Respiratory Medicine
Volume 103, Issue 8 , Pages 1231-1238, August 2009

Serum biomarkers as predictors of lung function decline in chronic obstructive pulmonary disease

  • Yuji Higashimoto

      Affiliations

    • Department of Respiratory Medicine and Allergology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511 Japan
    • Department of Rehabilitation Medicine, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511 Japan
    • Corresponding Author InformationCorresponding author. Department of Respiratory Medicine and Allergology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511 Japan. Tel.: +81 72 366 0221; fax: +81 72 366 0206.
  • ,
  • Takuya Iwata

      Affiliations

    • Department of Internal Medicine, Wakayama Medical University Kihoku Hospital, 219 Myoji, Katsuragi-cho, Ito-gun, Wakayama Prefecture 649-7113, Japan
  • ,
  • Morihiro Okada

      Affiliations

    • Department of Internal Medicine, Wakayama Medical University Kihoku Hospital, 219 Myoji, Katsuragi-cho, Ito-gun, Wakayama Prefecture 649-7113, Japan
  • ,
  • Hiroaki Satoh

      Affiliations

    • Department of Internal Medicine, Wakayama Medical University Kihoku Hospital, 219 Myoji, Katsuragi-cho, Ito-gun, Wakayama Prefecture 649-7113, Japan
  • ,
  • Kanji Fukuda

      Affiliations

    • Department of Rehabilitation Medicine, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511 Japan
  • ,
  • Yuji Tohda

      Affiliations

    • Department of Respiratory Medicine and Allergology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511 Japan

Received 7 July 2008; accepted 25 January 2009. published online 02 March 2009.

Summary 

Background

Recent studies show that COPD patients exhibit low-grade systemic inflammation, and that plasma fibrinogen and high neutrophil counts are related to faster declines in lung function. We examined correlations between serum biomarkers and the decline of lung function in COPD patients.

Method

Baseline levels of 9 serum biomarkers (TIMP-1, α1-antitrypsin, MMP-9, TNF-α, TGF-β, IL-6, IL-8, neutrophil elastase and CRP), fibrinogen and white blood cell counts (WCC) were measured in 96 COPD patients. Lung function was measured at the time of blood sampling and every 3–6 months during the observation period (median 25.0 months).

Results

Twenty patients were rapid decliners of lung function and 53 patients were non-decliners. Neutrophil counts, serum CRP and MMP-9 were significantly higher in the rapid decliners (p<0.05). The annual change of % predicted FEV1 was inversely correlated with MMP-9 (r=−0.288; p<0.01) and CRP (r=−0.354; p<0.005) (partial correlation coefficients adjusted for age, sex, cardiovascular disease, smoking history, and baseline % predicted FEV1). The remaining biomarkers were not correlated with the annual change of % predicted FEV1.

Conclusion

Serum CRP and MMP-9 levels were related to FEV1 decline. These markers are good candidates as predictors for rapid decline of FEV1 in COPD patients. Additional long-term and larger size studies of COPD patients could help determine the exact roles for these biomarkers.

Keywords: COPD, Systemic inflammation, Prognosis, Biomarker, c reactive protein, Matrix metalloproteinase

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PII: S0954-6111(09)00037-7

doi:10.1016/j.rmed.2009.01.021

Respiratory Medicine
Volume 103, Issue 8 , Pages 1231-1238, August 2009