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Biomedical subjects

W W Busse

Publications and source records attributed to W W Busse.

At least 181 records · Page 10Linked to original sources
PubMed1988

A comparison of oral procaterol and albuterol in reversible airflow obstruction.

The efficacy and safety of orally administered procaterol hydrochloride, a potent beta 2-adrenergic bronchodilator, was compared with that of albuterol in an eight-center, double-blind study conducted in 223 patients with mild to moderate, reversible bronchial airway obstruction. After a 1-wk placebo washout period, patients were administered either procaterol 0.05 mg twice daily for 2 wk followed by 0.10 mg twice daily for 10 wk or albuterol 2 mg three times a day for 2 wk followed by 4 mg three times a day for 10 wk. Spirometry determinations 1.5 h postdose showed consistently greater percent improvements from predose in FVC, FEV1, and FEF25-75 with procaterol than with albuterol at Weeks 1, 2, 4, 8, and 12. Treatment differences were statistically significant (alpha = 0.05) after 2 wk, 2 months, and 3 months of treatment. Bronchodilatation was evident 0.5 h after dosing and peaked at 1.5 to 3 h postdose for both treatments. The duration of action (i.e., time until spirometry determinations were lower than those at 0.5 h postdose) was at least 5 h after procaterol but only 3 h after albuterol. There was no evidence of tolerance with continued procaterol treatment, whereas a diminished duration of response to albuterol was observed with long-term treatment. Tremor was reported statistically more frequently in patients receiving procaterol than in those receiving albuterol (alpha = 0.05); the frequencies of other adverse events were similar for the two groups. No statistically significant treatment differences were noted for asthma symptoms, global evaluations, ECG results, vital signs, or clinical laboratory measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

The contribution of viral respiratory infections to the pathogenesis of airway hyperreactivity.

From this review, it is apparent that the effects of respiratory viral infection on airway reactivity are multiple. Although virus-associated changes are many, we have at present no evidence to show that respiratory viruses cause intrinsic abnormalities in airway smooth muscle function. Rather, respiratory viruses influence bronchial smooth muscle function through a variety of other means: epithelial injury, PMN-dependent inflammation, and greater mediator release. These observations suggest that a common pathway to development of airway hyperreactivity during respiratory viral illnesses is to enhance those factors which participate in the inflammatory response. When the target of this enhanced inflammatory response becomes the airway, greater bronchial reactivity and obstruction result. Although many questions remain to be answered, we feel that future studies to evaluate the biology of respiratory virus effects on mechanisms of airway responsiveness will lead to a greater understanding of asthma pathogenesis.

Adult↗
PubMed1988

Viral "bronchitis" in childhood: relationship to asthma and obstructive lung disease.

Lower respiratory tract infections in children, including group, bronchiolitis, and bronchitis are frequently associated with recurrent episodes of wheezing. Different respiratory viruses assume greater importance at different ages of children. Respiratory syncytial virus is the most prevalent viral respiratory infection in preschool children, while rhinovirus is of increasing importance in older children. Asymptomatic virus shedding and mild respiratory infections do not provoke asthma symptoms nor do bacteria, except in association with sinusitis. Furthermore, epidemiologic studies strongly suggest that viral lower respiratory tract illness in early childhood is associated with pulmonary abnormalities, including bronchial hyperreactivity and peripheral airway obstruction that may persist for many years, and is possibly a cause of chronic airway obstruction in adulthood. Several different mechanisms have been identified by which respiratory viruses provoke asthma. No one single mechanism, however, adequately explains virus-induced asthma. Nonetheless, a common thread to these various proposed mechanisms is the ability of respiratory viruses to cause airway inflammation, either directly, through cytopathic effects, or indirectly, by increasing the inflammatory processes of respiratory cells. The consequence of these effects causes increased airway responsiveness and asthma.

Asthma↗
PubMed1988

Increased alveolar macrophage chemiluminescence and airspace cell superoxide production in active pulmonary sarcoidosis.

Alveolar macrophages (AMs) and lymphocytes are activated in pulmonary sarcoidosis. Mediators from these cells are potentially important in the pathophysiology and pathogenesis of this disease. To determine whether the enhanced release of reactive oxygen species (ROS) participates in inflammatory events in sarcoidosis, and to explore the relationship between ROS release and clinical parameters, we studied ROS metabolism of AMs and other airspace cells by luminol-enhanced chemiluminescence and by direct biochemical measurement of superoxide anion production. Ten of 17 patients with sarcoidosis were prospectively found to have active disease by objective radiographic, functional, and laboratory criteria. In these subjects, ROS metabolism by AMs was significantly enhanced compared either with healthy control subjects or with patients with inactive sarcoidosis. Abnormalities in ROS metabolism were not seen in peripheral blood monocytes, suggesting that this increased metabolic activity is compartmentalized to the lung. Enhanced ROS metabolism by AMs was associated with recent adverse chest radiographic changes, recent decline in forced vital capacity, and more advanced radiographic type. These data support the hypothesis that ROS generated by airspace cells can promote parenchymal inflammation in sarcoidosis, are associated with physiologic and radiologic changes, and may thereby contribute to the pathogenesis of sarcoidosis.

