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Thousands of persons experience accidental high-level irritant exposures each year but most recover and few die. Irritants function differently than allergens because their actions proceed nonspecifically and by nonimmunologic mechanisms. For some individuals, the consequence of a single massive exposure to an irritant, gas, vapor or fume is persistent airway hyperresponsiveness and the clinical picture of asthma, referred to as reactive airways dysfunction syndrome (RADS). Repeated irritant exposures may lead to chronic cough and continual airway hyperresponsiveness. Cases of asthma attributed to repeated irritant-exposures may be the result of genetic and/or host factors.

Women have exhibited anaphylaxis, urticaria/angioedema, and autoimmune progesterone dermatitis (APD) coinciding with the progesterone premenstrual rise. We report a detailed immunological evaluation of such a woman responsive to a gonadotropin hormone-releasing agonist (GHRA).Skin testing, enzyme-linked immunosorbent assays (ELISAs), leukocyte histamine release (LHR), and inhibition assays were performed to demonstrate progesterone immunoresponsiveness.Serum specific-progesterone immunoglobulin G (IgG) and IgE were detected initially and disappeared 6 months after GHRA treatment. Dose-response LHR using patient basophils was observed for different hormones but after 3 months persisted only for 5β-pregnanediol. Preincubation with mouse antiprogesterone monoclonal antibody (PmAb) or mifepristone, a progesterone inhibitor, over a range of doses inhibited specific progesterone-induced LHR. Experiments with varying progesterone concentrations and a fixed dose of anti-IgE resulted in 100% LHR at a concentration as low as 0.016 nmol/mL, which, without anti-IgE, failed to release histamine.This is the first report of combined recurrent anaphylaxis, cyclic urticaria/angioedema, and APD induced by immunoresponsiveness to progesterone.

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

Objective To review the evolution of our understanding of hereditary angioedema (HAE) from the first historical reference to the present day. Data Sources MEDLINE and PubMed were searched using the following keywords: history of HAE, C1 inhibitor, complements system, genetics of HAE, mechanisms of HAE , and treatment of HAE . Study Selection Information was selected that outlines the advances made in complementology, the first report of HAE, and subsequent studies that elucidated the underlying mechanisms of this disease, leading to current therapy of this orphan disease. Results Generational research efforts in HAE have focused on the following: (1) several new clinical presentations, (2) acquired forms of non-histamine-induced angioedema, (3) the genetic basis for the inherited forms, (4) the effects of C1 inhibitor on contact phases of coagulation-fibrinolytic pathways, and (5) various therapies for short- and long-term control of the disease. Conclusion The progress made in understanding the pathogenesis and treatment of HAE is an excellent example of the "bench to the bedside" paradigm involving the collaboration between clinicians and researchers.

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

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.

Technology has improved the food supply since the first cultivation of crops. Genetic engineering facilitates the transfer of genes among organisms. Generally, only minute amounts of a specific protein need to be expressed to obtain the desired trait. Food allergy affects only individuals with an abnormal immunologic response to food--6% of children and 1.5-2% of adults in the United States. Not all diseases caused by food allergy are mediated by IgE. A number of expert committees have advised the U.S. government and international organizations on risk assessment for allergenicity of food proteins. These committees have created decision trees largely based on assessment of IgE-mediated food allergenicity. Difficulties include the limited availability of allergen-specific IgE antisera from allergic persons as validated source material, the utility of specific IgE assays, limited characterization of food proteins, cross-reactivity between food and other allergens, and modifications of food proteins by processing. StarLink was a corn variety modified to produce a (Italic)Bacillus thuringiensis(/Italic) (Bt) endotoxin, Cry9C. The Centers for Disease Control and Prevention investigated 51 reports of possible adverse reactions to corn that occurred after the announcement that StarLink, allowed for animal feed, was found in the human food supply. Allergic reactions were not confirmed, but tools for postmarket assessment were limited. Workers in agricultural and food preparation facilities have potential inhalation exposure to plant dusts and flours. In 1999, researchers found that migrant health workers can become sensitized to certain Bt spore extracts after exposure to Bt spraying.

