Highlights
In a nationwide Korean study of adults with chronic rhinosinusitis with nasal polyps (CRSwNP), higher oral corticosteroid exposure was associated with more systemic adverse events.
Exposure burden mattered more than prescription count alone: annual duration greater than 90 days and cumulative prednisolone-equivalent dose of at least 1.0 g per year carried the clearest signal of harm.
The strongest associations involved musculoskeletal and infection-related outcomes, especially avascular bone necrosis, osteoporosis, and pneumonia.
These findings reinforce the clinical rationale for steroid-sparing long-term strategies in CRSwNP, including optimized topical therapy, surgery when appropriate, and biologic treatment in selected patients.
Background
CRSwNP is a chronic inflammatory disorder of the sinonasal mucosa characterized by bilateral polyp formation, nasal obstruction, anosmia or hyposmia, rhinorrhea, facial pressure, and substantial impairment in quality of life. The disease often reflects type 2 inflammation, particularly in Western populations, although inflammatory patterns vary geographically. For many patients, the illness is recurrent, difficult to control, and closely linked to comorbid asthma, aspirin-exacerbated respiratory disease, sleep disturbance, and repeated health care use.
Oral corticosteroids remain one of the fastest ways to suppress polyp-related inflammation and improve symptoms, especially smell loss and nasal blockage. In routine practice, short courses are often used for flares, perioperative disease control, or as rescue treatment when intranasal corticosteroids are insufficient. Yet the same anti-inflammatory potency that makes systemic steroids effective also creates concern. Even intermittent oral corticosteroid exposure has been associated in other diseases with metabolic, cardiovascular, infectious, ocular, and skeletal complications. The unanswered clinical question has been how much this matters specifically in CRSwNP, where patients may receive repeated bursts over many years.
That question is increasingly important because treatment options have expanded. Endoscopic sinus surgery and biologics targeting type 2 inflammation offer alternatives for selected patients, but access, cost, and practice patterns differ across settings. In this context, understanding the real-world safety burden of oral corticosteroids is essential for balancing short-term symptom relief against cumulative systemic risk.
Study Design and Methods
Design and data source
Moon and colleagues conducted a retrospective, nationwide nested case-control study using the Korean Health Insurance Review and Assessment Service database from 2010 through 2023. This database captures claims-level information from a large, nationally representative insured population, making it well suited for studying relatively uncommon adverse outcomes and cumulative medication exposure at scale.
Population
The investigators identified adults aged 20 years or older with incident CRSwNP who had been prescribed at least one oral corticosteroid. To reduce confounding from pre-existing illnesses that themselves may require corticosteroids or predispose to study outcomes, patients with prior immune-mediated diseases or prior diagnoses of the adverse event outcomes were excluded.
Patients who developed a systemic adverse event served as case patients. Each case was matched 1:10 with controls on age, sex, and diagnosis date. The matched cohort included 523,316 patients: 51,647 case patients and 472,369 controls. The mean approximated age at the midpoint was 47.1 years, and 39.7% were women.
Exposure assessment
Oral corticosteroid exposure was operationalized in three complementary ways, all clinically relevant because they distinguish treatment intensity from total burden:
First, exposure intensity by annual duration: low at 30 days or fewer, moderate at 31 to 90 days, and high at more than 90 days per year.
Second, cumulative dose by annual prednisolone-equivalent exposure: less than 0.5 g, 0.5 to 1.0 g, and at least 1.0 g per year.
Third, prescription frequency. This allowed the authors to test whether repeated prescribing events independently predicted adverse outcomes after accounting for duration and dose.
Outcomes and analysis
The primary outcome was the first occurrence of systemic adverse events. Adjusted odds ratios with 95% confidence intervals were estimated using multivariable conditional logistic regression. While the abstract does not list every covariate in the regression model, the matching strategy and multivariable adjustment are important strengths in a large administrative dataset study.
Key Findings
Overall signal: cumulative burden, not simply number of prescriptions, predicted harm
The central message is straightforward: more oral corticosteroid exposure was associated with more systemic adverse events in adults with CRSwNP. The most consistent associations were seen with longer annual duration and higher cumulative annual dose. By contrast, prescription frequency alone was not independently associated with adverse event risk. Clinically, this suggests that counting steroid bursts is less informative than estimating the actual total days of exposure and cumulative prednisolone-equivalent dose.