Adult↗
PubMed1988

Respiratory infections: their role in airway responsiveness and pathogenesis of asthma.

A clear relationship between viral upper respiratory infections and exacerbations of asthma has been established in numerous clinical studies. However, a unifying concept to explain how respiratory viruses bring about these changes has not been established unless it is the ability of viral illnesses to promote the inflammatory process. These changes in inflammation potentially encompass several organ systems: airway epithelium, the autonomic nervous system, and immediate hypersensitivity reactions. Thus, enhanced airway reactivity in viral respiratory infections represents a complex orchestration of many factors and functions to create the end result of bronchial hyperresponsiveness. Insight into precisely how the respiratory virus initiates these changes should provide valuable and new information into the pathogenesis of asthma. Therefore, not only is virus-induced asthma an important clinical problem, but it may also serve as a window to mechanisms of airway hyperreactivity and asthma.

Acute Disease↗
PubMed1987

Comparison of inhaled albuterol powder and aerosol in asthma.

In this multicenter, randomized, double-blind study comparing the efficacy and safety of aerosolized albuterol with the dry powder formulation, 231 patients with chronic reversible obstructive airway disease were randomly allocated to receive either placebo albuterol aerosol followed immediately by active albuterol powder (200 micrograms) or active albuterol aerosol (two puffs, 180 micrograms) followed immediately by placebo lactose powder four times a day for a period of 12 weeks. No statistically significant differences were found between the powder and aerosol formulations with respect to pulmonary function, length of time mean FEV1 remained greater than or equal to 15% above baseline, physicians' assessments of patients' clinical response, or patients' subjective symptom scores. There were also no significant differences between treatment groups in cardiovascular effects, laboratory values, or adverse events. Among patients who expressed a preference for one of the delivery systems, half preferred using the powder. Results of this study demonstrate that 200 micrograms of albuterol powder is as safe and effective as 180 micrograms of albuterol aerosol.

Administration, Inhalation↗
PubMed1987

Effects of a dihydropyridine calcium antagonist and agonist on human basophil histamine release.

Calcium influx is important to basophil histamine release, and even though a cromolyn-binding protein has been proposed to constitute a Ca2+ channel, the pathway of Ca2+ influx or involvement of a Ca2+ channel in this process has yet to be established. We evaluated the effects of a dihydropyridine antagonist, nitrendipine, and agonist, BAY k 8644, on human basophil histamine release. Nitrendipine inhibited ragweed antigen E-dependent basophil histamine release in a dose-dependent fashion with a 50% inhibitory dose of 3.7 (+/- 1.1) X 10(-6) mol/L, and maximal inhibition of histamine release (41.8% +/- 7.1%) was achieved with 1.0 X 10(-5) mol/L nitrendipine. Increased extracellular concentrations of Ca2+ reduced nitrendipine inhibition of histamine release. In contrast, the Ca2+ agonist, BAY k 8644, enhanced antigen E-dependent histamine release with an ED50 value of 5.0 (+/- 1.1) X 10(-6) mol/L. BAY k 8644 by itself, however, did not cause basophil histamine release nor did it enhance histamine release to the calcium ionophore A23187. Further, when the effects of BAY k 8644 on basophil histamine release were evaluated in the presence of nitrendipine, the enhancing action of BAY k 8644 was diminished in a competitive fashion. Therefore, even though these compounds act at specific Ca2+ channels in other tissues, our data do not establish either the presence of such channels in the IgE-dependent histamine release process of basophils or the mechanism of action for dihydropyridines in basophil histamine secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

Food allergens: structure and immunologic properties.

Few of the food allergens have been purified and characterized. Complex mixtures of allergens seem to exist in some commonly allergenic foods. Much further research will be necessary to develop any detailed understanding of the chemistry of food allergens.

Administration, Oral↗
PubMed1986

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.

Administration, Inhalation↗
PubMed1986

Prevalence of sensitivity to sulfiting agents in asthmatic patients.

