All Publications


  • Allergy: Mechanistic insights into new methods of prevention and therapy. Science translational medicine Akdis, C. A., Akdis, M., Boyd, S. D., Sampath, V., Galli, S. J., Nadeau, K. C. 2023; 15 (679): eadd2563

    Abstract

    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.

    View details for DOI 10.1126/scitranslmed.add2563

    View details for PubMedID 36652536

  • Correction: Quake et al. Early Introduction of Multi-Allergen Mixture for Prevention of Food Allergy: Pilot Study. Nutrients 2022, 14, 737. Nutrients Quake, A. Z., Liu, T. A., D'Souza, R., Jackson, K. G., Woch, M., Tetteh, A., Sampath, V., Nadeau, K. C., Sindher, S., Chinthrajah, R. S., Cao, S. 2022; 15 (1)

    Abstract

    In the original publication [...].

    View details for DOI 10.3390/nu15010135

    View details for PubMedID 36615910

  • Improving planetary health is integral to improving children's health-a call to action. Pediatric research Sampath, V., Nadeau, K. C., Ebi, K. L., Narvaez, D., Tessema, M. T., Pak-Gorstein, S., Darmstadt, G. L. 2022

    Abstract

    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.

    View details for DOI 10.1038/s41390-022-02432-x

    View details for PubMedID 36564478

  • Characterization and regulation of microplastic pollution for protecting planetary and human health. Environmental pollution (Barking, Essex : 1987) Jung, Y. S., Sampath, V., Prunicki, M., Aguilera, J., Allen, H., LaBeaud, D., Veidis, E., Barry, M., Erny, B., Patel, L., Akdis, C., Akdis, M., Nadeau, K. 2022: 120442

    Abstract

    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.

    View details for DOI 10.1016/j.envpol.2022.120442

    View details for PubMedID 36272609

  • Global climate change: the defining issue of our time for our children's health. Pediatric research Bearer, C. F., Molloy, E. J., Tessema, M. T., Pak-Gorstein, S., Montecillo-Narvaez, D., Darmstadt, G. L., Sampath, V., Mulkey, S., Nadeau, K. C. 2022

    View details for DOI 10.1038/s41390-022-02290-7

    View details for PubMedID 36075986

  • Food allergy, mechanisms, diagnosis and treatment: Innovation through a multi-targeted approach. Allergy Sindher, S. B., Long, A., Chin, A. R., Hy, A., Sampath, V., Nadeau, K. C., Chinthrajah, R. S. 2022

    Abstract

    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, largescale 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.

    View details for DOI 10.1111/all.15418

    View details for PubMedID 35730331

  • Increases in ambient air pollutants during pregnancy are linked to increases in methylation of IL4, IL10, and IFNgamma. Clinical epigenetics Aguilera, J., Han, X., Cao, S., Balmes, J., Lurmann, F., Tyner, T., Lutzker, L., Noth, E., Hammond, S. K., Sampath, V., Burt, T., Utz, P. J., Khatri, P., Aghaeepour, N., Maecker, H., Prunicki, M., Nadeau, K. 2022; 14 (1): 40

    Abstract

    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 20weeks pregnant from Fresno, CA, an area with chronically elevated AAP levels. Associations of average pollution concentration estimates for 1week, 1month, 3months, and 6months prior to blood draw were associated with Th cell subset (Th1, Th2, Th17, and Treg) percentages and methylation of CpG sites (IL4, IL10, IFNgamma, 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 (1week/1 mo/3 mo: Q<0.05). Th2 cell percentages were negatively associated with PM2.5 (1week/1 mo/3 mo/6 mo: Q<0.06), and NO2 (1week/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 (1week/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 (1week/1 mo/3 mo: Q<0.01), NO2 (1 mo/3 mo/6 mo: Q<0.08), PAH456 (1week/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 (1week/1 mo/3 mo/6 mo: Q<0.09). Also, IFNgamma gene methylation was positively associated with CO (1week/1 mo/3 mo: Q<0.05) and PAH456 (1week/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 IFNgamma 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.

    View details for DOI 10.1186/s13148-022-01254-2

    View details for PubMedID 35287715

  • Early Introduction of Multi-Allergen Mixture for Prevention of Food Allergy: Pilot Study. Nutrients Quake, A. Z., Liu, T. A., D'Souza, R., Jackson, K. G., Woch, M., Tetteh, A., Sampath, V., Nadeau, K. C., Sindher, S., Chinthrajah, R. S., Cao, S. 2022; 14 (4)

    Abstract

    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.

    View details for DOI 10.3390/nu14040737

    View details for PubMedID 35215387

  • Climate Change and Global Health: A Call to more Research and more Action. Allergy Agache, I., Sampath, V., Aguilera, J., Akdis, C., Akdis, M., Barry, M., Bouagnon, A., Chinthrajah, S., Collins, W., Dulitzki, C., Erny, B., Gomez, J., Goshua, A., Jutel, M., Kizer, K. W., Kline, O., LaBeaud, A. D., Pali-Scholl, I., Perrett, K. P., Peters, R. L., Plaza, M. P., Prunicki, M., Sack, T., Salas, R. N., Sindher, S. B., Sokolow, S. H., Thiel, C., Veidis, E., Wray, B. D., Traidl-Hoffmann, C., Witt, C., Nadeau, K. C. 1800

    Abstract

    There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.

    View details for DOI 10.1111/all.15229

    View details for PubMedID 35073410

  • A phase 2, randomized multi oral immunotherapy with Omalizumab 'real life' study. Allergy Sindher, S. B., Kumar, D., Cao, S., Purington, N., Long, A., Sampath, V., Zedeck, S. S., Woch, M. A., Garcia-Lloret, M., Chinthrajah, R. S. 2022

    Abstract

    Oral immunotherapy (OIT) is frequently discontinued due to adverse events (AEs) and current data suggests that lowering OIT doses can minimize severity and frequency of AEs. However, the minimum daily dose that can enable desensitization and induce immune responses in multi-food OIT (mOIT) is unknown.Participants aged 2-25 years with multi-food allergies were pretreated with fixed dose omalizumab (150 mg, 3 doses, every 4 weeks), and randomized 1:1 to receive mOIT to a total maintenance dose of either 300 or 1200 mg total protein, (total dose includes at least two and up to a max of five allergens) and then transitioned to real food protein equivalents after 18 weeks of treatment. The primary endpoint was the proportion of subjects with increases in IgG4/IgE ratio of at least 2 allergens by ≥25% from baseline after 18 weeks of therapy. The primary efficacy and safety analyses was done in the intention-to-treat population.Sixty participants were enrolled across two sites. Seventy percent of participants in both arms showed changes in sIgG4/sIgE ratio in at least 2 allergens with no difference between the treatment groups (OR (95% CI) =1.00 (0.29, 3.49)). Overall, there were no differences in AEs between the 300 and 1200 mg groups (19% vs. 17%, P = 0.69), respectively.Our data suggests that plasma marker changes are induced early, even at a total protein dose of 300 mg inclusive of multiple allergens when mOIT is combined with fixed dose omalizumab. Identification of optimal mOIT dosing with adjunct omalizumab is needed for the long-term success of OIT.

