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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.

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.

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.

Background: The presence of IgE-mediated occupational respiratory sensitization to microbial enzymes has been well documented in a variety of industries. Aspergillus oryzae -derived lactase is used as a dietary aid for patients with lactose intolerance., Objective: In 1993, a cross-sectional survey of 94 pharmaceutical workers exposed to lactase for a mean duration of 23 months and 24 nonexposed recently hired employees was initiated to identify lactase-sensitized workers and potential risk factors that could be used in making recommendations for preventing future cases of lactase sensitization., Methods: The survey included a physician-administered questionnaire, skin prick testing to lactase enzyme and a panel of common aeroallergens, and spirometry., Results: Twenty-seven of 94 lactase-exposed workers (29%) had positive skin test responses to lactase. These workers were 9 times more likely to have upper or lower respiratory symptoms compared with workers with negative skin test responses. Atopic workers were 4 times more likely to have lactase skin sensitivity than nonatopic workers. However, atopy was not a risk factor for the development of upper and/or lower respiratory symptoms. Lactase skin reactivity was not observed in the 24 nonexposed employees., Conclusion: This cross-sectional survey revealed that atopic workers were more likely to have lactase sensitization and that lactase-sensitized workers were more likely to have upper and/or lower respiratory symptoms, but atopy was not a risk factor for upper or lower respiratory symptoms. In spite of these findings, the company allowed only nonatopic, nonlactase-sensitized workers to continue working in high lactase-exposure areas with careful symptom monitoring and use of protective clothing. Although this strategy was successful in total prevention of new cases of occupational respiratory disease after 5 years, the results of this cross-sectional survey do not support exclusion of atopic workers from working with industrial enzymes.

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.

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 > or = 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 < 0.001). In all treated patients, including those who did and did not complete the trial, significant reduction (> or = 50% of baseline) in oral corticosteroid dosage was achieved in the auranofin group (60%) compared with the placebo group (32%) (p < 0.001). There were no significant differences between treatment groups in symptoms, concomitant medication use, or lung function. Mean serum total IgE levels decreased significantly from baseline in the auranofin group (-44.63 IU/ml) compared with the placebo group (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.

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.

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.

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.

The quaternary amine, benzalkonium chloride, has been associated with cutaneous and mucosal delayed hypersensitivity reactions and with paradoxical bronchoconstriction after use of aerosolized asthma medications. Until now, quaternary amines have not been reported to cause occupational asthma. We describe a case of occupational asthma caused by prolonged exposure to a cleaning solution containing benzalkonium chloride in the workplace. Single-blind, placebo-controlled, open-room challenges were performed to determine the specific agent responsible for the patient's symptoms. Pulmonary function and epicutaneous challenge tests were also performed. The patient had positive responses to challenges with a liquid toilet bowl cleaner containing benzalkonium chloride but was unreactive to other agents tested. Removal from the workplace resulted in complete resolution of symptoms. The exact mechanisms responsible for occupational asthma induced by quaternary amines remain unknown; however, this case emphasizes the importance of recognizing reactive chemicals as possible causes.

Background: Diisocyanate chemicals are leading causes of occupational asthma (OA)., Methods: We conducted a cross-sectional study of 243 workers exposed to diphenylmethane diisocyanate (MDI) in a urethane mold plant that had been designed to minimize MDI exposure (levels were maintained below 0.005 ppm and were continuously monitored). All participants were screened by questionnaire and tests for serum antibodies to MDI-human serum albumin (HSA). On the basis of questionnaire responses, diagnoses were derived that included OA; non-OA; work-related and non-work-related rhinitis; and lower respiratory irritant responses. Serial peak expiratory flow rate studies were performed for 2 weeks in 43 workers with and in 23 workers without lower respiratory symptoms., Results: Results of serial peak expiratory flow rate studies were abnormal in 3 (33%) of 9 workers with OA, in 2 (50%) of 4 with non-OA, and in 2 (9%) of 23 case control subjects. A significant association was found between peak flow rate variability and a questionnaire asthma diagnosis (chi 2 p < 0.002). Physicians confirmed three cases of OA, one of which occurred in a control worker who was free of symptoms. In all three cases asthma symptoms remitted after the worker left the workplace. Serum specific IgE and IgG levels were elevated in 2 of 243 workers, one of whom was prick test positive to MDI-HSA and had had cutaneous anaphylaxis after MDI exposure., Conclusions: On the basis of these cases, specific work activities associated with exposure to MDI were identified and corrective measures were instituted. Strict control and monitoring of ambient MDI exposure was associated with a low prevalence of specific sensitization to MDI and a lower than expected prevalence of OA.

