Commentary from Joint Congress Speakers
We reached out to a variety of Joint Congress speakers for highlights from their presentations. Read the highlights they provided below.
Plenary 1601: Environmental Impacts on Asthma: Biology to Intervention
Epigenetic Changes Ascribed to Pollutant Exposures
Rachel L. Miller, MD FAAAAI
Recipient of the AAAAI Foundation and Sheldon L. Spector, MD FAAAAI Memorial Lectureship: Inaugural Year
This presentation discussed air pollution, airway disease and the contribution of epigenetic regulation. Cohort studies and meta-analyses have established that air pollution can cause asthma and trigger asthma exacerbations. While multiple mechanisms underlie air pollution-related asthma, this talk focused on the importance of epigenetic regulation. This includes emerging topics in epigenetic regulation, such as those related to furthering our understanding of time windows of susceptibility, and new studies that consider multiple environmental determinants, dynamic effects and genetic interactions. Interventions that may mitigate epigenetic effects of air pollution exposure were also explored. As epigenetic modifications are believed to be reversible, the identification of key molecular changes induced by environmental exposure ultimately may lead to new targeted treatments of respiratory disease.
Indoor Home Remediations and Interventions
Elizabeth Matsui, MD MHS
Recipient of the AAAAI Foundation and Gary S. Rachelefsky, MD FAAAAI Lectureship Investing Together in Our Future: Inaugural Year
Although there is skepticism about the effectiveness of home environmental interventions, closer examination of recent trials indicates that interventions in pediatric populations that result in substantial reductions in indoor exposures are, in fact, effective. In addition, results of three clinical trials published in the last year that targeted single allergens challenge the prevailing view that only individually-tailored, multi-faceted approaches are effective. The emerging data supporting single allergen interventions also provide a rationale for developing population-level interventions to target endemic allergens in communities with a high burden of asthma. For the largely minority children living in poor, urban neighborhoods, eradication of pest allergens may be impossible because of deteriorated housing and neighborhoods that have resulted from more than a century of discriminatory housing policies. Policy-related interventions that address the poor housing and neighborhood conditions hold promise as an approach that could result in larger and more sustained reductions in environmental exposures implicated in asthma symptoms and exacerbations.
Symposium 1808: The Epithelial Cell, Barrier Dysfuction and Immune Regulation in Allergic Inflammation
Defective Airway Epithelial Barrier and the Impact of Environmental Factors in Asthma
Stephen T. Holgate, MD DSc FAAAAI
The airway epithelium is the interface between the external environment and the lung tissue and circulation. The epithelium is proposed to be the master orchestrator of disordered airway function in asthma and restricts the disease processes to the conducting airways. GWAS have identified numerous susceptibility genes preferentially expressed in the epithelium linked to increased sensitivity to stress and injury, disordered repair and defective innate immunity. The net result is a stressed and injured epithelium that secretes alarmins (such as IL-33, IL-25 and TSLP) to drive dendritic cell/T cell inflammatory responses, frequently of the Th2-type, but other subtypes are being identified. The epithelium is also the source of increased mucus secretion and growth factor driven remodeling which can be recapitulated through epithelial explants in immunodeficient mice indicating an intrinsic abnormality. Analyses of airway epithelial transcriptome shows that, for asthma to emerge in an atopic individual, activation of a range of epithelial gene pathways is required, especially those involved in epithelial regeneration and integrity. The sentinel functional role of the epithelium in asthma provides new opportunities for prevention and treatment based on restoration of normal barrier functions.
Plenary 2101: Asthma and Allergic Disorders in an Environment of Continuous Climate Change
The Effect of Climate Change on Pollen Allergy and Respiratory Allergic Diseases
Nelson Augusto Rosario, MD PhD FAAAAI
Evidence that the earth’s temperature is increasing is provided by warming of the oceans, melting of glaciers, rising sea levels and diminished snow cover in the Northern Hemisphere. Climate change is associated with the intensity and frequency of rain, extreme weather events, like heat waves, droughts, snow blizzards, floods, and hurricanes. These changes are probably due to increased air pollution, greenhouse gases, deforesting, wildfires, etc., that contribute to global warming. Climate changes affect allergenic plants and pollen distribution in the following ways: plants grow faster and more; each plant produces more pollen and thus are perhaps more allergenic; phenology observations have shown that pollen season start earlier and they are longer. The consequences for patients with seasonal allergic rhinoconjunctivitis and asthma are intensification of symptoms and need of medication.
Keynote 2701: Global Environmental Change and Our Health
Linda Birnbaum, PhD DABT ATS
Recipient of the AAAAI Foundation and Dr. William and Judith H. Busse Lectureship: Investing Together in Our Future: 5th year
Non-communicable diseases stemming from environmental exposures and factors are becoming an ever increasing contributor to the global burden of disease. Dr. Linda Birnbaum, Director of the National Institute of Environmental Health Sciences and National Toxicology Program, shared with AAAAI/WAO several of the environmental factors that have the greatest impact on public health and her vision on how we can mitigate many of the effects. Within this context, she focused on the air we breathe both indoors and outdoors, the water we drink and the health effects associated with climate change. Finally Dr. Birnbaum closed by highlighting some of the opportunities we have to improve public health resiliency through the creation of healthier environments.
