Metabolomic profiles during early childhood and risk of food allergies and asthma in multiethnic children from a prospective birth cohort

Diabetes Care

OBJECTIVE Breastfeeding duration is inversely associated with risks of cardiovascular disease (CVD) and type 2 diabetes in parous women. However, the association among women at high risk, including women with type 2 diabetes or gestational diabetes (GDM) is unclear. RESEARCH DESIGN AND METHODS We included 15,146 parous women with type 2 diabetes from the Nurses’ Health Study I and II (NHS, NHS II) and 4,537 women with a history of GDM from NHS II. Participants reported history of breastfeeding via follow-up questionnaires. Incident CVD by 2017 comprised stroke or coronary heart disease (CHD: myocardial infarction, coronary revascularization). Adjusted hazard ratios (aHRs) and 95% CIs were estimated using Cox models. RESULTS We documented 1,159 incident CVD cases among women with type 2 diabetes in both cohorts during …

Metabolism

BackgroundMetabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion.MethodsThe study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was …

Clinical Pediatrics

Dr. Lester F. Soyka: E. M., a 13-year-old girl, was referred to the Massachusetts General Hospital because of uncontrolled hyper-tension. She was in apparent good health until four years ago when she had an episode of dysuria and pyuria diagnosed as cystitis and treated with Furadantin. She had two subsequent attacks three years ago and one year ago similarly treated. She seemed well until six weeks prior to admission when gross hematuria developed with no associated symptoms and no previous history of recent upper respiratory infection. Penicillin was started. In the next few days she developed headache, abdominal cramps, and anorexia. On admission to another hospital it was found that her blood pressure was 270/190, there was marked arteriolar spasm on funduscopy, and her urine was loaded with red and white blood cells with no casts. Intravenous and retrograde pyelography showed a shrunken …

JCI insight

Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9 …

BJOG: An International Journal of Obstetrics & Gynaecology

Objective There is a secular trend towards earlier age of menarche in the US and globally. Earlier age at menarche (AAM) has been associated with metabolic disorders that increase risk for preterm delivery (PTD), yet no studies in the US have investigated whether AAM influences risk of PTD. This study tested the hypothesis that AAM is associated with PTD. Design A case–control study. Setting The Boston Medical Center (BMC) in Boston, Massachusetts. Population or Sample 8264 mother‐newborn dyads enrolled at birth at BMC between 1998 and 2019, of which 2242 mothers had PTD (cases) and 6022 did not have PTD (controls). Methods Multivariable‐adjusted logistic regression models and restricted cubic splines were used to examine the association between AAM and risk of PTD. The combined impact of AAM and age at delivery on the risk of PTD was also examined. Main Outcome Measures …

Increased fossil fuel usage has increased CO2 concentrations leading to global warming and climate change with increased frequency and intensity of extreme weather events such as thunderstorms, wildfires, droughts, heat waves, and others. These changes increase the risk of adverse health effects for all human beings. However, these experiences do not impact everyone equally. Underserved communities, including people of color, the elderly, people living with chronic conditions, and socioeconomically disadvantaged groups have greater vulnerability to the impacts of climate change. These vulnerabilities are a result of multiple factors such as disparities in healthcare, lower educational status, systemic racism, and many others. These social inequities are exacerbated by extreme weather events, which act as threat multipliers increasing disparities in health outcomes. It is clear that without human action, these …

Allergy

Background Immunological traits and functions have been consistently associated with environmental exposures and are thought to shape allergic disease susceptibility and protection. In particular, specific exposures in early life may have more significant effects on the developing immune system, with potentially long‐term impacts. Methods We performed RNA‐Seq on peripheral blood mononuclear cells (PBMCs) from 150 children with atopic dermatitis and healthy nonallergic children in rural and urban settings from the same ethnolinguistic AmaXhosa background in South Africa. We measured environmental exposures using questionnaires. Results A distinct PBMC gene expression pattern was observed in those children with atopic dermatitis (132 differentially expressed genes [DEGs]). However, the predominant influences on the immune cell transcriptome were related to early life exposures including …

