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Inter-alpha-trypsin inhibitor heavy chain 4: a novel biomarker for environmental exposure to particulate air pollution in patients with chronic obstructive pulmonary disease

Authors Lee KY, Feng PH, Ho SC, Chuang KJ, Chen TT, Su CL, Liu WT, Chuang HC

Received 26 January 2015

Accepted for publication 10 March 2015

Published 24 April 2015 Volume 2015:10(1) Pages 831—841

DOI https://doi.org/10.2147/COPD.S81611

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Richard Russell

Kang-Yun Lee,1–3 Po-Hao Feng,1,2 Shu-Chuan Ho,4 Kai-Jen Chuang,5,6 Tzu-Tao Chen,2,3 Chien-Ling Su,2,4 Wen-Te Liu,2,4 Hsiao-Chi Chuang2,4

1Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, 2Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, 3Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 4School of Respiratory Therapy, College of Medicine, Taipei Medical University, 5Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, 6School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan

Abstract: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that is correlated with environmental stress. Particulate matter ≤10 µm (PM10) is considered to be a risk factor for COPD development; however, the effects of PM10 on the protein levels in COPD remain unclear. Fifty subjects with COPD and 15 healthy controls were recruited. Gene ontology analysis of differentially expressed proteins identified immune system process and binding as the most important biological process and molecular function, respectively, in the responses of PM10-exposed patients with COPD. Biomarkers for PM10 in COPD were identified and compared with the same in healthy controls and included proteoglycan 4 (PRG4), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), and apolipoprotein F (APOF). PRG4 and ITIH4 were associated with a past 3-year PM10 exposure level. The receiver operating characteristic curve analysis showed that ITIH4 is a sensitive and specific biomarker for PM10 exposure (area under the curve [AUC] =0.690, P=0.015) compared with PRG4 (AUC =0.636, P=0.083), APOF (AUC =0.523, P=0.766), 8-isoprostane (AUC =0.563, P=0.405), and C-reactive protein (CRP; AUC =0.634, P=0.086). ITIH4 levels were correlated with CRP (r=0.353, P=0.005), suggesting that ITIH4 may be involved in an inflammatory mechanism. In summary, serum ITIH4 may be a PM10-specific biomarker in COPD and may be related to inflammation.

Keywords: air pollution, apolipoprotein F, C-reactive protein, inflammation, proteoglycan 4, oxidative stress

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