Asthma treatment with inhaled corticosteroids versus antileukotrienes: what exhaled nitric oxide studies do and do not tell us.
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Biomedical subjects
Publications and source records attributed to M S Dykewicz.
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BACKGROUND: Folic acid (the synthetic form of folate B vitamins in foods) is widely used in vitamin supplements. Anaphylaxis from ingestion or injection of folic acid suggests IgE antibody-mediated mechanisms, but this has not been demonstrated previously in vitro. OBJECTIVE: This study was conducted to better define the mechanism of folic acid hypersensitivity and cross-reactivity among folic acid congeners. METHODS: Skin testing was performed with folic acid congeners in a woman who developed anaphylaxis after ingestion of 2 different multivitamin preparations containing folic acid. In vitro immunologic serum studies were conducted using a folate-human serum albumin (HSA) conjugate prepared by a novel application of carbodiimide condensation. RESULTS: The patient had positive immediate-type skin test reactions to folic acid and several folate analogues including leucovorin (folinic acid). Urticaria developed during graded oral test dosing with leucovorin. Using a dot immunoblot assay or an ELISA for IgE antibody to folate-HSA, results of the patient's serum testing were positive, whereas results of sera from normal control subjects were negative, the first in vitro demonstration of IgE to a folic acid-protein conjugate. By ELISA, the positive result of the patient's serum was inhibited significantly by serum coincubation with folate-HSA, but not HSA or folic acid. CONCLUSIONS: Immediate hypersensitivity to folic acid and possibly other vitamins can be mediated by IgE antibody to conjugates formed between vitamins and self-proteins or polypeptides. Leucovorin can have clinically important immunologic cross-reactivity with folic acid. A diet rich in natural folates (pteroylpolyglutamates) appears useful as a management strategy for providing adequate nutrition to patients with folic acid hypersensitivity.
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This algorithm on the diagnosis and treatment of asthma is intended to complement and update the previously published Practice Parameters for the Diagnosis and Treatment of Asthma. Both documents were developed by the Joint Task Force on Practice Parameters, representing the AAAAI, ACAAI, and the JCAAI. The authors of this asthma algorithm have attempted to include all the elements essential for the diagnosis and care of patients with asthma. Every effort was made to keep the algorithm clear and concise, yet thorough and complete (Fig 1). Each component of the algorithm is elaborated further in a brief annotation. For further discussion, the reader is referred to the more extensive Practice Parameters for the Diagnosis and Treatment of Asthma.
Rhinitis is a significant cause of widespread morbidity, medical treatment costs, reduced work productivity and lost school days. Although sometimes mistakenly viewed as a trivial disease, symptoms of allergic and non-allergic rhinitis may significantly impact a patient's quality of life, by causing fatigue, headache, cognitive impairment and other systemic symptoms. In addition, many antihistamines commonly used for treatment can themselves cause performance impairment that may contribute to fatal automobile accidents, work place accidents, decreased work productivity and in children, impaired school performance. Appropriate management of rhinitis may be an important component in effective management of coexisting or complicating respiratory conditions, such as asthma, sinusitis, or chronic otitis media. Rhinitis may be caused by allergic, non-allergic, infectious, hormonal, occupational, and other factors. Defining the causes of rhinitis in an individual is important because different rhinitis syndromes may require different therapeutic approaches for optimal management, an important consideration as more treatment options become available. This Executive Summary reviews key points about diagnosis and management of rhinitis contained in the comprehensive document, Diagnosis and Management of Rhinitis: Complete Guidelines of Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, and Joint Task Force Algorithm and Annotations for Diagnosis and Management of Rhinitis. These documents represent a consensus opinion of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, a national panel co-sponsored by the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Council on Allergy, Asthma and Immunology.
The algorithm and text annotations in this document are intended to assist clinical decision making about patients who present with symptoms of rhinitis. This document complements the Executive Summary of Joint Task Force Practice Parameters for Diagnosis and Management of Rhinitis (Ann Allergy, Asthma, Immunol 1998; 81:463-468) and Diagnosis and Management of Rhinitis: Complete Guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology (Ann Allergy, Asthma, Immunol 1998;81:478-578). The Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology is co-sponsored by the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology and the Joint Council of Allergy, Asthma and Immunology.