The density and species prevalence of dust mites were determined at various times over a 5-year-period in 252 homes of dust mite sensitive people with asthma who lived in eight geographic areas of the United States (Cincinnati, Ohio; New Orleans, La.; Memphis, Tenn.; Galveston, Texas; Greenville, N.C.; Delray Beach, Fla.; San Diego and Los Angeles, Calif.). The most common dust mites found in the homes were Dermatophagoides farinae (DF), D. pteronyssinus (DP), Euroglyphus maynei (EM), and Blomia tropicalis. All homes in all locations contained Dermatophagoides spp. mites, but few homes were populated exclusively by either DF or DP alone. Most homes (81.7%) were coinhabitated by both DF and DP. In coinhabited homes one species was predominant and usually made up at least 75% of the total mite population. Prevalence of the dominant or only species present varied between homes within a geographic area. EM occurred in significant numbers in 35.7% of homes in New Orleans, Memphis, Galveston, Delray Beach, and San Diego. Blomia tropicalis occurred in these same cities but in low densities. For all dust samples, only 13 homes of the 252 sampled had 100 or fewer mites/gm dust, which is considered to be the threshold for sensitivity. Most homes had average mite densities of 500 or more mites/gm dust. The results of the present study suggest a significant and widespread occurrence of both DF and DP. Therefore extracts of both mite species should be considered for diagnostic tests and immunotherapy. Significant levels of EM were present in some areas. Thus sensitivity to EM should be considered in these areas.

We recently demonstrated morphine-6-hemisuccinate-human serum albumin conjugate (M-6-HS-HSA)-specific IgG in serum from ethic narcotics-manufacturing workers. In this article, we present results of epicutaneous tests to opiate compounds and lung-function studies in these same workers. Thirty-nine workers, exposed to opiates, were evaluated for possible work-related changes in lung function and were administered a questionnaire concerning opiate exposure and health history in February 1988. In December 1988, 33 employees with occupational exposure to opiates, six other workers (New Jersey referent) employed at the same factory with minimal exposure to opiate compounds, and 17 nonexposed individuals from Cincinnati, Ohio, were subjected to epicutaneous threshold testing with a panel of six opiate compounds and nine common aeroallergens. In opiate-exposed workers, significantly lower epicutaneous threshold concentrations were detected (compared to New Jersey referent and Cincinnati control subjects) for dihydrocodeine (p less than 0.01), hydrocodone (p less than 0.05), codeine (p less than 0.01), and morphine (p less than 0.05). Significant associates existed among epicutaneous threshold concentrations between the agents tested; that is, individuals with a positive morphine skin test would generally have a positive codeine skin test, etc. Atopic status (positive cutaneous test results to two or more of nine common aeroallergens) was not significantly associated (p greater than 0.05) with positive opiate skin sensitivity. Although the mean cross-shift decrements in FEV1 for all workers were nonsignificant, five opiate-exposed individuals demonstrated cross-shift decrements in FEV1 of greater than 10%. Daily maximum-minus-minimum changes in workweek PEFR (PEFRmax-min) were significantly reduced for Monday through Thursday (p less than 0.05) compared to PEFRmax-min changes during a nonwork, nonexposure 3-day weekend. Ten exposed workers demonstrated daily PEFRmax-min changes of greater than 20%, suggesting acute airway obstruction. Increased cutaneous reactivity to opiate compounds among opiate-exposed workers may reflect development of pharmacologic hyperresponsiveness to opiate compounds.

