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, 2024.

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.

All chronic rhinosinusitis endotype clusters demonstrate improvement in patient-reported and clinical outcome measures after endoscopic sinus surgery.

BACKGROUND: It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient-reported and clinically measured post-operative outcome measures. METHODS: Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient-reported outcome measures included the 22-item Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Dysfunction (QOD). Additional clinical measures of disease severity included threshold, discrimination, and identification (TDI) scores using "Sniffin' Sticks" testing and Lund-Kennedy endoscopic score (LKES). RESULTS: A total of 115 patients were clustered into type 2 inflammatory, non-type 2 inflammatory, noninflammatory, and two indeterminate clusters based on individual protein levels. Overall, the type 2 inflammatory cluster was found to have the highest mean improvement in both SNOT-22 (-28.3 [standard deviation, ±16.2]) and TDI (6.5 [standard deviation, ±7.9]) scores 6 months after ESS. However, on average, all endotype clusters demonstrated improvement in all outcome measures after ESS without statistically significant between-group differences in SNOT-22 (p = 0.738), QOD (p = 0.306), TDI (p = 0.358), or LKES (p = 0.514) measures. CONCLUSIONS: All CRS endotype clusters responded favorably to surgery and showed improvements in patient-reported and objective outcome measures. Thus, ESS should be considered a more generalized CRS therapy, and benefits appear to not be limited to specific endotypes.

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.

Determining the minimal clinically important difference for the questionnaire of olfactory disorders in people with cystic fibrosis and factors associated with improvement after highly effective modulator therapy.

INTRODUCTION: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory-specific quality-of-life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF. METHODS: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution-based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement. RESULTS: Of 129 PwCF included, 65 had QOD scores before and 3-6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was -1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04). CONCLUSION: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner.

Employee Cardiometabolic Risk Following a Cluster-Randomized Workplace Intervention From the Work, Family and Health Network, 2009-2013.

Objectives. To examine whether workplace interventions to increase workplace flexibility and supervisor support and decrease work-family conflict can reduce cardiometabolic risk. Methods. We randomly assigned employees from information technology (n = 555) and long-term care (n = 973) industries in the United States to the Work, Family and Health Network intervention or usual practice (we collected the data 2009-2013). We calculated a validated cardiometabolic risk score (CRS) based on resting blood pressure, HbA1c (glycated hemoglobin), HDL (high-density lipoprotein) and total cholesterol, height and weight (body mass index), and tobacco consumption. We compared changes in baseline CRS to 12-month follow-up. Results. There was no significant main effect on CRS associated with the intervention in either industry. However, significant interaction effects revealed that the intervention improved CRS at the 12-month follow-up among intervention participants in both industries with a higher baseline CRS. Age also moderated intervention effects: older employees had significantly larger reductions in CRS at 12 months than did younger employees. Conclusions. The intervention benefited employee health by reducing CRS equivalent to 5 to 10 years of age-related changes for those with a higher baseline CRS and for older employees. Trial Registration. ClinicalTrials.gov Identifier: NCT02050204. (Am J Public Health. 2023;113(12):1322-1331. https://doi.org/10.2105/AJPH.2023.307413).

A Comparison of Safety, Health, and Well-Being Risk Factors Across Five Occupational Samples.

Objective: The aim of this study was to present safety, health and well-being profiles of workers within five occupations: call center work (N = 139), corrections (N = 85), construction (N = 348), homecare (N = 149), and parks and recreation (N = 178). Methods: Baseline data from the Data Repository of Oregon's Healthy Workforce Center were used. Measures were compared with clinical healthcare guidelines and national norms. Results: The prevalence of health and safety risks for adults was as follows: overweight (83.2%), high blood pressure (16.4%), injury causing lost work (9.9%), and reported pain (47.0%). Young workers were least likely to report adequate sleep (46.6%). Construction workers reported the highest rate of smoking (20.7%). All of the adult workers reported significantly lower general health than the general population. Conclusion: The number of workers experiencing poor safety, health and well-being outcomes suggest the need for improved working conditions.

Endotyping chronic rhinosinusitis based on olfactory cleft mucus biomarkers.

