Use of ipratropium bromide in asthma. Results of a multi-clinic study.

A multi-center, double-blind, 90-day study compared an ipratropium bromide metered-dose inhaler (40 microgram four times a day) with a metaproterenol metered-dose inhaler (1,500 micrograms four times a day) in 164 patients with asthma; of the 144 patients who completed the study, 71 received ipratropium and 73 received metaproterenol. Our results suggest that both drugs were equally effective bronchodilators. Although the shape of the pulmonary function response curves suggested that ipratropium has different bronchodilator kinetics than metaproterenol (in that it has a slower onset of action and a more prolonged duration), comparison of the areas under the curves for the two drugs showed that there was no statistical difference between ipratropium or metaproterenol. The only significant side effects noted with ipratropium were cough and exacerbation of symptoms; no anticholinergic side effects were noted.

Efficacy and safety of triamcinolone acetonide aerosol in chronic asthma. Results of a multicenter, short-term controlled and long-term open study.

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 less than 0.001) improvement from baseline in pulmonary function tests (FEV1, 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 wtih 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 less than 0.0001). Eighty-eight patients continued into the one-year, open-label phase of the study. Highly significant (P less than 0.001) improvement from baseline was observed in pulmonary function tests and in asthmatic symptoms at each bimonthly evaluation during the 12-month segment. Mean plasma-cortisol level changes were not statistically significant. At the end of the long-term study, the performance of TAA was subjectively rated by the investigators (excellent or good in 92 percent of the patients) and by the patients (excellent or good in 89 percent). Mild-to-moderate adverse reactions (sore throat, hoarseness) were reported by six patients during the six-week phase and by ten patients during the 12-month phase. Thus, TAA was a safe and effective treatment in this series of bronchial asthma patients.

Assessment of tachyphylaxis following prolonged therapy of asthma with inhaled albuterol aerosol.

Controversy exists concerning possible tachyphylaxis of the acute bronchodilating effect of albuterol, especially with regard to the duration of its acute bronchodilating action. We evaluated 140 patients with bronchial asthma in a prospective double-blind controlled study of possible tachyphylaxis to albuterol aerosol as compared to isoproterenol aerosol. We demonstrated statistically significant tachyphylaxis with regard to duration of acute bronchodilating effect. We believe that this tachyphylaxis is not clinically significant because there was no tachyphylaxis with regard to peak bronchodilating effect and because the duration of bronchodilating effect remains significantly greater, both quantitatively and statistically, when compared to isoproterenol aerosol. Moreover, it appeared that most of the tachyphylaxis was present at four weeks of therapy. There was a small increment of tachyphylaxis after eight weeks of therapy, but no further increase in tachyphylaxis was demonstrated after 13 weeks of inhaled albuterol therapy. We therefore feel that clinically significant tachyphylaxis to inhaled albuterol aerosol must be quite unusual and that chronic therapy with inhaled albuterol aerosol is probably both safe and efficacious for bronchospastic disorders.

Alternative drug therapy for asthma.

Individualized management of asthma requires consideration of single or combined pharmacologic alternatives. This article reviews experimental and clinical data on the efficacy, safety, mode of action, and therapeutic indications for cromolyn and related inhalational compounds; ketotifen; alpha-adrenergic blockers; calcium-channel blockers; nonsteroidal anti-inflammatory drugs; and such diverse agents as immunosuppressive drugs, ether, alcohol, ascorbic acid, and other nutritional substances.

Controlled assessment of oral bronchodilators for asthmatic children.

Various pulmonary function changes were determined in twenty paediatric patients after a single oral dose of theophylline, ephedrine, or their combination in a double-blind crossover study. The possible contributions of guaifenesin and butabarbital, components of some formulations in clinical use, were also examined. Bronchodilatory efficacy in decreasing order, when compared to placebo, was observed for theophylline-ephedrine and theophylline (nearly comparable), and for ephedrine-butabarbital and ephedrine (nearly comparable). Butabarbital and guaifenesin did not enhance or decrease bronchodilatory effect. Adverse reactions appeared to be more frequently related to ephedrine intake, although no serious reactions were noted.

