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The Journal of Allergy and Clinical... Oct 2023Epinephrine intramuscular (IM) autoinjector is a life-saving drug for the emergency treatment of immediate-type allergic reactions (type I). Nevertheless, it is... (Clinical Trial)
Clinical Trial
BACKGROUND
Epinephrine intramuscular (IM) autoinjector is a life-saving drug for the emergency treatment of immediate-type allergic reactions (type I). Nevertheless, it is sometimes applied incorrectly or underused because of short shelf life, high costs, fear of use, or inconvenience of carrying. FMXIN002, a nasal powder spray of epinephrine, was developed as a needle-free alternative.
OBJECTIVE
To compare epinephrine pharmacokinetics, pharmacodynamics, and safety after the administration of the FMXIN002 nasal spray versus autoinjector.
METHODS
An open-label trial was performed in 12 adults with seasonal allergic rhinitis without asthma. Epinephrine pharmacokinetics, pharmacodynamics, and safety were compared between FMXIN002 (1.6 mg and 3.2 mg) administered intranasally with/without a nasal allergen challenge and IM (0.3 mg) EpiPen.
RESULTS
FMXIN002 3.2 mg, administered after a nasal allergen challenge, displayed a shorter Tmax than EpiPen (median: 2.5 minutes vs 9.0 minutes, statistically nonsignificant [NS]) and a significantly shorter time when the measured analyte concentration is 100 pg/mL during the absorption phase pg/mL (median: 1.0 minutes vs 3.0 minutes for FMXIN002, P < .02). Moreover, FMXIN002 3.2 mg administered after the challenge test has resulted in a doubling of the maximal measured plasma analyte concentration over the sampling period (1110 vs 551 pg/mL, NS); area under the curve from 0 to 8 hours was 56% higher (672 vs 431 hours pg/mL, compared with EpiPen, NS). Pharmacodynamic response was comparable at all treatments. FMXIN002 was well tolerated, and treatment-emergent adverse events (AEs) were mild, local, and resolved spontaneously. No AEs were reported after the administration of EpiPen in our study. FMXIN002 was stable for 2 years at room temperature conditions. However, variability in the pharmacokinetics (expressed in coefficient of variation) is high. Having a prior nasal allergen challenge results in a substantial increase and speed of absorption.
CONCLUSIONS
Intranasal absorption of dry powder epinephrine is faster than EpiPen offering a clinical advantage in the short therapeutic window for the treatment of anaphylaxis. The FMXIN002 product offers a needle-free, pocket-size, safe, user-friendly, and stable alternative to epinephrine autoinjectors.
Topics: Adult; Humans; Administration, Intranasal; Allergens; Anaphylaxis; Epinephrine; Powders
PubMed: 37394178
DOI: 10.1016/j.jaip.2023.06.044 -
The Journal of Allergy and Clinical... Aug 2023Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype.
OBJECTIVE
This study aimed to identify historical and clinical features and biomarkers associated with AD severity.
METHODS
A US registry of extensively phenotyped AD participants (aged 0.73-80 years) were enrolled at 9 academic centers. Information on family and personal medical history, examination, skin swabs (culture), and serum biomarkers was collected to evaluate their association with AD severity.
RESULTS
Participants with AD (N = 2862) whose disease was categorized as mild (11.6%), moderate (58.0%), or severe (30.4%) based on Rajka-Langeland scoring were enrolled. The trend test, when adjusting for gender, race, and age, demonstrated that severity was strongly (P ≤ .04) associated with a personal/family history of allergic disorders, history of alopecia, exposure to passive smoke, ocular herpes infection, skin bacterial and viral infections, and history of arrhythmia. Features observed more frequently (P ≤ .002), as a function of severity, included skin infections (impetigo, human papillomavirus, and molluscum contagiosum virus), Staphylococcus aureus colonization, excoriations, hyperlinear palms, ichthyosis, blepharitis, conjunctivitis, ectropion, and wheezing. Serum IgE, allergen and food (≤6 years) Phadiatop, and eosinophilia were strongly linked to severity (P < .001).
CONCLUSIONS
In a diverse US AD population, severity was associated with a history of atopic disorders, skin and extracutaneous bacterial and viral infections (by history and physical examination), higher IgE, eosinophilia and allergen sensitization, atopic skin manifestations (ie, excoriation, hyperlinear palms, and ichthyosis), and atopic ocular features (ie, blepharitis, conjunctivitis, and ectropion) as well as asthma findings (ie, wheezing). Data from our prospective registry significantly advance our understanding of AD phenotypes and endotypes, which is critical to achieve optimal management.
