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

Int J Chron Obstruct Pulmon Dis. 2015 Apr 24:10:831-41. doi: 10.2147/COPD.S81611. eCollection 2015.


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: C-reactive protein; air pollution; apolipoprotein F; inflammation; oxidative stress; proteoglycan 4.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Air Pollutants / adverse effects*
  • Apolipoproteins / blood
  • Area Under Curve
  • Biomarkers / blood
  • Blood Proteins
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Female
  • Forced Expiratory Volume
  • Glycoproteins / blood*
  • Humans
  • Inflammation Mediators / blood*
  • Inhalation Exposure / adverse effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Particle Size
  • Particulate Matter / adverse effects*
  • Predictive Value of Tests
  • Proteinase Inhibitory Proteins, Secretory / blood*
  • Proteoglycans / blood
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • ROC Curve
  • Taiwan


  • Air Pollutants
  • Apolipoproteins
  • Biomarkers
  • Blood Proteins
  • Glycoproteins
  • ITIH4 protein, human
  • Inflammation Mediators
  • PRG4 protein, human
  • Particulate Matter
  • Proteinase Inhibitory Proteins, Secretory
  • Proteoglycans
  • apolipoprotein F
  • 8-epi-prostaglandin F2alpha
  • C-Reactive Protein
  • Dinoprost

Associated data

  • ChiCTR/CHICTR-OCC-13004025