Research Priorities in Pediatric Asthma Morbidity: Addressing the Impacts of Systemic Racism on Children with Asthma in the United States. An Official American Thoracic Society Workshop Report.

Background: In the United States, Black and Latino children with asthma are more likely than White children with asthma to require emergency department visits or hospitalizations because of an asthma exacerbation. Although many cite patient-level socioeconomic status and access to health care as primary drivers of disparities, there is an emerging focus on a major root cause of disparities-systemic racism. Current conceptual models of asthma disparities depict the historical and current effects of systemic racism as the foundation for unequal exposures to social determinants of health, environmental exposures, epigenetic factors, and differential healthcare access and quality. These ultimately lead to biologic changes over the life course resulting in asthma morbidity and mortality. Methods: At the 2022 American Thoracic Society International Conference, a diverse panel of experts was assembled to identify gaps and opportunities to address systemic racism in childhood asthma research. Panelists found that to examine and address the impacts of systemic racism on children with asthma, researchers and medical systems that support biomedical research will need to 1) address the current gaps in our understanding of how to conceptualize and characterize the impacts of systemic racism on child health, 2) design research studies that leverage diverse disciplines and engage the communities affected by systemic racism in identifying and designing studies to evaluate interventions that address the racialized system that contributes to disparities in asthma health outcomes, and 3) address funding mechanisms and institutional research practices that will be needed to promote antiracism practices in research and its dissemination. Results: A thorough literature review and expert opinion discussion demonstrated that there are few studies in childhood asthma that identify systemic racism as a root cause of many of the disparities seen in children with asthma. Community engagement and participation in research studies is essential to design interventions to address the racialized system in which patients and families live. Dissemination and implementation studies with an equity lens will provide the multilevel evaluations required to understand the impacts of interventions to address systemic racism and the downstream impacts. To address the impacts of systemic racism and childhood asthma, there needs to be increased training for research teams, funding for studies addressing research that evaluates the impacts of racism, funding for diverse and multidisciplinary research teams including community members, and institutional and financial support of advocating for policy changes based on study findings. Conclusions: Innovative study design, new tools to identify the impacts of systemic racism, community engagement, and improved infrastructure and funding are all needed to support research that will address impacts of systemic racism on childhood asthma outcomes.

Impact of sinus surgery in people with cystic fibrosis and chronic rhinosinusitis in the era of highly effective modulator therapy: Protocol for a prospective observational study.

INTRODUCTION: Cystic fibrosis (CF) is commonly complicated by chronic rhinosinusitis (CRS). Despite highly effective management options, CRS in people with CF (PwCF+CRS) may be refractory to medical therapy, eventually requiring endoscopic sinus surgery. The impact of sinus surgery on pulmonary, quality of life (QOL), and other outcomes in PwCF+CRS in the expanding era of highly effective modulator therapy has not been fully elucidated. This study aims to determine if endoscopic sinus surgery can offer superior outcomes for PwCF+CRS when compared to continued medical treatment of CRS. METHODS AND ANALYSIS: This multi-institutional, observational, prospective cohort study will enroll 150 adults with PwCF+CRS across nine US CF Centers who failed initial medical therapy for CRS and elected to pursue either endoscopic sinus surgery or continue medical treatment. To determine if sinus surgery outperforms continued medical therapy in different outcomes, we will assess changes in pulmonary, CF-specific QOL, CRS-specific QOL, sleep quality, depression, headache, cognition, olfaction, productivity loss, and health utility value after treatment. The influence of highly effective modulator therapy on these outcomes will also be evaluated. This study will provide crucial insights into the impact of endoscopic sinus surgery for PwCF+CRS and aid with development of future treatment pathways and guidelines. ETHICS AND DISSEMINATION: This study has been approved by each institution's internal review board, and study enrollment began August 2019. Results will be disseminated in conferences and peer-reviewed journals. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04469439).

CLINICAL MANAGEMENT OF CHRONIC ORANGUTAN RESPIRATORY DISEASE SYNDROME IN THREE ADULT MALE BORNEAN ORANGUTANS (PONGO PYGMAEUS).