BACKGROUND: Although chronic rhinosinusitis (CRS) is considered the most treatable form of olfactory dysfunction, there has been relatively little clinical attention focused on assessing endotypes as they pertain to olfactory loss. OBJECTIVES: The goal of this study was to explore inflammatory endotypes in CRS using an unsupervised cluster analysis of olfactory cleft (OC) biomarkers in a phenotype-free approach. METHODS: Patients with CRS were prospectively recruited and psychophysical olfactory testing, Questionnaire of Olfactory Dysfunction (QOD-NS), and bilateral OC endoscopy were obtained. Mucus was collected from the OC and evaluated for 26 biomarkers using principal component analysis. Cluster analysis was performed using only OC biomarkers and differences in olfactory measures were compared across clusters. RESULTS: A total of 198 subjects (128 with CRS and 70 controls) were evaluated. Evaluation of OC biomarkers indicated 6 principal components, explaining 69.50% of the variance, with type 2, mixed type 1/Th17-cell, growth factor, and neutrophil chemoattractant inflammatory signatures. A total of 10 clusters were identified that differed significantly in frequency of controls, and subjects with CRS with nasal polyps, and subjects with CRS without nasal polyps across the clusters (likelihood ratio test, χ182=178.64; P < .001). Olfactory measures differed significantly across clusters, including olfactory testing, QOD-NS, and OC endoscopy (P < .001 for all). CONCLUSIONS: Clustering based solely on OC biomarkers can organize patients into clinically meaningful endotypes that discriminate between subjects with CRS and controls. Validation studies are necessary to confirm these findings and further refine olfactory endotypes.

Does Medical Therapy Improve SinoNasal Outcomes Test-22 Domain Scores? An Analysis of Clinically Important Differences.

OBJECTIVES/HYPOTHESIS: Minimum clinically important differences (MCIDs) for the 22-item SinoNasal Outcomes Test (SNOT-22) in patients with chronic rhinosinusitis (CRS) electing endoscopic sinus surgery (ESS) are well described. However, similar estimations for the MCID have not been investigated for patients electing continued appropriate medical therapy (CAMT). We sought to determine MCID values for a medically treated CRS cohort and compare them to historical MCIDs associated with ESS. STUDY DESIGN: Prospective observational cohort study. METHODS: One hundred twenty patients with refractory CRS electing CAMT were prospectively enrolled from academic referral clinics into an observational cohort study. Baseline and posttreatment SNOT-22 survey responses were collected. Four distribution-based methods for calculating MCIDs (e.g., half-standard deviation, Cohen's d, standard error of measurement, and minimum detectable change) were used to identify a range of MCID values for SNOT-22 total and domain scores. RESULTS: The average MCID value for SNOT-22 total scores was 8.0, whereas mean MCID values for rhinologic, extranasal rhinologic, ear/facial, psychological, and sleep symptom domain scores were 3.9, 2.5, 3.3, 3.4, and 2.9, respectively, comparable to previously reported values for patients electing ESS. Although change in SNOT-22 total scores following CAMT exceeded the MCID, none of the average SNOT-22 domain score improvements surpassed their respective MCID thresholds. CONCLUSIONS: MCID values for SNOT-22 total and domain scores in patients electing CAMT are similar to previously published MCID values associated with ESS, indicating that MCID values are independent of treatment modality selection. Therefore, despite evidence of statistical significance, CAMT for CRS may not be associated with clinically discernable improvements in average SNOT-22 domain scores. LEVEL OF EVIDENCE: 2c Laryngoscope, 129:31-36, 2019.

Investigating the minimal clinically important difference for SNOT-22 symptom domains in surgically managed chronic rhinosinusitis.

BACKGROUND: Prior work has described 5 domains within the 22-item Sino-Nasal Outcomes Test (SNOT-22) that allow for stratification of symptoms into similar clusters and that can be used to direct therapy. Although the outcomes of various interventions on these symptom domains have been reported, minimal clinically important difference (MCID) values have not been investigated, which has limited clinical interpretation of these results. METHODS: This study was designed as a secondary analysis of a prospective, multi-institutional, observational cohort. A total of 276 patients with medically refractory CRS who underwent surgical management were enrolled. Distribution-based methods (half-standard deviation, standard error of measurement, Cohen's d, and the minimum detectable change) were used to compute MCID values for both SNOT-22 total and domain scores. The Medical Outcomes Study Short Form 6D (SF-6D) health utility score was used to operationalize anchor-based associations using receiver-operating characteristic (ROC) curves. RESULTS: The mean MCID of several distribution-based methods for total SNOT-22 scores was 9.0, in agreement with previously published metrics. Average MCID values for the rhinologic, extranasal rhinologic, ear/facial, psychological, and sleep domain scores were 3.8, 2.4, 3.2, 3.9, and 2.9, respectively. Anchor-based approaches with the SF-6D did not have strong predictive accuracy across total SNOT-22 scores or domains (ROC areas under-the-curve ≤ 0.71), indicating weak associations between improvement in SNOT-22 scores and health utility as measured by the SF-6D. CONCLUSION: This estimation of MCID values for the SNOT-22 symptom domains allows for improved clinical interpretation of results from past, present, and future rhinologic outcomes research.

Defining the minimal clinically important difference for olfactory outcomes in the surgical treatment of chronic rhinosinusitis.