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) micrograms 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 micrograms of fraction 2 on day 1. On day 2, rapid IT with fraction 2 was administered until the patient experienced a mild SR after having received a cumulative dose of 102.8 micrograms. There was a one-log10 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 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway reactivity and disease severity were investigated in 24 subjects with stable chronic bronchial asthma. Disease severity was determined by assigning a disease severity score (DSS) representing six clinical and therapeutic parameters. Airway hyperresponsiveness was assessed in two ways: airway reactivity score (ARS) based on the number of positive responses to a question concerning exposure to 22 nonspecific inhaled irritants and methacholine challenge testing and determining the cumulative dose causing a 20% reduction in FEV2 (CMD20). A significant correlation between DDS and CMD20 (r = 0.57; p less than 0.003) and DSS and ARS (r = 0.67; p less than 0.0003) attested to the important influence of airway hyperresponsiveness on disease severity. Significant correlations for ARS with CMD20 (r = -0.60; p less than 0.002) suggested the consistency with which the ARS estimated methacholine hyperresponsiveness. We found no statistically significant correlations between DSS, ARS, or CMD20 and the age of subject, duration of asthma, or other host characteristics. There was not a significant correlation between the degree of airway obstruction and DSS or ARS noted. The results of this investigation demonstrate the value of the use of clinical information for assessing airway hyperresponsiveness and disease severity in patients with chronic stable asthma. Both ARS and DSS are useful clinical tools for estimating methacholine reactivity.

Fluocortin butyl (FCB) is a newly synthesized corticosteroid with a high ratio of topical to systemic activity. FCB was studied in a multi-center, double-blind, placebo-controlled trial of therapy of perennial rhinitis. The study was conducted between January and May 1981. Patients evaluated suffered from either chronic allergic or chronic nonallergic rhinitis or both. A total of 306 patients from 16 investigative centers were evaluated by comparing FCB to placebo. Three separate dosage regimens were employed. Patients received a total daily dose of 2, 4, or 8 mg. FCB was found to be an effective therapeutic agent. It reduced symptoms of nasal congestion, rhinorrhea, postnasal drainage, and sneezing. It also markedly reduced the use of concomitant medications (chlorpheniramine maleate and/or pseudoephedrine). Relief of symptoms was noted as early as the first week of therapy, and the degree of improvement increased progressively during the study. There was little difference between the relief produced by the 4 mg and 8 mg regimens. Both of these were superior to the 2 mg regimen. The drug was well tolerated; no significant side effects were noted.

Two strains of guinea pigs were parenterally immunized with well-characterized diisocyanate-protein conjugates. Hapten-specific IgE antibodies were detected in the sera of English short-hair strain guinea pigs immunized with either toluene diisocyanate-human serum albumin (TDI-HSA) or hexamethylene diisocyanate-HSA (HDI-HSA) when these sera were analyzed by the 168 hr passive cutaneous anaphylaxis (PCA) technique followed by intravenous challenges with conjugates of respective ligands coupled to an unrelated carrier protein, transferrin. IgG1 antibodies and precipitating antibodies were demonstrated in Hartley strain guinea pigs immunized with TDI/HDI-HSA conjugates. The hapten specificity of these antibodies was proved by PCA inhibition experiments and antibody absorption experiments. In the precipitating antibody system, this was further confirmed by immunoelectrophoretic analysis. Cross-reactivity between HDI and TDI was not observed in the PCA experiments. However, apparent cross-reactivity in the double gel diffusion experiments was due to new antigenic determinants formed by isocyanates after conjugation with proteins. It was therefore apparent that immune responses of guinea pigs immunized with protein conjugates of bifunctional isocyanates were heterogeneous and involved multiple specificities for hapten, carrier protein, and new antigenic determinants. It was postulated that the complex nature of the immune response generated by diisocyanate compounds in the guinea pig may also serve as a more appropriate model of isocyanate-induced human sensitivity reactions, which are known to involve diverse immunologic and nonimmunologic mechanisms.