OBJECTIVE: To identify an index population of Gulf War couples with burning semen syndrome and to determine whether burning semen syndrome was secondary to seminal plasma hypersensitivity. METHODS: Questionnaire surveys, screening laboratory testing for underlying medical disorders, including sexually transmitted diseases and immunoglobulin G and E immunoassays specific for seminal plasma protein, were performed. If subjects met the criteria for seminal plasma hypersensitivity, the Gulf War male veteran’s seminal plasma proteins were used to desensitize his female sexual partner. RESULTS: Eighty-nine percent (188 of 211) of respondents had either personally experienced burning after contact with their own semen or had a sexual partner who had burning after contact with their semen. Asymptomatic female partners (three of five) of Gulf War veterans who exhibited specific immunoglobulin E skin and antibody responses to seminal plasma proteins responded successfully to rapid desensitization. Treatment results were confirmed by a provocative office challenge, consisting of instillation of whole seminal fluid into the female’s vaginal vault and, if negative, subsequently by natural coitus. CONCLUSION: The results of this study indicate that seminal plasma hypersensitivity may present as burning semen syndrome in a subpopulation of Gulf War couples. Proper screening of Gulf War couples with clinical features of burning semen syndrome should include assessment for seminal plasma hypersensitivity reactions, as seminal plasma protein desensitization may induce remission of burning semen syndrome.

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 annotations. For further discussion, the reader is referred to the more extensive Practice Parameters for the Diagnosis and Treatment of Asthma.

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 rhi-nitis. The document emphasizes the importance of rhinitis management for co-morbid 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.

Objective To determine the ability of budesonide via an inhaler (Pulmicort Turbuhaler; Astra Draco AB) to replace oral glucocorticosteroids (GCSs) in adult subjects with moderate-to-severe asthma. Design Double-blind, randomized, and placebo-controlled study, with parallel groups. Setting Multicenter study in outpatient setting. Participants Eighty men and 79 women, aged 20 to 69 years, with moderate-to-severe asthma and a mean FEV 1 of 58.3% predicted normal. All subjects were receiving oral GCS treatment and 79% of subjects were also receiving inhaled beclomethasone dipropionate (BDP). The mean daily doses of prednisone at baseline, including converted dose of BDP, for the placebo, budesonide 400 pg, and budesonide 800 pg, respectively, were 19.7 mg, 19.5 mg, and 18.7 mg. Measurements and interventions After a 2-week baseline period, subjects entered a 20-week treatment period, during which the oral dose of prednisone was reduced by forced down-titration at 2-weekly intervals. Results Subjects receiving 400 μg or 800 μg bid of budesonide achieved a significantly greater reduction (82.9% and 79.0% respectively) in oral GCS dose compared with placebo-treated subjects (27%; p Conclusion Budesonide administered via Turbuhaler has a significant oral GCS-sparing capacity with maintained or improved asthma control in adult subjects with moderate-to-severe asthma.

INTRODUCTION Atopic dermatitis is an important manifestation of the atopic diathesis.1,2 It not only frequently accompanies allergic respiratory disease but often precedes it as the initial clinical manifestation of allergic disease. The evaluation and management of patients with atopic dermatitis is therefore an integral part of an allergist’s practice and training. Since atopic dermatitis affects more than 10% of children, it is important for the primary care physician/provider to be familiar with the evaluation and management of this common skin condition, and know when to consult a qualified subspecialist, particularly when the diagnosis may not be established (Table 1). Although the exact role of IgE antibodies in the pathogenesis of atopic dermatitis is not clear, most individuals with atopic dermatitis have elevated serum IgE levels and there is evidence that the eosinophil plays a role in disease pathogenesis, based on elevated tissue and serum levels of eosinophil derived cationic proteins.3,4 Research into the pathogenesis of allergic disease continues to suggest a complex inflammatory process involving mast cells, lymphocytes, and infiltrating leukocytes which are orchestrated by a cytokine profile that has been identified with the T Helper Type 2 (TH2) lymphocyte.5 Recent advances in our understanding of the immunopathogenesis of atopic dermatitis are leading to the development of novel forms of therapy that may be helpful in selected patients. The response to topical corticosteroids as the mainstay of treatment for atopic dermatitis is likely to be the result of corticosteroid reduction of cellular immune activation. CLINICAL CRITERIA FOR DIAGNOSIS Intense pruritus and cutaneous reactivity associated with a lowered “itch threshold” are hallmarks of atopic dermatitis.6,7 Several skin lesions are commonly seen in atopic dermatitis. Acute lesions are characterized by intensely pruritic, erythematous papules and vesicles over erythematous skin. These are frequently associated with extensive excoriations and erosions which are accompanied by a serous exudate. Subacute lesions are characterized by erythema, excoriation, and scaling. Chronic lesions are characterized by thickened plaques of skin, accentuated skin markings (lichenification), and fibrotic papules (prurigo nodularis). In patients with chronic atopic dermatitis, all three skin reaction patterns may coexist in the same individual. Although atopic dermatitis may present at any age, it often begins between 2 and 6 months of age. The infantile form of atopic dermatitis involves the extensor surfaces of extremities, face, trunk and neck areas early, whereas the flexural aspects of the antecubital fossa and the popiliteal fossa become involved in chronic childhood and adult atopic dermatitis. Frequently, atopic dermatitis subsides in severity as the child matures, leaving an adult with skin that is prone to itching and inflammation when exposed to exogenous irritants.8 Last, chronic hand eczema may be the primary manifestation of many adults with atopic dermatitis. The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing atopic dermatitis parameters. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these Practice Parameters. Any request for information about or an interpretation of these Practice Parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. This document has been approved and endorsed by the Allergy & Immunology subsection of the American Academy of Pediatrics. ‡ Reviewers. Sami L Bahna, MD; Jean A Chapman, MD; John M James, MD; Gail G Shapiro, MD; F Estelle R Simons, MD; and Betty B Wray, MD Received for publication May 23, 1997. Accepted for publication in revised form June 24, 1997.

