Richard W. Weber

Incidence of bronchoconstriction due to aspirin, azo dyes, non-azo dyes, and preservatives in a population of perennial asthmatics

Forty-five patients with moderately severe perennial bronchial asthma were challenged by ingestion of: acetylsalicyclic acid (ASA); 4 azo dyes (tartrazine, sunset yellow, amaranth, and ponceau); 3 non-azo dyes (erythrosine, brilliant blue, and indigotin); sodium benzoate (NaB); parahydroxybenzoic acid (OHBA); butylated hydroxyanisole (BHA); and butylated hydroxytoluene (BHT). A fall in forced expiratory volume is one second (FEV1) greater than 25% from baseline was considered positive. Seven patients who gave an unequivocal history of aspirin intolerance were not challenged with ASA; an additional 13 had positive open challenges to ASA, giving an apparent incidence of aspirin sensitivity of 20/45. The presence of nasal polyps, simusitis, or the regular use of corticosteroids, either singly or in combination, was not associated with an increased incidence of reactions to ASA. Significant bronchoconstriction to open challenges with agents other than ASA was less frequent. Positive open challenges to all substances except aspirin were followed by double-blind challenges which were positive in only 3 instances: 1 each with erythrosine, ponceau, and NaB/OHBA. Our findings confirm that ASA intolerance is relatively common but suggest on the other hand that reactions to dyes and preservatives are uncommon cause of clinically significant bronchoconstriction in moderately severe perennial asthmatics.

Aerosolized terbutaline in asthmatics: development of subsensitivity with long-term administration☆

The peak response and the duration of bronchodilator effect were measured after four inhalations at 20 min intervals of 250 micrograms of aerosolized terbutaline in 13 patients with bronchial asthma. Patients were initially studied after strict avoidance of all adrenergic agents for 2 wk; they were then studied at 2 wk intervals for 12 wk while receiving 500 micrograms of aerosolized terbutaline q.i.d. The initial testing (TI) and the testing at the end of 12 wk (TII) were double blind. Both peak response and duration of action decreased significantly between TI and TII. Cumulative dose-response curves showed that further improvement occurred after each inhalation during TI but that there was significant improvement only after the first inhalation during TII.

Methotrexate in the treatment of steroid-dependent asthma☆

A double-blind, placebo-controlled, crossover study was designed to compare steroid requirements between placebo and methotrexate (MTX) treatment in subjects with corticosteroid-requiring asthma. Subjects began with a steroid taper and then were randomized to a 3-month trial of drug or placebo therapy. Subjects received 15 mg of MTX a week or identical placebo. A 1-month washout period was completed before the crossover trial. Symptom scores, peak flow rates, spirometry, and beta-agonist frequency were closely monitored. Ten subjects completed the study. The average dose of prednisone during the placebo-treatment period was 11.97 mg/day compared to 8.37 mg/day while subjects were taking MTX. This was a 30% reduction in daily steroid requirement (p less than 0.01). Symptom scores and spirometry did not differ between the crossover trials, and overall clinical status was not altered. Complications from MTX were mild and included anorexia, alopecia, and stomatitis. All complications resolved with dose reduction or when MTX was stopped at the end of the study. No subjects withdrew from the study because of MTX complications. Low-dose MTX significantly reduced the steroid requirement in this group of subjects with steroid-dependent asthma. This reduction in steroid requirement was obtained without altering clinical status and without significant complication.

Aerosolized terbutaline in asthmatics. Comparison of dosage strength, schedule, and method of administration.

Sixteen patients with bronchial asthma participated in three studies of inhaled terbutaline. Onset of action, duration, and peak effects were compared for a dose of 0.5 mg given in one, two, or four inhalations at 1 min intervals from a freon-propelled, metered-dose aerosol. There was no significant difference in the response between the schedules. Dose-response curves were compared for terbutaline from a metered-dose aerosol, and pressure nebulized with and without intermittent positive pressure breathing (IPPB). There was no difference between the response with IPPB and simple nebulization. Improvement continued to the total dose administered of 9.0 mg. For a given bronchial response, six to eight times as much terbutaline was required by pressure nebulization as from the metered-dose aerosol.

Use of standardized and conventional allergen extracts in prick skin testing

This study examined whether commercially available conventional and standardized allergen extracts differ enough in potency to affect routine prick skin test results. Extracts of white oak, timothy, Bermuda, Russian thistle, short ragweed, sagebrush, Alternaria, and cat dander were examined in allergic patients and in nonatopic subjects with no personal or family history of asthma, rhinitis, or eczema. Conventional nonstandardized extracts (1:10 or 1:20 wt/vol) from two sources were compared with three concentrations (100,000, 10,000, and 1000 AU/ml) of a single standardized extract. Preparations were compared in the allergic patients with computerized planimetry, and in all patients and subjects with a conventional skin test grading system. Skin test area for the conventional extracts generally fell between the 10,000 and 100,000 AU/ml concentrations of the standardized extract. Skin test reactivity to at least one allergen extract occurred in 31% of the nonatopic subjects; there was no difference between the number of 3+ and 4+ reactions for conventional and standardized extracts. Results indicate that standardized and conventional extracts are frequently similar, but are not directly interchangeable.

Hypereosinophilia, neurologic, and gastrointestinal symptoms after bee-pollen ingestion

A patient developed hypereosinophilia (13,440 cells per cubic millimeter) 6 weeks after beginning the ingestion of bee pollen. Symptoms included generalized malaise, headache, nausea, abdominal pain diarrhea, generalized pruritus, and decreased memory. Evaluation revealed no other known cause for the patients hypereosinophilia, which resolved after bee-pollen ingestion was stopped. The product contained a mixture of entomophilous and anemophilous pollens to which the patient was skin test positive. An open challenge with the bee pollen later reproduced the presenting symptoms with a concomitant rise of the eosinophil count from 207 to 890 cells per cubic millimeter. The patient has since remained well avoiding bee pollen. This study strongly suggests that hypereosinophilia with attendant pathophysiologic disturbances may be an adverse reaction to bee-pollen ingestion in atopic individuals.

Pirbuterol Hydrochloride: Evaluation of Beta Adrenergic Agonist Activity in Reversible Obstructive Pulmonary Disease and Congestive Heart Failure

Pirbuterol hydrochloride is a beta2 adrenergic agonist with a structure similar to that of albuterol, except for the substitution of a pyridine ring for the benzene ring. It is comparable in duration of action to albuterol when given by inhalation, but it is threefold less potent by weight. In man, pirbuterol and albuterol have similar beta2 selectivity. In the acute therapy of chronic obstructive pulmonary disease, pirbuterol is most effective in oral doses of 15–20 mg, and by aerosol in doses of 400 μg or greater. Long‐term studies of oral pirbuterol in doses between 30–60 mg/day are promising, but further research is warranted. The combination of pirbuterols beta2 and lesser beta1 activity has proven helpful in the therapy of refractory congestive heart failure. Improvement of function of both right and left ventricles and systemic and pulmonic circulations has been demonstrated acutely. Drug effect wanes, as with other beta adrenergic agonists, due to the development of tolerance; however, long‐term benefit appears to persist in both pulmonary and cardiac patients. Pirbuterol will be marketed in the United States as 10 and 15 mg tablets and as a 200 μg per actuation metered dose aerosol for use in pulmonary patients only; it will not be approved for use in congestive heart failure. In terms of beta2 selectivity, duration of action, potency and frequency of side effects, pirbuterol is comparable to the two beta2 agonists already available in the United States, albuterol and terbutaline.