    View details for DOI 10.1111/all.15217

    View details for PubMedID 35014049

  • Food allergy across the globe. The Journal of allergy and clinical immunology Sampath, V., Abrams, E. M., Adlou, B., Akdis, C., Akdis, M., Brough, H. A., Chan, S., Chatchatee, P., Chinthrajah, R. S., Cocco, R. R., Deschildre, A., Eigenmann, P., Galvan, C., Gupta, R., Hossny, E., Koplin, J. J., Lack, G., Levin, M., Shek, L. P., Makela, M., Mendoza-Hernandez, D., Muraro, A., Papadopoulous, N. G., Pawankar, R., Perrett, K. P., Roberts, G., Sackesen, C., Sampson, H., Tang, M. L., Togias, A., Venter, C., Warren, C. M., Wheatley, L. M., Wong, G. W., Beyer, K., Nadeau, K. C., Renz, H. 2021; 148 (6): 1347-1364

    Abstract

    The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and diverse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will alsodiscuss similarities and differences between FA guidelines.

    View details for DOI 10.1016/j.jaci.2021.10.018

    View details for PubMedID 34872649

  • Climate change: A call to action for the United Nations. Allergy Nadeau, K. C., Agache, I., Jutel, M., Annesi Maesano, I., Akdis, M., Sampath, V., D'Amato, G., Cecchi, L., Traidl-Hoffmann, C., Akdis, C. A. 2021

    Abstract

    In recent decades, increased burning of fossil fuels for electricity, heating and transportation have led to increases in greenhouse gases (e.g., carbon dioxide (CO2 ), methane, nitrous oxide, and fluorinated gases) while deforestation and decreased biodiversity has reduced the Earth's ability to remove CO2 , the major greenhouse gas emission. Greenhouse gases trap the sun's energy leading to fundamental shifts in the physical and chemical nature of our planet. They also increase global temperatures both on land and in the oceans and increase acidification of the ocean. More than 90 percent of the warming that happened on Earth between 1971-2010 occurred in the oceans. In the 141 years that the National Oceanic and Atmospheric Administration (NOAA) has tracked global heat, the 10 warmest years on record have occurred since 2005.1.

    View details for DOI 10.1111/all.15079

    View details for PubMedID 34476822

  • Early intervention and prevention of allergic diseases. Allergy Brough, H. A., Lanser, B. J., Sindher, S. B., Teng, J. M., Leung, D. Y., Venter, C., Chan, S. M., Santos, A. F., Bahnson, H., Guttman-Yassky, E., Gupta, R. S., Lack, G., Ciaccio, C., Sampath, V., Nadeau, K. C., Nagler, C. R. 2021

    Abstract

    Food Allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of 1) an intact epidermal barrier to prevent epicutaneous antigen presentation, 2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and 3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.

    View details for DOI 10.1111/all.15006

    View details for PubMedID 34255344

  • Increased duration of pollen and mold exposure are linked to climate change. Scientific reports Paudel, B., Chu, T., Chen, M., Sampath, V., Prunicki, M., Nadeau, K. C. 2021; 11 (1): 12816

    Abstract

    Pollen and molds are environmental allergens that are affected by climate change. As pollen and molds exhibit geographical variations, we sought to understand the impact of climate change (temperature, carbon dioxide (CO2), precipitation, smoke exposure) on common pollen and molds in the San Francisco Bay Area, one of the largest urban areas in the United States. When using time-series regression models between 2002 and 2019, the annual average number of weeks with pollen concentrations higher than zero increased over time. For tree pollens, the average increase in this duration was 0.47weeks and 0.51weeks for mold spores. Associations between mold, pollen and meteorological data (e.g., precipitation, temperature, atmospheric CO2, and area covered by wildfire smoke) were analyzed using the autoregressive integrated moving average model. We found that peak concentrations of weed and tree pollens were positively associated with temperature (p<0.05 at lag 0-1, 0-4, and 0-12weeks) and precipitation (p<0.05 at lag 0-4, 0-12, and 0-24weeks) changes, respectively. We did not find clear associations between pollen concentrations and CO2 levels or wildfire smoke exposure. This study's findings suggest that spore and pollen activities are related to changes in observed climate change variables.

    View details for DOI 10.1038/s41598-021-92178-z

    View details for PubMedID 34140579

  • Maternal gestational mercury exposure in relation to cord blood T cell alterations and placental gene expression signatures. Environmental research Movassagh, H., Halchenko, Y., Sampath, V., Nygaard, U. C., Jackson, B., Robbins, D., Li, Z., Nadeau, K. C., Karagas, M. R. 2021: 111385

    Abstract

    The immunotoxic impacts of mercury during early life is poorly understood. We investigated the associations between gestational mercury exposure and frequency of cord blood T cells as well as placental gene expression. Frequency of natural Treg cells was positively associated with prenatal and postpartum mercury toenail concentrations. Frequency of NKT and activated naive Th cells was positively associated with prenatal toenail mercury concentrations and number of maternal silver-mercury dental amalgams, respectively. Placental gene expression analyses revealed distinct gene signatures associated with mercury exposure. Decreased placental expression of a histone demethylase, KDM4DL, was associated with both higher prenatal and postpartum maternal toenail mercury levels among male infants and remained statistically significant after adjustment for fish and seafood consumption. The results suggest that gestational exposure to mercury concentrations contribute to alterations in both T cells and gene expression in placenta at birth. These alterations may inform mechanisms of mercury immunotoxicity.

