title: Risk factors for an acute exacerbation of idiopathic pulmonary fibrosis.
abstract: Acute exacerbations of idiopathic pulmonary fibrosis are major causes of morbidity and mortality among patients with idiopathic pulmonary fibrosis. However, acute exacerbations remain unpredictable. The aim of this study was to investigate risk factors for acute exacerbations of idiopathic pulmonary fibrosis.
  
  
  
  We performed a retrospective cohort study of patients with idiopathic pulmonary fibrosis who visited our institutions from January 1999 to September 2014. We investigated risk factors for acute exacerbations in patients with idiopathic pulmonary fibrosis diagnosed retrospectively based on the official 2011 idiopathic pulmonary fibrosis ATS/ERS/JRS/ALAT Update Statement.
  
  
  
  The idiopathic pulmonary fibrosis study cohort included 65 subjects. The median follow-up period was 2.6 years. During follow-up, 24 patients (36.9 %) experienced acute exacerbations. A Kaplan-Meier curve demonstrated that the 1-year, 2-year, and 3-year incidences of acute exacerbation were 9.6, 19.2 and 31.0 %, respectively. Acute exacerbation exerted a significant impact on overall survival among those with the disease. A log-rank test showed that baseline cardiovascular diseases, higher GAP (gender, age, physiology) stage (≥II), higher serum lactate dehydrogenase level (≥180 U/L), higher serum surfactant protein-D level (≥194.7 ng/mL), higher neutrophil (≥1.77 %) and eosinophil (≥3.21 %) percentages in bronchoalveolar lavage fluid samples, and treatment with an immunosuppressive agent after diagnosis were associated with poor acute exacerbation-free probability. In the Cox analysis adjusted for treatment with an immunosuppressive agent, baseline cardiovascular diseases, higher GAP stage (≥II), and higher eosinophil percentage (≥3.21 %) in bronchoalveolar lavage fluid samples were predictors of an acute exacerbation of idiopathic pulmonary fibrosis.
  
  
  
  This study demonstrated that baseline cardiovascular diseases, higher GAP stage (≥II), and higher eosinophil percentage (≥3.21 %) in bronchoalveolar lavage fluid samples were associated with the onset of an acute exacerbation of idiopathic pulmonary fibrosis.
authors.affiliation: Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. kakugawa@nagasaki-u.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kakugawa
authors.affiliation: Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Noriho
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Clinical Research Center, Nagasaki University Hospital, Nagasaki, Japan.|Division of Biostatistics, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yura
authors.affiliation: Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hara
authors.affiliation: Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishimoto
authors.affiliation: Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.affiliation: Department of Cardiopulmonary Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishimatsu
authors.affiliation: Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Obase
authors.affiliation: Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
authors.affiliation: Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015897:Comorbidity; D018450:Disease Progression; D004804:Eosinophils; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000401:mortality; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011657:Pulmonary Eosinophilia / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents
keywords: Bronchoalveolar lavage; Cardiovascular disease; GAP (gender, age, Physiology) stage; Krebs von den Lungen-6; Lactate dehydrogenase; Surfactant protein-D