Michelle Huffaker, MD

All Publications

• Dosing Reactions and Missed Doses Affect Peanut Oral Immunotherapy Outcomes. The journal of allergy and clinical immunology. In practice Olayiwola, O., Mudd, L., Dunaway, L., Laidlaw, T. M., Jones, S. M., Fulkerson, P. C., Sanda, S., Huffaker, M. F. 2025

  Abstract

  Peanut oral immunotherapy (pOIT) is a recognized treatment for patients with peanut allergy, though not all patients who undergo this therapy achieve desensitization or remission.To determine whether missed doses or dosing-reactions predict clinical outcomes with pOIT.Data from the IMPACT trial, a randomized, double-blind, placebo-controlled trial of pOIT in children aged 1 to 4 years with peanut allergy, was analyzed to determine whether treatment-emergent variables influence desensitization (ability to consume 5000mg of peanut protein without reaction during a blinded oral food challenge after 134 weeks of pOIT) and remission (six months after discontinuation of pOIT). Logistic regression models, controlling for age and Ara h2-specific IgE, were performed to assess the relationship between dosing reactions, missed doses, and outcomes.Consecutive missed doses during build-up significantly correlated with reduced likelihood of desensitization (p = 0.03, OR 0.69 (0.49, 0.96)), whereas consecutive missed doses during maintenance did not (p = 0.10, OR 0.79 (0.59, 1.05)). Furthermore, the total individual missed doses did not significantly correlate with desensitization or remission in either phase of pOIT. Conversely, dosing-reactions during maintenance did significantly correlate with reduced likelihood of desensitization (p = 0.01, OR 0.71 (0.54, 0.93)) while dosing-reactions during build-up did not significantly correlate with desensitization (p = 0.57, OR 0.95 (0.79, 1.14)) . Fewer than 10% of missed doses were attributed to dosing reactions.Missed doses during therapy and dosing-reactions during maintenance associated with poorer pOIT outcomes. Clinicians should support adherence during build-up and consider dose adjustments for patients having dosing-reactions during maintenance therapy.

  View details for DOI 10.1016/j.jaip.2025.11.008

  View details for PubMedID 41270832

• Multiomics approach to evaluating personalized biomarkers of allergen immunotherapy. The Journal of allergy and clinical immunology Shamji, M. H., Fulton, W. T., Animashaun, I., Palmer, E., Baerenfaller, K., Sokolowska, M., Barber, D., Huffaker, M., Baloh, C., Pfaar, O., Ollert, M., Klimek, L., Rabin, R. L., Tripathi, A., Togias, A., Vieths, S., Shreffler, W. G., Layhadi, J. A. 2025; 156 (3): 523-534

  Abstract

  Recent advancements in genomics and "omic" technologies have ushered in a transformative era referred to as personalized or precision medicine. This innovative approach considers the unique genetic profiles of individuals, along with a range of variability factors, to devise tailored disease treatments and prevention strategies that cater to the distinct needs of each patient. Although the terms personalized medicine and precision medicine are frequently utilized interchangeably, it is essential to delineate the subtle distinctions between them. Personalized medicine concentrates on bespoke treatments and prevention strategies that are meticulously tailored for each individual. Conversely, precision medicine utilizes advanced gene sequencing and comprehensive data analytics to formulate specific treatments and prevention strategies for defined groups of individuals based on genetic, environmental, and lifestyle factors rather than focusing exclusively on individual patients. Therefore, precision medicine constitutes an extension of traditional personalized care, improving the accuracy of diagnosis, prognosis, and therapy estimations for each patient through the application of sophisticated molecular diagnostics and advanced imaging techniques enabled by recent technological innovations. The shift from personalized to precision medicine has gained considerable traction, particularly in the wake of the 2015 US Precision Medicine Initiative, which has further stimulated advancements in this domain. This review will explore multiomics approaches that have facilitated the evaluation of personalized biomarkers associated with allergen immunotherapy, particularly in the treatment of allergic diseases. By leveraging these innovative methodologies, we aspire to cultivate more effective and individualized patient care, ultimately enhancing health outcomes for individuals with allergies.

  View details for DOI 10.1016/j.jaci.2025.06.036

  View details for PubMedID 40914606

• Evaluation of Intestinal Permeability Using Serum Biomarkers in Learning Early About Peanut Allergy Trial ALLERGY Aktas, O., Mateja, A., Li, M., Chatman, L., Grieco, M. C., Baloh, C. H., Huffaker, M., Wheatley, L. M., du Toit, G., Lack, G., Brittain, E., Frischmeyer-Guerrerio, P. A. 2025; 80 (8): 2286-2296

  Abstract

  Intestinal barrier dysfunction may lead to a break in tolerance and development of food allergy (FA). There is contradictory evidence on whether intestinal permeability (IP) is altered in IgE-mediated FA. Thus, we sought to determine whether IP differed between children with eczema who did (FA group) or did not (atopic controls, ACs) develop FA and whether peanut sensitization, allergy, and early introduction impacted IP using serum biomarkers zonulin, soluble CD14, and Intestinal Fatty Acid Binding Protein among randomly selected participants enrolled in the Learning Early About Peanut allergy trial.FA group was defined as having at least one FA at either baseline (4-11 months) or 60 months of age (V60). ACs had eczema at baseline and no FA at either visit. Serum IP markers (sIPMs) were measured by ELISA at baseline and V60, and their relationship with the clinical characteristics of participants was analyzed using parametric tests and linear regression models.We evaluated 237 FA subjects and 76 ACs. sIPM levels were similar in FA subjects and ACs at baseline and V60. Age when the child first developed any FA (< 1 year vs. > 1 year), eczema severity, peanut sensitization, peanut allergy, and early peanut introduction were not statistically significantly associated with sIPM levels. Total IgE and eosinophil levels, peanut-specific IgE, IgG4, and IgG4/IgE ratio were not correlated with sIPM levels.No differences in sIPMs were detected to support altered IP in infants with FA compared to ACs or following early peanut introduction among peanut-sensitized children.