Orangutan respiratory disease syndrome (ORDS) is a disease unique to orangutans (Pongo sp), characterized by chronic bacterial infection and inflammation of any region or combination of regions of the respiratory tract, including the sinuses, air sacs, cranial bones, airways, and lung parenchyma. Aggressive early intervention during a first episode may prevent progression to chronic disease. However, in the setting of an established chronic disease, intermittent acute exacerbations are associated with worsening symptoms and increased infection and inflammation. ORDS is ultimately fatal due to loss of respiratory function resulting from chronic structural damage. Utilizing potentially lifelong medications to slow the progression of chronic, destructive inflammation in the respiratory tract, chronic treatment is aimed at stabilizing the animals' respiratory function, decreasing the frequency of recurrent exacerbations, and improving their general well-being. Three adult male Bornean orangutans (Pongo pygmaeus) housed at an orangutan rehabilitation and reintroduction center in Indonesia have long histories of recurrent respiratory disease. Each underwent CT scans confirming ORDS with chronic airway disease prior to initiation of a long-term treatment protocol. Based on data-driven medical management of bronchiectasis in humans, the three orangutans have been treated with long-term combination regimens of oral azithromycin, nebulized salbutamol, and nebulized hypertonic saline. Follow-up CT scans in all three animals at least 1 yr following treatment initiation showed improvements throughout their respiratory tracts. The duration of each exacerbation period decreased, and the orangutans have longer symptom-free periods compared to before the start of treatment. At an average of 5 yr into the long-term treatment protocol, all three orangutans are thriving. Chronic medical management of ORDS modeled after human treatment of bronchiectasis has been efficacious in these three orangutans and encourages further study of this approach.

Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulators on Maternal Outcomes During and After Pregnancy.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are available to the majority of people with CF in the United States (US); little is known about pregnancy outcomes with modulator use. This retrospective study aims to determine the impact of CFTR modulators on maternal outcomes. RESEARCH QUESTION: Does pregnancy differentially impact outcomes in females with CF with and without CFTR modulators? STUDY DESIGN AND METHODS: We collected data on pregnancies from 2010-2021 from 11 US adult CF centers. We conducted multivariable longitudinal regression analysis to assess whether changes in percent predicted forced expiratory volume in 1 second (ppFEV1), body mass index (BMI), pulmonary exacerbations (PEx), and Pseudomonas aeruginosa prevalence differed from before, during, and after pregnancy by CFTR modulator use, while adjusting for confounders. We also describe infant outcomes based on maternal modulator use. RESULTS: Among 307 pregnancies, mean age at conception was 28.5 years (range: 17-42), pre-pregnancy ppFEV1 was 74.2 and BMI was 22.3 kg/m2. One hundred and fourteen pregnancies (37.1%) had CFTR modulator exposure during pregnancy (77 with highly effective modulator therapy [HEMT] and 37 with other modulators). The adjusted mean change in ppFEV1 from pre- to during pregnancy was -2.36 (95%CI: -3.56, -1.16) in the unexposed group and +2.60(95%CI: 0.23, 4.97) in the HEMT group, with no significant change from during to one-year post-pregnancy. There was an overall decline in ppFEV1 from pre- to post-pregnancy in the no modulator group (-2.56; 95%CI:-3.62, -1.49) that was not observed in the HEMT group (1.10; 95%CI: -1.13, 3.34). PEx decreased from pre- to post-pregnancy in the HEMT group and BMI increased from pre- to during pregnancy in all groups but without a significant change post-pregnancy. Missing infant outcome data precluded firm conclusions. INTERPRETATION: We observed superior pregnancy and post-pregnancy pulmonary outcomes in individuals who used HEMT, including a preservation of ppFEV1, compared with those unexposed to HEMT.

Pregnancy and fertility in people with cystic fibrosis following lung transplantation.

