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1.
World Allergy Organ J ; 16(6): 100792, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37448849

ABSTRACT

Hereditary angioedema (HAE) is a rare, chronic, debilitating genetic disorder characterized by recurrent, unpredictable, and potentially life-threatening episodes of swelling that typically affect the extremities, face, abdomen, genitals, and larynx. The most frequent cause of HAE is a mutation in the serpin family G member 1 (SERPING1) gene, which either leads to deficient plasma levels of the C1-esterase inhibitor (C1-INH) protein (type I HAE-C1-INH) or normal plasma levels of dysfunctional C1-INH protein (type II HAE-C1-INH). Mutations in SERPING1 are known to be associated with dysregulation of the kallikrein-bradykinin cascade leading to enhancement of bradykinin production and increased vascular permeability. However, some patients present with a third type of HAE (HAE-nl-C1-INH) that is characterized by normal plasma levels and functionality of the C1-INH protein. While mutations in the factor XII, angiopoietin-1, plasminogen, kininogen-1, myoferlin, and heparan sulfate-glucosamine 3-O-sulfotransferase-6 genes have been identified in some patients with HAE-nI-C1-INH, genetic cause remains unknown in many cases with further research required to fully elucidate the pathology of disease in these patients. Here we review the challenges that arise on the pathway to a confirmed diagnosis of HAE and explore the multifactorial impact of receiving a HAE diagnosis. We conclude that it is important to continue to raise awareness of HAE because delays to diagnosis have a direct impact upon patient suffering and quality of life. Since many patients will seek help from hospitals during their first swelling attack it is vital that emergency department staff are aware of the different pathological pathways that distinguish HAE from other forms of angioedema to ensure that the most appropriate treatment is administered. As disease awareness increases, it is hoped that patients will be diagnosed earlier and that pre-authorization and insurance coverage of HAE treatments will become easier to obtain, ultimately reducing the burden of treatment for these patients and their caregivers.

2.
J Food Allergy ; 2(1): 119-123, 2020 Sep.
Article in English | MEDLINE | ID: mdl-39022148

ABSTRACT

Food additives are natural or synthetic substances added to foods at any stage of production to enhance flavor, texture, appearance, preservation, safety, or other qualities. Common categories include preservatives and antimicrobials, colorings and dyes, flavorings, antioxidants, stabilizers, and emulsifiers. Natural substances rather than synthetics are more likely to cause hypersensitivity. Although rare, food additive hypersensitivity should be suspected in patients with immunoglobulin E (IgE)-mediated reactions to multiple, unrelated foods, especially if the foods are prepared outside of the home or when using commercial products. A complete and thorough history is vital. Skin prick testing and/or specific IgE blood testing to food additives, if available, additive avoidance diets, and blind oral challenges can help establish the diagnosis. Once an allergy to a food additive is confirmed, management involves avoidance and, if necessary, carrying self-injectable epinephrine.

4.
Int Arch Allergy Immunol ; 170(2): 138-40, 2016.
Article in English | MEDLINE | ID: mdl-27505292

ABSTRACT

Selective immunoglobulin M deficiency (SIgMD) is a rare disorder with varying clinical features. The prevalence of SIgMD is 0.03-3%. Patients may be asymptomatic or else present with recurrent infection, autoimmunity, atopic disease and/or malignancy. About 50% of patients with symptomatic SIgMD also have impaired antibody responses to the pneumococcal polysaccharide vaccine. We report on an adult who presented with symptomatic SIgMD with impaired pneumococcal polysaccharide antibody responses and lymphopenia, who experienced a significant clinical improvement in the frequency of infections after subcutaneous immunoglobulin replacement therapy.