Despite optimal anti-inflammatory treatment of asthma, including use of high dosage, high potency inhaled corticosteroids, a subset of corticosteroid-dependent patients require substantial amounts of daily systemic corticosteroids for adequate control. Several anti-inflammatory modulating agents (auranofin, methotrexate and cyclosporin) have been evaluated for their corticosteroid-sparing properties under such circumstances. This analysis was gleaned primarily from randomised, double-blind, placebo-controlled trials of these agents. Global assessment of corticosteroid-sparing efficacy of these drugs revealed an advantage of auranofin over both methotrexate and cyclosporin. In addition, the comparative adverse event profiles of these drugs indicated that auranofin exhibited milder, more tolerable adverse effects. Therefore, auranofin presents a better risk : benefit option in initial attempts to wean dependent patients from corticosteroids.

Experience with human seminal plasma hypersensitivity in the last decade has led to increased physician awareness of symptoms consistent with human seminal plasma sensitization in women. Incidence and prevalence of human seminal plasma hypersensitivity in women are unknown.A questionnaire survey was distributed to determine the prevalence of human seminal plasma hypersensitivity among a population of women suspected of having this disorder.A questionnaire designed to elicit age, symptoms, duration of symptoms, number of sexual partners, time to onset of symptoms after first human seminal plasma exposure, onset of symptoms after first intercourse, recent gynecologic procedures, history of atopy, vaginitis, food or drug allergy and family history of atopy was distributed to 1,073 women who suspected they had symptoms consistent with human seminal plasma hypersensitivity. Women were considered "possible" for human seminal plasma hypersensitivity if they reported two or more symptoms consistent with localized or systemic human seminal plasma hypersensitivity. Women were considered "probable" for disease if they fulfilled the "ultimate criterion" defined as complete prevention of symptoms with a condom. Women with "possible" localized or systemic human seminal plasma hypersensitivity who had persistent symptoms despite use of a condom served as cohort control groups.Two-hundred sixty-six women reported symptoms "possible" for human seminal plasma hypersensitivity (88 localized and 178 systemic). When the "ultimate criterion" was applied, 130 (46 localized and 84 systemic) of the 266 women were identified as having "probable" human seminal plasma hypersensitivity. The responses to most of the questions from each group were very similar. A significantly shorter time interval to symptom onset after initial human seminal plasma exposure was more common for women with "probable" localized human seminal plasma hypersensitivity compared with their cohort control group (49 months versus 108 months; P.02) whereas a significantly increased number of women with "probable" systemic human seminal hypersensitivity gave positive food allergy histories compared with their cohort control group (31 versus 20; P.05). Atopy did not appear to be a risk factor for human seminal plasma hypersensitivity.Evaluation of women with symptoms suggestive of human seminal plasma hypersensitivity using a validated questionnaire indicates that this disorder is more common than previously recognized.

A variety of chemicals and proteins can sensitize the respiratory tract. Among these are materials of industrial importance, including certain diisocyanates, acid anhydrides, reactive dyes, and enzymes. Currently, no widely accepted or well-validated methods for the prospective identification of respiratory allergens exist. Most progress has been made with guinea pig methods where sensitizing potential is measured usually by assessment of changes in pulmonary function induced following sensitization and challenge. However, these methods are often prohibitively expensive, particularly for screening purposes. A number of alternative approaches are under consideration and are described here. The nature of the health problems associated with occupational respiratory sensitization, chemical structure–activity analyses as a tool for detecting pulmonary allergens, approaches used to test for respiratory allergens in guinea pigs, and alternative approaches using mice are all discussed. Finally, regulatory issues and needs with respect to respiratory sensitization are outlined.

