Serum Krebs von den Lungen-6 as a potential biomarker for distinguishing combined pulmonary fibrosis and emphysema from chronic obstructive pulmonary disease: A retrospective study
Aiyuan Zhou,
Xiyan Zhang,
Rongli Lu,
Wenzhong Peng,
Yanan Wang,
Haiyun Tang,
Pinhua Pan
Affiliations
Aiyuan Zhou
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, 410008, China; Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China
Xiyan Zhang
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, 410008, China; Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China
Rongli Lu
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, 410008, China; Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China
Wenzhong Peng
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, 410008, China; Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China
Yanan Wang
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, 410008, China; Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China
Haiyun Tang
Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Corresponding author.
Pinhua Pan
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, 410008, China; Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China; Corresponding author. Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Background: The presence of fibrotic interstitial lung disease (ILD) is relatively common in patients with emphysema. This has been designated combined pulmonary fibrosis and emphysema (CPFE). CPFE had worse prognosis than emphysema alone. Krebs von den Lungen-6 (KL-6) levels as a biomarker of alveolar type 2 epithelial cell injury, which is widely used to identify the presence of ILD, whether it can differentiate CPFE from COPD remains unknown. Methods: 259 patients from Xiangya Hospital with diagnosis of COPD, with or without ILD, and who had KL-6 tests were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. Results: Among 259 patients, 52 patients were diagnosed with CPFE. The mean age was 67.39 ± 8.14 yeas. CPFE patients had higher ratio of rheumatic diseases (21.2 % vs 7.2 %, P = 0.003). CPFE patients exhibited higher values of FEV1 (1.97 vs 1.57, P = 0.002) and FEV1/FVC ratio (69.46 vs 57.64, P < 0.001) compared to COPD patients. CPFE patients had higher eosinophil counts, percentage of eosinophils, lactate dehydrogenase, total bilirubin levels and lower platelet counts. Serum KL-6 levels were higher in CPFE group compared to COPD group (574.95 vs 339.30 U/mL, P < 0.001). Multiple logistic regression showed that KL-6 level was an independent predictive factor for the presence of ILD among COPD patients. The AUC of serum KL-6 levels to differentiate CPFE was 0.711, with 95 % CI being 0.635 to 0.787. The cutoff point of KL-6 level was 550.95 U/mL with 57.7 % sensitivity and 79.7 % specificity for the discrimination of CPFE from COPD. Conclusion: CPFE patients show higher KL-6 levels compared to isolated COPD, suggesting the potential of KL-6 as a practical screening tool for interstitial lung disease, specifically CPFE. A KL-6 threshold of 550.95 U/mL in COPD patients may indicate a high need for high-resolution chest computed tomography to detect fibrosis.
