The usefulness of serum KL-6 levels for the diagnosis of disease activity in idiopathic interstitial pneumonia]

Serum KL-6 levels were measured in 29 patients with idiopathic interstitial pneumonia (IIP) as a means of evaluating disease activity. Levels of serum KL-6 were significantly higher in patients with active IIP (n = 11) than in those with inactive IIP (n = 18). The levels of serum KL-6 were 2,546 +/- 1,703 U/ml in patients with active IIP and 795 +/- 385 U/ml in patients with inactive IIP, respectively. The levels of serum LDH, CEA, P-III-P, and 7 S collagen in patients with active IIP did not differ significantly from those in patients with inactive IIP. For the diagnosis of active IIP, the sensitivity of serum KL-6 (cut off value of 1,500 U/ml) was 81.8% and the specificity, 94.4%. These results were almost identical to findings obtained with chest Ga-67 scintigraphy. Furthermore, they suggested that serum KL-6 levels may be a useful marker for the diagnosis of disease activity in IIP, as well as a useful indicator for the administration of steroid therapy to patients with IIP.     

Comparative evaluation of KL-6 and surfactant protein D as serum markers for interstitial pneumonia associated with collagen diseases

We evaluated the usefulness of serum levels of KL-6 and surfactant protein D (SP-D) as markers of interstitial pneumonia (IP) associated with collagen diseases in 115 patients. KL-6 and SP-D levels in patients with IP (n = 38) were significantly higher than those in patients without IP (n = 77). Moreover, KL-6 and SP-D levels in patients with active IP (n = 8) were significantly higher than those in patients with inactive IP (n = 30). Both KL-6 and SP-D proved useful for the diagnosis of IP associated with collagen diseases and for the evaluation of disease activity. We classified IP into three groups according to the extent of the lesion on computed tomographs of the chest. There was a significant difference among three groups in serum levels of KL-6, but not in serum levels of SP-D. KL-6 proved to be useful as an indicator of the extent of the IP lesions. We monitored changes in KL-6 and SP-D levels in seven of eight patients with active IP. Chronological changes of serum KL-6 and SP-D in patients with active IP were different. In fatal cases in particular, serum levels of SP-D decreased at the terminal stage of IP while levels of KL-6 continued to increase. Received: April 11, 2000 / Accepted: November 27, 2000     

High serum KL-6 levels predict the deterioration of pulmonary function in patients with rheumatoid arthritis

KL-6 has been reported to be a serum marker for interstitial pneumonitis (IP). The purpose of this study was to determine the predictive value of KL-6 on the deterioration of vital capacity (VC) in rheumatoid arthritis (RA) patients with IP. In 32 RA patients we evaluated both the serum KL-6 level and VC in a prospective design. The diagnosis of IP was determined by clinical symptoms, chest X-ray, high-resolution computed tomography (HRCT) scanning and/or pulmonary function tests. Findings such as reticulonodular and/or cystic shadows on HRCT scanning were accepted as IP signs. The IP signs with ground-glass opacity were set as active. The mean period of observation was 31.2 (5.6) months. The initial and/or final serum KL-6 levels were more than 520 U/ml in seven patients (H-KL group). In the other 25 patients, both the initial and final KL-6 levels were 520 U/ml or less (L-KL group). Among the H-KL group patients, their percent VC (%VC) was significantly reduced (P < 0.01) during the observation period. No significant changes of KL-6 and %VC levels were seen in the L-KL group. Thus, we conclude that in RA patients with IP, abnormal levels of serum KL-6 may predict the deterioration of VC.     

