Kari Nadeau

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 …

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 …

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 …

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 …

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 …

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 …

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.

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 …

In the published article, there was an error in the section Metabolomics/lipidomics in FA development. The sentence “Untargeted serum metabolomics from infants identified an increase in several unsaturated fatty acids, such as free fatty acid (FFA) 16: 1 (palmitoleic acid) and FFA 20: 1 (eicosenoic acid), and a decrease in conjugated bile acids, such as glycocholic acid and taurocholic acid, in infants with FA (80).”[80: Huang et al., 2014] was referring to a study in atopic dermatitis as opposed to food allergy. This sentence has been removed from the manuscript.

Background Allergic rhinitis (AR) is a common condition that is frequently associated with atopic inferior turbinate hypertrophy (ITH) resulting in nasal obstruction. Current guidelines support the use of subcutaneous allergen immunotherapy (SCIT) when patients fail pharmacologic management. However, there is a lack of consensus regarding the role of inferior turbinate reduction (ITR), a treatment that we hypothesize is cost‐effective compared with other available treatments. Methods We conducted a cost‐effectiveness analysis comparing the following treatment combinations over a 5‐year time horizon for AR patients presenting with atopic nasal obstruction who fail initial pharmacotherapy: (1) continued pharmacotherapy alone, (2) allergy testing and SCIT, (3) allergy testing and SCIT and then ITR for SCIT nonresponders, and (4) ITR and then allergy testing and SCIT for ITR nonresponders. Results were …

Elucidating effects of the environmental pollutant benzo[a]pyrene [BaP] on cardiac arrhythmogenicity Elucidating effects of the environmental pollutant benzo[a]pyrene [BaP] on cardiac arrhythmogenicity J Mol Cell Cardiol. 2024 Apr 20:S0022-2828(24)00057-9. doi: 10.1016/j.yjmcc.2024.04.013. Online ahead of print. Authors Johnson Y Yang 1 , Gema Mondéjar-Parreño 1 , James WS Jahng 1 , Yu Lu 1 , Naomi Hamburg 2 , Kari C Nadeau 3 , Daniel J Conklin 4 , Ronglih Liao 1 , Mark Chandy 5 , Joseph C Wu 6 Affiliations 1 Stanford Cardiovascular Institute, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA. 2 Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston University School of Public Health, Boston, MA, USA. 3 Department of Environmental Health, Harvard TH Chan School of Public Health, …

The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 …

MethodsWe performed a post hoc analysis of PGIS in the POISED trial (NCT02103270) to understand the impact of PGIS on participant outcomes. PGIS was defined as at least 4 instances of abdominal pain, vomiting, and/or reflux over a 14-day period of OIT dosing.ResultsA total of 36 out of 95 participants who received peanut OIT met the definition of PGIS. The age and gender distributions were comparable between those with and without PGIS (65% male; ages 7-49 years). Baseline median peanut sIgE was significantly higher (115 kUA/L vs. 68 KUA/L; p= 0.03) and median sIgG4/sIgE ratio was significantly lower (2.8 vs. 7.6; p= 0.003) among those with and without PGIS respectively. Despite a longer time (55 vs 46 weeks; p= 0.001) to reach the maintenance dose for the PGIS group, there were no significant differences in study completion rates (week 117 per protocol, 83% vs 86%, p= 0.91) or desensitization …

MethodsCashew or shrimp allergic participants aged 7-55 years were enrolled in the phase 2 clinical trial-MOTIF (NCT03504774) and underwent cognate allergen-specific OIT to a maintenance dose of 1,000 mg until week 52. Oral food challenge (OFC) at weeks 52 and 58 evaluated desensitization and sustained unresponsiveness (SU) respectively to a cumulative allergen dose of 2043 mg. We examined immune changes in allergen-reactive CD4+ T cells and plasma at baseline, week 52, and week 58 using flow cytometry and Luminex.ResultsWe enrolled 40 cashew and 12 shrimp allergic participants, of whom 25 cashew-treated (62.5%) and 7 shrimp-treated (58.3%) participants completed and passed week 58 OFC. Overall, cashew and shrimp OIT was safe with only mild (90%) or moderate (10%) adverse events, with gastrointestinal symptoms (31%) being the most common. OIT induced a significant …

We review current knowledge on the trends and drivers of global wildfire activity, advances in the measurement of wildfire smoke exposure, and evidence on the health effects of this exposure. We describe methodological issues in estimating the causal effects of wildfire smoke exposures on health and quantify their importance, emphasizing the role of nonlinear and lagged effects. We conduct a systematic review and meta-analysis of the health effects of wildfire smoke exposure, finding positive impacts on all-cause mortality and respiratory hospitalizations but less consistent evidence on cardiovascular morbidity. We conclude by highlighting priority areas for future research, including leveraging recently developed spatially and temporally resolved wildfire-specific ambient air pollution data to improve estimates of the health effects of wildfire smoke exposure.

Systematic review using GRADE of the impact of exposure to volatile organic compounds (VOCs), cleaning agents, mould/damp, pesticides on the risk of (i) new‐onset asthma (incidence) and (ii) adverse asthma‐related outcomes (impact). MEDLINE, EMBASE and Web of Science were searched for indoor pollutant exposure studies reporting on new‐onset asthma and critical and important asthma‐related outcomes. Ninety four studies were included: 11 for VOCs (7 for incidenceand 4 for impact), 25 for cleaning agents (7 for incidenceand 8 for impact), 48 for damp/mould (26 for incidence and 22 for impact) and 10 for pesticides (8 for incidence and 2 for impact). Exposure to damp/mould increases the risk of new‐onset wheeze (moderate certainty evidence). Exposure to cleaning agents may be associated with a higher risk of new‐onset asthma and with asthma severity (low level of certainty). Exposure to …

BackgroundShort-term increases in air pollution are associated with poor asthma and COPD outcomes. Short-term elevations in fine particulate matter (PM2.5) due to wildfire smoke are becoming more common.Research QuestionAre short-term increases in PM2.5 and ozone in wildfire season and in winter inversion season associated with a composite of emergency or inpatient hospitalization for asthma and COPD?Study Design and MethodsCase-crossover analyses evaluated 63,976 and 18,514 patients hospitalized for primary discharge diagnoses of asthma and COPD, respectively, between January 1999 and March 2022. Patients resided on Utah’s Wasatch Front where PM2.5 and ozone were measured by Environmental Protection Agency-based monitors. ORs were calculated using Poisson regression adjusted for weather variables.ResultsAsthma risk increased on the same day that PM2.5 increased …

Global warming and climate change have increased the pollen burden and the frequency and intensity of wildfires, sand and dust storms, thunderstorms, and heatwaves—with concomitant increases in air pollution, heat stress, and flooding. These environmental stressors alter the human exposome and trigger complex immune responses. In parallel, pollutants, allergens, and other environmental factors increase the risks of skin and mucosal barrier disruption and microbial dysbiosis, while a loss of biodiversity and reduced exposure to microbial diversity impairs tolerogenic immune development. The resulting immune dysregulation is contributing to an increase in immune-mediated diseases such as asthma and other allergic diseases, autoimmune diseases, and cancer. It is now abundantly clear that multisectoral, multidisciplinary, and transborder efforts based on Planetary Health and One Health approaches (which consider the dependence of human health on the environment and natural ecosystems) are urgently needed to adapt to and mitigate the effects of climate change. Key actions include reducing emissions and improving air quality (through reduced fossil fuel use), providing safe housing (e.g., improving weatherization), improving diets (i.e., quality and diversity) and agricultural practices, and increasing environmental biodiversity and green spaces. There is also a pressing need for collaborative, multidisciplinary research to better understand the pathophysiology of immune diseases in the context of climate change. New data science techniques, biomarkers, and economic models should be used to measure the impact of climate …

