Sociodemographic factors linked to food allergy diagnosis among high-risk children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a known risk factor for the development of food allergy (FA). Prior work has suggested disparities in diagnosis/management of FA in urban populations. OBJECTIVE: To determine whether socioeconomic conditions, as measured by the area deprivation index and insurance status, or racial/ethnic self-identity was associated with risk of FA diagnosis (DFA), evaluation by an allergist, or objective FA testing among high-risk children with AD. METHODS: This is a retrospective cohort study of pediatric patients with physician-diagnosed AD who had received primary care at a single urban academic tertiary care center between 2009 and 2022. Statistical analysis in SPSS (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0, Armonk, NY) used χ2, analysis of variance, and logistic regression. RESULTS: In a total of 3365 pediatric subjects, 41.3% identified as non-Hispanic Black, 33.9% Hispanic, 6.9% Asian, and 14.9% non-Hispanic White. Hispanic children with AD and DFA were significantly less likely to be evaluated by an allergist than White or Asian children (65.9% vs 82.8% and 80.3%, P = .001 and P = .02). Non-Hispanic Black children with AD and DFA were more likely to have no objective FA testing than White children (20.9% vs 12.1%, P = .04). The White and Asian children were more likely to undergo the thorough combination of both blood and skin testing for DFA than Black or Hispanic children (15.5% and 22.4% vs 7.1% and 7.9%, respectively, P = .007, P = .00005, P = .03, P = .0008). CONCLUSION: Labeling at-risk young children with FA without thorough objective testing can affect their nutrition and quality of life. Barriers to equitable evaluation of DFA should be further investigated and addressed.

Pharmacoequity and Biologics in the Allergy Clinic: Providing the Right Care, at the Right Time, Every Time, to Everyone.

Pharmacoequity refers to equity in access to pharmacotherapy for all patients and is an especially large barrier to biologic agents in patients with allergic diseases. Value-based care models can prompt clinicians to address social determinants of health, promoting pharmacoequity. Pharmacoequity is influenced by numerous factors including socioeconomic status, which may be mediated through insurance status, educational attainment, and access to specialist care. In addition to lower socioeconomic status, race and ethnicity, age, locations isolated from care systems, and off-label indications for biologic agents all constitute barriers to pharmacoequity. Whereas pharmaco-inequity is more apparent for expensive biologics, it also affects many other allergy treatments including epinephrine autoinjectors and SMART for asthma. Current programs aimed at alleviating cost barriers are imperfect. Patient assistance programs, manufacturer-sponsored free drug programs, and rebates often increase the complexity of care, with resultant inequity, particularly for patients with lower health literacy. Ultimately, single silver-bullet solutions are elusive. Long-term improvement instead requires a combination of research, advocacy, and creative problem-solving to design more intelligent and efficient systems that provide timely access to necessary care for every patient, every time.

Food Allergy Reaction Severity and Management in a Diverse Population.

BACKGROUND: Definitive treatment for food allergy reactions including anaphylaxis varies widely by reaction severity and socioeconomic status, but little data exist to characterize the relationship between severity, management, and race and ethnicity. OBJECTIVE: To analyze the differences in reaction severity, epinephrine use, and emergency room (ER) use by race and ethnicity in a large, diverse, food-allergic cohort. METHODS: We analyzed intake data from participants in the Food Allergy Outcomes Related to White and African-American Racial Differences cohort on the history of food allergy reactions, severity of the reactions, and management associated with each reaction. We used descriptive statistics as well as mixed-effects logistic and Poisson models to describe the differences in reaction severity, ER visits, and total lifetime epinephrine use by race and ethnicity. RESULTS: A total of 784 children were included in the analysis: 425 (54.2%) were non-Hispanic White, 282 (36.0%) were non-Hispanic Black, and 77 (9.8%) were Hispanic/Latino. Non-Hispanic Black children had increased odds of more severe reactions (odds ratio, 1.7; 95% CI, 1.2-2.3) and higher odds of going to the ER (odds ratio, 2.8; 95% CI, 1.4-5.4). Both non-Hispanic Black (incidence rate ratio, 0.4; 95% CI, 0.3-0.5) and Hispanic/Latino (incidence rate ratio, 0.3; 95% CI, 0.2-0.5) children had lower rates of total lifetime epinephrine use. CONCLUSIONS: There are significant disparities in the severity and treatment of food allergy reactions by race and ethnicity, resulting in increased ER use and decreased total lifetime epinephrine use. Equipping parents with resources and tools on management of food allergy reactions may result in decreased disparity in access to definitive care.

Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2).

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration-approved for the most common form, CRS without nasal polyps (also called "chronic sinusitis"). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays. OBJECTIVE: Assess EDS-FLU efficacy for CRS (irrespective of nasal polyps). METHODS: Two randomized, EDS-placebo-controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24. RESULTS: ReOpen1 (N = 332) composite symptom score least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -1.58 and -1.60 versus -0.62 (P < .001, P < .001); ReOpen2 (N = 223), -1.54 and -1.74 versus -0.81 (P = .011, P = .001). In ReOpen1, sinus opacification least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -5.58 and -6.20 versus -1.60 (P = .045, P = .018), and in ReOpen2, -7.00 and -5.14 versus +1.19 (P < .001, P = .009). Acute disease exacerbations were reduced by 56% to 66% with EDS-FLU versus EDS-placebo (P = .001). There were significant, and similar magnitude, symptom reductions in patients using standard-delivery nasal steroid products just before entering the study (P < .001). Adverse events were similar to standard-delivery intranasal steroids. CONCLUSIONS: EDS-FLU is the first nonsurgical treatment demonstrated to reduce symptoms, intrasinus opacification, and exacerbations in replicate randomized clinical trials in CRS, regardless of polyp status.

Human cytomegalovirus infection enhances 5­lipoxygenase and cycloxygenase­2 expression in colorectal cancer.

Colorectal cancer (CRC) is one of the most common and fatal types of cancer. Inflammation promotes CRC development, however, the underlying etiological factors are unknown. Human cytomegalovirus (HCMV), a virus that induces inflammation and other cancer hallmarks, has been detected in several types of malignancy, including CRC. The present study investigated whether HCMV infection was associated with expression of the pro­inflammatory enzymes 5­lipoxygenase (5­LO) and cyclooxygenase­2 (COX­2) and other molecular, genetic and clinicopathological CRC features. The present study assessed 146 individual paraffin­embedded CRC tissue microarray (TMA) cores already characterized for TP53 and KRAS mutations, microsatellite instability (MSI) status, Ki­67 index and EGFR by immunohistochemistry (IHC). The cores were further analyzed by IHC for the expression of two HCMV proteins (Immediate Early, IE and pp65) and the inflammatory markers 5­LO and COX­2. The CRC cell lines Caco­2 and LS­174T were infected with HCMV strain VR1814, treated with antiviral drug ganciclovir (GCV) and/or anti­inflammatory drug celecoxib (CCX) and analyzed by reverse transcription­quantitative PCR and immunofluorescence for 5­LO, COX­2, IE and pp65 transcripts and proteins. HCMV IE and pp65 proteins were detected in ~90% of the CRC cases tested; this was correlated with COX­2, 5­LO and KI­67 expression, but not with EGFR immunostaining, TP53 and KRAS mutations or MSI status. In vitro, HCMV infection upregulated 5­LO and COX­2 transcript and proteins in both Caco­2 and LS­174T cells and enhanced cell proliferation as determined by MTT assay. Treatment with GCV and CCX significantly decreased the transcript levels of COX­2, 5­LO, HCMV IE and pp65 in infected cells. HCMV was widely expressed in CRC and may promote inflammation and serve as a potential new target for CRC therapy.

Gut microbiome is associated with asthma and race in children with food allergy.

