I. Leonard Bernstein

Diagnosis and Management of Rhinitis: Complete Guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology

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.

Practice parameter for the diagnosis and management of primary immunodeficiency

TABLE OF CONTENTS I. Preface S1 II. Executive Summary S2 III. Algorithms S7 IV. Summary Statements S14 V. General Considerations S20 VI. Humoral Immunodeficiencies S24 VII. Cellular Immunodeficiencies S30 VIII. Combined Immunodeficiencies S33 IX. Phagocytic Cell Disorders S40 X. Complement Deficiencies S43 XI. Acknowledgments S45 XII. References S45 XIII. Appendix S61

Allergy diagnostic testing: an updated practice parameter.

I. Leonard Bernstein, MD; James T. Li, MD, PhD; David I. Bernstein, MD; Robert Hamilton, PhD, DABMLI; Sheldon L. Spector, MD; Ricardo Tan, MD; Scott Sicherer, MD; David B. K. Golden, MD; David A. Khan, MD; Richard A. Nicklas, MD; Jay M. Portnoy, MD; Joann Blessing-Moore, MD; Linda Cox, MD; David M. Lang, MD; John Oppenheimer, MD; Christopher C. Randolph, MD; Diane E. Schuller, MD; Stephen A. Tilles, MD; Dana V. Wallace, MD; Estelle Levetin, PhD; and Richard Weber, MD

Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis☆☆☆★★★

BACKGROUND Increased serum levels of antigen-specific IgE are often associated with allergic respiratory disorders. RhuMAb-E25, a recombinant humanized monoclonal antibody, decreases free serum IgE by forming biologically inactive immune complexes with free IgE. OBJECTIVE We hypothesized that rhuMAb-E25 would decrease total serum IgE and reduce symptoms. METHODS Two hundred forty subjects were enrolled into five groups to determine the safety, tolerance, and efficacy of repeated administration of rhuMAb-E25 in adults with ragweed-induced allergic rhinitis and to explore the pharmacodynamic relationship of rhuMAb-E25 and IgE. One hundred eighty-one subjects received an initial intravenous loading dose (day 0, 1 month before ragweed season), followed by administration of rhuMAb-E25 (in mg/kg body weight) of 0.15 mg/kg subcutaneously, 0.15 mg/kg intravenously, or 0.5 mg/kg intravenously on days 7, 14, 28, 42, 56, 70, and 84. A subcutaneous placebo group and an intravenous placebo group were included. The total evaluation time included the 84-day treatment period, followed by a 42-day observation period. RESULTS Adverse events were mild, and no differences were observed in the rates between the three active and two placebo treatment groups. Ragweed-specific IgE levels correlated with symptom scores. RhuMAb-E25 decreased serum free IgE levels in a dose- and baseline IgE-dependent fashion. However, only 11 subjects had IgE levels that were suppressed to undetectable levels (< or = 24 ng/ml), a sample too small to demonstrate significant differences and clinical efficacy. Thus the case for efficacy was not proven. Nonetheless, the study confirms that it is safe to repeatedly administer rhuMAb-E25 over a period of months. CONCLUSIONS Because rhuMAb-E25 decreased serum free IgE in a dose-dependent fashion and because symptom scores correlated with antigen-specific IgE levels, the results suggest that if given in adequate doses, rhuMAb-E25 should be an effective therapy for allergic diseases.

Allergen immunotherapy: a practice parameter

Editors James T. Li, MD, PhD; Rochester, MN Richard F. Lockey, MD; Tampa, FL I. Leonard Bernstein, MD; Cincinnati, OH Jay M. Portnoy, MD; Kansas City, MO Richard A. Nicklas, MD*; Washington, DC *This parameter was edited by Dr. Nicklas in his private capacity and not in his capacity as a medical officer with the United States Food and Drug Administration (FDA). No official support or endorsement by the FDA is intended or should be inferred.

Relationship between numbers of beta adrenergic receptors in lymphocytes and disease severity in asthma.

Abstract In order to assess the status of beta adrenergic receptors in bronchial asthma, binding studies using (−) [ 3 H] dihydroalprenolol (DHA) were performed on lymphocytes of 10 control subjects and 11 stable asthmatic patients. Specific DHA binding was generally lower at all DHA concentrations in asthmatics. At 12 nM DHA concentration, specific DHA binding was 391 ± 40 fM/mg protein in controls and 263 ± 35 fM/mg protein for asthmatic subjects (p