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was …

Background Food allergy is a leading cause of anaphylaxis worldwide. Allergen‐specific immunotherapy is the only treatment shown to modify the natural history of allergic disease, but application to food allergy has been hindered by risk of severe allergic reactions and short‐lived efficacy. Allergen‐derived peptides could provide a solution. PVX108 comprises seven short peptides representing immunodominant T‐cell epitopes of major peanut allergens for treatment of peanut allergy. Methods Pre‐clinical safety of PVX108 was assessed using ex vivo basophil activation tests (n = 185). Clinical safety and tolerability of single and repeat PVX108 doses were evaluated in a first‐in‐human, randomized, double‐blind, placebo‐controlled trial in peanut‐allergic adults (46 active, 21 placebo). The repeat‐dose cohort received six doses over 16 weeks with safety monitored to 21 weeks. Exploratory immunological …

Can artificial intelligence (AI) replace oral food challenge? Can artificial intelligence (AI) replace oral food challenge? J Allergy Clin Immunol. 2024 Jan 21:S0091-6749(24)00042-3. doi: 10.1016/j.jaci.2024.01.008. Online ahead of print. Authors Sindy Ky Tang 1 , Nicolas Castaño 1 , Kari C Nadeau 2 , Stephen J Galli 3 Affiliations 1 Department of Mechanical Engineering, Stanford University, Stanford, California 94305, USA. 2 Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, Massachusetts 02115, USA. 3 Departments of Pathology and of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA. Electronic address: sgalli@stanford.edu. PMID: 38262500 DOI: 10.1016/j.jaci.2024.01.008 No abstract available Keywords: (BAT); (artificial intelligence); (food allergy); (oral food challenge); (specific IgE); AI; Basophil Activation Test; FA; OFC…

MethodsWe analyzed whole genomic DNA in peripheral blood mononuclear cells (PBMC) of pregnant women with (n= 12), or without (n= 24), allergy and non-pregnant women with (n= 4), or without (n= 16), allergy. Each group included participants exposed to high (> 12μg/m 3) or low (< 12μg/m 3) PM 2.5 concentrations prior to blood collection. Allergic women had histories of food or medicine allergy, allergic rhinitis, eczema, and/or asthma. We performed epigenetic landscape profiling using cytometry by time-of-flight (EpiTOF) to test whether immune cell type-specific epigenetic profiles are associated with allergy during pregnancy and PM 2.5 exposure.ResultsIn a mixed-effect model, our results suggest that the effect of PM 2.5 on epigenetic markers depend on allergy status. Plasmacytoid dendritic cells (pDCs) have a significant interaction between allergy and PM 2.5 exposure for 12 of the 37 epigenetic marks …

IgE-mediated food allergy (IgE-FA) occurs due to a breakdown in immune tolerance that leads to a detrimental type 2 helper T cell (TH2) adaptive immune response. While the processes governing this loss of tolerance are incompletely understood, several host-related and environmental factors impacting the risk of IgE-FA development have been identified. Mounting evidence supports the role of an impaired epithelial barrier in the development of IgE-FA, with exposure of allergens through damaged skin and gut epithelium leading to the aberrant production of alarmins and activation of TH2-type allergic inflammation. The treatment of IgE-FA has historically been avoidance with acute management of allergic reactions, but advances in allergen-specific immunotherapy and the development of biologics and other novel therapeutics are rapidly changing the landscape of food allergy treatment. Here, we discuss the …

Aim:The 4th Davos Declaration, convened during the Global Allergy Forum (GAF) in Davos, aimed to elevate patient care for patients with atopic dermatitis (AD) by uniting experts and stakeholders. The forum addressed the high prevalence of AD, with a strategic focus on advancing research, treatment, and management to meet the evolving challenges in the field.Methods:: This multidisciplinary forum brought together top leaders from research, clinical practice, policy, and patient advocacy to discuss the critical aspects of AD, including neuroimmunology, environmental factors, comorbidities, and breakthroughs in prevention, diagnosis, and treatment. The discussions were geared towards fostering a collaborative approach to integrate these advancements into practical, patient-centric care.Results:The forum underlined the mounting burden of AD, attributing it to significant environmental and lifestyle changes. It acknowledged the progress in understanding AD and in developing targeted therapies but recognized a gap in translating these innovations into clinical practice. Emphasis was placed on the need for enhanced awareness, education, and stakeholder engagement to address this gap effectively and to consider environmental and lifestyle factors in a comprehensive disease management strategy.Conclusion:The 4th Davos Declaration marks a significant milestone in the journey to improve care for people with AD. By promoting a holistic approach that combines research, education, and clinical application, the Forum sets a roadmap for stakeholders to work together to improve patient outcomes in AD, reflecting a commitment to adapt and …

The epithelial barrier theory links the recent rise in chronic non-communicable diseases, notably autoimmune and allergic disorders, to environmental agents disrupting the epithelial barrier. Global pollution and environmental toxic agent exposure have worsened over six decades because of uncontrolled growth, modernization, and industrialization, affecting human health. Introducing new chemicals without any reasonable control of their health effects through these years has led to documented adverse effects, especially on the skin and mucosal epithelial barriers. These substances, such as particulate matter, detergents, surfactants, food emulsifiers, micro- and nano-plastics, diesel exhaust, cigarette smoke, and ozone, have been shown to compromise the epithelial barrier integrity. This disruption is linked to the opening of the tight-junction barriers, inflammation, cell death, oxidative stress, and metabolic …

BackgroundFossil fuel combustion and climate change are endangering respiratory health. As these threats increase, healthcare delivery systems must adapt and build resilience. In this scoping review, we aim to assess the current landscape of respiratory care impacts from climate change, identifying priorities for future study.MethodsWe performed a scoping review of scientific and gray literature, and selected institutional websites, to understand the impacts of climate change on respiratory healthcare.ResultsMedline, Embase, Scopus, Cochrane Library, Lens.org, and Google Scholar were searched from database inception through 28 July 2023. The initial search yielded 1207 unique articles. Of the 67 articles identified as relevant to the impacts of climate change on respiratory care, 50 (74.6%) had been published between 2020 and 2023. The most studied climate change and severe weather exposures were …

Background Epithelial barrier impairment is associated with many skin and mucosal inflammatory disorders. Laundry detergents have been demonstrated to affect epithelial barrier function in vitro using air–liquid interface cultures of human epithelial cells. Methods Back skin of C57BL/6 mice was treated with two household laundry detergents at several dilutions. Barrier function was assessed by electric impedance spectroscopy (EIS) and transepidermal water loss (TEWL) measurements after the 4 h of treatments with detergents. RNA sequencing (RNA‐seq) and targeted multiplex proteomics analyses in skin biopsy samples were performed. The 6‐h treatment effect of laundry detergent and sodium dodecyl sulfate (SDS) was investigated on ex vivo human skin. Results Detergent‐treated skin showed a significant EIS reduction and TEWL increase compared to untreated skin, with a relatively higher sensitivity …

The fact that genetic and environmental factors could trigger disruption of the epithelial barrier and subsequently initiate a Th2 inflammatory cascade conversely proposes that protecting the same barrier and promoting adequate interactions with other organs, like the gut, may be crucial for lowering the risk and preventing atopic diseases particularly, food allergies. In this review, we provide an overview of structural characteristics that support the epithelial barrier hypothesis in AD patients, including the most relevant filaggrin gene mutations, the recent discovery of the role of the transient receptor potential vanilloid 1 (TRPV1), and the role involvement of the microbiome in healthy and damaged skin. We present experimental and human studies that support the mechanisms of allergen penetration, particularly the dual allergen exposure and the outside-in, inside-out, and outside-inside-outside hypotheses. We …

