Constantine J. Falliers

Therapeutic and investigational evaluation of asthmatic children

Abstract Five areas commonly used in the measurement of asthma were examined. These are the clinical examination, history, pulmonary physiology, medication requirements, and school activity levels. Correlations between these measurements were possible by using two investigations in order to provide the necessary data. The value and shortcomings of each of these measures are discussed. The need for frequent observations has been shown in order to improve the low order of correlations obtained, even with those that are statistically significant. All five measurements are a requirement if research in this field is contemplated.

Aspirin and subtypes of asthma: Risk factor analysis☆

Abstract Among 1,298 children 6 to 16 years old, initially observed in a residential center for chronic asthma and subsequently followed over a 14 year period, 25 (1.9 per cent) exhibited adverse reactions (urticaria, angioedema, asthma, hypotension) to ordinary doses of aspirin. A survey of individual clinical characteristics of these patients indicated that the small group with acetylsalicylic acid (ASA) intolerance differed from the rest of the asthmatic population in several respects. Onset of asthma in the former was sudden and later (median 11 years) vs. early (median 2 years) for the rest of the patients. Girls outnumbered boys (M:F ratio 0.8 vs. 2.6); eczema was noted only in one case (4 per cent vs. 46 per cent), and personal as well as family histories for Type I, reagin-mediated allergic reactions, were mostly negative. Nasal polyps were noted in 27 per cent of the ASA reactors but in none of the other patients. On the basis of the observed concurrence, the probability (risk) of ASA reactions, atopic eczema, nasal polyposis, and a heightened familial incidence of asthma were estimated for subsets of asthmatic patients. The complexity inherent in studies of clinical phenomena with variable age of onset is recognized.

Discordant allergic manifestations in monozygotic twins: Genetic identity versus clinical, physiologic, and biochemical differences

Clinical observations, blood group genotyping, and fingerprints established with a high degree of probability the monozygosity of two pairs of twins. Medical histories, skin test reactions, biochemical studies, pulmonary function tests, and exercise and methacholine challenges of these four individuals demonstrated that monozygotic twins: (1) may show comparable wheal and erythema skin reactions and clinical sensitivity to selected inhaled substances, but can vary in allergic specificity; (2) may be clinically disordant, one twin having chronic asthma and the other not, this difference not necessarily related to allergic sensitivities and to serum IgE levels; (3) do develop marked bronchoconstriction after inhalation of methacholine if they have a history of asthma, while non-asthmatic siblings tolerate much higher doses of this parasympathomimetic drug; (4) may experience significant impairment in ventilatory function after exercise if they have had persistent chronic asthma, while the unaffected twins can exercise with impunity; (5) may show enzymatic changes in leukocyte membranes consistent with the hypothesis that hypofunction of adenyl cyclase 29 and hyperfunction of membrane transport ATPasc 35 may be acquired abnormalities related to the presence and progression of asthma. Extended observations and continuous monitoring of twins discordant with respect to asthma ought to provide additional insight into the genetics, the pathogenesis, and the frequently unpredictable variability of this intermittent obstructive airway disease.

Triamcinolone acetonide aerosols for asthma. I. Effective replacement of systemic corticosteroid therapy

Triamcinolone acetonide, a water-insoluble corticosteroid preparation in a Freon-propelled metered-dose aerosol, was administered via a specially designed nebulizer to 22 adult patients with severe, chronic asthma. All patients had required oral corticosteroid therapy, daily, for several years, in order to control their incapacitating obstructive airways disease. During 4 wk of treatment with triamcinolone acetonide, taken in 4 daily doses totaling 8 to 28 inhalations (400-1,400 mcg) per day: (1) asthma remained under satisfactory control; (2) oral corticosteroids were stopped in 19 patients and reduced in 2, and 1 patient withdrew from the study; (3) adrenal cortical function returned to normal or near normal levels; (4) spirometric and plethysmographic measurements improved significantly; (5) daily self-measurements of peak expiratory flow showed a marked improvement in median weekly levels, as well as a reduction in daily variability. No immediate undesirable side effects were noted. These observations indicated that more extensive applications of topical corticosteroid therapy are justified as an effective, convenient, and relatively safe method for the preventive management of severe, persistent asthma.

Asthma and cybernetics: (or why doesn't everyone have asthma)

Abstract The human mind, socioeconomic cycles, or the aesthetic value of a work of art cannot be understood or explained by even the most thorough fractional analysis of their component parts. Likewise, while individual disciplines can make their (often outstanding) contributions to a study of asthma by identifying specific characteristics of that state, the ultimate appreciation of this disease as a subjective experience as well as a disordered respiratory behavior will depend on our ability to approach it as an entity. Cybernetics promises to teach us how.

Assessment of oral antiasthmatic drugs by inhalation challenges

Elective inhalation of incremental doses of aerosolized allergenic extracts by sensitive subjects results in fairly reproducible bronchoconstriction and thus can be useful in the detection of etiologically significant airborne allergens. ’ 2 Another application of bronchial inhalational tests is the demonstration of a possible protection against induced bronchoconstriction by pretreatment with systemic or topical antiasthmatic drugs .:l. 4 Obviously, the meaningful interpretation of both the detective and the protective tests is entirely conditioned by (1) the criteria for the selection of subjects to be tested, (2) the type and dose of the antigens to be inhaled, and (3) the methodology and timing of the pulmonary function tests, including the question of what is defined as a “positive” immediate or late response.“-’ Furthermore, the protective effect of individual pharmacologic agents and their possible combinations can be assessed correctly only if guidelines can be established regarding (1) the dosage of the drug to be administered, (2) the route and timing of treatment, and (3) a possible dose-response range, relating the required therapeutic levels of the drug to the total amount of the inhalational antigenic challenge. It must also be recognized that, somewhat paradoxically, the clinical efficacy of certain drugs and their capacity to block inhalational challenge responses do not correlate.” For instance, corticosteroids (Table I), which are almost invariably effective in suppressing asthma, do not protect against inhalation provocation tests. On the opposite side, cromolyn sodium, which can block experimentally induced bronchoconstrictive reactions to inhaled allergens,* is therapeutically inconsistent or totally ineffective. Atropine-like, anticholinergic drugs have been the subject of conflicting reports but generally do not seem to ensure protection against bronchial challenge ,4. !) and only the adrenergic agonists and the methylxanthines appear to inhibit bronchial responses to inhaled antigens to a degree commensurate with their known clinical efficacy.” The studies to be pre-

INHALATION BRONCHIAL CHALLENGES WITH HOUSE DUST ANTIGEN: TECHNIQUE, REACTIONS, COMPARISON WITH THE RESULTS OF SKIN TESTS

The history, the physical examination, the observation of the environment, the skin tests (ST), are all factors used to decide whether or not to start immunotherapy. Routine inhalation bronchial challenges (BC) are often not performed due to i) lack of knowledge of the technique, 2) lack of equipment, 3) fear of secondary reactions, or because 4) the test is considered too time-consuming. The authors intend to show how important and easy it is to perform them and how to control the reactions when they occur. Problems described (6) are probably related to the different technique used. The equipment may be minimal. The time spent can be shortened since three tests can be done at the same time with the help of a trained technician. The authors agree with Fagerberg (4) that the results of the BC is important to decide whether or not to start immunotherapy and they recognize, as Pham et al. (5), that BC technique is not enough sensitive and that small quantitative differences in the results do not count.