BACKGROUND: The composition of the gut microbiome has been associated with development of atopic conditions such as food allergy (FA) and asthma. African American or Black children with FA have higher rate of asthma compared to their White counterparts. OBJECTIVE: We sought to investigate whether the diversity and relative abundance (RA) of gut microbiota is different between children with FA from different racial backgrounds living in the same cities. Furthermore, we aimed to understand whether the difference in the gut microbiota is associated with asthma in children with FA. METHODS: We analyzed and compared the stool microbiome of a cohort of Black and White children with FA by shotgun genomic sequencing. RESULTS: A total of 152 children with IgE-mediated FA enrolled onto FORWARD (Food Allergy Outcomes Related to White and African American Racial Differences); 30 Black and 122 White children were included. The RA of several bacteria was associated with race and asthma. Most notably the RA of Bacteroides thetaiotaomicron, Chlamydia thrachomatis, Parabacteroides goldsteinii, and Bacteroides eggerthii were significantly higher, while the RA of Bifidobacterium sp CAG:754, Parabacterium johnsonii, Bacteroides intestinalis, and Bifidobacterium breve were significantly lower in stool samples of Black children compared to White children. Asthma was associated with lower RA of B breve, Bifidobacterium catenulatum, Prevotella copri, Veilloella sp CAG:933, and Bacteroides plebius, and higher RA of 3 Bacteroides species. CONCLUSIONS: The observed variations in the gut microbiota of Black and White children such as differences in the Bacteroides and Bifidobacterium species along with their association to history of asthma in our cohort is indicative of their potential role in the higher rate of asthma observed among Black children with FA.

Reorganization of pancreas circadian transcriptome with aging.

The evolutionarily conserved circadian system allows organisms to synchronize internal processes with 24-h cycling environmental timing cues, ensuring optimal adaptation. Like other organs, the pancreas function is under circadian control. Recent evidence suggests that aging by itself is associated with altered circadian homeostasis in different tissues which could affect the organ's resiliency to aging-related pathologies. Pancreas pathologies of either endocrine or exocrine components are age-related. Whether pancreas circadian transcriptome output is affected by age is still unknown. To address this, here we profiled the impact of age on the pancreatic transcriptome over a full circadian cycle and elucidated a circadian transcriptome reorganization of pancreas by aging. Our study highlights gain of rhythms in the extrinsic cellular pathways in the aged pancreas and extends a potential role to fibroblast-associated mechanisms.

Reorganization of Pancreas Circadian Transcriptome with Aging.

The evolutionarily conserved circadian system allows organisms to synchronize internal processes with 24-h cycling environmental timing cues, ensuring optimal adaptation. Like other organs, the pancreas function is under circadian control. Recent evidence suggests that aging by itself is associated with altered circadian homeostasis in different tissues which could affect the organ's resiliency to aging-related pathologies. Pancreas pathologies of either endocrine or exocrine components are age-related. Whether pancreas circadian transcriptome output is affected by age is still unknown. To address this, here we profiled the impact of age on the pancreatic transcriptome over a full circadian cycle and elucidated a circadian transcriptome reorganization of pancreas by aging. Our study highlights gain of rhythms in the extrinsic cellular pathways in the aged pancreas and extends a potential role to fibroblast-associated mechanisms.

Histopathologic Features of Chronic Rhinosinusitis in Diabetic Patients.