    View details for DOI 10.1016/j.envres.2021.111385

    View details for PubMedID 34129869

  • Vaccines and Allergic reactions: the past, the current COVID-19 pandemic, and future perspectives. Allergy Sampath, V., Rabinowitz, G., Shah, M., Jain, S., Diamant, Z., Jesenak, M., Rabin, R., Vieths, S., Agache, I., Akdis, M., Barber, D., Breiteneder, H., Chinthrajah, S., Chivato, T., Collins, W., Eiwegger, T., Fast, K., Fokkens, W., O'Hehir, R. E., Ollert, M., O'Mahony, L., Palomares, O., Pfaar, O., Riggioni, C., Shamji, M. H., Sokolowska, M., Torres, M. J., Traidl-Hoffmann, C., van Zelm, M., Wang, D. Y., Zhang, L., Akdis, C., Nadeau, K. C. 2021

    Abstract

    Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur aftervaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

    View details for DOI 10.1111/all.14840

    View details for PubMedID 33811364

  • Early intervention of atopic dermatitis as a preventive strategy for progression of food allergy. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology Sweeney, A., Sampath, V., Nadeau, K. C. 2021; 17 (1): 30

    Abstract

    BACKGROUND: Atopic diseases, such as atopic dermatitis (AD) and food allergy (FA), have increased in prevalence in industrialized countries during the past few decades and pose a significant health burden. They appear to have a common underlying mechanism and a natural disease progression. AD is generally the first atopic disease to manifest followed by other atopic diseases, such as FA, allergic rhinitis, or allergic asthma suggesting that they are likely different manifestations of the same disease. BODY: Evidence suggests that allergic sensitization occurs through an impaired skin barrier, while consumption of these foods at an early age may actually result in tolerance. This has been termed the Dual-Allergen-Exposure hypothesis. Loss of barrier integrity has been hypothesized to enable penetration of allergens, pollutants, and microbes and initiation of an inflammatory immune cascade of events leading to sensitization. The immune dysfunction is thought to further exacerbate the impaired skin barrier to form a vicious cycle. There is much interest in preventing or protecting the skin barrier from developing a proinflammatory atopic state, which may potentially lead to the development of AD and subsequently, FA.CONCLUSION: Research on preventing or treating skin barrier dysfunction is ongoing. A number of studies have evaluated the efficacy of emollients in preventing AD and FA with mixed results. Studies have differed in the study design, population characteristics, emollients type, and frequency, duration, and area of application. Emollient type has varied widely from oils, creams, petrolatum-based lotions, and trilipid creams. Current research is directed towards the use of trilipid emollients that are similar to the skin's natural lipid composition with a 3:1:1 ratio of ceramides, cholesterol and free fatty acids and a pH that is similar to that of skin to determine their effectiveness for skin barrier repair and prevention of AD and FA.

    View details for DOI 10.1186/s13223-021-00531-8

    View details for PubMedID 33726824

  • COVID-19 pandemic: Practical considerations on the organization of an allergy clinic-An EAACI/ARIA Position Paper. Allergy Pfaar, O. n., Klimek, L. n., Jutel, M. n., Akdis, C. A., Bousquet, J. n., Breiteneder, H. n., Chinthrajah, S. n., Diamant, Z. n., Eiwegger, T. n., Fokkens, W. J., Fritsch, H. W., Nadeau, K. C., O'Hehir, R. E., O'Mahony, L. n., Rief, W. n., Sampath, V. n., Schedlowski, M. n., Torres, M. J., Traidl-Hoffmann, C. n., Wang, D. Y., Zhang, L. n., Bonini, M. n., Brehler, R. n., Brough, H. A., Chivato, T. n., Del Giacco, S. R., Dramburg, S. n., Gawlik, R. n., Gelincik, A. n., Hoffmann-Sommergruber, K. n., Hox, V. n., Knol, E. F., Lauerma, A. n., Matricardi, P. M., Mortz, C. G., Ollert, M. n., Palomares, O. n., Riggioni, C. n., Schwarze, J. n., Skypala, I. n., Untersmayr, E. n., Walusiak-Skorupa, J. n., Ansotegui, I. J., Bachert, C. n., Bedbrook, A. n., Bosnic-Anticevich, S. n., Brussino, L. n., Canonica, G. W., Cardona, V. n., Carreiro-Martins, P. n., Cruz, A. A., Czarlewski, W. n., Fonseca, J. A., Gotua, M. n., Haahtela, T. n., Ivancevich, J. C., Kuna, P. n., Kvedariene, V. n., Larenas-Linnemann, D. E., Abdul Latiff, A. H., Mäkelä, M. n., Morais-Almeida, M. n., Mullol, J. n., Naclerio, R. n., Ohta, K. n., Okamoto, Y. n., Onorato, G. L., Papadopoulos, N. G., Patella, V. n., Regateiro, F. S., Samoliński, B. n., Suppli Ulrik, C. n., Toppila-Salmi, S. n., Valiulis, A. n., Ventura, M. T., Yorgancioglu, A. n., Zuberbier, T. n., Agache, I. n. 2021; 76 (3): 648–76

    Abstract

    The coronavirus disease 2019 (COVID-19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on the front line, taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.The scientific information on COVID-19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet.Based on the diagnostic and treatment standards developed by EAACI, on international information regarding COVID-19, on guidelines of the World Health Organization (WHO) and other international organizations, and on previous experience, a panel of experts including clinicians, psychologists, IT experts, and basic scientists along with EAACI and the "Allergic Rhinitis and its Impact on Asthma (ARIA)" initiative have developed recommendations for the optimal management of allergy clinics during the current COVID-19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID-19 pandemic.

    View details for DOI 10.1111/all.14453

    View details for PubMedID 32531110

    View details for PubMedCentralID PMC7323448

  • Targeted DNA methylation profiling reveals epigenetic signatures in peanut allergy. JCI insight Zhou, X. n., Han, X. n., Lyu, S. C., Bunning, B. J., Kost, L. n., Chang, I. n., Cao, S. n., Sampath, V. n., Nadeau, K. C. 2021

    Abstract

    DNA methylation (DNAm) has been shown to play a role in mediating food allergy, however, the mechanism by which it does so is poorly understood. In this study, we used targeted NextGen bisulfite sequencing to evaluate DNAm levels in 125 targeted highly informative genomic regions containing 602 CpG sites on 70 immune-related genes to understand whether DNAm can differentiate peanut allergy (PA) vs non-allergy (NA). We found PA-associated DNAm signatures associated with 12 genes (7 novel to food allergy, 3 associated with Th1/Th2, and 2 associated with innate immunity) as well as DNAm signature combinations with superior diagnostic potential compared to serum peanut specific-IgE for PA vs. NA. Further, we found that following peanut protein stimulation, peripheral blood mononuclear cell (PBMCs) from PA participants showed increased production of cognate cytokines compared to NA participants. The varying responses between PA and NA participants may be associated with the interaction between the modification of DNAm and the interference of environment. Using Euclidean distance analysis, we found that the distances of methylation profile comprising 12 DNAm signatures between PA and NA pairs in monozygotic (MZ) twins were smaller than that in randomly paired genetically unrelated individuals, suggesting that PA related DNAm signatures may be associated with genetic factors.

