Azithromycin Improves Antiviral Defenses in Uncontrolled Asthma, Finds Study

A new research published in The European Respiratory Journal revealed have reported that azithromycin may strengthen the natural antiviral defense of airway while reducing inflammation linked to asthma attacks, offering fresh insight into how the drug helps prevent virus-induced asthma exacerbations.

Viral respiratory infections are the leading cause of asthma flare-ups, often triggering severe symptoms that require additional treatment or hospitalization. Scientists have long known that people with asthma can have weakened antiviral immune responses in the airway lining, but the mechanisms behind azithromycin’s protective effects have remained uncertain.

Thus, this double-blind, placebo-controlled clinical study which involved 40 adults was set to evaluate the effect of azithromycin on epithelial antiviral immunity in patients with uncontrolled asthma. These participants were randomly assigned to receive either azithromycin (500 mg three times a week) or a matching placebo for 12 weeks. Bronchial epithelial cells were collected through bronchoscopy before and after treatment. These cells were then exposed to rhinovirus, the most common cause of the common cold and a frequent trigger of asthma attacks, to evaluate antiviral and inflammatory responses.

Azithromycin significantly enhanced the production of two critical antiviral proteins, interferon-beta (IFN-β) and interferon-lambda (IFN-λ), following rhinovirus infection. When compared with baseline levels, treated patients showed a marked increase in these antiviral immune responses, whereas no meaningful change was observed in the placebo group. The findings suggest that azithromycin helps airway cells mount a stronger defense against viral infections that commonly worsen asthma symptoms.

Also, azithromycin significantly reduced levels of interleukin-33 (IL-33), which is released during airway injury that is known to amplify allergic inflammation and asthma exacerbations. However, concentrations of thymic stromal lymphopoietin (TSLP) remained unchanged after treatment. Although patients receiving azithromycin experienced numerical improvements in clinical outcomes over the 12-week treatment period, these differences were not statistically significant when compared to placebo.

Overall, azithromycin offers benefits beyond its antimicrobial activity by directly modulating immune responses within the airway epithelium. By simultaneously enhancing antiviral interferon production and suppressing IL-33-driven inflammation, the drug may help reduce the likelihood of virus-induced asthma exacerbations. Larger clinical studies will be needed to confirm whether these immune changes translate into greater reductions in asthma attacks and improved long-term disease control.

Source:

Ghanizada, M., Malm Tillgren, S., Menzel, M., Praeger-Jahnsen, L., Said, N. M., Ditlev, S., Sverrild, A., Porsbjerg, C., Uller, L., Lapperre, T., & AZIMUNE Study Group. (2026). Azithromycin enhances epithelial antiviral immunity in uncontrolled asthma: results from the AZIMUNE randomised controlled trial. The European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology, 68(2), 2502441. https://doi.org/10.1183/13993003.02441-2025