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Association of Prescribed Opioids With Increased Risk of Community-Acquired Pneumonia Among Patients With and Without HIV

E. Jennifer Edelman, MD, MHS1,2; Kirsha S. Gordon, PhD1,3; Kristina Crothers, MD4; et alKathleen Akgün, MD1,3; Kendall J. Bryant, PhD5; William C. Becker, MD1,3; Julie R. Gaither, PhD1; Cynthia L.
Gibert, MD6,7; Adam J. Gordon, MD8,9; Brandon D. L. Marshall, PhD10; Maria C. Rodriguez- Barradas, MD11; Jeffrey H. Samet, MD12,13; Amy C. Justice, MD1,2,3; Janet P. Tate, ScD1,3; David A. Fiellin, MD1,2 Author Affiliations JAMA Intern Med. Published online January 7, 2019. doi:10.1001/jamainternmed.2018.6101

Question What is the association between prescribed opioids and communityacquired pneumonia requiring hospitalization among patients living with and without HIV?

Findings In this nested case-control study of 4246 cases and 21 146 controls (25 392 participants), prescribed opioids were independently associated with community-acquired pneumonia in patients living with and without HIV. In addition, the risk for community-acquired pneumonia increased with higher opioid doses and opioids with known immunosuppressive properties.

Meaning These findings suggest that prescribed opioids independently contribute to communityacquired pneumonia risk among patients living with and without HIV; efforts to minimize prescribed opioid use, as well as to minimize use of higher doses and immunosuppressive opioids, may help mitigate this risk.

Abstract
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.

Zusammenfassung:
Im April wurde in Infomed eine Studie veröffentlicht https://annals.org/aim/articleabstract/ 2672601/opioid-analgesic-use-risk-invasive-pneumococcal-diseases-nested-case-control  in der sich ein positiver Zusammenhang zwischen Opioiden und Pneumokokkeninfekten gezeigt hatte.
Jetzt erfolgte eine neue Fall-Kontroll-Studie, wo man das auch bestätigt hat, und zwar wies man nach, dass Personen, die ausserhalb des KH an einer Pneumonie erkrankt waren, signifikant häufiger ein Opioid eingenommen hatten als diejenigen der Kontrollgruppe. Das Risiko einer Pneumonie stieg mit der eingenommenen Opioiddosis; ausserdem war es höher bei Opioiden, denen immunsupprimierende Eigenschaften zugeschrieben werden (z.B. Morphin, Fentanyl, Codein), bzw. bei Personen mit einer HIV-Erkrankung, solange sie unter einer Opioidbehandlung standen.

Fazit:

Wir haben kaum HIV-Patienten. Wir haben aber viele immunsupprimierte
Tumorpatienten. Für diese könnte die erhöhte Pneumonierate bei gleichzeitiger Gabe von Opioiden gelten.
Wir haben aber viele Patienten mit chronischen Schmerzen und Opioiden – die sind dann ja auch gefährdet, eine Pneumonie zu entwickeln.

Fazit Regen:

Auch wenn es diese Schwierigkeiten bei hohen Opioid-Dosen gibt, werden wir immer die Schmerzreduktion im Vordergrund sehen.