Circulating KL-6 Predicts the Outcome of Rapidly  Progressive Idiopathic Pulmonary Fibrosis

Yokoyama, Akihito; Kohno, Nobuoki; Hamada, Hironobu; Sakatani, Mitsunori; Ueda, Einosuke; Kondo, Keiichi; Hirasawa, Yutaka; Hiwada, Kunio

doi:10.1164/ajrccm.158.5.9803115

Cited by 198 publications

(135 citation statements)

References 24 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…Future studies should also consider whether sLOXL2, along with other promising prognostic IPF biomarkers (e.g. matrix metalloproteinase (MMP)1, MMP7, KL-6, periostin, surfactant protein-A and D, CC chemokine ligand 18, vascular endothelial growth factor and YKL-40) [19][20][21][22][23][24][25][26][27][28][29], as well as prognostic scores [30,31] and radiological modalities [32], might have prognostic value for helping physicians and patients anticipate the patient's IPF disease progression. This might include evaluation of serially collected sLOXL2 levels and their relationship to IPF acute exacerbations, which represent a terminal event for many IPF patients [33].…”

Section: Discussionmentioning

confidence: 99%

Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression

Chien¹,

et al. 2013

View full text Add to dashboard Cite

We evaluated whether lysyl oxidase-like 2 (LOXL2), which promotes cross-linking of collagen in pathological stroma, was detectable in serum from idiopathic pulmonary fibrosis (IPF) patients, and assessed its relationship with IPF disease progression.Patients from the ARTEMIS-IPF (n569) and the Genomic and Proteomic Analysis of Disease Progression in IPF (GAP) (n5104) studies were analysed. Baseline serum LOXL2 (sLOXL2) levels were compared with baseline clinical and physiological surrogates of disease severity, and the association with IPF disease progression was assessed using a classification and regression tree (CART) method. sLOXL2 correlated weakly with forced vital capacity and carbon monoxide diffusion capacity (r -0.24-0.05) in both cohorts. CART-determined thresholds were similar: ARTEMIS-IPF 800 pg?mL -1 and GAP 700 pg?mL -1. In ARTEMIS-IPF, higher sLOXL2 (.800 pg?mL -1 ) was associated with increased risk for disease progression (hazard ratio (HR) 5.41, 95% CI 1.65-17.73). Among GAP subjects with baseline spirometric data (n570), higher sLOXL2 levels (.700 pg?mL -1 ) were associated with more disease progression events (HR 1.78, 95% CI 1.01-3.11). Among all GAP subjects, higher sLOXL2 levels were associated with increased risk for mortality (HR 2.28, 95% CI 1.18-4.38).These results suggest that higher sLOXL2 levels are associated with increased risk for IPF disease progression. However, due to multiple limitations, these results require validation. Clinical trial: This study is registered at www.ClinicalTrials.gov with identifier number NCT00768300 and NCT 00373841.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression

Chien¹,

et al. 2013

View full text Add to dashboard Cite

show abstract

“…To produce a high circulating KL-6 level, severe damage to both the pulmonary epithelium and interstitium would be necessary (7). In addition, serum KL-6 levels are known to be well correlated with KL-6 levels in bronchoalveolar lavage fluid (10,14) and can be used to predict the response to corticosteroid therapy in patients with interstitial lung disease (15). Accordingly, circulating KL-6 is recognized as a specific indicator of pulmonary injury affecting the alveolar epithelium and interstitium (7).…”

mentioning

confidence: 99%

Plasma KL-6 Predicts the Development and Outcome of Bronchopulmonary Dysplasia

et al. 2006

View full text Add to dashboard Cite

Circulating KL-6 is a specific indicator of pulmonary injury affecting the alveolar epithelium and interstitium. Our preliminary study suggested the usefulness of plasma KL-6 as a marker of bronchopulmonary dysplasia (BPD). To confirm the diagnostic value of KL-6 for BPD as well as to determine the reference range, we conducted a larger prospective study in 135 preterm infants Ͻ32 wk GA. Among the infants without oxygen dependence at a postconceptional age of 36 wk, the plasma KL-6 level showed no significant association with GA at any time. Among 42 infants Ͻ28 wk GA, plasma KL-6 levels were significantly higher in those with moderate/ severe BPD compared with those with no/mild BPD. A plasma level of 199 U/mL at 1 wk or 232 U/mL at 2 wk was an excellent predictor of moderate/severe BPD Ͻ28 wk GA (positive predictive value of 83% and 80%, respectively). Unlike nonspecific markers of inflammation or fibrosis, KL-6 objectively reflects the severity of pulmonary injury irrespective of the treatment or the radiographic changes. Therefore, not only as a good marker, measurement of KL-6 may also help to provide new insights into the pathogenesis of BPD.

