CATIE News

12 February 2019 

Prescribed opioids associated with increased risk of pneumonia

  • U.S. researchers found that opioid use increased the risk of pneumonia
  • Opioids may increase susceptibility by weakening the immune response to infection
  • The risk was two to three times higher among HIV-positive people using opioids

Opioids are prescribed for relief of severe pain among people with and without HIV infection. However, over the past decade, accumulating research suggests that the use of prescribed opioids has been linked to an increased risk of infections, particularly bacterial pneumonia that requires hospitalization.

Opioids may play a role in increasing susceptibility to bacterial infections in the following ways:

  • weakening the immune response to bacterial infections
  • reducing the body’s ability to cough and rid itself of germs in the lungs
  • reducing the body’s ability to produce mucus that helps protect the lungs

Researchers in the United States recently completed a large observational study comparing health-related information from more than 4,000 people who required hospitalization for pneumonia and more than 25,000 other people who did not require hospitalization for pneumonia. They found that people who had developed pneumonia were more likely to have had the following:

  • past and current prescription opioids
  • had been prescribed, on average, higher doses of opioids
  • had been prescribed a group of opioids that researchers described as immunosuppressive

Also, people who were HIV positive were more likely to develop pneumonia when prescribed opioids than HIV-negative people.

The researchers urged doctors and nurses to bear in mind the study’s results when prescribing opioids.

Study details

Researchers at Veterans’ Administration hospitals and clinics at several centres in the U.S. analysed health-related information collected from the year 2000 to the end of 2012. They compared data from 4,246 people who had been hospitalized for pneumonia and 25,392 people who did not get pneumonia. They focused on the use of opioids 12 months prior to the episode of pneumonia or at the time pneumonia was diagnosed.

Researchers classified opioids as follows:

  • immunosuppressive – codeine, dihydrocodeine, fentanyl, morphine
  • non-immunosuppressive – hydrocodone, hydromorphone, oxycodone, tramadol
  • unknown immunological effects – levorphanol, meperidine, methadone, pentazocine, propoxyphene, tapentadol

Key findings

Overall, taking into account many factors, researchers found statistical links between the use of opioids (immunosuppressive or not) and an increased risk for pneumonia. That is, the use of opioids generally increased the risk of developing pneumonia.

When researchers examined the use of immunosuppressive opioids in particular (vs. no opioids), the risk of pneumonia was even higher.

Dosage matters

When researchers assessed the use of opioids by dose, they found the following relationships:

  • currently using high-dose immunosuppressive opioids – a three-fold increased risk of pneumonia
  • currently using high-dose non-immunosuppressive or unknown immunosuppressive opioids – a two-fold increased risk of pneumonia

HIV infection

Researchers found that, in general, HIV-positive people had a two-to three-fold increased risk for developing pneumonia when using opioids compared to HIV-negative people who used opioids.

Bear in mind

In the present study, researchers found what they called a “strong, independent association between prescribed opioids and the risk of [pneumonia]-related hospitalization.” This risk was present in people regardless of HIV infection status, but the risk was greater for HIV-positive people.

Among people currently using opioids, the risk of pneumonia was heightened if higher doses of opioids were used.

According to the researchers, HIV-positive people had an increased risk for pneumonia at lower doses of opioids, “particularly with immunosuppressive opioids.”

Adjusting for possible sources of bias

Observational studies can sometimes draw conclusions that have inadvertently been skewed by hidden sources of bias. To reduce this possibility, the researchers took the following factors into account: diagnoses of opioid addiction, excess intake of alcohol, tobacco smoking and the use of other immunosuppressive drugs such as corticosteroids and transplant medicines. After doing so, they still found a link between the use of prescribed opioids and an increased risk for pneumonia. Due to the rigour applied to the data analysis, the study’s findings are highly suggestive and important.

What to do?

The study provides important information about the potential harm associated with the medical use of opioids. The researchers stated that healthcare practitioners should be aware of the risk of pneumonia when prescribing opioids. As there are times when prescribing opioids is medically necessary, the researchers stated that “care should be implemented to address other factors known to modify [pneumonia] risk”—including smoking cessation and vaccination against bacterial pneumonia.

—Sean R. Hosein

REFERENCES:

  1. 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 Internal Medicine. 2019; in press.
  2. Wiese AD, Griffin MR, Schaffner W, et al. Opioid analgesic use and risk for invasive pneumococcal diseases. Annals of Internal Medicine. 2018 Sep 4;169(5):355.
  3. Plein LM, Rittner HL. Opioids and the immune system - friend or foe. British Journal of Pharmacology. 2018 Jul;175(14):2717-2725.

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