    View details for DOI 10.1172/jci.insight.143058

    View details for PubMedID 33571165

  • Towards personalization of asthma treatment according to trigger factors. The Journal of allergy and clinical immunology Niespodziana, K., Borochova, K., Pazderova, P., Schlederer, T., Astafyeva, N., Baranovskaya, T., Barbouche, M., Beltiukov, E., Berger, A., Borzova, E., Bousquet, J., Bumbacea, R. S., Bychkovskaya, S., Caraballo, L., Chung, K. F., Custovic, A., Docena, G., Eiwegger, T., Evsegneeva, I., Emelyanov, A., Errhalt, P., Fassakhov, R., Fayzullina, R., Fedenko, E., Fomina, D., Gao, Z., Giavina-Bianchi, P., Gotua, M., Greber-Platzer, S., Hedlin, G., Ilina, N., Ispayeva, Z., Idzko, M., Johnston, S. L., Kalayci, O., Karaulov, A., Karsonova, A., Khaitov, M., Kovzel, E., Kowalski, M. L., Kudlay, D., Levin, M., Makarova, S., Matricardi, P. M., Nadeau, K. C., Namazova-Baranova, L., Naumova, O., Nazarenko, O., O Byrne, P. M., Osier, F., Pampura, A. N., Panaitescu, C., Papadopoulos, N. G., Park, H., Pawankar, R., Pohl, W., Renz, H., Riabova, K., Sampath, V., Sekerel, B. E., Sibanda, E., Siroux, V., Sizyakina, L. P., Sun, J., Szepfalusi, Z., Umanets, T., Van Bever, H. P., van Hage, M., Vasileva, M., von Mutius, E., Wang, J., Wong, G. W., Zaikov, S., Zidarn, M., Valenta, R. 2020

    Abstract

    Asthma is a severe and chronic disabling disease affecting more than 300 million people world-wide. While in the past few drugs for treatment of asthma were available, new treatment options are currently emerging which appear to be highly effective in certain subgroups of patients. Accordingly there is a need for biomarkers which allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on micro-arrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed which may discriminate two of the most common forms of asthma, i.e., allergen- and virus-triggered asthma. In this perspective we argue that classification of asthma patients according to these common trigger factors may open new possibilities for personalized management of asthma.

    View details for DOI 10.1016/j.jaci.2020.02.001

    View details for PubMedID 32081759

  • Epigenetics and the Environment in Airway Disease: Asthma and Allergic Rhinitis. Advances in experimental medicine and biology Long, A., Bunning, B., Sampath, V., DeKruyff, R. H., Nadeau, K. C. 2020; 1253: 153–81

    Abstract

    Asthma and rhinitis are complex, heterogeneous diseases characterized by chronic inflammation of the upper and lower airways. While genome-wide association studies (GWAS) have identified a number of susceptible loci and candidate genes associated with the pathogenesis of asthma and allergic rhinitis (AR), the risk-associated alleles account for only a very small percent of the genetic risk. In allergic airway and other complex diseases, it is thought that epigenetic modifications, including DNA methylation, histone modifications, and non-coding microRNAs, caused by complex interactions between the underlying genome and the environment may account for some of this "missing heritability" and may explain the high degree of plasticity in immune responses. In this chapter, we will focus on the current knowledge of classical epigenetic modifications, DNA methylation and histone modifications, and their potential role in asthma and AR. In particular, we will review epigenetic variations associated with maternal airway disease, demographics, environment, and non-specific associations. The role of specific genetic haplotypes in environmentally induced epigenetic changes are also discussed. A major limitation of many of the current studies of asthma epigenetics is that they evaluate epigenetic modifications in both allergic and non-allergic asthma, making it difficult to distinguish those epigenetic modifications that mediate allergic asthma from those that mediate non-allergic asthma. Additionally, most DNA methylation studies in asthma use peripheral or cord blood due to poor accessibility of airway cells or tissue. Unlike DNA sequences, epigenetic alterations are quite cell- and tissue-specific, and epigenetic changes found in airway tissue or cells may be discordant from that of circulating blood. These two confounding factors should be considered when reviewing epigenetic studies in allergic airway disease.

    View details for DOI 10.1007/978-981-15-3449-2_6

    View details for PubMedID 32445095

  • Advances and novel developments in environmental influences on the development of atopic diseases. Allergy Alkotob, S. S., Cannedy, C. n., Harter, K. n., Movassagh, H. n., Paudel, B. n., Prunicki, M. n., Sampath, V. n., Schikowski, T. n., Smith, E. n., Zhao, Q. n., Traidl-Hoffmann, C. n., Nadeau, K. C. 2020

    Abstract

    Although genetic factors play a role in the etiology of atopic disease, the rapid increases in the prevalence of these diseases over the last few decades suggest that environmental, rather than genetic factors are the driving force behind the increasing prevalence. In modern societies, there is increased time spent indoors, use of antibiotics, and consumption of processed foods and decreased contact with farm animals and pets, which limit exposure to environmental allergens, infectious parasitic worms, and microbes. The lack of exposure to these factors is thought to prevent proper education and training of the immune system. Increased industrialization and urbanization has brought about increases in organic and inorganic pollutants. In addition, Caesarian birth, birth order, increased use of soaps and detergents, tobacco smoke exposure and psychosomatic factors are other factors that have been associated with increased rate of allergic diseases. Here, we review current knowledge on the environmental factors that have been shown to affect the development of allergic diseases and the recent developments in the field.

