title: Risk factors for acute exacerbation of idiopathic pulmonary fibrosis--Extended analysis of pirfenidone trial in Japan.
abstract: BACKGROUND
  Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a lifethreatening event and one of the important endpoints in clinical trials involving IPF. Despite this, there has been little evaluation of the potential risk factors for AE-IPF in clinical trials. We evaluated the risk factors for AE-IPF in a phase III clinical trial of pirfenidone in Japanese IPF patients.
  
  
  METHODS
  The study population comprised 267 patients. The effects of various baseline characteristics as possible risk factors for AE-IPF during the study, as well as those of a ≥10% decline in percent vital capacity (%VC) within 6 months, were evaluated using Cox׳s proportional hazard model. The ≥10% decline in %VC was calculated in two ways: (1) an absolute decline (e.g. from 60% predicted to 50%); and (2) a relative decline (e.g. from 60% predicted to 54%).
  
  
  RESULTS
  Over 52 weeks, 14 patients experienced AE-IPF. Univariate analysis using Cox׳s proportional hazards model showed that both relative and absolute ≥10% decline in %VC within 6 months were significant risk factors for AE-IPF. Stepwise multivariate analysis demonstrated that absolute or relative decline in both %VC and alveolar to arterial oxygen pressure difference (AaDO2) were significant risk factors for AE. The model using absolute decline [Hazard Ration (HR)=7.405, p=0.0007] and baseline AaDO2 (HR=1.063, p=0.0266) had a better fit than the model using relative decline and baseline AaDO2.
  
  
  CONCLUSIONS
  Rapid %VC decline (≥10% within 6 months), and high baseline AaDO2, may be risk factors for AE-IPF.
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwake-cho, Seto, Aichi 489-8642, Japan. Electronic address: konyasu2003@yahoo.co.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kondoh
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwake-cho, Seto, Aichi 489-8642, Japan. Electronic address: taniguchi@tosei.or.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Respiratory Medicine, Tohoku Pharmaceutical University, 1-12-1, Fukumuro, Miyagino-ku, Sendai 983-8512, Japan. Electronic address: ebinam@hosp.tohoku-pharm.ac.jp.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ebina
authors.affiliation: Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyou-ku, Tokyo 113-8603, Japan. Electronic address: azuma_arata@yahoo.co.jp.
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.affiliation: Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1, Tomiokahigashi, Kanazawa-ku, Yokohama 236-0051, Japan. Electronic address: Ogura@kanagawa-junko.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogura
authors.affiliation: Department of Respiratory Medicine, Tenri Hospital, 200, Mishima-cho, Tenri 632-8552, Japan. Electronic address: ytaguchi@tenriyorozu.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Taguchi
authors.affiliation: Center for Preventive Medicine, Saiseikai Kumamoto Hospital, 5-3-1, Tikami, Minami-ku, Kumamoto 861-4193, Japan. Electronic address: suga-taka-0825@rose.odn.ne.jp.
authors.forename: Moritaka
authors.initials: M
authors.lastname: Suga
authors.affiliation: Third Department of Internal Medicine, Sapporo Medical University Hospital, 16-291, Minami-ichijo-nishi, Tyuou-ku, Sapporo 060-8543, Japan. Electronic address: htaka@sapmed.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Respiratory Medicine, Nakata Clinic, 2-2-1, Naikoucho, Chiyodaku, Tokyo 100-0011, Japan. Electronic address: nakata@nakata-clinic.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Department of Medicine, Division of Pulmonary Medicine, Jichi Medical University, 3311-1, Yakushiji, Simono, Tochigi 329-0498, Japan. Electronic address: sugiyuki@jichi.ac.jp.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugiyama
authors.affiliation: Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyou-ku, Tokyo 113-8603, Japan; Department of Respiratory Medicine, Fukujuji Hospital, 3-1-24, Matsuyama, Kiyose, Tokyo 204-8522, Japan. Electronic address: kudous@fukujuji.org.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Department of Respiratory Medicine, Tohoku Pharmaceutical University, 1-12-1, Fukumuro, Miyagino-ku, Sendai 983-8512, Japan; Department of Respiratory Medicine, South Miyagi Medical Center, 38-1, Ohkawara-cho-aza-nishi, Shibata-gun, Miyagi 989-1253, Japan. Electronic address: toshinkw47@gmail.com.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010101:Oxygen Consumption; D016016:Proportional Hazards Models; D011650:Pulmonary Alveoli / Q000378:metabolism; D011728:Pyridones / Q000627:therapeutic use*; D012307:Risk Factors; D014797:Vital Capacity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; C093844:pirfenidone
keywords: Absolute decline in VC; Acute exacerbation; Idiopathic pulmonary fibrosis (IPF); Relative decline in VC; Risk factor