BACKGROUND: Olfactory dysfunction is a common and defining symptom of chronic rhinosinusitis (CRS). Many measures of olfactory dysfunction in CRS are limited by scoring criteria defined within general populations with interpretations of statistical significance to infer clinically meaningful improvement. In this investigation we define a minimal clinically important difference (MCID) for the Brief Smell Identification Test (BSIT) in CRS patients electing endoscopic sinus surgery (ESS). METHODS: A multicenter cohort of 290 adult patients electing ESS for medically recalcitrant CRS were prospectively enrolled between March 2011 and June 2015 and completed BSIT evaluations before and after ESS. Distribution and anchor-based analytic approaches were utilized to define MCID values of the BSIT across patient cofactors. RESULTS: A total of 92 (∽32%) patients were found to have preoperative olfactory dysfunction (BSIT <9), significantly associated with nasal polyposis (χ2 = 35.0; p < 0.001). The effect-size distribution-based approach identified 1.0 as a MCID criterion value between "small" and "medium" effect (range, 0.61-1.52) overall. Significant mean postoperative change (ΔM) was reported for patients with olfactory dysfunction (ΔM = 2.28; p < 0.001), both with (n = 54; ΔM = 2.52; p < 0.001) and without (n = 38; ΔM = 1.95; p < 0.001) nasal polyposis, significantly exceeding the MCID criterion. Anchor-based approaches with regression modeling confirmed associations between MCID values and postoperative changes to olfactory-specific survey responses (p < 0.001). CONCLUSION: Clinically meaningful change in BSIT scores may be defined as an absolute value difference of at least 1.0 unit for heterogeneous patients electing ESS for CRS. Significantly exceeding this criterion may be restricted to CRS patients with baseline olfactory dysfunction, regardless of nasal polyposis.

Sleep, Dietary, and Exercise Behavioral Clusters Among Truck Drivers With Obesity: Implications for Interventions.

OBJECTIVE: The objectives of the study were to describe a sample of truck drivers, identify clusters of drivers with similar patterns in behaviors affecting energy balance (sleep, diet, and exercise), and test for cluster differences in health safety, and psychosocial factors. METHODS: Participants' (n = 452, body mass index M = 37.2, 86.4% male) self-reported behaviors were dichotomized prior to hierarchical cluster analysis, which identified groups with similar behavior covariation. Cluster differences were tested with generalized estimating equations. RESULTS: Five behavioral clusters were identified that differed significantly in age, smoking status, diabetes prevalence, lost work days, stress, and social support, but not in body mass index. Cluster 2, characterized by the best sleep quality, had significantly lower lost workdays and stress than other clusters. CONCLUSIONS: Weight management interventions for drivers should explicitly address sleep, and may be maximally effective after establishing socially supportive work environments that reduce stress exposures.

Development of a clinically relevant endoscopic grading system for chronic rhinosinusitis using canonical correlation analysis.

BACKGROUND: Diagnostic nasal endoscopy is a routine measure of sinonasal inflammation in patients with chronic rhinosinusitis (CRS). Although multiple staging systems have been proposed and evaluated, evidence of association between concurrent symptoms and endoscopic findings remains discordant. The goal of this study is to identify the relevant endoscopic attributes associated with symptom burden, and to systematically derive a weighted endoscopic scale that optimizes prediction of concurrent symptoms. METHODS: Reported baseline symptom (22-item Sino-Nasal Outcome Test [SNOT-22]) and endoscopic evaluation scores (Lund-Kennedy [LK]) were obtained from patients with CRS enrolled in a prospective cohort study. Canonical correlation analysis of the SNOT-22 subdomains and LK variables was completed. RESULTS: A total of 629 patients were included in analysis including 343 with prior endoscopic sinus surgery. Significant canonical correlations outperformed aggregate correlations in explaining variance of the data (33% vs 3%, respectively). The first canonical correlation was dominated by the rhinologic symptom domain and the endoscopic polyp score (r = 0.54; p < 0.05) whereas additional significant canonical correlation was found between the extra-rhinologic symptom subdomain and the edema score in patients without prior ESS (r = 0.21; p < 0.05), and discharge in patients with prior ESS (r = 0.22; p < 0.05). All other domains and endoscopic variables did not significantly contribute to the canonical correlation. CONCLUSION: Although aggregate symptoms and endoscopic scores demonstrate minimal correlation, a weighted combination of symptom domains and endoscopic attributes greatly improves this correlation. A simple approximation of the weights of each of the endoscopic variables of polyps, edema, discharge, scarring, and crusting, is an approximate ratio of 4:2:1:0:0, respectively.

SNOT-22 quality of life domains differentially predict treatment modality selection in chronic rhinosinusitis.