Ingestion of sulfiting agents can induce wheezing in some asthmatic patients. However, neither the prevalence of sulfite sensitivity nor the clinical characteristics of the affected asthmatic population are known. In a prospective single-blind screening study, 120 non-steroid-dependent and 83 steroid-dependent asthmatic patients underwent challenge with oral capsules of potassium metabisulfite. Five non-steroid-dependent and 16 steroid-dependent asthmatic patients experienced a greater than 20 percent reduction in their one-second forced expiratory volume within 30 minutes following the oral challenge. Twelve of these sulfite reactors were rechallenged with metabisulfite capsules in a double-blind protocol. Under these conditions, only three of seven steroid-dependent patients had a positive response. Moreover, only one of five non-steroid-dependent patients had a response to double-blind challenge. On the basis of this challenge study, the best estimate of the prevalence of sulfite sensitivity in the asthmatic patients studied is 3.9 percent. This population, however, contained a larger number of steroid-dependent asthmatic patients than would be found in the general asthmatic population. It is concluded, therefore, that the prevalence of sulfite sensitivity in the asthmatic population as a whole would be less than 3.9 percent and that steroid-dependent asthmatic patients are most at risk.

Adult↗
PubMed1986

The use of a single daily theophylline dose and metered-dose albuterol in asthma treatment.

Sustained-release, 24-hour theophylline preparations have been formulated and may provide for convenient once-a-day dosing, although the use of such products in clinical asthma has yet to be fully established. This study compared single daily versus twice daily dosing with a 24-hour theophylline, Uniphyl, in asthma and further evaluated for the additional effect of metered-dose albuterol on each theophylline regimen. Twenty-eight patients with asthma were enrolled in this randomized crossover trial. Before enrollment, all demonstrated at least a 15% improvement in FEV1 after a beta-adrenergic aerosol and had serum theophylline levels ranging from 5 to 20 micrograms/ml with a predetermined 800 mg daily dose of Uniphyl. The patients were then randomly entered into four treatment regimens for one week each: Uniphyl, 800 mg four times a day (qd); metered-dose albuterol, active, 180 micrograms four times a day (qid); Uniphyl, 400 mg twice daily; metered-dose albuterol, active, 180 micrograms qid; Uniphyl, 800 mg qd; placebo, two puffs qid; and Uniphyl, 400 mg twice daily; placebo, two puffs qid. On the morning of the seventh day of each treatment regimen, pulmonary functions and a trough serum theophylline level were measured. The patient then received the same medication that he had taken for the preceding week. Spirometry was measured hourly, and a serum theophylline level was measured 6 hours later. The daily symptom scores, peak flow values, and pulmonary functions on the test day were similar with either single or twice daily Uniphyl dosing. Routine administration of albuterol by metered dose did not enhance asthma control in an unequivocal fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Enhanced basophil histamine release to concanavalin A in allergic rhinitis.

It has been suggested that IgE-dependent basophil histamine release (HR) does not necessarily relate to the amount of cell-bound IgE and, therefore, basophil "releasability" must be considered an important factor in this secretory process. To compare an IgE-dependent basophil HR process in nonatopic subjects and patients with allergic rhinitis, concanavalin A (Con A) was used as a secretagogue to stimulate mediator secretion. In 1.0 mmol/L of calcium-containing buffer, basophil HR to Con A (3.0 mcg/ml) was 50.2 +/- 8.6% in patients with allergic rhinitis and only 10.1 +/- 3.9% in nonatopic subjects. To evaluate whether this enhanced HR might be related to increased membrane influx of calcium, the following strategy was followed. Strontium (3.0 and 10.0 mmol/L) enhances immunologic (IgE) release of basophil histamine. Although the mechanism for strontium enhancement is not established, strontium may pass through the membrane channel more easily than calcium to increase secretion. We reasoned that if the enhanced release of histamine to Con A was related to increased membrane permeability to calcium, stimulation of basophil histamine secretion in the presence of strontium would reduce this difference. In both nonatopic subjects and patients with allergic rhinitis, strontium (3.0 and 10.0 mmol/L) enhanced HR. Enhanced HR with strontium was greater with basophils from normal subjects than from subjects with allergic rhinitis. Whether our observations with strontium indicate that the enhanced histamine releasability to Con A in subjects with allergic rhinitis may, in part, be due to a greater influx of calcium after immunologic stimulation must await characterization of the strontium effect or direct measurements of calcium ion disposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Enhanced eosinophil luminol-dependent chemiluminescence in allergic rhinitis.