Subject(s)
Agammaglobulinemia/blood , Agammaglobulinemia/complications , Antibodies/administration & dosage , Immunization, Passive/methods , Immunoglobulin M/blood , Pneumococcal Infections/etiology , Pneumococcal Infections/therapy , Adult , Humans , Immunoglobulins/blood , Injections, Subcutaneous , Male , Treatment Outcome
6.
Allergy Asthma Proc ; 32(4): 288-94, 2011.
Article in English | MEDLINE | ID: mdl-21781404

ABSTRACT

The use of epinephrine for anaphylaxis to subcutaneous allergen immunotherapy (SCIT) is the standard of care, but its use for mild systemic reactions (SRs) is somewhat controversial. The objective of this study is to determine the rate of SR to SCIT, the symptoms reported, and the response to intramuscular (i.m.) epinephrine over a 1 year period. This retrospective study was designed to evaluate SRs to SCIT to any combination of approximately 20 allergens (pollens, animal emanations, molds, and Hymenoptera) in 773 subjects representing 14,707 visits, receiving approximately 28,000 injections over 1 year. Nurses were instructed to administer epinephrine (1:1000 v/v) 0.2 mL i.m. for signs or symptoms of a SR. SRs were graded using the universal grading system proposed by the World Allergy Organization (WAO) Joint Task Force for Grading SR to Immunotherapy. Thirty-one patients (4%) had 32 SRs, 22 (71%) female, average age 40 yr. Nineteen (61%) had a history of asthma; 7 (22.6%) had a history of a previous SR. SRs were reported on average 24 minutes after injection. Symptoms included: generalized pruritus, 34.4%; upper airway pruritus, 28.1%; cough, 25.0%; shortness of breath, 21.9%. Fourteen SRs were classified as Grade 1, thirteen Grade 2, two Grade 3, and three Grade 4. No Grade 5 or late phase reactions were reported. 29 (90.6%) reactions were treated with epinephrine, 27 (84.4%) glucocorticosteroid, and 30 (93.8%) H1 antihistamine. SRs occurred in 4% of patients receiving SCIT and all who received early intervention with epinephrine responded successfully. The WAO Grading system was useful.


Subject(s)
Allergens/adverse effects , Desensitization, Immunologic/adverse effects , Epinephrine/administration & dosage , Adrenergic alpha-Agonists/administration & dosage , Adrenergic alpha-Agonists/therapeutic use , Adult , Allergens/administration & dosage , Allergens/immunology , Anaphylaxis/drug therapy , Animals , Desensitization, Immunologic/methods , Epinephrine/therapeutic use , Female , Humans , Hypersensitivity, Immediate/drug therapy , Injections, Intramuscular , Injections, Subcutaneous , Male , Severity of Illness Index , Treatment Outcome
7.
Cell Transplant ; 20(5): 609-18, 2011.
Article in English | MEDLINE | ID: mdl-21054942

ABSTRACT

Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route. Additionally, Sertoli cells were preloaded with chitosan nanoparticles coupled with the anti-inflammatory compound curcumin and then injected intravenously into control or experimental mice with deep lung inflammation. By 24 h postinjection, most of the curcumin load (∼90%) delivered in the injected Sertoli cells was present and distributed throughout the lungs, including the perialveloar sac area in the lower lungs. This was based on the high-density, positive quantification of both nanoparticles and curcumin in the lungs. There was a marked positive therapeutic effect achieved 24 h following curcumin treatment delivered by this Sertoli cell nanoparticle protocol (SNAP). Results identify a novel and efficient protocol for targeted delivery of drugs to the deep lung mediated by extratesticular Sertoli cells. Utilization of SNAP delivery may optimize drug therapy for conditions such as ARDS, status asthmaticus, pulmonary hypertension, lung cancer, and complications following lung transplantation where the use of high concentrations of anti-inflammatory drugs is desirable, but often limited by risks of systemic drug toxicity.


Subject(s)
Drug Carriers/chemistry , Pneumonia/drug therapy , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Chitosan/chemistry , Curcumin/administration & dosage , Female , Fluorescein-5-isothiocyanate/chemistry , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Microscopy, Confocal , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Pneumonia/pathology , Rats , Rats, Sprague-Dawley , Sertoli Cells/cytology , Sertoli Cells/transplantation
8.
Expert Opin Drug Metab Toxicol ; 5(8): 933-40, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19619072

ABSTRACT

BACKGROUND: Treating asthma with a combination of inhaled corticosteroid and a long-acting beta-2-agonist is often preferred when asthma is not controlled when using a low-medium dose of an inhaled corticosteroid. OBJECTIVE: To review the pharmacology, efficacy and safety of inhalers containing combinations of long-acting bronchodilators and inhaled corticosteroids to treat moderate-to-severe, persistent asthma. METHODS: Using a list of keywords, we conducted a PubMed search of the literature. Data provided by the manufacturer were also reviewed. RESULTS: Fluticasone propionate with salmeterol and budesonide with formoterol are both well tolerated, have equal clinical efficacy and have recent data affirming their safe use in diverse patient populations. CONCLUSIONS: Combination inhalers improve asthma control in patients previously uncontrolled on inhaled corticosteroids.