BACKGROUND: Prior study demonstrated that baseline 22-item Sino-Nasal Outcome Test (SNOT-22) aggregate scores accurately predict selection of surgical intervention in patients with chronic rhinosinusitis (CRS). Factor analysis of the SNOT-22 survey has identified five distinct domains that are differentially impacted by endoscopic sinus surgery (ESS). This study sought to quantify SNOT-22 domains in patient cohorts electing both surgical or medical management and postinterventional change in these domains. METHODS: CRS patients were prospectively enrolled into a multi-institutional, observational cohort study. Subjects elected continued medical management or ESS. SNOT-22 domain scores at baseline were compared between treatment cohorts. Postintervention domain score changes were evaluated in subjects with at least six-month follow-up. RESULTS: A total of 363 subjects were enrolled with 72 (19.8%) electing continued medical management, whereas 291 (80.2%) elected ESS. Baseline SNOT-22 domain scores were comparable between treatment cohorts in sinus-specific domains (rhinologic, extranasal rhinologic, and ear/facial symptoms; p > 0.050); however, the surgical cohort reported significantly higher psychological (mean ± standard deviation [SD]: 16.0 ± 8.4 vs 12.0 ± 7.1; p < 0.001) and sleep dysfunction (13.7 ± 6.8 vs 10.5 ± 6.2; p < 0.001) than the medical cohort. Effect sizes for ESS varied across domains with rhinologic and extranasal rhinologic symptoms experiencing the greatest gains (1.067 and 0.997, respectively), whereas psychological and sleep dysfunction experiencing the smallest improvements (0.805 and 0.818, respectively). Patients experienced greater mean improvements after ESS in all domains compared to medical management (p < 0.001). CONCLUSION: Subjects electing ESS report higher sleep and psychological dysfunction compared to medical management but have comparable sinus-specific symptoms. Subjects undergoing ESS experience greater gains compared to medical management across all domains; however, these gains are smallest in the psychological and sleep domains.

Response shift in quality of life after endoscopic sinus surgery for chronic rhinosinusitis.

IMPORTANCE: Patient-reported measures are designed to detect a true change in outcome, but they are also subject to change from biases inherent to self-reporting: changing internal standards, changing priorities, and changing interpretations of a given instrument. These biases are collectively known as "response shifts" and can obscure true change after medical interventions. OBJECTIVE: To determine the presence of response shifts in patients with chronic rhinosinusitis (CRS) after endoscopic sinus surgery. DESIGN, SETTING, AND PARTICIPANTS: Multisite, prospective, observational cohort study conducted at academic tertiary care centers between February 2011 and May 2013. Study participants comprised a population-based sample of 514 adults (age ≥18 years) with CRS, who elected surgical intervention for continuing medically refractory symptoms. INTERVENTION: Endoscopic sinus surgery. MAIN OUTCOMES AND MEASURES: Preoperative and postoperative data from the 22-item Sinonasal Outcome Test (SNOT-22) survey instrument was characterized using exploratory factor analysis. Subsequent longitudinal structural equation models were estimated to test structure, potential response shifts, and true change in the SNOT-22 scores. RESULTS: A total of 339 participants (66.0%) provided survey evaluations at baseline and 6-month follow-up. Factor analysis of the SNOT-22 revealed 5 correlated, yet distinguishable, underlying factors. Endoscopic sinus surgery had a differential impact across these factors, with the largest effect size in rhinologic symptoms (mean [SD] SNOT-22 scores before and after surgery, 13.18 [5.11] and 7.37 [5.48], respectively; d = -1.13 [P < .001]) and extranasal rhinologic symptoms (8.31 [3.46] and 4.83 [3.68], respectively; d = -1.00 [P < .05]) (d is an effect size measure defined as the difference in means divided by the presurgery SD). Endoscopic sinus surgery had a smaller, yet significant, effect size on the remaining 3 factors: ear/facial symptoms (7.32 [4.6]) and 3.90 [4.07], respectively; d = -0.74 [P < .001]), psychological dysfunction (11.90 [7.21] and 6.50 [6.69], respectively; d = -0.75 [P < .05]), and sleep dysfunction (10.12 [5.59] and 5.88 [5.37], respectively; d = -0.76 [P < .001]). Participants were found to undergo recalibration, reprioritization, and reconceptualization of symptoms after intervention; however, the magnitude of these response shifts was small and not clinically significant. CONCLUSIONS AND RELEVANCE: The SNOT-22 measures 5 distinct factors, not a single construct. Reporting of individual subscale scores may improve sensitivity of this instrument in future studies. Participants undergoing endoscopic sinus surgery experience only clinically insignificant response shifts, validating assessment of change through use of presurgery and postsurgery SNOT-22 responses. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01332136.