Effects of extreme weather on health in underserved communities.

Increased fossil fuel use has increased carbon dioxide concentrations leading to global warming and climate change with increased frequency and intensity of extreme weather events such as thunderstorms, wildfires, droughts, and heat waves. These changes increase the risk of adverse health effects for all human beings. However, these experiences do not affect 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 health care, lower educational status, and systemic racism. 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 global temperatures will continue to increase to unbearable levels creating an existential crisis. There is now global consensus that climate change is caused by anthropogenic activity and that actions to mitigate and adapt to climate change are urgently needed. The 2015 Paris Accord was the first truly global commitment that set goals to limit further warming. It also aimed to implement equity in action, founded on the principle of common but differentiated responsibilities. Meeting these goals requires individual, community, organizational, national, and global cooperation. Health care professionals, often in the frontline with firsthand knowledge of the health impacts of climate change, can play a key role in advocating for just and equitable climate change adaptation and mitigation policies.

The Immunobiology and Treatment of Food Allergy.

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 pathogenesis and immunobiology of IgE-FA in addition to its diagnosis, prognosis, and treatment.

Impact of climate change on immune responses and barrier defense.

Climate change is not just jeopardizing the health of our planet but is also increasingly affecting 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 hyperstimulate 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 spectrum of noncommunicable diseases such as autoimmune conditions, allergy, respiratory illnesses, metabolic diseases, obesity, and others. As new evidence unfolds, there is a need for additional research in climate change and immunology that covers diverse environments in different global settings and uses modern biologic and epidemiologic tools.

Effect of air pollution on asthma.

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, and airway epithelial barrier dysfunction. Air pollution promotes the release of epithelial cytokines, driving TH2 responses, and induces oxidative stress and the production of proinflammatory cytokines. The enhanced type 2 inflammation, furthered by air pollution-induced dysfunction of the airway epithelial barrier, may be associated with the exacerbation of asthma. Disruption of the TH17/regulatory T cell balance by air pollutants is also related to asthma exacerbation. As the effects of air pollution exposure may accumulate over time, with potentially stronger impacts in the development of asthma during certain sensitive life periods, we also reviewed the effects of air pollution on asthma across the lifespan. Future research is needed to better characterize the sensitive period contributing to the development of air pollution-induced asthma and to map air pollution-associated epigenetic biomarkers contributing to the epigenetic ages onto asthma-related genes.

Air pollution and pregnancy.

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 finding ways to protect the health of vulnerable populations in the face of increasing air pollution.

Cross-reactive MHC class I T cell epitopes may dictate heterologous immune responses between respiratory viruses and food allergens.

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 criteria, including clinical relevance. In both bioinformatics approaches, we found that shortlisted peptide pairs that are potentially binding to MHC class II molecules scored up to 10 × lower compared to MHC class I candidate epitopes. For MHC class I food allergen epitopes, several potentially cross-reactive peptides from shrimp, kiwi, apple, soybean and chicken were identified. The shortlisted set of peptide pairs may be implicated in heterologous immune responses and translated to peptide immunization strategies with immunomodulatory properties.

Health-based strategies for overcoming barriers to climate change adaptation and mitigation.

Climate change poses an unequivocal threat to the respiratory health of current and future generations. Human activities-largely through the release of greenhouse gases-are driving rising global temperatures. Without a concerted effort to mitigate greenhouse gas emissions or adapt to the effects of a changing climate, each increment of warming increases the risk of climate hazards (eg, heat waves, floods, and droughts) that that can adversely affect allergy and immunologic diseases. For instance, wildfires, which release large quantities of particulate matter with a diameter of less than 2.5 µm (an air pollutant), occur with greater intensity, frequency, and duration in a hotter climate. This increases the risk of 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 infrastructural improvements, have been effectively deployed to increase resilience and alleviate adverse health effects. Mitigation strategies aimed at reducing greenhouse gas emissions can not only address the problem at the source but also provide numerous direct health cobenefits. Although it is possible to limit the impacts of climate change, urgent and sustained action must be taken now. The health and scientific community can play a key role in promoting and implementing climate action to ensure a more sustainable and healthy future.

Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80.

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 starting at a 0.1% (v/v) concentration across all models. Epithelial barrier disruption correlated with decreased TEER, increased paracellular-flux and irregular TJ immunostaining. RNA-seq and targeted proteomics analyses demonstrated upregulation of cell development, signaling, proliferation, apoptosis, inflammatory response, and response to stress at 0.05%, a concentration lower than direct cell toxicity. A proinflammatory response was characterized by the secretion of several cytokines and chemokines, interaction with their receptors, and PI3K-Akt and MAPK signaling pathways. CXCL5, CXCL10, and VEGFA were upregulated in response to P20 and CXCL1, CXCL8 (IL-8), CXCL10, LIF in response to P80. CONCLUSIONS: The present study provides direct evidence on the detrimental effects of food emulsifiers P20 and P80 on intestinal epithelial integrity. The underlying mechanism of epithelial barrier disruption was cell death at concentrations between 1% and 0.1%. Even at concentrations lower than 0.1%, these polysorbates induced a proinflammatory response suggesting a detrimental effect on gastrointestinal health.