Annals of Allergy, Asthma & Immunology

It is widely accepted and rigorously evidenced that topical corticosteroids (TCS) are effective treatments for atopic dermatitis (AD). Although TCS are known to have various adverse effects, including skin atrophy, telangiectasia, and perioral dermatitis, clear instructions from prescribers on how and where to apply and when to taper or stop use can mitigate these risks, in addition to close monitoring by the prescribing clinician before refilling prescriptions. An emphasis on the basics of AD management, such as liberal emollient use, can reduce the requirement for TCS. 1 One of the most divisive and debated adverse effects of TCS is topical steroid withdrawal (TSW). First described in 1969, the last 15 years have seen a sharp increase in publications mentioning TSW in the medical literature. There has also been a trend in coverage and discussion of the condition across social media alongside the topic of steroid …

EClinicalMedicine

BackgroundUltra-processed foods (UPFs) are emerging as a risk factor for colorectal cancer (CRC), yet how post-diagnostic UPF intake may impact CRC prognosis remains unexplored.MethodsData collected from food frequency questionnaires were used to estimate intakes of total UPFs and UPF subgroups (serving/d) at least 6 months but less than 4 years post-diagnosis among 2498 patients diagnosed with stages I–III CRC within the Nurses' Health Study and Health Professionals Follow-up Study during 1980–2016. Hazard ratios (HR) and 95% confidence intervals (CIs) of all-cause, CRC- and cardiovascular disease (CVD)-specific mortality in association with UPF consumption were estimated using an inverse probability weighted multivariable Cox proportional hazards regression model, adjusted for confounders.FindingsThe mean (SD) age of patients at diagnosis was 68.5 (9.4) years. A total of 1661 deaths …

Frontiers in Cellular and Infection Microbiology

Understanding antigen-specific T-cell responses, for example, following virus infections or allergen exposure, is of high relevance for the development of vaccines and therapeutics. We aimed on optimizing immunophenotyping of T cells after antigen stimulation by improving staining procedures for flow and mass cytometry. Our method can be used for primary cells of both mouse and human origin for the detection of low-frequency T-cell response using a dual-barcoding system for individual samples and conditions. First, live-cell barcoding was performed using anti-CD45 antibodies prior to an in vitro T-cell stimulation assay. Second, to discriminate between stimulation conditions and prevent cell loss, sample barcoding was combined with a commercial barcoding solution. This dual-barcoding approach is cell sparing and, therefore, particularly relevant for samples with low cell numbers. To further reduce cell loss and to increase debarcoding efficiency of multiplexed samples, we combined our dual-barcoding approach with a new centrifugation-free washing system by laminar flow (Curiox™). Finally, to demonstrate the benefits of our established protocol, we assayed virus-specific T-cell response in SARS-CoV-2–vaccinated and SARS-CoV-2–infected patients and compared with healthy non-exposed individuals by a high-parameter CyTOF analysis. We could reveal a heterogeneity of phenotypes among responding CD4, CD8, and gd-T cells following antigen-specific stimulations. Our protocol allows to assay antigen-specific responses of minute populations of T cells to virus-derived peptides, allergens, or other antigens from the same donor …

Journal of Allergy and Clinical Immunology

MethodsATAC-seq was utilized to assess chromatin accessibility in CD4+ T cell subsets (Naïve, Th2, and Th1 cells), obtained from asthmatic and non-asthmatic participants, including discordant twin pairs and non-twin individuals. The inclusion of asthma-discordant monozygotic twins, matched for genetics, age, sex, cohort effects and maternal influences, enhances the power in detecting disease-related epigenetic differences compared to unrelated cases and controls.ResultsWe identified differential peaks between asthmatic and non-asthmatic samples in CD4+ T cell types. We determined the transcription factor (TF) motifs enriched in these cell-type specific differential peaks. Specifically, TF JUNB in the AP-1 family exhibited increased expression in asthmatic twins compared to their non-asthmatic twin pairs, and we elucidated the network of JUNB with other TFs. GSEA analysis indicated that genes proximal to …

Cell Reports Medicine

Bivalent COVID vaccines containing mRNA for ancestral and Omicron BA.5 spike proteins do not induce stronger T cell responses to Omicron BA.5 spike proteins than monovalent vaccines that contain only ancestral spike mRNA. The reasons for this finding have not been elucidated. Here, we show that healthy donors (HDs) and people living with HIV (PLWH) on antiretroviral therapy mostly target T cell epitopes that are not affected by BA.5 mutations. We use the functional expansion of specific T cells (FEST) assay to determine the percentage of CD4+ T cells that cross-recognize both spike proteins and those that are monoreactive for each protein. We show a predominance of cross-reactive CD4+ T cells; less than 10% percent of spike-specific CD4+ T cell receptors were BA.5 monoreactive in most HDs and PLWH. Our data suggest that the current bivalent vaccines do not induce robust BA.5-monoreactive T cell …