  View details for DOI 10.1111/all.16464

  View details for Web of Science ID 001556362500012

  View details for PubMedID 39803811

  View details for PubMedCentralID PMC12255823

• Kinetics of early peanut allergy development and resolution in the EAT, LEAP, and PAS cohorts. The Journal of allergy and clinical immunology Foong, R., Bahnson, H. T., Du Toit, G., Huffaker, M., Sampson, H. A., Suarez-Farinas, M., Logan, K., Perkin, M., van Ree, R., Santos, A. F., Lack, G. 2025

  Abstract

  BACKGROUND: Little is known about the development and resolution of early peanut allergy (PA).OBJECTIVE: We examined the natural history and biomarkers of PA longitudinally in 3 cohorts.METHODS: PA development was examined in the Enquiring About Tolerance (EAT), Learning Early About Peanut (LEAP), and Peanut Allergy Sensitization (PAS) cohorts. Early PA was defined by skin prick test result of >4 mm by 12 months or oral food challenge at study entry. PA was confirmed by oral food challenge at study end point (36 months for EAT, 60 months for LEAP/PAS). Four groups were defined: early PA development with persistence (EP); early PA development with resolution (ER); late PA development (LA); and never peanut allergic. Clinical characteristics and biomarkers were compared between the groups.RESULTS: A total of 56.3% of peanut-allergic children developed PA by 12 months; 32.1% had early PA resolution by study end point. The rate of early PA resolution was 54.2% in EAT, 41.4% in LEAP, and 18.6% in PAS cohorts. Median skin prick test wheals for EP, ER, and LA were 6, 2, and 0 mm at baseline, and 10, 0, 9 mm at study end point. Median peanut-specific IgE (sIgE) levels for EP, ER, and LA were 5.9, 0.4, and 0.3 kUA/L (P < .001) at baseline; 4.7, 1.3, and 0.9 kUA/L (P < .001) at 12 months; and 20.1, 0.2, and 5.1 kUA/L (P < .001) at study end point. LA had slower component expansion (number of components Ara h 1-sIgE, Ara h 2-sIgE, Ara h 3-sIgE > 0.1 kUA/L) compared to EP. ER showed component expansion from baseline to 12 months but component retraction by study end point. Absence of eczema and egg allergy, low peanut-sIgE, or skin prick test result were predictive of PA resolution.CONCLUSION: A significant proportion of PA resolves in early childhood. Different phenotypes of PA display different biomarkers trajectories.

  View details for DOI 10.1016/j.jaci.2024.10.042

  View details for PubMedID 40609697

• Sticking With It: The Continued Benefits of 2 Years of Peanut Epicutaneous Immunotherapy in Young Children JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE Huffaker, M. F. 2025; 13 (5): 1188-1189

  View details for DOI 10.1016/j.jaip.2025.02.037

  View details for Web of Science ID 001509354500001

  View details for PubMedID 40340085

• Peanut-specific fi c IgG subclasses as biomarkers of peanut allergy in LEAP study participants WORLD ALLERGY ORGANIZATION JOURNAL Baloh, C. H., Lim, N., Huffaker, M., Patel, P., Tversky, J., Du Toit, G., Lack, G., Laidlaw, T. M., MacGlashan, D. W. 2024; 17 (8): 100940

  Abstract

  Antigen-specific IgG2 and IgG3 are rarely measured in food allergy clinical trials despite known function in preventing mast cell and basophil activation. Our objective was to determine whether measuring peanut-specific IgG2 and IgG3 levels would correlate with peanut allergy status. Peanut-specific IgG subclasses were measured via ELISA assays in Learning Early About Peanut allergy (LEAP) trial participants at 5 years of age and were correlated with peanut allergy vs peanut sensitization vs non-peanut allergic and peanut consumption vs peanut avoidance. Peanut-specific IgG1, IgG2, IgG3, and IgG4 levels were significantly different between participants with peanut allergy vs peanut sensitization vs non-peanut allergic, and a multivariate logistic regression model and stepwise selection found that IgG1 most closely associated with peanut allergy status. Similarly, all subclasses differentiated those consuming vs those avoiding peanut, but subsequent modeling found that IgG4 most closely associated with consumption status. Amongst the peanut-specific IgG subclasses, IgG1 was the best biomarker for peanut allergy, while IgG4 was the best biomarker for peanut antigen exposure in this highly atopic cohort. Our study did not find added value from evaluating peanut-specific IgG 2 and 3 as biomarkers of peanut allergy, although they did correlate with peanut allergy. Subsequent studies should assess the value of adding IgG subclasses to multivariate models predicting peanut allergy status.

