How accurate is the human olfactory system in detecting peanuts?

KEY POINTS: This is the first study to quantify the accuracy, sensitivity, and specificity of the human olfactory system in detecting peanuts in common food items. With more competing sensory input, the human olfactory sensitivity to peanuts decreases; this is especially evident when peanuts are mixed in sauces. Metrics established in this study can be used to develop standards for determining the clinical utility of allergen detecting devices that are currently under development.

Esophageal IgE, IgG4, and mucosal eosinophilia in individuals with dysphagia.

BACKGROUND: Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, producing failure to thrive in infants and dysphagia with food impaction in older children and adults. Although most people with EoE manifest atopic/allergic disease, the specific allergens to which immunoglobulin E (IgE) is directed, if any, have not yet been characterized. METHODS: Mucosal brush biopsy (MBB) and solid tissue biopsy (STB) specimens were prospectively obtained from 25 individuals with dysphagia and suspicion of EoE. Specific IgE (sIgE) against 112 epitopes from airborne and food proteins, antigens known to cause a polyclonal IgE response and IgG4 to food allergens, were measured. RESULTS: There was no difference in total IgE harvested between the 2 biopsy methods (p > 0.05) or between the EoE-positive (N = 12) and EoE-negative (N = 13) groups (p > 0.05). None of the samples in either group contained measurable serum IgE to any of the airborne or food proteins tested, but low levels of IgE specific to Candida and Staphylococcus enterotoxins were detected. Low levels of IgG4 specific to wheat, soy, peanut, and egg were also detected. CONCLUSIONS: Both MBB and STB are able to harvest measureable levels of IgE and IgG4 from the esophageal mucosa. Low levels of serum-specific IgE suggest that other inflammatory mechanisms, besides type I, IgE-mediated, allergen-specific hypersensitivity, may act as the primary catalyst for mucosal eosinophilia. Clarifying the role of both IgE-mediated and non-IgE-mediated inflammatory mechanisms will help identify more targeted diagnostic and treatment strategies for individuals who present with dysphagia and esophageal eosinophilia.

Sensitivity, specificity, and predictive value of oral mucosal brush biopsy for the diagnosis of peanut allergy.

BACKGROUND: Current diagnostic testing methods for peanut allergy, including serum specific immunoglobulin E (sIgE) and skin-prick testing (SPT), have low specificity, whereas oral food challenge (OFC) carries significant risk of provoking adverse events. Mucosal brush biopsy (MBB) from the oral cavity is currently being studied as a new diagnostic test for peanut allergy, but normative data is not yet available with which to begin measuring specificity and predictive value. METHODS: Twenty individuals with no history of adverse reactions from eating peanuts underwent oral MBB and serum testing for peanut sIgE. These data were then compared with previously published data from 10 individuals with a history of clinical peanut allergy, in order to generate receiver operating characteristic (ROC) curves and calculate the sensitivity, specificity, and positive and negative predictive values for both testing modalities. RESULTS: The optimal cutoff levels for oral MBB and sIgE testing were 0.12 kU/L and 1.0 kU/L, respectively. At 0.12 kU/L, the sensitivity of oral MBB testing was 80% and the specificity was 85%, whereas at 1.0 kU/L, the sensitivity of sIgE testing was 50% and the specificity was 100%. From the ROC curves, the areas under the ROC curve (AUC) for oral MBB and sIgE were 0.91 (p < 0.001) and 0.74 (p = 0.007), respectively. Combination testing further increased both sensitivity and accuracy over oral MBB alone. CONCLUSION: In this pilot study, oral MBB demonstrated high sensitivity and specificity for screening individuals with and without oral cavity clinical reactivity to peanuts and may represent a potentially useful testing method for the diagnosis of peanut allergy in the future.

Airborne and food sensitization patterns in children and adults with eosinophilic esophagitis.