    View details for DOI 10.1111/all.14624

    View details for PubMedID 33037680

  • Oral immunotherapy for peanut allergy: The pro argument. The World Allergy Organization journal Chinthrajah, R. S., Cao, S. n., Dunham, T. n., Sampath, V. n., Chandra, S. n., Chen, M. n., Sindher, S. n., Nadeau, K. n. 2020; 13 (8): 100455

    Abstract

    Food allergy (FA) is a growing public health problem with personal, social, nutritional, and economic consequences. In the United States, it is estimated that 8% of children and 10.8% of adults have food allergies. Allergies to peanuts are particularly worrisome as unlike allergies to other allergenic foods, such as milk and egg, which are commonly outgrown by 5 or 10 years of age, 80% of peanut allergies persist into adulthood. The first drug for peanut allergy, Palforzia, was approved by the US Food and Drug Administration (FDA) in January 2020. For other food allergies, the current standard of care for the management of FA is suboptimal and is limited to dietary elimination of the offending allergen, vigilance against accidental ingestion, and treatment of allergic reactions with antihistamines and epinephrine. However, dietary avoidance can be challenging, and it is estimated that approximately 40% of patients with food allergies report at least one food allergy-related emergency department in their lifetime. Reactions, even from minimal exposures, can be life-threatening. Oral immunotherapy (OIT) has been the best researched therapeutic approach for treating FA over the last decade, with clinical trials investigating its efficacy, safety, and ability to improve participants' quality of life (QoL). A number of studies and meta-analyses have shown that OIT treatment is effective in raising the threshold of reactivity to peanuts and other foods in addition to producing a measurable serum immune response to such therapy. Although OIT-related adverse events (AEs) are common during treatment, serious reactions are rare. In fact, while the majority of patients experience AEs related to dosing, most continue daily dosing in hopes of achieving protection against the culprit food. Moreover, the majority of participants report improvement of QoL after OIT and are positive about undergoing OIT. These results show patients' commitment to OIT and their optimism regarding the benefits of treatment. As a first step in therapeutic options to protect from reactions to unintentional ingestion of allergenic foods, and importantly, to address the many psychosocial aspects of living with FA, OIT shows promise. Future research will focus on identifying optimal OIT regimens that maintain protection after therapy and allow for regular food consumption without allergic symptoms. Education and informed shared decision making between patients and providers are essential in optimizing current therapy regimens.

    View details for DOI 10.1016/j.waojou.2020.100455

    View details for PubMedID 33005286

    View details for PubMedCentralID PMC7519204

  • Cumulative Lifetime Burden of Cardiovascular Disease From Early Exposure to Air Pollution. Journal of the American Heart Association Kim, J. B., Prunicki, M. n., Haddad, F. n., Dant, C. n., Sampath, V. n., Patel, R. n., Smith, E. n., Akdis, C. n., Balmes, J. n., Snyder, M. P., Wu, J. C., Nadeau, K. C. 2020; 9 (6): e014944

    Abstract

    The disease burden associated with air pollution continues to grow. The World Health Organization (WHO) estimates ≈7 million people worldwide die yearly from exposure to polluted air, half of which-3.3 million-are attributable to cardiovascular disease (CVD), greater than from major modifiable CVD risks including smoking, hypertension, hyperlipidemia, and diabetes mellitus. This serious and growing health threat is attributed to increasing urbanization of the world's populations with consequent exposure to polluted air. Especially vulnerable are the elderly, patients with pre-existing CVD, and children. The cumulative lifetime burden in children is particularly of concern because their rapidly developing cardiopulmonary systems are more susceptible to damage and they spend more time outdoors and therefore inhale more pollutants. World Health Organization estimates that 93% of the world's children aged <15 years-1.8 billion children-breathe air that puts their health and development at risk. Here, we present growing scientific evidence, including from our own group, that chronic exposure to air pollution early in life is directly linked to development of major CVD risks, including obesity, hypertension, and metabolic disorders. In this review, we surveyed the literature for current knowledge of how pollution exposure early in life adversely impacts cardiovascular phenotypes, and lay the foundation for early intervention and other strategies that can help prevent this damage. We also discuss the need for better guidelines and additional research to validate exposure metrics and interventions that will ultimately help healthcare providers reduce the growing burden of CVD from pollution.

    View details for DOI 10.1161/JAHA.119.014944

    View details for PubMedID 32174249

  • New Developments in Non-allergen-specific Therapy for the Treatment of Food Allergy. Current allergy and asthma reports Long, A. n., Borro, M. n., Sampath, V. n., Chinthrajah, R. S. 2020; 20 (1): 3

    Abstract

    The prevalence of food allergy is increasing. At the current time, there are no approved treatments for food allergy. Major limitations of immunotherapy are long treatment periods (months or years), frequent clinic visits, high costs, increased risk of adverse events during treatment, and lack of durability of desensitization. Additionally, it is allergen-specific, and in those allergic to multiple allergens, the length and cost of treatment are further increased. In this review, we summarize recent developments in novel non-allergen-specific treatments for food allergy.A number of monoclonal antibodies that block IgE or specific pro-allergenic cytokines or their receptors have shown promise in clinical trials for food allergy. The insight we have gained through the use of one drug for the treatment of an atopic disease is quickly being translated to other atopic diseases, including food allergy. The future for food allergy treatment with biologics looks bright.

    View details for DOI 10.1007/s11882-020-0897-8

    View details for PubMedID 31950290

  • The future of omics for clinical practice ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY Long, A., Bunning, B., Borro, M., Sampath, V., Nadeau, K. C. 2019; 123 (6): 535–36

    View details for DOI 10.1016/j.anai.2019.07.016

    View details for Web of Science ID 000498692800004

    View details for PubMedID 31351978

  • Phase 2a randomized, placebo-controlled study of anti-IL-33 in peanut allergy. JCI insight Chinthrajah, S., Cao, S., Liu, C., Lyu, S., Sindher, S. B., Long, A., Sampath, V., Petroni, D., Londei, M., Nadeau, K. C. 2019; 4 (22)

    Abstract

    BACKGROUNDIL-33, found in high levels in participants with allergic disorders, is thought to mediate allergic reactions. Etokimab, an anti-IL-33 biologic, has previously demonstrated a good safety profile and favorable pharmacodynamic properties in many clinical studies.METHODSIn this 6-week placebo-controlled phase 2a study, we evaluated the safety and the ability of a single dose of etokimab to desensitize peanut-allergic adults. Participants received either etokimab (n = 15) or blinded placebo (n = 5). Clinical tests included oral food challenges and skin prick tests at days 15 and 45. Blood samples were collected for IgE levels and measurement of ex vivo peanut-stimulated T cell cytokine production.RESULTSEfficacy measurements for active vs. placebo participants at the day 15 and 45 food challenge (tolerating a cumulative 275 mg of peanut protein, which was the food challenge outcome defined in this paper) demonstrated, respectively, 73% vs. 0% (P = 0.008) to 57% vs. 0% (ns). The etokimab group had fewer adverse events compared with placebo. IL-4, IL-5, IL-9, IL-13, and ST2 levels in CD4+ T cells were reduced in the active vs. placebo arm upon peanut-induced T cell activation (P = 0.036 for IL-13 and IL-9 at day 15), and peanut-specific IgE was reduced in active vs. placebo (P = 0.014 at day 15).CONCLUSIONThe phase 2a results suggest etokimab is safe and well tolerated and that a single dose of etokimab could have the potential to desensitize peanut-allergic participants and possibly reduce atopy-related adverse events.TRIAL REGISTRATIONClinicalTrials.gov NCT02920021.FUNDINGThis work was supported by NIH grant R01AI140134, AnaptysBio, the Hartman Vaccine Fund, and the Sean N. Parker Center for Allergy and Asthma Research at Stanford University.

