Abstract Objective Rituximab causes B‐cell depletion and hypogammaglobulinemia, increasing risk for infections. This study aims to determine the incidence of chronic rhinosinusitis (CRS) in patients following rituximab therapy. Study Design Retrospective cohort study using chart review of patients prescribed rituximab between January 2019 and January 2025. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Patients with documented rituximab use were included; those with pre‐existing CRS were excluded. Demographic and clinical data—including timing and duration of rituximab therapy, CRS diagnosis, comorbidities (asthma, allergic rhinitis, GERD), and need for sinus surgery—were collected. Descriptive statistics summarized patient characteristics. Group comparisons were performed using t ‐tests, Mann‐Whitney U , and chi‐square tests. Analyses were conducted using SPSS v28. Results Among 17,851 patients prescribed rituximab (median age 64.0 years, M:F ratio 1.1:1), 1105 (6.2%) developed CRS, with an annual incidence of 1.03% (1032 cases per 100,000 person‐years). The median duration of rituximab therapy for those diagnosed with CRS was 5.9 months (IQR, 0.5‐42.6). Most CRS cases occurred after rituximab discontinuation (62.7%, n = 693) compared to during active treatment (37.3%, n = 412). The median delay between rituximab discontinuation and CRS diagnosis was 17.0 months (IQR, 4.3‐41.7). Conclusions This study demonstrates an annual incidence of 1.03% for CRS diagnoses following rituximab. While prior studies report varying CRS incidences in the general population (0.25%‐0.73%), our findings suggest increased risk among rituximab users. Most CRS diagnoses occurred after rituximab discontinuation, emphasizing the need for a comprehensive medication history review during CRS evaluation.
Urinary Leukotriene E4 as a Biomarker of Disease Burden in Aspirin‐Exacerbated Respiratory Disease: A Retrospective Cohort Study
Abstract Objective To examine the impact of immunosuppressive regimens on chronic rhinosinusitis (CRS) development in kidney and liver transplant recipients. Study Design Retrospective cohort study. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Patients who underwent kidney or liver transplantation between November 1, 2021, and November 1, 2022, were included. Patients with documented sinonasal complaints before transplantation were excluded. Diagnoses were based on ICD‐10 codes assigned by board‐certified otolaryngologists, with follow‐up extending through November 2024. Demographic data, relevant comorbidities, CRS diagnoses, and immunosuppressive regimens were collected. Results In total, 1459 transplant recipients (986 kidney, 473 liver) with a mean age of 55.1 years and M:F ratio of 1.5:1 were included. Kidney recipients who received anti‐thymocyte globulin (ATG, Thymoglobulin®) for immunosuppressive induction had a greater risk of CRS compared to those who did not (odds ratio [OR] = 3.0, 95% CI [1.3, 6.9], P = .005). Among liver recipients, patients on cyclosporine, mycophenolate mofetil (MMF), and corticosteroids had a greater risk of CRS compared to those on tacrolimus‐based regimens (OR = 6.0, 95% CI [1.5, 24.1], P = .027). Cyclosporine use was also associated with an increased rate of endoscopic sinus surgery (ESS) compared to tacrolimus (4.2% vs 0.3%, P = .015). Conclusion Tacrolimus‐based regimens are associated with significantly decreased rates of CRS compared to cyclosporine, suggesting that immunosuppressive choice is a modifiable risk factor for sinonasal morbidity in this population.
Incidence and Risk Factors for De Novo Chronic Rhinosinusitis in Kidney and Liver Transplant Recipients
Abstract Objective To estimate the incidence of de novo chronic rhinosinusitis and identify associated risk factors in kidney and liver transplant recipients without pre‐existing sinonasal complaints. Study design Retrospective cohort study. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Records of all patients who underwent kidney or liver transplantation between November 1, 2021, and November 1, 2022 were reviewed. Patients with documented sinonasal complaints prior to transplantation were excluded. Diagnoses were based on ICD‐10 codes assigned by board‐certified otolaryngologists, with follow‐up extending through November 2024. Demographic and clinical variables were collected, and multivariable logistic regression was used to identify predictors of de novo chronic rhinosinusitis. Results Among 1459 transplant recipients (mean age 55.1 years, 59.8% male), the cumulative 2‐year incidence of de novo chronic rhinosinusitis was 2.4% (24/986) in kidney and 2.3% (11/473) in liver transplant recipients ( P = .89). The overall incidence rate was 12.0 cases per 1000 person‐years, exceeding general population estimates. Transplant rejection (OR 3.2, 95% CI 2.5‐3.9, P < .001) and additional organ transplantation (OR 5.0, 95% CI 3.4‐6.5, P = .041) were independently associated with chronic rhinosinusitis development. Conclusion Kidney and liver transplant recipients experience a higher incidence of de novo chronic rhinosinusitis compared to the general population. Transplant rejection and additional organ transplantation significantly increase this risk. Early recognition and management of chronic rhinosinusitis in this population may support improved postoperative outcomes.
