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.

Surgical and medical management of chronic rhinosinusitis in pediatric cystic fibrosis patients: Impact on olfactory symptoms.

BACKGROUND AND PURPOSE: Olfactory dysfunction (OD) commonly occurs in patients with sinonasal dysfunction, but the prevalence and severity of olfactory issues in adolescents with cystic fibrosis (AwCF) is unclear. OD may contribute to dietary deficiencies and exacerbate nutritional challenges. We sought to review literature on the effectiveness of medical and surgical management of sinonasal symptoms in AwCF and the associated impact on olfactory function. METHODS: We performed a systematic literature search of PubMed, Embase, Web of Science, and Ebsco CINAHL from 1980 to 2022 per PRISMA-ScR protocols to conduct a scoping review in an effort to compile data on study design, patient demographics, clinical characteristics and outcomes, along with risk of bias. RESULTS: Of 368 abstracts, 3 articles exclusively evaluated AwCF for a total of 34 patients. Two studies evaluated endoscopic sinus surgery (ESS) and dornase alfa. An additional 6 articles were included for mixed pediatric and adult CF populations totaling 313 patients. Interventions included ESS, elexacaftor-tezacaftor-ivacaftor (ETI), ivacaftor, saline, dornase alfa, hyaluronic acid, and hyaluronic acid-tobramycin combination. Outcome measures included subjective assessment of OD using non-validated (4/9) and validated (4/9) surveys, and psychophysical (1/9) smell testing. Studies evaluating ESS, FESS, dornase alfa, ivacaftor, and both hypertonic and isotonic saline reported statistically significant improvement in OD, whereas ETI failed to improve OD despite improvement in other quality of life measures. CONCLUSIONS: There is limited data regarding the impact of medical and surgical interventions on olfaction for AwCF. Assessment of olfaction was often limited to subjective and qualitative self-report. We suggest that tracking of olfactory outcomes with psychophysical testing is critical in this population with dietary challenges and weight management issues.

Associations between olfactory dysfunction and cognition: a scoping review.

INTRODUCTION: Strong evidence suggests that olfactory dysfunction (OD) can predict additional neurocognitive decline in neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. However, research exploring olfaction and cognition in younger populations is limited. The aim of this review is to evaluate cognitive changes among non-elderly adults with non-COVID-19-related OD. METHODS: We performed a structured comprehensive literature search of PubMed, Ovid Embase, Web of Science, and Cochrane Library in developing this scoping review. The primary outcome of interest was the association between OD and cognitive functioning in adults less than 60 years of age. RESULTS: We identified 2878 studies for title and abstract review, with 167 undergoing full text review, and 54 selected for data extraction. Of these, 34 studies reported on populations of individuals restricted to the ages of 18-60, whereas the remaining 20 studies included a more heterogeneous population with the majority of individuals in this target age range in addition to some above the age of 60. The etiologies for smell loss among the included studies were neuropsychiatric disorders (37%), idiopathic cause (25%), type 2 diabetes (7%), trauma (5%), infection (4%), intellectual disability (4%), and other (18%). Some studies reported numerous associations and at times mixed, resulting in a total number of associations greater than the included number of 54 studies. Overall, 21/54 studies demonstrated a positive association between olfaction and cognition, 7/54 demonstrated no association, 25/54 reported mixed results, and only 1/54 demonstrated a negative association. CONCLUSION: Most studies demonstrate a positive correlation between OD and cognition, but the data are mixed with associations less robust in this young adult population compared to elderly adults. Despite the heterogeneity in study populations and outcomes, this scoping review serves as a starting point for further investigation on this topic. Notably, as many studies in this review involved disorders that may have confounding effects on both olfaction and cognition, future research should control for these confounders and incorporate non-elderly individuals with non-psychiatric causes of smell loss.

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.

BMI Increases in Individuals with COVID-19-Associated Olfactory Dysfunction.