BACKGROUND: The pathogenesis of eosinophilic esophagitis (EoE) is currently unknown, but evidence suggests that allergic sensitization to food and airborne allergens may play a key role. This retrospective study examines the rate of sensitization to both food and airborne allergens in EoE patients, and compares their sensitivity patterns to control groups. METHODS: We identified 103 patients with a diagnosis of EoE via esophageal eosinophilia (≥15 eosinophils/high-power field [hpf]), who had undergone comprehensive food and/or airborne allergen testing through either skin or in vitro methods. Food and airborne allergen sensitization was defined as positive testing in at least 1 food subgroup (milk, peanut, tree nut, seafood/fish, soy, grain, egg) or airborne subgroup (tree, grass, weed, mite/cockroach, animal, mold), respectively. The same sensitization criterion was applied to allergic rhinitis (AR) patients, with and without a clinical suspicion of food allergy (FA), in order to create control groups. RESULTS: Sensitization in the EoE group to at least 1 subgroup of food allergen and airborne allergen was seen in 77.1% (64/83) and 71.7% (38/53), respectively (p = 0.82). There were significant differences in sensitization between EoE and control groups for tree nut, soy, grain, and egg, but no differences noted in any of the other food or airborne allergen subgroups, even after accounting for age and gender. CONCLUSION: EoE and control groups had similar airborne allergen sensitization patterns, yet dissimilar food allergen sensitization patterns, suggesting that specific allergens may play a more prominent role in the pathogenesis of EoE. The EoE group had a more uniform distribution pattern for food allergens, compared to controls.

Quality-of-life outcomes in patients who underwent subcutaneous immunotherapy and sublingual immunotherapy in a real-world clinical setting.

OBJECTIVE: To compare changes in quality of life (QOL) that resulted from sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) in a real-world clinical setting. BACKGROUND: SLIT is established as a viable alternative to SCIT for the treatment of allergic rhinitis. Although comparative trials are increasingly available, few studies have examined QOL outcomes between these two treatments. METHODS: One hundred and five participants who underwent immunotherapy for airborne allergies were enrolled in this prospective, single-center study. Forty participants completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at initiation of therapy, after 6 months, and after 1 year of therapy. Only patients with complete time points were included in the ultimate analysis. Twenty-nine of these participants underwent SCIT and 11 underwent SLIT. The effects of age, sex, and asthma history were also examined. RESULTS: The participants in both groups demonstrated improvements in QOL regarding allergic rhinoconjunctivitis over the study period. However, the change in the RQLQ score from both baseline to 6 months and baseline to 1 year was only statistically significant in the SCIT group (p = 0.002, 6 months and 1 year). The participants in the SCIT group also demonstrated statistically significant improvement from baseline to 1 year in the specific domains of practical and emotional functioning, nasal symptoms, non-nasal/eye symptoms, and sleep. After 1 year, both SCIT and SLIT demonstrated a minimally important difference from baseline in the overall RQLQ score. Age <35 years in the SCIT group had a significant positive impact on QOL improvement (p = 0.038). CONCLUSION: Although improvements in QOL were noted in both groups, changes in overall scores and the majority of domains only achieved statistical significance in the SCIT group. A small study population and difficulties adhering to immunotherapy dosing schedules in the SLIT group may be contributing factors.

Immunotherapy for food allergy.

PURPOSE OF REVIEW: The current review discusses strategies for administering specific immunotherapy (SIT) for the treatment of food allergy. It focuses on three delivery routes for food allergens, immunomodulatory adjuvants and allergen modifications. RECENT FINDINGS: Interest in SIT for food allergy has been increasing significantly. Sublingual immunotherapy is effective for desensitization with a very favorable adverse event profile. Epicutaneous immunotherapy is also effective, most notably in younger children, with a high rate of local reactions. Oral immunotherapy demonstrates high efficacy, but with a higher risk of gastrointestinal and systemic adverse events. The need for long-term application to sustain desensitization is currently unclear. Immunomodulatory adjuvants may be added to enhance or diminish the immunogenicity of proteins, whereas genetic modifications of food allergens are designed to limit the risk of adverse reactions and address the issues of standardization and supply. SUMMARY: SIT for food allergy is reaching the point where it may soon be used routinely in clinical practice. Current research focuses on new delivery routes and methods to enhance the effectiveness of the therapy while minimizing the risk of adverse reactions. Future efforts are underway to determine the optimal dose for each delivery method and the length of maintenance dosing required to retain the protective effect.

