Importance of serial changes in biomarkers in idiopathic pulmonary fibrosis

Sokai, Akihiko; Tanizawa, Kiminobu; Handa, Tomohiro; Kumiko, Kanatani; Kubo, Takeshi; Ikezoe, Kohei; Nakatsuka, Yoshinari; Tokuda, Shinsaku; Oga, Toru; Hirai, Toyohiro; Nagai, Sonoko; Chin, Kazuo; Mishima, Michiaki

doi:10.1183/23120541.00019-2016

Cited by 42 publications

(39 citation statements)

References 43 publications

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“…Since KL-6 is more highly expressed in injured or regenerating epithelial cells than in normal epithelial cells [15,16], KL-6 could be used as a biomarker of lung injury. Previous studies showed that KL-6 might be a useful biomarker in evaluation of disease severity, and prediction of prognosis in patients with IPF [17][18][19][20]. In the case of RA-ILD, Kinoshita et al reported that KL-6 levels are correlated with the extent of the reticular opacities or total disease extent on HRCT in 47 patients with RA-ILD [21].…”

Section: Introductionmentioning

confidence: 99%

Prognostic role of blood KL-6 in rheumatoid arthritis–associated interstitial lung disease

Kim¹,

Choi²,

Jacob³

et al. 2020

PLoS ONE

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Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) has a variable clinical course for which predicting prognosis is difficult. However, the role of blood biomarkers in RA-ILD is ill-defined. The aim of this study was to investigate the prognostic value of Krebs von den Lungen-6 (KL-6) levels in RA-ILD patients. The medical records of 84 patients with RA-ILD were retrospectively reviewed. Plasma KL-6 levels were measured by Nanopia KL-6 assay (SEKISUI MEDICAL, Tokyo), using latex-enhanced immunoturbidimetric assay. The median follow-up period was 61 months. Mean age was 61.4 years, 45.2% were men, 44.0% were ever-smokers, and 35.7% showed a usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography. The median KL-6 level at baseline was 741.2 U/ mL (interquartile range, 439.7-1308.9 U/mL). On multivariate logistic regression analysis, a high KL-6 level (� 640 U/mL) was an independently associated with a UIP pattern (odds ratio [OR], 5.173; P = 0.005) with old age (OR, 1.104, P = 0.005). On multivariate Cox analysis, a high KL-6 level (� 685 U/mL) was an independent prognostic factor for the mortality (hazard ratio [HR], 2.984; P = 0.016) with a older age (HR, 1.061; P = 0.030), male sex (HR, 3.610; P = 0.001), lower forced vital capacity (HR, 0.957; P = 0.002), and a UIP pattern (HR, 4.034; P = 0.002). Our results suggest that high KL-6 levels might be useful as a biomarker for the presence of a UIP pattern and prognosis in patients with RA-ILD.

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Section: Introductionmentioning

confidence: 99%

Prognostic role of blood KL-6 in rheumatoid arthritis–associated interstitial lung disease

Kim¹,

Choi²,

Jacob³

et al. 2020

PLoS ONE

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“…The expression level of KL-6 signi cantly increases in alveolar tissue affected by interstitial pneumonia and enters the blood circulation through the damaged alveoli [6]. The alveolar surface protein SP-A, which is synthesized and secreted by airway and alveolar epithelial cells, is an important marker of alveolar injury [7,8]. In Japan [9,10], serum KL-6, SP-A and SP-D levels are widely used as biomarkers for the diagnosis and prognosis of idiopathic pulmonary brosis and ILD.…”

Section: Surfactant Protein-a (Sp-a) Andmentioning

confidence: 99%

Serum SP-A and KL-6 levels can predict the improvement and deterioration of patients with interstitial pneumonia with autoimmune features

Wang

Zheng

Huang

et al. 2020

Preprint

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BackgroundSome patients with interstitial pneumonia with autoimmune features (IPAF) showed a progressive course despite therapy. This study aimed to evaluate whether serial changes in the serum levels of surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) can predict disease progression. MethodsSixty-four patients with IPAF and 41 patients with non-fibrotic lung disease (non-FLD) were examined. Based on long-term changes in lung function, 36 IPAF patients who were followed up for more than 3 months were divided into a progressive group (n=9), an improvement group (n=13), and a stable group (n=14). Serum KL-6 and SP-A levels were measured. The sensitivity, specificity, cut-off value, and area under the curve (AUC) value for each of the indices were determined using receiver operating characteristic (ROC) curve analysis. The expression differences in these biomarkers and their correlation with disease severity were analyzed. ResultsCompared with non-FLD patients, serum SP-A and KL-6 levels in IPAF patients were increased significantly [SP-A: (p < 0.001); KL-6: (p < 0.001)] and negatively correlated with DLCO (SP-A: rS = -0.323, p = 0.018; KL-6: rS = -0.348, p = 0.0011). In patients with progressive disease, the posttreatment serum SP-A and KL-6 levels were increased significantly compared with pretreatment levels [SP-A: (p = 0.021); KL-6: (p = 0.008)]. In patients showing improvement, the levels were decreased significantly [SP-A (p = 0.007) and KL-6 (p = 0.002)]. Changes in serum biomarkers (Delta SP-A and Delta KL-6) were significantly negatively correlated with changes in lung function (Delta FVC, Delta DLCO and Delta FEV1) (rS = 0.482, p < 0.05). A significant positive correlation was found between Delta SP-A and Delta KL-6 (rS = 0.482, p < 0.001).ConclusionsSerum SP-A and KL-6 offer high sensitivity and specificity for the diagnosis of IPAF. The decrease in serum SP-A and/or KL-6 levels in patients with IPAF is related to the improvement in pulmonary function. SP-A and KL-6 may be important biomarkers for predicting disease progression in patients with IPAF.

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“…However, on the other hand, some patients experience an accelerated clinical and functional deterioration [3] that could represent another phenotype. Rapid progressors have been associated with low FVC and DLCO as well as with the upregulation of several genes such as those involved in cell motility, myofibroblast differentiation, coagulation, oxidative stress, and development, among them TLR9 , CCL18 , antibodies against HSP70 , and KL-6 [65]. Lung microbiome has also been related to a faster deterioration of lung function [66]…”

Section: Phenotypesmentioning

confidence: 99%

Idiopathic Pulmonary Fibrosis: Epidemiology, Natural History, Phenotypes

et al. 2018

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Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It is characterized by a chronic, progressive, fibrotic interstitial lung disease of unknown cause that occurs primarily in older adults. Its prevalence and incidence have appeared to be increasing over the last decades. Despite its unknown nature, several genetic and environmental factors have been associated with IPF. Moreover, its natural history is variable, but could change depending on the currently suggested phenotypes: rapidly progressive IPF, familial, combined pulmonary fibrosis and emphysema, pulmonary hypertension, and that associated with connective tissue diseases. Early recognition and accurate staging are likely to improve outcomes and induce a prompt initiation of antifibrotics therapy. Treatment is expected to be more effective in the early stages of the disease, while developments in treatment aim to improve the current median survival of 3–4 years after diagnosis.

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Importance of serial changes in biomarkers in idiopathic pulmonary fibrosis

Cited by 42 publications

References 43 publications

Prognostic role of blood KL-6 in rheumatoid arthritis–associated interstitial lung disease

Prognostic role of blood KL-6 in rheumatoid arthritis–associated interstitial lung disease

Serum SP-A and KL-6 levels can predict the improvement and deterioration of patients with interstitial pneumonia with autoimmune features

Idiopathic Pulmonary Fibrosis: Epidemiology, Natural History, Phenotypes

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