High serum KL-6 levels predict the deterioration of pulmonary function in patients with rheumatoid arthritis

Abstract

KL-6 has been reported to be a serum marker for interstitial pneumonitis (IP). The purpose of this study was to determine the predictive value of KL-6 on the deterioration of vital capacity (VC) in rheumatoid arthritis (RA) patients with IP. In 32 RA patients we evaluated both the serum KL-6 level and VC in a prospective design. The diagnosis of IP was determined by clinical symptoms, chest X-ray, high-resolution computed tomography (HRCT) scanning and/or pulmonary function tests. Findings such as reticulonodular and/or cystic shadows on HRCT scanning were accepted as IP signs. The IP signs with ground-glass opacity were set as active. The mean period of observation was 31.2 (5.6) months. The initial and/or final serum KL-6 levels were more than 520 U/ml in seven patients (H-KL group). In the other 25 patients, both the initial and final KL-6 levels were 520 U/ml or less (L-KL group). Among the H-KL group patients, their percent VC (%VC) was significantly reduced ( P < 0.01) during the observation period. No significant changes of KL-6 and %VC levels were seen in the L-KL group. Thus, we conclude that in RA patients with IP, abnormal levels of serum KL-6 may predict the deterioration of VC.     

Clinical impact of interstitial pneumonia following surgery for lung cancer

BACKGROUND: Operative morbidity in patients with lung cancer associated with perioperative interstitial pneumonia (IP) has emerged as a serious problem. PATIENTS AND METHODS: We studied the clinical impact of perioperative related IP in 11 patients (IP group: 7 preoperative known, 4 acute onset) of 473 lung cancer patients who received a pulmonary resection. The IP group was compared to the remaining 462 patients (non-IP group). Demographic data, clinical presentation, and serum KL-6 levels were compared. RESULTS: There were no differences in age, gender, type of surgery, and pulmonary function except for % DLco between the non-IP and IP groups. The IP group showed a higher in-hospital mortality (n=2: 18.3%) than that of the non-IP group (n=3: 0.6%) (P<0.005). Seven patients with underlying IP with high KL-6 levels showed an uneventful recovery. Two patients with postoperative onset of acute IP had a fatal course associated with elevation of serum KL-6 levels. CONCLUSIONS: Postoperative development IP is a serious complication with high mortality, and serial measurement of KL-6 levels is useful to assess the activity of IP.     

KL-6 as a novel serum marker for interstitial pneumonia associated with collagen diseases

OBJECTIVE: To investigate the diagnostic value of the serum concentrations of KL-6, a mucinous glycoprotein expressed on type II pneumocytes, for interstitial pneumonia (IP) in various collagen diseases. METHODS: Serum KL-6 levels were measured by ELISA. RESULTS: The mean values and the positive rates of serum KL-6 levels for patients with rheumatoid arthritis, systemic sclerosis, or polymyositis/dermatomyositis with IP were significantly higher than those without IP. Sensitivity, specificity, positive and negative predictive values of serum KL-6 level for IP associated with collagen diseases were 60.7, 98.9, 97.4, and 77.1%, respectively. The mean serum KL-6 level of patients with active IP was significantly (p = 0.0001) higher than that of patients with inactive IP. Serum KL-6 levels increased with the deterioration of IP, while the successful treatment of IP resulted in a significant decrease of these levels. CONCLUSION: Serum KL-6 concentration levels are a useful marker for diagnosis and evaluation of the disease activity of IP associated with collagen diseases.     

Serum KL-6 as a possible marker for amiodarone-induced pulmonary toxicity

Amiodarone is a useful drug for the treatment of life-threatening cardiac arrhythmias. However, amiodarone can induced pulmonary toxicity (APT) and may cause life-threatening lung damage. APT can be difficult to diagnose, but early diagnosis is important. Here, in a 51-year-old man with APT, the high serum KL-6 level was correlated with the severity of symptoms and chest X-ray findings, and it was inversely correlated with PaO2 and diffusion capacity for carbon monoxide levels. The findings suggest that the serum KL-6 level may be increased in APT and that therefore it's the determination of serum KL-6 may provide a useful indicator and/or monitoring marker of APT. KL-6 is believed to be produced and secreted by type II pneumocytes. Typical pathological findings of APT include proliferation of type II pneumocytes which may produce KL-6, and result in increased serum KL-6 levels.     