BACKGROUND: Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma. OBJECTIVES: The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma. METHODS: Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations. Two hundred seventy-nine patients with chronic corticosteroid-dependent asthma (requiring ≥ 10 mg/day) were randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month clinical trial, which was divided into three phases including: a 4-week baseline period (phase I), a 6-month double-blind treatment and steroid reduction period (phase II), and a 4-week posttreatment observation period during which steroid and auranofin doses or placebo doses were maintained at levels achieved by the end of phase II (phase III). The primary efficacy variable was "therapeutic success" or reduction of daily corticosteroid use by 50% or more. RESULTS: The proportion of patients in the auranofin group achieving therapeutic success (41%) was significantly higher than that in the placebo group (27%) ( p = 0.01). This effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day at baseline ( p p p = 0.001). Gastrointestinal and cutaneous adverse events were greater in the auranofin group. CONCLUSIONS: Auranofin demonstrated a steroid-sparing effect without concomitant worsening of symptoms or lung function and appeared to be more effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore this study has demonstrated that auranofin is useful as a steroid-sparing agent in the treatment of chronic corticosteroid-dependent asthma. (J ALLERGY CLIN IMMUNOL 1996;98:317-24.)

Six auto parts manufacturing workers were referred for evaluation of a 6-week history of work-related dyspnea, cough, and fatigue. Two workers also reported fever and weight loss. All six worked in a machining area where a waterbased metalworking fluid was used and recirculated under high pressure, thereby creating an aerosol. Chest radiographs revealed pulmonary interstitial infiltrates in four workers. Lung function tests showed that four workers had decreased diffusing capacity. After removal from the work area, all workers recovered. The metalworking fluid was cultured for bacteria and fungi. Isolates from broth cultures were sonicated to obtain antigen extracts. Serum precipitins to one or more of the microbial isolates were identified in all six workers but not in eight of nine nonexposed control subjects. The most frequent precipitin response (six of six workers) was against antigens of Pseudomonas fluorescens, which was cultured from the metalworking fluid. In all workers, precipitins to at least one other cultured organism were detected; these included Aspergillus niger, Staphylococcus capitas, an acid-fast Rhodococcus sp, and Bacillus pumilus. This represents the first report of hypersensitivity pneumonitis associated with industrial exposure to aerosolized metalworking fluid. Observed precipitin responses to a variety of microbial contaminants in metalworking fluid strongly suggest a causative role for microbial antigens in the induction and elicitation of this manifestation of hypersensitivity pneumonitis.

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. (J A LLERGY CLIN I MMUNOL 1995;95:529-40.)

We observed that a group of detergent enzyme workers with known exposure to the subtilisin enzyme, Alcalase (Novo Industries, Bagsvaerde, Denmark), exhibited percutaneous sensitivity to Savinase (Novo Industries), a microbial protease, to which there was no previous occupational exposure. This was attributed to either cross-reactivity between these enzymes or to foreign enzyme contaminants contained in the Savinase antigen. The aims of this study were to determine the range of concentrations eliciting percutaneous responses to Alcalase and to another enzyme, Rapidase (an alpha-amylase) (Gist Brocades, Belgie, Netherlands); to compare the sensitivity of RAST and skin prick testing; and to characterize the relationship between wheal size and antigen concentration. Prick testing was conducted over six log10 antigen dilutions of Alcalase and Rapidase in 30 workers with previous exposure and skin reactivity to enzymes (group 1) and compared to nonexposed control groups, which included 60 atopic subjects (group 2) and 30 nonatopic subjects (group 3). The RAST was performed with Alcalase and Rapidase antigens. The percutaneous threshold concentrations in group 1 subjects varied widely from 10(3) to 10(-3) micrograms of protein per milliliter. Of 19 group 1 workers with skin test reactivity to Alcalase, 84% had positive RAST results; 83% of 24 workers who were reactive to Rapidase had positive RAST results. It was concluded that skin prick testing is preferred over in vitro methods for longitudinal monitoring of human sensitization to workplace allergens. In addition, the data predicted that based on a known Alcalase level of 0.07% in Savinase, 26% of Alcalase-sensitized subjects could react to Savinase. An excellent correlation (r > 0.97) was found between log concentration of antigen and wheal size parameters, with the log diameter and log area performing equally as well (r > 0.98). Analysis of variance revealed that more than 60% of intragroup variation represented human variability in wheal parameters at each concentration tested, whereas at least 95% of intergroup variation was due to regression. The excellent correlations of both wheal diameter and area with antigen concentrations were attributed to the very small changes observed between test concentrations.

