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Background: Few studies have examined long‐term outcomes following oral immunotherapy (OIT); none have examined long‐term risks and benefits associated with distinct clinical outcomes (desensitization, remission). Methods: Participants completing the probiotic and peanut oral immunotherapy (PPOIT) ‐003 randomized trial were enrolled in a follow‐on study, PPOIT‐003LT. Peanut ingestion, reactions, and health‐related quality of life (HRQOL) were monitored prospectively. Outcomes at 1‐year and 2‐years post‐treatment were examined by treatment group and by post‐OIT clinical outcome (remission, desensitization without remission [DWR], allergic). Results: 86% (151/176) of eligible children enrolled. Post‐treatment peanut ingestion at 2‐years post‐treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2‐years post‐treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI −0.03, 0.20), p =.127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD −0.21 (95%CI −0.39; −0.03), p =.02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p =.001) participants. At 2‐years post‐treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD −0.54 (95%CI −0.99, −0.10), p =.017) and allergic (MD −0.82 (95%CI −1.25, −0.38), p <.001). Conclusion: By 2‐years post‐treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient‐preferred treatment outcome over desensitization or remaining allergic. [ABSTRACT FROM AUTHOR]

Introduction: Physical activity (PA) during pregnancy has numerous benefits, which may be mediated via effects on the immune system. However, supportive evidence is inconsistent and is mainly from studies in high‐risk groups. We estimated the effect of PA during pregnancy on systemic inflammatory markers and cytokines in mothers recruited in the Barwon infant study. Material and Methods: The Barwon infant study is a prebirth cohort of 1064 mothers recruited in the Barwon Region of Victoria, Australia. Participants reported their previous week's PA at their 28‐week antenatal appointment using the International PA Questionnaire. Women were grouped into low, moderate, and high PA categories based on daily duration and weekly frequency of walking, moderate‐ or vigorous‐intensity PA. Women reporting moderate levels of PA, consistent with current recommendations, served as the comparison group. Markers of systemic inflammation, high‐sensitivity C‐reactive protein (hsCRP), glycoprotein acetyls (GlycA), and 17 cytokines were measured at 28 weeks gestation and log transformed as appropriate. Regression analyses adjusted for maternal smoking, gestational diabetes mellitus, prepregnancy BMI, and household size were performed. Results: Compared to women in the moderate group (n = 371, 42%), women reporting low PA (n = 436, 50%) had 10.1% higher hsCRP (95% CI (3.7% to 16.6%), p < 0.01) while women in high PA (n = 76, 9%) had a 14% higher hsCRP (95% CI (3.1% to 24.8%), p = 0.01). Women in the high PA category had higher interleukin (IL)‐4 (q = 0.03) and IL‐9 (q = 0.03) levels compared to those in moderate category. Each vigorous MET minute/week was associated with lower GlycA (β = −0.004, 95% CI (−0.044 to 0.035); p = 0.03). Conclusions: Low and high PA are each associated with higher hsCRP than moderate PA, suggesting that undertaking the recommended moderate PA during pregnancy decreases systemic inflammation. High PA affects T cell‐associated cytokines during pregnancy. Evidence from our study suggests that PA can modulate the immune responses during pregnancy. Studies are now required to assess whether PA during pregnancy impacts maternal and infant clinical outcomes by modifying inflammatory responses. [ABSTRACT FROM AUTHOR]

Background: There are no studies of longitudinal immunoglobulin measurements in a population‐based cohort alongside challenge‐confirmed peanut allergy outcomes. Little is known about biomarkers for identifying naturally resolving peanut allergy during childhood. Objectives: To measure longitudinal trends in whole peanut and component Ara h 2 sIgE and sIgG4 in the first 10 years of life, in a population cohort of children with challenge‐confirmed peanut allergy, and to determine whether peanut‐specific immunoglobulin levels or trends are associated with peanut allergy persistence or resolution by 10 years of age. Methods: One‐year‐old infants with challenge‐confirmed peanut allergy (n = 156) from the HealthNuts study (n = 5276) were prospectively followed at ages 4, 6, and 10 years with questionnaires, skin prick tests, oral food challenges, and plasma total‐IgE, sIgE and sIgG4 to peanut and Ara h 2. Results: Peanut allergy resolved in 33.9% (95% CI = 25.3%, 43.3%) of children by 10 years old with most resolving (97.4%, 95% CI = 86.5%, 99.9%) by 6 years old. Decreasing Ara h 2 sIgE (p =.01) and increasing peanut sIgG4 (p <.001), Ara h 2 sIgG4 (p =.01), peanut sIgG4/sIgE (p <.001) and Ara h 2 sIgG4/sIgE (p <.001) from 1 to 10 years of age were associated with peanut allergy resolution. Peanut sIgE measured at 1 year old had the greatest prognostic value (AUC = 0.75 [95% CI = 0.66, 0.82]); however, no single threshold produced both high sensitivity and specificity. Conclusion: One third of infant peanut allergy resolved by 10 years of age. Decreasing sIgE and sIgG4 to peanut and Ara h 2 over time were associated with natural resolution of peanut allergy. However, biomarker levels at diagnosis were not strongly associated with the natural history of peanut allergy. [ABSTRACT FROM AUTHOR]

