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 \u3c 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

Impact of Sociodemographic Status and Sex on Chronic Rhinosinusitis and Olfaction in People with Cystic Fibrosis.

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

Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138837/1/cncr30802.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138837/2/cncr30802_am.pd

CML24, Regulated in Expression by Diverse Stimuli, Encodes a Potential Ca(2+) Sensor That Functions in Responses to Abscisic Acid, Daylength, and Ion Stress

Changes in intracellular calcium (Ca(2+)) levels serve to signal responses to diverse stimuli. Ca(2+) signals are likely perceived through proteins that bind Ca(2+), undergo conformation changes following Ca(2+) binding, and interact with target proteins. The 50-member calmodulin-like (CML) Arabidopsis (Arabidopsis thaliana) family encodes proteins containing the predicted Ca(2+)-binding EF-hand motif. The functions of virtually all these proteins are unknown. CML24, also known as TCH2, shares over 40% amino acid sequence identity with calmodulin, has four EF hands, and undergoes Ca(2+)-dependent changes in hydrophobic interaction chromatography and migration rate through denaturing gel electrophoresis, indicating that CML24 binds Ca(2+) and, as a consequence, undergoes conformational changes. CML24 expression occurs in all major organs, and transcript levels are increased from 2- to 15-fold in plants subjected to touch, darkness, heat, cold, hydrogen peroxide, abscisic acid (ABA), and indole-3-acetic acid. However, CML24 protein accumulation changes were not detectable. The putative CML24 regulatory region confers reporter expression at sites of predicted mechanical stress; in regions undergoing growth; in vascular tissues and various floral organs; and in stomata, trichomes, and hydathodes. CML24-underexpressing transgenics are resistant to ABA inhibition of germination and seedling growth, are defective in long-day induction of flowering, and have enhanced tolerance to CoCl(2), molybdic acid, ZnSO(4), and MgCl(2). MgCl(2) tolerance is not due to reduced uptake or to elevated Ca(2+) accumulation. Together, these data present evidence that CML24, a gene expressed in diverse organs and responsive to diverse stimuli, encodes a potential Ca(2+) sensor that may function to enable responses to ABA, daylength, and presence of various salts

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\u27s 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

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\u27s 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

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\u27s 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\u27s alpha was ≥0.85. The MCID estimates were as follows: Cohen\u27s 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 \u3c 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

Factors That Predict Pursuing Sinus Surgery in the Era of Highly Effective Modulator Therapy

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