A 2- to 5-hour regimen of rapid venom immunotherapy (RVIT) was administered to 33 patients with anaphylactic sensitivity to Hymenoptera venom in a hospital setting in which full emergency resuscitation equipment was available. The RVIT was administered as 10 increasing doses of each treatment venom every 10 to 15 minutes to achieve a final dose on day 1 of 58.55 micrograms per venom. Patients returned for booster venom injections of 60 micrograms on day 3, 70 micrograms on day 7, 80 micrograms on day 21, and 100 micrograms on day 35 after RVIT. Serial antigen-induced leukocyte histamine release studies were performed on day 1 in 10 patients before and after RVIT, as well as 3 1/2 months after initiation of RVIT. Of 33 patients, 32 achieved a cumulative venom dose on day 1 of at least 50 micrograms, and the entire group received a mean dose of 95.46 micrograms. Local reactions during RVIT occurred in 18 (55%) patients. Four patients (12%) experienced mild systemic reactions during or after completion of RVIT. Subsequent booster venom doses administered to 29 patients were well tolerated. A decrease in venom-induced leukocyte-histamine release from baseline was detected in three (30%) patients immediately after RVIT and in seven (70%) patients months after achieving maintenance doses. Cutaneous sensitivity decreased by at least one log10 concentration in eight (32%) of 25 patients. Twenty-two natural re-sting events occurred in 12 (50%) of 24 patients surveyed after successful completion of RVIT, of whom seven identified the insect as one for which they had been treated. No systemic reactions were reported. Results of this study indicate that RVIT is a safe, alternative method of venom administration for patients who are at immediate risk for re-sting anaphylactic episodes.

Cross-reactivity between major classes of aeroallergenic pollens has been estimated by comparing the inhibitory effects of selected allergens upon the reaginic activity of other native and non-native varieties, as measured by the radioallergosorbent technique (RAST). Common allergenic determinants were demonstrated in indigenous and nonindigenous ragween species. Although patterns of inhibitory capacity were less uniform among grass pollens, endemic species tended to have more common allergenic properties than nonendemic species. Tree pollens exhibited the greatest degree of heterogeneity, confirming the previous view that these pollens tend to be less cross-reactive. Concomitant skin test threshold studies utilizing the same groups of pollens were in general agreement with in vitro results. Because, threshold skin testing was affected by a number of uncontrollable variables, however, the current modification of RAST in estimating cross-allergenicity was more accurate and reliable than data based upon cutaneous tests. It was concluded that reagin neutralization by the RAST method is the best currently available method of assessing cross-allergenic properties of pollens.

In general, a history of exposure to "moldy" hay, birds, or other incriminated occupational or environmental inhalants in a patient with clinical and radiologic features consistent with HSP should lead to the demonstration of serum precipitins to the suspected antigen and an established diagnosis, confirmed by avoidance of the agent involved. Occasionally, other diagnostic procedures are required. The diagnosis is often difficult in domestic exposures, such as humidification and air conditioning systems. A careful environmental history is essential, and at times the physician must inspect the patient's environment personally. In most cases, the diagnosis is established if (1) the history and physical findings and pulmonary function tests indicate an interstitial lung disease, (2) the x-ray film is consistent, (3) there is exposure to a recognized cause, and (4) there is antibody to that antigen. In other exceptional circumstances, bronchoalveolar lavage may help. Biopsy is rarely needed. Special environmental studies and identification of new antigens require research facilities. Provocation tests are research procedures, not necessary for the diagnosis, and not needed in contested workmen's compensation adjudications.

Acid anhydride compounds cause IgE-mediated respiratory sensitization in the workplace. In this study reaginic responses in four workers sensitized to phthalic anhydride (PA), hexahydrophthalic (HHPA), or himic anhydride (HA) were determined by direct RAST by use of PA-human serum albumin (HSA), HPPA-HSA, and HA-HSA methylcellulose disc substrates. RAST inhibition of binding to anhydride-HSA substrates was done with various concentrations of sodium salts, lysine, and HSA conjugates of PA, HHPA, HA, and trimellitic anhydride (TMA) in order to characterize cross-reactivity and specificity of humoral responses in these workers. Molar concentrations of anhydride bound to lysine and HSA carriers were assayed by protein hydrolysis followed by gas chromatographic analysis. Significant direct RAST binding against PA-HSA, HHPA-HSA, and HA-HSA was found in all four workers. PA-HSA-IgE binding in one PA-sensitive worker (no. 1) was inhibited significantly by PA-HSA alone and not by sodium PA or PA lysine. In contrast, another PA-sensitized worker (no. 2) exhibited 50% inhibition of PA-HSA binding by PA-HSA (1 X 10(-9) M), PA-lysine (7 X 10(-8) M), and NaPA (1 X 10(-7) M); no inhibition of PA-HSA by heterologous HHPA-, HA-, or TMA-inhibitory reagents was found in either of the PA workers. RAST binding to HHPA-HSA in the HHPA-sensitive worker was inhibited by HHPA-HSA alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

