Abstract

Weight loss progresses with the progression of idiopathic pulmonary fibrosis (IPF), and acute exacerbation of IPF (AE-IPF) frequently occurs in its advanced stage. Adiponectin and leptin are adipokines produced from adipose tissue, and are related to thinness and obesity, respectively. Additionally, these adipokines are implicated in the regulation of inflammation and fibrosis centering on peroxisome proliferator-activated receptor γ (PPARγ). However, the relationship between adiponectin/leptin and AE-IPF remains poorly known. We conducted this study to evaluate levels of serum adiponectin/leptin, and to elucidate the clinical importance of adiponectin and leptin in patients with AE-IPF. Thirty-two patients (39 episodes) who were diagnosed with AE-IPF at our hospital from 1997 to 2016 were retrospectively studied. Serum adiponectin and leptin concentrations were measured with enzyme-linked immunosorbent assay. Patients with AE-IPF showed higher levels of serum adiponectin and leptin than those at initial diagnosis of IPF (p = 0.007 and p = 0.027, respectively). Serum adiponectin/leptin (A/L) ratio was negatively correlated with body mass index at AE-IPF (r = −0.456, p = 0.003) and PaO2 before AE-IPF (r = −0.498, p = 0.034), and positively correlated with C-reactive protein at AE-IPF (r = 0.316, p = 0.049). Patients with higher A/L ratios had worse survival than those with lower A/L ratios (log-rank, p = 0.026). Further, in multivariate analysis, serum A/L ratio was a significant prognostic factor in patients with AE-IPF (HR 2.60, p = 0.042). In conclusion, the higher adiponectin/leptin ratio may be associated with a poor prognosis in patients with AE-IPF.

Highlights

  • Idiopathic pulmonary fibrosis (IPF) shows a catastrophic prognosis[1], and one of the leading causes of death in patients with idiopathic pulmonary fibrosis (IPF) is acute exacerbation of IPF (AE-IPF)[2]

  • We evaluated serum adipokine concentrations and determined whether adipokines were important to predict prognosis in patients with AE-IPF

  • A/L ratio negatively correlated with BMI and PaO2 before AE-IPF, and positively correlated with C-reactive protein (CRP)

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Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) shows a catastrophic prognosis[1], and one of the leading causes of death in patients with IPF is acute exacerbation of IPF (AE-IPF)[2]. Adiponectin and leptin are adipokines produced from adipose tissue and are related to obesity and emaciation. Plasma leptin levels increased at AE-IPF, and AE-IPF patients with higher leptin levels at AE showed worse prognosis than those with lower levels[13]. These results lead us to hypothesize that leptin and adiponectin, which have opposite effects on PPARγ expression, may be related to pathogenesis of AE-IPF in the advanced stage of IPF. To the best of our knowledge, this is the first study to show the relationship between these two adipokines, and the relationship between adipokines and clinical parameters/prognosis in patients with AE-IPF

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