Multi-tiered Reorganization of the Genome during B Cell Affinity Maturation Anchored by a Germinal Center-Specific Locus Control Region.

During the humoral immune response, B cells undergo a dramatic change in phenotype to enable antibody affinity maturation in germinal centers (GCs). Using genome-wide chromosomal conformation capture (Hi-C), we found that GC B cells undergo massive reorganization of the genomic architecture that encodes the GC B cell transcriptome. Coordinate expression of genes that specify the GC B cell phenotype-most prominently BCL6-was achieved through a multilayered chromatin reorganization process involving (1) increased promoter connectivity, (2) formation of enhancer networks, (3) 5' to 3' gene looping, and (4) merging of gene neighborhoods that share active epigenetic marks. BCL6 was an anchor point for the formation of GC-specific gene and enhancer loops on chromosome 3. Deletion of a GC-specific, highly interactive locus control region upstream of Bcl6 abrogated GC formation in mice. Thus, large-scale and multi-tiered genomic three-dimensional reorganization is required for coordinate expression of phenotype-driving gene sets that determine the unique characteristics of GC B cells.

Oral mucosal immunotherapy for allergic rhinitis: A pilot study.

BACKGROUND: The sublingual mucosa has been used for many years to apply allergenic extracts for the purpose of specific immunotherapy (IT). Although sublingual IT (SLIT) is both safe and efficacious, the density of antigen-presenting cells is higher in other regions of the oral cavity and vestibule, which make them a potentially desirable target for IT. OBJECTIVE: To present the concept of oral mucosal IT (OMIT) and to provide pilot data for this extended application of SLIT. METHODS: An open-label, 12-month, prospective study was undertaken as a preliminary step before a full-scale clinical investigation. Twenty-four individuals with allergic rhinitis received IT by applying allergenic extracts daily to either the oral vestibule plus oral cavity mucosa by using a glycerin-based toothpaste or to the sublingual mucosa by using 50% glycerin liquid drops. Adverse events, adherence rates, total combined scores, rhinoconjunctivitis quality-of-life questionnaire scores, changes in skin reactivity, and changes in serum antibody levels were measured for each participant. RESULTS: No severe adverse events occurred in either group. The adherence rate was 80% for the OMIT group and 62% for the SLIT group (p = 0.61). Decreased total combined scores were demonstrated for both the OMIT group (15.6%) and the SLIT group (22.3%), although this decrease did not reach statistical significance in either group. Both groups achieved a meaningful clinical improvement of at least 0.5 points on rhinoconjunctivitis quality-of-life questionnaire. A statistically significant rise in specific immunoglobulin G4 (IgG4) was seen in both groups over the first 6 months of treatment. CONCLUSION: OMIT and SLIT demonstrated similar safety profiles and adherence rates. Measurements of clinical efficacy improved for both groups, but only changes in IgG4 achieved statistical significance. These pilot data provide enough evidence to proceed with a full-scale investigation to explore the role of OMIT in the long-term management of allergic rhinitis.

New advances in allergy immunotherapy.

PURPOSE OF REVIEW: The present article reviews the literature on new methods for administering specific immunotherapy for the treatment of immunoglobulin E-mediated hypersensitivity to airborne and food allergens. The discussion will focus on allergen modifications, and new routes for delivering proteins to allergen-presenting cells. RECENT FINDINGS: Modified allergens address the issues of supply and standardization, but also have the potential to enhance the allergenicity of the protein, while decreasing the risk of producing severe reactions. The use of immunostimulatory adjuvants and recombinant proteins has increased, whereas new technologies, such as the encapsulation of allergens into nanoparticles, have also gained much attention. New delivery routes for specific immunotherapy continue to be explored, often in combination with allergen modification strategies, in order to shorten the duration of therapy, limit adverse events, and optimize patient adherence. Safety and long-term efficacy have been demonstrated for many of these new methods, and it is clear that there are multiple ways to stimulate the immune system for the purpose of allergen desensitization. SUMMARY: Developments in the field of specific immunotherapy for allergic disease are accelerating rapidly because of advances in technology, but also because of the recognition that this disease-modifying therapy is a well tolerated, efficacious, and cost-effective option for individuals, which can improved their quality of life in a long-term fashion. VIDEO ABSTRACT.

