated glomerular filtration rates—a review. Braz J Med Biol Res 43:528–536PubMedCrossRef Salgado JV, Neves FA, Bastos MG et al (2010) Monitoring renal function: measured and estimated glomerular filtration rates—a review. Braz J Med Biol Res 43:528–536PubMedCrossRef
34.
Zurück zum Zitat Lafarge JC, Naour N, Clement K, Guerre-Millo M (2010) Cathepsins and cystatin C in atherosclerosis and obesity. Biochimie 92:1580–1586PubMedCrossRef Lafarge JC, Naour N, Clement K, Guerre-Millo M (2010) Cathepsins and cystatin C in atherosclerosis and obesity. Biochimie 92:1580–1586PubMedCrossRef
35.
Zurück zum Zitat Shlipak MG, Marnak MJ, Katz R et al (2005) Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med 352:2049–2060PubMedCrossRef Shlipak MG, Marnak MJ, Katz R et al (2005) Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med 352:2049–2060PubMedCrossRef
36.
Zurück zum Zitat Finlay GA, Russell KJ, McMahon KJ et al (1997) Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients. Thorax 52:502–506PubMedCrossRef Finlay GA, Russell KJ, McMahon KJ et al (1997) Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients. Thorax 52:502–506PubMedCrossRef
37.
Zurück zum Zitat Henskens YM, Veerman EC, Amerongen AV (1996) Cystatins in health and diseases. Biol Chem Hoppe Seyler 377:71–86PubMed Henskens YM, Veerman EC, Amerongen AV (1996) Cystatins in health and diseases. Biol Chem Hoppe Seyler 377:71–86PubMed
38.
Zurück zum Zitat Abrahamson M, Alvarez-Fernandez M, Nathanson CM (2003) Cystatins. Biochem Soc Symp 70:179–199PubMed Abrahamson M, Alvarez-Fernandez M, Nathanson CM (2003) Cystatins. Biochem Soc Symp 70:179–199PubMed
39.
Zurück zum Zitat Finkelstein R, Fraser RS, Ghezzo H, Cosio MG (1995) Alveolar inflammation and its relation to emphysema in smokers. Am J Respir Crit Care Med 152:1666–1672PubMed Finkelstein R, Fraser RS, Ghezzo H, Cosio MG (1995) Alveolar inflammation and its relation to emphysema in smokers. Am J Respir Crit Care Med 152:1666–1672PubMed
40.
Zurück zum Zitat Takeyabu K, Betsuyaku T, Nishimura M et al (1998) Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema. Eur Respir J 12:1033–1039PubMedCrossRef Takeyabu K, Betsuyaku T, Nishimura M et al (1998) Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema. Eur Respir J 12:1033–1039PubMedCrossRef
41.
Zurück zum Zitat Chapman HA, Reilly JJ, Yee R, Grubb A (1990) Identification of cystatin C, a cysteine proteinase inhibitor, as a major secretory product of human alveolar macrophages in vitro. Am Rev Respir Dis 141:698–705PubMedCrossRef Chapman HA, Reilly JJ, Yee R, Grubb A (1990) Identification of cystatin C, a cysteine proteinase inhibitor, as a major secretory product of human alveolar macrophages in vitro. Am Rev Respir Dis 141:698–705PubMedCrossRef
42.
Zurück zum Zitat Sloane BF, Rozhin J, Robinson D, Honn KV (1990) Role for cathepsin B and cystatins in tumor growth and progression. Biol Chem Hoppe Seyler 371:193–198PubMed Sloane BF, Rozhin J, Robinson D, Honn KV (1990) Role for cathepsin B and cystatins in tumor growth and progression. Biol Chem Hoppe Seyler 371:193–198PubMed
43.
Zurück zum Zitat Woischnik M, Bauer A, Aboutaam R et al (2008) Cathepsin H and napsin A are active in the alveoli and increased in alveolar proteinosis. Eur Respir J 31:1197–1204PubMedCrossRef Woischnik M, Bauer A, Aboutaam R et al (2008) Cathepsin H and napsin A are active in the alveoli and increased in alveolar proteinosis. Eur Respir J 31:1197–1204PubMedCrossRef
Metadaten
Titel
Serum Cystatin C and Emphysema: Results from the National Health and Nutrition Examination Survey (NHANES)
verfasst von
Haala K. Rokadia
Shikhar Agarwal
Publikationsdatum
01.06.2012
Verlag
Springer-Verlag
Erschienen in
Lung / Ausgabe 3/2012
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-012-9374-z

Weitere Artikel der Ausgabe 3/2012

Lung 3/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

So sicher sind Tattoos: Neue Daten zur Risikobewertung

22.05.2024 Melanom Nachrichten

Das größte medizinische Problem bei Tattoos bleiben allergische Reaktionen. Melanome werden dadurch offensichtlich nicht gefördert, die Farbpigmente könnten aber andere Tumoren begünstigen.

CAR-M-Zellen: Warten auf das große Fressen

22.05.2024 Onkologische Immuntherapie Nachrichten

Auch myeloide Immunzellen lassen sich mit chimären Antigenrezeptoren gegen Tumoren ausstatten. Solche CAR-Fresszell-Therapien werden jetzt für solide Tumoren entwickelt. Künftig soll dieser Prozess nicht mehr ex vivo, sondern per mRNA im Körper der Betroffenen erfolgen.

Frühzeitige HbA1c-Kontrolle macht sich lebenslang bemerkbar

22.05.2024 Typ-2-Diabetes Nachrichten

Menschen mit Typ-2-Diabetes von Anfang an intensiv BZ-senkend zu behandeln, wirkt sich positiv auf Komplikationen und Mortalität aus – und das offenbar lebenslang, wie eine weitere Nachfolgeuntersuchung der UKPD-Studie nahelegt.

Update Innere Medizin

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