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Published in: BMC Pulmonary Medicine 1/2014

Open Access 01-12-2014 | Research article

Role of C-reactive protein as a biomarker for prediction of the severity of pulmonary exacerbations in patients with cystic fibrosis

Authors: Rosa Maria Girón-Moreno, José L Justicia, Sara Yamamoto, Claudia Valenzuela, Carolina Cisneros, Rosa Mar Gómez-Punter, Gilda Fernandes-Vasconcelos, Julio Ancochea

Published in: BMC Pulmonary Medicine | Issue 1/2014

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Abstract

Background

Pulmonary exacerbation is one of the main risk factors for death in patients with cystic fibrosis. Several biomarkers have proven useful in the diagnosis and treatment of pulmonary exacerbations, although none has been associated with severity. The objective of the present study was to investigate whether C-reactive protein (CRP) level was associated with the severity of pulmonary exacerbation requiring admission to hospital in patients with cystic fibrosis.

Methods

We designed a severity index for exacerbations based on 4 clinical parameters and determined whether there was an association between CRP levels and severity of the exacerbation. We also investigated the association between CRP and baseline functional and clinical variables.

Results

Twenty-seven patients with cystic fibrosis required 62 admissions to hospital. CRP levels were not significantly associated with the severity index, although they were associated with specific patient characteristics: colonization by Pseudomonas aeruginosa, allergic bronchopulmonary aspergillosis, treatment with oral corticosteroids, and number of severe exacerbations treated with intravenous antibiotics during the previous year.

