Bronchodilator effect of ephedrine and theophylline after two to four weeks of repeated dosing.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C E Reed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Allergic bronchopulmonary aspergillosis (ABPA), a serious complication of asthma, is thought to rarely afflict infants. We report three children less than 2 years of age in whom this disorder developed. The major criteria for the diagnosis include: (1) asthma, (2) recurrent pulmonary infiltrations with peripheral eosinophilia, (3) positive aspergillus skin tests at 15 minutes and at 4 to 6 hours, (4) serum precipitating antibodies to aspergillus, and (5) elevated serum IgE levels. Early diagnosis and treatment of ABPA in infants may prevent the ravages of the disease and help to sharpen our concepts of the course and immunopathogenesis.
Decreased beta adrenergic regulation of cyclic adenosine monophosphate (cAMP) in lymphocytes has been described in asthma. We investigated adrenergic stimulation of glycogenolysis and responses to prostaglandin E1 (PGE1). Lymphocytes from 24 normal and 24 mild asthmatic subjects who had no drugs for at least 2 weeks were separated on Ficoll-hypaque and incubated in medium 199 with Hepes buffer. Beta adrenergic stimulation of cAMP and glycogenolysis was reduced in the asthmatics (p less than 0.05). PGE produced less of a rise in cAMP in asthmatics than in normals, but the difference was not significant (p greater than 0.05) and glycogenolysis was normal. Cortisol added in vitro potentiates the effect of isoproterenol and PGE1--but in the presence of cortisol the response of the asthmatic cells to isoproterenol is still lower than that of normal cells. This observation would support that "beta adrenergic blockade" is the major defect of asthmatic cells. The conclusion is further supported by the observation that the degree of the blockade is associated with a pathologic condition.
Each of 5 patients with acute nitrofurantoin pleuropulmonary reactions had profound lymphopenia and 4 had eosinophilia developing early in the clinical course after the drug was withdrawn. The 2 patients tested had only one third of the normal numbers of E rosettes (T lymphocytes) in the peripheral blood during recovery. Lymphoblastic transformation tests with purified nitrofurantoin were done in 3 patients and all of them were negative; responses to phytohemagglutinin, concanavalin A, and pokeweed were decreased but still normal. The diagnosis of various nitrofurantoin hypersensitivity reactions relies on clinical data. The mechanisms of these reactions presently remain unclear.
Concentrations of 10(-6) to 10(-3) M ephedrine did not increase cyclic adenosine monophosphate (cAMP) levels of normal human lymphocytes even in the presence of theophylline or cortisol, which enhance the response to isoproterenol or prostaglandin E1. Preincubation for 2 hr with ephedrine did not reduce the subsequent effect of isoproterenol, although preincubation with isoproterenol itself did. Therefore, ephedrine is not a direct beta-adrenergic agonist on human peripheral blood lymphocytes.
The frequency of W4 and W6 antigens was determined in 39 perennial, nonallergic asthmatics and 53 normal controls. The data indicated that the frequency of asthmatics homozygous for W4 or W6 was not different from the unrelated control population. Hence, our data dispute the hypothesis that intrinsic asthma is an autosomal-recessive disease associated with the W6 antigen.
Using a 51Cr-labeled, antibody-coated chicken red blood cell assay system, mononuclear cell and granulocyte preparations from infectious asthmatics, noinfectious asthmatics, and normal controls were tested for antibody-dependent cellular cytotoxicity (ADCC) capacity. The corrected cytotoxic indices of mononuclear cell preparations from infectious asthmatics were reduced (34 +/- 10 SD) as compared to noninfectious asthmatiics (47 +/- 7 SD) or normal controls (47 +/- 6 SD). Granulocyte preparations from infectious asthmatics and normal controls had a severity of the disease or in vivo drug treatment.
Twenty-three steroid-dependent severely asthmatic patients, ranging in age from 20 to 67 years, tolerated reduction in their oral dosage of steroids during a one-year trial of triamcinolone acetonide aerosol. Sixteen patients maintained their initial one-second forced expiratory volume without oral therapy with steroids, two required resumption of daily steroid dosage because of lethargy and arthralgia, and four required 2.5 to 20 mg of prednisone every other day to control their asthma. Five-day oral courses of steroids were occasionally required because of episodes of asthma from a variety of external causes. One patient failed to benefit within two months and withdrew from the study. One patient had precipitins to Candida albicans prior to the study, and he developed transient oropharyngeal culture-positive thrush, which subsided with use of a gargle containing nystatin. None of the other patients had oral candidiasis, and laryngoscopic examination revealed no lesions attributed to the aerosol. The mean fasting cortisol level did not increase throughout the one-year trial. Thus, the use of triamcinolone acetonide aerosol (2,000 microgram or less daily) can eliminate or greatly reduce oral requirements for steroids in patients with severe steroid-dependent asthma. Side effects are mild, but adrenal recovery may be exceedingly slow.
The bioavailability of theophylline from formulations containing this drug alone and also in combination with phenobarbital and ephedrine has been studied in normal volunteers and asthmatic subjects. Neither of the latter two drugs had any significant influence on the bioavailability of theophylline. A complexation phenomenon, previously reported to inhibit dissolution of theophylline and phenobarbital in vitro, does not affect the bioavailability of theophylline from solid formulations. No differences were observed in the pharmacokinetics of theophylline between normal and asthmatic subjects.
