Serum CXCL9 and CCL17 as biomarkers of declining pulmonary function in chronic bird-related hypersensitivity pneumonitis

Yoshihisa Nukui,Takashi Yamana,Makoto Tomita,Mitsuhiro Kishino,Takashi Aritsu,Ukihide Tateishi,Tomoya Tateishi,Masahiro Masuo,Yasunari Miyazaki,Takehiro Hasegawa,Gernot Zissel

doi:10.1371/journal.pone.0220462

Abstract

The clinical course of chronic hypersensitivity pneumonitis (HP) with fibrosis is similar to that of idiopathic pulmonary fibrosis (IPF). Current research is expected to identify biomarkers effective in predicting the deterioration of lung function in a clinical setting. Our group analyzed the relationships between the following parameters in chronic bird-related HP: patient characteristics, serum markers, lung function, HRCT findings, BALF profiles, and the worsening of lung function. We also analyzed serum levels of CXCL9, CCL17, and Krebs von den Lungen 6 (KL-6) as serum markers. Patients showing declines in vital capacity (VC) of over 5% at 6 months after first admission were categorized as the “decline group”; the others were categorized as the “stable group.” The serum level of CCL17 and the percentage of BALF macrophages were significantly higher in the decline group compared to the stable group. Serum levels of CXCL9 and CCL17 were significant variables in a multivariate logistic regression analysis of factors associated with VC decline. Patients with a chemokine profile combining lower serum CXCL9 and higher serum CCL17 exhibited significantly larger VC decline in a cluster analysis. Higher serum CCL17 and lower serum CXCL9 were important predictors of worsening lung function in patients with chronic bird-related HP.

Highlights

Hypersensitivity pneumonitis (HP) is an immune-mediated lung disease triggered by the inhalation of a wide variety of antigens [1]
The patient characteristics, CXCL9, CCL17, and Krebs von den Lungen 6 (KL-6), serum levels, and pulmonary function tests (PFTs) results are shown in Table 1 and S1 Fig. The high-resolution computed tomography (HRCT) findings and bronchoalveolar lavage fluid (BALF) profiles are shown in S1 and S2 Tables
The CXCL9, CCL17, and KL-6 serum levels were significantly higher in the patients with chronic bird-related HP than in the healthy volunteers (CXCL9; chronic bird-related HP vs. HV, 19.3 (13.2–35.6) vs. 10.5 (7.6–15.6) pg/ml, P < 0.001

Summary

Introduction

Hypersensitivity pneumonitis (HP) is an immune-mediated lung disease triggered by the inhalation of a wide variety of antigens [1]. The clinical presentation of HP is traditionally classified into acute and chronic types. Acute HP strikes in acute episodes and can be successfully cured by allergen avoidance. Chronic HP is categorized into two subgroups, (recurrent type and insidious type, according to the clinical features) [2]. Patients with the recurrent type experience repeated acute episodes of mild exertional dyspnea, cough, and low-grade fever. Patients with the insidious type suffer from chronic, slowly progressing respiratory disease without

Methods

Results

Conclusion