PURPOSE OF REVIEW: The purpose of this review is to summarize available data on fertility, fertility preservation, pregnancy and parenthood following lung transplantation for people with cystic fibrosis (pwCF). RECENT FINDINGS: In the era of cystic fibrosis transmembrane conductance regulator (CFTR) modulator use, oral therapies that positively impact fundamental CFTR protein abnormalities, the number of pregnancies has increased dramatically with a concomitant decrease in lung transplantation. Nonetheless, some pwCF still require lung transplantation as a life-saving measure, and a fraction of those individuals desires parenthood. Cystic fibrosis (CF) providers infrequently discuss fertility preservation with pwCF, and pwCF feel uneducated about their fertility options posttransplant. However, because the immunosuppression required to successfully maintain lung allografts may impact future fertility, pwCF should receive genetic and reproductive counseling prior to lung transplantation. While pregnancies posttransplantation are high-risk, selected females with CF may be able to pursue this path to parenthood. SUMMARY: Although there is a paucity of data specific to pwCF who have undergone lung transplantation, recently developed general guidelines should inform discussions regarding fertility, pregnancy and parenthood in pwCF who desire parenthood following lung transplantation for optimal shared decision-making.

Differential times of submission and approval of CFTR modulators for the treatment of Cystic Fibrosis in the United States and the European Union.

BACKGROUND: The objective of this study was to assess the differential times of submission and approval of CFTR modulators in the United States (US) and the European Union (EU). METHODS: By collecting publicly available data from the websites of the Food and Drug Administration and the European Medicines Agency, we quantified differential times in submission, review duration, and approvals of initial marketing authorization and variation of indications of CFTR modulators in the US and the EU by December 31, 2023. RESULTS: Applications regarding marketing of 4 CFTR modulators were submitted 103 (SD ±143) days later in the EU than in the US: 31 (SD ±39) days later for initial approval, and 124 (SD ±155) days for supplemental indications. The regulatory review process was completed in 181 days [IQR, 179 - 182] in the US and 325 days [IQR, 276 - 382] in the EU: 167 days [IQR, 102 - 232] in the US and 346 days [IQR, 302 - 400] in the EU for first approvals, 181 days [IQR, 181 - 182] in the US and 324 days [IQR, 264 - 382] in the EU for supplemental indication approvals. CFTR modulators were approved 267 (SD 143) days later in the EU than in the US: 220 (SD ±76) days for initial approval and 280 (SD ±157) days for supplemental indications. CONCLUSION: We found significant differences in times of submission and for approval of CFTR modulators between the US and EU, whereby initial approvals and subsequent indication approvals were always first granted in the US.

Cystic fibrosis.

Cystic fibrosis is a rare genetic disease caused by mutations in CFTR, the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). The discovery of CFTR in 1989 has enabled the unravelling of disease mechanisms and, more recently, the development of CFTR-directed therapeutics that target the underlying molecular defect. The CFTR protein functions as an ion channel that is crucial for correct ion and fluid transport across epithelial cells lining the airways and other organs. Consequently, CFTR dysfunction causes a complex multi-organ disease but, to date, most of the morbidity and mortality in people with cystic fibrosis is due to muco-obstructive lung disease. Cystic fibrosis care has long been limited to treating symptoms using nutritional support, airway clearance techniques and antibiotics to suppress airway infection. The widespread implementation of newborn screening for cystic fibrosis and the introduction of a highly effective triple combination CFTR modulator therapy that has unprecedented clinical benefits in up to 90% of genetically eligible people with cystic fibrosis has fundamentally changed the therapeutic landscape and improved prognosis. However, people with cystic fibrosis who are not eligible based on their CFTR genotype or who live in countries where they do not have access to this breakthrough therapy remain with a high unmet medical need.

Impact of sociodemographic status and sex on chronic rhinosinusitis and olfaction in people with cystic fibrosis.