OBJECTIVE: To explore how diabetes mellitus impacts chronic rhinosinusitis clinically and on structured histopathology to provide insights on new potential chronic rhinosinusitis endotypes. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic center. METHODS: A retrospective study of chronic rhinosinusitis patients who underwent functional endoscopic sinus surgery from 2015 to 2020 was performed. Structured 13-variable histopathology reports were generated from intraoperative sinonasal specimens. These variables were compared against demographic factors, comorbidities, culture data, and preoperative Lund-Mackay and SNOT-22 scores using logistic regression. RESULTS: There were 411 patients, including 52 diabetics. Diabetes was associated with higher mean body mass index (34.9 vs 29.2; p < .001), age (57.8 vs 48.0; p < .001), and Gram-negative (40.2% vs 22.7%; p < .030) and coagulase-negative Staphylococcus (49.0% vs 28.5%; p = .008) culture rates. Black (23.1% vs 18.7%) and Hispanic (23.1% vs 8.6%) races were more common with diabetes (p = .026). Gender, smoking, polyp status, and Lund-Mackay and SNOT-22 scores did not differ between groups. Diabetics had more fungal elements (13.5% vs 3.3%, p = .018); no other histopathological differences were seen. When controlling for demographic variables and comorbidities, diabetes independently predicted the presence of fungal elements (HR 4.38, p = .018). CONCLUSION: Diabetic chronic rhinosinusitis patients demonstrated increased fungal elements on structured histopathology. Other histopathological features were unaffected by diabetes. These findings may have important implications on the medical and surgical management of diabetic chronic rhinosinusitis patients in which early fungal disease assessment is paramount.

Understanding the CRSwNP Patient as Whole.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a distinct inflammatory disease of the upper airways with a significant impact on the health and quality of life of affected patients. Several comorbid conditions such as allergic rhinitis, asthma, sleep disorders, and gastroesophageal reflux disease are commonly reported in patients with CRSwNP. OBJECTIVE: In this article, we intended to review the UpToDate information on how these comorbidities can impact CRSwNP patients' health and well-being. METHODS: A PUBMED search was performed to review relevant recent article on the topic. RESULTS: While there have been significant advances in the knowledge and management options for CRSwNP in the past few years, additional studies are needed to understand the underlying pathophysiologic mechanisms of these associations. In addition, awareness of the impact of CRSwNP on mental health, quality of life, and cognition is paramount to treating this condition. CONCLUSION: Recognition and addressing CRSwNP comorbidities such as allergic rhinitis, asthma, sleep disorders, gastroesophageal reflux disease, and cognitive function impairment are important to optimally understand and manage the patient with CRSwNP as a whole.

Accelerating Food Allergy Research: Need for a Data Commons.

Food allergy is a significant health problem affecting approximately 8% of children and 11% of adults in the United States. It exhibits all the characteristics of a "complex" genetic trait; therefore, it is necessary to look at very large numbers of patients, far more than exist at any single organization, to eliminate gaps in the current understanding of this complex chronic disorder. Advances may be achieved by bringing together food allergy data from large numbers of patients into a Data Commons, a secure and efficient platform for researchers, comprising standardized data, available in a common interface for download and/or analysis, in accordance with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles. Prior data commons initiatives indicate that research community consensus and support, formal food allergy ontology, data standards, an accepted platform and data management tools, an agreed upon infrastructure, and trusted governance are the foundation of any successful data commons. In this article, we will present the justification for the creation of a food allergy data commons and describe the core principles that can make it successful and sustainable.

Assessing Disparities in the Prevalence of Atopic Comorbidities Among Food-Allergic Children.

BACKGROUND: Previous studies have reported that Black children with food allergy (FA) have higher risk of atopic comorbidities than White children. OBJECTIVE: Our study sought to understand if disparities in the prevalence of atopic comorbidities among children with FA are driven by individual and community-level socioeconomic status (SES). METHODS: We analyzed data from a prospective, multicenter cohort investigating the natural history of pediatric atopy: the Food Allergy Outcomes Related to White and African American Racial Differences (FORWARD) study. A validated, multicomponent area deprivation index (ADI) percentile score was tabulated by the census block group for each subject's home address. The association of ADI with atopic comorbidities in FA was assessed via multivariable regression analysis. RESULTS: Of the 700 children in this study, the mean ADI was 37.7 (95% confidence interval: 35.6-39.7). The mean ADI was higher in children with asthma (43.3) compared with those without asthma (31.8), which remained significant after adjusting for race (P < .0001). Children with allergic rhinitis (AR) had a higher mean ADI (39.1) compared with those without (33.4) (P = .008). ADI was associated with secondhand smoking, parents' education, and household income. Black children had a higher risk for asthma after adjusting for ADI and SES-related factors. CONCLUSION: The independent association of ADI with asthma and AR, regardless of race, suggests a role of neighborhood-level socioeconomic deprivation in the development of these conditions among children with FA. Black children with FA remained at higher risk for asthma after adjusting for SES-related variables, which can indicate an independent risk for asthma in these children.