Conclusions

CRP level is not associated with the severity of pulmonary exacerbations, but it is associated with specific clinical characteristics. This simple scoring system (severity index) could prove very useful for evaluating the severity of exacerbations.
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Literature
1.
go back to reference Salcedo Posadas A, Gartner S, Girón Moreno RM, García Novo MD: (Eds): Tratado de Fibrosis Quística. 2012, Madrid: Editorial Justim SL Salcedo Posadas A, Gartner S, Girón Moreno RM, García Novo MD: (Eds): Tratado de Fibrosis Quística. 2012, Madrid: Editorial Justim SL
2.
go back to reference Mayer-Hamblett N, Rosenfeld M, Emerson J, Goss CH, Aitken ML: Developingcystic fibrosis lung transplant referral criteria using predictors of 2-year mortality. Am J Respir Crit Care Med. 2002, 166: 1550-1555. 10.1164/rccm.200202-087OC.CrossRefPubMed Mayer-Hamblett N, Rosenfeld M, Emerson J, Goss CH, Aitken ML: Developingcystic fibrosis lung transplant referral criteria using predictors of 2-year mortality. Am J Respir Crit Care Med. 2002, 166: 1550-1555. 10.1164/rccm.200202-087OC.CrossRefPubMed
3.
go back to reference Amadori A, Antonelli A, Balteri I, Schreiber A, Bugiani M, De Rose V: Recurrent exacerbations affect FEV(1) decline in adult patients with cystic fibrosis. Respir Med. 2009, 103: 407-413. 10.1016/j.rmed.2008.09.024.CrossRefPubMed Amadori A, Antonelli A, Balteri I, Schreiber A, Bugiani M, De Rose V: Recurrent exacerbations affect FEV(1) decline in adult patients with cystic fibrosis. Respir Med. 2009, 103: 407-413. 10.1016/j.rmed.2008.09.024.CrossRefPubMed
4.
go back to reference de Boer K, Vandemheen KL, Tullis E, Doucette S, Fergusson D, Freitag A, Paterson N, Jackson M, Lougheed MD, Kumar V, Aaron SD: Exacerbation frequency and clinical outcomes in adult patients with cystic fibrosis. Thorax. 2011, 66: 680-5. 10.1136/thx.2011.161117.CrossRefPubMed de Boer K, Vandemheen KL, Tullis E, Doucette S, Fergusson D, Freitag A, Paterson N, Jackson M, Lougheed MD, Kumar V, Aaron SD: Exacerbation frequency and clinical outcomes in adult patients with cystic fibrosis. Thorax. 2011, 66: 680-5. 10.1136/thx.2011.161117.CrossRefPubMed
5.
go back to reference Fuchs HJ, Borowitz DS, Christiansen DH, Morris EM, Nash ML, Ramsey BW, Rosenstein BJ, Smith AL, Wohl ME: Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med. 1994, 331: 637-42. 10.1056/NEJM199409083311003.CrossRefPubMed Fuchs HJ, Borowitz DS, Christiansen DH, Morris EM, Nash ML, Ramsey BW, Rosenstein BJ, Smith AL, Wohl ME: Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med. 1994, 331: 637-42. 10.1056/NEJM199409083311003.CrossRefPubMed
6.
go back to reference Dakin C, Henry RL, Field P, Morton J: Defining an exacerbation of pulmonary disease in cystic fibrosis. Pediatr Pulmonol. 2001, 31: 436-442. 10.1002/ppul.1072.CrossRefPubMed Dakin C, Henry RL, Field P, Morton J: Defining an exacerbation of pulmonary disease in cystic fibrosis. Pediatr Pulmonol. 2001, 31: 436-442. 10.1002/ppul.1072.CrossRefPubMed
8.
go back to reference Smyth A: Update on treatment of pulmonary exacerbations in cystic fibrosis. Curr Opin Pulm Med. 2006, 12: 440-444. 10.1097/01.mcp.0000245711.43891.16.CrossRefPubMed Smyth A: Update on treatment of pulmonary exacerbations in cystic fibrosis. Curr Opin Pulm Med. 2006, 12: 440-444. 10.1097/01.mcp.0000245711.43891.16.CrossRefPubMed
10.
11.
go back to reference Rosenfeld M, Emerson J, Williams-Warren J, Pepe M, Smith A, Montgomery AB, Ramsey B: Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr. 2001, 139: 359-65. 10.1067/mpd.2001.117288.CrossRefPubMed Rosenfeld M, Emerson J, Williams-Warren J, Pepe M, Smith A, Montgomery AB, Ramsey B: Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr. 2001, 139: 359-65. 10.1067/mpd.2001.117288.CrossRefPubMed
12.
go back to reference Cystic Fibrosis Foundation Patient Registry: Annual Data Report Bethesda, Maryland ©2013. 2012, Cystic Fibrosis: Foundation Cystic Fibrosis Foundation Patient Registry: Annual Data Report Bethesda, Maryland ©2013. 2012, Cystic Fibrosis: Foundation
13.