The antigens and allergens in the storage mite Tyrophagus putrescentiae, commonly found in grain and hay and sometimes in house dust, were characterized by crossed immunoelectrophoresis and crossed radioimmunoelectrophoresis. Three mite extracts, T. putrescentiae (TP) mite bodies, feces, and a combination of mites, feces, and culture medium (TP + CM) were studied. TP and TP + CM (primarily feces) extracts exhibited 20 and 18 antigens, respectively. By use of serum from two skin test-positive patients, autoradiograms demonstrated TP contained two allergens and TP + CM contained five allergens, three of which probably originated from feces. CM (whole wheat flour) did not stimulate antibody production in rabbits. TP feces shared 10 antigenic determinants with TP and 14 with TP + CM. Two antigens common to TP feces and TP were also shared allergens.

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.

The efficacy and safety of astemizole (AST), a new long-acting H1 antagonist with minimal sedative or anticholinergic side effects, were studied in an 8-week double-blind trial of 51 patients with chronic idiopathic urticaria. Patients with chronic idiopathic urticaria were randomized to AST-treated (10 mg every day) or placebo-treated groups. Patients were followed at weekly intervals and evaluated for pruritus, erythema, extent of wheals, frequency of urticarial episodes, and total control of urticaria. Only three of 27 AST-treated patients stopped the double-blind phase before 8 weeks because of inadequate response as compared to 11 of 24 placebo-treated subjects (p = 0.027). On the last evaluable visit of the double-blind phase of the study, 85% of the AST-treated patients reported an excellent or good response compared to 30% of the placebo-treated group (p = 0.0001). AST-treated patients also reported significant improvement compared to placebo-treated patients in pruritus (p = 0.0001), erythema (p = 0.0001), and extent of wheals (p = 0.003). Mild sedative effects were observed in only two of 27 patients receiving AST. It was concluded that AST is a potent and safe drug for symptomatic control of chronic idiopathic urticaria.

A 24-yr-old man developed sensitization to Quillaja bark (soapbark) dust at his work place. Within 3 mo of being employed in a factory processing Quallaja bark to produce saponin, he experienced asthma symptoms while handling the bark but only nasal symptoms on being exposed to the purified saponin. Bronchial provocation using Quillaja bark dust resulted in immediate bronchoconstriction as well as faintness, diffuse erythema, and hypotension. Radioallergosorbent test (RAST) using the pulverized crude Quillaja bark was markedly positive, and cross-reactivity between gum acacia and gum tragacanth was demonstrated using this technique.