MethodsBlood was collected from pregnant women (n= 168) in the second trimester of pregnancy and neonates (n= 33) from the matching mothers, along with non-pregnant women (control group; n= 151). We quantified immune biomarkers from plasma samples and cell-type specific HPTMs from both pregnant and non-pregnant women. Multivariable linear regression and network analysis were used to elucidate the dysregulated components in pregnant women due to high PM2. 5 exposure.ResultsWe found a significant association between PM2. 5 exposure and levels of immune biomarkers (IL1RA, IL8/CXCL8, IL18, IL27) and of HPTMs (H3K9ac, H3S10ph, H3K23ac, H4K20me1) at B cells, classical monocytes, and NKT. The impact of PM2. 5 differs between pregnant and non-pregnant women. Neonates with high maternal exposure had lower IL27 and higher IL4. Maternal exposure affected co-expression of …

Background Conventional basophil activation tests (BATs) measure basophil activation by the increased expression of CD63. Previously, fluorophore‐labeled avidin, a positively‐charged molecule, was found to bind to activated basophils, which tend to expose negatively charged granule constituents during degranulation. This study further compares avidin versus CD63 as basophil activation biomarkers in classifying peanut allergy. Methods Seventy subjects with either a peanut allergy (N = 47), a food allergy other than peanut (N = 6), or no food allergy (N = 17) were evaluated. We conducted BATs in response to seven peanut extract (PE) concentrations (0.01–10,000 ng/mL) and four control conditions (no stimulant, anti‐IgE, fMLP (N‐formylmethionine‐leucyl‐phenylalanine), and anti‐FcεRI). We measured avidin binding and CD63 expression on basophils with flow cytometry. We evaluated logistic …

Air pollution is one of the biggest environmental threats for asthma. Its impact is augmented by climate change. To inform the recommendations of the EAACI Guidelines on the environmental science for allergic diseases and asthma, a systematic review (SR) evaluated the impact on asthma‐related outcomes of short‐term exposure to outdoor air pollutants (PM2.5, PM10, NO2, SO2, O3, and CO), heavy traffic, outdoor pesticides, and extreme temperatures. Additionally, the SR evaluated the impact of the efficacy of interventions reducing outdoor pollutants. The risk of bias was assessed using ROBINS‐E tools and the certainty of the evidence by using GRADE. Short‐term exposure to PM2.5, PM10, and NO2 probably increases the risk of asthma‐related hospital admissions (HA) and emergency department (ED) visits (moderate certainty evidence). Exposure to heavy traffic may increase HA and deteriorate asthma …

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 …

BackgroundCardiac allograft vasculopathy (CAV) remains the leading cause of long-term graft failure and mortality after heart transplantation. Effective preventive and treatment options are not available to-date, largely because underlying mechanisms remain poorly understood. We studied the potential role of leukotriene B4 (LTB4), an inflammatory lipid mediator, in development of CAV.MethodsWe used an established pre-clinical rat CAV model to study the role of LTB4 in CAV. We performed syngeneic and allogeneic orthotopic aortic transplantation, after which neointimal proliferation was quantified. Animals were then treated with Bestatin, an inhibitor of LTB4 synthesis, or vehicle control for 30 days post-transplant, and evidence of graft CAV was determined by histology. We also measured serial LTB4 levels in a cohort of 28 human heart transplant recipients with CAV, 17 matched transplant controls without …

The EAACI Guidelines on the impact of short‐term exposure to outdoor pollutants on asthma‐related outcomes provide recommendations for prevention, patient care and mitigation in a framework supporting rational decisions for healthcare professionals and patients to individualize and improve asthma management and for policymakers and regulators as an evidence‐informed reference to help setting legally binding standards and goals for outdoor air quality at international, national and local levels. The Guideline was developed using the GRADE approach and evaluated outdoor pollutants referenced in the current Air Quality Guideline of the World Health Organization as single or mixed pollutants and outdoor pesticides. Short‐term exposure to all pollutants evaluated increases the risk of asthma‐related adverse outcomes, especially hospital admissions and emergency department visits (moderate certainty of …

BackgroundDespite their central role in peanut allergy, human monoclonal IgE antibodies have eluded characterization.ObjectiveWe sought to define the sequences, affinities, clonality, and functional properties of human monoclonal IgE antibodies in peanut allergy.MethodsWe applied our single-cell RNA sequencing–based SEQ SIFTER discovery platform to samples from allergic individuals who varied by age, sex, ethnicity, and geographic location in order to understand commonalities in the human IgE response to peanut allergens. Select antibodies were then recombinantly expressed and characterized for their allergen and epitope specificity, affinity, and functional properties.ResultsWe found striking convergent evolution of IgE monoclonal antibodies (mAbs) from several clonal families comprising both memory B cells and plasmablasts. These antibodies bound with subnanomolar affinity to the …

Asthma is a chronic inflammatory airway disease characterized by respiratory symptoms, variable airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Exposure to air pollution has been linked to an increased risk of asthma development and exacerbation. This review aims to comprehensively summarize recent data on the impact of air pollution on asthma development and exacerbation. Specifically, we reviewed the effects of air pollution on the pathogenic pathways of asthma, including type 2 and non-type 2 inflammatory responses, as well as airway epithelial barrier dysfunction. Air pollution promotes the release of epithelial cytokines, driving Th2 responses, and induces oxidative stress and the production of pro-inflammatory cytokines. The enhanced type 2 inflammation, furthered by air pollution-induced dysfunction of the airway epithelial barrier, may be associated with the …

MethodsFormalin-Fixed Paraffin-Embedded GI tissue sections (Tissues: stomach & duodenum) from 7 (5 active and 2 placebo) OIT participants at 4 different time points, viz., baseline, week 52, 104, and 117 were subjected to MIBI. We quantified 37 markers on each section and predicted the cell types based on the expression profile of immune markers using deep-learning models.ResultsDuodenum shows higher cell count than Stomach, wherein plasma cells were found to be the most prominent immune cell type. In the stomach, MCT+ mast cells, including FcαRI+ cells, were found be higher in OIT-treated patients than placebo. These cells are found to change their spatial vicinity with other cell types, including CD4+/CD8+ T cells. In the duodenum, HLA-DR+ CD8+ T cells and Myeloid cell subsets were shown to have higher cell count in the treatment group.ConclusionsMultiplexed screening of GI biopsies …

BackgroundAsthma and other atopic disorders can present with varying clinical phenotypes marked by differential metabolomic manifestations and enriched biological pathways.ObjectiveWe sought to identify these unique metabolomic profiles in atopy and asthma.MethodsWe analyzed baseline nonfasted plasma samples from a large multisite pediatric population of 470 children aged <13 years from 3 different sites in the United States and France. Atopy positivity (At+) was defined as skin prick test result of ≥3 mm and/or specific IgE ≥ 0.35 IU/mL and/or total IgE ≥ 173 IU/mL. Asthma positivity (As+) was based on physician diagnosis. The cohort was divided into 4 groups of varying combinations of asthma and atopy, and 6 pairwise analyses were conducted to best assess the differential metabolomic profiles between groups.ResultsTwo hundred ten children were classified as At−As−, 42 as At+As−, 74 as At−As …

Climate change is not just jeopardizing the health of our planet, but it is increasingly impacting our immune health. There is an expanding body of evidence that climate-related exposures, such as air pollution, heat, wildfires, extreme weather events, and biodiversity loss significantly disrupt the functioning of the human immune system. These exposures manifest in a broad range of stimuli including antigens, allergens, heat stress, pollutants, microbiota changes, and other toxic substances. Such exposures pose a direct and indirect threat to our body's primary line of defense, the epithelial barrier, affecting its physical integrity and functional efficacy. Furthermore, these climate-related environmental stressors can hyper-stimulate the innate immune system and influence adaptive immunity, notably in terms of developing and preserving immune tolerance. The loss or failure of immune tolerance can instigate a wide …