  View details for DOI 10.1016/j.waojou.2024.100940

  View details for Web of Science ID 001298181300001

  View details for PubMedID 39247520

  View details for PubMedCentralID PMC11380385

• Follow-up to Adolescence after Early Peanut Introduction for Allergy Prevention NEJM EVIDENCE Du Toit, G., Huffaker, M. F., Radulovic, S., Feeney, M., Fisher, H. R., Byron, M., Dunaway, L., Calatroni, A., Johnson, M., Foong, R., Marques-Mejias, A., Bartha, I., Basting, M., Brough, H. A., Baloh, C., Laidlaw, T. M., Bahnson, H. T., Roberts, G., Plaut, M., Wheatley, L. M., Lack, G., Immune Tolerance Network LEAP Trio Trial Team 2024; 3 (6): EVIDoa2300311

  Abstract

  A randomized trial demonstrated consumption of peanut from infancy to age 5 years prevented the development of peanut allergy. An extension of that trial demonstrated the effect persisted after 1 year of peanut avoidance. This follow-up trial examined the durability of peanut tolerance at age 144 months after years of ad libitum peanut consumption.Participants from a randomized peanut consumption trial were assessed for peanut allergy following an extended period of eating or avoiding peanuts as desired. The primary end point was the rate of peanut allergy at age 144 months.We enrolled 508 of the original 640 participants (79.4%); 497 had complete primary end point data. At age 144 months, peanut allergy remained significantly more prevalent in participants in the original peanut avoidance group than in the original peanut consumption group (15.4% [38 of 246 participants] vs. 4.4% [11 of 251 participants]; P<0.001). Participants in both groups reported avoiding peanuts for prolonged periods of time between 72 and 144 months. Participants at 144 months in the peanut consumption group had levels of Ara h2-specific immunoglobulin E (a peanut allergen associated with anaphylaxis) of 0.03 ± 3.42 kU/l and levels of peanut-specific immunoglobulin G4 of 535.5 ± 4.98 μg/l, whereas participants in the peanut avoidance group had levels of Ara h2-specific immunoglobulin E of 0.06 ± 11.21 kU/l and levels of peanut-specific immunoglobulin G4 of 209.3 ± 3.84 μg/l. Adverse events were uncommon, and the majority were related to the food challenge.Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.).

  View details for DOI 10.1056/EVIDoa2300311

  View details for Web of Science ID 001534706200004

  View details for PubMedID 38804779

• The kinetics of early peanut allergy development and resolution in the EAT, LEAP, and PAS cohorts Foong , R., Bahnson, H., Du Toit , H., Huffaker , M., Sampson , H., Suarez-Farinas , M., Logan , K., Perkin , M., Van Ree , R., Santos , A., Lack , G. Journal of Allergy and Clinical Immunology. 2024
• Developing a Prediction Model for Determination of Peanut Allergy Status in the Learning Early About Peanut Allergy (LEAP) Studies JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE Sever, M. L., Calatroni, A., Roberts, G., du Toit, G., Bahnson, H. T., Radulovic, S., Larson, D., Byron, M., Santos, A. F., Huffaker, M. F., Wheatley, L. M., Lack, G. 2023; 11 (7): 2217-+

  Abstract

  The Learning Early About Peanut Allergy (LEAP) study team developed a protocol-specific algorithm using dietary history, peanut-specific IgE, and skin prick test (SPT) to determine peanut allergy status if the oral food challenge (OFC) could not be administered or did not provide a determinant result.To investigate how well the algorithm determined allergy status in LEAP; to develop a new prediction model to determine peanut allergy status when OFC results are not available in LEAP Trio, a follow-up study of LEAP participants and their families; and to compare the new prediction model with the algorithm.The algorithm was developed for the LEAP protocol before the analysis of the primary outcome. Subsequently, a prediction model was developed using logistic regression.Using the protocol-specified algorithm, 73% (453/617) of allergy determinations matched the OFC, 0.6% (4/617) were mismatched, and 26% (160/617) participants were nonevaluable. The prediction model included SPT, peanut-specific IgE, Ara h 1, Ara h 2, and Ara h 3. The model inaccurately predicted 1 of 266 participants as allergic who were not allergic by OFC and 8 of 57 participants as not allergic who were allergic by OFC. The overall error rate was 9 of 323 (2.8%) with an area under the curve of 0.99. The prediction model additionally performed well in an external validation cohort.The prediction model performed with high sensitivity and accuracy, eliminated the problem of nonevaluable outcomes, and can be used to estimate peanut allergy status in the LEAP Trio study when OFC is not available.

  View details for DOI 10.1016/j.jaip.2023.04.032

  View details for Web of Science ID 001040814100001

  View details for PubMedID 37146884

  View details for PubMedCentralID PMC11837399

• Epidermal differentiation complex genetic variation in atopic dermatitis and peanut allergy JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Huffaker, M. F., Kanchan, K., Bahnson, H. T., Ruczinski, I., Shankar, G., Leung, D. Y. M., Baloh, C., Du Toit, G., Lack, G., Nepom, G. T., Mathias, R. A. 2023; 151 (4): 1137-+