Clinical significance of serum KL-6 in pulmonary sarcoidosis]

We investigated whether the level of serum KL-6 could be an activity marker for pulmonary sarcoidosis. In 33 patients with pulmonary sarcoidosis, the relationships between serum KL-6 levels and diagnostic imaging, serum angiotensin-converting enzyme (ACE) levels, serum lysozyme levels, steroid therapy, and prognosis were evaluated. There were no significant differences in the level of serum KL-6 when the patients were divided on the basis of radiographic findings, but the level of serum KL-6 was markedly elevated in some patients with stage-II pulmonary sarcoidosis. There was a significant correlation between serum KL-6 levels and the following two parameters: serum ACE and lysozyme levels. Among patients with a high initial level of serum KL-6, pulmonary sarcoidosis tended to become exacerbated within one year. Steroid therapy significantly decreased the level of serum KL-6, suggesting that the level of serum KL-6 could be an activity indicator for pulmonary sarcoidosis. Immunohistochemical staining by anti-KL-6 antibody revealed that KL-6 was localized in proliferating type-II alveolar epithelial cells.     

Serum levels of KL-6 as a useful marker for evaluating pulmonary fibrosis in patients with systemic sclerosis

OBJECTIVE: KL-6 is a mucin-like glycoprotein that is strongly expressed on type II pneumocytes in the lung. Circulating KL-6 has been shown to be a sensitive marker of the disease activity of interstitial lung diseases. We determined the serum levels of KL-6 in patients with systemic sclerosis (SSc) and investigated whether these levels would serve as a useful marker of pulmonary fibrosis (PF) in patients with SSc. METHODS: The serum KL-6 levels were determined using a specific ELISA in 91 patients with SSc, and in 38 healthy controls. RESULTS: The serum levels of KL-6 were significantly higher in patients with SSc than in healthy controls (923+/-860 vs. 382+/-55 U/ml; p<0.0001). The serum KL-6 levels of the patients with diffuse cutaneous SSc (dSSc) tended to be higher than those with limited cutaneous SSc (ISSc) (1054+/-1000 vs. 800+/-694 U/ml), but there was no significant difference between these 2 groups. The serum KL-6 levels in the patients with PF were significantly elevated compared to those without PF (1283+/-1056 vs. 520+/-148 U/ml; p<0.0001). Moreover, DLCO and VC were also significantly decreased in the patients with elevated KL-6 levels compared to those with normal levels (62+/-22% vs. 72+/-17%, p<0.05; 87 +/-20% vs. 100+/-18%, p<0.01, respectively). CONCLUSION: Serum KL-6 level may be a useful serum marker for evaluating pulmonary fibrosis in patients with SSc.     

Elevation of Serum KL-6 Levels in Patients with Hematological Malignancies Associated with Cytomegalovirus or Pneumocystis carinii Pneumonia

The level of serum KL-6 antigen has been reported to be a sensitive indicator of various interstitial pneumonitis, but in patients with hematological malignancies who were accompanied by infective interstitial pneumonitis like Pneumocystis carinii or cytomegalovirus (CMV) pneumonia, it is still unknown whether serum KL-6 level is useful as a good marker for the diagnosis or disease activity. In this study, the serum levels of KL-6 and soluble intercellular adhesion molecule 1 (sICAM-1) were evaluated in five patients with malignant lymphoma or adult T-cell leukemia. Serum KL-6 and sICAM-1 levels at the time of diagnosis of P. carinii or CMV pneumonia were 1220±323 U/ml (mean±SD) and 1246±485 ng/ml, respectively. These levels were apparently high, when compared with standard value of serum KL-6 (<520 U/ml) and that of sICAM-1 (115-306 ng/ml). In patients without P. carinii or CMV pneumonia, who had hematological malignancies or AIDS, serum level of KL-6 was not high (299±122 U/ml), but sICAM-1 was high (651±495 ng/ml) because of the elevation of sICAM-1 in four of five cases. These findings suggest that, in patients with hematological malignancies, serum level of KL-6 antigen rather than sICAM-1 may be useful in the evaluation of CMV or P. carinii pneumonia.     