MethodsParticipants’ PBMCs at baseline (ie, pre-OIT), week 52, and week 58 were stimulated with cognate allergen (cashew or shrimp) solution for 24 hours, stained with a 21-marker panel of flow antibodies, and acquired using BD FACS Symphony™ A5 cytometer. Allergen-reactive (ie CD69+ CD40L+) CD4+ T cells were identified and analyzed using manual gating.ResultsSU 4043 participants showed a significantly lower frequency of total allergen-reactive CD4+ T cells at week 58 (p= 0.0115) as well as markedly reduced frequency of CRTH2+ allergen-reactive CD4+ T cells at week 52 (p= 0.024) compared to SU 2043. In addition, a trend of lower expression of the key co-stimulatory marker CD28 was observed on allergen-reactive CD4+ T cells of SU 4043 participants vs. SU 2043 at baseline (p= 0.126).ConclusionsFrequency of total and CRTH2+ allergen-reactive CD4+ T cells and expression of CD28 may …

The current monkeypox disease (MPX) outbreak constitutes a new threat and challenge for our society. With more than 55,000 confirmed cases in 103 countries, World Health Organization declared the ongoing MPX outbreak a Public Health Emergency of International Concern (PHEIC) on July 23, 2022. The current MPX outbreak is the largest, most widespread, and most serious since the diagnosis of the first case of MPX in 1970 in the Democratic Republic of the Congo (DRC), a country where MPX is an endemic disease. Throughout history, there have only been sporadic and self‐limiting outbreaks of MPX outside Africa, with a total of 58 cases described from 2003 to 2021. This figure contrasts with the current outbreak of 2022, in which more than 55,000 cases have been confirmed in just 4 months. MPX is, in most cases, self‐limiting; however, severe clinical manifestations and complications have been …

In one aspect, methods of generating human monoclonal antibodies that specifically binds to an allergen are provided. In some embodiments, the monoclonal antibodies are generated from sequences identified from isolated single B cells from a human subject who is allergic to the allergen.

Human activity, particularly the burn-ing of fossil fuels and the industrialization of agriculture, has contributed to global climate change through the generation of carbon dioxide (CO2) and other greenhouse gases (GHGs). In 2019, GHG emissions were approximately 60 gigatons of CO2 equivalent (GtCO2-eq), 54% higher than in 1990 (Intergovernmental Panel on Climate Change, 2022). GHGs, by trapping heat within the atmosphere, have raised Earth’s average surface temperature by 1.1 C since preindustrial times. Deforestation and urbanization further exacerbate climate change by removing plants and trees, which have the ability to absorb and decrease atmospheric CO2 levels. Elevated surface temperatures have altered global weather patterns and the frequency and severity of extreme weather events, including heat waves, droughts, sandstorms, wildfires, floods, and tropical storms. Wildfires release large …

Climate change is considered the greatest threat to global health. Greenhouse gases as well as global surface temperatures have increased causing more frequent and intense heat and cold waves, wildfires, floods, drought, altered rainfall patterns, hurricanes, thunderstorms, air pollution, and windstorms. These extreme weather events have direct and indirect effects on the immune system, leading to allergic disease due to exposure to pollen, molds, and other environmental pollutants. In this review, we will focus on immune mechanisms associated with allergy and asthma-related health risks induced by climate change events. We will review current understanding of the molecular and cellular mechanisms by which the changing environment mediates these effects.

BackgroundMultiplexed protein analysis platforms are a novel and efficient way to characterize biomarkers in a variety of biological samples. Few studies have compared protein quantitation and reproducibility of results across platforms. We utilize a novel nasosorption technique to collect nasal epithelial lining fluid (NELF) from healthy subjects, and compare the detection of proteins in NELF across three commonly used platforms.MethodsNELF was collected from both nares of twenty healthy subjects using an absorbent fibrous matrix and analyzed using three different protein analysis platforms: Luminex, Meso Scale Discovery (MSD), and Olink. Twenty-three protein analytes were shared across two or more platforms, and correlations across platforms were assessed using Spearman correlations.ResultsAmong the twelve proteins represented on all three platforms, IL1⍺ and IL6 were very highly correlated …

BackgroundDespite similar clinical symptoms, peanut-allergic (PA) individuals may respond quite differently to the same therapeutic interventions.ObjectiveThis study aimed to determine whether inherent qualities of cell response at baseline could influence response to peanut oral immunotherapy (PnOIT).MethodsWe first performed ex vivo T-cell profiling on peanut-reactive CD154+CD137+ T (pTeff) cells from 90 challenge-confirmed PA individuals. We developed a gating strategy for unbiased assessment of the phenotypic distribution of rare pTeff cells across different memory CD4+ T-cell subsets to define patient immunotype. In longitudinal samples of 29 PA participants enrolled onto the IMPACT trial of PnOIT, we determined whether patient immunotype at baseline could influence response to PnOIT.ResultsOur data emphasize the heterogeneity of pTeff cell responses in PA participants with 2 mutually …

Background An impaired epithelial barrier integrity in the gastrointestinal tract is important to the pathogenesis of many inflammatory diseases. Accordingly, we assessed the potential of biomarkers of epithelial barrier dysfunction as predictive of severe COVID‐19. Methods Levels of bacterial DNA and zonulin family peptides (ZFP) as markers of bacterial translocation and intestinal permeability and a total of 180 immune and inflammatory proteins were analyzed from the sera of 328 COVID‐19 patients and 49 healthy controls. Results Significantly high levels of circulating bacterial DNA were detected in severe COVID‐19 cases. In mild COVID‐19 cases, serum bacterial DNA levels were significantly lower than in healthy controls suggesting epithelial barrier tightness as a predictor of a mild disease course. COVID‐19 patients were characterized by significantly elevated levels of circulating ZFP. We identified 36 …

Background Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with complex pathogenesis for which the cellular and molecular crosstalk in AD skin has not been fully understood. Methods Skin tissues examined for spatial gene expression were derived from the upper arm of 6 healthy control (HC) donors and 7 AD patients (lesion and nonlesion). We performed spatial transcriptomics sequencing to characterize the cellular infiltrate in lesional skin. For single‐cell analysis, we analyzed the single‐cell data from suction blister material from AD lesions and HC skin at the antecubital fossa skin (4 ADs and 5 HCs) and full‐thickness skin biopsies (4 ADs and 2 HCs). The multiple proximity extension assays were performed in the serum samples from 36 AD patients and 28 HCs. Results The single‐cell analysis identified unique clusters of fibroblasts, dendritic cells, and macrophages in the …

Background The rising prevalence of many chronic diseases related to gut barrier dysfunction coincides with the increased global usage of dietary emulsifiers in recent decades. We therefore investigated the effect of the frequently used food emulsifiers on cytotoxicity, barrier function, transcriptome alterations, and protein expression in gastrointestinal epithelial cells. Methods Human intestinal organoids originating from induced pluripotent stem cells, colon organoid organ‐on‐a‐chip, and liquid–liquid interface cells were cultured in the presence of two common emulsifiers: polysorbate 20 (P20) and polysorbate 80 (P80). The cytotoxicity, transepithelial electrical resistance (TEER), and paracellular‐flux were measured. Immunofluorescence staining of epithelial tight‐junctions (TJ), RNA‐seq transcriptome, and targeted proteomics were performed. Results Cells showed lysis in response to P20 and P80 exposure …

3. Zhu Z, Lee PH, Chaffin MD, et al. A genome-wide cross-trait analysis from UK biobank highlights the shared genetic architecture of asthma and allergic diseases. Nat Genet. 2018; 50: 857-864. 4. Du X, Hu H. The roles of 2-Hydroxyglutarate. Front Cell Dev Biol. 2021; 9: 651317.5. Donas C, Carrasco M, Fritz M, et al. The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on DCs. J Autoimmun. 2016; 75: 105-117. 6. Clement RL, Daccache J, Mohammed MT, et al. Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses. Nat Immunol. 2019; 20: 1360-1371.