    View details for DOI 10.1172/jci.insight.131347

    View details for PubMedID 31723064

  • Conflicting verdicts on peanut OIT from the ICER and FDA Advisory Committee; where do we go from here? The Journal of allergy and clinical immunology Eiwegger, T., Anagnostou, K., Arasi, S., Begin, P., Ben-Shoshan, M., Beyer, K., Blumchen, K., Brough, H., Caubet, J., Chan, E. S., Chen, M., Chinthrajah, S., Davis, C. M., Roches, A. D., Du Toit, G., Elizur, A., Galli, S. J., Haland, G., Hoffmann-Sommergruber, K., Kim, H., Leung, D. Y., Long, A., Muraro, A., Nurmatov, U. B., Pajno, G. B., Sampath, V., Saxena, J., Sindher, S., Upton, J., Worm, M., Nadeau, K. 2019

    View details for DOI 10.1016/j.jaci.2019.10.021

    View details for PubMedID 31678426

  • Newly identified T cell subsets in mechanistic studies of food immunotherapy. The Journal of clinical investigation Sampath, V., Nadeau, K. C. 2019; 129 (4): 1431–40

    Abstract

    Allergen-specific immunotherapy has shown promise for the treatment of food allergy and is currently being evaluated in clinical trials. Although immunotherapy can induce desensitization, the mechanisms underlying this process are not completely understood. Recent advances in high-throughput technologies along with concomitant advances in data analytics have enabled monitoring of cells at the single-cell level and increased the research focus on upstream cellular factors involved in the efficacy of immunotherapy, particularly the role of T cells. As our appreciation of different T cell subsets and their plasticity increases, the initial simplistic view that restoring Th1/Th2 balance by decreasing Th2 or increasing Th1 responses can ameliorate food allergy is being enhanced by a more complex model involving other T cell subsets, particularly Tregs. In this Review, we focus on the current understanding of T cell functions in food allergy, tolerance, and immunotherapy.

    View details for DOI 10.1172/JCI124605

    View details for PubMedID 30932909

  • Can food allergy be cured? What are the future prospects? Allergy Sampath, V. n., Sindher, S. B., Alvarez Pinzon, A. M., Nadeau, K. C. 2019

    Abstract

    Food allergies have become a significant heath burden as prevalence continues to rise, affecting 6-13% of the global population. In the absence of drugs approved by regulatory agencies, the current standard of care remains avoidance of allergenic foods and management of acute allergic reactions with antihistamines and epinephrine auto-injectors. Allergen immunotherapy has been shown to increase the threshold of reactivity in the majority of food-allergic individuals. However, challenges include long treatment periods, high rates of adverse reactions, and lack of permanence of desensitization and established protocols. To address these limitations, adjunctive allergen-specific immunotherapy, vaccines, and non-allergen specific therapies (e.g., monoclonal antibodies) are being explored. The future of food allergy treatment is promising with a number of clinical trials in progress. Currently, although desensitization can be achieved for the majority of individuals with food allergy through immunotherapy, continued ingestion of allergen is needed for most individuals to maintain desensitization. Further understanding of the mechanisms of food allergy and identification of biomarkers to distinguish between temporary and permanent resolution of allergies is needed before a cure, where reactivity to the allergen is permanently lost enabling the individual to consume the allergen in any amount at any time, can be envisioned.

    View details for DOI 10.1111/all.14116

    View details for PubMedID 31733120

  • The Use of Biomarkers to Predict Aero-Allergen and Food Immunotherapy Responses CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY Sindher, S. B., Long, A., Acharya, S., Sampath, V., Nadeau, K. C. 2018; 55 (2): 190–204
  • Comparison of sublingual immunotherapy and oral immunotherapy in peanut allergy ALLERGO JOURNAL Zhang, W., Sindher, S. B., Sampath, V., Nadeau, K. 2018; 27 (6): 22–30
  • Comparison of sublingual immunotherapy and oral immunotherapy in peanut allergy. Allergo journal international Zhang, W., Sindher, S. B., Sampath, V., Nadeau, K. 2018; 27 (6): 153-161

    Abstract

    The prevalence of food allergy has been increasing over the past few decades at an alarming rate with peanut allergy affecting about 2% of children. Both oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) have shown promise as a treatment option for peanut allergy. Immunotherapy induces desensitization and reduces the risk of reaction during accidental ingestion and may also enable those who are successfully desensitized to include the food allergen in their diet. OIT has been very well studied and has been found to be more efficacious that SLIT with an acceptable safety profile. However, SLIT is associated with fewer side effects. Studies indicate that a combination of SLIT and OIT may together induce a significant increase in challenge thresholds with fewer adverse events. More head-to-head clinical trials that direct compare OIT and SLIT as well as SLIT and OIT combination studies are warranted.

    View details for DOI 10.1007/s40629-018-0067-x

    View details for PubMedID 31440440

    View details for PubMedCentralID PMC6705598

  • High dimensional immune biomarkers demonstrate differences in phenotypes and endotypes in food allergy and asthma ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY Chinthrajah, R., Purington, N., Sampath, V., Andorf, S., Manohar, M., Prunicki, M., Zhou, X., Tupa, D., Nadeau, K. C. 2018; 121 (1): 117–19
  • Impact of allergen immunotherapy in allergic asthma IMMUNOTHERAPY Zhang, W., Lin, C., Sampath, V., Nadeau, K. 2018; 10 (7): 579–93
  • Impact of allergen immunotherapy in allergic asthma. Immunotherapy Zhang, W., Lin, C., Sampath, V., Nadeau, K. 2018

    Abstract

    Although traditional pharmacological approaches improve outcomes in disease management for allergic asthma, these fail to modify the underlying immune responses. Allergen immunotherapy remains the only etiological therapy for the treatment of respiratory allergies for which clinical efficacy has been demonstrated through several well-controlled studies. In this review, we examine evidence from the past 5 years regarding the impact of allergen immunotherapy on allergic asthma to inform practitioners and stimulate further discussion and research.