  Abstract

  Deleterious variation in the epidermal differentiation complex (EDC) on chromosome 1 is a well-known genetic determinant of atopic dermatitis (AD) and has been associated with risk of peanut allergy (PA) in population-based studies.Our aim was to determine the effect of genetic variation in the EDC on AD trajectory and risk of PA in early life.Genome sequencing was used to measure genetic variation in the EDC in the Learning Early about Peanut Allergy (LEAP) study participants. Association tests were done to identify gene- and variant-level predicted deleterious variation associated with AD severity by using the Scoring Atopic Dermatitis (SCORAD) tool (n = 559) at baseline and each follow-up visit, as well as PA and food allergy in peanut avoiders (n = 275). Predicted deleterious variants included missense variants that were frameshift insertions, frameshift deletions, stop-gain mutations, or stop-loss mutations. Associations between variant load, SCORAD score, and PA were tested by using linear and generalized linear regression models.The genes FLG, FLG2, HRNR, and TCHH1 harbored the most predicted deleterious variation (30, 6, 3, and 1 variant, respectively). FLG variants were associated with SCORAD score at all time points; 4 variants (R1798X, R501X, S126X, and S761fs) drove the association with SCORAD score at each time point, and higher variant load was associated with greater AD severity over time. There was an association between these variants and PA, which remained significant independent of baseline AD severity (odds ratio = 2.63 [95% CI = 1.11-6.01] [P = .02]).Variation in FLG predicted to be deleterious is associated with AD severity at baseline and longitudinally and has an association with PA independent of baseline severity.

  View details for DOI 10.1016/j.jaci.2022.11.008

  View details for Web of Science ID 000982202300001

  View details for PubMedID 36403663

  View details for PubMedCentralID PMC12369244

• Incorporating genetics in identifying peanut allergy risk and tailoring allergen immunotherapy: A perspective on the genetic findings from the LEAP trial. The Journal of allergy and clinical immunology Huffaker, M. F., Kanchan, K., Bahnson, H. T., Baloh, C., Lack, G., Nepom, G. T., Mathias, R. A. 2023; 151 (4): 841-847

  Abstract

  Examining the genetics of peanut allergy (PA) in the context of clinical trial interventions and outcomes provides an opportunity to not only understand gene-environment interactions for PA risk but to also understand the benefit of allergen immunotherapy. A consistent theme in the genetics of food allergy is that in keeping with the dual allergen exposure hypothesis, barrier- and immune-related genes are most commonly implicated in food allergy and tolerance. With a focus on PA, we review how genetic risk factors across 3 genes (FLG, MALT1, and HLA-DQA1) have helped delineate distinct allergic characteristics and outcomes in the context of environmental interventions in the Learning Early about Peanut Allergy (LEAP) study and other clinical trials. We specifically consider and present a framework for genetic risk prediction for the development of PA and discuss how genetics, age, and oral consumption intertwine to predict PA outcome. Although there is some promise in this proposed framework, a better understanding of the mechanistic pathways by which PA develops and persists is needed to develop targeted therapeutics for established disease. Only by understanding the mechanisms by which PA develops, persists, and resolves can we identify adjuvants to oral immunotherapy to make older children and adults immunologically similar to their younger, more malleable counterparts and thus more likely to achieve long-term tolerance.

  View details for DOI 10.1016/j.jaci.2022.12.819

  View details for PubMedID 36732171

• HLA-associated outcomes in peanut oral immunotherapy trials identify mechanistic and clinical determinants of therapeutic success. Frontiers in immunology Kanchan, K., Shankar, G., Huffaker, M. F., Bahnson, H. T., Chinthrajah, R. S., Sanda, S., Manohar, M., Ling, H., Paschall, J. E., Toit, G. D., Ruczinski, I., Togias, A., Lack, G., Nadeau, K. C., Jones, S. M., Nepom, G. T., Mathias, R. A. 2022; 13: 941839

  Abstract

  Previous studies identified an interaction between HLA and oral peanut exposure. HLA-DQA1*01:02 had a protective role with the induction of Ara h 2 epitope-specific IgG4 associated with peanut consumption during the LEAP clinical trial for prevention of peanut allergy, while it was a risk allele for peanut allergy in the peanut avoidance group. We have now evaluated this gene-environment interaction in two subsequent peanut oral immunotherapy (OIT) trials - IMPACT and POISED - to better understand the potential for the HLA-DQA1*01:02 allele as an indicator of higher likelihood of desensitization, sustained unresponsiveness, and peanut allergy remission.We determined HLA-DQA1*01:02 carrier status using genome sequencing from POISED (N=118, age: 7-55yr) and IMPACT (N=126, age: 12-<48mo). We tested for association with remission, sustained unresponsiveness (SU), and desensitization in the OIT groups, as well as peanut component specific IgG4 (psIgG4) using generalized linear models and adjusting for relevant covariates and ancestry.While not quite statistically significant, a higher proportion of HLA-DQA1*01:02 carriers receiving OIT in IMPACT were desensitized (93%) compared to non-carriers (78%); odds ratio (OR)=5.74 (p=0.06). In this sample we also observed that a higher proportion of carriers achieved remission (35%) compared to non-carriers (22%); OR=1.26 (p=0.80). In POISED, carriers more frequently attained continued desensitization (80% versus 61% among non-carriers; OR=1.28, p=0.86) and achieved SU (52% versus 31%; OR=2.32, p=0.19). psIgG4 associations with HLA-DQA1*01:02 in the OIT arm of IMPACT which included younger study subjects recapitulated patterns noted in LEAP, but no associations of note were observed in the older POISED study subjects.Findings across three clinical trials show a pattern of a gene environment interaction between HLA and oral peanut exposure. Age, and prior sensitization contribute additional determinants of outcomes, consistent with a mechanism of restricted antigen recognition fundamental to driving protective immune responses to OIT.