BACKGROUND: Sociodemographic status (SDS) including race/ethnicity and socioeconomic status as approximated by education, income, and insurance status impact pulmonary disease in people with cystic fibrosis (PwCF). The relationship between SDS and chronic rhinosinusitis (CRS) remains understudied. METHODS: In a prospective, multi-institutional study, adult PwCF completed the 22-Question SinoNasal Outcome Test (SNOT-22), Smell Identification Test (SIT), Questionnaire of Olfactory Disorder Negative Statements (QOD-NS), and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Lund-Kennedy scores, sinus computed tomography, and clinical data were collected. Data were analyzed across race/ethnicity, sex, and socioeconomic factors using multivariate regression. RESULTS: Seventy-three PwCF participated with a mean age of 34.7 ± 10.9 years and 49 (67.1%) were female. Linear regression identified that elexacaftor/tezacaftor/ivacaftor (ETI) use (ß = â€’4.09, 95% confidence interval [CI] [‒6.08, ‒2.11], p < 0.001), female sex (ß = â€’2.14, 95% CI [‒4.11, ‒0.17], p = 0.034), and increasing age (ß = â€’0.14, 95% CI [‒0.22, ‒0.05], p = 0.003) were associated with lower/better endoscopy scores. Private health insurance (ß = 17.76, 95% CI [5.20, 30.32], p = 0.006) and >16 educational years (ß = 13.50, 95% CI [2.21, 24.80], p = 0.020) were associated with higher baseline percent predicted forced expiratory volume in one second (ppFEV1). Medicaid/Medicare insurance was associated with worse endoscopy scores, CFQ-R respiratory scores, and ppFEV1 (all p < 0.017), and Hispanic/Latino ethnicity was associated with worse SNOT-22 scores (p = 0.047), prior to adjustment for other cofactors. No other SDS factors were associated with SNOT-22, QOD-NS, or SIT scores. CONCLUSIONS: Differences in objective measures of CRS severity exist among PwCF related to sex, age, and ETI use. Variant status and race did not influence patient-reported CRS severity measures or olfaction in this study. Understanding how these factors impact response to treatment may improve care disparities among PwCF. CLINICAL TRIALS: NCT04469439.

Standards for the care of people with cystic fibrosis (CF); Planning for a longer life.

This is the final of four papers updating standards for the care of people with CF. That this paper "Planning a longer life" was considered necessary, highlights how much CF care has progressed over the past decade. Several factors underpin this progress, notably increased numbers of people with CF with access to CFTR modulator therapy. As the landscape for CF changes, so do the hopes and aspirations of people with CF and their families. This paper reflects the need to consider people with CF not as a "problem" to be solved, but as a success, a potential and a voice to be heard. People with CF and the wider CF community have driven this approach, reflecting many of the topics in this paper. This exercise involved wide stakeholder engagement. People with CF are keen to contribute to research priorities and be involved in all stages of research. People with CF want healthcare professionals to respect them as individuals and consider the impact of our actions on the world around us. Navigating life presents challenges to all, but for people with CF these challenges are heightened and complex. In this paper we highlight the concerns and life moments that impact people with CF, and events that the CF team should aim to support, including the challenges around having a family. People with CF and their care teams must embrace the updated standards outlined in these four papers to enjoy the full potential for a healthier life.

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis.

OBJECTIVES: The 22-question SinoNasal Outcome Test (SNOT-22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT-22 score improvement following highly effective modulator therapy (HEMT) initiation and to corroborate the SNOT-22 minimal clinically important difference (MCID) in adults with cystic fibrosis (CF). METHODS: Prospective observational data was pooled from four studies across 10 US centers investigating people with CF (PwCF) and CRS. Three studies evaluated HEMT's impact on CRS. For participants enrolled prior to HEMT initiation, SNOT-22 scores were obtained at baseline and after 3-6 months of HEMT. Multivariate regression identified predictors of improvement. Cronbach's alpha and four distribution-based methods were used to assess internal consistency and calculate the MCID of the SNOT-22. RESULTS: A total of 184 PwCF participated with mean baseline SNOT-22 scores ranging from 18.1 to 56.7. Cronbach's alpha was ≥0.90 across sites. Participants at sites with pre- and post-HEMT data reported improvement in SNOT-22 scores after initiating HEMT (all p < 0.05). Worse baseline SNOT-22 score (odds ratio (OR): 1.05, p < 0.001, 95% CI: 1.02-1.08), F508del homozygosity (OR: 4.30, p = 0.040, 95% CI: 1.14-18.99), and absence of prior modulator therapy (OR: 4.99, p = 0.017, 95% CI: 1.39-20.11) were associated with greater SNOT-22 improvement. The mean MCID calculated via distribution-based methods was 8.5. CONCLUSION: Worse baseline sinonasal symptoms, F508del homozygosity, and absence of prior modulator therapy predicted greater improvement after HEMT initiation. The mean MCID for SNOT-22 in PwCF is 8.5 points, similar to non-CF individuals with CRS, and provides a threshold specifically for PwCF. The SNOT-22 has strong internal consistency in PwCF. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3965-3973, 2024.

