Harold S. Novey

Role of Altemaria and Penicillium spores in the pathogenesis of asthma

The ability to harvest spore-rich isolates of molds permitted quantitative studies of their role in the pathogenesis of asthma. Alternaria and Penicillium were selected as examples of ubiquitous molds that readily induce IgE antibodies and are of contrasting sizes. Extracts from those spores were prepared for skin tests and aerosol bronchial challenges. Intact spores were used in the same subjects in bronchial challenges delivered by a Spinhaler. Seven patients with a history of mild asthma received a total of 16 bronchial challenges with the mold to which they had been sensitized. Provocative doses in spore equivalents for a 35% drop in SGaw, 20% drop in FEV1, or 25% drop in PEFR were sought for each challenge. Density dependence-flow rates were also determined. Environmental spore survey data were obtained and compared with the challenge doses for these spores. It was found that immediate-type asthma was readily provoked by both whole spores and by their extracts, in some subjects fewer intact than extracted spores were required, delayed-type asthma occurred only after whole spore challenges, SGaw was the most sensitive and equally specific of the pulmonary function tests, and provocative doses of spore equivalents were within natural exposure ranges. The study confirmed that Alternaria and Penicillium spores in relatively natural states and numbers were potent immunopathogens for asthma.

Asthma and IgE antibodies induced by chromium and nickel salts

Metal plating with chromium and nickel has secured an occupational relation with asthma for which an allergic basis has been postulated but not confirmed. A worker who developed de novo asthma after plating with nickel and chromium but not other metals was subjected to inhalational challenge and immunoserologic tests to evaluate this association. He developed acute asthma to chromium sulfate and a biphasic asthma-like response to nickel sulfate. Radioimmunoassays incorporating the challenge materials revealed specific IgE antibodies to the provocative agents but not to another metal, gold, which he could tolerate. The findings support the postulates that bronchial reactivity can be specifically induced by fumes of metallic salts, even in a previously nonallergic individual, and that an IgE type I immunopathogenic mechanism is involved.

Postprandial exercise-induced anaphylaxis

A variety of systemic reactions associated with exercise are increasingly being recognized. We studied an atopic individual whose job-related activities involved strenuous running that often terminated in an episode of syncope and hypotension preceded by cutaneous pruritus, warmth, urticaria, and angioedema. These attacks occurred only after meals, but no foods appeared to elicit symptoms without subsequent exercise. The subject underwent three exercise challenges in the laboratory under the following conditions: (1) fasting state, with heat-dissipating clothing. (2) fasting, with heat-retention clothes, and (3) after a meal. Blood pressure decreases and minimum skin reactivity were observed for (1) and (2), and reproduction of syncope, hypotension, and further cutaneous manifestation were observed only after (3). Venous and arterial plasma determinations for complement activation (C4, C4d, and CH50) and histamine before, during, and after exercise were not abnormal. Although other vasodepressor mediators may have been liberated, at least part of the mechanism for postprandial exercise-related syncope may be attributed to a shift of blood flow to the splanchnic as well as skeletal muscle vasculature.

Papain-induced asthma—physiological and immunological features

Increasing reports of respiratory disease associated with exposure to papain prompted clinical, physiological, and immunological studies of the supervisor of a meat tenderizer factory who developed asthma after long-term contact with papain dust. His symptoms were worse at work and better on weekends and vacations. Bronchial inhalation challenges produced both immediate and late asthma to papain but not to the other ingredients in the food product. Immunological studies revealed the presence of specific IgE antibodies by direct and passive transfer skin tests and the radioallergosorbent test, and specific precipitating antibodies by immunodiffusion tests. These findings are indicative of a dual type I and III hypersensitivity. Papain acting as an allergen in an occupational setting is a risk factor for eliciting asthma even in a nontropic individual.

Transcendental Meditation and Asthma

A 6-month study with crossover at 3 months was designed to evaluate the possible beneficial effects of transcendental meditation upon bronchial asthma. 21 patients kept daily diaries of symptoms and medications and answered questionnaires at the end of the study and 6 months later. Other measurements included physician evaluation, pulmonary function testing, and galvanic skin resistance. The results indicated that transcendental meditation is a useful adjunct in treating asthma.

