Increased risk of asthma at age 10 years for children sensitized to multiple allergens

BACKGROUND: Childhood sensitization patterns have been previously found to be related to variable risk of early life allergic disease in several birth cohorts. OBJECTIVE: To determine whether these risks persist into later childhood. METHODS: In the birth cohort of the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, previous latent class analysis based on sensitization to 10 allergens found the following 4 early life sensitization patterns at age 2 years: highly sensitized, milk/egg dominated, peanut and inhalant(s), and low to no sensitization. At an age 10 study-specific visit, children were evaluated by an allergist for current asthma and atopic dermatitis through a physical examination and interviews with the child and parent or guardian. Total and specific immunoglobulin E (IgE), spirometry, and methacholine challenge were also completed. RESULTS: Compared with children sensitized to none or 1 allergen, children sensitized to 4 or more food and inhalant allergens at age 2 had the highest risk of current asthma (relative risk [RR], 4.42; 95% confidence interval [CI], 2.58-7.59; P \u3c .001) and bronchial hyperresponsiveness (RR, 1.77; 95% CI, 1.29-2.42; P \u3c .001). In addition, they had the highest levels of total IgE (geometric mean, 800 IU/mL; 95% CI, 416-1536) among the 4 groups. Risk of current atopic dermatitis did not depend on pattern of sensitization but remained increased for children with any sensitization (RR, 2.23; 95% CI, 1.40-3.55; P \u3c .001). No differences in spirometry (forced expiratory volume in 1 second, forced expiratory flow between 25% and 75%, and forced expiratory volume in 1 second/forced vital capacity) were identified. CONCLUSION: The previously reported importance of a specific pattern of sensitization in early life (sensitization to ≥4 inhalant and food allergens) continues to be associated with an increased risk of asthma, bronchial hyperresponsiveness, and high total IgE at age 10 years

Association between prenatal antimicrobial use and offspring attention deficit hyperactivity disorder

BACKGROUND: Gut-brain cross-talk may play an important role in modulating neurodevelopment. Few studies have examined the association between antimicrobials that influence infant gut microbiota assemblage and attention deficit hyperactivity disorder (ADHD). OBJECTIVE: To examine the association between maternal prenatal antimicrobial use and ADHD in offspring at 10 years of age. METHODS: Data are from the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, a racially and socioeconomically diverse birth cohort in metropolitan Detroit, Michigan. Maternal antimicrobial use was extracted from the medical record. ADHD diagnoses were based on parental report at the 10-year study visit. Poisson regression models with robust error variance were used to calculate risk ratios (RR). Cumulative frequency of exposure to antibiotics, and effect modification were also evaluated. RESULTS: Among the 555 children included in the analysis, 108 were diagnosed with ADHD. During pregnancy, 54.1% of mothers used antibiotics while 18.7% used antifungals. Overall, there was no evidence of an association between prenatal antibiotic exposure and ADHD (RR [95% CI] = 0.98 [0.75, 1.29]), but there was an increased risk of ADHD among those with mothers using 3+ courses of antibiotics (RR [95%CI] = 1.58 [1.10, 2.29]). Prenatal exposure to antifungals was associated with a 1.6 times higher risk of ADHD (RR [95% CI] = 1.60 [1.19, 2.15]). In examining effect modification by child sex for antifungal use, there was no evidence of an association among females (RR [95% CI] = 0.97 [0.42, 2.23]), but among males, prenatal antifungal use was associated with 1.82 times higher risk of ADHD (RR [95% CI] = 1.82 [1.29, 2.56]). CONCLUSIONS: Maternal prenatal antifungal use and frequent prenatal antibiotic use are associated with an increased risk of ADHD in offspring at age 10. These findings highlight the importance of the prenatal environment and the need for careful use of antimicrobials

Prenatal pet keeping and caregiver-reported attention deficit hyperactivity disorder through preadolescence in a United States birth cohort