This study was designed to investigate the prevalence of skin sensitization using detoxified cyanobacterial reagents in a chronic rhinitis population. Subjects ≥6 years of age who presented for allergy consultation to a community allergy practice and required skin-prick testing (SPT) to common seasonal and perennial aeroallergens were enrolled after signing an informed consent. Detoxified cyanobacteria species were used for skin testing. Skin testing of unexposed, nonsensitized control subjects using these detoxified cyanobacterial skin test reagents was performed to identify irritant threshold responses. All subjects signed an Institutional Review Board-approved informed consent before participation. Two hundred fifty-nine patients ranging in age between 7 and 78 years old underwent testing. The majority were white female patients and over two-thirds (73.4%) were atopic. Seventy-four (28.6% of the population) patients were SPT(+) to at least one of the cyanobacteria species. Positive SPTs were present in 86% of patients to Microcystis aeruginosa and 12% of patients to Aphanizomenon-flos aquae. There was a strong association between severity of atopy (number of positive SPTs), having allergic rhinitis and sensitization to one or more cyanobacteria species (p < 0.001). This is the first study to show that cyanobacterial allergenicity resides in nontoxin-containing components of this organism.

Background There is growing public awareness regarding the risk associated with poor indoor air quality in the home and workplace. Because Americans spend approximately 22 hours every day indoors, susceptible individuals are at much greater risk of adverse health effects from chronic low levels of exposure to indoor air pollutants over time. Along with particulate matter, gases such as ozone, nitrogen dioxide, carbon monoxide, and sulfur dioxide; microbial and chemical volatile organic compounds; passive smoke; and outdoor ambient air are the most common types of air pollutants encountered indoors. Objective To provide the allergists with necessary information that will assist them in making useful recommendations to patients seeking advice regarding indoor environmental triggers beyond traditional perennial allergens. Methods Review of the literature pertaining to indoor exposure and health effects of gaseous and particular matter. Results Indoor pollutants act as respiratory irritants, toxicants, and adjuvants or carriers of allergens. Conclusion The allergist should be prepared to evaluate patient exposure to allergic and nonallergic triggers and understand how outdoor air pollution is affecting indoor environments. This requires being familiar with methodologies for monitoring and interpreting indoor air quality and interpreting results in the context of the patients exposure history and advising patients about rational environmental control interventions.

Definitions vary with time according to the current status of evidence and changing diagnostic means. Definitions also vary according to purposes for which they are used as in epidemiology, surveillance programs, clinical diagnosis, and medicolegal jurisdiction. Because the consensus definition of asthma has improved its recognition and management in recent years, precise and workable definitions of occupational asthma (OA) are required to improve its investigation and management.

As a prelude to a discussion of compensation issues specifically concerned with occupational asthma (OA), it is useful to review how occupational diseases per se evolved from the pre-eminence of injury as a raison d’etre for workers’ disability and compensation. The concept of protecting workers from the consequences of occupational disease—as contrasted to occupational injury—is a relatively recent development among industrial countries. In the late 19th century, middle European countries, starting with Switzerland, Germany, and Austria, began to compensate workers for work-related injuries (1). Similar legislation appeared in Britain in the first decade of the 20th century. This change is reflected in the transformation of the names given to agencies that are responsible for compensation. For example, in Quebec, the first name of the agency was Commission of Labor Injuries (‘‘Commission des accidents de travail’’), and it was only in 1980 that the name of the agency became Commission of Health and Security at Work (‘‘Commission de la sante

These parameters were developed by the Joint Task Force on Practice Parameters, representing 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. The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing "Attaining optimal asthma control: A practice parameter." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.

These parameters were developed by the Joint Task Force on Practice Parameters, representing 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. The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing "The diagnosis and management of anaphylaxis: an updated practice parameter." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients.

The general public, especially patients with upper or lower respiratory symptoms, is aware from media reports that adverse respiratory effects can occur from air pollution. It is important for the allergist to have a current knowledge of the potential health effects of air pollution and how they might affect their patients to advise them accordingly. Specifically, the allergist–clinical immunologist should be keenly aware that both gaseous and particulate outdoor pollutants might aggravate or enhance the underlying pathophysiology of both the upper and lower airways. Epidemiologic and laboratory exposure research studies investigating the health effects of outdoor air pollution each have advantages and disadvantages. Epidemiologic studies can show statistical associations between levels of individual or combined air pollutants and outcomes, such as rates of asthma, emergency visits for asthma, or hospital admissions, but cannot prove a causative role. Human exposure studies, animal models, and tissue or cellular studies provide further information on mechanisms of response but also have inherent limitations. The aim of this rostrum is to review the relevant publications that provide the appropriate context for assessing the risks of air pollution relative to other more modifiable environmental factors in patients with allergic airways disease.

These parameters were developed by the Joint Task Force on Practice Parameters, representing 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. The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing the "Stinging insect hypersensitivity: A Practice Parameter Update." Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients.