go back to reference Ferkol T, Rosenfeld M, Milla CE: Cystic fibrosis pulmonary exacerbations. J Pediatr. 2006, 148 (2): 259-264. 10.1016/j.jpeds.2005.10.019.CrossRefPubMed Ferkol T, Rosenfeld M, Milla CE: Cystic fibrosis pulmonary exacerbations. J Pediatr. 2006, 148 (2): 259-264. 10.1016/j.jpeds.2005.10.019.CrossRefPubMed
14.
go back to reference Bilton D, Canny G, Conway S, Dumcius S, Hjelte L, Proesmans M, Tümmler B, Vavrova V, De Boeck K: Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in clinical trials. J Cyst Fibros. 2011, 10 Suppl 2: S79-81.CrossRefPubMed Bilton D, Canny G, Conway S, Dumcius S, Hjelte L, Proesmans M, Tümmler B, Vavrova V, De Boeck K: Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in clinical trials. J Cyst Fibros. 2011, 10 Suppl 2: S79-81.CrossRefPubMed
15.
go back to reference Flume PA, Mogayzel PJ, Robinson KA, Goss CH, Rosenblatt RL, Kuhn RJ, Marshall BC: Clinical Practice Guidelines for Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009, 180 (9): 802-808. 10.1164/rccm.200812-1845PP.CrossRefPubMed Flume PA, Mogayzel PJ, Robinson KA, Goss CH, Rosenblatt RL, Kuhn RJ, Marshall BC: Clinical Practice Guidelines for Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009, 180 (9): 802-808. 10.1164/rccm.200812-1845PP.CrossRefPubMed
16.
go back to reference Hakimi Shoki A, Mayer-Hamblett N, Wilcox P, Sin D, Quon B: Systematic review of blood biomarkers in cystic fibrosis pulmonary exacerbations. Chest. 2013, 144 (5): 1659-1670. 10.1378/chest.13-0693.CrossRef Hakimi Shoki A, Mayer-Hamblett N, Wilcox P, Sin D, Quon B: Systematic review of blood biomarkers in cystic fibrosis pulmonary exacerbations. Chest. 2013, 144 (5): 1659-1670. 10.1378/chest.13-0693.CrossRef
17.
go back to reference Roderfeld M, Rath T, Schulz R, Seeger W, Tschuschner A, Graf J, Roeb E: Serum matrix metalloproteinases in adult CF patients: Relation to pulmonary exacerbation. J Cyst Fibros. 2009, 8 (5): 338-47. 10.1016/j.jcf.2009.06.001.CrossRefPubMed Roderfeld M, Rath T, Schulz R, Seeger W, Tschuschner A, Graf J, Roeb E: Serum matrix metalloproteinases in adult CF patients: Relation to pulmonary exacerbation. J Cyst Fibros. 2009, 8 (5): 338-47. 10.1016/j.jcf.2009.06.001.CrossRefPubMed
18.
go back to reference Davidson SJ, Paramothayan S, Hodson ME: Adult cystic fibrosis patients with and without infective exacerbations and their factor XII levels. Blood Coagul Fibrinolysis. 2009, 20 (6): 400-402. 10.1097/MBC.0b013e3283249ac6.CrossRefPubMed Davidson SJ, Paramothayan S, Hodson ME: Adult cystic fibrosis patients with and without infective exacerbations and their factor XII levels. Blood Coagul Fibrinolysis. 2009, 20 (6): 400-402. 10.1097/MBC.0b013e3283249ac6.CrossRefPubMed
19.
go back to reference Hendry J, Elborn JS, Nixon L, Shale DJ, Webb AK: Cystic fibrosis: inflammatory response to infection with Burkholderia cepacia and Pseudomonas aeruginosa. Eur Respir J. 1999, 14 (2): 435-438.CrossRefPubMed Hendry J, Elborn JS, Nixon L, Shale DJ, Webb AK: Cystic fibrosis: inflammatory response to infection with Burkholderia cepacia and Pseudomonas aeruginosa. Eur Respir J. 1999, 14 (2): 435-438.CrossRefPubMed
20.
go back to reference Rayner RJ, Wiseman MS, Cordon SM, Norman D, Hiller EJ, Shale DJ: Inflammatory markers in cystic fibrosis. Respir Med. 1991, 85 (2): 139-145. 10.1016/S0954-6111(06)80292-1.CrossRefPubMed Rayner RJ, Wiseman MS, Cordon SM, Norman D, Hiller EJ, Shale DJ: Inflammatory markers in cystic fibrosis. Respir Med. 1991, 85 (2): 139-145. 10.1016/S0954-6111(06)80292-1.CrossRefPubMed
21.
go back to reference Eichler I, Nilsson M, Rath R, Enander I, Venge P, Koller DY: Human neutrophil lipocalin, a highly specific marker for acute exacerbation in cystic fibrosis. Eur Respir J. 1999, 14 (5): 1145-1149. 10.1183/09031936.99.14511459.CrossRefPubMed Eichler I, Nilsson M, Rath R, Enander I, Venge P, Koller DY: Human neutrophil lipocalin, a highly specific marker for acute exacerbation in cystic fibrosis. Eur Respir J. 1999, 14 (5): 1145-1149. 10.1183/09031936.99.14511459.CrossRefPubMed
22.