To determine the efficacy of oral gold in asthma, 20 patients with steroid-dependent asthma received auranofin at a dose of 3 mg by mouth, twice daily, in a 24-week open clinical trial. Prospective evaluation of bronchial responsiveness to methacholine was determined before and 8 and 16 weeks after initiation of auranofin therapy. Serial spirometry (FEV1 and FVC), lung volumes, and diffusing capacities (single breath carbon monoxide diffusing capacity of the lungs) were measured before and at 10 and 20 weeks after treatment. All subjects were required to record concomitant medications, symptom scores, and morning and evening peak expiratory flow rates. In vitro immunologic studies performed before and after 8 and 20 weeks of auranofin therapy included leukocyte histamine release in response to antihuman IgE, lymphocyte blast transformation in response to concanavalin A and phytohemagglutinin, and leukocyte inhibitory factor activity in response to Candida albicans and tetanus toxoid antigens. In 18 patients evaluated, there were no significant differences between baseline and posttreatment spirometry, single breath carbon monoxide diffusing capacity of the lungs, and lung volumes. At week 16 of treatment, the steroid cumulative dose or the total prednisone dose administered from 7 days before through 10 days after each methacholine test day decreased from a mean of 293 +/- 125 mg at baseline to 192 +/- 115 mg. At week 16, nine of 18 patients (50%) exhibited decreased methacholine responsiveness as defined by a more than one-half log10 increase in the concentration of methacholine causing a 20% decrease in FEV1. A significant correlation (r = 0.60) was observed between the increase in the concentration of methacholine causing a 20% decrease in FEV1 and the decrease in steroid cumulative dose after 16 weeks of treatment. Leukocyte histamine release to anti-IgE exhibited significant reductions from baseline at week 20 to 10(-2) (p less than 0.002) and at 10(-3) (p less than 0.005) dilutions. At week 20, leukocyte inhibitory factor activity in response to Candida increased from baseline at the 0.1 mg per well (p = 0.025) and 1 mg per well (p = 0.05) concentrations; similarly, the responses to tetanus toxoid increased at the 1 mg per well (p less than 0.05) and 0.1 mg per well (p less than 0.01) concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Seventy-three adult, steroid-dependent asthmatic patients participated in a 16-wk, double-blind study testing the efficacy of flunisolide aerosol. Forty received flunisolide, and 33 received placebo. The mean daily prednisone requirement of patients receiving flunisolide fell 59.2% during the testing period, and that of the patients receiving placebo fell 19.7%. The median daily prednisone dose dropped 74.4% in the flunisolide group and 4.2% in the placebo group (p = 0.006). In the flunisolide group 75% tapered use of oral steroids 50% or more, and 27.5% stopped taking oral steroids completely. In the placebo group 36% tapered use of oral steroids 50% or more, and only 12% stopped taking them completely. Despite their reduction in systemic steroids, those patients receiving flunisolide achieved significantly greater reduction in the daily severity of wheezing (p = 0.014) and frequency of asthma attacks (p = 0.049) than did those receiving placebo. In the final evaluation of therapeutic response, 70% of patients receiving flunisolide were rated as having a very good or good response, and 30% were rated as having a fair or poor response. In contrast 33% of patients receiving placebo were rated as very good or good, and 67% were rated as fair or poor (p = 0.0009). No serious reactions were reported. Plasma cortisols showed an average increase of 42.9% in the flunisolide group but no change in the placebo group. Flunisolide aerosol is a well-tolerated and effective agent in the treatment of steroid-dependent asthma.

BDE added to dry bleach have been associated with immunologic sensitization and development of clinical allergic disease in detergent workers and occasionally in consumers. However, improved dust control and modification of the manufacturing process through encapsulation of enzyme were believed to have reduced or eliminated these problems. To determine whether or not immunologic sensitization could still develop in the detergent industry, we studied employees of a dry bleach manufacturing plant that incorporated encapsulated BDE into a consumer product. We performed air sampling for enzyme dust and total particulates, administered questionnaires, conducted physical examinations, and spirometry in 13 currently exposed, two previously exposed and nine nonexposed, employees. To assess sensitization status, RAST and ELISA were performed. Air concentrations of enzyme dust ranged from 0.002 to 1.57 micrograms/m3; all of these levels were below the TLV of 3.9 micrograms/m3. Positive BDE-specific RAST results (3.4%, 4.4%, and 8.0% binding) were obtained in three of 12 currently exposed workers. Results of personal breathing-zone air sampling indicated that these workers had high dust-exposure levels. Specificity of RAST was verified by RAST inhibition with BDE. BDE-RAST binding was not significantly elevated in the nonworkers (range: 0.6% to 1.4% binding). Positive results for specific IgG by ELISA were obtained in four of 12 currently exposed and in one of two previously exposed workers but in none of the nonexposed workers. We conclude that immunologic sensitization can develop after occupational exposure to encapsulated BDE in the dry bleach industry. We have not proved, however, that this immunologic reactivity is related to clinical sensitivity.

