Biomaterial Database

Diagnostic and prognostic biomarkers for progressive fibrosing interstitial lung disease. 2023

Mayuko Watase, and Takao Mochimaru, and Honomi Kawase, and Hiroyuki Shinohara, and Shinobu Sagawa, and Toshiki Ikeda, and Shota Yagi, and Hiroyuki Yamamura, and Emiko Matsuyama, and Masanori Kaji, and Momoko Kurihara, and Midori Sato, and Kohei Horiuchi, and Risa Watanabe, and Shigenari Nukaga, and Kaoru Irisa, and Ryosuke Satomi, and Yoshitaka Oyamada

Department of Respiratory Medicine, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

No biomarkers have been identified in bronchoalveolar lavage fluid (BALF) for predicting fibrosis progression or prognosis in progressive fibrosing interstitial lung disease (PF-ILD). We investigated BALF biomarkers for PF-ILD diagnosis and prognosis assessment. Overall, 120 patients with interstitial pneumonia who could be diagnosed with PF-ILD or non PF-ILD were enrolled in this retrospective study. PF-ILD was diagnosed according to Cottin's definition. All patients underwent bronchoscopy and BALF collection. We evaluated blood and BALF parameters, high-resolution computed tomography (HRCT) patterns, and spirometry data to identify factors influencing PF-ILD diagnosis and prognosis. On univariate logistic analysis, age, sex, the BALF white blood cell fraction (neutrophil, lymphocyte, eosinophil, and neutrophil-to-lymphocyte ratio), BALF flow cytometric analysis (CD8), and an idiopathic pulmonary fibrosis/usual interstitial pneumonia pattern on HRCT were correlated with PF-ILD diagnosis. Multivariate logistic regression analysis revealed that sex (male), age (cut-off 62 years, area under the curve [AUC] 0.67; sensitivity 0.80; specificity 0.47), white blood cell fraction in BALF (NLR, neutrophil, and lymphocyte), and CD8 in BALF (cut-off 34.2; AUC 0.66; sensitivity, 0.74; specificity, 0.62) were independent diagnostic predictors for PF-ILD. In BALF, the NLR (cut-off 8.70, AUC 0.62; sensitivity 0.62; specificity 0.70), neutrophil count (cut-off 3.0, AUC 0.59; sensitivity 0.57; specificity 0.63), and lymphocyte count (cut-off 42.0, AUC 0.63; sensitivity 0.77; specificity 0.53) were independent diagnostic predictors. In PF-ILD patients (n = 77), lactate dehydrogenase (cut-off 275, AUC 0.69; sensitivity 0.57; specificity 0.78), Krebs von den Lungen-6 (cut-off 1,140, AUC 0.74; sensitivity 0.71; specificity 0.76), baseline forced vital capacity (FVC) (cut-off 1.75 L, AUC 0.71; sensitivity, 0.93; specificity, 0.46), and BALF neutrophil ratio (cut-off 6.0, AUC 0.72; sensitivity 0.79; specificity 0.80) correlated with death within 3 years. The BALF cellular ratio, particularly the neutrophil ratio, correlated with the diagnosis and prognosis of PF-ILD. These findings may be useful in the management of patients with interstitial pneumonia.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D011379	Prognosis	A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.	Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012189	Retrospective Studies	Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.	Retrospective Study,Studies, Retrospective,Study, Retrospective
D014797	Vital Capacity	The volume of air that is exhaled by a maximal expiration following a maximal inspiration.	Forced Vital Capacity,Capacities, Forced Vital,Capacities, Vital,Capacity, Forced Vital,Capacity, Vital,Forced Vital Capacities,Vital Capacities,Vital Capacities, Forced,Vital Capacity, Forced
D015415	Biomarkers	Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc.	Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D017563	Lung Diseases, Interstitial	A diverse group of lung diseases that affect the lung parenchyma. They are characterized by an initial inflammation of PULMONARY ALVEOLI that extends to the interstitium and beyond leading to diffuse PULMONARY FIBROSIS. Interstitial lung diseases are classified by their etiology (known or unknown causes), and radiological-pathological features.	Diffuse Parenchymal Lung Disease,Diffuse Parenchymal Lung Diseases,Interstitial Lung Disease,Interstitial Lung Diseases,Pneumonia, Interstitial,Pneumonitis, Interstitial,Interstitial Pneumonia,Interstitial Pneumonias,Interstitial Pneumonitides,Interstitial Pneumonitis,Lung Disease, Interstitial,Pneumonias, Interstitial,Pneumonitides, Interstitial
D054990	Idiopathic Pulmonary Fibrosis	A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change.	Cryptogenic Fibrosing Alveolitis,Familial Idiopathic Pulmonary Fibrosis,Fibrocystic Pulmonary Dysplasia,Fibrosing Alveolitis, Cryptogenic,Idiopathic Fibrosing Alveolitis, Chronic Form,Idiopathic Pulmonary Fibrosis, Familial,Interstitial Pneumonitis, Usual,Pulmonary Fibrosis, Idiopathic,Usual Interstitial Pneumonia,Cryptogenic Fibrosing Alveolitides,Dysplasia, Fibrocystic Pulmonary,Fibrocystic Pulmonary Dysplasias,Fibrosing Alveolitides, Cryptogenic,Idiopathic Pulmonary Fibroses,Interstitial Pneumonia, Usual,Pneumonitides, Usual Interstitial,Pneumonitis, Usual Interstitial,Pulmonary Dysplasia, Fibrocystic,Pulmonary Fibroses, Idiopathic,Usual Interstitial Pneumonias,Usual Interstitial Pneumonitides,Usual Interstitial Pneumonitis
D018450	Disease Progression	The worsening and general progression of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.	Clinical Course,Clinical Progression,Disease Exacerbation,Exacerbation, Disease,Progression, Clinical,Progression, Disease