Climate Change and Public Health

Climate change is a contributing cause to these cases of asthma, COPD, and allergic rhinitis. And it is increasing the frequency and severity of new cases and exacerbations of these and other respiratory disorders. While climate change is not the most frequent cause of cases of chronic respiratory disorders, many cases are climate-sensitive. 1Higher temperatures increase airborne concentrations of ozone if there are sufficiently high levels of nitrogen oxides, volatile organic compounds (VOCs), and other ozone precursors. 2 Higher temperature also contributes to increased probability of wildfires—and, in desert regions, sand and dust storms—which produce particulate matter and other airborne pollutants that contribute to newonset and exacerbation of respiratory disorders. And higher temperature leads to increased pollen production and longer pollen seasons, increasing the incidence and severity of allergic rhinitis.

ERJ Open Research

BackgroundLower respiratory tract infections (LRTIs) are the leading cause of infant morbidity and mortality worldwide, and altered metabolite production is recognised as a critical factor in LRTI pathogenesis.MethodsThis study aimed to identify prenatal metabolic changes associated with LRTI risk in infancy, using liquid chromatography-mass spectrometry unbiased metabolomics analysis on cord blood from 810 full-term newborns.ResultsWe identified 22 compounds linked to LRTIs in infancy, enriched for purine degradation pathway (PDP) metabolites. High cord blood PDP metabolites, including xanthine, hypoxanthine, xanthosine and inosine, were linked to reduced LRTI risk during infancy. Notably, a low xanthine to uric acid ratio at birth predicted a four-fold increased LRTI risk.ConclusionThis study is the first to reveal that high cord blood PDP metabolites identify newborns at lower LRTI risk, stratifying …

Cannabis, the most commonly used recreational drug, is illicit in many areas of the world. With increasing decriminalization and legalization, cannabis use is increasing in the United States and other countries. The adverse effects of cannabis are unclear because its status as a Schedule 1 drug in the United States restricts research. Despite a paucity of data, cannabis is commonly perceived as a benign or even beneficial drug. However, recent studies show that cannabis has adverse cardiovascular and pulmonary effects and is linked with malignancy. Moreover, case reports have shown an association between cannabis use and neuropsychiatric disorders. With growing availability, cannabis misuse by minors has led to increasing incidences of overdose and toxicity. Though difficult to detect, cannabis intoxication may be linked to impaired driving and motor vehicle accidents. Overall, cannabis use is on the rise …

Cardiovascular diabetology

BackgroundLegume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD.MethodsThe current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 …

Statistics in Biosciences

Statistical research functions much like a supply chain, beginning with the identification of demands, such as open problems in science and technology, and the gathering or generation of data (eg, through surveys, clinical trials, or scientific experiments). These demands and data fuel the creation of innovative analytical solutions, encompassing fresh theories and methodologies for study design and data analysis, and, increasingly, the development of software tools to disseminate these solutions to end-users. To ensure proper and effective utilization of new methods and tools, it is crucial to systematically evaluate them, enabling users to understand their properties, capabilities, and limitations. Ultimately, their value must be tested and demonstrated by solving real-world problems. Thus, demands, data, theory, methods, software, as well as their evaluation, validation, and application, all serve as vital components …

MethodsWe included 911 participants from the San Juan Overweight Adult Longitudinal Study, a 3-year prospective cohort of overweight Puerto Ricans. At baseline, using LC-MS, we quantified metabolites from saliva (n= 635) and plasma (n= 1,051). We used elastic net regression with 10-fold cross-validation to identify features from saliva, plasma, and saliva and plasma (multi-fluid) that were predictive of BMI and WC. We used Cox-proportional hazard models to evaluate associations between metabolomic profiles and diabetes progression, adjusting for age, sex, socioeconomic factors, lifestyle, and medication use.ResultsFor BMI metabolomic profiles, we identified 207 metabolites in plasma, 118 metabolites in saliva, and 225 in the multi-fluid profile. For WC, we identified 157, 89, and 210 metabolites for saliva, plasma, and multi-fluid profiles, respectively. Highly positively weighted metabolites across all BMI and WC metabolomic profiles included those in pathways of alanine and aspartate metabolism, purine metabolism, and sphingomyelins. Each SD increase in saliva, but not plasma or multi-fluid, metabolic profile of BMI was significantly associated with all stages of diabetes progression. Saliva, but not plasma or multi-fluid, metabolomic profile of WC was significantly associated with progression from pre-diabetes to T2D. All associations became stronger after further adjustment for anthropometric measures of BMI and WC.ConclusionSaliva is an underexplored and easily accessible biofluid to measure metabolites that are reflective of adiposity measures. Validation in future studies will confirm our findings that saliva, plasma, and multi-fluid …