The Role of Climate Change in Asthma.

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 Agreement. Clinicians need to take an active role in these efforts in order to prevent further increases in asthma prevalence. There is a role for clinician advocacy in both the clinical setting as well as in local, regional, and national settings to install measures to control and curb the escalating disease burden of childhood asthma in the setting of climate change.

Mechanisms of climate change and related air pollution on the immune system leading to allergic disease and asthma.

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.

Child-focused climate change and health content in medical schools and pediatric residencies.

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 overview of salient climate change and children's health topics that medical school and pediatric residency training curricula should cover. In addition, it highlights the strengths and limitations of existing medical school and residency climate change and pediatric health curricula. IMPACT: Provides insight into the current climate change and pediatric health curricular opportunities for medical trainees in North America at both the medical school and residency levels. Condenses climate change and pediatric health material relevant to trainees to help readers optimize curricula at their institutions.

Acute and chronic impacts of heat stress on planetary health.

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 further global warming. This review summarizes the effects of heat stress on plants and animals and the adaptative mechanisms that have evolved to counteract this stress.

Climate change and public health: The effects of global warming on the risk of allergies and autoimmune diseases: The effects of global warming on the risk of allergies and autoimmune diseases.

Global climate change and extreme weather events are associated with epigenetic modifications in immune cells, leading to the possible increased risk and prevalence of allergies and autoimmune diseases.

Allergy: Mechanistic insights into new methods of prevention and therapy.

In the past few decades, the prevalence of allergic diseases has increased worldwide. Here, we review the etiology and pathophysiology of allergic diseases, including the role of the epithelial barrier, the immune system, climate change, and pollutants. Our current understanding of the roles of early life and infancy; diverse diet; skin, respiratory, and gut barriers; and microbiome in building immune tolerance to common environmental allergens has led to changes in prevention guidelines. Recent developments on the mechanisms involved in allergic diseases have been translated to effective treatments, particularly in the past 5 years, with additional treatments now in advanced clinical trials.

Improving planetary health is integral to improving children's health-a call to action.

IMPACT: This article summarizes the adverse effects of climate and environmental change on children's health. We call for policy change, education, and advocacy to halt further deterioration of planetary health and for specific measures to prevent the negative effects of climate and environmental change on children's health. We offer an agenda for research, policy change, and healthcare practices to improve the resilience of pediatric populations in the face of climate change.

Characterization and regulation of microplastic pollution for protecting planetary and human health.

Microplastics are plastic particles <5 mm in diameter. Since the 1950s, there has been an exponential increase in the production of plastics. As of 2015, it is estimated that approximately 6300 million metric tons of plastic waste had been generated of which 79% has accumulated in landfills or the natural environment. Further, it is estimated that if current trends continue, roughly 12,000 million metric tons of plastic waste will accumulate by 2050. Plastics and microplastics are now found ubiquitously-in the air, water, and soil. Microplastics are small enough to enter the tissues of plants and animals and have been detected in human lungs, stools, placentas, and blood. Their presence in human tissues and the food chain is a cause for concern. While direct clinical evidence or epidemiological studies on the adverse effects of microplastic on human health are lacking, in vitro cellular and tissue studies and in vivo animal studies suggest potential adverse effects. With the ever-increasing presence of plastic waste in our environment, it is critical to understand their effects on our environment and on human health. The use of plastic additives, many of which have known toxic effects are also of concern. This review provides a brief overview of microplastics and the extent of the microplastic problem. There have been a few inroads in regulating plastics but currently these are insufficient to adequately mitigate plastic pollution. We also review recent advances in microplastic testing methodologies, which should support management and regulation of plastic wastes. Significant efforts to reduce, reuse, and recycle plastics are needed at the individual, community, national, and international levels to meet the challenge. In particular, significant reductions in plastic production must occur to curb the impacts of plastic on human and worldwide health, given the fact that plastic is not truly recyclable.

Food allergy, mechanisms, diagnosis and treatment: Innovation through a multi-targeted approach.

The incidence of food allergy (FA) has continued to rise over the last several decades, posing significant burdens on health and quality of life. Significant strides into the advancement of FA diagnosis, prevention, and treatment have been made in recent years. In an effort to lower reliance on resource-intensive food challenges, the field has continued work toward the development of highly sensitive and specific assays capable of high-throughput analysis to assist in the diagnosis FA. In looking toward early infancy as a critical period in the development of allergy or acquisition of tolerance, evidence has increasingly suggested that early intervention via the early introduction of food allergens and maintenance of skin barrier function may decrease the risk of FA. As such, large-scale investigations are underway evaluating infant feeding and the impact of emollient and steroid use in infants with dry skin for the prevention of allergy. On the other end of the spectrum, the past few years have been witness to an explosive increase in clinical trials of novel and innovative therapeutic strategies aimed at the treatment of FA in those whom the disease has already manifested. A milestone in the field, 2020 marked the approval of the first drug, oral peanut allergen, for the indication of peanut allergy. With a foundation of promising data supporting the safety and efficacy of single- and multi-allergen oral immunotherapy, current efforts have turned toward the use of probiotics, biologic agents, and modified allergens to optimize and improve upon existing paradigms. Through these advancements, the field hopes to gain footing in the ongoing battle against FA.

