Heme Oxygenase-1 in Patients With Interstitial Lung Disease: A Review of the Clinical Evidence

The clinical course and rate of progression of interstitial lung disease (ILD) are extremely variable among patients. For the purpose of monitoring disease activity, ILD diagnosis, and predicting disease prognosis, there are various biomarkers, including symptoms, physiological, radiological, and pathological findings, and peripheral blood and bronchoalveolar lavage fluid results. Of these, blood biomarkers such as sialylated carbohydrate antigen, surfactant proteins-A and -D, CC-chemokine ligand 18, matrix metalloprotease-1 and -7, CA19–9, and CA125 have been previously proposed. In the future, heme oxygenase-1 (HO-1) may also become a candidate ILD biomarker; it is a 32-kDa heat shock protein converting heme to carbon monoxide, biliverdin/bilirubin, and free iron to play a role in the pulmonary cytoprotective reaction in response to various stimuli. Recent research suggests that HO-1 can increase in lung tissues of patients with ILD, reflecting anti-inflammatory M2 macrophage activation, and the measurement of HO-1 levels in peripheral blood can be useful for evaluating the severity of lung damage in ILD and for predicting subsequent fibrosis formation.