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Role of serum surfactant protein-D as a prognostic predictor in fibrotic hypersensitivity pneumonitis
Institution:1. Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan;2. Department of Pulmonary Immunotherapeutics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan;3. Internal Medicine, Kudanzaka Hospital, 1-6-12 Kudan-minami, Chiyoda-ku, Tokyo, 102-0074, Japan;1. Department of Pediatrics, Tokai University School of Medicine, Japan;2. Department of Pediatrics, Tokai University Hachioji Hospital, Japan;3. Department of Respiratory Medicine, Tokai University Hachioji Hospital, Japan;1. Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan;2. Department of Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;1. Department of Pulmonary Medicine, Thoracic Center, St. Luke''s International Hospital, St. Luke''s International University, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan;2. Graduate School of Public Health, St. Luke''s International University, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan;3. Department of Social Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan;1. Department of Respiratory Medicine, Okayama City Hospital, 3-20-1, Kitanagaseomote-cho, Kita-Ku, Okayama, 700-8557, Japan;2. Department of Cardiovascular Medicine, Okayama City Hospital, 3-20-1, Kitanagaseomote-cho, Kita-Ku, Okayama, 700-8557, Japan;3. Department of Radiology, Okayama City Hospital, 3-20-1, Kitanagaseomote-cho, Kita-Ku, Okayama, 700-8557, Japan;1. Department of Medicine, ABVIMS and Dr. Ram Manohar Lohia Hospital, Baba Kharak Singh Marg, New Delhi, 110001, India;2. Department of Respiratory Medicine, ABVIMS and Dr. Ram Manohar Lohia Hospital, Baba Kharak Singh Marg, New Delhi, 110001, India;3. Department of Radiology, ABVIMS and Dr. Ram Manohar Lohia Hospital, Baba Kharak Singh Marg, New Delhi, 110001, India
Abstract:BackgroundSerum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) are candidate diagnostic and activity markers for fibrotic hypersensitivity pneumonitis (HP), although their correlation with prognosis remains unclear. We aimed to evaluate the prognostic usefulness of serum KL-6 and SP-D in patients with fibrotic HP.MethodsThis was a retrospective medical record review of 185 patients with fibrotic HP at a single center from 2005 to 2019. The baseline and minimum serum KL-6 and SP-D levels over two years were recorded. The contribution of KL-6 and SP-D levels to the incidence of progressive fibrosing interstitial lung disease (PF-ILD) and mortality were evaluated using multivariate analysis.ResultsThe respective baseline and minimum levels were 1441 and 808 U/ml for KL-6 and 254 and 132 ng/mL for SP-D. A high minimum SP-D level was significantly associated with a high incidence of PF-ILD by logistic regression, independent of baseline forced vital capacity and honeycombing. Similarly, a high minimum SP-D level was significantly associated with high mortality by Cox proportional hazard model analysis. The stratified minimum SP-D levels of <100, 100–200, and >200 revealed significantly distinct groups in the entire cohort, with PF-ILD incidence rates of 28%, 48%, and 74% and median survival times of 120, 74, and 45 months, respectively.ConclusionsHigh minimum SP-D levels over two years were correlated with an unfavorable prognosis in our cohort. Patient with consistently high SP-D levels during the clinical course may have a poor prognosis and be a candidate for early treatment intensification.
Keywords:Fibrotic hypersensitivity pneumonitis  Krebs von den Lungen-6 (KL-6)  Surfactant protein-D (SP-D)  Progressive fibrosing interstitial lung disease (PF-ILD)  Biomarker  KL-6"}  {"#name":"keyword"  "$":{"id":"kwrd0040"}  "$$":[{"#name":"text"  "_":"Krebs von den lungen-6  SP-D"}  {"#name":"keyword"  "$":{"id":"kwrd0050"}  "$$":[{"#name":"text"  "_":"Surfactant protein D  HP"}  {"#name":"keyword"  "$":{"id":"kwrd0060"}  "$$":[{"#name":"text"  "_":"Hypersensitivity pneumonitis  PF-ILD"}  {"#name":"keyword"  "$":{"id":"kwrd0070"}  "$$":[{"#name":"text"  "_":"Progressive fibrosing interstitial lung disease  IPF"}  {"#name":"keyword"  "$":{"id":"kwrd0080"}  "$$":[{"#name":"text"  "_":"Idiopathic pulmonary fibrosis  NSIP"}  {"#name":"keyword"  "$":{"id":"kwrd0090"}  "$$":[{"#name":"text"  "_":"Nonspecific interstitial pneumonia  HRCT"}  {"#name":"keyword"  "$":{"id":"kwrd0100"}  "$$":[{"#name":"text"  "_":"High-resolution computed tomography  GGA"}  {"#name":"keyword"  "$":{"id":"kwrd0110"}  "$$":[{"#name":"text"  "_":"Ground-glass attenuation  UIP"}  {"#name":"keyword"  "$":{"id":"kwrd0120"}  "$$":[{"#name":"text"  "_":"Usual interstitial pneumonia  BAL"}  {"#name":"keyword"  "$":{"id":"kwrd0130"}  "$$":[{"#name":"text"  "_":"Bronchoalveolar lavage  CI"}  {"#name":"keyword"  "$":{"id":"kwrd0140"}  "$$":[{"#name":"text"  "_":"Confidence interval  DLco"}  {"#name":"keyword"  "$":{"id":"kwrd0150"}  "$$":[{"#name":"text"  "_":"Diffusion capacity of lung for carbon monoxide  FEV1"}  {"#name":"keyword"  "$":{"id":"kwrd0160"}  "$$":[{"#name":"text"  "_":"Forced expiratory volume in 1 s  FVC"}  {"#name":"keyword"  "$":{"id":"kwrd0170"}  "$$":[{"#name":"text"  "_":"Forced vital capacity  HR"}  {"#name":"keyword"  "$":{"id":"kwrd0180"}  "$$":[{"#name":"text"  "_":"Hazard ratio  OR"}  {"#name":"keyword"  "$":{"id":"kwrd0190"}  "$$":[{"#name":"text"  "_":"Odds ratio  weighted κ statistic
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