Use of opioids or benzodiazepines and risk of pneumonia in older adults: a population-based case-control study

Abstract

Objectives: To examine whether use of opioids or benzodiazepines is associated with risk of community-acquired pneumonia in older adults.

Design: Population-based case-control study.

Setting: An integrated healthcare delivery system.

Participants: Community-dwelling, immunocompetent adults aged 65 to 94 from 2000 to 2003. Presumptive pneumonia cases were identified from health plan automated data and validated through medical record review. Two controls were selected for each case with pneumonia, matched on age, sex, and calendar year.

Measurements: Information about opioid and benzodiazepine use came from computerized pharmacy data. Information on covariates including comorbid illnesses and functional and cognitive status came from medical record review and electronic health data.

Results: One thousand thirty-nine validated cases of pneumonia and 2,022 matched controls were identified. One hundred forty-four (13.9%) cases and 161 (8.0%) controls used prescription opioids (adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08-1.76 vs nonuse). Risk was highest for opioids categorized as immunosuppressive based on immunological studies (OR = 1.88, 95% CI = 1.26-1.79 vs nonuse), whereas for nonimmunosuppressive opioids the OR was 1.23 (95% CI = 0.89-1.69). Risk was highest in the first 14 days of use (OR = 3.24, 95% CI = 1.64-6.39 vs nonuse). For long-acting opioids, the OR was 3.43 (95% CI = 1.44-8.21) versus nonuse, whereas for short-acting opioids, it was 1.27 (95% CI = 0.98-1.64). No greater risk was seen for current benzodiazepine use compared to nonuse (OR = 1.08, 95% CI = 0.80-1.47).

Conclusion: Use of opioids but not benzodiazepines was associated with pneumonia risk. The differences in risk seen for different opioid regimens warrant further study.

Figure 1

Selection of cases and controls for inclusion in the study. For this study, we extended the time period during which eligibility was assessed by obtaining additional administrative and pharmacy data to identify exclusion criterion after September 1 of each study year. This process led to the exclusion of an additional 86 cases and 213 controls from the original study. Many of these (61 cases and 17 controls) were people who developed an exclusion criterion during follow-up (after September 1 of their study year). Some additional people were excluded because they were found to have used an immunosuppressive medication during baseline (23 cases, 29 controls) or because the case was discovered to have been hospital-acquired (2 cases and their 4 matched controls). The other 163 controls were dropped because their matched cases had been excluded due to one of the above criteria.

Figure 2

Figure 2A: Risk estimates for the association between current opioid use and risk of pneumonia, stratified by characteristics of exposure. *Adjusted for matching variables (age, sex, index date), comorbidities, and functional and cognitive status measures. Referent group is non-users. †Current use was defined as receiving ≥ 1 opioid prescription in the 5–60 days prior to index date. ‡According to human and animal studies.^– Figure 2B: Risk estimates for the association between current benzodiazepine use and risk of pneumonia, stratified by characteristics of exposure. *Adjusted for matching variables (age, sex, index date), comorbidities, and functional and cognitive status measures. Referent group is non-users. †Current use was defined as receiving ≥ 1 benzodiazepine prescription in the 5–60 days prior to index date. ‡Total standardized doses.

Figure 2

Figure 2A: Risk estimates for the association between current opioid use and risk of pneumonia, stratified by characteristics of exposure. *Adjusted for matching variables (age, sex, index date), comorbidities, and functional and cognitive status measures. Referent group is non-users. †Current use was defined as receiving ≥ 1 opioid prescription in the 5–60 days prior to index date. ‡According to human and animal studies.^– Figure 2B: Risk estimates for the association between current benzodiazepine use and risk of pneumonia, stratified by characteristics of exposure. *Adjusted for matching variables (age, sex, index date), comorbidities, and functional and cognitive status measures. Referent group is non-users. †Current use was defined as receiving ≥ 1 benzodiazepine prescription in the 5–60 days prior to index date. ‡Total standardized doses.