Is serum iron responsive protein-2 level associated with pulmonary functions and frequent exacerbator phenotype in COPD?

Abstract

Chronic Obstructive Pulmonary Disease (COPD) exacerbations contribute to the overall severity in individual patients because they are associated with airway inflammation, pulmonary function loss, decreased quality of life and increased mortality. Although, identifying frequent exacerbator patients is important due to severe outcomes associated with frequent exacerbator phenotype in COPD patients there is no single biomarker which can differentiate this phenotype. Iron responding protein-2 (IRP2) is the protein product of IREB2 gene, which is a COPD susceptibility gene that regulates cellular iron homeostasis and has a key role in hypoxic conditions. Previous research indicates that IREB2 expression in lung tissue is associated with spirometric measurements and emphysema in COPD. In this study, our aim was to investigate whether serum IRP2 levels were associated with frequent exacerbator phenotype, to evaluate whether IRP2 levels in serum are associated with pulmonary functions and selected systemic inflammation biomarkers. Designed as a single tertiary care center based, crosssectional study, included high risk (GOLD C, D) COPD patients who admitted to outpatient clinic consecutively between December 2015 and July 2016. The study included 80 COPD patients. Serum IRP2 levels were negatively correlated with FEV1 ml (r= -0.25, p= 0.02) and body weight (r= -0.35, p= 0.002) but not with markers of systemic inflammation. COPD patients with at least one exacerbation history in the last year tended to have higher IRP2 levels than patients without any exacerbation [12.3 (IQR 25-75: 10.4- 17.1) vs 10.5 (IQR 25-75: 8.8-18.5), p= 0.06]. Serum IRP2 level is significantly correlated with FEV1 mL but not with FEV1 % predicted and cannot be used to differentiate frequent exacer bator patients. Although IREB2 gene expressions in lung tissue and bronchoalveolar lavage results have significant associations with emphysema and FEV1/FVC, FEV1 %predicted in COPD patients, our results suggests serum IRP2 level is not as promising.