KL-6 as a novel marker for activities of interstitial pneumonia in connective tissue diseases

The objective of this study was to determine the role of serum KL-6 levels as a marker for the activity of interstitial pneumonia in patients with connective tissue diseases. The serum concentrations of KL-6, a glycoprotein produced mainly by pulmonary type II epithelial cells, were measured in 21 patients with connective tissue disease. The activity of interstitial pneumonia was compared with the associated serum KL-6 concentrations. Serum KL-6 concentrations in patients with interstitial pneumonia were significantly higher than those in the controls. Among patients with active interstitial pneumonia, serum KL-6 concentrations following the treatment (after improvement) were significantly lower than the pretreatment values. The extent of the pulmonary fibrosis correlated positively with the serum KL-6 concentrations during the inactive phase of the interstitial pneumonia. These results suggest that sequential measurement of serum KL-6 levels is a new and useful means for the evaluation of interstitial pneumonia in patients with connective tissue diseases. Received: 10 January 2000 / Accepted: 20 March 2000     

Serum level of KL-6 as a marker of interstitial lung disease in patients with juvenile systemic sclerosis

OBJECTIVE: Serum KL-6 has been found to be elevated in diseases characterized by diffuse interstitial lung involvement. The purpose of this study was to evaluate serum KL-6 as a marker of interstitial lung disease (ILD) in patients with juvenile systemic sclerosis (JSS). METHODS: Serum concentrations of KL-6 were measured with an immunoassay in 39 serum samples from 12 children with diffuse cutaneous form of JSS (6 patients with and 6 patients without ILD) and from 20 healthy controls comparable for age. In patients sampled serially, the relationship of KL-6 concentrations with the severity of ILD and its response to treatment were evaluated. RESULTS: Serum concentrations of KL-6 were significantly higher in patients with ILD (1687 +/- 979 IU/ml) than in patients without (345 +/- 95 IU/ml, p < 0.01) and healthy controls (311 +/- 114 IU/ml, p < 0.001). Serum KL-6 concentrations of patients without ILD were not statistically different from those of healthy controls. We found a significant correlation of serum KL-6 concentrations with vital capacity and with diffusing capacity for carbon monoxide (DLCO). Analysis of individual patients showed that serum concentrations of KL-6 were correlated with ILD severity and its response to treatment. CONCLUSION: Measurement of serum KL-6 concentration is a useful noninvasive marker of pulmonary fibrosis in children with JSS. Its advantages over conventional methods of ILD assessment, such as pulmonary function test and high-resolution computerized tomography, are that it is easy to quantify and to measure repeatedly and it does not need children's cooperation.     

Study of Clara cell 16, KL-6, and surfactant protein-D in serum as disease markers in pulmonary sarcoidosis

STUDY OBJECTIVES: To determine the discriminative value of serum Clara cell 16 (CC16), KL-6, and surfactant protein (SP)-D as markers of interstitial lung diseases, and their ability to reflect pulmonary disease severity and prognosis in sarcoidosis. SUBJECTS: Seventy-nine patients with sarcoidosis and 38 control subjects. MEASUREMENTS: Serum CC16, KL-6, and SP-D concentrations at disease presentation were measured. Pulmonary function tests and chest radiographs were analyzed at presentation and 2-year follow-up. RESULTS: All markers co-correlated, and a significant difference was found between CC16, KL-6 (Krebs von den Lungen-6), and SP-D levels in patients with sarcoidosis and control subjects (p < 0.0001). Receiver operating characteristic curve analysis revealed largest area under the curve for KL-6. Significantly higher levels of CC16 and KL-6 were found in patients with parenchymal infiltration (stage II, III) compared to patients without parenchymal infiltration (stage I). In concordance, CC16 and KL-6 levels inversely correlated with diffusion capacity and total lung capacity, and KL-6 also with inspiratory vital capacity. Moreover, higher KL-6 levels were weakly but significantly associated with persistence or progression of parenchymal infiltrates at 2-year follow-up. CONCLUSION: In this study, KL-6 appears to be the best discriminative marker in differentiating patients with sarcoidosis from healthy control subjects; however, as it is not a specific marker for this condition, this quality is unlikely to be useful as a diagnostic tool. Both CC16 and KL-6 may be of value in reflecting disease severity, and KL-6 tends to associate with pulmonary disease outcome.     