Pine nut allergy in perspective.

Anaphylaxis and other acute allergic reactions following the ingestion of pine--or pinon--nuts are documented and reviewed in perspective. Systemic allergic reactions to other relatively uncommon or "exotic" foods are also considered. Although hypersensitivity to more than one type of "nuts" is reported by some individuals, no significant cross-reactivity between any of these, or between pine pollen, pine resin, and pine nuts has been demonstrated.

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.

Pharmacodynamic and spirometric responses to a sustained-release theophylline capsule.

A prolonged therapeutic effect following a single oral dose of theophylline and maintenance of an adequate therapeutic blood level of theophylline is an important factor in the management of chronic bronchial asthma. Eighteen adult asthmatics, nine of whom were females and nine males, aged between 21-53 years, were given a sustained release theophylline capsule, 250 mg, every 12 hours and pulmonary mechanical functions as well as serum theophylline levels were studied. All patients received Elixophyllin Elixir, 250 mg, and their serum level as well as pulmonary functions were studied and compared to those after receiving the sustained release capsules. In these patients, after isoproterenol inhalation, an average of 25.6% improvement in FEV1 was observed while after placebo there were very minimum changes. At the steady-state of sustained release theophylline capsule administration, an average of 20% improvement of FEV1 was observed at the five hour period and sufficient bronchodilation expressed as FEV1 was observed for a 10-12 hour period. Indeed, a sustained release theophylline capsule fulfilled the requirement that it adequately maintained therapeutic theophylline level of the blood and improved bronchodilation lasting up to 12 hours.

Acetaminophen and aspirin challenges in subgroups of asthmatics.

To determine whether the different modes of action of aspirin and acetaminophen are associated with different incidences of bronchoconstriction, and whether there is cross-reactivity in terms of intolerance, selected asthmatics were challenged with both analgesics. Clinical profiles were observed to characterize more precisely the aspirin-intolerant asthmatic. Inhalational challenges with PGF2 alpha were then performed on nine selected subjects. It was determined that a positive history of aspirin intolerance is a reliable indicator of potential for anaphylactoid reactions but is not associated with any detectable risk of acetaminophen intolerance. Inhalational PGF2 alpha tends to involve the larger airways; oral aspirin affects both large and small airways.

Controlled comparison of anew antihistamine-decongestant combination to its individual components.

A new antihistamine-decongestant combination tablet, containing azatadine maleate and pseudoephedrine sulfate, was compared to its individual ingredients and also to placebo, in a double-blind, randomized parallel-group clinical study. Two patient groups were treated, one with seasonal allergic rhinitis for two days during the peak of the ragweed season, and another with perennial allergic rhinitis for an extended six-week period. In both groups the combination was found better than its single components, and all three treatments better than placebo, in relieving the symptoms of allergic rhinitis. A few patients reported a transient drowsiness attributable to azatadine.

Controlled trial of bronchodilator-mucolytic aerosols, combined and separate.

In seven of 30 ambulatory asthmatics the inhalation of 10% acetylcysteine reduced the FEV1 by more than 10% (range: 14% to 53%). Inclusion of isoproterenol (0.05%) reversed this depression over the entire trial in six of these subjects, while the seventh responded similarly except for the last measurement. It is concluded that the addition of isoproterenol to an acetylcysteine aerosol in the above ratio can eliminate the ventilatory impairment induced by the latter and is therefore indicated for those patients with chronic obstructive lung disease who benefit from a mucolytic agent.

Pharmacologic modification of induced asthma.

Oral adrenergic substances (e.g., ephedrine) and phosphodiesterase inhibitors (e.g., theophylline) can have a prophylactic effect on natural or experimentally induced asthma by maintaining high levels of cyclic AMP in the target organ cells. This controlled, double-blind study evaluates these drugs alone and in a standard dosage combination in blocking asthma induced by the inhalation of pollen allergens among highly selected patients. The results support the claim that oral adrenergic drugs and xanthines can be useful in the prophylaxis of asthma.