Poonia, Seerat

Abstract RATIONALE. Significant sex-differences exist in asthma across the lifespan. Asthma prevalence and severity are greater in pre-pubescent boys compared to girls but greater in women after puberty. In women, asthma may improve after menopause when sex hormones wane. To address potential mechanisms underlying these changes, we compared the airway transcriptomics signatures of post-menopausal vs. premenopausal women. METHODS. We used bulk RNA seq data from bronchial epithelial cells from three different cohorts (SARP III, GEO-GSE85567, GEO-GSE201955) to perform a comprehensive analysis of differential gene expression and regulation. Data were combined into a meta-analysis, to compare pre-menopausal (n=114 cases with asthma, 48 controls) to post-menopausal women (n=52 cases with asthma, 13 controls). Differential gene expression between pre- and postmenopausal women was analyzed separately for asthma (Figure 1A) and control groups (not shown). Significant differentially expressed genes (DEGs) were identified by contrasting effect sizes (log fold-changes) between asthma and control groups using a Z-score interaction test. Accordingly, a scatter plot (Figure 1B) was created to represent whether differential gene expression between pre- and post-menopausal conditions is modified by disease status (asthma vs. control). The scatter plot also highlights that these findings are related to asthma per. se. and not to normal aging and menopausal transition. Pathway enrichment analysis was conducted using the differential expression data, followed by differential regulation analysis of the identified pathways. Statistical significance was assessed using a false discovery rate (FDR) threshold of 5%. RESULTS. Out of 15,468 genes that passed quality control, 19 genes were differentially expressed in bronchial epithelial cells from pre- and post-menopausal women with asthma (as compared to controls) (Figure 1A). Of these, 5 genes were down-regulated (ITLN1, POSTN, FCRL3, CCL22, PCSK6), and 14 genes were up-regulated (SPP1, S100A9, A2ML1, TNFRSF10C, CSF3R, OLFM1, C1QL2, NLRP3, HAL, PI3, RNASE1, TMEM178B, TNNI3, RNF175) when comparing pre- and post-menopausal women with asthma (Figure 1A). Of these 19 DEGs, 14 were differentially expressed in pre- as compared to post-menopausal women with asthma, but not in controls (Figure 1B). Comparing pre- to post-menopausal women with asthma, biologic pathways related to the innate and adaptive immune system activation and mitochondrial function (Electron transport Chain oxidative phosphorylation and ATP production) were both differentially regulated and expressed. CONCLUSIONS. This analysis highlights several DEGs and pathways that characterize asthma pathogenesis when comparing pre- and post-menopausal women, and emphasize the role of female sex hormones on the immune system response and mitochondrial function in asthma pathogenesis.

ObjectiveNonphysician health care workers are involved in high‐risk patient care during the COVID‐19 pandemic, placing them at high risk of mental health burden. The mental health impact of COVID‐19 in this crucial population has not been studied thus far. Thus, the objective of this study is to assess the psychosocial well‐being of these providers.Study DesignNational cross‐sectional online survey (no control group).SettingAcademic otolaryngology programs in the United States.Subjects and MethodsWe distributed a survey to nonphysician health care workers in otolaryngology departments across the United States. The survey incorporated a variety of validated mental health assessment tools to measure participant burnout (Mini‐Z assessment), anxiety (Generalized Anxiety Disorder–7), distress (Impact of Event Scale), and depression (Patient Health Questionnaire–2). Multivariable logistic regression analysis was performed to determine predictive factors associated with these mental health outcomes.ResultsWe received 347 survey responses: 248 (71.5%) nurses, 63 (18.2%) administrative staff, and 36 (10.4%) advanced practice providers. A total of 104 (30.0%) respondents reported symptoms of burnout; 241 (69.5%), symptoms of anxiety; 292 (84.1%), symptoms of at least mild distress; and 79 (22.8%), symptoms of depression. Upon further analysis, development of these symptoms was associated with factors such as occupation, practice setting, and case load.ConclusionFrontline otolaryngology health care providers exhibit high rates of mental health complications, particularly anxiety and distress, in the wake of COVID‐19. Adequate support systems must be put into place to address these issues.

AbstractBackgroundOtolaryngologists are among the highest risk for COVID‐19 exposure.MethodsThis is a cross‐sectional, survey‐based, national study evaluating academic otolaryngologists. Burnout, anxiety, distress, and depression were assessed by the single‐item Mini‐Z Burnout Assessment, 7‐item Generalized Anxiety Disorder Scale, 15‐item Impact of Event Scale, and 2‐item Patient Health Questionnaire, respectively.ResultsA total of 349 physicians completed the survey. Of them, 165 (47.3%) were residents and 212 (60.7%) were males. Anxiety, distress, burnout, and depression were reported in 167 (47.9%), 210 (60.2%), 76 (21.8%), and 37 (10.6%) physicians, respectively. Attendings had decreased burnout relative to residents (odds ratio [OR] 0.28, confidence interval [CI] [0.11‐0.68];P= .005). Females had increased burnout (OR 1.93, CI [1.12.‐3.32];P= .018), anxiety (OR 2.53, CI [1.59‐4.02];P< .005), and distress (OR 2.68, CI [1.64‐4.37];P< .005). Physicians in states with greater than 20 000 positive cases had increased distress (OR 2.01, CI [1.22‐3.31];P= .006).ConclusionDuring the COVID‐19 pandemic, the prevalence of burnout, anxiety, and distress is high among academic otolaryngologists.