show abstract

“…There are many studies suggesting plasma KL-6 is increased in adult patients with various types of interstitial pneumonia, characterized by type 2 alveolar hyperplasia and fibrosis (8)(9)(10)(11). KL-6 has also shown to be as a useful marker for increased alveolar vascular permeability associated with lung injury.…”

Section: Introductionmentioning

confidence: 99%

Predictive values of plasma KL-6 in bronchopulmonary dysplasia in preterm infants

Díllí¹,

Özyazici²,

Dursun³

et al. 2017

Turk J Med Sci

View full text Add to dashboard Cite

IntroductionBronchopulmonary dysplasia (BPD) is a syndrome of respiratory distress caused by chronic lung parenchymal injury, occurring especially in preterm infants (1). BPD remains a serious problem in very low birthweight (VLBW) infants despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome (RDS) (2,3). BPD has a complex and multifactorial etiology, including oxygen toxicity, preterm delivery, hypoxia/hyperoxia, infection, and inflammation (4).Many studies have suggested that lung inflammation is a major contributor to the pathogenesis of BPD (5,6). Various parameters of lung inflammation may be used to show lung inflammation. However, most of them such as N-terminal propeptide of type 3 collagen, SP-A, anti-SP-A immune complexes, nitrotyrosine, soluble E-selectin, intercellular adhesion molecule-1, allantoin, and aldehydes are not specific for lung disease or are complicated to measure (6). Krebs yon den Lundgen-6 (KL-6) is a mucinlike high-molecular weight glycoprotein that is classified into cluster 9 (MUC1) of lung tumor and differentiation antigens. It is preferentially expressed by alveolar type 2 cells and stimulates lung fibrosis through its action as a fibroblast chemotactic factor (7).There are many studies suggesting plasma KL-6 is increased in adult patients with various types of interstitial pneumonia, characterized by type 2 alveolar hyperplasia and fibrosis (8-11). KL-6 has also shown to be as a useful marker for increased alveolar vascular permeability associated with lung injury. However, plasma KL-6 levels are not elevated in noninterstitial lung diseases such as bacterial pneumonia, bronchial asthma, and pulmonary emphysema (9). Similar pathological changes seen in interstitial pneumonia in the lung are also predominant in BPD (7,12,13). Plasma KL-6 can be a clinically useful early marker for BPD. However, there are few data on the predictive characteristics of KL-6. Therefore, in the present study, we aimed to evaluate the predictive values of KL-6 in BPD within the first days of life. Materials and methods Study populationAll eligible preterm infants between May 2014 and April 2015 were prospectively enrolled in this study, specifically neonates with birthweight ≤1500 g and gestational age ≤32 Background/aim: It has been suggested that plasma KL-6 increases in premature infants with bronchopulmonary dysplasia (BPD). We aimed to evaluate the predictive values of KL-6 in BPD. Materials and methods:The study was performed in preterm neonates with birthweight ≤1500 g and gestational age ≤32 weeks. Plasma KL-6 levels were measured on postnatal days 1, 7, and 14.Results: BPD was identified in eight of the 28 study infants. On postnatal days 1 and 7, plasma KL-6 levels were similar in infants with BPD [on

show abstract

Circulating KL-6 Predicts the Outcome of Rapidly Progressive Idiopathic Pulmonary Fibrosis

Cited by 198 publications

References 24 publications

Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression

Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression

Plasma KL-6 Predicts the Development and Outcome of Bronchopulmonary Dysplasia

Predictive values of plasma KL-6 in bronchopulmonary dysplasia in preterm infants

Contact Info

Product

Resources

About