Association between CFTR modulators and changes in iron deficiency markers in cystic fibrosis.

BACKGROUND: Iron deficiency (ID) is a common extrapulmonary manifestation in cystic fibrosis (CF). CF transmembrane conductance regulator (CFTR) modulator therapies, particularly highly-effective modulator therapy (HEMT), have drastically improved health status in a majority of people with CF. We hypothesize that CFTR modulator use is associated with improved markers of ID. METHODS: In a multicenter retrospective cohort study across 4 United States CF centers 2012-2022, the association between modulator therapies and ID laboratory outcomes was estimated using multivariable linear mixed effects models overall and by key subgroups. Summary statistics describe the prevalence and trends of ID, defined a priori as transferrin saturation (TSAT) <20 % or serum iron <60 µg/dL (<10.7 µmol/L). RESULTS: A total of 568 patients with 2571 person-years of follow-up were included in analyses. Compared to off modulator therapy, HEMT was associated with +8.4 % TSAT (95 % confidence interval [CI], +6.3-10.6 %; p < 0.0001) and +34.4 µg/dL serum iron (95 % CI, +26.7-42.1 µg/dL; p < 0.0001) overall; +5.4 % TSAT (95 % CI, +2.8-8.0 %; p = 0.0001) and +22.1 µg/dL serum iron (95 % CI, +13.5-30.8 µg/dL; p < 0.0001) in females; and +11.4 % TSAT (95 % CI, +7.9-14.8 %; p < 0.0001) and +46.0 µg/dL serum iron (95 % CI, +33.3-58.8 µg/dL; p < 0.0001) in males. Ferritin was not different in those taking modulator therapy relative to off modulator therapy. Hemoglobin was overall higher with use of modulator therapy. The prevalence of ID was high throughout the study period (32.8 % in those treated with HEMT). CONCLUSIONS: ID remains a prevalent comorbidity in CF, despite availability of HEMT. Modulator use, particularly of HEMT, is associated with improved markers for ID (TSAT, serum iron) and anemia (hemoglobin).

Prioritizing sexual and reproductive health research and care for people with cystic fibrosis: A 2023 workshop report from the Cystic Fibrosis Foundation Sexual Health, Reproduction, and Gender (SHARING) Research Working Group.

BACKGROUND: To address sexual and reproductive health (SRH) concerns among people with cystic fibrosis(PwCF), the CF Foundation created the Sexual Health, Reproduction, and Gender Research (SHARING) Working Group. This report summarizes CF community SRH research priorities and workshop discussions/future study planning. METHODS: Pre-workshop, we distributed a community prioritization survey on CF SRH research/care. During the workshop, we used results and reviewed existing research to establish research priorities and design studies to address identified knowledge gaps. RESULTS: A total of 303 respondents (85 % PwCF, 15 % caregivers) completed the survey. Highly-rated SRH topics were: 1) effects of CF modulator therapy on sex hormones; 2) effects of sex hormones on CF; 3) fertility; 4) pregnancy; and 5) SRH/mental health. Twenty-four workshop participants established the need for further research on sex hormones and CF, optimizing SRH care provision, and fertility/ART. CONCLUSION: SRH is an important and emerging area in CF and thoughtful consideration of community perspectives can ensure that future research is relevant and responsive.

Patient perspectives on chronic rhinosinusitis in cystic fibrosis: Symptom prioritization in the era of highly effective modulator therapy.