Topics: Humans; Dermatitis, Atopic; Ectropion; Respiratory Sounds; Phenotype; Biomarkers; Allergens; Conjunctivitis; Immunoglobulin E; Blepharitis; Severity of Illness Index
PubMed: 37182563
DOI: 10.1016/j.jaip.2023.04.052 -
The Science of the Total Environment Dec 2023Aeroallergens or inhalant allergens, are proteins dispersed through the air and have the potential to induce allergic conditions such as rhinitis, conjunctivitis, and... (Review)
Review
Aeroallergens or inhalant allergens, are proteins dispersed through the air and have the potential to induce allergic conditions such as rhinitis, conjunctivitis, and asthma. Outdoor aeroallergens are found predominantly in pollen grains and fungal spores, which are allergen carriers. Aeroallergens from pollen and fungi have seasonal emission patterns that correlate with plant pollination and fungal sporulation and are strongly associated with atmospheric weather conditions. They are released when allergen carriers come in contact with the respiratory system, e.g. the nasal mucosa. In addition, due to the rupture of allergen carriers, airborne allergen molecules may be released directly into the air in the form of micronic and submicronic particles (cytoplasmic debris, cell wall fragments, droplets etc.) or adhered onto other airborne particulate matter. Therefore, aeroallergen detection strategies must consider, in addition to the allergen carriers, the allergen molecules themselves. This review article aims to present the current knowledge on inhalant allergens in the outdoor environment, their structure, localization, and factors affecting their production, transformation, release or degradation. In addition, methods for collecting and quantifying aeroallergens are listed and thoroughly discussed. Finally, the knowledge gaps, challenges and implications associated with aeroallergen analysis are described.
Topics: Allergens; Pollen; Asthma; Particulate Matter; Europe; Air Pollutants
PubMed: 37709071
DOI: 10.1016/j.scitotenv.2023.167042 -
Current Allergy and Asthma Reports Oct 2023The globally rising food allergy prevalence is associated with the urgent need for new disease prevention methods, efficient treatment, and reliable risk assessment... (Review)
Review
PURPOSE OF REVIEW
The globally rising food allergy prevalence is associated with the urgent need for new disease prevention methods, efficient treatment, and reliable risk assessment methods for characterization of food allergens. Due to inter-individual variations in the digestive system, food allergens are degraded to a different extent in each person. Food processing also influences allergen digestion.
RECENT FINDINGS
In this review, we provide an overview of the digestive system with focus on relevance for food allergy. Main food proteins causing allergic reactions are evaluated, and the combined role of food processing and digestion for allergen stability is highlighted. Finally, clinical implications of this knowledge are discussed. Recent literature shows that allergen digestibility is dependent on food processing, digestive conditions, and food matrix. Digestion affects proteins allergenicity. It is currently not possible to predict the immunogenicity of allergens solely based on protein stability.
Topics: Humans; Allergens; Food Hypersensitivity; Food; Food Handling; Risk Assessment
PubMed: 37665560
DOI: 10.1007/s11882-023-01107-9 -
International Journal of Molecular... Aug 2023Proteomics in respiratory allergic diseases has such a battery of techniques and programs that one would almost think there is nothing impossible to find, invent or... (Review)
Review
Proteomics in respiratory allergic diseases has such a battery of techniques and programs that one would almost think there is nothing impossible to find, invent or mold. All the resources that we document here are involved in solving problems in allergic diseases, both diagnostic and prognostic treatment, and immunotherapy development. The main perspectives, according to this version, are in three strands and/or a lockout immunological system: (1) Blocking the diapedesis of the cells involved, (2) Modifications and blocking of paratopes and epitopes being understood by modifications to antibodies, antagonisms, or blocking them, and (3) Blocking FcεRI high-affinity receptors to prevent specific IgEs from sticking to mast cells and basophils. These tools and targets in the allergic landscape are, in our view, the prospects in the field. However, there are still many allergens to identify, including some homologies between allergens and cross-reactions, through the identification of structures and epitopes. The current vision of using proteomics for this purpose remains a constant; this is also true for the basis of diagnostic and controlled systems for immunotherapy. Ours is an open proposal to use this vision for treatment.
Topics: Humans; Proteomics; Hypersensitivity; Respiration Disorders; Respiratory Tract Diseases; Epitopes; Allergens
PubMed: 37629105
DOI: 10.3390/ijms241612924 -
The Journal of Experimental Medicine Nov 2023CD4+ lung-resident memory T cells (TRM) generated in response to influenza infection confer effective protection against subsequent viral exposures. Whether these cells...
