Inhaled corticosteroids, which are typically used to treat common respiratory diseases such as chronic obstructive pulmonary disease (COPD), are associated with increased bacterial infections and can lead to worse health outcomes, a study in mice has found.
Most exacerbations experienced by patients with asthma and COPD are caused by viral infections. Although the use of inhaled corticosteroids (ICS) helps to reduce the frequency of these exacerbations in the short term, their long-term use has been linked to an increased risk of pneumonia.
Because the mechanisms behind this association are not fully understood, researchers at Imperial College London in the U.K. and the University of Newcastle in Australia aimed to identify how corticosteroid use correlates to an increased incidence of pneumonia and worse health outcomes in COPD patients.
Their findings were published in the study, “Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations,” in the journal Nature Communications.
Researchers used mice treated with a commonly used corticosteroid, fluticasone propionate (FP), to assess how they reacted to viral infections.
FP use was found to suppress the antiviral immune responses of mice, leading to a delay in virus clearance. It also enhanced the production of airway mucus in viral-infected mice, and impaired the antibacterial responses of the animals, resulting in an increased pulmonary bacterial load during virus-induced exacerbations.
These findings were also confirmed using samples from COPD patients.
Researchers also identified the immune-signaling molecules involved in FP’s effects on the immune response, namely by inhibiting interferon-beta. This is important because this information can potentially be used to devlop new treatments that will not cause the same negative effects as FP.
“Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect,” the researchers wrote.
The team concluded that inhaled corticosteroid use during viral infection-induced exacerbations in COPD patients can, in fact, suppress antimicrobial immunity while increasing mucus production and lung bacterial load.
“We’ve now identified mechanisms by which steroids interfere with the response to infection enabling us to now focus our research on developing treatments that promote airway immune responses to counteract the negative effects of steroids and improve overall benefit to the patient,” Nathan Bartlett, PhD, the study’s author, said in a press release.
Bartlett is an associate professor at the University of Newcastle School of Biomedical Sciences and Pharmacy and head of the HMRI Viral Immunology and Respiratory Disease Group.
“If we can minimize the severity of the exacerbations whilst protecting against the occurrence of secondary infections and pneumonia that cause further permanent damage to the lungs then we will improve the quality of life for people living with COPD,” he said.
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