MethodsUsing high-dimensional cytometry-based single cell analysis, we conducted a comprehensive phenotypic and functional investigation of immune cell responses from nonallergic (NA) and peanut allergic (PA) participants cultured with media alone or peanut protein.ResultsNK cell activation was strongly associated with the immune response to allergen in peanut allergy. The frequency of NK cells was increased following stimulation of PBMCs with peanut protein in PA participants compared with NA participants. Peanut responsive NK cells manifested a distinct expression pattern in PA compared with NA participants. Allergen-activated NK cells expressed both Th2 and immune regulatory cytokines, hinting at a potential functional role in mediating and regulating the Th2 allergic response. Depletion of CD3+ T cells attenuated the response of NK cells to peanut allergen stimulation, suggesting peanut …

Structural and functional information about food allergens is essential for understanding the allergenicity of food proteins. All allergens belong to a small number of protein families. Various allergens from different families have been successfully produced recombinantly in E. coli for their characterization and applications in allergy diagnosis and treatment. However, recombinant hexameric 11S seed storage protein has not been reported, although numerous 11S legumins are known to be food allergens, including the recently identified macadamia nut allergen Mac i 2. Here we report the production of a macadamia nut legumin by expressing it in E. coli with a substrate site of HRV 3C protease and cleaving the purified protein with HRV 3C protease. The protease divided the protein into two chains and left a native terminus for the C-terminal chain, resulting in a recombinant hexameric 11S allergen for the first time …

The prevalence of food allergy continues to rise in the Western world, carrying with it substantial safety, economic, and emotional burdens. Although preventative strategies do exist, the heterogeneity of allergy trajectories and clinical phenotypes has made it difficult to identify patients who would benefit from these strategies. Therefore, further studies investigating the molecular mechanisms that differentiate allergic trajectories are needed. Large-scale omics studies have identified key insights into the molecular mechanisms for many different diseases, however the application of these technologies to uncover the drivers of food allergy is in its infancy. Here we review the use of omics approaches in food allergy and highlight key gaps in knowledge for applying these technologies for the characterization of food allergy development.

As part of our internal review, we identified a point to be clarified in the methods. The omitted step involves the reclassification of all deaths to the most severe category of outcome trajectories (trajectory group 5), and corresponding reclassification of non-deaths in this category to the adjacent, less severe category (trajectory group 4). This is implied by our use of the descriptor ‘fatal’for the most severe category, but our description of methods omits the step to reclassify participants.

BackgroundThe prevalence of pediatric food allergy (FA) has increased in the past 2 decades. The previous literature suggests that FA presents burdens, both economically and psychosocially, to children and their caregivers, especially families in lower-income strata. Using data from a previously published needs assessment, the Food Allergy Management in Low-Income Youth study, the FA Passport and Workbook tools were developed to address identified needs.ObjectiveThis study evaluated the utility of the FA Passport in helping families insured by Medicaid to manage FA better and improve quality of life.MethodsFamilies insured through Illinois Medicaid were recruited from two Chicago-based allergy clinics. Caregivers of children with FA completed a pretest evaluating knowledge, attitudes, beliefs, and practices regarding FA management. A clinician guided caregivers through the FA Passport. The …

First worldwide family litigation filed litigation Critical https://patents. darts-ip. com/? family= 56689334&utm_source= google_patent&utm_medium= platform_link&utm_campaign= public_patent_search&patent= PL3258962 (T3)" Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

Immune responses during pregnancy need to be precisely regulated to protect the fetus from microbial infections and to maintain tolerance for the semi-allogeneic fetus. However, the mechanisms regulating fetal tolerance during pregnancy are not well understood. Recently we have identified KIR+ CD8+ T cells as a previously unappreciated subset with regulatory functions in humans to suppress harmful self-reactivity. Therefore, we asked whether KIR+ CD8+ T cells also play a role in inducing immune tolerance during pregnancy. We first observed an increased frequency of KIR+ CD8+ T cells, but not CD4+ regulatory T cells (Tregs), in the peripheral blood of pregnant women at second trimester compared to age-matched nonpregnant females. Interestingly, those with a male fetus had an even higher level of KIR+ CD8+ T cells than the ones with a female fetus. In vitro, we found that KIR+ CD8+ T cells can …

The One Health approach is a collaborative and interdisciplinary strategy with focal point on human, animal, and environmental health interconnections. One Health can support the advanced management of allergic diseases and asthma, as complex, multifactorial diseases driven by interactions between the resilience response to the exposome. According to the One Health concept allergic diseases and asthma arising from exposures to a wide range of allergens, infectious agents and irritants (such as pollutants) occurring indoors and outdoors can be heavily influenced by environmental health (air, water, and soil quality) intermingled with animal health. These are currently heavily impacted by climate change, land use, urbanization, migration, overpopulation, and many more. Thus, a coordinated response to address the underlying factors that contribute to the development of allergic diseases and asthma needs …

Air pollution negatively affects a range of health outcomes. Wildfire smoke is an increasingly important contributor to air pollution, yet wildfire smoke events are highly salient and could induce behavioral responses that alter health impacts. We combine geolocated data covering all emergency department (ED) visits to nonfederal hospitals in California from 2006 to 2017 with spatially resolved estimates of daily wildfire smoke PM concentrations and quantify how smoke events affect ED visits. Total ED visits respond nonlinearly to smoke concentrations. Relative to a day with no smoke, total visits increase by 1 to 1.5% in the week following low or moderate smoke days but decline by 6 to 9% following extreme smoke days. Reductions persist for at least a month. Declines at extreme levels are driven by diagnoses not thought to be acutely impacted by pollution, including accidental injuries and several nonurgent …

Heat waves are increasing in intensity, frequency, and duration causing significant heat stress in all living organisms. Heat stress has multiple negative effects on plants affecting photosynthesis, respiration, growth, development, and reproduction. It also impacts animals leading to physiological and behavioral alterations, such as reduced caloric intake, increased water intake, and decreased reproduction and growth. In humans, epidemiological studies have shown that heat waves are associated with increased morbidity and mortality. There are many biological effects of heat stress (structural changes, enzyme function disruption, damage through reactive oxygen or nitrogen species). While plants and animals can mitigate some of these effects through adaptive mechanisms such as the generation of heat shock proteins, antioxidants, stress granules, and others, these mechanisms may likely be inadequate with …

Wildfires are increasingly impacting the environment and human health. Among the top 20 California wildfires, those in 2020–2021 burned more acres than the last century combined. Lack of an adequate early warning system impacts the health and safety of vulnerable populations disproportionately and widens the inequality gap. In this project, a multi-modal wildfire prediction and early warning system has been developed based on a novel spatio-temporal machine learning architecture. A comprehensive wildfire database with over 37 million data points was created, including the historical wildfires, environmental and meteorological sensor data from the Environmental Protection Agency, and geological data. The data was augmented into 2.53 km × 2.53 km square grids to overcome the sensor network coverage limitations. Leading and trailing indicators for the wildfires are proposed, classified, and tested. The …

The dynamics of immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants and young children by analyzing blood samples and weekly nasal swabs collected before, during, and after infection with Omicron and non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, showed no sign of decay for up to 300 days. Infants mounted a robust mucosal immune response characterized by inflammatory cytokines, interferon (IFN) α, and T helper (Th) 17 and neutrophil markers (interleukin [IL]-17, IL-8, and CXCL1). The immune response in blood was characterized by upregulation of activation markers on innate cells, no inflammatory cytokines, but several chemokines and IFNα. The latter correlated with viral load and expression of interferon …