Assessing Recurrent Acute Rhinosinusitis Development in Posttransplant Patients: A Study on Sinus Surgery Necessity
Abstract Objective Recurrent acute rhinosinusitis (RARS) significantly decreases quality of life. Transplant recipients (TR) are particularly vulnerable to rhinologic conditions. There is a lack of guidelines for managing RARS in this population. Our study aims to determine the prevalence of and risk factors for RARS among TR and assess the need for sinus surgery within this group. Study Design Retrospective cohort. Setting Mayo Clinic between 2017 and 2022. Methods A total of 1116 patients met the inclusion criteria and were divided based on the presence or absence of a new incident RARS diagnosis during the posttransplant period and frequency of sinus surgery. Logistic regression (LR) analysis was performed to identify the odds ratio. Results In total, 111/1116 (9.95%) had RARS. Patients with RARS had an increased history of asthma, viral infection, and rheumatoid arthritis (RA) ( P = .003) in the pretransplant period. According to the LR analysis, patients with neutropenia, RA, and mantle cell lymphoma were 1.91, 2.71, and 4.02 times more likely to develop RARS (95% CI: 1.19‐3.05, P = .01), (95% CI: 0.90‐8.14, P = .07), and (95% CI: 1.16‐13.89, P = .02) during the posttransplant period, respectively. In those that developed RARS, only 5.5% failed medical therapy and required surgery. Conclusion This is the first cohort to investigate the incidence of RARS in TR and the predictive factors associated with its development posttransplant. We found that patients with pretransplant comorbidities such as RA, viral infections, hematologic deficiencies, and malignancies were at an increased risk for developing RARS, though this is not linked to an increased necessity for sinus surgery.
Beyond the Impact of Cadaveric Donor Transplant on Chronic Rhinosinusitis and Recalcitrant Disease
AbstractObjectiveThis study aimed to evaluate the impact of endoscopic sinus surgery (ESS) on asthma severity up to 12 months after surgical intervention.Study DesignRetrospective cohort.SettingTertiary care center.MethodsPatients with a history of asthma and Chronic Rhinosinusitis (CRS) who underwent ESS between 2013 and 2023 were included. Asthma severity was assessed according to current Global Initiative for Asthma (GINA) guidelines, classifying patients into mild, moderate, and severe based on medication requirements. Asthma severity was evaluated up to 3 months prior to ESS and 1‐year post‐ESS. Patients with aspirin‐exacerbated respiratory disease (AERD) were excluded. Statistical analysis was performed using McNemar test and Wilcoxon signed‐rank test to assess differences in asthma severity, medication doses, and number of medications.ResultsSixty‐five patients were included, of which 44 (67.7%) had CRS with nasal polyps (CRSwNP) and 21 (32.3%) had CRS without nasal polyps (CRSsNP). No significant differences were found in asthma severity pre‐ and post‐ESS (P = .175). Similarly, no differences were found in ICS doses (P = .999), total number of prescribed medications (P = .157) or presence of exacerbations before and after ESS (P = .078). However, a significant increase in time from last rescue inhaler use was noted after ESS, increasing from a median of 6.71 to 23.1 weeks (P = .004).ConclusionThis study is the first to assess the impact of ESS on asthma severity in a real‐world setting. Our findings suggest that ESS does not impact asthma severity classification. However, it might provide relief of asthma symptoms in the early postoperative period.
Relationship Between Alcohol Intolerance and Aspirin‐Exacerbated Respiratory Disease (AERD): Systematic Review
AbstractObjectivePrevious studies have suggested that patients with aspirin‐exacerbated respiratory disease (AERD) have a high likelihood of alcohol intolerance. The purpose of this systematic review is to identify if there is sufficient evidence to confirm this correlation and the impact of medical therapy on subsequent alcohol tolerance.Data SourcesPubMed, EMBASE, SCOPUS, EBSCO, Google Scholar, Cochrane Library, and Grey literature. We also performed snowballing on the identified observational studies (OS) for additional data.Review MethodsA systematic review was conducted from 1968 to 2022 to identify those studies describing AERD symptomatology triggered by alcohol intake. The primary outcome was to analyze the current literature for the association between alcohol intolerance and AERD symptoms. The secondary outcome looked for improvement in alcohol tolerance after aspirin desensitization or biological therapy.ResultsA total of 775 studies were identified and 40 abstracts were evaluated. From these, 5 studies met the inclusion criteria. Of the 5 manuscripts, there was 1 case‐control, 2 cohort, and 2 cross‐sectional studies. A total of 522 participants with AERD and a history of alcohol consumption were included, with 52.8% reporting at least 1 sinopulmonary exacerbation after alcohol intake. One of 3 studies noted improvement in alcohol tolerance after medical therapy with aspirin desensitization.ConclusionThe current literature suggests that patients with AERD have a high risk of alcohol intolerance. Additionally, aspirin desensitization may improve alcohol tolerance in this patient population.
Risk Factors for Recalcitrant Chronic Rhinosinusitis in Organ Transplant Recipients
AbstractObjectiveStudies suggest that transplant patients are at risk for chronic rhinosinusitis (CRS). However, there is limited information in the literature regarding frequency and reasons for failure of adequate medical therapy. We aim to determine the risk factors associated with the development of medically recalcitrant CRS requiring endoscopic sinus surgery (ESS).Study DesignRetrospective cohort.SettingMayo Clinic.MethodsThis is a retrospective chart review of 925 transplant recipients seen at Mayo Clinic between 2017 and 2022. Inclusion criteria: (1) a rhinologic consultation after transplant and (2) clinical diagnosis of CRS. A total of 549 patients met the inclusion criteria and were divided based on the need for ESS versus successful treatment with medical therapy. Univariate and logistic regression analyses were performed to identify risk factors and predictive variables related to failure of medical therapy.ResultsOf the 549 patients, 201/549 (37%) had medically recalcitrant disease requiring ESS, while 348/549 (63%) were successfully treated with medical therapy Based on logistic regression, patients with recurrent acute rhinosinusitis in the pretransplant period were 8.68 more likely to have a recalcitrant disease (95% confidence interval, 3.72‐20.28, p < 0.0001). Some of the largest determinants of medical therapy failure in the posttransplant period were CRS with nasal polyps, odontogenic CRS, and noninvasive fungal sinusitis. The presence of neutropenia, aplastic anemia, and living transplant were also associated with medically recalcitrant CRS requiring ESS.ConclusionOur predictive model identifies with high accuracy the patients who may be at risk of developing recalcitrant CRS in the organ transplant population.