    View details for PubMedID 29569506

  • New treatment directions in food allergy ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY Sampath, V., Sindher, S. B., Zhang, W., Nadeau, K. C. 2018; 120 (3): 254–62

    View details for PubMedID 29508712

  • The Use of Biomarkers to Predict Aero-Allergen and Food Immunotherapy Responses. Clinical reviews in allergy & immunology Sindher, S. B., Long, A., Acharya, S., Sampath, V., Nadeau, K. C. 2018

    Abstract

    The incidence of allergic conditions has continued to rise over the past several decades, with a growing body of research dedicated toward the treatment of such conditions. By driving a complex range of changes in the underlying immune response, immunotherapy is the only therapy that modulates the immune system with long-term effects and is presently utilized for the treatment of several atopic conditions. Recent efforts have focused on identifying biomarkers associated with these changes that may be of use in predicting patients with the highest likelihood of positive clinical outcomes during allergen immunotherapy (AIT), providing guidance regarding AIT discontinuation, and predicting symptomatic relapse and the need for booster AIT after therapy. The identification of such biomarkers in food allergy has the additional benefit of replacing oral food challenges, which are presently the gold standard for diagnosing food allergies. While several markers have shown early promise, research has yet to identify a marker that can invariably predict clinical response to AIT. Skin prick testing (SPT) and specific IgE have commonly been used as inclusion criteria for the initiation of AIT and prediction of reactions during subsequent allergen challenge; however, existing data suggests that changes in these markers are not always associated with clinical improvement and can be widely variable, reducing their utility in predicting clinical response. Similar findings have been described for the use of allergen-specific functional IgG4 antibodies, basophil activation and histamine release, and type 2 innate lymphoid cells. There appears to be a promising association between changes in the expression of dendritic cell-associated markers, as well as the use of DNA promoter region methylation patterns in the prediction of allergy status following therapy. The cellular and molecular changes brought about by immunotherapy are still under investigation, but major strides in our understanding are being made.

    View details for PubMedID 29455358

  • Food allergy and omics. The Journal of allergy and clinical immunology Dhondalay, G. K., Rael, E. n., Acharya, S. n., Zhang, W. n., Sampath, V. n., Galli, S. J., Tibshirani, R. n., Boyd, S. D., Maecker, H. n., Nadeau, K. C., Andorf, S. n. 2018; 141 (1): 20–29

    Abstract

    Food allergy (FA) prevalence has been increasing over the last few decades and is now a global health concern. Current diagnostic methods for FA result in a high number of false-positive results, and the standard of care is either allergen avoidance or use of epinephrine on accidental exposure, although currently with no other approved treatments. The increasing prevalence of FA, lack of robust biomarkers, and inadequate treatments warrants further research into the mechanism underlying food allergies. Recent technological advances have made it possible to move beyond traditional biological techniques to more sophisticated high-throughput approaches. These technologies have created the burgeoning field of omics sciences, which permit a more systematic investigation of biological problems. Omics sciences, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, and exposomics, have enabled the construction of regulatory networks and biological pathway models. Parallel advances in bioinformatics and computational techniques have enabled the integration, analysis, and interpretation of these exponentially growing data sets and opens the possibility of personalized or precision medicine for FA.

    View details for PubMedID 29307411

  • Observational long-term follow-up study of rapid food oral immunotherapy with omalizumab ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY Andorf, S., Manohar, M., Dominguez, T., Block, W., Tupa, D., Kshirsagar, R. A., Sampath, V., Chinthrajah, R., Nadeau, K. C. 2017; 13: 51

    Abstract

    A number of clinical studies focused on treating a single food allergy through oral immunotherapy (OIT) with adjunctive omalizumab treatment have been published. We previously demonstrated safety and tolerability of a rapid OIT protocol using omalizumab in a phase 1 study to achieve desensitization to multiple (up to 5) food allergens in parallel, rapidly (7-36 weeks; median = 18 weeks). In the current long-term, observational study, we followed 34 food allergic participants for over 5 years, who had originally undergone the phase 1 rapid OIT protocol.After reaching the maintenance dose of 2 g protein for each of their respective food allergens as a part of the phase 1 study, the long-term maintenance dose was reduced for some participants based on a pragmatic team-based decision. Participants were followed up to 62 months through standard oral food challenges (OFCs), skin prick tests, and blood tests.Each participant passed the 2 g OFC to each of their offending food allergens (up to 5 food allergens in total) at the end of the long-term follow-up (LTFU) study.Our data demonstrate the feasibility of long-term maintenance dosing of a food allergen without compromising the desensitized status conferred through rapid-OIT. Trial registration Registry: Clinicaltrials.gov. Registration numbers: NCT01510626 (original study), NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, retrospectively registered).

    View details for PubMedID 29296107

    View details for PubMedCentralID PMC5738812

  • Feasibility of sustained response through long-term dosing in food allergy immunotherapy ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY Andorf, S., Manohar, M., Dominguez, T., Block, W., Tupa, D., Kshirsagar, R. A., Sampath, V., Chinthrajah, R., Nadeau, K. C. 2017; 13: 52

    Abstract

    Clinical trials using oral immunotherapy (OIT) for the treatment of food allergies have shown promising results. We previously demonstrated the feasibility of desensitization for up to 5 food allergens simultaneously through OIT. In this observational study, we report the findings of long-term follow-up (LTFU) of the participants treated through a single site OIT phase 1 trial.The participants (n = 46) were followed up to 72 months since the time they reached 2 g maintenance dose per food in the initial phase 1 trial. During the long-term maintenance dosing, participants continued or reduced the initial maintenance dose of food allergen protein to high (median 2 g protein) vs. low (median 300 mg protein). Participant follow-up included clinical monitoring, standardized OFCs, and in some cases, skin prick tests and measurement of allergen-specific IgE and IgG4.Irrespective of the high vs. low long-term maintenance dose during LTFU, all participants were able to ingest 2 g protein of each food allergen protein during OFCs performed at the end of our LTFU.Our LTFU cohort of food OIT participants from a single site, phase 1 OIT study, supports the feasibility of sustained desensitization through long-term maintenance dosing. Trial registration Registry: Clinicaltrial.gov. Registration numbers: NCT01490177 (original study); NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, registered).