Assessment of serum markers KL-6 and SP-D for interstitial pneumonia associated with connective tissue diseases]

There are a lot of difficulties in the estimation of interstitial pneumonia and subsequent pulmonary fibrosis associated with connective tissue diseases. Recently, serum KL-6 (KL-6) and serum surfactant protein D (SP-D) have been reported to be useful to estimate the severity of interstitial pneumonia. We investigated the usefulness of these serum markers comparing to the spirometric parameters in patients with interstitial pneumonia associated with connective tissue diseases. We found significant inverse correlation between KL-6 and spirometric % VC. Furthermore, KL-6 was more significantly inverse-related with %DLco. On the other hand, we found neither correlation between SP-D and %VC, nor between SP-D and %DLco, suggesting SP-D level seems to be not affected by the degree of pulmonary fibrosis itself. These results indicate that KL-6 is useful to estimate the severity of pulmonary fibrosis more precisely than SP-D in patients with interstitial pneumonia associated with connective tissue diseases.     

KL-6 is a long-term disease-activity biomarker for interstitial lung disease associated with polymyositis/dermatomyositis,but is not a short-term disease-activity biomarker

Abstract

Objectives: We aimed to evaluate the usefulness of serum KL-6 for interstitial lung disease (ILD) with polymyositis/dermatomyositis (PM/DM).

Methods: All consecutive and previously untreated adult patients with PM/DM who were admitted to our hospital from 2010 to 2015 were included. The associations between serum KL-6 levels and clinical information were retrospectively analyzed.

Results: Baseline serum KL-6 levels were significantly higher in patients with ILD than in those without (n?=?41 and 15, respectively; p?<?.001). In the 14 patients whose ILD improved within 4 weeks post-treatment, their serum KL-6 levels did not significantly decrease at 2 weeks, 4 weeks, or 3 months post-treatment (p?=?1.00, 1.00, and .83, respectively). Conversely, their serum KL-6 levels significantly decreased at 6, 9, and 12 months post-treatment (p?=?.01 in all comparisons). In the 12 patients whose ILD remained unchanged or deteriorated in 4 weeks post-treatment, only the difference between their serum KL-6 levels at 3 and 12 months was significant (p?=?.003).

Conclusions: The present study validated the serum KL-6 as a diagnostic marker for ILD in PM/DM. However, serum KL-6 is not a short-term disease-activity biomarker for ILD with PM/DM, but it is a long-term disease-activity biomarker.     

