Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease

Abstract

Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, highresolution CT (HRCT) findings, and the uptake in gallium-67 ( 67 Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67 Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation.

Serum Heme Oxygenase-1 Measurement is Useful for Evaluating Disease Activity and Outcomes in Patients With Acute Respiratory Distress Syndrome and Acute Exacerbation of Interstitial Lung Disease

“…Cancer cells with persistent Nrf2 activation often develop Nrf2 addiction and show malignant phenotypes, leading to poor prognoses (26). In patients with ILDs, persistently high ethane levels, a product of lipid peroxidation that has been proposed as a biomarker of oxidative stress, may correlate with poor prognosis (23). In the present study, serum HO-1 levels tended to decrease 2 weeks after the start of treatment in both ARDS and AE-ILD patients.…”

“…S1, Supplementary Information). In addition, serum HO-1 signi cantly correlated with serum T-bil as the downstream product of active heme metabolism and serum LDH as a marker of cellular damage (21)(22)(23). Therefore, we speculate that the mechanism of HO-1 increase in the blood is as follows.…”

ELISA Development for Serum Hemeoxygenase-1 and Its Application to Patients with Acute Respiratory Distress Syndrome

“…In patients with DAD which is the typical pathological pattern of ARDS, HO-1 was reported to be overexpressed in lung tissues, including alveolar macrophages, epithelial cells, endothelial cells, and fibroblasts, reflecting a pulmonary cellular protective reaction [ 6 ]. In our preliminary data, we found that the arterial concentration of carboxyhemoglobin, which is the breakdown product of HO-1, was significantly higher in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) (pathological DAD) than in patients with stable IPF [ 20 , 21 ]. In the present study, the serum HO-1 concentration of patients with ARDS was significantly higher than that of normal control subjects.…”

Clinical Significance of Serum Hemeoxygenase-1 as a New Biomarker for the Patients with Interstitial Pneumonia

“…HO-1 generates biliverdin IXα, ferrous iron, and CO from the oxidation of heme, and exhaled CO reflects active heme metabolism [18]. We previously reported that arterial carboxyhemoglobin (CO-Hb, the end-product of heme metabolism) levels are elevated in patients with ILD, particularly during an AE, and these levels have been shown to correlate with parameters that reflect lung inflammation [19]. Therefore, in the present research, we evaluated whether serum HO-1 measurement could be a useful marker for estimating ILD severity and disease prognosis.…”