The impact of insomnia and depression on asthma control.

BACKGROUND: Poor sleep quality is often reported by individuals with asthma, particularly by those who have poor asthma control overall. However, there is little understanding of how underlying sleep disorders such as insomnia may impact asthma control. Furthermore, given the frequent overlap of depression and insomnia, the incremental impact of mood disorders and insomnia on asthma control remains unclear. METHODS: We conducted a retrospective analysis of patients at a large asthma center to further elucidate connections between these disease processes. Asthma patients with and without a diagnosis of insomnia were matched by age, sex, Charlson comorbidity index, and biologic therapy. We evaluated the presence of concurrent obstructive sleep disorder, mood disorders, exacerbation frequency, and asthma control test (ACT) scores. RESULTS: From a cohort of 659 patients with an asthma diagnosis, 89 subjects with insomnia (13.5%) were matched 1:1 to patients without insomnia. Compared to those without insomnia, patients with insomnia were more likely to have a concurrent diagnosis of obstructive sleep apnea (57.3% vs. 18%, p < 0.001) and to have a diagnosis of depression or anxiety (68.5% vs. 11.4%, p < 0.001). Among insomnia patients, there was an average of 0.93 asthma exacerbations per year, compared to 0.59 exacerbations per year for those without insomnia (p = 0.039). CONCLUSION: Our data reveal a considerable interaction between insomnia, depression, and obstructive sleep apnea in individuals with asthma. The increased exacerbation rate suggests that underlying sleep and mood disorders negatively affect asthma control.

Allergen skin test responses in broad U.S. asthma population in those with and without rhinitis.

Background: Asthma and allergic rhinitis are pathologically interlinked conditions. Despite skin testing (ST) being pivotal for evaluating allergic sensitization, U.S. data that date back to 1960s on ST reactivity patterns in subjects with asthma remain sparse. Objective: The purpose of this study was to elucidate seasonal, perennial ST responses, and their relationship with asthma severity, early versus late onset disease, and immunoglobulin E (IgE) levels. Methods: Five hundred patients with asthma were randomly selected from the National Jewish Health electronic medical record over a 3-year span. Demographic, clinical, and allergen ST reactivity data for a battery of seasonal and perennial allergens were procured, including total IgE levels, asthma onset, and severity, by using t-tests, χ² tests, and Analysis of Variance (ANOVA), patterns of reactivity were assessed for overall, seasonal, and perennial allergens in relation to IgE levels, asthma onset, and severity. Results: Of the 500 patients, 398 were analyzed. 63.3% were women, 50.1% had adult-onset asthma, and 86.1% had rhinitis; 75.3% tested positive to one or more allergens, with men demonstrating higher overall (p = 0.039) and perennial (p = 0.035) sensitization. ST reactivity varied based on the presence of rhinitis for seasonal (p = 0.028) but not perennial (p = 0.733) allergens. Asthma severity was not significantly associated with ST reactivity (p > 0.10). ST positivity for perennial (p < 0.001) but not seasonal (p = 0.128) allergens was higher in childhood-onset asthma versus adult-onset asthma despite both groups having a large percentage of reactors. Elevated IgE levels correlated with ST reactivity (p < 0.01). Conclusion: Our study represents a unique comprehensive evaluation of ST reactivity in a U.S. asthma population, which is lacking in the literature, when factoring in asthma onset, severity, and IgE levels. Our findings underscore the importance of allergen sensitization in asthma, regardless of severity, concurrent rhinitis symptoms, or asthma onset, which challenge some of the prevailing assumptions about the relationship between allergen sensitization and asthma onset.

Total IgE as a biomarker of omalizumab response in chronic spontaneous urticaria: A meta-analysis.

Background: Omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) that is refractory to antihistamines. Total immunoglobulin E (IgE) levels have emerged as a possible biomarker to predict response to omalizumab. However, the existing literature is heterogenous, with conflicting conclusions with regard to the role of total IgE levels. Objective: We sought to clarify the role of evaluating total IgE levels in patients with CSU by performing a meta-analysis on the existing literature to determine if meaningful changes exist between responders and nonresponders to omalizumab. Methods: A total of 68 unique citations were returned and screened by two independent reviewers. Editorials, reviews, and case reports were excluded, and a total of 33 original articles were identified and underwent secondary evaluation. Studies that present mean ± standard deviation total IgE levels and/or 95% confidence intervals (CI) were included, whereas studies with < 25 subjects were excluded. Three studies ultimately met these criteria. Results: We found a mean difference in total IgE levels between those who responded to omalizumab versus those without a response of 49.76 (95% CI, 7.13-92.38; p = 0.02), which demonstrated higher mean IgE values in responders compared with nonresponders. Conclusion: This study presents additional evidence that supports evaluation of total IgE levels as it pertains to response to omalizumab therapy in CSU. When considering the current evidence, it seems reasonable to consider the baseline total IgE level as a biomarker to predict the treatment response to omalizumab. Based on the existing literature, we cannot conclude at what threshold nonresponse is more likely to occur.

Chronic rhinosinusitis and olfaction after highly effective modulator therapy: The role of individual sinus inflammation.

KEY POINTS: Individual sinus opacification (ISO) is measurable via a convolutional neural network approach. ISO decreased through 2 years after highly effective modulator therapy was initiated. In adults with cystic fibrosis, ISO did not correlate with quality of life or olfaction.

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.

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.