特发性肺纤维化患者肺泡灌洗液和血清中Napsin A、KL-6、SP-A、SP-D表达的意义及与肺功能相关性

目的特发性肺纤维化(IPF)是一种不明原因的慢性进行性间质性肺疾病。其发病率、死亡率均较高。但IPF的发病机制至今尚未完全清楚,临床上对此病发生发展的掌握不够,检验指标的敏感性及特异性不高,从而影响诊断及临床判断的准确性。因此寻找IPF发生发展的生物标记物成为近年来较为热门的研究方向。方法挑选2017年3月-2019年3月间在我院就诊并诊断明确的30例IPF患者入组IPF观察组,20例临床症状类似的I期肺结节病患者作为阴性对照组。采用双抗体夹心酶联免疫吸附(ELISA)法检测IPF和I期肺结节病对照组BALF和血清中Napsin A/KL-6/SP-A/SP-D水平,并对患者的肺功能进行检测,评估上述生物标记物与肺纤维化病程进展的相关性。结果IPF组患者的血清/肺泡灌洗液中Napsin A/KL-6/SP-A/SP-D水平均明显高于由I期肺结节病阴性对照组(P<0.05)。灌洗液中Napsin A/KL-6/SP-D含量与肺通气功能呈负相关(P<0.05),而Napsin A/KL-6含量与弥散功能呈现负相关(P<0.05)。血清中Napsin A/KL-6/SP-A/SP-D水平均与肺通气功能呈负相关(P<0.05),Napsin A/KL-6血清含量与肺弥散功能呈明显负相关(P<0.05),与肺泡灌洗液检测结果一致。结论Napsin A/KL-6/SP-A/SP-D在IPF患者灌洗液中的含量亦显著升高。其中血清Napsin A/KL-6水平相关度最高,高水平的血清及灌洗液中Napsin A/KL-6浓度提示IPF病灶进展,且与肺通气功能及弥散指标呈负相关,可作为诊断IPF严重程度判断的指标之一。而SP-A、SP-D也可以作为IPF早期的一种早期预测指标,敏感性特异性差于Napsin A/KL-6,但SP-D对于肺功能下降、肺纤维化早期炎症反应,优于SP-A。     

Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis

OBJECTIVE: To investigate the association between serum levels and clinical signs of lung fibrosis in patients with systemic sclerosis and inflammatory myopathies. METHODS: ELISA tests for a mucin-like glycoprotein KL-6, von Willebrandt factor (vWF), soluble E-selectin (sES) and surfactant protein D (SP-D) were performed in sera of 104 patients with systemic sclerosis, 31 patients with poly/dermatomyositis) and 24 patients with Raynaud's phenomenon as controls. The clinical and laboratory data were evaluated by a simple standard protocol including chest x-ray, lung function tests, echocardiography and, in selected cases, high resolution computer tomography (HRCT). Clinically significant pulmonary fibrosis (PF) defined as a simultaneous presence of radiological sign of pulmonary fibrosis and restrictive impairment. Severe PF was established if HRCT scans showed diffuse interstitial lung disease with low diffusing capacity. End stage PF was determined as severe PF with very low diffusing capacity. RESULTS: Patients with pulmonary fibrosis on chest x-ray showed significantly elevated serum levels of KL-6, SP-D and vWF. Inverse correlation was found between serum levels of KL-6/SP-D and lung function parameters, such as DLCO% and FVC. With regard to HRCT findings, patients with elevated serum level of KL-6 showed significantly more frequently ground glass opacity, diffuse and honeycombing fibrosis than patients with normal level of KL-6. The sensitivity of KL-6 for PF in SSc is increased with the severity of PF (PF on chest x-ray < severe PF < end stage of PF). Lung fibrosis occurred more frequently in patients with simultaneously elevated KL-6 and sES compared to cases with a single positivity of either KL-6 or sES. CONCLUSION: KL-6, SP-D, vWF and ES are good surrogate factors of pulmonary fibrosis but can not replace conventional diagnostic procedures. However, these markers are suitable for the assessment of progression and severity of pulmonary fibrosis in systemic autoimmune disorders once the diagnosis is established.     