BACKGROUND: While the keeping of pets has been shown to protect against childhood allergic disease and obesity, less is known regarding potential associations of prenatal pet keeping and attention deficit hyperactivity disorder (ADHD). We sought to examine the associations between prenatal dog or cat keeping with caregiver-reported ADHD in preadolescents in the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) birth cohort (N = 1258). METHODS: At an interview with the caregiver at child age 10-12 years, caregivers reported if the WHEALS child had ever been diagnosed with ADHD. Similarly, during an interview with the mother prenatally, pet keeping (defined as dog or cat kept inside ≥1 h/day) was ascertained. Logistic regression models were fit to examine the association of prenatal pet keeping (dog keeping and cat keeping, separately) with ADHD. RESULTS: A subset of 627 children were included in the analyses: 93 who had ADHD and 534 with neurotypical development. After accounting for confounders and loss to follow-up, maternal prenatal dog exposure was associated with 2.23 times (95% CI: 1.15, 4.31; p = 0.017) greater odds of ADHD among boys. Prenatal dog keeping was not statistically significantly associated with ADHD in girls (odds ratio = 0.27, 95% CI: 0.06, 1.12; p = 0.070). Prenatal cat keeping was not associated with ADHD. CONCLUSIONS: In boys, but not girls, maternal prenatal dog keeping was positively associated with ADHD. Further study to confirm these findings and to identify potential mechanisms of this association (e.g., modification of the gut microbiome, exposure to environmental toxicants or pet-related medications) is needed

The Burnout Epidemic Within A Viral Pandemic: Impact of a Wellness Initiative

Background: Anesthesiologists are at high risk of developing burnout, a condition which can lead to many deleterious effects for the physician, and far-reaching effects on their patients and hospital systems. The COVID-19 pandemic has presented new challenges that have further exacerbated the risk of burnout in anesthesiologists. It is critical to develop effective strategies to promote well-being and decrease burnout for physicians in this specialty. The purpose of this observational study was to evaluate the impact of a Physician Well-Being Initiative on distress and well-being in anesthesiologists. It was hypothesized that the wellness intervention would promote an improvement in well-being scores. Methods: The Physician Well-Being Initiative was launched in August 2019 in the Department of Anesthesiology, Pain Management and Perioperative Medicine at Henry Ford Hospital in Detroit, Michigan. The Physician Well-Being Initiative was designed to address several of the key factors that improve physician wellness, including 1) a sense of autonomy; 2) positive view of leadership; and 3) flexible schedule opportunities. To assess the impact of the Physician Well-Being Initiative on the well-being and distress scores of participating anesthesiologists, the physicians were emailed the validated Well-Being Index survey at baseline and 3, 6 and 12 months. The Well-Being Index evaluates multiple items of distress in the healthcare setting. The sample size was limited to the 54 anesthesiologists at Henry Ford Hospital. Results: Forty-four of the 54 anesthesiologists completed the baseline questionnaire. A total of 44 physicians answered the questionnaire at baseline, with more male than female physicians (35 males and 7 females) and the majority (17/44) in practice for 5-10 years. Thirty-two physicians completed the survey at 3 and 6 months, and 31 physicians at 12 months after the launch of the Physician Well-Being Initiative. Twenty-one physicians completed the questionnaire at all 4 time points. Although the COVID-19 pandemic started shortly after the 6-month surveys were submitted, results indicated that there was a 0.05 decrease in the Well-Being Index sum score for every 1-month of time (coefficient -0.05, 95% CI -0.01, -0.08, P = 0.013). This study shows that, with the wellness initiative in place, the department was able to maintain and potentially even reduce physician distress despite the concurrent onset of the pandemic. Conclusions: Following the launch of a sustained wellness initiative, this study demonstrates that physician wellness improved with time. This suggests that it takes time for a wellness initiative to have an effect on well-being and distress in anesthesiologists