Sheldon L. Spector, MD; Richard A. Nicklas, MD; Jean A. Chapman, MD; I. Leonard Bernstein, MD;William E. Berger, MD; Joann Blessing-Moore, MD; Mark S. Dykewicz, MD;Stanley M. Fineman, MD; Rufus E. Lee, MD; James T. Li, MD, PhD; Jay M. Portnoy, MD;Diane E. Schuller, MD; David Lang, MD; and Stephen A. Tilles, MD

Background There is limited information pertaining to clinical outcomes and economic consequences of natural rubber latex (NRL) allergy in health care workers (HCWs). Objectives To evaluate retrospectively health and economic outcomes in HCWs identified with NRL allergy and percutaneous reactivity to NRL. Methods Sixty-seven HCWs with NRL allergy, confirmed by percutaneous reactivity to non-ammoniated latex (NAL) extract, were administered a detailed questionnaire to evaluate clinical and economic outcomes of active work and environmental interventions subsequent to recognition of work-related symptoms associated with NRL gloves. Results Diagnoses based on predetermined case definitions associated with direct or indirect exposure to NRL gloves included contact urticaria in 67 (100%); work-related rhinitis in 23; work-related asthma symptoms in 25; and work-related anaphylaxis in 4 workers. Work related symptoms reportedly resolved in 44 of 49 (90%) of NAL skin test-positive workers who had reported skin, respiratory, and/or systematic symptoms and remained in their current work area and who switched to non-NRL gloves. Four of 24 (17%) workers with work-related asthma symptoms were compelled to change employment to NRL-safe workplaces, resulting in a mean 24% reduction in annual income. Conclusions Clinical outcomes in this group of HCWs with NRL allergy were favorable after institution of interventions but incurred deleterious consequences in a minority of workers.

Background Topical nasal solution and suspension delivery systems are available for short- and long-acting vasoconstrictors, ipratropium, cromolyn, azelastine, and glucocorticosteroids. The use of intranasal glucocorticosteroids has increased substantially because the efficacy of these agents has been well established for the treatment of perennial and seasonal allergic rhinitis. Adverse local effects of burning, irritation, and dryness are occasionally associated with glucocorticosteroid nasal preparations. Benzalkonium chloride (BKC) is a quaternary ammonium antimicrobial agent included in some nasal solutions (including glucocorticosteroids) to prevent the growth of bacteria. Some reports suggest that BKC in nasal sprays may cause adverse effects, including reduced mucociliary transport, rhinitis medicamentosa, and neutrophil dysfunction. Objective This article summarizes recent literature about possible adverse biologic effects associated with BKC as a nasal spray preservative by examining its effects on the following properties of mucociliary transport: ciliary motion, ciliary form, ciliary beat frequency, electron microscopy, and particle movement/saccharin clearance tests. Conclusion Both animal and human in vitro data suggest that BKC promotes ciliostasis and reduction in mucociliary transport that may be partially masked by absorption and dilution effects occurring in respiratory mucus. These possible confounding factors may account for several disparate human in vivo results. The use of BKC-free glucocorticosteroid formulations should be considered, particularly in patients who complain of nasal burning, dryness, or irritation.

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.

Background: We performed a cost-benefit analysis of a previously described self-management program for adult asthma. Methods: Direct and indirect cost data from 47 subjects who participated in the self-management program were analyzed. In particular, costs incurred by the subjects 1 year before participation were compared with costs incurred 1 year after participation. Results: The cost-benefit analysis indicated that the program was beneficial, reducing the cost of asthma to each patient by $475.29. The benefit came primarily from reductions in hospital admissions (reduced from $18,488 to $1538) and income lost as a result of asthma (reduced from $11,593 to $4589). The asthma self-management program cost $208.33 per patient. Comparison of the program cost with the program benefit produced a 1:2.28 cost-benefit ratio, demonstrating that the program more than paid for itself. Conclusion: A self-management program for adult asthma effectively reduced the cost associated with asthma. The findings are especially salient because the subjects' asthma was generally under good medical control when they participated in the program. The savings were therefore not the result of improved medical treatment; medical treatment was a controlled parameter, not a variable, in the self-management study. The self-management program for adult asthma was cost-beneficial. (J ALLERGY CLIN IMMUNOL 1995;95:672-76.)