Late reactions consisting of fever, malaise, and swelling at the site, 4 to 6 hr after injections of Alternaria extract occurred in several patients receiving immunotherapy with Alternaria. These patients had in common serum IgG precipitins and exquisite leukocyte histamine release sensitivity to Alternaria. Such precipitins were 3 times more frequent in patients receiving Alternaria immunotherapy than a control group of patients receiving immunotherapy with other antigens. A prospective study revealed that 5 of 23 Alternaria-sensitive persons had precipitins before immunotherapy and another 6 developed precipitins during therapy. Only one of the 23 experienced a late Alternaria reaction. Thus, precipitins to Alternaria are common and do not seem to be the basis for the late reactions we observed. The finding of precipitins does not contraindicate immunotherapy.
Patients with atopic dermatitis have abnormal autonomic responses of the arterioles, pilomotor smooth muscle, and sweat glands. Their lesions have been reported to contain increased amounts of the neurohumors, acetylcholine and norepinephrine, as well as increased activity of acetylcholinesterase and catechol-O-methyltransferase. In vitro studies of epidermis show that beta adrenergic agonists fail to evoke the normal inhibition of mitosis of basal cells of patients with atopic dermatitis. Epidermis removed not only from the lesions, but also from normal-appearing skin, responded abnormally. The increase in intracellular levels of cAMP after exposure to catecholamines was similar in normal and atopic epidermis. Lymphocytes and PMN leukocytes isolated from patients with atopic dermatitis show both a decreased physiologic response (glycogenolysis and inhibition of lysosome enzyme release) and a decreased rise in intracellular levels of cAMP upon incubation with beta agonists, but a normal response to PGE1. Cortisol increases the response of lymphocyte adenyl cyclase to both agonists and, in the case of the patients with atopic disease, more than overcomes the depressed response to beta agonists. Because the leukocytes respond normally to PGE1 and because others have reported normal activities of skin and adenyl cyclase, phosphodiesterase, and protein kinases, we conclude that the step responsible for the diminished beta adrenergic response lies antecedent to the catalytic site of adenyl cyclase.
Specimens from 49 persons, 3 to 60 years of age, who were prone to attacks of apparently infectious asthma were cultured for viruses and bacteria during episodes of symptomatic respiratory infection from September 1972 to June 1973. Seventy-one of 128 episodes (55 per cent) of symptomatic respiratory infection occurred with asthma. Shedding of respiratory pathogens was associated with 43 of the 128 episodes, and 19 of the 43 etiologically defined episodes occurred with wheezing. Seven of 15 rhinovirus symptomatic respiratory infections were linked with asthma, as were 4 of 5 influenza type A (H3N2) and 2 of 3 respiratory syncytial virus infections. A total of 21 different rhinovirus serotypes have been identified from asthmatic patients during 2 years of study; 14 of these were associated with wheezing, indicating that the ability to cause asthma is not restricted to only a few types. Other viruses that were shed during wheezing-associated symptomatic respiratory infections included para-influenza type 3, adenovirus type 7, and 2 unidentified viruses. Although infectious asthma was not easily defined in adults and some older children, viruses that appeared to precipitate asthma were distributed among patients of widely differing ages.
To evaluate the usefulness of precipitin tests as a screening method to detect hypersensitivity pneumonitis, we compared persons with precipitins to organic antigens with precipitin-negative subjects from the same population of 1,072 office workers participating in a health survey examination. Thirty-three of the 53 persons with preciptins to Micropolyspora faeni, Thermoactinomyces vulgaris, T. candidus, pigeon serum, aspergillus, alternaria, pullularia, penicillium, cephalosporium, trichoderma, and phoma were matched according to age, sex, height, and smoking habits with precipitin-negative subjects. The subjects completed a self-administered standard questionnaire, they were interviewed and examined, chest radiograms were taken, and pulmonary functions were evaluated at rest and during mild and moderate exercise. No significant differences were found between the 2 populations in any of the pulmonary function measurements. In addition, clinical and radiologic evidence failed to distinguish between the 2 groups. No cases of hypersensitivity pneumonitis were found. In this population, precipitins had no apparent relationship to long disease. The frequency of precipitins was considerably higher than the frequency of hypersensitivity pneumonitis. We concluded that the detection of hypersensitivity pneumonitis in population surveys attempting to establish prevalence of the disease cannot be accomplished by the simple analysis of serum precipitating antibodies but requires, in addition, a more complex analysis of historical, radiologic, and immunologic data.
The numbers of mononuclear cells having receptors for sheep red blood cells (T lymphocytes) or complement (B lymphocytes) in the peripheral blood of farmer's lung patients were determined. In patients recovering from a clinical episode of farmer's lung or exposed to moldy hay or fodder, both the percentage of T lymphocytes and the T lymphocytes per mm3 were reduced, whereas the number of B lymphocytes remained within normal limits. Farmer's lung patients having no exposure to moldy hay or fodder had T and B lymphocyte numbers similar to a normal population.
Twenty-five steroid-dependent severely asthmatic patients, ranging in age from 20 to 67 years, were hospitalized. Baseline laboratory and pulmonary function testing was followed by reduction of prednisone therapy to 5 mg daily and by entry into a randomized double-blind study of placebo vs active aerosol triamcinolone acetonide (300mug four times daily). In this four-week trial, aerosol triamcinolone acetonide further reversed airway obstruction and proved to be an effective substitute for large oral doses of steroids in steroid-dependent patients with severe asthma. No significant improvement occurred in the maximum midexpiratory flow or the maximum velocity of air flow after 50 percent or 75 percent of the vital capacity had been expelled. There was no significant difference in the frequency of untoward effects between the groups taking aerosol triamcinolone acetonide and its vehicle. No patient demonstrated any definite return of adrenal function.