BACKGROUND: Chronic rhinosinusitis (CRS) is common in people with cystic fibrosis (PwCF). Rhinologic symptom prioritization and areas that influence CRS treatment choices, including pursuing endoscopic sinus surgery (ESS), remain understudied. METHODS: Adult PwCF + CRS were enrolled at eight centers into a prospective, observational study (2019-2023). Participants were administered the 22-SinoNasal Outcome Test (SNOT-22) survey and a modified SNOT-22 instrument examining symptom importance. We determined importance rankings for individual symptoms and SNOT-22 symptom importance subdomains in two sets of subgroups-those pursuing ESS versus continuing medical management (CMT), and those on elexacaftor/tezacaftor/ivacaftor (ETI) versus not on ETI. RESULTS: Among 69 participants, the highest priorities were nasal congestion (n = 48, 69.6% important), post-nasal discharge (32, 46.4%), facial pain (29, 43.3%), waking up tired (27, 39.1%), and fatigue (26, 37.7%). Those electing surgery (n = 23) prioritized sleep and psychological dysfunction symptoms compared to those pursuing CMT (n = 49) (sleep median score = 19.0 [interquartile range: 12.0, 25.0] vs. 4.5 [0.0, 12.8]; p < 0.0001; psychological = 17.0 [7.0, 26.0] vs. 7.0 [0.0, 15.8]; p = 0.002). ETI users had comparable SNOT-22 total symptom importance scores to non-ETI users (p = 0.14). Non-ETI users (n = 34) showed a trend toward prioritizing sleep symptoms compared to ETI users (n = 35) (13.0 [2.8, 22.3] vs. 6.0 [2.0, 17.0]; p = 0.055). CONCLUSIONS: Nasal congestion and post-nasal discharge were top priorities reported by PwCF + CRS. Those electing surgery prioritized sleep and psychological symptoms, highlighting their importance in pre-operative discussions. Non-ETI users' prioritization of sleep improvement may highlight their unique disease impact and therapeutic needs; however, additional investigation is required.

Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis.

Airway inflammation underlies cystic fibrosis (CF) pulmonary exacerbations. In a prospective multicenter study of randomly selected, clinically stable adolescents and adults, we assessed relationships between 24 inflammation-associated molecules and the future occurrence of CF pulmonary exacerbation using proportional hazards models. We explored relationships for potential confounding or mediation by clinical factors and assessed sensitivities to treatments including CF transmembrane regulator (CFTR) protein synthesis modulators. Results from 114 participants, including seven on ivacaftor or lumacaftor-ivacaftor, representative of the US CF population during the study period, identified 10 biomarkers associated with future exacerbations mediated by percent predicted forced expiratory volume in 1 s. The findings were not sensitive to anti-inflammatory, antibiotic, and CFTR modulator treatments. The analyses suggest that combination treatments addressing RAGE-axis inflammation, protease-mediated injury, and oxidative stress might prevent pulmonary exacerbations. Our work may apply to other airway inflammatory diseases such as bronchiectasis and the acute respiratory distress syndrome.

Factors that predict pursuing sinus surgery in the era of highly effective modulator therapy.

BACKGROUND: Comorbid chronic rhinosinusitis (CRS) remains unresolved for many people with cystic fibrosis (PwCF). While highly effective modulator therapy improves quality-of-life and symptom severity, the impact of this intervention and other factors associated with pursuing endoscopic sinus surgery (ESS) remains understudied. METHODS: Adult PwCF + CRS were enrolled into a prospective, observational, multi-institutional study. Participants completed validated outcome measures to evaluate respiratory symptom severity, depression, headache, and sleep quality, as well as nasal endoscopy, sinus computed tomography (CT), and olfactory testing. Bivariate comparisons and regression modeling evaluated treatment cofactors, disease characteristics, and outcome measures associated with pursuing ESS. RESULTS: Sixty PwCF were analyzed, including 24 (40%) who elected ESS. Pursuing ESS was associated with worse SinoNasal Outcome Test (SNOT-22) total, rhinologic, psychological, and sleep dysfunction domain scores; worse Patient Health Questionnaire-9-Revised depression scores; worse Pittsburgh Sleep Quality Index total scores; worse weight, role, emotion, and eating domain scores on the Cystic Fibrosis Questionnaire-Revised; more severe disease on nasal endoscopy; and lack of modulator therapy (all p < 0.050). Multivariable regression identified that worse SNOT-22 total score was associated with electing ESS (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.16, p = 0.015) and elexacaftor/tezacaftor/ivacaftor (ETI) treatment (OR 0.04, 95% CI 0.004-0.34, p = 0.004) was associated with pursing medical therapy. CONCLUSIONS: Worse sinonasal symptom burden, lack of ETI treatment, sleep quality, depression, and nasal endoscopy scores were associated with electing ESS, while lung disease severity and sinus CT scores were not. ETI use was associated with lower odds of pursuing ESS independent of sinonasal symptom burden.