Evaluation of changes in the serum levels of Krebs von den Lungen-6 and surfactant protein-D over time as important biomarkers in idiopathic fibrotic nonspecific interstitial pneumonia

Yamakawa, Hideaki; Hagiwara, Eri; Ikeda, Satoshi; Iwasawa, Tae; Otoshi, Ryota; Tabata, Erina; Okuda, Ryo; Sekine, Akimasa; Baba, Tomohisa; Iso, Shinichiro; Okihara, Koji; Takemura, Tamiko; Ogura, Takashi

doi:10.1016/j.resinv.2019.03.006

Cited by 18 publications

(18 citation statements)

References 29 publications

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“…The initial KL-6 and SP-A levels correlated inversely with %DLCO at the time of IPAF diagnosis. In CTD-associated interstitial pneumonia, the serum levels of KL-6 and SP-D are negatively correlated with FVC and %DLCO [25,[29][30][31][32]. However, it is noteworthy that, in the present study, the serum levels of KL-6 and SP-A at the initial visit did not correlate with FVC.…”

Section: Discussioncontrasting

confidence: 67%

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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Section: Discussioncontrasting

confidence: 67%

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

View full text Add to dashboard Cite

show abstract

“…The initial KL-6 and SP-A levels correlated inversely with %DLCO at the time of IPAF diagnosis. In CTD-associated interstitial pneumonia, the serum levels of KL-6 and SP-D are negatively correlated with FVC and %DLCO [24,[28][29][30][31]. In the report by Lee et al [15], serum SP-A and KL-6 levels in CTD-ILD patients were significantly negatively correlated with FVC and DLCO.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Background Some 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. Methods Sixty-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. Results Compared 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). Conclusions Serum 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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“…This biomarker represents type II pneumocyte injury and/or permeability enhancement after the destruction of the alveolar–capillary barrier [ 7 , 8 ]. KL-6 is a biomarker for interstitial lung diseases (ILDs), including interstitial pulmonary fibrosis (IPF) and connective-tissue disease-associated ILD, and ARDS [ 9 , 10 ]. Elevation of serum KL-6 levels is also reported in pulmonary mycobacterial infection [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019

Yamaya

Hagiwara

Baba

et al. 2021

Respiratory Investigation

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Background The serum Krebs von den Lungen-6 (KL-6) level is a predictive factor for acute respiratory distress syndrome (ARDS). The development of ARDS has been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to determine whether serum KL-6 levels are associated with mortality and severity in patients with COVID-19. Methods Among 361 Japanese patients with COVID-19 who were hospitalized at Kanagawa Cardiovascular and Respiratory Center between February 2020 and December 2020, 356 patients with data on serum KL-6 levels were enrolled and their medical records were retrospectively analyzed. Results A negative correlation was observed between KL-6 levels and the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen on admission. The KL-6 levels on admission and the maximal KL-6 levels were higher in patients with severe disease (n = 60) than in those with nonsevere disease (n = 296). Furthermore, the maximal KL-6 levels were higher in nonsurvivors (n = 6) than in survivors (n = 350). In nonsurvivors, the KL-6 levels increased as the disease progressed. The optimal cutoff value of the maximal KL-6 level for discriminating between survivors and nonsurvivors was 684 U/mL, with a sensitivity of 83.3%, a specificity of 90.5%, and an area under the curve of 0.89. Conclusions The serum KL-6 level was associated with disease severity. Patients with KL-6 levels ≥ 684 U/mL had a significantly poorer outcome than those with KL-6 levels < 684 U/mL.

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Evaluation of changes in the serum levels of Krebs von den Lungen-6 and surfactant protein-D over time as important biomarkers in idiopathic fibrotic nonspecific interstitial pneumonia

Cited by 18 publications

References 29 publications

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

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

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

Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019

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