This review summarizes recent advances in characterizing the transcriptional pathways associated with outcomes following Oral Immunotherapy. Recent technological advances including single‐cell sequencing are transforming the ways in which the transcriptional landscape is understood. The application of these technologies is still in its infancy in food allergy but here we summarize current understanding of gene expression changes following oral immunotherapy for food allergy and specific signatures underpinning the different clinical outcomes of desensitization and remission (sustained unresponsiveness). T helper 2A cells have been identified as a cell type which correlates with disease activity and is modified by treatment. Molecular features at study entry may differentiate individuals who achieve more positive outcomes during OIT. Recent findings point to T cell anergy and Type 1 interferon pathways as potential mechanisms supporting redirection of the allergen‐specific immune response away from allergy towards remission. Despite these developments in our understanding of immune mechanisms following OIT, there are still significant gaps. Additional studies examining immune signatures associated with long term and well‐defined clinical outcomes are required to gain a more complete understanding of the pathways leading to remission of allergy, in order to optimize treatments and gain improved outcomes for patients. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) is a known risk factor for a range of adverse outcomes, such as facial dysmorphism, adverse birth outcomes, and neurodevelopmental changes. Preclinical research shows that PAE also inhibits lung development, lowers surfactant protein expression, has detrimental effects on alveolar macrophages, and decreases both T and B cell numbers. However, clinical evidence of respiratory impacts from PAE is limited. This study explored whether lung function, wheeze, and incidence of respiratory infections differ in children with PAE compared with unexposed children. Methods: Data from the Barwon Infant Study (n = 1074) were examined. PAE data were extracted from maternal questionnaires at trimesters 1 and 2 (combined), and trimester 3, and included as "total standard drinks" during each trimester and total pregnancy intake, a binary yes/no for PAE, and binge drinking (>5 standard drinks in one session). Respiratory outcomes were parent‐reported wheeze, lung function (measured by multiple breath washout), and parent report and medical record indicators of health service attendances for respiratory conditions. Linear and logistic regressions were performed to quantify relationships between PAE and respiratory outcomes, controlling for socioeconomic status, birthweight, sex, gestational age, and maternal smoking. Results: Binge drinking was associated with increased health service attendance for respiratory condition(s) in the first 12 months of life (OR = 5.0, 95% CI (1.7, 20.7), p = 0.008). We did not find a relationship between binary PAE and binge drinking with lung function at 4 weeks of age or wheeze at 12 months. The number of standard drinks consumed in trimester two was associated with a lower lung clearance index (β = −0.011 turnovers, 95% CI (−0.0200, −0.0013), p = 0.03), and a small increase in functional residual capacity (β = 0.34 mL, 95% CI (0.02, 0.66), p = 0.04). Conclusions: We found an association between binge drinking and health service utilization for respiratory conditions in infancy, but no evidence that low‐level PAE was associated with adverse respiratory outcomes. [ABSTRACT FROM AUTHOR]