Isocyanate-induced pulmonary diseases: a current perspective☆

Abstract Chemicals of the isocyanate family are required for the production of a variety of commercial products, including insulation materials, automobile upholstery, furniture, and surface coatings. They are highly reactive with other chemicals containing hydrogen atoms. Early reports of medical toxicity appeared 25 yr ago and have been confirmed on a worldwide basis. Adverse respiratory symptoms have been the chief concern, and a wide spectrum of work-related lung diseases has been described. Although some of these reactions were undoubtedly due to primary irritation, the majority presented with airways obstructive abnormalities clearly identified as classic asthma. The possibility of an underlying hypersensitivity mechanism was suggested by the insidious onset of symptoms, a latency period of weeks to months, peripheral and tissue eosinophilia, and the elicitation of symptoms after exposure to very small subtoxic levels of these chemicals. Some cases consistent with the unique clinical features of hypersensitivity pneumonitis have also been recognized. Early animal experimental studies had suggested that immunologic factors were important etiologic components of these syndromes. However, when several independent groups of investigators could not confirm these preliminary results, the pathogenesis of these diseases soon became a highly controversial subject. Current experimental and clinical approaches have therefore been redirected to encompass the role of nonimmunologic mechanisms in the pathogenesis of adverse isocyanate reactions. Collectively, these recent investigations suggest that both immunologic and nonimmunologic mechanisms appear to be operative as causes of isocyanate-induced asthma. There is in vitro evidence both for and against possible specific pharmacologic effects of diisocyanate compounds. Parallel bronchoprovocation studies comparing the activities of diisocyanates, methacholine, and histamine suggest that diisocyanates may act either as direct pharmacologic agonists or as inducers of nonspecific bronchial reactivity. Recent evidence of immunoreactivity to both monofunctional and bifunctional isocyanates in several animal models and sensitized workers has also mandated a reassessment of immunologic factors. Hapten-specific, IgE-mediated antibody responses have been observed in both animal and human investigations. However, only a small subset of sensitized workers developed specific IgE antibodies to p-tolyl monoisocyanate and/or hexyl monoisocyanate. Both IgE and precipitating antibodies have been reported in several cases of workers sensitized to methylene diphenyl diisocyanate. Some toluene diisocyanate-sensitive patients also exhibit other types of immunologic responses, including antigen-induced lymphocyte transformation and synthesis of a leukocyte inhibitory factor. Detailed immunologic investigations have not yet been carried out in most of the suspected cases of hypersensitivity pneumonitis. Other possible nonimmunologic sequelae of isocyanate reactions include chronic bronchitis, recurrent pneumonia, pulmonary edema, and pulmonary emphysema. However, the question of chronic pulmonary disability associated with these diseases is poorly understood and requires further long-term investigation. Despite the brisk controversy that still exists about the pathogenesis of isocyanate-induced pulmonary diseases, new data derived from animal models and clinical investigation of sensitized workers suggest that application of several innovative approaches could result in early detection and treatment of clinical reactions. These are considered in the context of pre-employment screening, serial monitoring in the workplace, and postemployment surveillance.

A self-management program for adult asthma. Part I: Development and evaluation☆☆☆★★★

BACKGROUND We developed and evaluated a self-management program for adult asthma. In developing the program, we considered questions of format and behavior control. The format we selected included components known to be effective in educational settings. We regulated asthma management behavior through the introduction of environmental cues. METHODS Seventy-six subjects, whose asthma was generally under medical control, were assigned randomly to either a treatment group or a waiting-list control group. Those in the treatment group were exposed to a 7-week program that incorporated proven features of providing effective training and establishing behavioral control. Subsequently, subjects in the control group received the treatment. Short-term evaluation of the treatment was made after the subjects in the experimental group were trained but before the control subjects were trained. Long-term evaluation was conducted after both groups of subjects were trained. RESULTS Over the short term, self-management training led to fewer asthma symptoms and physician visits and improvement in asthma management skills and cognitive abilities. Over the long term, self-management training was related to lower asthma attack frequency, reduced medication use, improvement in cognitive measures, and increased use of self-management skills. CONCLUSIONS The program improved asthma management in patients whose conditions were already under good medical control. The effects of the program were apparent a year after the conclusion of self-management training.

Disease management of atopic dermatitis: an updated practice parameter

ratory disease but often is the first manifestation of allergic disease. Most patients with atopic dermatitis will develop allergic rhinitis or asthma. The evaluation and management of atopic dermatitis are, therefore, an integral part of an allergist/immunologist’s training and practice. It is also important for the primary care physician to understand the basis for effective evaluation and management of patients with this condition, since atopic dermatitis affects more than 10% of children and can have a significant impact on the patient’s quality of life. As discussed in this document, it is also important for the primary care physician to know when to appropriately consult a specialist in atopic dermatitis.

Occupational asthma induced by inhalation and ingestion of garlic

Repeated exposure to garlic dust induced severe asthma in an atopic patient. Subsequently, the patient also developed marked adverse responses after ingestion of garlic. Immunologic investigations carried out in an asymptomatic period revealed significant skin reactivity and bronchospasm after challenge with both garlic dust and extract. The results of a controlled oral challenge test to garlic dust were also positive. The patients serum contained unusually high quantities of garlic-specific IgE. Cross allergenicity between garlic and other members of the Liliaceae family were documented by the RAST inhibition technique.