A Normal Range of KL-6/MUC1 Independent of Elevated SP-D Indicates a Better Prognosis in the Patients with Honeycombing on High-Resolution Computed Tomography

Shu Hisata,Shigeki Chiba,Hiromitsu Ohta,Shuichi Ono,Yuichiro Kimura,Toshihiro Nukiwa,Takao Kobayashi,Naoko Shibata,Masahito Ebina

doi:10.1155/2011/806014

Abstract

Both SP-D and KL-6/MUC1 are established biomarkers of the interstitial pneumonias, including idiopathic pulmonary fibrosis (IPF), but the causes and clinical outcomes based on their independent effects are not known. Eleven asymptomatic patients, detected with honeycombing on high-resolution computed tomography (HRCT), were compared with 17 other IPF outpatients having slight respiratory symptoms and honeycombing as well. Although SP-D was increased in both groups, KL-6 was significantly higher in the symptomatic IPF group. When the patients (n = 11) having both biomarkers elevated were compared with the other patients (n = 6) with only SP-D elevated, the distribution of fibrotic lesions with honeycombing on HRCT was larger and the survival time was shorter in the patients having both biomarkers elevated. Immunohistochemical analysis also differentiated these biomarkers in the lung. These results suggest both a cause and the prognostic value of dissociation of these biomarkers.

Highlights

The prognosis for patients with idiopathic pulmonary fibrosis (IPF) is very poor after a diagnosis of respiratory symptoms, that is, a median survival of 2– 4 yrs [1], the natural history of IPF, from the point of view of asymptomatic status, is not well understood
It was shown here that (1) the serum level of KL-6/MUC1 was maintained within the normal range in dissociation with the surfactant protein D (SP-D) level, which was elevated in asymptomatic patients with honeycombing on high-resolution computed tomography (HRCT), (2) these patients with high SP-D but low KL-6 in their serum exhibited prolonged survival, (3) there are obvious differences in the distribution patterns between SP-D and KL-6/MUC1 in the IPF lung, especially in the clearance route, which may cause the observed dissociation between these biomarkers
The finding of honeycombing on HRCT is believed to be mostly associated with usual interstitial pneumonia (UIP), as it is reported that honeycombing in at least one lobe indicate UIP, with a 90% sensitivity and 86% specificity [18]

Summary

Introduction

The prognosis for patients with idiopathic pulmonary fibrosis (IPF) is very poor after a diagnosis of respiratory symptoms, that is, a median survival of 2– 4 yrs [1], the natural history of IPF, from the point of view of asymptomatic status, is not well understood. According to the American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement in 2002, “respiratory symptoms and abnormalities on pulmonary function test are required for the diagnosis of IPF in the absence of surgical biopsy” [2]. The detection of early stage of asymptomatic patients with IPF is important for the understanding the pathogenesis of this progressive pulmonary fibrosis, and for developing more effective treatments of IPF. Arakawa et al followed dust-exposed patients and reported that honeycombing required a median of 12 years to develop in normal or nearnormal lungs [3]. Radiological findings on high-resolution computed tomography (HRCT) has been reported [3, 6], there is only limited information on the relevant biomarkers, such as surfactant protein D (SP-D) and Krebs von den Lungen-6 Antigen/MUC1 (KL-6/MUC1) in early stages of IPF [4]

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