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

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.