Eosinophils were isolated from patients with seasonal allergic rhinitis, and their functional activity was evaluated by their luminol-dependent chemiluminescence (CL) response to opsonized zymosan and phorbol 12-myristate 13-acetate (PMA). We found that eosinophils from patients with allergic rhinitis produced a significantly greater CL response to opsonized zymosan than did normal cells. Eosinophils from both subjects with allergic rhinitis and control subjects were isolated to a purity of 95% and elicited peak values of 1,101, 901 +/- 133,708 cpm/5 X 10(5) cells (n = 7) and 417,278 +/- 25,910 cpm/5 X 10(5) cells (n = 5), respectively. The enhanced eosinophil CL to zymosan was found at times when the patients were maximally symptomatic with hay fever symptoms to ragweed pollen and again when they were asymptomatic. Eosinophils from these patients with allergic rhinitis also had enhanced CL to PMA (0.01 mcg/ml), but this increased activity was largely limited to times of hay fever symptoms. No correlation was found between enhanced eosinophil CL activity and the number of circulating eosinophils in allergic individuals. In contrast to the increased eosinophil activity, neutrophil CL to zymosan and PMA was similar in allergic and normal individuals throughout the study. These data provide evidence for the existence of enhanced oxidative metabolic function in eosinophils from patients with allergic rhinitis and raise the possibility that this particular activity is important in hay fever.

Adult↗
PubMed1986

Enhanced IgE-dependent basophil histamine release and airway reactivity in asthma.

IgE-dependent basophil histamine release does not necessarily correlate with the amount of cell-bound IgE, thus it has been suggested that basophil "releasability" is an important, but yet undefined, factor in this secretory process. Because mast cell, and possibly basophilic leukocyte, mediator release contributes to airway reactivity, any enhancement of this secretory process would favor asthma provocation. To evaluate IgE-dependent basophil histamine releasability in asthma, suspensions of leukocytes were isolated from patients with an allergic and nonallergic component to their airway disease and stimulated with concanavalin A (Con A) (0.03 to 10.0 micrograms/ml) and anti-IgE (10 to 1,000 ng/ml). Basophil histamine release to Con A and anti-IgE was significantly greater in both allergic and nonallergic asthmatic patients when compared with normal subjects. In contrast, basophil histamine release to the calcium ionophore A23187 was similar in leukocytes from normal subjects and asthmatic patients, suggesting the observed abnormality in secretion may be limited to an IgE-dependent process. To further determine if basophil histamine releasability in asthma correlated to measures of airway reactivity, bronchial provocation with histamine was performed. An inverse correlation was found between the provocative dose of inhaled histamine required to produce a 20% decrease, PD20, in the FEV1 and the leukocyte histamine release to Con A (p less than 0.05) and anti-IgE (p less than 0.05). Thus, we have new evidence that enhanced IgE-dependent release of leukocyte histamine correlates with airway reactivity in asthma. The mechanism of basophil releasability and its relationship to the pathogenesis of airway reactivity in asthma have yet to be established.

Adult↗
PubMed1985

Comparison of morning and evening dosing with a 24-hour sustained-release theophylline, Uniphyl, for nocturnal asthma.

Sixteen adults who had chronic asthma with nocturnal symptoms were selected to evaluate and compare the effectiveness of 7 A.M. versus 7 P.M. single daily dosing with the 24-hour sustained-release theophylline Uniphyl. The study was a randomized, double-blind, placebo-controlled trial in which the patients were given 800 mg of Uniphyl at either 7 A.M. or 7 P.M. for one week each. Serum theophylline levels showed significantly higher peak (18.1 +/- 1.8 micrograms/ml versus 12.7 +/- 1.2 microgram/ml) and trough (12.4 +/- 1.3 microgram/ml versus 7.6 +/- 1.0 microgram/ml) concentrations during evening dosing. Furthermore, daily peak flow values were higher in the morning when Uniphyl was given at 7 P.M. Thus, nocturnal dosing with Uniphyl gives higher serum theophylline concentrations and, with this, better control of nocturnal asthma.

Adult↗
PubMed1985

Monkey dander asthma.

We recently cared for two patients who experienced acute asthma with exposure to dander of the cotton top tamarin, a species of New World monkey. Both patients had serologic evidence for an IgE antibody to monkey dander as determined by RAST and a positive immediate skin test response to an extract prepared from monkey dander. Furthermore, by RAST we were able to determine that cotton top tamarin urine and newborn cotton top tamarin dander had antigens that reacted with IgE in the serum of the affected patients. Thus we report two patients with asthma to monkey dander that appears to be mediated by an IgE mechanism. We also found that serum from a subject exposed to another species of New World monkey, the capuchin, yielded a positive RAST to the cotton top tamarin, suggesting that allergenic cross-reactivity may exist between the two species.

Acute Disease↗