CD4+ lung-resident memory T cells (TRM) generated in response to influenza infection confer effective protection against subsequent viral exposures. Whether these cells can be altered by environmental antigens and cytokines released during heterologous, antigen-independent immune responses is currently unclear. We therefore investigated how influenza-specific CD4+ Th1 TRM in the lung are impacted by a subsequent Th2-inducing respiratory house dust mite (HDM) exposure. Although naïve influenza-specific CD4+ T cells in the lymph nodes do not respond to HDM, influenza-specific CD4+ TRM in the lungs do respond to a subsequent allergen exposure by decreasing expression of the transcription factor T-bet. This functional alteration is associated with decreased IFN-γ production upon restimulation and improved disease outcomes following heterosubtypic influenza challenge. Further investigation revealed that ST2 signaling in CD4+ T cells during allergic challenge is necessary to induce these changes in lung-resident influenza-specific CD4+ TRM. Thus, heterologous antigen exposure or ST2-signaling can drive persistent changes in CD4+ Th1 TRM populations and impact protection upon reinfection.
Topics: Animals; Humans; Influenza, Human; Interleukin-1 Receptor-Like 1 Protein; CD4-Positive T-Lymphocytes; Th1 Cells; Pyroglyphidae; Allergens
PubMed: 37698553
DOI: 10.1084/jem.20230112 -
Frontiers in Allergy 2023Allergic reactions are mediated by human IgE antibodies that bind to and cross-link allergen molecules. The sites on allergens that are recognized by IgE antibodies have...
INTRODUCTION
Allergic reactions are mediated by human IgE antibodies that bind to and cross-link allergen molecules. The sites on allergens that are recognized by IgE antibodies have been difficult to investigate because of the paucity of IgE antibodies in a human serum. Here, we report the production of unique human IgE monoclonal antibodies to major inhaled allergens and food allergens that can be produced at scale in perpetuity.
MATERIALS AND METHODS
The IgE antibodies were derived from peripheral blood mononuclear cells of symptomatic allergic patients, mostly children aged 3-18 years, using hybridoma fusion technology. Total IgE and allergen-specific IgE was measured by ImmunoCAP. Their specificity was confirmed through ELISA and immunoblotting. Allergenic potency measurements were determined by ImmunoCAP inhibition. Biological activity was determined by comparing -hexosaminidase release from a humanized rat basophilic cell line.
RESULTS
Human IgE monoclonal antibodies ( = 33) were derived from 17 allergic patients with symptoms of allergic rhinitis, asthma, atopic dermatitis, food allergy, eosinophilic esophagitis, or red meat allergy. The antibodies were specific for five inhaled allergens, nine food allergens, and alpha-gal and had high levels of IgE (53,450-1,702,500 kU/L) with ratios of specific IgE to total IgE ranging from <0.01 to 1.39. Sigmoidal allergen binding curves were obtained through ELISA, with low limits of detection (<1 kU/L). Allergen specificity was confirmed through immunoblotting. Pairs of IgE monoclonal antibodies to Ara h 6 were identified that cross-linked after allergen stimulation and induced release of significant levels of -hexosaminidase (35%-80%) from a humanized rat basophilic cell line.
CONCLUSIONS
Human IgE monoclonal antibodies are unique antibody molecules with potential applications in allergy diagnosis, allergen standardization, and identification of allergenic epitopes for the development of allergy therapeutics. The IgE antibody probes will enable the unequivocal localization and validation of allergenic epitopes.
PubMed: 37901762
DOI: 10.3389/falgy.2023.1270326 -
Allergy and Asthma Proceedings Jul 2023Allergen specific immunotherapy (SIT) has been used for more than a century. Researchers have been working to improve efficacy and reduce the side effects. We have...
Allergen specific immunotherapy (SIT) has been used for more than a century. Researchers have been working to improve efficacy and reduce the side effects. We have reviewed the literature about peptides immunotherapy for inhaled allergens. The mechanism of SIT is to induce regulatory T (Treg) cells and to reduce T helper (Th)2 cells to induce class switching from IgE to IgG and induce blocking antibodies to inhibit allergen binding of IgE. The relevant published literatures on the peptide SIT for aeroallergens have been searched on the medline. Modification of allergens and routes of treatment has been performed. Among them, many researchers were interested in peptide immunotherapy. T-cell epitope peptide has no IgE epitope, that is able to bind IgE, but rather induces Treg and reduces Th2 cells, which was considered an ideal therapy. Results from cellular and animal model studies have been successful. However, in clinical studies, T-cell peptide immunotherapy has failed to show efficacy and caused side effects, because of the high effective rate of placebo and the development of IgE against T-cell epitope peptides. Currently, the modifications of IgE-allergen binding by blocking antibodies are considered for successful allergen immunotherapy. Newly developed hypoallergenic B cell epitope peptides and computational identification methods hold great potential to develop new peptide immunotherapies.