MethodsData from double blind placebo-controlled food challenges from four IRB-approved research cohorts that included multi-allergen immunotherapy with adjunct omalizumab or single allergen immunotherapy were summarized. A cutoff of success was defined as being able to ingest ten times the initial cumulative ingested dose following OIT. Mixed effect models were used to examine predictors of successful desensitization while controlling for omalizumab and study with a cut of statistical significance at p< 0.05.ResultsData was analyzed from 211 participants (ages u= 10.63,[4, 53]). A mean value of 2.13 g was ingested at 10X cut off following OIT. Participants were able to ingest doses ranging from 25mg to 12000mg of an allergen post-OIT. Forty-one (17.45%) participants failed to increase their dose by 10X. Number of allergens (u= 2.33, p= 0.0162) and omalizumab (p= 0.0186) were found to be positively …

Air pollution is known to negatively affect a range of health outcomes. Wildfire smoke is an increasingly important contributor to air pollution, yet extreme smoke events are highly salient and could induce behavioral responses that alter health impacts. We combine geolocated data covering the near universe of 127 million emergency department (ED) visits in California with estimates of daily surface wildfire smoke PM2. 5 concentrations and quantify how increasingly acute wildfire smoke events affect ED visits. Low or moderate levels of ambient smoke increase total visits by 1-1.5% in the week following exposure, but extreme smoke days reduce total visits by 6-9%, relative to a day with no smoke. Reductions persist for at least a month. Declines during extreme exposures are driven by diagnoses not thought to be acutely impacted by pollution, including accidental injuries, and come disproportionately from less insured populations. In contrast, health outcomes with the strongest physiological link to short-term air pollution increase dramatically: ED visits for asthma, COPD, and cough all increase by 30-110% in the week after one extreme smoke day. Because low and moderate smoke days vastly outweigh extreme smoke days in our sample, we estimate that smoke exposure was responsible for roughly 3,000 additional ED visits per year in CA from 2006-2017.

It is now longer than half a century, humans, animals, and nature of the world are under the influence of exposure to many newly introduced noxious substances. These exposures are nowadays pushing the borders to be considered as the causative or exacerbating factors for many chronic disorders including allergic, autoimmune/inflammatory, and metabolic diseases. The epithelial linings serve as the outermost body’s primary physical, chemical, and immunological barriers against external stimuli. The “epithelial barrier theory” hypothesizes that these diseases are aggravated by an ongoing periepithelial inflammation triggered by exposure to a wide range of epithelial barrier–damaging insults that lead to “epithelitis” and the release of alarmins. A leaky epithelial barrier enables the microbiome’s translocation from the periphery to interepithelial and even deeper subepithelial areas together with allergens, toxins …

Introduction: Short-term increases (days to weeks) in fine particulate matter (PM2.5) air pollution are associated with atrial fibrillation (AF) episodes. We previously reported that PM2.5 was not associated with severe AF measured as emergency or inpatient hospitalization for the primary diagnosis of AF. Mild AF, though, may influence all-cause hospitalizations. This study evaluated if short-term increases in PM2.5 and ozone were associated with all-cause hospitalization at 11 Intermountain Health hospitals in patients with AF, and if this differed between wildfire (June-Oct.) and winter inversion (Nov.-March) seasons. Methods: Patients carrying an AF diagnosis (N=347,157) were evaluated for all-cause hospitalization and, secondarily, AF hospitalization (N=25,601) and first AF diagnosis (N=77,893). PM2.5 levels were measured from January 1, 1999 to March 31, 2022 (ozone: 2006-2022) in subjects residing on Utah …

Editorial comments on “Early initiation of short‐term emollient use for the prevention of atopic dermatitis in high‐risk infants—The STOP‐AD randomized controlled trial”—Is emollient therapy enough?-Brough-2023-Allergy-Wiley Online Library

Anthropogenic climate change—driven primarily by the combustion of fossil fuels that form greenhouse gases—has numerous consequences that impact health, including extreme weather events of accelerating frequency and intensity (e.g., wildfires, thunderstorms, droughts, and heat waves), mental health sequelae of displacement from these events, and the increase in aeroallergens and other pollutants. Children are especially vulnerable to climate-related exposures given that they are still developing, encounter higher exposures compared to adults, and are at risk of losing many healthy future years of life. In order to better meet the needs of generations of children born into a world affected by climate change, medical trainees must develop their knowledge of the relationships between climate change and children’s health—with a focus on applying that information in clinical practice. This review provides an …

Background Multiplexed proteomics platforms are a novel and efficient way to characterize biomarkers in a variety of biological samples. However, few studies have compared protein quantitation and reproducibility of results across platforms. In this study, we utilize a novel nasosorption technique to collect nasal epithelial lining fluid from healthy subjects, and compare the detection of proteins in nasal fluid across three commonly used proteomics platforms. Methods Nasal epithelial lining fluid was collected from both nares of twenty healthy subjects using an absorbent fibrous matrix. Samples from both nares were eluted from the matrix, combined, and subdivided into three aliquots, then analyzed using three different protein analysis platforms: Human Immunotherapy Luminex Performance Assay 24-plex Fixed Panel (R&D Systems, Minneapolis, MN); V-Plex Human Cytokine 30-plex Kit (Meso Scale Discovery …

Background The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma, are not well understood. We investigated whether ambient levels of fine PM with aerodynamic diameter ≤2.5 microns (PM2.5) are associated with alterations in circulating monocytes in children with or without asthma. Methods Monocyte phenotyping was performed by cytometry time‐of‐flight (CyTOF). Cytokines were measured using cytometric bead array and Luminex assay. ChIP‐Seq was utilized to address histone modifications in monocytes. Results Increased exposure to ambient PM2.5 was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation …

Human activity and increased use of fossil fuels have led to climate change. These changes are adversely affecting human health, including increasing the risk of developing asthma. Global temperatures are predicted to increase in the future. In 2019, asthma affected an estimated 262 million people and caused 455,000 deaths. These rates are expected to increase. Climate change by intensifying climate events such as drought, flooding, wildfires, sand storms, and thunderstorms has led to increases in air pollution, pollen season length, pollen and mold concentration, and allergenicity of pollen. These effects bear implications for the onset, exacerbation, and management of childhood asthma and are increasing health inequities. Global efforts to mitigate the effects of climate change are urgently needed with the goal of limiting global warming to between 1.5 and 2.0 °C of preindustrial times as per the 2015 Paris …

Climate change poses an unequivocal threat to the respiratory health of current and future generations. Human activities—largely through the release of greenhouse gases (GHGs)—are driving rising global temperatures. Without a concerted effort to mitigate GHG emissions or adapt to the effects of a changing climate, each increment of warming increases the risk of climate hazards (e.g. heat waves, floods, and droughts) that that can adversely affect allergy and immunological diseases. For instance, wildfires, which release large quantities of the air pollutant PM2.5, occur with greater intensity, frequency, and duration in a hotter climate. This elevates the risk of PM2.5-associated respiratory outcomes such as allergy and asthma. Fortunately, many mitigation and adaptation strategies can be applied to limit the impacts of global warming. Adaptation strategies, ranging from promotions of behavioral changes to …

Increased fossil fuel usage and extreme climate change events have led to global increases in greenhouse gases and particulate matter with 99% of the world's population now breathing polluted air that exceeds the World Health Organization's recommended limits. Pregnant women and neonates with exposure to high levels of air pollutants are at increased risk of adverse health outcomes such as maternal hypertensive disorders, postpartum depression, placental abruption, low birth weight, preterm birth, infant mortality, and adverse lung and respiratory effects. While the exact mechanism by which air pollution exerts adverse health effects is unknown, oxidative stress as well as epigenetic and immune mechanisms are thought to play roles. Comprehensive, global efforts are urgently required to tackle the health challenges posed by air pollution through policies and action for reducing air pollution as well as …