Progression of C-reactive protein from birth through preadolescence varies by mode of delivery

INTRODUCTION: Delivery via caesarean section (C-section) has been associated with an increased risk of childhood chronic diseases such as obesity and asthma, which may be due to underlying systemic inflammation. However, the impact of specific C-section types may be differential, as emergency C-sections typically involve partial labor and/or membrane rupture. Our objectives were to determine if mode of delivery associates with longitudinal profiles of high sensitivity CRP (hs-CRP) -a marker of systemic inflammation-from birth through preadolescence, and to examine if CRP mediates the association between mode of delivery and preadolescent body mass index (BMI). METHODS: Data from the WHEALS birth cohort (N = 1,258) were analyzed; 564 of the 1,258 children in the cohort had data available for analysis. Longitudinal plasma samples (birth through 10-years of age) from 564 children from were assayed for hs-CRP levels. Maternal medical records were abstracted to obtain mode of delivery. Growth mixture models (GMMs) were used to determine classes of hs-CRP trajectories. Poisson regression with robust error variance was used to calculate risk ratios (RRs). RESULTS: Two hs-CRP trajectory classes were identified: class 1 (76% of children) was characterized by low hs-CRP, while class 2 (24% of children) was characterized by high and steadily increasing hs-CRP. In multivariable models, children delivered via planned C-section had 1.15 times higher risk of being in hs-CRP class 2, compared to vaginal deliveries (p = 0.028), while no association was found for unplanned C-section deliveries [RR (95% CI) = 0.96 (0.84, 1.09); p = 0.49]. Further, the effect of planned C-section on BMI z-score at age 10 was significantly mediated by hs-CRP class (percent mediated = 43.4%). CONCLUSIONS: These findings suggest potentially beneficial effects of experiencing partial or full labor, leading to a lower trajectory of systemic inflammation throughout childhood and decreased BMI during preadolescence. These findings may have implications for chronic disease development later in life

Longitudinal Characterization of Atopic Dermatitis Phenotypes in The Children\u27s Respiratory and Environmental Workgroup (CREW) Birth Cohort Consortium

Rationale: Previously identified longitudinal patterns of atopic dermatitis (AD) may lack generalizability and precision due to small sample size and limited time points. We identify and describe longitudinal AD phenotypes in a large consortium study. Methods: Data from 11 birth cohorts across the United States from the CREW (Children’s Respiratory and Environmental Workgroup) consortium were harmonized to determine physician diagnosis of AD in each year of life from 0-7 years of age (N=7,900). AD phenotypes were identified using Longitudinal Latent Class Analysis, and relationships with demographic variables were determined using multinomial logistic regression with a 3-step procedure to account for uncertainty in class membership. Results: We identified 5 classes of AD expression, selected based on model fit, interpretability, and clinical utility: Persistent AD (15.4%), Early AD with Potential Reoccurrence (2.7%), Late-Onset AD (7.0%), Transient Early AD (3.0%), and Minimal/No AD (72.0%). Males had significantly higher odds of Persistent AD (OR [95% CI]=1.47 [1.22, 1.75]) and Early AD with Potential Reoccurrence (OR [95% CI]=1.89 [1.19, 2.94]). Relative to White children, Black children had higher odds of Persistent AD (OR [95% CI]=2.50 [2.05, 3.05]), Early AD with Potential Reoccurrence (OR [95% CI]=3.07 [1.94, 4.85]), and Transient Early AD (OR [95% CI]=4.12 [2.62, 6.48]). Conclusions: Five AD phenotypes exist in a diverse national sample of children. Black children and males are at increased risk of early and persistent AD. These findings illustrate potential risk factors to target AD prevention

Longitudinal assessment of Allergic Outcomes and Atopic Dermatitis Phenotypes in The Children\u27s Respiratory and Environmental Workgroup (CREW) Birth Cohort Consortium