Subject(s)
Adrenergic beta-2 Receptor Agonists , Adrenergic beta-Agonists/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Glucocorticoids/therapeutic use , Administration, Inhalation , Adrenergic beta-Agonists/adverse effects , Adrenergic beta-Agonists/pharmacokinetics , Adrenergic beta-Agonists/pharmacology , Animals , Anti-Asthmatic Agents/adverse effects , Anti-Asthmatic Agents/pharmacokinetics , Anti-Asthmatic Agents/pharmacology , Bronchodilator Agents/adverse effects , Bronchodilator Agents/pharmacokinetics , Bronchodilator Agents/pharmacology , Bronchodilator Agents/therapeutic use , Drug Combinations , Glucocorticoids/adverse effects , Glucocorticoids/pharmacokinetics , Glucocorticoids/pharmacology , Humans
9.
J Allergy Clin Immunol ; 123(1): 224-230.e4, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18995892

ABSTRACT

BACKGROUND: Toll-like receptors contribute to the establishment of adaptive immune responses. OBJECTIVE: The reported studies were conducted to examine the effects of the Toll-like receptor (TLR)-7 ligand, resiquimod, on human naive B-cell differentiation. METHODS: Naive human B cells were cultured with resiquimod in the presence or absence of IL-2 and IL-10. Secreted IgM and IgG were measured by ELISA, and IL-6, IL-10, and IFN-alpha were measured by a multiplex protein array. Cell proliferation was assessed by measuring [(3)H]thymidine uptake. mRNA for activation-induced cytidine deaminase and I(gamma 1)-C(mu) circle transcripts was measured by means of RT-PCR. RESULTS: Resiquimod induced the production of IgM and, to a lesser extent, IgG by naive human B cells in association with the secretion of IL-6 and IL-10, and a weak proliferative response. IL-2 and IL-10 synergized with resiquimod in markedly augmenting resiquimod-induced IgM and IgG production and proliferation. Resiquimod also stimulated production of IgG by B cells isolated from the blood of a patient with the X-linked hyper-IgM syndrome, with a greater response when these cells were costimulated with IL-2 and IL-10. The stimulated naive B cells from healthy volunteers displayed molecular evidence of immunoglobulin class-switch recombination-namely the appearance of activation-induced cytidine deaminase and I(gamma 1)-C(mu) circle transcripts. CONCLUSION: Perturbation of TLR-7 on naive human B cells can lead to the induction of immunoglobulin class switch and IgG production in the absence of B-cell receptor cross-linking and CD40-CD40L interaction. The results are relevant to vaccine development and mechanisms by which microbial infection may lead to autoimmunity.


Subject(s)
Antibody Formation/immunology , B-Lymphocytes/immunology , Imidazoles/pharmacology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Toll-Like Receptor 7/immunology , Adult , Antibody Formation/drug effects , Antibody Formation/genetics , CD40 Antigens/genetics , CD40 Antigens/immunology , CD40 Ligand/genetics , CD40 Ligand/immunology , Cell Proliferation/drug effects , Cells, Cultured , Drug Synergism , Female , Gene Rearrangement, B-Lymphocyte/drug effects , Gene Rearrangement, B-Lymphocyte/genetics , Gene Rearrangement, B-Lymphocyte/immunology , Humans , Hyper-IgM Immunodeficiency Syndrome, Type 1/genetics , Hyper-IgM Immunodeficiency Syndrome, Type 1/immunology , Imidazoles/immunology , Immunoglobulin G/genetics , Immunoglobulin M/genetics , Interferon-alpha/genetics , Interferon-alpha/immunology , Interleukin-10/immunology , Interleukin-10/pharmacology , Interleukin-2/immunology , Interleukin-2/pharmacology , Interleukin-6/genetics , Interleukin-6/immunology , Ligands , Male , Middle Aged , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/immunology , Toll-Like Receptor 7/agonists , Toll-Like Receptor 7/genetics
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