Plenary 3101: Environmental Influences on Innate Immunity: Insights and Mechanisms
Trained Innate Immunity: Environmental Effects and Implications
Siroon Bekkering, PhD
In recent years, emerging evidence has shown that after infection or vaccination, innate immune cells (such as monocytes, macrophages, or natural killer cells) can display long-term changes in their functional programs. These changes lead to increased responsiveness upon secondary stimulation by microbial pathogens, increased production of inflammatory mediators, and enhanced capacity to eliminate infection. Furthermore, sterile inflammatory mediators have also been shown to induce similar effects, resulting in increased inflammation in for example inflammatory diseases such as cardiovascular disease. Mechanistic studies have demonstrated that trained immunity is based on epigenetic reprogramming, as well as metabolic rewiring of the cells. The discovery of trained immunity has revealed an important and previously unrecognized property of human immune responses. This opens the door for future research to explore trained immunity’s effect on disease, for both diseases with impaired host defense, such as postsepsis immune paralysis or cancers, and autoinflammatory diseases, in which there is inappropriate activation of inflammation. In this talk, the major findings of trained immunity research were highlighted and the environmental changes that can influence the innate immune response, such as diet, infections or the circadian rhythm were discussed.
Environmental and Agricultural Modifications of Macrophage Functions: Impact on Innate Immunity
Jill A. Poole, MD FAAAAI
The role of macrophages and innate immunity with complex environmental exposures was discussed. Organic dusts from microbial component-enriched agriculture environments was the model exposure agent employed to understand how environmental exposures impact airway diseases. The presentation highlighted that exposure to these complex environmental dusts activates and enhances lung macrophages that function to control and regulate the airway inflammatory response. Toll-like receptor/MyD88 and scavenger receptor A signaling pathways were shown to be important for mediating inflammation. Of these, MyD88 signaling is central in regulating the airway inflammatory response, and moreover, the protective effect of farming exposures for allergic asthma disease can be modulated through MyD88. The session ended with a reminder that allergy and asthma healthcare practitioners should recommend protective respiratory equipment for exposed workers.
Symposium 3305: New Developments in Atopic Dermatitis and Implications for the Atopic March
Cytokines and Anticytokine Therapies in AD and Other Atopic Diseases
Emma Guttman-Yassky, MD PhD
Recipient of the Hugh A. Sampson Lectureship in Food Allergy: 3rd year
Biomarkers coupled with targeted therapeutics establish atopic dematitis (AD) as a reversible, immune-mediated disease, similar to psoriasis. The AD phenotype cannot be explained by a single cytokine pathway, like psoriasis, but Th2 is activated across all AD phenotypes. Clinical trials with IL-22, IL-4/IL-13, IL-31 antagonists (coupled with mechanistic studies) are needed to determine the relative pathogenic contribution of each axis to various AD phenotypes across the globe. Our long term goal is to develop biomarkers to predict which drug to use in an individual patient based on baseline biomarkers. This will allow for personalized treatment.
Therapeutic Interventions to Prevent AD and the Atopic March
Donald Y. M. Leung, MD PhD FAAAAI
Atopic dermatitis is the first step in systemic allergen sensitization leading to the atopic march. Skin barrier dysfunction and immune pathway activation play essential roles in driving of the atopic march.
New approaches for prevention of the atopic march involve a stepwise approach to skin barrier protection, proactive anti-inflammatory therapy, control of microbial dysbiosis and targeted immune intervention.
Symposium 4304: Update in PIDD Diagnostics and Treatments
Pearls and Pitfalls of Genetic Testing in PIDDs
Isabelle Meyts, MD PhD
The advent of next-generation sequencing (NGS) has transformed the diagnosis of primary immunodeficiency disorders (PIDDs). Fixed PIDD panels, whole-exome sequencing (WES) and whole genome sequencing (WGS) are all in use in diagnostic strategies. The diagnostic challenge consists in selecting 1 or 2 candidate variants among thousands of NGS calls. The key to successful filtering of these variants (i.e. not filtering out the pathogenic variant and not focusing erroneously on a benign variant) is a well-informed genetic hypothesis on 3 key aspects: mode of inheritance, clinical penetrance, and genetic heterogeneity of the condition. These hypotheses will drive the filtering approach. Even in the case of a novel variant in a known PIDD gene, functional validation of the disease-causing effect of the candidate variant is crucial. Several gene-level and variant-level approaches can be used to filter out the causative variant. Both panel diagnoses, WES and WGS have their pros and cons. Nevertheless, despite the technical improvements, the detailed description of the clinical phenotype is key. Ultimately, however, NGS has absolutely boosted the molecular diagnosis of PIDD, which is crucial for counseling, prognosis and guided treatment.
Plenary 4101: Cutting Edge-Food Allergy Pathogenesis, Diagnosis and Therapy
Component Resolved Diagnostics for Food Allergy
Motohiro Ebisawa, MD PhD FAAAAI
The use of allergen components is rapidly evolving and increases our possibility to manage food allergic patients with a more individual approach. Using component resolved diagnostics (CRD), we can now better diagnose, prognose and grade food allergy. We can also get help in deciding which patient should receive OFC or not. Daily routine molecular allergy diagnostics (CRD) offers a number of benefits that give us a higher diagnostic precision and allow for better management.