期刊论文详细信息
BMC Pulmonary Medicine
Potential prognostic value of biomarkers in lavage, sputum and serum in a five year clinical follow-up of smokers with and without COPD
Jens M Hohlfeld4  Cornelia Faulenbach1  Gereon Lauer3  Henrik Watz2  Stefan Roepcke3  Benjamin Waschki2  Olaf Holz4 
[1] Department of Clinical Airway Research, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover 30625, Germany;Pulmonary Research Institute at LungenClinic Grosshansdorf, LungenClinic Grosshansdorf, Airway Research Centre North (ARCN), Member of the German Center for Lung Research, Grosshansdorf, Germany;Takeda Pharmaceuticals International GmbH, Zürich, Switzerland;Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Hannover, Germany
关键词: Lung function;    Clinical value;    Airway inflammation;   
Others  :  866535
DOI  :  10.1186/1471-2466-14-30
 received in 2013-11-12, accepted in 2014-02-14,  发布年份 2014
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【 摘 要 】

Background

The aim of this study was to test whether repeatable biomarkers collected from serum, bronchoalveolar lavage (BAL) and sputum of healthy smokers and smokers with COPD would have a prognostic value with respect to the decline in lung function over a 5 year period.

Methods

In 2006/2007 we had repeatedly collected serum, BAL and sputum of 23 healthy smokers and 24 smokers with COPD (GOLD II) and analysed a panel of more than 100 different parameters. In 2012 we reinvited these subjects to assess the change in lung function to enable the investigation of the potential prognostic value of the 2006/2007 markers and to determine the long-term repeatability of selected blood and serum markers. In this follow-up study we performed body-plethysmography, a blood gas analysis and collected blood and urine samples. The change in lung function was compared with 67 markers from BAL, sputum, serum and whole blood that were shown in the 2006/2007 assessment to be repeatable over a 6 week period.

Results

We were able to recruit 13 (54%) smokers with COPD and 11 (48%) former healthy smokers that participated in the 2006/2007 study. The decline in lung function was larger in COPD smokers; five of them changed to GOLD III, one to GOLD IV. Two healthy smokers changed to GOLD I. Blood cells, serum von Willebrand factor and alpha-1-antitrypsin showed a good repeatability over 5 years. In COPD smokers a weak correlation between 2006/2007 sputum markers of neutrophilic inflammation and the 5 year change in FEV1/FVC was found.

Conclusions

Our data suggests that inter-individual and group differences are maintained over a five year period. Despite the large panel of markers available for this analysis, a potential prognostic value appears to exist only for some sputum inflammatory markers. If these data can be confirmed in larger COPD cohorts, it would emphasize the value of sputum markers in clinical trials and support the assumption that an anti-inflammatory treatment can have long term benefits in COPD.