Race and ethnicity define disparate clinical outcomes in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common upper airways inflammatory disease requiring multidisciplinary care. OBJECTIVE: To evaluate if African Americans (AA), Latinxs, and nonLatinx White (White) patients have different chronic rhinosinusitis outcomes and to identify associated factors impacting these outcomes. METHODS: We conducted a large prospective cohort study of CRS patients who were evaluated and followed for several clinical variables at the initial encounter and after continuous management of CRS for a mean of 40 months. The Sinonasal Outcome Test (SNOT-22) and Lund-MacKay scores were measured on initial visits, and SNOT-22 was repeated at the end of follow-up. Logistic regression was used to compare outcomes between the different groups adjusted for comorbidities and demographics. RESULTS: Among the 977 enrolled CRS cases, 615 (63.0%), 235 (24.1%) and 138 (13.0%) were White, AA and Latinx respectively. There was no difference in severity of CRS based on Lund-MacKay scores and SNOT-22 scores, and frequency of other comorbidities at presentation among the 3 groups. During the follow-up period, compared with Whites, AA and Latinx were less frequently evaluated by an allergist. AAs had less frequent CRS related visits and lower final SNOT-22 score compared with Whites. CONCLUSION: Although our enrolled patients from the 3 ethnic groups had similar clinical characteristics and disease burden at baseline, AAs had less frequent follow-up visits and worse final SNOT-22 after 40 months of follow-up. The observed poorer outcomes in AAs are likely owing to inequity in healthcare access evidenced by differences in insurance and suboptimal management of CRS.

Self-Efficacy Among Caregivers of Children With Food Allergy: A Cohort Study.

OBJECTIVE: The prevalence of pediatric food allergy (FA) is increasing and, due to early disease onset, requires significant caregiver management that is associated with psychosocial burden. Caregiver perception of how they cope and handle FA-related events (self-efficacy) has been linked to psychosocial outcomes in racially/geographically homogenous samples. This study explores FA-related caregiver self-efficacy and associations with FA-related caregiver quality of life (QoL) in a diverse cohort. METHODS: Caregivers of children, diagnosed with IgE-mediated FA who identified as non-Hispanic Black or White, were recruited from U.S. academic allergy clinics. Caregivers completed demographic and medical questionnaires, the Food Allergy Self-Efficacy Scale for Parents (FASE-P), Food Allergy Independent Measure-Parent Form (FAIM), and the Food Allergy Quality of Life-Parental Burden (FAQL-PB). Bivariate and multivariate associations estimated relationships between study variables. RESULTS: Caregivers of 365 children (Mage = 5.8 years, 62.2% male, 31.1% Black) were enrolled. Caregivers reported high FA self-efficacy (M = 82.06/100), moderate perceptions of risk/FA severity (FAIM: M = 3.9/7), and some limitations on the FAQL-PB (M = 3.9/7). Self-efficacy was related to lower perceptions of risk/FA severity across all demographic groups (r = -.42, p < .001). Caregivers who reported higher self-efficacy reported better QoL, particularly Black caregivers (r = .67). CONCLUSIONS: In this sample of caregivers of children with FA, greater self-efficacy was related to improved QoL regardless of sociodemographic factors. Caregivers' perception of risk was lower for those with greater self-efficacy. Future research into the impact of FA management on QoL among diverse caregivers is needed.