Rationale: Atopic dermatitis (AD) is a heterogenous inflammatory skin disease often associated with other allergic diseases. We characterized AD phenotypes and associated allergic outcomes longitudinally across a multi-site consortium. Methods: AD expression in 11 U.S. birth cohorts from the CREW (Children’s Respiratory and Environmental Workgroup) consortium was assessed in each year of life from age 0-7 years (N=7,900). Longitudinal Latent Class Analysis was performed to identify AD phenotypes. Five classes of AD were identified: Persistent AD (15.4%), Early AD with Potential Reoccurrence (2.7%), Late-Onset AD (7.0%), Transient Early AD (3.0%), and Minimal/No AD (72.0%). Serum allergen sensitization patterns and allergic clinical disease were associated with AD phenotype using multinomial logistic regression with a 3-step procedure to account for uncertainty in class membership. Results: Children with Persistent AD, Early AD with Potential Reoccurrence, and Transient Early AD were more likely to have food allergy compared to those with Minimal/No AD (OR[95% CI]=2.73[2.15, 3.45], 2.69[1.63, 4.45], 2.54[1.55, 4.16], respectively). These groups had similarly higher odds of food sensitization. Persistent AD (OR[95% CI]=1.81[1.48, 2.21]) and Early AD with Potential Reoccurrence (OR[95% CI]=3.66[1.90, 7.05]) had significantly higher odds of ever asthma relative to Minimal/No AD. At both 2-4 years and 5-7 years, persistent AD (OR[95% CI]=1.35[1.04, 1.74], 1.25[1.01, 1.53]) and Late-Onset AD (OR[95% CI]=1.68[1.13, 2.50], 2.22[1.33, 3.70]) relative to Minimal/No AD had higher odds of allergic rhinitis. Conclusions: Longitudinal AD phenotypes had varying associations with allergic sensitization, food allergy, asthma and allergic rhinitis, demonstrating the heterogeneity of allergic comorbidity risk associated with AD

Impact of Spirometry Race-Correction on Preadolescent Black and White Children

BACKGROUND: Race-correction for Black patients is standard practice in spirometry testing. History suggests that these corrections are at least partially a result of racist assumptions regarding lung anatomy among Black individuals, which can potentially lead to less frequent diagnoses of pulmonary diseases in this population. OBJECTIVE: To evaluate the impact of race-correction in spirometry testing among Black and White preadolescents, and examine the frequency of current asthma symptoms in Black children who were differentially classified depending on whether race-corrected or race-uncorrected reference equations were deployed. METHODS: Data from Black and White children who completed a clinical examination at age 10 years from a Detroit-based unselected birth cohort were analyzed. Global Lung Initiative 2012 reference equations were applied to spirometry data using both race-corrected and race-uncorrected (ie, population-average) equations. Abnormal results were defined as values less than the fifth percentile. Asthma symptoms were assessed concurrently using the International Study of Asthma and Allergies in Childhood questionnaire, while asthma control was assessed using the Asthma Control Test. RESULTS: The impact of race-correction on FEV1/FVC ratio was minimal, but abnormal classification of FEV1 results more than doubled among Black children when race-uncorrected equations were used (7% vs. 18.1%) and were almost 8 times greater based on FVC classification (1.5% vs. 11.4%). More than half of Black children differentially classified on FEV1 (whose FEV1 was classified as normal with race-corrected equations but abnormal with race-uncorrected equations) experienced asthma symptoms in the past 12 months (52.6%), which was significantly higher than Black children consistently classified as normal (35.5%, p=0.049), but similar to that of Black children consistently classified as abnormal using both race-corrected and race-uncorrected equations (62.5%, p=0.60). ACT scores were not different based on classification. CONCLUSIONS: Race-correction had an extensive impact on spirometry classification in Black children, and differentially classified children had a higher rate of asthma symptoms than children consistently classified as normal. Spirometry reference equations should be reevaluated to be aligned with current scientific perspectives on the use of race in medicine