  View details for DOI 10.3389/fimmu.2022.941839

  View details for PubMedID 36466872

  View details for PubMedCentralID PMC9717393

• Biomarkers and mechanisms of tolerance induction in food allergic patients drive new therapeutic approaches FRONTIERS IN IMMUNOLOGY Baloh, C. H. H., Huffaker, M. F. F., Laidlaw, T. 2022; 13: 972103

  Abstract

  Immunotherapy for food-allergic patients has been effective in inducing desensitization in some populations, but long-term tolerance has remained an elusive target. A challenge facing our field is how to differentiate immune markers that are impacted by immunotherapy from those that are critical biomarkers of tolerance. Data from recent clinical trials have identified several biomarkers and mechanisms for achieving tolerance. These biomarkers include younger age, lower food-specific IgE, lower food component-specific IgE, specific linear epitope profiles, and subsets of food-specific CD4+ T cells. Additional biomarkers under investigation for their relevance in tolerance induction include TCR repertoires, gastrointestinal and skin microbiome, and local tissue immunity. This mini-review highlights recent advances in understanding biomarkers and mechanisms of tolerance induction in food immunotherapy and how these are influencing clinical trial development.

  View details for DOI 10.3389/fimmu.2022.972103

  View details for Web of Science ID 000871294500001

  View details for PubMedID 36263023

  View details for PubMedCentralID PMC9574092

• Translating lessons learned on the role of HLA in immunological responses in LEAP to peanut OIT Trials: IMPACT and POISED Kanchan, K., Shankar, G., Huffaker, M., Bahnson, H., Chinthrajah, R., Sanda, S., Manohar, M., Du Toit, G., Ruczinski, I., Lack, G., Nadeau, K., Jones, S., Nepom, G., Mathias, R. MOSBY-ELSEVIER. 2022: AB314

  View details for Web of Science ID 000778999300704

• The Prevention of Milk Allergy and the Risks of Stopping Too Soon JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE Huffaker, M. F. 2022; 10 (1): 180-181

  View details for DOI 10.1016/j.jaip.2021.09.011

  View details for Web of Science ID 000779016600023

  View details for PubMedID 35000732

• Approaches to Establishing Tolerance in Immune Mediated Diseases FRONTIERS IN IMMUNOLOGY Huffaker, M. F., Sanda, S., Chandran, S., Chung, S. A., St Clair, E., Nepom, G. T., Smilek, D. E. 2021; 12: 744804

  Abstract

  The development of rational approaches to restore immune tolerance requires an iterative approach that builds on past success and utilizes new mechanistic insights into immune-mediated pathologies. This article will review concepts that have evolved from the clinical trial experience of the Immune Tolerance Network, with an emphasis on lessons learned from the innovative mechanistic studies conducted for these trials and new strategies under development for induction of tolerance.

  View details for DOI 10.3389/fimmu.2021.744804

  View details for Web of Science ID 000703246900001

  View details for PubMedID 34616405

  View details for PubMedCentralID PMC8488342

• The efficacy of a novel monitoring device on asthma control in children with asthma ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY Behrooz, L., Dilley, M. A., Petty, C. R., Huffaker, M., Sheehan, W. J., Phipatanakul, W. 2020; 125 (3): 352-354

  View details for Web of Science ID 000572423200023

  View details for PubMedID 32574599

  View details for PubMedCentralID PMC7483778

• Racial and socioeconomic differences in school peanut-free policies JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE Bartnikas, L. M., Huffaker, M. F., Sheehan, W. J., Kanchongkittiphon, W., Petty, C. R., Leibowitz, R., Young, M. C., Phipatanakul, W. 2020; 8 (1): 340-+

  View details for DOI 10.1016/j.jaip.2019.06.036

  View details for Web of Science ID 000507942100045

  View details for PubMedID 31319221

  View details for PubMedCentralID PMC6960368

• Case series of sebelipase alfa hypersensitivity reactions and successful sebelipase alfa rapid desensitization. JIMD reports Huffaker, M. F., Liu, A. Y., Enns, G. M., Vijay, S., Amor, A. J., Adkinson, N. F. 2019; 49 (1): 30–36

  Abstract

  Allergic immune-mediated hypersensitivity reactions are known potential complications of enzyme replacement therapy. Sebelipase alfa, recombinant lysosomal acid lipase (LAL), is a potentially life-altering treatment for patients with LAL deficiency. There is very little information on the diagnosis and management of immediate hypersensitivity reactions to this drug. Here we present three unique cases of hypersensitivity reactions to sebelipase alfa, spanning a broad age spectrum from infancy to adulthood, each managed with successful rapid desensitization.

  View details for DOI 10.1002/jmd2.12066

  View details for PubMedID 31497479

• Usability of a Novel Digital Asthma Management Program Harris, B. U., Carchia, M., Huffaker, M. F., Cornfield, D. N. MOSBY-ELSEVIER. 2019: AB170

  View details for DOI 10.1016/j.jaci.2018.12.521

  View details for Web of Science ID 000457771200514

• Case series of sebelipase alfa hypersensitivity reactions and successful sebelipase alfa rapid desensitization Huffaker , M., Liu , A., Enns , G., Vijay, S., Amor , A., Adkinson , N. JIMD . 2019 30-36
• Passive Nocturnal Physiologic Monitoring Enables Early Detection of Exacerbations in Children with Asthma A Proof-of-Concept Study AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Huffaker, M. F., Carchia, M., Harris, B. U., Kethman, W. C., Murphy, T. E., Sakarovitch, C. C. D., Qin, F., Cornfield, D. N. 2018; 198 (3): 320–28