Patient preferences for route of allergy immunotherapy: a comparison of four delivery methods.

BACKGROUND: Allergen-specific immunotherapy (IT) is a disease-modifying treatment for allergic rhinitis, and adherence to the treatment schedule is important for a successful outcome. Several methods for delivering IT are now available, but little information is known concerning patient preference for these options. METHODS: Over a 12-month period, 228 adults scheduled to undergo outpatient allergy testing were offered a survey to rank 4 different IT delivery methods: subcutaneous IT (SCIT), sublingual IT using liquid extracts (SLIT), sublingual allergy immunotherapy tablets (AIT), and oral mucosal immunotherapy (OMIT) using a toothpaste delivery vehicle. RESULTS: Of the participants who completed the survey, ranking scores (mean ± SD) for SCIT, SLIT, AIT, and OMIT, with 1 being the highest rank, were 3.36 ± 1.02, 2.03 ± 0.92, 2.30 ± 1.02, and 2.32 ± 1.05, respectively. The number of participants who ranked SCIT, SLIT, AIT, or OMIT as their number 1 choice was 24 (10.5%), 79 (34.6%), 61 (26.8%), and 64 (28.1%), respectively. When comparing first choice rankings, there were no statistically significant differences between SLIT, AIT, or OMIT, yet all 3 groups ranked higher than SCIT (p < 0.0001). CONCLUSION: SCIT earned the lowest mean rank and had the least number of participants rank it as the most preferred method. Among the other 3 choices, by mean scores, SLIT was preferred most compared to either AIT or OMIT; but when considering first choices only, there were no significant differences in preference. Most of the study participants identified the convenience of home IT administration as the most important factor in their ranking.

Total and allergen-specific immunoglobulin E in the serum and nasal mucosa of a nonallergic population.

BACKGROUND: There has been a growing interest in measuring allergen-specific immunoglobulin E (sIgE) directly from the nasal mucosal epithelium of individuals with sinonasal disease. However, there is currently no normative data with which to estimate sensitivity, specificity, and the appropriate positive cutoff level for new testing methods. METHODS: Twenty individuals with no history of sinonasal disease or food allergies underwent serum IgE testing and nasal mucosal brush biopsy (MBB) testing for total and sIgE to 7 common airborne allergens and 1 food allergen. The correlation between sIgE in serum and nasal samples was determined at both the 0.10-kU/L and 0.35-kU/L positive cutoff levels. RESULTS: sIgE at the 0.35-kU/L cutoff level was detected for at least 1 allergen in 7 of 20 (35%) participants in both the serum and nose. At the 0.10-kU/L cutoff level, 8 of 20 (40%) and 19 of 20 (95%) participants had sIgE to at least 1 allergen in the serum and nose, respectively. At the 0.35-kU/L cutoff level, total serum IgE levels were significantly higher when at least 1 allergen was detected in the nose (p = 0.01). There was a strong association between sIgE in the serum and nasal mucosa (p < 0.0001) at both cutoff levels. CONCLUSION: The significant association between serum and nasal samples for both total and sIgE suggests that nasal IgE and serum IgE are not independent of one another. Understanding levels of IgE in the nonallergic population will help answer the questions surrounding sensitization as new diagnostic tests for locally-present IgE become available.

New routes of allergen immunotherapy.