Diagnostic usefulness of KL-6 measurements in patients with pulmonary complications after administration of amiodarone

Amiodarone-induced pulmonary toxicity is one of the major complications in patients receiving administration of amiodarone. KL-6 is a useful indicator to evaluate the activity of interstitial pneumonitis. We studied the clinical utility of KL-6 as a marker for amiodarone-induced pulmonary toxicity. We investigated 6 patients in whom chest radiography revealed abnormal consolidations after administration of amiodarone from 1997 to 1999. All patients were male aged 56 to 76 years (mean 66 +/- 7 years). The indications for amiodarone included sustained ventricular tachycardia in 5 patients and atrial fibrillation in one patient with refractory heart failure. The mean left ventricular ejection fraction was 31 +/- 12% (22-52%). KL-6 levels were measured by a sandwich type enzyme immunoassay using a murine monoclonal antibody (KL-6 antibody), and the cutoff level was determined at 520 U/ml. Complications occurred from 17 days to 45 months after treatment with amiodarone. The KL-6 levels were abnormally high (2,100 and 3,000 U/ml) in 2 patients with amiodarone-induced pneumonitis but under the cutoff level in the non-pneumonitis patients. In one patient with amiodarone-induced pneumonitis, the KL-6 level increased from 695 to 2,100 U/ml concurrently with worsening interstitial changes shown by high resolution computed tomography. We conclude that KL-6 has practical uses as a marker for the detection and evaluation of amiodarone-induced pulmonary toxicity.     

Serum KL-6 level is a useful biomarker for evaluating the severity of coronavirus disease 2019

BackgroundCoronavirus disease 2019 (COVID-19) is currently spreading worldwide. This study examined whether serum Krebs von den Lungen-6 (KL-6) level is a useful biomarker for evaluating the severity of COVID-19.MethodsWe retrospectively examined patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center between February 1, 2020, and May 15, 2020. Patients were divided into four categories based on clinical and radiological findings: mild, moderate, severe, and critical. Patients who presented with a mild or moderate illness and patients who started with or worsened to a severe or critical illness were classified as the non-severe and severe groups, respectively. The two groups were compared for patient characteristics, including serum KL-6 levels. Receiver operating characteristic curves were used to define the optimum cut-off value of serum KL-6 level to evaluate COVID-19 severity.ResultsA total of 54 patients were enrolled, including 33 in the non-severe group and 21 in the severe group, of which four died. Compared with those in the non-severe group, more patients in the severe group were significantly older and had comorbidities. Serum KL-6 levels were significantly higher in the severe group than in the non-severe group both at diagnosis (median, 338 U/mL) and at peak levels within one week after diagnosis (median, 781 U/mL) (both p < 0.001). Serum KL-6 value at peak level (371 U/mL) was used as the optimal cut-off to evaluate disease severity (sensitivity, 85.7%; specificity, 96.6%).ConclusionsSerum KL-6 levels were significantly elevated in severe COVID-19 and is useful for evaluating its severity.     

Significance of Serum Vascular Endothelial Growth Factor Level in Patients with Idiopathic Pulmonary Fibrosis

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, which has been implicated in the pathogenesis of fibrotic lung diseases, including idiopathic pulmonary fibrosis (IPF). The aim of this study was to examine the clinical significance of the serum VEGF level for evaluating disease severity and progression. The levels of VEGF in serum were measured in 41 patients with IPF, 14 patients with lung cancer, and 43 healthy volunteers. We measured the serum levels of CRP, LDH, KL-6, SP-D, and the parameters obtained from arterial blood gas analysis and pulmonary function tests. High-resolution computed tomography (HRCT) was performed to determine the extent of the interstitial and the alveolar opacities. The ability of each biomarker to predict disease severity was estimated by measuring the area under the receiver operating characteristic curve (AUC). The VEGF levels of IPF patients with high alveolar–arterial difference of oxygen (AaDO₂) levels were significantly elevated than those with low AaDO₂ levels and those of healthy volunteers. When examined within the IPF group, a significant positive correlation was found between the VEGF levels and the HRCT interstitial score (p = 0.027) and the KL-6 levels (p = 0.037). Among several serum biomarkers, VEGF showed the largest AUC for predicting disease severity as defined by a high AaDO₂ value. There was an inverse correlation between the baseline VEGF level and the monthly change in percent predicted vital capacity. The serum VEGF level may reflect the severity of IPF and offer clinical benefits to predict the disease’s progression.