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

Abstract

Background Oxidative stress plays an important role in acute lung injury, which is associated with the development and progression of acute respiratory failure. Here, we investigated whether the degree of oxidative stress as indicated by serum heme oxygenase-1 (HO-1) is clinically useful for predicting prognosis among the patients with acute respiratory distress syndrome (ARDS) and acute exacerbation of interstitial lung disease (AE-ILD). Methods Serum HO-1 levels of newly diagnosed or untreated ARDS and AE-ILD patients were measured at diagnosis. Relationships between serum HO-1 and other clinical parameters and 1 and 3-month mortality were evaluated. Results Fifty-five patients including 22 of ARDS and 33 of AE-ILD were assessed. Serum HO-1 level at diagnosis was significantly higher in ARDS patients than AE-ILD patients (87.8 ± 60.0 ng/mL vs. 52.5 ± 36.3 ng/mL, P < 0.001). Serum HO-1 correlated with serum total bilirubin (R = 0.454, P < 0.001) and serum LDH (R = 0.500, P < 0.001). In both patients with ARDS and AE-ILDs, serum HO-1 level tended to decrease from diagnosis to 2 weeks after diagnosis, however, did not normalized. Composite parameters including serum HO-1, age, sex, and partial pressure of oxygen in arterial blood/fraction of inspired oxygen (P/F) ratio for prediction of 3-month mortality showed a higher AUC (ARDS: 0.925, AE-ILDs: 0.892) than did AUCs of a single predictor or combination of two or three predictors. Conclusion Oxidative stress assessed by serum HO-1 is persistently high among enrolled patients for 2 weeks after diagnosis. Also, serum HO-1 levels at the diagnosis combined with age, sex, and P/F ratio could be clinically useful for predicting 3-month mortality in both ARDS and AE-ILD patients.

Heme oxygenase-1 as an important predictor of the severity of COVID-19

“…Serum HO-1 levels were measured on admission using the ImmunoSet ™ HO-1 enzyme-linked immunosorbent assay (ELISA) development set (Enzo, Farmingdale, NY, USA) and sCD163 levels were measured using Quantikine ELISA Human CD163 Immunoassay (R&D Systems, Minneapolis, MN, USA) according to the manufacturers’ instructions. The details of this ELISA method for serum HO-1 measurement were described previously [ 27 , 28 ]. The serum concentrations of HO-1 and sCD163 of normal controls were measured from 19 biobank samples from healthy volunteers before 2019.…”

Clinical importance of serum heme oxygenase-1 measurement in patients with acute exacerbation of idiopathic pulmonary fibrosis triggered by coronavirus disease 2019

“…In addition, the disease mechanism of this case was AE of IPF limited to the lung, not CARDS with systemic inflammation (cytokine storm). Because as previously research, serum HO-1 in ARDS is higher than AE of IPF, we speculated that the HO-1 is abundantly produced from reticuloendothelial tissues macrophages such as spleen, liver, and bone marrow in CARDS [ 7 ]. Therefore, serum HO-1 measurement could contribute to the distinction between CARDS and AE of IP.…”

“…Serum HO-1 measurement was reported to be useful to assess disease activity and predict treatment outcomes in patients with ARDS and AE of IPF [ 7 ]. Consistent with the previous research, in this case diagnosed with AE of IPF triggered by COVID-19, serum HO-1 at the diagnosis of both first AE and second AE increased (first AE: 44.08 ng/mL, second AE: 30.44 ng/mL) than that at the diagnosis of IPF (18.78 ng/mL) and the serial changes of serum HO-1 levels seemed to reflect disease activity of AE.…”

“…HO-1 is expressed exclusively on anti-inflammatory M2 macrophage linage, but not pro-inflammatory M1 macrophage by heat shock and oxidative stress conditions and the anti-inflammatory and anti-oxidative actions of each product originating from HO-1, CO and biliverdin (bilirubin), sustain the properties of M2 [ 3 , 5 ]. The prior research suggested that serum HO-1 measurement increased mainly in alveolar macrophages of patients with AE of interstitial pneumonia (IP) reflecting protection against oxidative stress and activated M2 macrophages and contributed to detect AE and predict disease prognosis in patients with IP [ 6 , 7 ].…”

Hemin shows antiviral activity in vitro, possibly through suppression of viral entry mediators

“…Heme catabolism by HO-1 has demonstrated benefits in several conditions with strong relevance to COVID-19 including; acute lung injury (X. Chen et al, 2018), sepsis (Takaki et al, 2010), and ARDS (Nagasawa et al, 2020). Antiviral activity of HO-1 has also been reported in dengue virus, hepatitis C virus, influenza, and respiratory syncytial virus (Espinoza et al, 2017;Olagnier et al, 2014;Tseng et al, 2016;Wang et al, 2017;Zhu et al, 2008).…”