OBJECTIVES: Allergen immunotherapy is the only cure for immunoglobulin E mediated type I respiratory allergies. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are the most common treatments. In this article, we reviewed new routes of allergen immunotherapy. METHODS: Data on alternative routes to allow intralymphatic immunotherapy (ILIT), epicutaneous immunotherapy (EPIT), local nasal immunotherapy (LNIT), oral immunotherapy (OIT), and oral mucosal immunotherapy (OMIT) were gathered from the literature and were discussed. RESULTS: ILIT features direct injection of allergens into lymph nodes. ILIT may be clinically effective after only a few injections and induces allergen-specific immunoglobulin G, similarly to SCIT. A limitation of ILIT is that intralymphatic injections are required. EPIT features allergen administration by using patches mounted on the skin. EPIT seeks to target epidermal antigen-presenting Langerhans cells rather than mast cells or the vasculature; this should reduce both local and systemic adverse effects. LNIT involves the spraying of allergen extracts into the nasal cavity. Natural or chemically modified allergens (the latter, termed allergoids, lack immunoglobulin E reactivity) are prepared in a soluble form. OIT involves the regular administration of small amounts of a food allergen by mouth and commences with low oral doses, which are then increased as tolerance develops. OMIT seeks to deliver allergenic proteins to an expanded population of Langerhans cells in the mucosa of the oral cavity. CONCLUSIONS: ILIT, EPIT, LNIT, OIT, and OMIT are new routes for allergen immunotherapy. They are safe and effective.

Intradermal testing after negative skin prick testing for patients with high suspicion of allergy.

BACKGROUND: Skin testing is a widely accepted method for identifying inhalant allergies. Intradermal (ID) testing is often performed after negative skin prick testing (SPT) when a practitioner has a high level of clinical suspicion for a particular allergen. METHODS: A retrospective chart review study was performed over a 5-year period in patients with negative SPT for airborne allergens who also underwent ID testing based on a high level of suspicion for clinical allergy. RESULTS: Eighty-seven patients had negative SPT and went on to receive an average of 7 ID tests per patient. A total of 592 ID tests were performed after negative SPT. Of these, 20.8% (123/592) had a positive ID result with negative SPT. The allergens with the greatest percentage of positive ID results with negative SPTs were dog, cat, D. farinae, and D. pteronyssinus (33.3%, 34.3%, 39.4%, and 39.6%, respectively). The allergens least likely to test positive on ID testing after negative SPT were red maple, Cladosporium, and Alternaria (0%, 6.3%, and 6.5%, respectively). CONCLUSION: Approximately 20% of all negative results on SPT will have a positive ID test, more likely for indoor allergens. If a high suspicion for allergy exists in a patient with a negative SPT result, it may be useful to proceed with ID testing. However, the clinical significance of a positive ID test after negative SPT still needs to be elucidated.

Oral mucosal immunotherapy using a toothpaste delivery system for the treatment of allergic rhinitis.

Oral Mucosal Immunotherapy is a novel method of delivering allergenic extracts to the tolerogenic oropharyngeal mucosa using a compounded toothpaste vehicle. This article describes three cases where individuals with seasonal allergic rhinitis demonstrated symptom improvement as well as decreased skin reactivity after using Oral Mucosal Immunotherapy in a pre-seasonal and co-seasonal fashion.

Supernumerary nasal tooth in close proximity to a dental implant.

Supernumerary nasal teeth (SNT) are a rare phenomenon. Supernumerary teeth occur in 0.1 to 1% of the population. They are most commonly found in the upper incisor area, when they are known as mesiodentes. They also are fairly common elsewhere on the intraoral palate and in the maxillary sinus. Nasal teeth are quite rare, with only case reports and small case series found in the literature. SNT can present with different symptoms, including unilateral nasal obstruction, nasal drainage, and infections, or they can be asymptomatic and found incidentally. This report describes a case of a nasal tooth in close proximity to a noninfected dental implant that became symptomatic with unilateral nasal obstruction. The diagnosis was based on endoscopic and radiologic findings, and the patient's symptoms resolved after endoscopic surgical removal of the tooth through the nasal cavity.

Asthma and the otolaryngologist.

