Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome

Ishizaka, Akitoshi; Matsuda, Tomoyuki; Albertine, Kurt H.; Koh, Hidefumi; Tasaka, Sadatomo; Hasegawa, Naoki; Kohno, Nobuoki; Kotani, Toru; Morisaki, Hiroshi; Takeda, Junzo; Nakamura, Morio; Fang, Xiaohui; Martin, Thomas R.; Matthay, Michael A.; Hashimoto, Satoru

doi:10.1152/ajplung.00420.2002

Cited by 159 publications

(162 citation statements)

References 30 publications

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“…It was assumed before starting this study that serum levels of KL-6 and SP-D in AE-IPF would be higher than those in S-IPF patients because previous reports have suggested that KL-6 and SP-D might be useful markers for interstitial pneumonias (Ohnishi et al 2002;Takahashi et al 2000). However, Ishizaka et al reported that at the onset of acute lung injury, plasma levels of KL-6 were similar to those of controls, perhaps because of its relatively large molecular size (Ishizaka et al 2004). In addition, in the current study, serum levels of KL-6 and SP-D levels were elevated even in patients with S-IPF (when compared with normal ranges), consistent with previous reports (Ohnishi et al 2002;Takahashi et al 2000).…”

Section: Discussionmentioning

confidence: 92%

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Kakugawa

Yokota

Ishimatsu

et al. 2013

Cell Stress and Chaperones

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Little is known about the pathophysiology of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for biosynthesis and secretion of collagen molecules. Previous studies in experimental animal fibrosis models have shown that downregulation of HSP47 expression reduces collagen production and diminishes fibrosis progression. In this study, serum HSP47 levels were evaluated to elucidate pathogenic differences involving HSP47 between AE-IPF and stable (S)-IPF. -013-0411-5 and lactate dehydrogenase (LDH) were measured. Immunohistochemical analysis of lung HSP47 expression was determined in biopsy and autopsy tissues diagnosed as diffuse alveolar damage (DAD) and usual interstitial pneumonia (UIP). Serum levels of HSP47 were significantly higher in AE-IPF than in S-IPF patients, whereas serum levels of KL-6, SP-A, and SP-D did not differ significantly. Receiver operating characteristic curves revealed that HSP47 was superior for discriminating AE-IPF and S-IPF. The cutoff for HSP47 resulting in the highest diagnostic accuracy was 559.4 pg/mL; sensitivity, specificity, and diagnostic accuracy were 100.0 %, 93.9 %, and 96.2 %, respectively. Immunohistochemical analysis revealed that pulmonary HSP47 expression was greater in DAD than UIP tissues. Serum HSP47 was significantly higher in AE-IPF than in S-IPF patients, suggesting that underlying fibrogenic mechanisms involving HSP47 differ in the two conditions.Cell Stress and Chaperones (2013) 18:581-590 DOI 10.1007/s12192

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Section: Discussionmentioning

confidence: 92%

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Kakugawa

Yokota

Ishimatsu

et al. 2013

Cell Stress and Chaperones

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“…This is in contrast to bronchoalveolar lavage (BAL), which samples two sites of infection, i.e., fluid lining the small airways distal to the point of the wedge of the tip of the bronchoscope (alveolar ELF) and alveolar macrophage (AM). BMS is useful for measuring the concentrations of biochemical substances, such as KL-6, albumin, and tumor markers, in bronchial ELF [4,5]. We have also used this technique to obtain bronchial ELF on the airway surface and determine the time versus concentration profile of levofloxacin, a model antibiotic [6].…”

Section: Bronchoscopic Microsampling (Bms) Is a New Technique For Repmentioning

confidence: 99%

Pharmacokinetics of telithromycin using bronchoscopic microsampling after single and multiple oral doses

Kikuchi

Yamazaki

Kikuchi

et al. 2007

Pulmonary Pharmacology & Therapeutics

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Objectives: Bronchoscopic microsampling (BMS) is a new technique for repeated sampling of bronchial epithelial lining fluid (ELF) to obtain the pharmacokinetic profile of drugs. We analyzed the time versus concentration profiles of telithromycin in bronchial ELF obtained by BMS and compared these finding to those in plasma and alveolar ELF obtained by bronchoalveolar lavage (BAL).Methods: Bronchial ELF samples were obtained from five healthy subjects using BMS probe at 0, 2, 3, 4, 6, 10 and 24 h after single or multiple oral doses of 600 mg of telithromycin. Alveolar ELF was also obtained by BAL 3 h after single or multiple oral doses of 600 mg of telithromycin. Results:The areas under the concentration-time curve from 0 to 24 h (AUC0-24) of telithromycin in plasma and bronchial ELF were 2.86 ± 0.60 and 19.5 ± 10.4 mg·h/l after single treatment and 3.60 ± 0.49 and 42.2 ± 22.7 mg·h/l after multiple treatments, respectively. Single and multiple oral doses of telithromycin produced significantly (p<0.05) higher AUC0-24 in bronchial ELF compared to those in plasma. While concentrations in bronchial ELF obtained by BMS were significantly lower than those in alveolar ELF obtained by BAL, they tended to be higher than those in plasma after multiple administration. The telithromycin concentrations obtained by BMS method were very consistent in bronchial ELF at different bronchi at one time point and at the same bronchus at different time points.Conclusions: Using the BMS technique, we could describe the pharmacokinetics of telithromycin in bronchial ELF. Furthermore, BMS was reasonably validated and reconfirmed to be a feasible and reliable method for measuring antimicrobial concentrations in bronchial ELF.-2 -

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“…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.…”

Section: Introductionmentioning

confidence: 70%

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

Díllí¹,

Özyazici²,

Dursun³

et al. 2017

Turk J Med Sci

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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

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Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome

Cited by 159 publications

References 30 publications

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Pharmacokinetics of telithromycin using bronchoscopic microsampling after single and multiple oral doses

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

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