A 26-year-old man employed in a company which manufactured hen egg white derived lysozyme for use in the pharmaceutical industry was evaluated for occupational asthma. The worker began to experience immediate-onset asthmatic symptoms two months after starting to work with egg lysozyme powder. The work process involved the production of approximately 1,000 kg of purified dried lysozyme powder per week. Prick skin testing was positive to egg lysozyme (50 mg/ml) and other egg protein components, but negative to whole egg white and egg yolk reagents. Serum specific IgE to egg lysozyme was documented. Decrements in serial peak expiratory flow rates were associated with lysozyme exposure at work. A specific bronchoprovocation challenge to lysozyme powder was positive demonstrating an isolated immediate asthmatic response (48 percent decrease from baseline FEV1). This is the first reported case of lysozyme-induced asthma specifically caused by inhalational exposure to egg lysozyme.

Single blind allergen (Ag) and saline solution bronchial challenges were performed on two successive study days in ten asthmatic subjects. Histamine challenges were performed before, at approximately 2 h (or after resolution of the immediate bronchial response [IR]), and 24 h after saline solution or Ag inhalation. Specific airway conductance (SGaw) was measured after delivery of challenge agents until a 50 percent fall in SGaw was observed. The SGaw was monitored over 8 h for immediate and late asthmatic responses (LAR). Results were expressed as provocative concentrations eliciting a 50 percent decrease in SGaw (SGawPC50HIS). No significant changes from baseline SGaw or SGawPC50HIS were demonstrated after saline solution. Eight subjects (dual reactors) exhibited both an IR and LAR after Ag and two had isolated IRs. Of the eight dual reactors, five had greater than 50 percent decreases in SGawPC50HIS immediately after resolution of the IR and six exhibited such decrements 24 h after Ag provocation. Mean baseline SGawPC50HIS (N = 10) on the Ag challenge day was 3.2 +/- 4.59 mg/ml and decreased to 0.92 +/- 4.56 mg/ml at 102 to 187 minutes after Ag (p = 0.0009) and was significantly decreased from baseline at 1.47 +/- 3.8 mg/ml 24 h after Ag (p = 0.0004). One of the two patients with isolated IR also showed an early onset increase in airway responsiveness (EOR). There was a significant correlation between the percentage of fall from baseline in SGawPC50HIS immediately after the IR and that at 24 h after Ag (r = 0.811, p = 0.005). There was no significant correlation between the decrease in SGawPC50HIS after the IR and the magnitude of the LAR. These data suggest that (1) the early events occurring prior to the LAR may determine changes in airway responsiveness observed at 24 h after Ag challenge, and (2) the EAR to histamine is not exclusively associated with the LAR.

A 24-year-old white woman reported sexual intercourse-related pruritus, hives, wheezing, and dyspnea within 5 minutes after ejaculation. Systemic reactions (SRs) were prevented by use of condoms. Prick testing confirmed sensitization to five Sephadex G-100-separated fractions of her husband's seminal plasma. The intradermal end point threshold concentrations (ETC) were 10 −4 and 10 −1 μg of protein per milliliter to fractions 2 and 3, respectively. Leukocyte histamine release studies exhibited 100% release to fraction 2 and 37% release to fraction 3. A 2-day protocol of rapid immunotherapy (IT) was performed with subcutaneous incremental doses of human seminal plasma (HuSePl) fractions 2 and 3. The patient experienced an SR after receiving a cumulative dose of 38.55 μg of fraction 2 on day 1. On day 2, rapid IT with fraction 2 was administered until the patient experienced a mild SR after havin received a cumulative dose of 102.8 μg. There was a one-log 10 increase in the intradermal ETC to both fractions 2 and 3 at the end of day 2. It was continued three times weekly for 4 months until the patient tolerated 100 μg doses of both fractions 2 and 3. At 4 months, coitus was resumed without SRs, and HuSePl IT was stopped. The intradermal ETC to fractions 1, 3, 4, and 5 was increased 6 months after cessation of HuSePl injections, but there was a one-log decrease in the ETC to fraction 2. Our experience demonstrated that systemic tolerance can be achieved by parenteral administration of selected HuSePl fractions. Partial immunologic desensitization of patients with anaphylactic sensitivity can be achieved. This appears to be selective for most, but not all, allergenic fractions contained in HuSePl.

A cross-sectional evaluation was performed of workers in a steel foundry in which methylene diphenyldiisocyanate (MDI) was used as a component of a binder system used to make cores and molds. Preshift and postshift spirometry and clinical evaluations were performed on 26 currently exposed (group I), on six formerly exposed (group II), and on 14 nonexposed workers to MDI (group III). Serum samples were assayed for total antibody binding, specific IgG by ELISA, and specific IgE by the RAST method to MDI-human serum albumin (HSA). Symptoms compatible with occupational asthma were elicited from seven (27%) of 26 group I workers and from three of six group II workers. No symptoms were reported by group III workers. Intrashift change in FEV1 (a mean decrease of 0.049 L) in group I workers was significantly decreased compared to that in unexposed group III workers (a mean increase of 65 ml; p = 0.043). Specific IgG and total antibody responses to MDI-HSA were detected only in workers with current or former exposure to MDI. Only one worker was identified with IgE-mediated occupational asthma exhibiting a positive prick test and elevated RAST to MDI-HSA of 25.5% bound. In this occupational setting, polyclonal immune responses to MDI-HSA and clinical sensitization to MDI were demonstrated to occur.

