Table 2.
Summary of studies of exposure to benzodiazepine (BZD) and benzodiazepine-related drugs (BZRD) and risk of pneumonia included in review
| Study, year, country and data source | Study type | Participants (sample size) | Age (years) | Living arrangement | Confounders adjusted for | Population | Drugs investigated | Exposure definition | Comparison group | Outcome or case definition | Risk of pneumonia |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Cohort studies | |||||||||||
| Taipale et al. [190]*, 2017, Finland, nationwide registers | Cohort | New BZD users (n = 5232), new BZRD users (n = 3269), nonusers (n = 8501) | Mean age 80 | Community-dwelling | 1:1 propensity-score matched, adjusted for other psychotropic drugs | AD | BZDs, BZRDs | BZD or BZRD initiation after AD dg | Non-users | Hospitalization or death due to pneumonia |
BZD: aHR 1.28, 95% CI 1.07–1.54 BZRD: aHR 1.10, 95% CI 0.84–1.44 |
| Maeda et al. [191]*, 2016, Japan, late stage elderly health insurance | Cohort | BZD users (n = 13,015), with non-users (n = 13,015) | ≥65 | Not reported | Propensity-score matching | N/A | Triazolam | BZD initiation ≥ 180 days in a year | Non-users | Pneumonia dg (ICD codes) | aOR 1.40, 95% CI 1.30–1.51 |
| Vozoris et al. [129], 2014, Canada, linked health care databases | Cohort | New BZD users (n = 48,915), non-users (n = 48,915) | >65 | Community-dwelling | 1:1 propensity-score matching | COPD | BZDs | BZD initiation | Non-users | Hospitalization for COPD exacerbation or pneumonia within 30-days of drug initiation | RR 1.09, 95% CI 1.00–1.20 |
| Huybrechts et al. [130], 2011, Canada, linked health care databases | Cohort | New BZD users (n = 4887) and new SGA users (n = 1942) | ≥65 | Nursing homes | Propensity score | N/A | BZDs | BZD or SGA initiation after admission to nursing home | SGA users | Hospitalization for pneumonia within 180-days of drug initiation | RR 0.85, 95% CI 0.56–1.31 |
| Case–control studies | |||||||||||
| Wang et al. [128], 2017, Taiwan, National Health Insurance | Case–control | Cases (n = 4533) pneumonia dg, controls (n = 16,388) no pneumonia dg | Mean age 80 | Not reported | Adjusted for covariates | CKD | BZDs, BZRDs | BZD or BZRD initiation within 1 year prior to pneumonia dg | Non-users | Pneumonia dg with radiographic findings and initiation of antibiotic |
Current BZD: aOR 1.31 95% CI 1.18–1.46 Current BZRD: aOR 1.07, 95% CI 0.80–1.44 |
| Jung et al. [192]*, 2016, USA, Kaiser Permanent integrated health care system | Case–control | Cases (n = 51,029) pneumonia, controls (n = 188,391) no pneumonia | ≥65 | Community-dwelling | Adjusted for covariates | N/A | BZDs, BZRDs | BZD or BZRD initiation prior to pneumonia dg | Non-users | Pneumonia dg (ICD codes) |
BZD: aOR 1.16, 95% CI 1.13–1.20 BZRD: aOR 1.14, 95% CI 1.08–1.20 |
| Chung et al. [127], 2015, Taiwan, National Health Insurance | Case–control | Cases (n = 5171) pneumonia, controls (n = 11,342) with no adverse respiratory event | Mean age > 65 | Not reported | Adjusted for covariates | COPD | BZDs, BZRDs | BZD or BZRD initiation prior to pneumonia dg | Non-users | Pneumonia dg (ICD codes) |
Current BZD: aOR 9.30, 95% CI 6.11–14.1 Current BZRD: aOR 11.3, 95% CI 8.16–15.6) |
| Dublin et al. [74]*, 2011, USA, Group Health electronic health data | Case–control | Cases (n = 1039) CAP, controls (n = 2022) no pneumonia dg | ≥65 | Community-dwelling | Adjusted for covariates | N/A | BZDs | BZD initiation prior to pneumonia dg | Non-users | CAP dg (ICD codes) validated with radiographic finds or hospitalization records | aOR 1.08, 95% CI 0.80–1.47 |
| Hennessy et al. [125], 2007, UK, General Practice Research Database | Case–control | Cases (n = 12,044) pneumonia dg, controls (n = 48,176) no hospitalization for pneumonia | ≥65 | Not reported | Matched 1:4 for general practitioner practice, adjusted for covariates | N/A | BZDs | BZD initiation | Non-users | Hospitalization for pneumonia | aOR 1.55, 95% CI 1.44–1.67 |
AD Alzheimer’s disease, aHR adjusted hazard ratio, aOR adjusted odds ratio, BZD benzodiazepine, BZRD benzodiazepine-related drug, CAP community-acquired pneumonia, CI confidence interval, CKD chronic kidney disease, COPD chronic obstructive pulmonary disorder, dg diagnosis, ICD International Statistical Classification of Diseases and Related Health Problems, N/A not available, RR risk ratio, SGA second-generation antipsychotic
*Article used in Sun et al. systematic review and meta-analysis [126]