High annual duration was associated with important complications
Patients with high exposure intensity, defined as more than 90 days of oral corticosteroid use per year, had significantly increased risks of avascular bone necrosis, osteoporosis, and pneumonia. This pattern is biologically plausible. Longer systemic steroid exposure accelerates bone resorption, suppresses osteoblast function, impairs host immune responses, and increases vulnerability to infection. The clustering of skeletal and infection-related complications is therefore unsurprising, but it is clinically meaningful because these are not trivial outcomes: osteoporotic injury can lead to long-term disability, avascular necrosis may require orthopedic intervention, and pneumonia can trigger hospitalization.
Higher annual cumulative dose increased overall adverse event risk
An annual cumulative prednisolone-equivalent dose greater than 1.0 g was associated with a 23% higher overall adverse event risk compared with lower exposure categories, with an adjusted odds ratio of 1.23 and a 95% confidence interval of 1.11 to 1.36. This is a modest relative increase, but in a common chronic disease treated repeatedly across large populations, even moderate relative risk elevations can translate into substantial absolute harm.
At this higher annual dose threshold, specific adverse outcomes included avascular bone necrosis, pneumonia, dyslipidemia, heart failure, hypertension, and type 2 diabetes. This constellation is notable because it spans several organ systems and aligns with the known physiology of glucocorticoid excess. Steroids can worsen insulin resistance, raise blood pressure, alter lipoprotein metabolism, promote sodium retention, and aggravate fluid balance, all of which can contribute to cardiometabolic disease expression in susceptible individuals.
Why the prescription count result matters
Prescription frequency not being independently associated with risk may appear counterintuitive at first. However, it likely means that multiple short, low-dose courses are not equivalent to prolonged or higher-dose exposure once cumulative burden is taken into account. A patient receiving several brief rescue prescriptions in a year may have lower net exposure than someone on a few extended courses. For clinicians, this finding supports a more nuanced medication history: asking how many times a patient received steroids is less useful than documenting the total number of days and estimating prednisolone-equivalent grams over time.
Clinical Interpretation
What this changes in practice
For otolaryngologists, allergists, pulmonologists, and primary care clinicians who co-manage CRSwNP, the study sharpens a familiar concern into a more actionable message. Oral corticosteroids remain effective for short-term symptom rescue, but longer annual exposure and higher cumulative yearly dose appear to carry measurable systemic risk. This means steroid courses should be framed as limited interventions rather than default maintenance tools.
Several practical implications follow. First, every course should have a clearly defined indication, dose, and stop date. Second, clinicians should document cumulative annual exposure, not only whether steroids were prescribed. Third, repeated need for systemic steroids should trigger reassessment of disease control and treatment strategy rather than simple repetition of the same approach.
Steroid-sparing strategies become more compelling
The findings strongly support steroid-sparing management for patients with recurrent or difficult-to-control CRSwNP. In clinical practice, this includes meticulous optimization of intranasal corticosteroid delivery, saline irrigations, adherence support, management of comorbid asthma or aspirin-exacerbated respiratory disease, and appropriate use of endoscopic sinus surgery when topical access or disease burden justifies it.
For selected patients with persistent severe disease, biologic therapy may reduce reliance on systemic steroids. Current international guidance, including EPOS 2020 and subsequent type 2 inflammation–focused recommendations, recognizes biologics as an option in patients with uncontrolled CRSwNP despite surgery and/or standard medical therapy, particularly when systemic corticosteroids are repeatedly required. Although this study did not evaluate biologics directly, its safety findings strengthen the case for considering them when oral corticosteroid dependence emerges.
Monitoring high-risk patients
Patients approaching or exceeding the exposure thresholds highlighted in this study merit closer surveillance. Bone health assessment, infection risk review, blood pressure monitoring, glucose evaluation, and lipid assessment are reasonable, especially in patients with other risk factors. Counseling should also be explicit: many patients think of sinus steroid tablets as benign because they are intermittent, but repeated exposure can accumulate meaningfully over a year.
Strengths of the Study
The first major strength is scale. Nationwide claims data provided a very large CRSwNP cohort, enabling assessment of multiple adverse outcomes that would be difficult to study in smaller datasets.
The second is the nested case-control design, which is efficient for rare or delayed adverse events and allows more refined exposure assessment before the event.
The third is the multidimensional exposure framework. By separating annual duration, cumulative dose, and prescription frequency, the investigators generated clinically useful information rather than a single crude exposure variable.
Finally, the focus on incident CRSwNP and exclusion of patients with prior immune-mediated disease or outcome diagnoses improved interpretability by reducing some of the background noise that complicates pharmacoepidemiologic analyses.