Cardiopulmonary effects of long-term bronchodilator administration

Because of reports of drug tolerance occurring with chronic use of adrenergic agents in asthma, we investigated cardiopulmonary responsiveness to ephedrine and to the beta-2 agent, tebutaline, following chronic drug administration for periods up to one year. With chronic drug administration baseline (prior to daily medication) FEV increased 19% in the terbutaline group and 3.5% in the ephedrine group. An additional increase of FEV above baseline of 23% for terbutaline and 12% for ephedrine was noted after daily medication. Terbutaline also had a longer duration of effect; peak response after ephedrine occurred at 2 hr while terbutaline effect was maximal at 3 to 4 hr. There was no evidence for reduced responsiveness to the bronchodilator actions of either drug at any time. Despite prolonged use, both drugs continue to increase heart rate and pulse pressure moderately following ingestion, with a peak effect occurring at 3 hr; however, pulse pressure widened after terbutaline because of a diastolic fall, while the major effect of ephedrine was to increase systolic pressure. Baseline blood pressure, particularly diastolic, declined progressively with continued drug use. No evidence of cardiac, ehpatic, renal, or ophthalmologic toxicity or change in need for other bronchodilator agents was noted during the study with either drug.

Pulmonary disease in workers exposed to papain: clinico-physiological and immunological studies.

Of the twenty‐three employees at a pharmaceutical plant manufacturing a new product containing papain, twelve had respiratory symptoms of cough, wheezing, dyspnoea, or chest paint. Most were studied with in‐depth interviews by a doctor, extensive pulmonary function tests, and imnunoserological tests for IgE and precipitating antibodies specific for papain, as well as total IgE levels and IgE antibodies to common natural allergens.

Bronchocentric granulomatosis: A complication of allergic bronchopulmonary aspergillosis☆

Hypersensitivity to the fungal antigens of Aspergillus fumigatus may result in a spectrum of immune injury collectively known as allergic bronchopulmonary aspergillosis (ABPA). This report describes a 14-yr-old boy who presented clinical findings consistent with ABPA,including a history of asthma, blood eosinophilia, serum precipitins, and IgE antibodies to Aspergillus fumigatus. Sputum Aspergillus, pulmonary infiltrates, and dual types I and III skin reactions to Aspergillus fumigatus were observed also. Pathology of the resected right upper lobe revealed severe bronchial destruction with the findings of bronchocentric granulomatosis. Noninvasive septate fungal hyphae compatible with Aspergillus were identified. Cultures from sputum and surgical specimens grew Aspergillus and Mycobacterium intracellulare avium. The PPD-B (purified protein derivative-Batty) intradermal skin test produced a 6 mm induration (PPD-S was negative). The patients condition has been well controlled with prednisone and several antituberculous drugs. In addition, inflammatory and immunologic parameters have begun to return to normal. The relationship between ABa and the atypical mycobacterial infection is not clear. The association of ABPA with the severe bronchial destruction seen in bronchocentric granulomatosis is emphasized to alert physicans to this serious sequelae of ABa seen in the asthmatic.

A device for overcoming discoordination with metered-dose inhalers

BACKGROUND Despite widespread acceptance of metered-dose inhalers (MDIs) in the treatment of asthma, many patients fail to operate these devices correctly. Inability to properly coordinate activation with onset of inhalation is regarded as the major factor in suboptimal MDI therapy. METHODS We evaluated Autohaler Inhalation Device (3M Pharmaceuticals, St. Paul, Minn.), a breath-activated MDI that is typically activated at a triggering flow rate of approximately 0.5 L/sec. We compared bronchodilator effect of pirbuterol acetate (Maxair), inhaled from Autohaler and a standard MDI, under conditions that ensured optimal technique in 20 patients with asthma. Spirometric variables (forced expiratory volume in 1 second [FEV1], forced expiratory flow between 25% and 75% of vital capacity [FEF25-75], forced vital capacity [FVC]) were measured before and at 15, 30, 60, and 90 minutes after two inhalations of full inspiratory reserve volume for each device. RESULTS Both devices produced significant and similar bronchodilation. Mean FEV1 increased 32% above baseline 60 minutes after use of Autohaler and 31% after use of a standard MDI. Similar changes were noted in FEF25-75 and FVC for the two devices. Differences between devices for all spirometric variables were not statistically significant. CONCLUSION Autohaler provides a promising alternative to the standard MDI by overcoming breath-hand discoordination.

Hypersensitivity angiitis caused by fumes from heat-activated photocopy paper.

A 53-year-old librarian had recurrent palpable purpura on her ankles and legs that was found to be caused by the fumes released from heat-activated photocopy paper at her place of employment. Behenic acid was identified as the responsible chemical component through a series of challenge studies that simulated her work exposure. Behenic acid, a fatty acid, is volatilized when heat-activated photocopy paper is developed. Absorption through the upper respiratory mucosa was the likely route of entry of this agent. The mechanism of this reaction is unclear. Skin biopsies, complement studies, and immune complex assays failed to confirm a type III immune response. Physicians should be aware that chemical fumes released from microfilm copying machines or other devices that use heat-activated photocopy paper may cause palpable purpura.