We assessed the effect of prednisone pretreatment (50 mg/day for three days) on the development of the early increase in histamine reactivity that occurs soon after resolution of the immediate response in allergic humans. Four allergic subjects who were known to develop only isolated immediate responses upon Kentucky bluegrass inhalation, as well as four mild allergic asthmatic subjects known to develop typical dual phase responses, were evaluated. All testing was done more than nine weeks after the grass pollen season had ended. Allergen inhalation produced an immediate response in all subjects. However, upon resolution of the immediate response to allergen in these pretreated subjects, the PC 200 His in all dual responding asthmatics and in three of the four isolated immediate responders had substantially increased above baseline values. We conclude that prednisone pretreatment leads to histaminic hypor eactivity soon after resolution of the immediate allergic response in both dual responding asthmatics and isolated immediate responders. It would seem that this prednisone effect is independent of its potential influence on the influx of inflammatory cells into diseased airways. (Chest 1989; 95:314-19) PC 200 His = dose of histamine that doubled SRaw; EOR=early onset increase in airway reactivity.

The potential hazards of biological products contaminated by asbestos fibers are quite properly being reviewed by the food and pharmaceutical industries. We have demonstrated that glycerinated saline solutions can be contaminated with asbestos fibers under certain conditions of simulated clinical use of asbestos-packed syringes. Because the fibrogenic and carcinogenic effects of asbestos are subtle and may not be manifest for a long latent period, the future use of asbestos-containing materials in allergy practice might be more harmful than now realized.

Cromolyn sodium has matured as a first-line drug in the management of asthma in the United States. New pharmacokinetic assays reveal that it exerts classic dose-response effects both in vitro and in vivo. The protective effect of cromolyn sodium is due chiefly to its ability to inhibit mediator release from mast cells, but there is considerable evidence that it may affect reflex-induced asthma and bronchial hyperreactivity. It may also reduce the number of inflammatory effector cells such as eosinophils and decrease the IgE-mediated local immune response. Two formulations are currently available in the United States: the powdered Spinhaler apparatus and a solution that can be aerosolized by a nebulizer. A metered-dose aerosol preparation containing 1 mg/drug per activation is being investigated in other parts of the world and appears to be equally as effective as the powdered and nebulized forms of cromolyn. Recent controlled studies reveal that cromolyn sodium and theophylline have equal efficacy in the first-line management of asthma, but troublesome cardiovascular and psychoneurologic side effects are often observed after theophylline therapy. If used properly, cromolyn sodium is a valuable agent in the pharmacologic treatment of asthma.

Four new isolates, identified as Alternaria tenuis, 34–016, 34–039, 35–056 and 35–193 were grown on revised tobacco medium. Mycelial and broth extracts were prepared and their biochemical and immunological properties were examined. Compared to the mycelial extracts, the four broth extracts had lower protein contents and showed fewer protein bands in isoelectric focusing, crossed-immunoelectrophoresis and sodium dodecylsulphate polyacrylamide gel electrophoresis. However, direct radioallergosorbent and passive cutaneous anaphylaxis tests with mouse IgE revealed that mycelial and broth extracts were of similar potency and had extensive cross-reactivity. In crossed-radioimmunoelectrophoresis using human atopic sera, the mycelial extracts showed 1–2 dominant and 3–4 minor allergens while the broth extracts had one dominant and one minor allergen. In RAST inhibition tests, two isolates, 34–039 and 35–056, had 100-fold more allergen content in the broth extracts compared to the mycelial extracts, where...

Triamcinolone acetonide aerosol (TAA) and a placebo aerosol were compared in a six-week, double-blind multicenter study. Ninety-six steroid-independent asthmatic patients were randomized into two parallel groups. Each patient was evaluated weekly. After four weeks of treatment, those patients treated with TAA showed highly significant (P 1 , FVC, and FEF25-75%) and in asthmatic symptoms, whereas no significant improvement was observed in those patients who received placebo aerosol. In the TAA-treated patients, 78 percent were rated with an excellent or good response, compared with 24 percent in the placebo patients. During the subsequent one-week washout period, mean pulmonary function test values of the TAA-treated group were significantly reduced (P