title: Association between benzodiazepine use and exacerbations and mortality in patients with asthma: a matched case-control and survival analysis using the United Kingdom Clinical Practice Research Datalink.
abstract: OBJECTIVE
  To investigate the association between the gamma-aminobutyric acid (GABA)ergic drugs, benzodiazepines or zopiclone and the occurrence of asthma exacerbations and subsequent mortality in a cohort of asthma patients.
  
  
  METHODS
  The number of patients that were included were 105,747 for those without asthma exacerbation and 25,895 for those with exacerbated asthma. A nested case-control study probed the association between benzodiazepines or zopiclone and occurrence of asthma exacerbation (primary outcome) using conditional logistic regression. Cox regression was used to determine the association between the drugs and all-cause mortality in patients with recorded asthma exacerbation. Adjusted matched odds ratios (adj mOR) and adjusted hazard ratios (adj HR) with 95% confidence intervals (CI) are presented.
  
  
  RESULTS
  Current benzodiazepine use was associated with increased occurrence of asthma exacerbation (adj mOR 1.49; 95%CI [1.15, 1.93]; P = 0.001) as was current zopiclone use (adj mOR 1.59; 95%CI [1.37, 1.85]; P < 0.001). In patients with an asthma exacerbation, current benzodiazepine use was associated with increased all-cause mortality during a median follow-up of 2 years (adj HR 2.78; 95%CI [1.26, 6.12]; P = 0.011), and the association between zopiclone use and all-cause mortality showed borderline statistical significance (adj HR 1.58; 95%CI [0.98, 2.54]; P = 0.058).
  
  
  CONCLUSIONS
  Benzodiazepines and zopiclone may increase the likelihood of asthma exacerbation, and benzodiazepines may also increase the likelihood of mortality following exacerbation. These data suggest that caution should be exercised when prescribing benzodiazepines to patients with asthma.
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
authors.forename: Georgina
authors.initials: G
authors.lastname: Nakafero
authors.affiliation: Department of Anesthesiology, University of Wisconsin, Madison, WI, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sanders
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Nguyen-Van-Tam
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
authors.forename: Puja R
authors.initials: PR
authors.lastname: Myles
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents / Q000009:adverse effects*; D001249:Asthma / Q000175:diagnosis / Q000401:mortality*; D053961:Azabicyclo Compounds / Q000009:adverse effects; D001569:Benzodiazepines / Q000009:adverse effects*; D016022:Case-Control Studies; D002423:Cause of Death; D015897:Comorbidity; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D017891:Pharmacoepidemiology; D010879:Piperazines / Q000009:adverse effects; D019338:Polypharmacy; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; D001569:Benzodiazepines
keywords: asthma exacerbation; benzodiazepines; mortality; pharmacoepidemiology; zopiclone