Journal of allergy and clinical immunology

BackgroundMost genetic studies of asthma and allergy have focused on common variation in individuals primarily of European ancestry. Studying the role of rare variation in quantitative phenotypes and in asthma phenotypes in populations of diverse ancestries can provide additional, important insights into the development of these traits.ObjectiveWe sought to examine the contribution of rare variants to different asthma- or allergy-associated quantitative traits in children with diverse ancestries and explore their role in asthma phenotypes.MethodsWe examined whole-genome sequencing data from children participants in longitudinal studies of asthma (n = 1035; parent-identified as 67% Black and 25% Hispanic) to identify rare variants (minor allele frequency < 0.01). We assigned variants to genes and tested for associations using an omnibus variant-set test between each of 24,902 genes and 8 asthma-associated …

Journal of Allergy and Clinical Immunology

MethodsUsing the American Academy of Pediatrics multi-state (27 states) Comparative Effectiveness Research through Collaborative Electronic Reporting electronic health record database, we identified children with IgE-FA, defined as having≥ 2 corresponding diagnosis codes separated by≥ 6 months,≥ 1 epinephrine autoinjector prescription, and≥ 1 food allergen. Subjects were observed for≥ 1 year. We determined the cumulative incidence of IgE-FA and individual food allergies during the periods 09/01/2012–08/31/2015 (pre-LEAP) and 09/01/2015–08/31/2018 (post-LEAP).ResultsThe cumulative incidences of IgE-FA in the pre-LEAP (median age 1.5 years) and post-LEAP (median age 1.3 years) cohorts were 1.29%(n= 966 of 74,250 subjects) and 1.49%(n= 927 of 61,487 subjects), respectively. The top 5 food allergens (and cumulative incidences pre-LEAP vs. post-LEAP) in both the pre-LEAP and post …

Journal of Allergy and Clinical Immunology

MethodsTwo waves of interviews were done 3 years apart between 2002 and 2015. The initial interviews were carried with 12,218 adults representative of the general population in 8 US states (wave 1 [W1]), of which, 10,931 were re-interviewed 3 years later (wave 2 [W2]). The sample was divided into “no allergies and/or asthma (no FAAG/ATA)”;“Food allergy alone (FA)”;“Food allergy and other allergies (FA+ AG)” and “Food allergy and asthma (FA+ ATA)”. Odd ratios were adjusted for age, gender, race and body mass index (AOR).ResultsAs many as 7.0%(95% CI, 6.5%-7.5%) and 7.2%(95% CI, 6.7%-7.7%) of the participants in W1 and W2, respectively had food allergies. Among them, 30.6% also have asthma and 53.9% have a non-food related allergy. The odds of having a mood disorder are 2.4 and 2.6 higher in the FA and FA+ ATA groups. FA and FA+ ATA groups were more likely to report at least 2 non …

Journal of Allergy and Clinical Immunology

MethodsRetrospective study was performed during 3 years in our allergy department. Clinical history, PROMs, skin/basic tests were performed before and after 1 year of treatment with OMA.ResultsOf the total 56 CSU patients treated with OMA, 42 (75%) were women (average age 45.5 years) 49.1% presented type-I autoimmunity; 17% type-IIB; 7, 5% overlapped between 2 endotypes and 26.4% didnt meet criteria. Type-I: 23% pneumoallergen positive; 15% TPO-antibodies; 12% both and 50% history of atopic disease. Of them, 57% rapid response to OMA. Type-IIB: 33.3% ANCAS, 22.2% TG-antibodies, 11.1% ANAS, 22.2% vitiligo, 11.1% hypothyroidism. 66, 6% rapid response to OMA. Fishers exact test was used to compare the autoimmunity with the type of response with a result (p= 0.915). Focused on 22 patients completing one year of OMA: 54, 5% presented type-I autoimmunity and 50% rapid response (p= 0 …