Food allergy (FA) prevalence has expanded over recent decades and affects 220 million people worldwide. 1 Although oral immunotherapy can help achieve desensitization, 2 limited alternative treatment options exist outside of allergen avoidance. Clinical diagnosis of FA remains challenging today. Currently, the gold standard for FA diagnosis is the oral food challenge, in which patients gradually ingest increasing amounts of their allergen in a supervised environment to test for an allergic response. 3 Other diagnostic procedures (eg skin prick testing and Immunoglobulin E (IgE) blood testing) can be resource-dependent, time-consuming, and distressing for patients. The medical literature has shown that FA status can be linked to increased levels of several anti-inflammatory cytokines, such as Interleukin-13 (IL-13). Recent studies have demonstrated that IL-13 production is upregulated during IgE-mediated …

Continuing insight into the molecular mechanisms of atopic disorders has enabled the development of biologics to precisely target these diseases. Food allergy (FA) and eosinophilic gastrointestinal disorders (EGIDs) are driven by similar inflammatory molecular mechanisms and exist along the same atopic disease spectrum. Therefore, many of the same biologics are being investigated to target key drivers of mechanisms shared across the disease states. The enormous potential of biologics for the treatment of FA and EGIDs is highlighted by the significant increases in the number of ongoing clinical trials (more than 30) evaluating their use in these disease states, as well as by the recent US Food and Drug Administration approval of dupilumab for the treatment of eosinophilic esophagitis. Here we discuss past and current research into the use of biologics in FA and EGIDs and their potential role in improving …

Using very sensitive “spheromer” peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in very robust peripheral blood responses to predicted SARS-CoV-2 spike peptides bound to either class-I or class-II MHC alleles. These peaked at 9.7% and 7.5% for the dominant CD4+(HLA-DRB1* 15: 01/S191) and CD8+(HLA-A* 02/S691) T cell epitopes. Interestingly, the antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring one week post the second vaccination (boost), whereas CD8+ T cells didn’t peak until two weeks later. These responses were much higher than in COVID-19 patients. We also found that prior SARS-CoV-2 infection decreased the CD8+ T cell response post vaccination by 7.3-fold at peak, and that the remaining cells were less responsive, suggesting that the virus can profoundly damage an individuals’ CD8+ T cell response.

Background: Short-term increases (days to weeks) in fine particulate matter (PM2.5) air pollution are associated with hospitalization for acute coronary syndromes (ACS). A changing climate is shifting sources of PM2.5 toward summer wildfires in the western US. This study evaluated if short-term increases in PM2.5 and ozone were associated with ACS risks in wildfire (June-October) and winter inversion (Nov.-March) seasons. Methods: Case-crossover analyses examined N=21,414 subjects with emergency or inpatient hospitalization at 11 Intermountain hospitals for ACS, including the primary diagnosis of myocardial infarction (AMI, n=20,287) or unstable angina (USA, n=1,127). PM2.5 data were collected in January 1, 1999 to March 31, 2022 (ozone: 2006-2022) from community monitors on Utah’s Wasatch Front. Odds ratios (OR) and 95% confidence intervals (CI) were computed by Poisson regression with …

BackgroundEvidence in the literature suggests that air pollution exposures experienced prenatally and early in life can be detrimental to normal lung development, however the specific timing of critical windows during development is not fully understood.ObjectivesWe evaluated air pollution exposures during the prenatal and early-life period in association with lung function at ages 6–9, in an effort to identify potentially influential windows of exposure for lung development.MethodsOur study population consisted of 222 children aged 6–9 from the Fresno-Clovis metro area in California with spirometry data collected between May 2015 and May 2017. We used distributed-lag non-linear models to flexibly model the exposure-lag-response for monthly average exposure to fine particulate matter (PM2.5) and ozone (O3) during the prenatal months and first three years of life in association with forced vital capacity (FVC …

We review current knowledge on the trends and drivers of global wildfire activity, advances in the measurement of wildfire smoke exposure, and evidence on the health effects of this exposure. We discuss methodological issues in estimating the causal effects of wildfire smoke exposures on health. We conduct a systematic review and meta-analysis of the effects of wildfire smoke exposure on all-cause mortality and respiratory and cardiovascular morbidity. We conclude by highlighting high priority areas for future research, including leveraging recently-developed spatially and temporally resolved wildfire specific ambient air pollution data to improve estimates of the health effects of wildfire smoke exposure.

BackgroundGiven the increasing prevalence of wildfires worldwide, understanding the effects of wildfire air pollutants on human health—particularly in specific immunologic pathways—is crucial. Exposure to air pollutants is associated with cardiorespiratory disease; however, immune and epithelial barrier alterations require further investigation.ObjectiveWe sought to determine the impact of wildfire smoke exposure on the immune system and epithelial barriers by using proteomics and immune cell phenotyping.MethodsA San Francisco Bay area cohort (n = 15; age 30 ± 10 years) provided blood samples before (October 2019 to March 2020; air quality index = 37) and during (August 2020; air quality index = 80) a major wildfire. Exposure samples were collected 11 days (range, 10-12 days) after continuous exposure to wildfire smoke. We determined alterations in 506 proteins, including zonulin family peptide (ZFP …

Detection of gut and mucosal peptides through TOMAHAQ in healthy individuals Detection of gut and mucosal peptides through TOMAHAQ in healthy individuals Allergy. 2023 Jul;78(7):2052-2055. doi: 10.1111/all.15698. Epub 2023 Mar 20. Authors ES Parsons 1 , F Liu 2 , A Kaushik 1 , A Lee 1 , J Schuetz 1 , D Dunham 1 , H Seastedt 1 , I Ogulur 3 , A Heider 3 , G Tan 3 , A Shah 1 , S Cao 1 , E Smith 1 , L Kost 1 , S Acharya 1 , M Prunicki 1 , M Rothenberg 4 , S Sindher 1 5 , R Leib 2 , CA Akdis 3 , K Nadeau 1 6 , S Lejeune 1 7 Affiliations 1 Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Palo Alto, California, USA. 2 Mass Spectrometry Center, Stanford University, Palo Alto, California, USA. 3 Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland. 4 Department of Pediatrics, Department of Allergy and Immunology, Cincinnati …

Mixed allergen compositions of two or more different allergens are provided. In some instances, the mixed allergen compositions include: a nut allergen; an animal allergen; and at least one of: a non-nut plant allergen; a biotic agent; and a vitamin. Also provided are methods of administering the mixed allergen compositions to a subject. The mixed allergen compositions find use in a variety of applications, including health maintenance, immune balance, gut balance, immune support, health improvement and therapeutic applications.

Respiratory virus infections play a major role in asthma, while there is a close correlation between asthma and food allergy. We hypothesized that T cell-mediated heterologous immunity may induce asthma symptoms among sensitized individuals and used two independent in silico pipelines for the identification of cross-reactive virus- and food allergen- derived T cell epitopes, considering individual peptide sequence similarity, MHC binding affinity and immunogenicity. We assessed the proteomes of human rhinovirus (RV1b), respiratory syncytial virus (RSVA2) and influenza-strains contained in the seasonal quadrivalent influenza vaccine 2019/2020 (QIV 2019/2020), as well as SARS-CoV-2 for human HLA alleles, in addition to more than 200 most common food allergen protein sequences. All resulting allergen-derived peptide candidates were subjected to an elaborate scoring system considering multiple …

Pollution in the world and exposure of humans and nature to toxic substances is continuously worsening at a rapid pace. In the last 60 years, human and domestic animal health has been challenged by continuous exposure to toxic substances and pollutants because of uncontrolled growth, modernization, and industrialization. More than 350,000 new chemicals have been introduced to our lives, mostly without any reasonable control of their health effects and toxicity. A plethora of studies show exposure to these harmful substances during this period with their implications on the skin and mucosal epithelial barrier and increasing prevalence of allergic and autoimmune diseases in the context of the “epithelial barrier hypothesis”. Exposure to these substances causes an epithelial injury with peri-epithelial inflammation, microbial dysbiosis and bacterial translocation to sub-epithelial areas, and immune response to …