go back to reference Watkin SL, Elborn JS, Cordon SM, Hiller EJ, Shale DJ: C-reactive protein is not a useful indicator of intermittent bacterial colonization in early lung disease of patients with cystic fibrosis. Pediatr Pulmonol. 1994, 17 (1): 6-10. 10.1002/ppul.1950170103.CrossRefPubMed Watkin SL, Elborn JS, Cordon SM, Hiller EJ, Shale DJ: C-reactive protein is not a useful indicator of intermittent bacterial colonization in early lung disease of patients with cystic fibrosis. Pediatr Pulmonol. 1994, 17 (1): 6-10. 10.1002/ppul.1950170103.CrossRefPubMed
23.
go back to reference Peckham D, Crouch S, Humphreys H, Lobo B, Tse A, Knox AJ: Effect of antibiotic treatment on inflammatory markers and lung function in cystic fibrosis patients with Pseudomonas cepacia. Thorax. 1994, 49 (8): 803-807. 10.1136/thx.49.8.803.CrossRefPubMedPubMedCentral Peckham D, Crouch S, Humphreys H, Lobo B, Tse A, Knox AJ: Effect of antibiotic treatment on inflammatory markers and lung function in cystic fibrosis patients with Pseudomonas cepacia. Thorax. 1994, 49 (8): 803-807. 10.1136/thx.49.8.803.CrossRefPubMedPubMedCentral
24.
go back to reference Sequeiros IM, Jarad NA: Extending the course of intravenous antibiotics in adult patients with cystic fibrosis with acute pulmonary exacerbations. Chron Respir Dis. 2012, 9 (4): 213-220. 10.1177/1479972312445903.CrossRefPubMed Sequeiros IM, Jarad NA: Extending the course of intravenous antibiotics in adult patients with cystic fibrosis with acute pulmonary exacerbations. Chron Respir Dis. 2012, 9 (4): 213-220. 10.1177/1479972312445903.CrossRefPubMed
25.
go back to reference Gray RD, Imrie M, Boyd AC, Porteous D, Innes JA, Greening AP: Sputum and serum calprotectin are useful biomarkers during CF exacerbation. J Cyst Fibros. 2010, 9 (3): 193-198. 10.1016/j.jcf.2010.01.005.CrossRefPubMed Gray RD, Imrie M, Boyd AC, Porteous D, Innes JA, Greening AP: Sputum and serum calprotectin are useful biomarkers during CF exacerbation. J Cyst Fibros. 2010, 9 (3): 193-198. 10.1016/j.jcf.2010.01.005.CrossRefPubMed
26.
go back to reference Sequeiros IM, Jarad N: Factors associated with a shorter time until the next pulmonary exacerbation in adult patients with cystic fibrosis. Chron Respir Dis. 2012, 9 (1): 9-16. 10.1177/1479972311433575.CrossRefPubMed Sequeiros IM, Jarad N: Factors associated with a shorter time until the next pulmonary exacerbation in adult patients with cystic fibrosis. Chron Respir Dis. 2012, 9 (1): 9-16. 10.1177/1479972311433575.CrossRefPubMed
27.
go back to reference Nixon LS, Yung B, Bell SC, Elborn JS, Shale DJ: Circulating immunoreactive interleukin-6 in cystic fibrosis. Am J Respir Crit Care Med. 1998, 157 (6 Pt 1): 1764-1769.CrossRefPubMed Nixon LS, Yung B, Bell SC, Elborn JS, Shale DJ: Circulating immunoreactive interleukin-6 in cystic fibrosis. Am J Respir Crit Care Med. 1998, 157 (6 Pt 1): 1764-1769.CrossRefPubMed
28.
go back to reference Elborn JS, Cordon SM, Parker D, Delamere FM, Shale DJ: The host inflammatory response prior to death in patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection. Respir Med. 1993, 87 (8): 603-607. 10.1016/S0954-6111(05)80263-X.CrossRefPubMed Elborn JS, Cordon SM, Parker D, Delamere FM, Shale DJ: The host inflammatory response prior to death in patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection. Respir Med. 1993, 87 (8): 603-607. 10.1016/S0954-6111(05)80263-X.CrossRefPubMed
29.
go back to reference Valletta EA, Rigo A, Bonazzi L, Zanolla L, Mastella G: Modification of some markers of inflammation during treatment for acute respiratory exacerbation in cystic fibrosis. Acta Paediatr. 1992, 81 (3): 227-230. 10.1111/j.1651-2227.1992.tb12209.x.CrossRefPubMed Valletta EA, Rigo A, Bonazzi L, Zanolla L, Mastella G: Modification of some markers of inflammation during treatment for acute respiratory exacerbation in cystic fibrosis. Acta Paediatr. 1992, 81 (3): 227-230. 10.1111/j.1651-2227.1992.tb12209.x.CrossRefPubMed
30.
go back to reference Duggan C, Colin AA, Agil A, Higgins L, Rifai N: Vitamin A status in acute exacerbations of cystic fibrosis. Am J Clin Nutr. 1996, 64 (4): 635-639.PubMed Duggan C, Colin AA, Agil A, Higgins L, Rifai N: Vitamin A status in acute exacerbations of cystic fibrosis. Am J Clin Nutr. 1996, 64 (4): 635-639.PubMed
31.