Journal of Allergy and Clinical Immunology

Methods3 cases of malignancy following dupilumab use in our hospitals were studied. The literature was reviewed for published cases of dupilumab-related malignancy. Mechanisms of oncogenesis were extrapolated from published IL-4-JAK-STAT axis abnormalities.ResultsIn our single institution three patients treated with dupilumab for fungal sinusitis, asthma and eczema developed rapidly progressive and aggressive cancers including glioblastoma multiforme, fatal pancreatic cancer and advanced sinonasal cancer. Over 30 cases of cutaneous T-cell lymphoma (CTCL) related to dupilumab use have been published. Hematological malignancies such as anaplastic lymphoma, Sezary syndrome and Hodgkin’s lymphoma, and solid tumors, specifically sinonasal, pancreatic, lung, testicular and prostate cancers, have been reported.ConclusionsMulticenter and single institutional studies have shown sporadic …

Journal of Allergy and Clinical Immunology

BackgroundThere are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations.ObjectiveWe sought to identify metabolites unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort, the Boston Birth Cohort.MethodsMass spectrometry–based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (n = 811). FA was diagnosed according to clinical symptoms consistent with an acute hypersensitivity reaction at food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined on the basis of physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders.ResultsDuring a …

Journal of Allergy and Clinical Immunology

MethodsObservational, descriptive, cross-sectional study which assessed demographics, PROMs knowledge, frequency of use, PROM preferences, satisfaction, physician training, attitudes, and barriers of using PROMs. Data collection was carried out in collaboration with research networks worldwide.ResultsOverall, 2528 physicians were surveyed, and 51.7%(n= 1308) reported using PROMs. Most of them (57.9%) were 30-49 years old (yo), attending both public and private settings (41.4%) and respiratory-related specialties (RRS, 41.1%). The use of PROMs in asthma was higher than in RA and RS (28.6%, 15.6%, and 8.9% respectively). The most frequently PROMs used were ACT and AQLQ, the RCAT, and SNOT22 (RS). The principal reason for use was to monitor control, treatment, and severity of disease (≈ 90%), time constraints were the principal barrier (≈ 76%), and most requested being trained in the …

Journal of Allergy and Clinical Immunology

MethodsEthmoid sinus EpCs from 19 adults with CRS were sorted into subsets (basal, transitional, differentiated), bulk RNA-sequenced, and analyzed for differentially expressed genes and pathways. Single cell RNA-seq (scRNA-seq) datasets of CRSwNP [GSE202100, HRA000772] and a bulk RNA-seq dataset from mild-to-moderate and severe asthmatic epithelium [GSE158752] were also assessed. Immunofluorescent staining and ex vivo analysis of sinus EpCs were used to validate findings.ResultsExpression of the Hallmark glycolysis gene set was enriched in CRSwNP throughout all EpC subsets (padj< 0.05). Spearman correlation analysis identified mammalian target of rapamycin complex 1 (mTORC1) as a potential regulator of enhanced glycolysis (p< 0.05) and identified expression of wound healing genes and EpC cytokines as potential sequelae. Phospho-6SRP staining demonstrated that mTORC1 …

Journal of Allergy and Clinical Immunology

BackgroundElevated TCRαβ+CD4−CD8− double-negative T cells (DNT) and serum biomarkers help identify FAS mutant patients with autoimmune lymphoproliferative syndrome (ALPS). However, in some patients with clinical features and biomarkers consistent with ALPS, germline or somatic FAS mutations cannot be identified on standard exon sequencing (ALPS-undetermined: ALPS-U).ObjectiveWe sought to explore whether complex genetic alterations in the FAS gene escaping standard sequencing or mutations in other FAS pathway–related genes could explain these cases.MethodsGenetic analysis included whole FAS gene sequencing, copy number variation analysis, and sequencing of FAS cDNA and other FAS pathway–related genes. It was guided by FAS expression analysis on CD57+DNT, which can predict somatic loss of heterozygosity (sLOH).ResultsNine of 16 patients with ALPS-U lacked FAS …