Increases in ambient air pollutants during pregnancy are linked to increases in methylation of IL4, IL10, and IFNγ.

BACKGROUND: Ambient air pollutant (AAP) exposure is associated with adverse pregnancy outcomes, such as preeclampsia, preterm labor, and low birth weight. Previous studies have shown methylation of immune genes associate with exposure to air pollutants in pregnant women, but the cell-mediated response in the context of typical pregnancy cell alterations has not been investigated. Pregnancy causes attenuation in cell-mediated immunity with alterations in the Th1/Th2/Th17/Treg environment, contributing to maternal susceptibility. We recruited women (n = 186) who were 20 weeks pregnant from Fresno, CA, an area with chronically elevated AAP levels. Associations of average pollution concentration estimates for 1 week, 1 month, 3 months, and 6 months prior to blood draw were associated with Th cell subset (Th1, Th2, Th17, and Treg) percentages and methylation of CpG sites (IL4, IL10, IFNγ, and FoxP3). Linear regression models were adjusted for weight, age, season, race, and asthma, using a Q value as the false-discovery-rate-adjusted p-value across all genes. RESULTS: Short-term and mid-term AAP exposures to fine particulate matter (PM2.5), nitrogen dioxide (NO2) carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAH456) were associated with percentages of immune cells. A decrease in Th1 cell percentage was negatively associated with PM2.5 (1 mo/3 mo: Q < 0.05), NO2 (1 mo/3 mo/6 mo: Q < 0.05), and PAH456 (1 week/1 mo/3 mo: Q < 0.05). Th2 cell percentages were negatively associated with PM2.5 (1 week/1 mo/3 mo/6 mo: Q < 0.06), and NO2 (1 week/1 mo/3 mo/6 mo: Q < 0.06). Th17 cell percentage was negatively associated with NO2 (3 mo/6 mo: Q < 0.01), CO (1 week/1 mo: Q < 0.1), PM2.5 (3 mo/6 mo: Q < 0.05), and PAH456 (1 mo/3 mo/6 mo: Q < 0.08). Methylation of the IL10 gene was positively associated with CO (1 week/1 mo/3 mo: Q < 0.01), NO2 (1 mo/3 mo/6 mo: Q < 0.08), PAH456 (1 week/1 mo/3 mo: Q < 0.01), and PM2.5 (3 mo: Q = 0.06) while IL4 gene methylation was positively associated with concentrations of CO (1 week/1 mo/3 mo/6 mo: Q < 0.09). Also, IFNγ gene methylation was positively associated with CO (1 week/1 mo/3 mo: Q < 0.05) and PAH456 (1 week/1 mo/3 mo: Q < 0.06). CONCLUSION: Exposure to several AAPs was negatively associated with T-helper subsets involved in pro-inflammatory and anti-inflammatory responses during pregnancy. Methylation of IL4, IL10, and IFNγ genes with pollution exposure confirms previous research. These results offer insights into the detrimental effects of air pollution during pregnancy, the demand for more epigenetic studies, and mitigation strategies to decrease pollution exposure during pregnancy.

Early Introduction of Multi-Allergen Mixture for Prevention of Food Allergy: Pilot Study.

The incidence and prevalence of food allergy (FA) is increasing. While several studies have established the safety and efficacy of early introduction of single allergens in infants for the prevention of FA, the exact dose, frequency, and number of allergens that can be safely introduced to infants, particularly in those at high or low risk of atopy, are still unclear. This 1-year pilot study evaluated the safety of the early introduction of single foods (milk, egg, or peanut) vs. two foods (milk/egg, egg/peanut, milk/peanut) vs. multiple foods (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/salmon/hazelnut at low, medium, or high doses) vs. no early introduction in 180 infants between 4-6 months of age. At the end of the study, they were evaluated for plasma biomarkers associated with food reactivity via standardized blood tests. Two to four years after the start of the study, participants were evaluated by standardized food challenges. The serving sizes for the single, double, and low dose mixtures were 300 mg total protein per day. The serving sizes for the medium and high dose mixtures were 900 mg and 3000 mg total protein, respectively. Equal parts of each protein were used for double or mixture foods. All infants were breastfed until at least six months of age. The results demonstrate that infants at either high or low risk for atopy were able to tolerate the early introduction of multiple allergenic foods with no increases in any safety issues, including eczema, FA, or food protein induced enterocolitis. The mixtures of foods at either low, medium, or high doses demonstrated trends for improvement in food challenge reactivity and plasma biomarkers compared to single and double food introductions. The results of this study suggest that the early introduction of foods, particularly simultaneous mixtures of many allergenic foods, may be safe and efficacious for preventing FA and can occur safely. These results need to be confirmed by larger randomized controlled studies.