Association of pre-hospital theophylline use and mortality in chronic obstructive pulmonary disease patients with sepsis.
Although theophylline has been shown to have anti-inflammatory effects, the therapeutic use of theophylline before sepsis is unknown. The aim of our study was to determine the effect of theophylline on COPD patients presenting with sepsis.



This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan's National Health Insurance program. Patients with COPD who were hospitalized for sepsis between 2000 and 2011 were divided into theophylline users and non-users. The primary outcome was 30-day mortality. The secondary outcome was in-hospital death, intensive care unit admission, and need for mechanical ventilation. Cox proportional hazard model and conditional logistic regression were used to calculate the risk between groups.



A propensity score-matched cohort of 51,801 theophylline users and 51,801 non-users was included. Compared with non-users, the 30-day (HR 0.931, 95% CI 0.910-0.953), 180-day (HR 0.930, 95% CI 0.914-0.946), 365-day (HR 0.944, 95% CI 0.929-0.960) and overall mortality (HR 0.965, 95% CI 0.952-0.979) were all significantly lower in theophylline users. Additionally, the theophylline users also had lower risk of in-hospital death (OR 0.895, 95% CI 0.873-0.918) and need for mechanical ventilation (OR 0.972, 95% CI 0.949-0.997).



Theophylline use is associated with a lower risk of sepsis-related mortality in COPD patients. Pre-hospital theophylline use may be protective to COPD patients with sepsis.
Division of Emergency Critical Care Medicine, Department of Emergency Medicine, Brigham and Women's Hospital, USA; Surgical ICU Translational Research (STAR) Center, Brigham and Women's Hospital, Boston, MA, USA; Department of Chest Medicine, Taipei City Hospital, Heping Fuyou Branch, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Harvard Medical School, Boston, MA, USA.
Yu-Ning
YN
Shih
Department of Nephrology, Taipei City Hospital, Heping Fuyou Branch, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Yung-Tai
YT
Chen
Department of Chest Medicine, Taipei City Hospital, Heping Fuyou Branch, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Hsi
H
Chu
School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Medicine, Taipei Veterans General Hospital, Yuanshan Branch, Yilan, Taiwan, ROC.
Chia-Jen
CJ
Shih
School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Shuo-Ming
SM
Ou
Department of Chest Medicine, Taipei City Hospital, Heping Fuyou Branch, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Yen-Tao
YT
Hsu
School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Radiology, Taipei City Hospital, Heping Fuyou Branch, Taipei, Taiwan, ROC.
Ran-Chou
RC
Chen
Department of Anesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Sadeq A
SA
Quraishi
Division of Emergency Critical Care Medicine, Department of Emergency Medicine, Brigham and Women's Hospital, USA; Harvard Medical School, Boston, MA, USA.
Imoigele P
IP
Aisiku
Division of Emergency Critical Care Medicine, Department of Emergency Medicine, Brigham and Women's Hospital, USA; Surgical ICU Translational Research (STAR) Center, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Raghu R
RR
Seethala
Surgical ICU Translational Research (STAR) Center, Brigham and Women's Hospital, Boston, MA, USA; Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Gyorgy
G
Frendl
Division of Emergency Critical Care Medicine, Department of Emergency Medicine, Brigham and Women's Hospital, USA; Surgical ICU Translational Research (STAR) Center, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: phou@bwh.harvard.edu.
Peter C
PC
Hou
D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D017052:Hospital Mortality / Q000639:trends; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D057216:Propensity Score; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D012307:Risk Factors; D018805:Sepsis / Q000150:complications* / Q000401:mortality; D013624:Taiwan / Q000453:epidemiology; D013806:Theophylline / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D001993:Bronchodilator Agents; D013806:Theophylline
COPD; Mortality; Sepsis; Theophylline