Journal of Allergy and Clinical Immunology

MethodsWe developed a quality improvement (QI) project to increase the percent of eligible children transitioned to SMART while hospitalized at our pediatric tertiary care center. We first conducted focus groups to determine barriers to guideline implementation. We then developed interventions to address barriers, including educating providers, developing decision-support tools and streamlining insurance prior authorization. To evaluate project impact, we conducted a retrospective chart review of patients aged 5 to 18 years with 2 or more asthma emergency department visits and/or hospitalizations in the preceding 12 months who were eligible for SMART and admitted with an asthma exacerbation between Jan 2021 and Jun 2023 (n= 255). We then constructed a run chart depicting the percent of eligible inpatients discharged on SMART over time.ResultsThe percent of eligible inpatients discharged on SMART …

Journal of Allergy and Clinical Immunology

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks …

Journal of Allergy and Clinical Immunology

MethodsCord blood plasma from 391 neonates from the Boston birth cohort was analyzed for 28 soluble immune factors. LRTI was defined as bronchiolitis, bronchitis, or pneumonia during the first year. Principal component analyses were employed to identify subsets of newborns at risk of LRTI. Multivariate survival models were used to determine risk associations.ResultsThere were 29 infants with LRTI and 362 unaffected. Newborns with high cord blood levels of IFNγ (aHR= 4.01, 95% CI 1.62-9.91), IL-5 (aHR= 4.00, 95% CI 1.69-9.46) and IL-17 (aHR= 2.70, 95% CI 1.19-6.13) had significantly higher risk of LRTI during infancy, while the opposite was true of RANTES abundance (aHR= 0.45, 95% CI= 0.20-0.98). Notably, principal component analysis with the above factors identified two distinct at-risk subsets of newborns, factoring in LRTI-associated variables (sex, prematurity, maternal smoking and pre …

Journal of Allergy and Clinical Immunology

BackgroundMUPPITS-2 was a randomized, placebo-controlled clinical trial that demonstrated mepolizumab (anti-interleukin-5) reduced exacerbations and blood and airway eosinophils in urban children with severe eosinophilic asthma. Despite this reduction in eosinophilia, exacerbation risk persisted in certain patients treated with mepolizumab. This raises the possibility that subpopulations of airway eosinophils exist that contribute to breakthrough exacerbations.ObjectiveDetermine the effect of mepolizumab on airway eosinophils in childhood asthma.MethodsSputum samples were obtained from 53 MUPPITS-2 participants. Airway eosinophils were characterized using mass cytometry and grouped into subpopulations using unsupervised clustering analyses of 38 surface and intracellular markers. Differences in frequency and immunophenotype of sputum eosinophil subpopulations were assessed based on …

Journal of Allergy and Clinical Immunology

BackgroundDedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD).ObjectiveWe sought to understand the mechanisms of eczema in DOCK8 deficiency.MethodsSkin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression. Skin barrier function was measured by transepidermal water loss. Allergic skin inflammation was elicited in mice by epicutaneous sensitization with ovalbumin (OVA) or cutaneous application of Staphylococcus aureus.ResultsSkin lesions of DOCK8-deficient patients exhibited type 2 inflammation, and the patients’ skin was colonized by S aureus, as in AD. Unlike in AD, DOCK8-deficient patients had a reduced FOXP3:CD4 ratio in their skin lesions, and their skin barrier function was intrinsically intact. Dock8−/− mice exhibited reduced numbers of cutaneous T …

Journal of Allergy and Clinical Immunology

MethodsThis is a cross-sectional study using an online survey that was distributed by physicians to patients with CU from UCARE, ACARE, and ADCARE networks. Descriptive analysis was performed for all questions in the questionnaire: mean and standard deviation for quantitative variables and frequency and percentage for categorical variables.ResultsThe study comprised 65 participants, the majority of whom were between the ages of 25 and 40. When measuring knowledge, 6 out of every 10 participants reported that their understanding of PROMs was based on information supplied by their physician. 40% of those polled expect PROMs to have the ability to inform about the disease's severity and management. When questioned about PROMs' evaluation of treatment impact, 83% correctly replied, and 90% correctly recognized PROMs acquire patients' own perceptions of their health state. In terms of …