We assessed the nature and progression of airway mucosal disease and histaminic reactivity in English short-haired guinea pigs at 2, 24, 72, 168, and 504 hours after toluene diisocyanate (TDI) exposure (4 hours of 3 ppm of TDI for 5 consecutive days). To also determine whether TDI-specific, IgE-like antibodies developed in TDI-exposed animals, passive cutaneous anaphylaxis testing was done 28 days after TDI. Bronchial reactivity was determined serially by measuring specific airway conductance as a function of increasing doses of aerosolized histamine in six exposed and three control animals studied intact and unanesthetized. The remaining 10 exposed and 10 control guinea pigs were sacrificed in groups of two at each time point to obtain airway tissue for light microscopic examination. We found that airway hyperreactivity to histamine occurred after TDI in all animals tested. It was maximal 2 hours after the 5-day exposure and remitted by 72 hours. In addition, marked airway obstruction occurred after TDI that persisted for at least 168 hours. There were dramatic signs of airway mucosal damage associated with the bronchial hyperreactivity that included substantial decreases in epithelial cilia, mucin content, and mast cells, as well as squamous metaplasia, numerous mitotic figures, and a prominent polymorphonuclear leukocytic infiltrate. Passive cutaneous anaphylaxis tests in exposed animals were negative. Our results suggest that TDI-induced bronchial hyperreactivity may be related to airway mucosal injury and inflammation.

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 patient's 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.

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.

Heterologous crossed immunoelectrophoresis (CIE) analysis demonstrated that Dermatophagoides pteronyssinus body and D. farinae body extracts contained up to 21 cross-reacting antigens (Ags). Incubation of CIE gels with two mite-sensitive individual sera and a serum pool of mite-sensitive patients indicated that up to nine cross-reacting Ags bound mite-specific IgE on crossed radioimmunoelectrophoresis and were common allergens. Likewise, heterologous CIE analysis of D. pteronyssinus feces and D. farinae feces extracts demonstrated approximately 13 cross-reacting Ags. Up to eight of these cross-reacting fecal Ags bound mite feces-specific human IgE. Additional cross antigenicity and allergenicity was evident between body extract of one species and feces extract of the other species. The amount of specific IgE binding to cross-reacting Ags in interspecific extracts varied both between and within individual sera. Different cross-reacting Ags contained potent allergens, and these varied from patient to patient. Also of major significance was the fact that body and fecal extracts of each species contained Ags and allergens that were unique and species specific.

Bitolterol mesylate, 1.0 mg, or isoproterenol hydrochloride, 1.5 mg, was administered three times daily for 3 months in a double-blind, multicenter study via closed-port, intermittent-flow, compressor-driven nebulizer system (CPIF) to 182 nonsteroid-using patients with asthma. Mean baseline FEV1 was approximately 60% of predicted normal for both groups. Pulmonary function tests and vital signs were measured before and for up to 8 hours after treatments on test days 1, 30, 60, and 90. Mean maximum increases in FEV1 were 51%, 54%, 52%, and 55% for bitolterol versus 48%, 46%, 50%, and 43% for isoproterenol on these monthly test days. The mean FEV1 response remained greater than 15% over zero time (baseline) for greater than or equal to 8 hours after medication with bitolterol on each of four monthly pulmonary function test days and 2 1/2 to 5 hours for isoproterenol. Median durations of bronchodilator activity for bitolterol were 7.3, 6.5, 6.5, and 6.0 hours versus 4.0, 1.7, 3.7, and 1.9 hours for isoproterenol on the monthly test days. On these test days, 37% to 49% of the patients treated with bitolterol had a duration of action of at least 8 hours compared with 16% to 29% after isoproterenol treatment. The onset of activity was within 5 minutes for both drugs. Bitolterol provided superior bronchodilator activity with fewer adverse effects compared with isoproterenol, and there was no evidence for drug tolerance during this 3-month study.

Sensitization to HMW allergens is a relatively common immunopathogenic factor in occupational asthma. The mechanism of sensitization is an IgE-mediated, type I reaction. High molecular weight allergen refers to proteins and polymers of organic compounds over 5 kd and usually in the 20 to 50 kd range. In most cases diagnosis requires: 1. A high index of suspicion of job-related asthma. 2. Exposure to HMW compounds and clinical findings associated with such an exposure. 3. Confirmation of sensitization by appropriate in vitro or in vivo tests. 4. Confirmation of a pathogenic role by physiologic measurements in either a natural setting or during laboratory-controlled challenges.