  View details for DOI 10.1164/rccm.201712-2606OC

  View details for Web of Science ID 000440607200012

• Passive Nocturnal Physiologic Monitoring Enables Early Detection of Exacerbations in Asthmatic Children: A Proof of Concept Study. American journal of respiratory and critical care medicine Huffaker, M. F., Carchia, M., Harris, B. U., Kethman, W. C., Murphy, T. E., Sakarovitch, C. C., Qin, F., Cornfield, D. N. 2018

  Abstract

  RATIONALE: Asthma management depends on prompt identification of symptoms, which challenges both patients and providers. In asthma, a misapprehension of health between exacerbations can compromise compliance. Thus, there is a need for a tool that permits objective longitudinal monitoring without increasing the burden of patient compliance.OBJECTIVES: We sought to determine whether changes in nocturnal physiology are associated with asthma symptoms in pediatric patients.METHODS: Using a contactless bed sensor, nocturnal heart rate, respiratory rate, relative stroke volume, and movement in asthmatic children 5-18 years old (n=16) were recorded. Asthma symptoms and Asthma Control Test score were reported every two weeks. Random forest model was used to identify physiologic parameters associated with asthma symptoms. Elastic net regression was used to identify variables associated with Asthma Control Test score.MEASUREMENTS AND MAIN RESULTS: The model on the full cohort performed with sensitivity of 47.2%, specificity of 96.3%, and accuracy of 87.4%; heart rate and respiratory parameters were the most important variables in this model. The model predicted asthma symptoms 35% of the time on the day prior to perception of symptoms, and 100% of the time for a select subject for which the model performed with greater sensitivity. Multivariable and bivariable analyses demonstrated significant association between heart rate and respiratory rate parameters and Asthma Control Test score.CONCLUSIONS: Nocturnal physiologic changes correlate with asthma symptoms, supporting the notion that nocturnal physiologic monitoring represents an objective diagnostic tool capable longitudinally assessing disease control and predicting asthma exacerbations in asthmatic children at home.

  View details for PubMedID 29688023

• Four cases of delayed onset systemic reaction to shellfish JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE Huffaker, M., McGhee, S. 2018; 6 (2): 656–57

  View details for PubMedID 28734856

• Impact of school peanut-free policies on epinephrine administration. journal of allergy and clinical immunology Bartnikas, L. M., Huffaker, M. F., Sheehan, W. J., Kanchongkittiphon, W., Petty, C. R., Leibowitz, R., Hauptman, M., Young, M. C., Phipatanakul, W. 2017

  Abstract

  Children with food allergies spend a large proportion of time in school but characteristics of allergic reactions in schools are not well studied. Some schools self-designate as peanut-free or have peanut-free areas, but the impact of policies on clinical outcomes has not been evaluated.We sought to determine the effect of peanut-free policies on rates of epinephrine administration for allergic reactions in Massachusetts public schools.In this retrospective study, we analyzed (1) rates of epinephrine administration in all Massachusetts public schools and (2) Massachusetts public school nurse survey reports of school peanut-free policies from 2006 to 2011 and whether schools self-designated as "peanut-free" based on policies. Rates of epinephrine administration were compared for schools with or without peanut-restrictive policies.The percentage of schools with peanut-restrictive policies did not change significantly in the study time frame. There was variability in policies used by schools self-designated as peanut-free. No policy was associated with complete absence of allergic reactions. Both self-designated peanut-free schools and schools banning peanuts from being served in school or brought from home reported allergic reactions to nuts. Policies restricting peanuts from home, served in schools, or having peanut-free classrooms did not affect epinephrine administration rates. Schools with peanut-free tables, compared to without, had lower rates of epinephrine administration (incidence rate per 10,000 students 0.2 and 0.6, respectively, P = .009).These data provide a basis for evidence-based school policies for children with food allergies. Further studies are required before decisions can be made regarding peanut-free policies in schools.

  View details for DOI 10.1016/j.jaci.2017.01.040

  View details for PubMedID 28347736

• Are There Racial and Socioeconomic Disparities in School Peanut-Free Policies? Bartnikas, L. M., Huffaker, M. F., Sheehan, W. J., Kanchongkittiphon, W., Petty, C. R., Leibowitz, R., Hauptman, M., Gaffin, J. M., Young, M. C., Phipatanakul, W. MOSBY-ELSEVIER. 2017: AB221

  View details for DOI 10.1016/j.jaci.2016.12.713

  View details for Web of Science ID 000401699800595

• School Environmental Intervention to Reduce Particulate Pollutant Exposures for Children with Asthma JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE Jhun, I., Gaffin, J. M., Coull, B. A., Huffaker, M. F., Petty, C. R., Sheehan, W. J., Baxi, S. N., Lai, P. S., Kang, C., Wolfson, J. M., Gold, D. R., Koutrakis, P., Phipatanakul, W. 2017; 5 (1): 154-+

