Efficacy of concurrent treatments in idiopathic pulmonary fibrosis patients with a rapid progression of respiratory failure: an analysis of a national administrative database in Japan.
BACKGROUND
Some IPF patients show a rapid progression of respiratory failure. Most patients are treated with high-dose corticosteroids. However, no large clinical studies have investigated the prognosis or efficacy of combined treatments including high-dose corticosteroids in IPF patients with a rapid progression of respiratory failure.


METHODS
We enrolled IPF patients who received mechanical ventilation and high-dose corticosteroids between April 2010 and March 2013. Records were extracted from a Japanese nationwide inpatient database. We conducted a retrospective epidemiologic and prognostic analysis.


RESULTS
Two hundred nine patients receiving an average of 12.8 days of ventilatory support were enrolled. There were 138 (66 %) fatal cases; the median survival was 21 days. The short-term (within 30 days) and long-term (within 90 days) survival rates were 44.6 and 24.6 %, respectively. The average monthly admission rate among the IPF patients with the rapid progression of respiratory failure in the winter was significantly higher than that in spring (p = 0.018). Survival did not differ to a statistically significant extent in the different geographic areas of Japan. Survivors were significantly younger (p = 0.002) with higher rates of mild dyspnea on admission (p = 0.012), they more frequently underwent bronchoscopy (p < 0.001), and received anticoagulants (p = 0.027), co-trimoxazole (p < 0.001) and macrolide (p = 0.02) more frequently than non-survivors. A multivariate logistic analysis demonstrated that two factors were significantly associated with a poor prognosis: >80 years of age (OR = 2.94, 95 % Cl 1.044-8.303; p = 0.041) and the intravenous administration of high-dose cyclophosphamide (OR = 3.17, 95 % Cl 1.101-9.148; p = 0.033). Undergoing bronchoscopy during intubation (OR = 0.25, 95 % Cl 0.079-0.798; p = 0.019) and the administration of co-trimoxazole (OR = 0.28, 95 % Cl 0.132-0.607; p = 0.001) and macrolides (OR = 0.37, 95 % Cl 0.155-0.867; p = 0.033) were significantly associated with a good prognosis. The dosage of co-trimoxazole significantly correlated with survival.


CONCLUSIONS
Co-trimoxazole and macrolides may be a good addition to high-dose corticosteroids in the treatment of IPF patients with a rapid progression of respiratory failure.
Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
Keishi
K
Oda
Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan. yatera@med.uoeh-u.ac.jp.
Kazuhiro
K
Yatera
Department of Preventive Medicine and Community Health, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
Yoshihisa
Y
Fujino
Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.|Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Hiroshi
H
Ishimoto
Miyazaki Prefectural Nursing University, 3-5-1 Manabino, Miyazaki city, Miyazaki, 880-0929, Japan.
Hiroyuki
H
Nakao
Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
Tetsuya
T
Hanaka
Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
Takaaki
T
Ogoshi
Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
Takashi
T
Kido
Department of Health Care Informatics, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8510, Japan.
Kiyohide
K
Fushimi
Department of Preventive Medicine and Community Health, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
Shinya
S
Matsuda
Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.|Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Hiroshi
H
Mukae
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D001999:Bronchoscopy; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000150:complications*; D007362:Intensive Care Units; D007564:Japan; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D018942:Macrolides / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage*
D000305:Adrenal Cortex Hormones; D018942:Macrolides; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
Acute exacerbation of idiopathic pulmonary fibrosis; Acute respiratory failure; Co-trimoxazole; Corticosteroid; Macrolide; Mechanical ventilation; Nationwide database