The epithelial barrier represents the point of contact between the host and the external environment. It is the first line of defense against external insults in the skin, gastrointestinal and upper and lower respiratory tracts. The steep increase in chronic disorders in recent decades, including allergies and autoimmune disorders, has prompted studies to investigate the immune mechanisms of their underlying pathogeneses, all of which point to a thought-provoking shared finding: disrupted epithelial barriers. Climate change with global warming has increased the frequency of unpredictable extreme weather events, such as wildfires, droughts, floods, aberrant and longer pollination seasons, among many others. These increasingly frequent natural disasters can synergistically damage the epithelial barrier integrity in the presence of environmental pollution. A disrupted epithelial barrier induces proinflammatory activation …

The widespread presence of autoantibodies in acute infection with SARS-CoV-2 is increasingly recognized, but the prevalence of autoantibodies in non–SARS-CoV-2 infections and critical illness has not yet been reported. We profiled IgG autoantibodies in 267 patients from 5 independent cohorts with non–SARS-CoV-2 viral, bacterial, and noninfectious critical illness. Serum samples were screened using Luminex arrays that included 58 cytokines and 55 autoantigens, many of which are associated with connective tissue diseases (CTDs). Samples positive for anti-cytokine antibodies were tested for receptor blocking activity using cell-based functional assays. Anti-cytokine antibodies were identified in> 50% of patients across all 5 acutely ill cohorts. In critically ill patients, anti-cytokine antibodies were far more common in infected versus uninfected patients. In cell-based functional assays, 11 of 39 samples positive …

Desert dust and sandstorms are recurring environmental phenomena that are reported to produce serious health risks worldwide. This scoping review was conducted to identify the most likely health effects of desert dust and sandstorms and the methods used to characterize desert dust exposure from the existing epidemiological literature. We systematically searched PubMed/MEDLINE, Web of Science, and Scopus to identify studies that reported the effects of desert dust and sandstorms on human health. Search terms referred to desert dust or sandstorm exposure, names of major deserts, and health outcomes. Health effects were cross‐tabulated with study design variables (e.g., epidemiological design and methods to quantify dust exposure), desert dust source, health outcomes and conditions. We identified 204 studies that met the inclusion criteria for the scoping review. More than half of the studies (52.9 …

The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano‐technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in‐depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally …

Food allergies have increased in prevalence over the last few decades and continue to increase. Consumption of even trace amounts of common foods can cause a rapid allergic reaction (generally within minutes) which can be mild to severe to even life-threatening. For those with food allergies, eating at restaurants poses a risk of allergic reactions due to inadequate, inconsistent labeling of allergens in foods. Here, we review food labeling rules and practices in the restaurant industry and compare and contrast it with food labeling for prepackaged foods. We review global and US trends, and provide a brief historical overview. The paper describes the key legal and economic motivations behind restaurant food labeling. We describe novel risk-driven policies and new biotechnologies that have the potential to change food labeling practices worldwide. Finally, we outline desirable federal regulations and voluntary information disclosures that would positively impact the public health aspects of restaurant food labeling and improve the quality of life for people with serious food allergies.

T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using "spheromer" peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific T cell responses for the dominant CD4+ (HLA-DRB1∗15:01/S191) and CD8+ (HLA-A∗02/S691) T cell epitopes. Antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring 1 week post the second vaccination (boost), whereas CD8+ T cells peaked 2 weeks later. These peripheral T cell responses were elevated compared with COVID-19 patients. We also found that previous SARS-CoV-2 infection resulted in decreased CD8+ T cell activation and expansion, suggesting that previous infection can influence the T cell response to …

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined …

Allergic diseases and asthma are intrinsically linked to the environment we live in and to patterns of exposure. The integrated approach to understanding the effects of exposures on the immune system includes the ongoing collection of large‐scale and complex data. This requires sophisticated methods to take full advantage of what this data can offer. Here we discuss the progress and further promise of applying artificial intelligence and machine‐learning approaches to help unlock the power of complex environmental data sets toward providing causality models of exposure and intervention. We discuss a range of relevant machine‐learning paradigms and models including the way such models are trained and validated together with examples of machine learning applied to allergic disease in the context of specific environmental exposures as well as attempts to tie these environmental data streams to the full …

IntroductionPeanut oral immunotherapy (pOIT) is the only FDA-approved treatment for food allergy and its adoption amongst allergist immunologists and their patients is growing. pOIT is the subject of numerous clinical trials, however, the focus is often on treatment efficacy, safety, and tolerability, rather than identifying patients most likely to benefit from pOIT. Here, we review existing data on the clinical and immunological outcomes of pOIT that inform best practices for pOIT candidate selection.Areas CoveredIn this review, we describe the natural history of peanut allergy, summarize immunological and clinical outcomes of pOIT at different ages, discuss the optimization of pOIT in key age groups, and finally suggest an ideal age range at which to initiate pOIT for best outcomes.Expert OpinionpOIT is currently underutilized by patients and allergist-immunologists. Developing guidelines for selecting appropriate …

Health care professionals (HCPs) and researchers in the health care sector dedicate their professional life to maintaining and optimizing the health of their patients. To achieve this, significant amounts of resources are used and currently it is estimated that the health care sector contributes to more than 4% of net greenhouse gas (GHG) emissions. GHG emissions adversely impact planetary health and consequently human health, as the two are intricately linked. There are many factors of health care that contribute to these emissions. Hospitals and research labs also use high amounts of consumables which require large amounts of raw materials and energy to produce. They are further responsible for polluting the environment via disposal of plastics, drug products, and other chemicals. To maintain and develop state‐of‐the‐art best practices and treatments, medical experts exchange and update their knowledge …

The current disclosure provides methods and compositions for treating autoimmune conditions, including allergic conditions such as food allergy. Certain aspects of the disclosure relate to methods for treatment of food allergy comprising administering a composition comprising Phascolarctobacterium faecium and/or Ruminococcus bromii. In some aspects, disclosed are compositions comprising isolated, lyophilized bacteria such as Phascolarctobacterium faecium and/or Ruminococcus bromii.

Increased use of fossil fuels has led to global warming with concomitant increases in the severity and frequency of extreme weather events such as wildfires and sand and dust storms. These changes have led to increases in air pollutants such as particulate matter and greenhouse gases. Global warming is also associated with increases in pollen season length and pollen concentration. Particulate matter, greenhouse gases, and pollen synergistically increase incidence and severity of allergic diseases. Other indirect factors such as droughts, flooding, thunderstorms, heat waves, water pollution, human migration, deforestation, loss of green space, and decreasing biodiversity (including microbial diversity) also affect incidence and severity of allergic disease.Global warming and extreme weather events are expected to increase in the coming decades, and further increases in allergic diseases are expected …

Since the 1960 s, our health has been compromised by exposure to over 350,000 newly introduced toxic substances, contributing to the current pandemic in allergic, autoimmune and metabolic diseases. The "Epithelial Barrier Theory" postulates that these diseases are exacerbated by persistent periepithelial inflammation (epithelitis) triggered by exposure to a wide range of epithelial barrier-damaging substances as well as genetic susceptibility. The epithelial barrier serves as the body's primary physical, chemical, and immunological barrier against external stimuli. A leaky epithelial barrier facilitates the translocation of the microbiome from the surface of the afflicted tissues to interepithelial and even deeper subepithelial locations. In turn, opportunistic bacterial colonization, microbiota dysbiosis, local inflammation and impaired tissue regeneration and remodelling follow. Migration of inflammatory cells to …