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This document contains complete guidelines for diagnosis and management of rhinitis developed by the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology and the Joint Council on Allergy, Asthma and Immunology. The guidelines are comprehensive and begin with statements on clinical characteristics and diagnosis of different forms of rhinitis (allergic, non-allergic, occupational rhinitis, hormonal rhinitis [pregnancy and hypothyroidism], drug-induced rhinitis, rhinitis from food ingestion), and other conditions that may be confused with rhinitis. Recommendations on patient evaluation discuss appropriate use of history, physical examination, and diagnostic testing, as well as unproven or inappropriate techniques that should not be used. Parameters on management include use of environmental control measures, pharmacologic therapy including recently introduced therapies and allergen immunotherapy. Because of the risks to patients and society from sedation and performance impairment caused by first generation antihistamines, second generation antihistamines that reduce or eliminate these side effects should usually be considered before first generation antihistamines for the treatment of allergic rhinitis. The document emphasizes the importance of rhinitis management for comorbid conditions (asthma, sinusitis, otitis media). Guidelines are also presented on special considerations in patients subsets (children, the elderly, pregnancy, athletes and patients with rhinitis medicamentosa); and when consultation with an allergist-immunologist should be considered.
The management of asthma is becoming increasingly complex as more pharmacologic agents become available and we gain increased understanding of the pathogenetic processes of asthma and the risks for potentially irreversible airway remodeling that might be increased by suboptimal management and interactions with concomitant disease states such as gastroesophageal reflux. Although physicians now have greater responsibility to make use of this increasing knowledge to provide more effective management for their asthma patients, they also have a greater opportunity to increase the overall quality of life of patients under their care.
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BACKGROUND: Anisoylated plasminogen-streptokinase complex (APSAC, anistreplase) is a thrombolytic agent (131 kd) used for treatment of myocardial infarction. Like its principal antigenic determinant, streptokinase, APSAC has been reported to cause a variety of allergic reactions. OBJECTIVE: This study was intended to determine any association between isotypic antibody responses to streptokinase and observed allergic reactions to APSAC. METHODS: We measured sequential IgM, IgG, IgA, and IgE antistreptokinase serum levels in 21 patients who received APSAC or tissue-type plasminogen activator in a prospective, double-blind study. RESULTS: Of 11 patients who received APSAC, four had maculopapular rashes and one had urticaria; those with maculopapular rashes had significantly higher rises in serum IgM, IgG, IgA, and IgE antistreptokinase levels. We could not, however, define a temporal relationship between rises in antistreptokinase levels of a particular isotype and the onset of maculopapular rashes. The patient who had urticaria had no antistreptokinase responses but had also received several other potentially causal drugs. None of 10 patients who received tissue-type plasminogen activator had allergic reactions or significant rises in serum antistreptokinase levels. CONCLUSION: The more vigorous panisotypic antistreptokinase responses observed in patients who received APSAC and had maculopapular rashes may reflect generalized immune system activation that included other immune responses (such as cell-mediated hypersensitivity) that were responsible for these reactions.
BACKGROUND: Alum-precipitated allergenic extract (Allpyral) used for immunotherapy has been associated with subcutaneous nodule formation at injection sites. OBJECTIVE: We describe a severe localized reaction at the site of Allpyral injections and evaluate possible mechanisms for this reaction. METHODS: Case report with cutaneous patch testing and CAT scan imaging. RESULTS: The patient developed extensive subcutaneous inflammation and fibrosis with overlying skin changes which appear to be permanent. CAT scan findings were corroborative and cutaneous patch testing to aluminium was positive. CONCLUSIONS: Alum-precipitated allergenic extract used for immunotherapy caused extensive subcutaneous fibrosis with overlying skin changes at the site of injections. The lesions are disfiguring and appear to be permanent. This may be due in part to a type IV hypersensitivity response to the aluminum component of Allpyral extract. A CAT scan was valuable in demonstrating structural changes associated with this lesion.