(1) Background: Reports suggest COVID-19-associated olfactory dysfunction (OD) may result in alterations in dietary behaviors and perceived weight change, but few studies using psychophysical evaluation of post-COVID-19-associated chemosensory dysfunction and body mass index (BMI) exist. The purpose of this study is to assess the impact of both quantitative and qualitative features of COVID-19-associated OD on BMI; (2) Methods: Recruitment of thirty-one participants with self-reported OD in the form of quantitative loss with and without qualitative features. Surveys with questions specific to qualitative olfactory function, Sniffin' Sticks tests, and BMI measures were completed at two visits, one year apart. Group differences were assessed with Wilcoxon signed-rank tests and the Holm-Bonferroni method; (3) Results: Individuals with persistent quantitative OD (n = 15) and self-reported parosmia (n = 19) showed statistically significant increases in BMI after 1 year (p = 0.004, adjusted α = 0.0125; p = 0.011, adjusted α = 0.0167). Controls with transient quantitative OD (n = 16) and participants without self-reported parosmia (n = 12) showed no statistically significant changes in BMI over the same time period (p = 0.079, adjusted α = 0.05; p = 0.028, adjusted α = 0.025); (4) Conclusions: This study shows an association between COVID-19-associated OD and BMI, suggesting olfaction may play a role in altering dietary habits and nutrition in this population. Larger study cohorts are needed to further evaluate this relationship.

Olfaction and neurocognition after COVID-19: a scoping review.

Introduction: COVID-19 induces both acute and chronic neurological changes. Existing evidence suggests that chemosensory changes, particularly olfactory loss, may reflect central neurological dysfunction in neurodegenerative diseases and mark progression from mild cognitive impairment to Alzheimer's. This scoping review summarizes the available literature to evaluate the relationship between neurocognition and olfaction in young to middle-aged adults with minimal comorbidities following COVID-19 infection. Methods: A literature search of PubMed, Ovid Embase, Web of Science, and Cochrane Library was conducted. Studies underwent title/abstract and full text screening by two reviewers, with a third reviewer resolving any conflicts. Remaining studies underwent data extraction. Results: Seventeen studies were eligible for data extraction after the review process, where 12 studies found significantly poorer cognition in those suffering from olfactory dysfunction, four studies showed no association between cognition and olfaction, and one study reported lower anosmia prevalence among patients with cognitive impairment. Conclusion: The majority of studies in this review find that olfactory dysfunction is associated with poorer cognition. More rigorous studies are needed to further elucidate the relationship between olfaction and cognition after COVID-19.

Olfaction, body mass index, and quality of life with cystic fibrosis combination therapy.

BACKGROUND: Triple-combination therapy of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to reduce morbidity and mortality in people with cystic fibrosis (PwCF). Although patient body mass index (BMI) favorably increases with ETI treatment, factors contributing to this improvement are poorly characterized. Olfaction contributes to appetite stimulation and anticipation of eating, where higher rates of olfactory impairment (OI) in PwCF may contribute to malnutrition and BMI instability in this population. METHODS: The authors performed a prospective cohort study analyzing 41 CF patient responses to the Cystic Fibrosis Questionnaire-Revised (CFQR) and the 22-Item Sino-Nasal Outcome Test (SNOT-22) and used generalized estimating equations to understand the change in survey variables from being untreated (baseline) to undergoing 3 months of ETI therapy (follow-up). RESULTS: Patients reported significant improvement in their sense of smell at follow-up (p = 0.0036). Their improvements in sense of smell were not confounded by changes in rhinologic or extranasal rhinologic symptoms. Self-reported quality of life (QoL) improved after 3 months of ETI therapy (p = < 0.0001) as did BMI (p = < 0.0001), but improved sense of smell did not independently mediate these changes in QoL and BMI. CONCLUSION: Our results support the impression that ETI therapy improves CF-associated rhinologic symptoms and reverses OI, while contributing to improvement in rhinologic QoL. Sense of smell is not an independent mediator of improved QoL and BMI in this population, suggesting that other factors may have a stronger role in these realms. However, given the subjective improvement in sense of smell, additional evaluation of OI using psychophysical chemosensory assessment will clarify the connection between olfaction, BMI, and QoL in PwCF.