Standardized Definition, Smarter Treatment Approaches Needed for Acute Chronic Rhinosinusitis Exacerbations

A review in Current Allergy and Asthma Reports highlights how acute exacerbations of chronic rhinosinusitis (AECRS) remain poorly defined, inconsistently diagnosed, and often overtreated with antibiotics and systemic corticosteroids despite limited supporting evidence.1

The authors of the review detail a new phase of AECRS research and treatment—one that requires consensus definitions, better diagnostic criteria, and clearer guidance on when to observe and when to intervene. With CRS already associated with high healthcare utilization, improving AECRS management could improve clinical management, advance research, and prevent unnecessary medication use.

The findings underscore the importance of more selective prescribing, culture-guided therapy, and further investigation into alternatives such as bacteriophage therapy. | Image credit: brizmaker - stock.adobe.com

CRS affects millions of adults and produces symptoms such as nasal congestion, facial pressure, rhinorrhea, and impaired smell. While CRS itself is persistent and inflammatory, many patients experience intermittent “flare-ups” marked by several days of intensified symptoms. Historically, these flares have been labeled AECRS, but the term lacked a formal definition until recently. As a result, clinical trials, observational studies, and routine practice have all used varying criteria, most commonly patient-reported symptom worsening or escalation of treatment.

The review emphasizes that the absence of a uniform definition has limited the reliability of AECRS research and complicated efforts to measure treatment effects. For example, while many studies classify an exacerbation based on the prescription of antibiotics or systemic corticosteroids (SCS), new data show that medication records capture only a fraction of true episodes. A 2025 study cited in the review found that although patients reported an average of 4.2 AECRS episodes over 6 months, they received antibiotics or steroids only 1.6 times during that period—meaning two-thirds of exacerbations were never documented through rescue medications. This discrepancy exposes a blind spot in both clinical research and clinical care.

A recently accepted regulatory definition, which was used in the REOPEN trials, offers a clearer framework, defining AECRS as acute worsening of 1 or more cardinal CRS symptoms lasting at least 3 days, accompanied by an escalation of care such as antibiotics, SCS, or an unscheduled medical visit.2 The authors noted that while this definition marks progress, it still relies heavily on treatment-based triggers and does not fully capture cases where patients choose observation or self-management instead of contacting a clinician.1

The review also synthesized emerging research on AECRS pathophysiology, suggesting that exacerbations likely involve a complex interplay of viral triggers, bacterial overgrowth, shifts in the sinonasal microbiome, and immune dysregulation. Several studies have documented elevated inflammatory markers, such as IL-5, IL-6, VEGF, and eosinophil major basic protein, during exacerbations, while microbiome analyses frequently reveal increased prevalence of pathogens like Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus species. Viral infections also appear to play a meaningful role; some studies have detected rhinovirus or influenza-related epithelial changes during exacerbations, and seasonal patterns show higher AECRS frequency in winter.

“It appears that both viruses and bacteria play a role in the development of AECRS,” wrote the researchers. “Viral infections may create a persistent hyper-responsiveness and inflammatory state to the sinonasal mucosa and microbiome via increased expression of deleterious cellular adhesion molecules and/or immuno-epithelial defense disruption, which then leads to an increased susceptibility to bacterial infections that ultimately are responsible for patients’ acute worsening of symptoms.”

The review also highlighted the substantial disease burden associated with AECRS. Each exacerbation often leads to missed workdays, urgent clinic visits, emergency department visits, and repeat nasal endoscopies. Overreliance on antibiotics and steroids not only increases costs but exposes patients to serious risks, including infection, venous thromboembolism, fractures, and antimicrobial resistance. Despite this, many clinicians prescribe these medications reflexively due to the lack of clear guidelines and the demands of symptom relief.

Evidence for antibiotic benefit in AECRS is limited. One double-blind trial found no meaningful difference in symptoms or quality of life between patients treated with amoxicillin–clavulanate and those receiving placebo, when both groups also used intranasal steroids and saline rinses. Meanwhile, bacteriologic studies show high rates of antibiotic resistance, with nearly half of AECRS isolates showing some resistance and many producing β-lactamase.

The findings underscore the importance of more selective prescribing, culture-guided therapy, and further investigation into alternatives such as bacteriophage therapy.

References

1. Frederick RM, Lam K, Han JK. Acute exacerbations of chronic rhinosinusitis. Curr Allergy Asthma Rep. Published online December 20, 2025. doi:10.1007/s11882-025-01239-0

2. Palmerrr JN, Adappa ND, Chandra RK, et al. Efficacy of EDS-FLU for chronic rhinosinusitis: two randomized controlled trials (ReOpen1 and ReOpen2). 2024;12(4):1049-1061. doi:10.1016/j.jaip.2023.12.016