Edelman EJ, Gordon KS, Crothers K, et al. Association of Prescribed Opioids With Increased Risk of Community-Acquired Pneumonia Among Patients With and Without HIV. JAMA Intern Med. 2019 Jan 7. pii: 2720137. doi: 10.1001/jamainternmed.2018.6101. (Original study)

Importance: Some opioids are known immunosuppressants; however, the association of prescribed opioids with clinically relevant immune-related outcomes is understudied, especially among people living with HIV.

Objective: To assess the association of prescribed opioids with community-acquired pneumonia (CAP) by opioid properties and HIV status.

Design, Setting, and Participants: This nested case-control study used data from patients in the Veterans Aging Cohort Study (VACS) from January 1, 2000, through December 31, 2012. Participants in VACS included patients living with and without HIV who received care in Veterans Health Administration (VA) medical centers across the United States. Patients with CAP requiring hospitalization (n = 4246) were matched 1:5 with control individuals without CAP (n = 21?146) by age, sex, race/ethnicity, length of observation, and HIV status. Data were analyzed from March 15, 2017, through August 8, 2018.

Exposures: Prescribed opioid exposure during the 12 months before the index date was characterized by a composite variable based on timing (none, past, or current); low (<20 mg), medium (20-50 mg), or high (>50 mg) median morphine equivalent daily dose; and opioid immunosuppressive properties (yes vs unknown or no).

Main Outcome and Measure: CAP requiring hospitalization based on VA and Centers for Medicare & Medicaid data.

Results: Among the 25 392 VACS participants (98.9% male; mean [SD] age, 55 [10] years), current medium doses of opioids with unknown or no immunosuppressive properties (adjusted odds ratio [AOR], 1.35; 95% CI, 1.13-1.62) and immunosuppressive properties (AOR, 2.07; 95% CI, 1.50-2.86) and current high doses of opioids with unknown or no immunosuppressive properties (AOR, 2.07; 95% CI, 1.50-2.86) and immunosuppressive properties (AOR, 3.18; 95% CI, 2.44-4.14) were associated with the greatest CAP risk compared with no prescribed opioids or any past prescribed opioid with no immunosuppressive (AOR, 1.24; 95% CI, 1.09-1.40) and immunosuppressive properties (AOR, 1.42; 95% CI, 1.21-1.67), especially with current receipt of immunosuppressive opioids. In stratified analyses, CAP risk was consistently greater among people living with HIV with current prescribed opioids, especially when prescribed immunosuppressive opioids (eg, AORs for current immunosuppressive opioids with medium dose, 1.76 [95% CI, 1.20-2.57] vs 2.33 [95% CI, 1.60-3.40]).

Conclusions and Relevance: Prescribed opioids, especially higher-dose and immunosuppressive opioids, are associated with increased CAP risk among persons with and without HIV.

Discipline Area Score
Physician 6 / 7
Nurse 5 / 7
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Comments from MORE raters

Nurse rater

This excellent article highlights the complications that could be overlooked in the management of complex cases.

Nurse rater

This reviewer is not able to accept a causal relationship between opioid use and community acquired pneumonia. There may be confounding variables not accounted for. Interesting but more studies needed.

Physician rater

This is a very well conducted study to highlight the risk of prescription opioids in the height of the opioid epidemic. This large, nested case control study shows an increasing risk of Community Acquired Pneumonia with increasing dose and immunosuppressive properties of prescribed opioids. This risk adds to the conversation with patients on pain management with opioids.

Physician rater

I'm not certain that the confounding variables could be controlled. The opioid users without HIV had increase current use of alcohol, smoking, benzo's, corticosteroids, "other drug related", and oral and inhaled corticosteroids. The HIV group had lower CD4 counts. It is not rocket science that one group would be at increased for pneumonia.

Physician rater

This is a comprehensive nested case control study of prescriptions of opiates and development of CAP requiring hospitalisation in veterans with and without HIV. The comorbidity of the total population is quite impressive. It demonstrated a dose response curve with higher doses of opiates and those with more risk of immunosuppression as well as timing of prescription closer to diagnosis of pneumonia, with greater impact on those with HIV. It fails to account for increased likelihood of hospitalisation for those with pneumonia and HIV as well as the likelihood of greater functional loss (and thus greater chance of hospitalisation) of those prescribed opioids in moderate to high doses. Further, it characterices opioids according to immunosuppressive effects when there does not appear to be an established mechanism of action or clear clinically relevant effects.

Physician rater

This is an interesting approach with a high novelty degree, a large sample, and significant result.
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