【 授权许可】

   
2014 Holz et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Roepcke S, Holz O, Lauer G, Mueller M, Rittinghausen S, Ernst P, Lahu G, Elmlinger M, Krug N, Hohlfeld JM: Repeatability of and relationship between potential COPD biomarkers in bronchoalveolar lavage, bronchial biopsies, serum, and induced sputum. PLoS One 2012, 7:e46207.
  • [2]Higashimoto Y, Iwata T, Okada M, Satoh H, Fukuda K, Tohda Y: Serum biomarkers as predictors of lung function decline in chronic obstructive pulmonary disease. Respir Med 2009, 103:1231-1238.
  • [3]Koutsokera A, Stolz D, Loukides S, Kostikas K: Systemic biomarkers in exacerbations of COPD: the evolving clinical challenge. Chest 2012, 141:396-405.
  • [4]Waschki B, Kirsten A, Holz O, Mueller KC, Meyer T, Watz H, Magnussen H: Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Chest 2011, 140:331-342.
  • [5]Suzuki M, Makita H, Ostling J, Konno S, Nagai K, Shimizu K, Maciewicz RA, Nishimura M: Elevated plasma adiponectin associated with lung function decline in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013, 187:A3490.
  • [6]Duvoix A, Dickens J, Haq I, Mannino D, Miller B, Tal-Singer R, Lomas DA: Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease. Thorax 2012, 68(7):670-676.
  • [7]Liesker JJ, Bathoorn E, Postma DS, Vonk JM, Timens W, Kerstjens HA: Sputum inflammation predicts exacerbations after cessation of inhaled corticosteroids in COPD. Respir Med 2011, 105:1853-1860.
  • [8]Agusti A, Edwards LD, Celli B, MacNee W, Calverley PM, Mullerova H, Lomas DA, Wouters E, Bakke P, Rennard S, Crim C, Miller BE, Coxson HO, Yates JC, Tal-Singer R, Vestbo J: Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort. Eur Respir J 2013, 42:636-646.
  • [9]Couper D, Lavange LM, Han M, Barr RG, Bleecker E, Hoffman EA, Kanner R, Kleerup E, Martinez FJ, Woodruff PG, Rennard S: Design of the subpopulations and intermediate outcomes in COPD study (SPIROMICS). Thorax 2013. doi:10.1136/thoraxjnl-2013-203897
  • [10]Watz H, Waschki B, Boehme C, Claussen M, Meyer T, Magnussen H: Extrapulmonary effects of chronic obstructive pulmonary disease on physical activity: a cross-sectional study. Am J Respir Crit Care Med 2008, 177:743-751.
  • [11]Fleiss JL: Design and Analysis of Clinical Experiments. New York: John WileySons, Inc; 1986:8-13.
  • [12]Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M: A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008, 359:1543-1554.
  • [13]Nishimura M, Makita H, Nagai K, Konno S, Nasuhara Y, Hasegawa M, Shimizu K, Betsuyaku T, Ito YM, Fuke S, Igarashi T, Akiyama Y, Ogura S: Annual change in pulmonary function and clinical phenotype in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012, 185:44-52.
  • [14]Vestbo J, Edwards LD, Scanlon PD, Yates JC, Agusti A, Bakke P, Calverley PM, Celli B, Coxson HO, Crim C, Lomas DA, MacNee W, Miller BE, Silverman EK, Tal-Singer R, Wouters E, Rennard SI: Changes in forced expiratory volume in 1 second over time in COPD. N Engl J Med 2011, 365:1184-1192.
  • [15]Doerschuk CM, Carretta E, O´Neal WK, Anderson WH, Couper D, Curtis JL, Woodruff PG, Rennard SI, Barr G: Circulating leukocytes, erythrocytes, and platelets in SPIROMICS. Am J Respir Crit Care Med 2013, 187:A1513.
  • [16]Agusti A, Edwards LD, Rennard SI, MacNee W, Tal-Singer R, Miller BE, Vestbo J, Lomas DA, Calverley PM, Wouters E, Crim C, Yates JC, Silverman EK, Coxson HO, Bakke P, Mayer RJ, Celli B: Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One 2012, 7:e37483.
  • [17]Celli BR, Locantore N, Yates J, Tal-Singer R, Miller BE, Bakke P, Calverley P, Coxson H, Crim C, Edwards LD, Lomas DA, Duvoix A, MacNee W, Rennard S, Silverman E, Vestbo J, Wouters E, Agusti A: Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012, 185:1065-1072.
  • [18]Thomsen M, Ingebrigtsen TS, Marott JL, Dahl M, Lange P, Vestbo J, Nordestgaard BG: Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease. JAMA 2013, 309:2353-2361.
  • [19]Sin DD, Miller BE, Duvoix A, Man SF, Zhang X, Silverman EK, Connett JE, Anthonisen NA, Wise RA, Tashkin D, Celli BR, Edwards LD, Locantore N, MacNee W, Tal-Singer R, Lomas DA: Serum PARC/CCL-18 concentrations and health outcomes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2011, 183:1187-1192.
  • [20]Hurst JR, Donaldson GC, Perera WR, Wilkinson TM, Bilello JA, Hagan GW, Vessey RS, Wedzicha JA: Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006, 174:867-874.
  • [21]Sin DD, Vestbo J: Biomarkers in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2009, 6:543-545.
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