Journal of Allergy and Clinical Immunology

MethodsData from the NIH/NIAID-funded (NCT03389893 [ADRN09]) multicenter study that enrolled adults with moderate-severe AD were analyzed. Bulk RNA-sequencing gene expression counts (rlog normalized) of skin biopsies were compared to bacterial colony forming units (CFU/cm 2) or associated PCR (rCFU/cm 2) in lesional (n= 57) and non-lesional (n= 55) pre-treatment samples. Genes of interest (GOIs) were determined based on association with CFU level (upper vs lower tertile) or early response to dupilumab and rCFU correlation (R 2≥ 0.10, p< 0.05).ResultsPre-treatment lesional vs non-lesional skin revealed increased S. aureus with remarkable variance in bacterial load between subjects (non-lesional 1.90±1.37 vs lesional 3.27±1.82 log 10 CFU/cm 2, p< 0.05). Multiple linear regression (rCFU∼ GOIs+ Sex+ Age±Lesion) identified a selective positive association of CERS1 (ceramide synthase 1 …

Journal of Allergy and Clinical Immunology

Two recent publications1, 2 in the Journal of Immunology and Clinical Allergy have set out to better understand the pathogenesis 48 of a skin disease that has remained a conundrum in dermatology for ages: prurigo nodularis (PN). PN is a chronic skin disease 49 characterized by intensely pruritic, hyperkeratotic nodules symmetrically distributed on the extremities and the trunk. The 50 severe pruritus forces patients to engage in self-mutilating scratching, leading to disfigurement, and poor quality of life. Despite 51 this significant disease burden, therapeutic options in PN have been very limited until recently, as evidenced by the majority 52 of PN patients reporting dissatisfaction with their therapy. 3 The previous lack in effective therapies is reflective of our poor 53 understanding of PN pathogenesis. While a broad range of pathogenetic factors have been proposed, including a dysregulated 54 immune response …

Journal of Allergy and Clinical Immunology

MethodsUrinary ttMA was measured by an ultraperformance liquid chromatograph-tandem mass spectrometer in 242 mothers COCOA birth cohort. Diagnosis of asthma at age 7 was determined using questionnaire. The serum concentrations of 11 cytokines were measured at age 7. The Nrf2 (rs6726395) and NAT2 (rs4271002) polymorphisms of cord blood were genotyped by using a TaqMan assay (ABI, Foster City, CA, USA).ResultsMaternal urinary ttMA increased the risk of pediatric asthma (aOR: 1.003, 95% CI: 1.000-1.006). IL-4 was increased in children with higher maternal urinary ttMA and IL-4 was highest in children with asthma and higher maternal urinary ttMA. Maternal urinary ttMA had significant associations with asthma in children with NAT2 GG and NRF2 GA/AA genotype (aOR: 1.004, 95% CI: 1.000-1.009 and aOR: 3.817, 95% CI: 1.312-11.103).ConclusionsThis study suggests that maternal …

Journal of Allergy and Clinical Immunology

BackgroundStudies have linked daily pollen counts to respiratory allergic health outcomes, but few have considered allergen levels.ObjectiveWe sought to assess associations of grass pollen counts and grass allergen levels (Phl p 5) with respiratory allergic health symptoms in a panel of 93 adults with moderate-severe allergic rhinitis and daily asthma hospital admissions in London, United Kingdom.MethodsDaily symptom and medication scores were collected from adult participants in an allergy clinical trial. Daily counts of asthma hospital admissions in the London general population were obtained from Hospital Episode Statistics data. Daily grass pollen counts were measured using a volumetric air sampler, and novel Phl p 5 levels were measured using a ChemVol High Volume Cascade Impactor and ELISA analyses (May through August). Associations between the 2 pollen variables and daily health scores …

Journal of Allergy and Clinical Immunology

MethodsPrimary care pediatric providers from the Arkansas Children’s Care Network (ACCN, the nation’s first statewide clinically integrated network (CIN) with 130 members) were invited twice by ACCN list-serve email to complete a 21-item, anonymous REDCAP survey (modified from Gupta) between May 2022-December 2023. Descriptive statistics were performed on collected data.ResultsThirty-five providers (27%) responded; 97% MD/DO with 51% completing training from 2000-2009. All respondents (100%) reported guideline familiarity, but only 46% reviewed guidelines at all infant visits and a minority (37%) followed the guidelines as published. Reported barriers for guidelines implementation included: conducting in-office peanut feedings (60%), lack of clinic time (43%), parental concerns for allergic reactions (31%) and blood draws (31%), and conducting/interpreting specific-IgE testing (26%). Barriers to …