    View details for PubMedID 29296108

    View details for PubMedCentralID PMC5738818

  • Combining anti-IgE with oral immunotherapy PEDIATRIC ALLERGY AND IMMUNOLOGY Lin, C., Lee, I. T., Sampath, V., Dinakar, C., DeKruyff, R. H., Schneider, L. C., Nadeau, K. 2017; 28 (7): 619–27

    Abstract

    Food allergy is a significant medical problem that affects up to 8% of children in developed countries. At present, there are no curative therapies available in routine practice and management of food allergy involves strict allergen avoidance, education, and prompt treatment upon accidental exposure. Oral immunotherapy (OIT) is an efficacious experimental approach to food allergy and has been shown to provide a substantial benefit in terms of allergen desensitization. However, OIT is associated with high rates of allergic reactions, and the period of protection offered by OIT appears to be limited and highly variable. Recurrence of allergen sensitivity after a period of treatment discontinuation is commonly observed. With the aim of overcoming these limitations of OIT, several trials have studied omalizumab (anti-IgE monoclonal antibody) as an adjuvant treatment for patients undergoing OIT. Results from these trials have shown that the addition of omalizumab to OIT leads to a significant decrease in the frequency and severity of reactions, which allows for an increase in the threshold of tolerance to food allergens. This review provides a summary of the current literature and addresses some of the key questions that remain regarding the use of omalizumab in conjunction with OIT.

    View details for PubMedID 28782296

  • Cord blood T cell subpopulations and associations with maternal cadmium and arsenic exposures PLOS ONE Nygaard, U. C., Li, Z., Palys, T., Jackson, B., Subbiah, M., Malipatlolla, M., Sampath, V., Maecker, H., Karagas, M. R., Nadeau, K. C. 2017; 12 (6): e0179606

    Abstract

    Arsenic and cadmium are environmental pollutants, and although the evidence for adverse immune effects after prenatal arsenic and cadmium exposures is increasing, little is known about the underlying immunological mechanisms.We investigated the relationship between prenatal arsenic and cadmium exposures and a variety of T cell subpopulations measured in cord blood for 63 participants in the New Hampshire Birth Cohort Study. Post-partum toenail concentrations of arsenic and cadmium were used as an estimate of maternal exposure during pregnancy. The characteristics of cord blood proportions of T lymphocytes and subpopulations (expression of markers for Th1, Th2, Th17, Th1Th17, induced and natural regulatory T cells and NKTs) are presented.In regression analyses, maternal arsenic exposure levels were inversely associated with cord blood T helper memory cells (-21%, 95% CI: -36%, -3%) and the association was found to be stronger in females. They were also inversely associated with activated T helper memory cells, particularly in males (-26%, 95% CI: -43%, -3%). Similarly, inverse associations were observed between cadmium exposure levels and activated T helper memory cells (-16%, 95% CI: -30%, -1%) and also for T helper memory cells in females (-20%, 95% CI: -35%, -3%).The results suggest that prenatal exposures to relatively low levels of arsenic and cadmium may contribute to altered distribution of T cell populations at birth. These changes in theory, could have contributed to the previously reported immunosuppressive effects observed later in infancy/childhood.

    View details for PubMedID 28662050

  • Association of Clinical Reactivity with Sensitization to Allergen Components in Multifood-Allergic Children. journal of allergy and clinical immunology. In practice Andorf, S., Borres, M. P., Block, W., Tupa, D., Bollyky, J. B., Sampath, V., Elizur, A., Lidholm, J., Jones, J. E., Galli, S. J., Chinthrajah, R. S., Nadeau, K. C. 2017

    Abstract

    Thirty percent of children with food allergies have multiple simultaneous allergies; however, the features of these multiple allergies are not well characterized serologically or clinically.We comprehensively evaluated 60 multifood-allergic patients by measuring serum IgE to key allergen components, evaluating clinical histories and medication use, performing skin tests, and conducting double-blind, placebo-controlled food challenges (DBPCFCs).Sixty participants with multiple food allergies were characterized by clinical history, DBPCFCs, total IgE, specific IgE, and component-resolved diagnostics (IgE and IgG4) data. The food allergens tested were almond, egg, milk, sesame, peanut, pecan, walnut, hazelnut, cashew, pistachio, soy, and wheat.Our data demonstrate that of the reactions observed during a graded DBPCFC, gastrointestinal reactions occurred more often in boys than in girls, as well as in individuals with high levels of IgE to 2S albumins from cashew, walnut, and hazelnut. Certain food allergies often occurred concomitantly in individuals (ie, cashew/pistachio and walnut/pecan/hazelnut). IgE testing to components further corroborated serological relationships between and among these clustered food allergies.Associations of certain food allergies were shown by DBPCFC outcomes as well as by correlations in IgE reactivity to structurally related food allergen components. Each of these criteria independently demonstrated a significant association between allergies to cashew and pistachio, as well as among allergies to walnut, pecan, and hazelnut.

    View details for DOI 10.1016/j.jaip.2017.01.016

    View details for PubMedID 28351786

  • Deciphering the black box of food allergy mechanisms. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Sampath, V., Tupa, D., Graham, M. T., Chatila, T. A., Spergel, J. M., Nadeau, K. C. 2017; 118 (1): 21-27

    Abstract

    To review our current understanding of immunotherapy, the immune mechanisms underlying food allergy, and the methodological advances that are furthering our understanding of the role of immune cells and other molecules in mediating food allergies.Literature searches were performed using the following combination of terms: allergy, immunotherapy, food, and mechanisms. Data from randomized clinical studies using state-of-the-art mechanistic tools were prioritized.Articles were selected based on their relevance to food allergy.Current standard of care for food allergies is avoidance of allergenic foods and the use of epinephrine in case of severe reaction during unintentional ingestion. During the last few decades, great strides have been made in understanding the cellular and molecular mechanisms underlying food allergy, and this information is spearheading the development of exciting new treatments.Immunotherapy protocols are effective in desensitizing individuals to specific allergens; however, recurrence of allergic sensitization is common after discontinuation of therapy. Interestingly, in a subset of individuals, immunotherapy is protective against allergens even after discontinuation of immunotherapy. Whether this protection is permanent is currently unknown because of inadequate long-term follow-up data. Research on understanding the underlying mechanisms may assist in modifying protocols to improve outcome and enable sustained unresponsiveness, rather than a temporary relief against food allergies. The cellular changes brought about by immunotherapy are still a black box, but major strides in our understanding are being made at an exciting pace.

    View details for DOI 10.1016/j.anai.2016.10.017

    View details for PubMedID 28007085

    View details for PubMedCentralID PMC5193239