  Abstract

  Home-based interventions to improve indoor air quality have demonstrated benefits for asthma morbidity, yet little is known about the effect of environmental interventions in the school setting.We piloted the feasibility and effectiveness of a classroom-based air cleaner intervention to reduce particulate pollutants in classrooms of children with asthma.In this pilot randomized controlled trial, we assessed the effect of air cleaners on indoor air particulate pollutant concentrations in 18 classrooms (9 control, 9 intervention) in 3 urban elementary schools. We enrolled 25 children with asthma (13 control, 12 intervention) aged 6 to 10 years. Classroom air pollutant measurements and spirometry were completed once before and twice after randomization. Asthma symptoms were surveyed every 3 months.Baseline classroom levels of fine particulate matter (particulate matter with diameter of <2.5 μm [PM2.5]) and black carbon (BC) were 6.3 and 0.41 μg/m3, respectively. When comparing the intervention to the control group, classroom PM2.5 levels were reduced by 49% and 42% and BC levels were reduced by 58% and 55% in the first and second follow-up periods, respectively (P < .05 for all comparisons). When comparing the children randomized to intervention and control classrooms, there was a modest improvement in peak flow, but no significant changes in forced expiratory volume in 1 second (FEV1) and asthma symptoms.In this pilot study, a classroom-based air cleaner intervention led to significant reductions in PM2.5 and BC. Future large-scale studies should comprehensively evaluate the effect of school-based environmental interventions on pediatric asthma morbidity.

  View details for DOI 10.1016/j.jaip.2016.07.018

  View details for Web of Science ID 000396493400023

  View details for PubMedID 27641483

  View details for PubMedCentralID PMC5222771

• School Air Cleaner Intervention to Improve Indoor Air Quality for Children with Asthma Jhun, I., Gaffin, J. M., Coull, B. A., Huffaker, M. F., Petty, C., Sheehan, W. J., Baxi, S. N., Gold, D. R., Koutrakis, P., Phipatanakul, W. MOSBY-ELSEVIER. 2016: AB193

  View details for DOI 10.1016/j.jaci.2015.12.762

  View details for Web of Science ID 000375005403075

• School Environmental Intervention to Improve Indoor Air Quality for Children with Asthma Jhun , I., Gaffin , J., Coull , B., Huffaker , M., Petty , C., Sheehan , W., Baxi , S., Gold , D., Koutrakis , P., Phipatanakul, W. Journal of Allergy and Clinical Immunolog: In Practice. 2016 154-159
• Pediatric Asthma Guidelines-Based Care, Omalizumab, and Other Potential Biologic Agents IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA Huffaker, M., Phipatanakul, W. 2015; 35 (1): 129-+

  Abstract

  Over the past several decades, the evidence supporting rational pediatric asthma management has grown considerably. As more is learned about the various phenotypes of asthma, the complexity of management will continue to grow. This article focuses on the evidence supporting the current guidelines-based pediatric asthma management and explores the future of asthma management with respect to phenotypic heterogeneity and biologics.

  View details for DOI 10.1016/j.iac.2014.09.005

  View details for Web of Science ID 000346686700009

  View details for PubMedID 25459581

  View details for PubMedCentralID PMC4254501

• Introducing an environmental assessment and intervention program in inner-city schools JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Huffaker, M., Phipatanakul, W. 2014; 134 (6): 1232-1237

  Abstract

  Home-based environmental interventions have demonstrated clinical benefit for children with asthma. Although much is known about school-based exposures, few studies have comprehensively examined the role the school environment plays in asthma and how effectively changing the environment might reduce morbidity when adjusting for exposures in the home. This review summarizes the importance and common challenges of school-based environmental assessment and intervention studies linked to health effects. We focus on the key components of study development and the challenges and benefits to implementation.

  View details for DOI 10.1016/j.jaci.2014.09.010

  View details for Web of Science ID 000346075400002

  View details for PubMedID 25441649

  View details for PubMedCentralID PMC4261007

• Utility of the Asthma Predictive Index in predicting childhood asthma and identifying disease-modifying interventions ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY Huffaker, M., Phipatanakul, W. 2014; 112 (3): 188-190

  View details for DOI 10.1016/j.anai.2013.12.001

  View details for Web of Science ID 000332396300002

  View details for PubMedID 24428961

  View details for PubMedCentralID PMC4019987

• Impact Of School Peanut-Free Guidelines On Epinephrine Administration Bartnikas, L. M., Huffaker, M. F., Sheehan, W. J., Kanchongkittiphon, W., Petty, C., Sheetz, A., Leibowitz, R., Young, M. C., Phipatanakul, W. MOSBY-ELSEVIER. 2014: AB207

  View details for DOI 10.1016/j.jaci.2013.12.743

  View details for Web of Science ID 000330241301035

• Assessing and introducing an environmental intervention program in schools Huffaker , M., Phipatanakul , W. Journal of Allergy and Clinical Immunology. 2014 1232-7
• A Patient with Syncope NEW ENGLAND JOURNAL OF MEDICINE Fox, M. C., Lakdawala, N., Miller, A., Loscalzo, J. 2013; 369 (10): 966-972

  View details for DOI 10.1056/NEJMcps1300093

  View details for Web of Science ID 000323906900014

  View details for PubMedID 24004124

• Livedo Reticularis: A Side Effect of Interferon Therapy in a Pediatric Patient with Melanoma PEDIATRIC DERMATOLOGY Fox, M., Tahan, S., Kim, C. C. 2012; 29 (3): 333-335

  Abstract

  Livedo reticularis is a lacy mottling of the skin that can have many etiologies. We report a case of an 8-year-old boy with a diagnosis of melanoma who developed persistent livedo reticularis during treatment with interferon alpha-2B. To our knowledge, this is the first case report of livedo reticularis occurring as a side effect of interferon treatment for pediatric melanoma. Given the increasing incidence of pediatric melanoma, it is important that dermatologists be aware of potential side effects of interferon therapy to optimize care and education for these patients.