BACKGROUND: Occupational asthma caused by latex has been reported in health care workers and workers in glove manufacturing plants. OBJECTIVE: We report occupational asthma from latex in a newly identified occupational setting, a latex doll manufacturing plant. METHODS: We evaluated an index case of asthma associated with work in a latex doll manufacturing plant by performing a workplace challenge and evaluating the work environment. We then performed an occupational survey and skin testing of 22 workers in the doll manufacturing plant. RESULTS: The patient, a 21-year-old woman, had severe immediate bronchospasm within minutes of beginning a workplace challenge where sanding of latex parts was performed. Two of 22 workers surveyed (including the patient) reported flushing, rhinoconjunctivitis, and wheezing on exposure to sanded doll parts. These two workers were the only subjects surveyed to have a history of atopy and positive immediate-type skin test responses to a raw latex extract and to common aeroallergens. CONCLUSIONS: Sanding or grinding of solid latex during the manufacturing process may result in a significant incidence of occupational asthma and rhinoconjunctivitis from latex sensitization. Atopic workers appear to be most susceptible to developing latex sensitivity in this setting.
We report the clinical and immunologic analysis of two patients with diabetes who had anaphylaxis to neutral protamine Hagedorn (NPH) human insulin in the absence of allergy to regular insulin. A 36-year-old woman without a recent history of local insulin reactions or interruption of insulin therapy experienced anaphylaxis within 15 minutes of her usual morning dose of subcutaneously administered NPH human insulin. A 62-year-old man with a history of generalized reactions to NPH human insulin and of anaphylaxis to intravenously administered protamine had generalized urticaria after injection of NPH human insulin. Both patients subsequently tolerated Lente human insulin. Skin test results in both patients were negative to regular and Lente insulin preparations but positive to NPH insulin and to protamine at concentrations tested. In vitro assays demonstrated that both patients had markedly elevated serum levels of IgE and IgG to protamine, but not to regular human insulin, and that their IgE antibodies to protamine recognized protamine antigenic determinants in NPH human insulin. We conclude that the anaphylactic reactions to NPH insulin in our patients were mediated by IgE to protamine, which should be a pathogenetic consideration in the evaluation of immediate-type reactions to protamine-containing insulins.
The mechanisms responsible for asbestos-induced pulmonary epithelial cell cytotoxicity, especially oxidant-independent mechanisms, are not established. We determined whether human polymorphonuclear leukocyte (PMN) proteases contribute to asbestos-induced damage to human pulmonary epithelial-like cells (PECs) assessed using an in vitro chromium-51 release assay. Serine antiproteases, phenylmethylsulfonyl fluoride and alpha 1-antitrypsin, each ameliorated PEC injury induced by amosite asbestos and PMNs. A role for a specific proteinase, human neutrophil elastase (HNE), is supported by the facts that (1) asbestos increased HNE release assessed by an enzyme-linked immunosorbent assay technique (1.7 +/- 0.5 vs. 2.8 +/- 0.5 micrograms/ml; P < .025), (2) purified HNE or porcine pancreatic elastase (PPE) each alone caused PEC detachment, (3) asbestos plus either HNE or PPE caused PEC lysis similar to that mediated by asbestos and PMNs, and (4) cationic agents released from PMNs were unlikely to be involved because polyanions did not ameliorate injury resulting from asbestos and PMNs. Compared to elastase, cathepsin G caused less PEC detachment and negligible augmentation in asbestos-induced PEC lysis. Asbestos increased the association of 125I-labeled elastase with PECs nearly 50-fold compared with PPE alone (14.4% vs. 0.3%, respectively; P < .01) and nearly 10-fold compared with another particle, opsonized zymosan. We conclude that PMN-derived proteases, especially elastase, may contribute to asbestos-induced lung damage by augmenting pulmonary epithelial cell injury.