BACKGROUND: Asthma is a chronic inflammatory disease of the lower airway that is commonly encountered by the otolaryngologist. This article provides information on how to recognize patients with asthma and discuss issues related to diagnosis, treatment, and continued management within the context of current guidelines. METHODS: A literature review was conducted and relevant sources are referenced concerning the epidemiology of asthma, the pathophysiology of asthma, diagnostic strategies, treatment options, and continued management. RESULTS: Asthma is a common condition worldwide and is often associated with other atopic diseases such as allergic rhinitis and eczema, though other genetic and environmental factors appear to be important as well. The lower airway and upper airways share similar histology, as well as patterns of inflammation in response to environmental triggers. The diagnosis of asthma involves a careful history and a complete physical exam, including auscultation of the lungs and pulmonary function testing. Pharmacotherapy represents the primary method of treating asthma, though current evidence supports a positive role for antigen-specific immunotherapy for both prevention and treatment. Guidelines are available that can assist the otolaryngologist in classifying the severity of asthma, determining the level of control and recommending modifications in the treatment plan. CONCLUSION: As airway specialists, otolaryngologists are in a unique position to recognize and manage asthma in their patients, particularly those with allergic disease. Maintaining a high index of suspicion and understanding the key elements of diagnosis and treatment are extremely important in order to achieve this goal.

Serum immunoglobulin e and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial.

Epidemiologic studies have consistently found that self-reported allergies are associated with reduced risk of pancreatic cancer. Our aim was to prospectively assess the relationship between serum immunoglobulin E (IgE), a marker of allergy, and risk. This nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) included subjects enrolled in 1994 to 2001 and followed through 2010. There were 283 cases of pancreatic cancer and 544 controls matched on age, gender, race, and calendar date of blood draw. Using the ImmunoCAP system, we measured total IgE (normal, borderline, elevated), IgE to respiratory allergens, and IgE to food allergens (negative or positive) in serum collected at baseline. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. We assessed interactions with age, gender, smoking, body mass index, and time between randomization and case diagnosis. Overall, there was no association between the IgE measures and risk. We found a statistically significant interaction by baseline age: in those aged ≥65 years, elevated risks were observed for borderline total IgE (OR, 1.43; 95% CI, 0.88-2.32) and elevated total IgE (OR, 1.98; 95% CI, 1.16-3.37) and positive IgE to food allergens (OR, 2.83; 95% CI, 1.29-6.20); among participants <65 years, ORs were <1. Other interactions were not statistically significant. The reduced risk of pancreatic cancer associated with self-reported allergies is not reflected in serum IgE.

Prevalence of antigen-specific immunoglobulin E on mucosal brush biopsy of the inferior turbinates in patients with nonallergic rhinitis.

BACKGROUND: This study investigates the prevalence of local, antigen-specific immunoglobulin E (IgE) from mucosal brush biopsy (MBB) of the inferior turbinates in people diagnosed with chronic, idiopathic, nonallergic rhinitis (NAR) based on negative skin and/or in vitro testing. METHODS: A standard cytology brush was used to harvest epithelial cells from the inferior turbinates of 20 adults. These cells were then processed and tested for the presence of total and antigen-specific IgE to 9 common aeroallergens using immunofluorescence. The relationships between detectable IgE and quality of life (QOL), self-reported seasonal symptoms and season of specimen collection were determined. RESULTS: Antigen-specific IgE for at least 1 antigen was detected on MBB in all of 20 (100%) study participants with a mean of approximately 3 sensitizations per participant. IgE to cockroach was present in 18 of 20 (90%) participants. There was no significant association noted between QOL scores or self-reported seasonal symptoms and the presence of specific IgE to any of the study antigens, although the presence of white oak and ragweed IgE was significantly higher in patients tested during the pollen season. CONCLUSION: This study demonstrated that, using MBB of the inferior turbinates, antigen-specific IgE to at least 1 airborne allergen is detectable in 100% of the idiopathic, NAR study population. This rate of sensitization is notably higher than previous reports, suggesting that the prevalence of atopic disease in the general population may be higher than current estimates. Testing for local sensitization should be considered as part of the complete evaluation for atopic disease.