Limitations and Cautions
As with any retrospective observational study using claims data, causation cannot be established. Residual confounding is possible. Patients with more severe CRSwNP are likely to receive more oral corticosteroids, and disease severity itself may correlate with health care contact, comorbidity burden, or vulnerability to some outcomes.
Claims data also do not guarantee medication ingestion. Prescription records estimate exposure but cannot confirm adherence. Similarly, diagnostic coding may misclassify both CRSwNP and some adverse events, although large administrative studies generally accept this tradeoff to gain statistical power and population representativeness.
The abstract does not detail all covariates included in the adjusted models, so readers will want to review the full article for the handling of confounders such as asthma, chronic obstructive pulmonary disease, obesity, smoking proxies, socioeconomic factors, and concomitant inhaled or injected corticosteroid exposure.
Generalizability also deserves consideration. Treatment patterns, thresholds for prescribing oral corticosteroids, and prevalence of endoscopic sinus surgery or biologic use vary by country. The Korean population and practice environment may not map perfectly onto other health systems. Even so, the fundamental biology of glucocorticoid toxicity is universal, making the directional message highly relevant.
How These Results Fit With Existing Evidence
The study is consistent with a broader body of literature showing that systemic corticosteroid burden is associated with cardiometabolic, skeletal, and infectious complications across chronic inflammatory diseases. In asthma, for example, repeated oral corticosteroid exposure has long been linked with diabetes, osteoporosis, cataracts, and infection risk, prompting a shift toward steroid-sparing treatment pathways. CRSwNP has lagged somewhat behind in generating similarly robust safety data, despite common reliance on oral steroids. This report helps close that evidence gap.
It also complements current guideline thinking. The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 emphasizes oral corticosteroids as short-term treatments with recognized systemic risks, not indefinite management tools. The present study adds large-scale real-world evidence quantifying the price of higher annual exposure in CRSwNP specifically.
Implications for Policy and Research
From a policy perspective, these findings support quality metrics that capture cumulative oral corticosteroid exposure in chronic airway diseases, including CRSwNP. Many systems track prescriptions, but fewer track annual prednisolone-equivalent burden in a way that is visible at the point of care. Incorporating cumulative exposure dashboards into electronic prescribing systems could help clinicians recognize when a patient is crossing a threshold that should prompt escalation or treatment redesign.
Future research should clarify dose-response relationships in even finer detail, explore whether risks differ by age, sex, asthma comorbidity, or surgery status, and assess the comparative effectiveness of steroid-sparing pathways. Pragmatic studies comparing repeated oral steroid rescue with earlier biologic initiation or earlier surgical intervention would be particularly valuable. It will also be important to estimate absolute risk increases and number-needed-to-harm figures, which are often more intuitive for shared decision-making than odds ratios alone.
Conclusion
This nationwide nested case-control study by Moon and colleagues provides strong real-world evidence that in adults with CRSwNP, greater oral corticosteroid exposure is associated with greater systemic harm. The clearest risk signals emerged with annual duration exceeding 90 days and cumulative prednisolone-equivalent dose above 1.0 g per year, particularly for avascular bone necrosis, osteoporosis, pneumonia, and several cardiometabolic outcomes. Prescription frequency alone was less informative than total duration and dose.
For practice, the message is clear: oral corticosteroids should remain rescue tools, not quiet maintenance therapy by accumulation. Repeated need for systemic steroids should prompt clinicians to reassess control, optimize local therapy, consider surgery or biologics where appropriate, and monitor for emerging toxicity. In CRSwNP, steroid-sparing management is not only a matter of symptom control; it is increasingly a matter of long-term safety.
Funding and Trial Registration
The abstract does not report funding information or a ClinicalTrials.gov registration number. As a retrospective database study, trial registration may not have been applicable.
References
1. Moon S, Lee M, Jung I, Rha MS. Oral Corticosteroids and Adverse Events in Chronic Rhinosinusitis With Nasal Polyps. JAMA Otolaryngology–Head & Neck Surgery. Published online June 4, 2026. PMID: 42241008. https://pubmed.ncbi.nlm.nih.gov/42241008/
2. Fokkens WJ, Lund VJ, Hopkins C, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020;58(Suppl S29):1-464. PMID: 32077450.
3. Han JK, Bachert C, Fokkens W, et al. Biological therapies in chronic rhinosinusitis with nasal polyps. Expert opinion and evolving guideline perspectives support steroid-sparing approaches in severe type 2 disease. Readers should consult current specialty guidance for local recommendations.