go back to reference Bell SC, Bowerman AM, Nixon LE, Macdonald IA, Elborn JS, Shale DJ: Metabolic and inflammatory responses to pulmonary exacerbation in adults with cystic fibrosis. Eur J Clin Invest. 2000, 30 (6): 553-559. 10.1046/j.1365-2362.2000.00667.x.CrossRefPubMed Bell SC, Bowerman AM, Nixon LE, Macdonald IA, Elborn JS, Shale DJ: Metabolic and inflammatory responses to pulmonary exacerbation in adults with cystic fibrosis. Eur J Clin Invest. 2000, 30 (6): 553-559. 10.1046/j.1365-2362.2000.00667.x.CrossRefPubMed
32.
go back to reference Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, Denning DW, Crameri R, Brody AS, Light M, Skov M, Maish W, Mastella G, participants in the Cystic Fibrosis Foundation Consensus Conference: Allergic bronchopulmonary aspergillosis in cystic fibrosis. State of the Art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003, 37 Suppl 3: S 225-64.CrossRef Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, Denning DW, Crameri R, Brody AS, Light M, Skov M, Maish W, Mastella G, participants in the Cystic Fibrosis Foundation Consensus Conference: Allergic bronchopulmonary aspergillosis in cystic fibrosis. State of the Art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003, 37 Suppl 3: S 225-64.CrossRef
33.
go back to reference Ibrahim M, Elborn J, Rendall J, Parkins M: Clinical features and outcomes of cystic fibrosis pulmonary exacerbations presenting with normal inflammatory markers. Journal of Cystic Fibrosis. 2010, Oxford, UK: Elsevier, S56- Ibrahim M, Elborn J, Rendall J, Parkins M: Clinical features and outcomes of cystic fibrosis pulmonary exacerbations presenting with normal inflammatory markers. Journal of Cystic Fibrosis. 2010, Oxford, UK: Elsevier, S56-
35.
go back to reference Zemanick ET, Harris JK, Wagner BD, Robertson CE, Sagel SD, Stevens MJ, Accurso FJ, Laguna TA: Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations. PLoS One. 2013 Apr 30, 8 (4): e62917-10.1371/journal.pone.0062917.CrossRefPubMedPubMedCentral Zemanick ET, Harris JK, Wagner BD, Robertson CE, Sagel SD, Stevens MJ, Accurso FJ, Laguna TA: Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations. PLoS One. 2013 Apr 30, 8 (4): e62917-10.1371/journal.pone.0062917.CrossRefPubMedPubMedCentral
36.
go back to reference Cantón R, Cobos N, de Gracia J, Baquero F, Honorato J, Gartner S: Tratamiento antimicrobiano frente a la colonización pulmonar por Pseudomonas aeruginosa en el paciente con fibrosis quística. Arch Bronconeumol. 2005, 41 (Supl 1): 1-25.CrossRef Cantón R, Cobos N, de Gracia J, Baquero F, Honorato J, Gartner S: Tratamiento antimicrobiano frente a la colonización pulmonar por Pseudomonas aeruginosa en el paciente con fibrosis quística. Arch Bronconeumol. 2005, 41 (Supl 1): 1-25.CrossRef
37.
go back to reference Downey DG, Brockbank S, Martin SL, Ennis M, Elborn JS: The effect of treatment of cystic fibrosis pulmonary exacerbations on airways and systemic inflammation. Pediatr Pulmonol. 2007, 42: 729-735. 10.1002/ppul.20646.CrossRefPubMed Downey DG, Brockbank S, Martin SL, Ennis M, Elborn JS: The effect of treatment of cystic fibrosis pulmonary exacerbations on airways and systemic inflammation. Pediatr Pulmonol. 2007, 42: 729-735. 10.1002/ppul.20646.CrossRefPubMed
38.
go back to reference Martin SL, Moffitt KL, McDowell A, Greenan C, Bright-Thomas RJ, Jones AM, Webb AK, Elborn JS: Association of airway cathepsin B and S with inflammation in cystic fibrosis. Pediatr Pulmonol. 2010 Sep, 45 (9): 860-68. 10.1002/ppul.21274.CrossRefPubMed Martin SL, Moffitt KL, McDowell A, Greenan C, Bright-Thomas RJ, Jones AM, Webb AK, Elborn JS: Association of airway cathepsin B and S with inflammation in cystic fibrosis. Pediatr Pulmonol. 2010 Sep, 45 (9): 860-68. 10.1002/ppul.21274.CrossRefPubMed
Metadata
Title
Role of C-reactive protein as a biomarker for prediction of the severity of pulmonary exacerbations in patients with cystic fibrosis
Authors
Rosa Maria Girón-Moreno
José L Justicia
Sara Yamamoto
Claudia Valenzuela
Carolina Cisneros
Rosa Mar Gómez-Punter
Gilda Fernandes-Vasconcelos
Julio Ancochea
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2014
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/1471-2466-14-150

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