Topics: Animals; Humans; Epitopes, T-Lymphocyte; Antibodies, Blocking; Immunoglobulin E; Allergens; Desensitization, Immunologic; Immunotherapy; Peptides
PubMed: 37480199
DOI: 10.2500/aap.2023.44.230028 -
American Journal of Physiology. Lung... Dec 2023Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. DNA methylation is one form of epigenetic modification that regulates gene...
Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. DNA methylation is one form of epigenetic modification that regulates gene expression and is both inherited and modified by environmental exposures throughout life. Prenatal development is a particularly vulnerable time period during which exposure to maternal asthma increases asthma risk in offspring. How maternal asthma affects DNA methylation in offspring and what the consequences of differential methylation are in subsequent generations are not fully known. In this study, we tested the effects of grandmaternal house dust mite (HDM) allergen sensitization during pregnancy on airway physiology and inflammation in HDM-sensitized and challenged second-generation mice. We also tested the effects of grandmaternal HDM sensitization on tissue-specific DNA methylation in allergen-naïve and -sensitized second-generation mice. Descendants of both allergen- and vehicle-exposed grandmaternal founders exhibited airway hyperreactivity after HDM sensitization. However, grandmaternal allergen sensitization significantly potentiated airway hyperreactivity and altered the epigenomic trajectory in second-generation offspring after HDM sensitization compared with HDM-sensitized offspring from vehicle-exposed founders. As a result, biological processes and signaling pathways associated with epigenetic modifications were distinct between lineages. A targeted analysis of pathway-associated gene expression found that Smad3 was significantly dysregulated as a result of grandmaternal allergen sensitization. These data show that grandmaternal allergen exposure during pregnancy establishes a unique epigenetic trajectory that reprograms allergen responses in second-generation offspring and may contribute to asthma risk. Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. This study shows that maternal allergen exposure during pregnancy promotes unique epigenetic trajectories in second-generation offspring at baseline and in response to allergen sensitization, which is associated with the potentiation of airway hyperreactivity. These effects are one mechanism by which maternal asthma may influence the inheritance of asthma risk.
Topics: Pregnancy; Humans; Female; Mice; Animals; Allergens; Epigenomics; Prenatal Exposure Delayed Effects; Asthma; Disease Susceptibility; Epigenesis, Genetic; Pyroglyphidae
PubMed: 37814791
DOI: 10.1152/ajplung.00103.2023 -
Molecules (Basel, Switzerland) Mar 2024Cosmetic products are chemical substances or mixtures used on the skin, hair, nails, teeth, and the mucous membranes of the oral cavity, whose use is intended to clean,... (Review)
Review
Cosmetic products are chemical substances or mixtures used on the skin, hair, nails, teeth, and the mucous membranes of the oral cavity, whose use is intended to clean, protect, correct body odor, perfume, keep in good condition, or change appearance. The analysis of cosmetic ingredients is often challenging because of their huge complexity and their adulteration. Among various analytical tools, mass spectrometry (MS) has been largely used for compound detection, ingredient screening, quality control, detection of product authenticity, and health risk evaluation. This work is focused on the MS applications in detecting and quantification of some common cosmetic ingredients, i.e., preservatives, dyes, heavy metals, allergens, and bioconjugates in various matrices (leave-on or rinse-off cosmetic products). As a global view, MS-based analysis of bioconjugates is a narrow field, and LC- and GC/GC×GC-MS are widely used for the investigation of preservatives, dyes, and fragrances, while inductively coupled plasma (ICP)-MS is ideal for comprehensive analysis of heavy metals. Ambient ionization approaches and advanced separation methods (i.e., convergence chromatography (UPC)) coupled to MS have been proven to be an excellent choice for the analysis of scented allergens. At the same time, the current paper explores the challenges of MS-based analysis for cosmetic safety studies.
Topics: Cosmetics; Perfume; Allergens; Preservatives, Pharmaceutical; Mass Spectrometry; Coloring Agents; Metals, Heavy
PubMed: 38542972
DOI: 10.3390/molecules29061336