  View details for DOI 10.1111/j.1525-1470.2011.01426.x

  View details for Web of Science ID 000304139900022

  View details for PubMedID 21575046

• MicroRNA miR-125a controls hematopoietic stem cell number PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Guo, S., Lu, J., Schlanger, R., Zhang, H., Wang, J. Y., Fox, M. C., Purton, L. E., Fleming, H. H., Cobb, B., Merkenschlager, M., Golub, T. R., Scadden, D. T. 2010; 107 (32): 14229-14234

  Abstract

  MicroRNAs influence hematopoietic differentiation, but little is known about their effects on the stem cell state. Here, we report that the microRNA processing enzyme Dicer is essential for stem cell persistence in vivo and a specific microRNA, miR-125a, controls the size of the stem cell population by regulating hematopoietic stem/progenitor cell (HSPC) apoptosis. Conditional deletion of Dicer revealed an absolute dependence for the multipotent HSPC population in a cell-autonomous manner, with increased HSPC apoptosis in mutant animals. An evolutionarily conserved microRNA cluster containing miR-99b, let-7e, and miR-125a was preferentially expressed in long-term hematopoietic stem cells. MicroRNA miR-125a alone was capable of increasing the number of hematopoietic stem cells in vivo by more than 8-fold. This result was accomplished through a differentiation stage-specific reduction of apoptosis in immature hematopoietic progenitors, possibly through targeting multiple proapoptotic genes. Bak1 was directly down-regulated by miR-125a and expression of a 3'UTR-less Bak1 blocked miR-125a-induced hematopoietic expansion in vivo. These data demonstrate cell-state-specific regulation by microRNA and identify a unique microRNA functioning to regulate the stem cell pool size.

  View details for DOI 10.1073/pnas.0913574107

  View details for Web of Science ID 000280767700047

  View details for PubMedID 20616003

  View details for PubMedCentralID PMC2922532

• Pyrin Modulates the Intracellular Distribution of PSTPIP1. PloS one Waite, A. L., Schaner, P., Richards, N., Balci-Peynircioglu, B., Masters, S. L., Brydges, S. D., Fox, M., Hong, A., Yilmaz, E., Kastner, D. L., Reinherz, E. L., Gumucio, D. L. 2009; 4 (7): e6147

  Abstract

  PSTPIP1 is a cytoskeleton-associated adaptor protein that links PEST-type phosphatases to their substrates. Mutations in PSTPIP1 cause PAPA syndrome (Pyogenic sterile Arthritis, Pyoderma gangrenosum, and Acne), an autoinflammatory disease. PSTPIP1 binds to pyrin and mutations in pyrin result in familial Mediterranean fever (FMF), a related autoinflammatory disorder. Since disease-associated mutations in PSTPIP1 enhance pyrin binding, PAPA syndrome and FMF are thought to share a common pathoetiology. The studies outlined here describe several new aspects of PSTPIP1 and pyrin biology. We document that PSTPIP1, which has homology to membrane-deforming BAR proteins, forms homodimers and generates membrane-associated filaments in native and transfected cells. An extended FCH (Fes-Cip4 homology) domain in PSTPIP1 is necessary and sufficient for its self-aggregation. We further show that the PSTPIP1 filament network is dependent upon an intact tubulin cytoskeleton and that the distribution of this network can be modulated by pyrin, indicating that this is a dynamic structure. Finally, we demonstrate that pyrin can recruit PSTPIP1 into aggregations (specks) of ASC, another pyrin binding protein. ASC specks are associated with inflammasome activity. PSTPIP1 molecules with PAPA-associated mutations are recruited by pyrin to ASC specks with particularly high efficiency, suggesting a unique mechanism underlying the robust inflammatory phenotype of PAPA syndrome.

  View details for DOI 10.1371/journal.pone.0006147

  View details for PubMedID 19584923

  View details for PubMedCentralID PMC2702820

• Pyrin and ASC co-localize to cellular sites that are rich in polymerizing actin. Experimental biology and medicine (Maywood, N.J.) Waite, A. L., Schaner, P., Hu, C., Richards, N., Balci-Peynircioglu, B., Hong, A., Fox, M., Gumucio, D. L. 2009; 234 (1): 40-52

  Abstract

  Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the MEFV locus, which encodes the protein pyrin. While it is known that pyrin is expressed in myeloid cells and several fibroblastic cell types, the exact function of pyrin in these cells and the mechanism underlying the pathological effect of pyrin mutations have yet to be revealed. Here, we document that in migrating human monocytes, pyrin protein is dramatically polarized at the leading edge, where it co-localizes with polymerizing actin. ASC (Apoptosis-associated Speck protein with CARD domain), a known pyrin-interacting protein and a critical component of the inflamma-some, is also located at the leading edge in migrating monocytes. Similarly, both pyrin and ASC concentrate in dynamically polymerizing actin-rich tails generated by Listeria monocytogenes. Pyrin's B-box and coiled-coil region is required for its association with Listeria tails. Pyrin also binds, with low affinity and via the same domains, to actin, VASP, and Arp3. Though disease-causing mutations in pyrin do not appear to alter its localization to the leading edge or to Listeria rocket tails, they could potentially have important functional consequences in the context of processes such as migration and cell synapse formation. The co-localization of pyrin and ASC together at such sites may provide an important link between cytoskeletal signaling and inflammasome function.

  View details for DOI 10.3181/0806-RM-184

  View details for PubMedID 19109554