Background: Previous systematic reviews have focused on associations between single time point measures of Body Mass Index (BMI) and asthma and allergic diseases. As BMI changes dynamically during childhood, examination of associations between longitudinal trajectories in BMI and allergic diseases is needed to fully understand the nature of these relationships. Objective: To systematically synthesise the association between BMI trajectories in childhood (0–18 years) and allergic diseases (asthma, eczema, allergic rhinitis, or food allergies outcomes). Design: We conducted a systematic review following the PRISMA guidelines, and two independent reviewers assessed the study quality using the ROBINS‐E and GRADE tools. A narrative synthesis was performed as the statistical heterogeneity did not allow a meta‐analysis. Data Sources: A search was performed on PubMed and EMBASE databases on 4th January 2023. Eligibility Criteria: Longitudinal cohort studies assessing the associations between childhood BMI trajectories and allergic diseases were included. Results: Eleven studies met the inclusion criteria with a total of 37,690 participants between 0 and 53 years of age. Ten studies examined asthma outcomes, three assessed association with allergic rhinitis, two assessed eczema, and one assessed food allergy. High heterogeneity and high risk of bias were observed. Overall, the quality of evidence was very low. Nevertheless, two consistent findings were identified: (1) a persistently high BMI between 6 and 10 years of age may be associated with an increased risk of asthma at 18 years and (2) a rapid increase in BMI in the first 2 years of life may be associated with subsequent asthma. Conclusions: Maintaining a normal BMI trajectory during childhood may reduce the risk of asthma. Future research that adequately addresses confounding and includes longer‐term follow‐up is needed. Moreover, additional studies examining potential associations with eczema, food allergies, and allergic rhinitis outcomes are needed. [ABSTRACT FROM AUTHOR]

Background: The extent to which biomarkers of asthma activity persist in spontaneous asthma remission and whether such markers are associated with future respiratory outcomes remained unclear. We investigated the association between sub‐clinical inflammation in adults with spontaneous asthma remission and future asthma relapse and lung function decline. Methods: The Tasmanian Longitudinal Health Study is a population‐based cohort (n = 8583). Biomarkers of systemic inflammation were measured on participants at age 45, and latent profile analysis was used to identify cytokine profiles. Bronchial hyperresponsiveness (BHR) and nitric oxide products in exhaled breath condensate (EBC NOx) were measured at age 50. Participants with spontaneous asthma remission at ages 45 (n = 466) and 50 (n = 318) were re‐evaluated at age 53, and associations between baseline inflammatory biomarkers and subsequent asthma relapse and lung function decline were assessed. Results: We identified three cytokine profiles in adults with spontaneous asthma remission: average (34%), Th2‐high (42%) and Th2‐low (24%). Compared to the average profile, a Th2‐high profile was associated with accelerated decline in post‐BD FEV1/FVC (MD −0.18% predicted per‐year; 95% CI −0.33, −0.02), while a Th2‐low profile was associated with accelerated decline in both post‐BD FEV1 (−0.41%; −0.75, −0.06) and post‐BD FVC (−0.31%; −0.62, 0.01). BHR and high TNF‐α during spontaneous remission were associated with an increased risk of asthma relapse. In contrast, we found no evidence of association between EBC NOx and either asthma relapse or lung function decline. Conclusion: BHR and serum inflammatory cytokines have prognostic value in adults with spontaneous asthma remission. At‐risk individuals with BHR, Th2‐high or Th2‐low cytokine profiles may benefit from closer monitoring and on‐going follow‐up. [ABSTRACT FROM AUTHOR]

Background/Objectives: Eczema is a common chronic debilitating skin condition in childhood. Data on the epidemiology and natural history of eczema across the life course are lacking. This analysis aimed to describe these epidemiological features in Australian children and adults. Methods: Data collected on eczema from four Australian cohort studies were analysed: namely HealthNuts, Melbourne Atopic Cohort Study (MACS), Tasmanian Longitudinal Health Study (TAHS) and the Australian arm of the European Community Respiratory Health Survey (ECRHS). Results: Among children aged under 6 years, 28.8%–35.6% have ever‐had eczema, and 16.7%–26.6% had 'current eczema'. Among those aged 6–12 years, 14.6%–24.7% had 'current eczema' with 12.0%–18.5% of those at ages of 6 and 10 years classified as having moderate‐to‐severe eczema according to the Scoring of Atopic Dermatitis (SCORAD) index. In adults, the prevalence of 'eczema ever' ranged between 13.8% and 48.4%. The 12‐month period prevalence of eczema was 15.1% at age 18, while current eczema was 8.5% at an average age of 51, and 8.8% at an average age 53 years. Eczema was more common among young boys, but this difference became non‐significant for older children and early adolescents. In contrast, eczema was more common for adult women than men. Conclusions: Eczema is common both in children and adults. The proportion of severe eczema in children was substantial. [ABSTRACT FROM AUTHOR]