Determinants of allergen-induced asthma: dose of allergen, circulating IgE antibody concentration, and bronchial responsiveness to inhaled histamine.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R E Ruffin.
Explore the source record for details and available documents.
A radiotracer technique is described which enables direct measurement of the dose and distribution of inhaled aerosol bronchodilator in man. The mean (+/-SD) amounts of the B2-adrenergic agonist, fenoterol, administered to a group of 12 asthmatic subjects in a double-blind randomized fashion were: placebo, 0 microgram; low dose, 5.6 (+/-1.2) microgram; medium dose, 32.7 (+/-7.3) microgram; and high dose, 127.5 (+/-29.2) microgram, with a mean of 86.3% of the total subject dose being deposited in the lungs. The medium and high doses of fenoterol produced similar increases above baseline in forced expired volume in 1 sec (FEV1), maximum flow at 50% of vital capacity (V max 50), and maximum flow at 25% of vital capacity (V max 25). These increases were greater than those with placebo for the entire 4-hr study (p less than 0.01). The low dose of fenoterol was more effective than placebo in increasing FEV1, V max 50, and V max 25 above baseline values (p less than 0.05), but not for the entire 4-hr study. The high-dose fenoterol caused palpitations and tremor in 3 of the 12 subjects, and the medium-dose fenoterol caused palpitations in one of these subjects.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Carefully controlled allergen inhalation tests were carried out in twelve subjects to provoke early asthmatic responses with a mean maximum FEV1 fall of 30.7 +/- 5.2% (mean +/- s.d.). Four subjects had additional late asthmatic responses with a maximum mean FEV1 fall of 21.0 +/- 5.9%. The tests were repeated at intervals of 7 days in an identical way, following inhalation of Sch1000 (80 microgram) and placebo, each given 45 min before the onset of the early asthmatic response. This dose of Sch1000 produced a marked and uniform inhibition of methacholine-induced bronchoconstriction in the same subjects. The allergen-induced responses were reproducible in eleven out of the twelve subjects; the coefficient of variation for the decrease in FEV1 in the early responses being +/- 7% and in the late response +/- 43%. Sch1000 produced a slight and variable inhibition of early asthmatic responses (P less than 0.02) and no inhibition of late asthmatic responses. We examined the relationship between the degree of inhibition of the early asthmatic response by Sch1000 and : (a) the degree of inhibition produced by Sch1000 on histamine- and methacholine-induced bronchoconstriction; (b) the level of non-specific bronchial reactivity measured by inhaled histamine and methacholine; and (c) the degree of bronchodilatation produced by Sch1000. No relationship was found.
This study was conducted to determine whether small doses of salbutamol solution, aerosolised and delivered by intermittent positive-pressure breathing (IPPB), would be as effective as the 5 to 10 mg dose usually recommended for inhalational use. In nine asthmatic subjects we found that there was no significant difference between the peak bronchodilator effect of 1.0, 2.5, and 5.0 mg of salbutamol solution as assessed by FEV1 (P greater than 0.05). The 5 mg dose of salbutamol solution caused a significantly longer duration of effect than the 1.0 mg and smaller doses of salbutamol, but it also caused four of the nine subjects to complain of unwanted effects. In addition, a radiotracer technique in four normal subjects showed that an inverse relationship exists between the amount of aerosol deposited in the lungs and the tidal folume of IPPB. The maximum dose deposited in the lungs was about 10% of that initially present in the nebuliser.
Two inhalation techniques were performed to obtain airway and diffuse airway deposition of histamine aerosol. A radiotracer method was used to confirm the patterns of aerosol deposition and to measure the dose of histamine aerosol in the airways. In 5 subjects the effect of cumulative doses of histamine aerosol given either centrally or diffusely to the airways was measured. Histamine aerosol deposited predominantly in the large airways was more effective in increasing airway obstruction that was diffusely deposited histamine aerosol, suggesting that the receptors mediating the action of histamine reside mainly in the large airways.
The anticholinergic bronchodilator drug, Sch 1000, was administered as an aerosol by a metered-dose inhaler (200 microgram) to six normal and six bronchitic subjects. The short-term effect on mucociliary clearance was assessed and compared to a placebo (propellant and dispersal agent) in a double-blind crossover study. Mucociliary clearance in the normal group was significantly faster with administration of Sch 1000 than with placebo (P less than 0.01). There was no significant difference between the effects of administration of Sch 1000 and placebo on mucociliary clearance in the bronchitic group. Pulmonary function was significantly increased by therapy with Sch 1000 (as compared to administration of placebo) in the bronchitic group for two hours (P less than 0.05) and in the normal group for one hour (P less than 0.05). In another study, 12 normal subjects inhaled aerosols containing 40 microgram of placebo or 400 microgram of Sch 1000 from metered-dose inhalers on separate days in a randomized double-blind fashion. A significant sustained improvement in pulmonary function (P less than 0.05) and a transient fall in diastolic blood pressure were observed after administration of Sch 1000.
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.
The effects of the beta 2-adrenergic agonist, salbutamol, 200 mug, and the cholinergic antagonist, Sch 1000, 40 mug, have been compared in 25 asthmatic patients using a single dose, double-blind, crossover trial design. Salbutamol aerosol produces a greater degree of bronchodilatation than Sch 1000 aerosol during the initial three hours following drug administration. There is no significant difference in the bronchodilator effects of the two drugs in the interval four to eight hours after drug administration. Nonatopic patients showed less difference in bronchodilator response to each of the two drugs than atopic patients. Neither drug showed any significant adverse effect on blood pressure, pulse rate, or electrocardiogram. In six asthmatic patients the effect of the combination of salbutamol, 200 mug, and Sch 1000, 40 mug, was evaluated. The combination produced a longer duration of bronchodilatation than either drug alone when compared to placebo.
Non-allergic bronchial hyper-reactivity is a feature of most patients with asthma. We have measured non-allergic bronchial reactivity to inhaled histamine and methacholine in thirteen asthmatic subjects before and after allergen inhalation in the laboratory. The allergen inhalation produced mild early asthmatic responses (19-40% FEV1 fall) in all thirteen, additional definite late asthmatic responses (17-29% FEV1 fall) in four, and equivocal late asthmatic responses (5-11% FEV1 fall) in five. Following allergen inhalation, non-allergic bronchial reactivity increased in seven for up to 7 days. The seven included all four with definite late asthmatic responses and three of the five with equivocal late asthmatic responses. We conclude that allergens make asthma worse, partly through non-allergic mechanisms, and that avoidance of allergens is important in reducing non-allergic bronchial hyper-reactivity.
In addition to its diverse role in many physiological systems, zinc (Zn) has now been shown to be an important regulator of apoptosis. The purpose of this review is to integrate previously published knowledge on Zn and apoptosis with current attempts to elucidate the mechanisms of action of this biometal. This paper begins with an introduction to apoptosis and then briefly reviews the evidence relating Zn to apoptosis. The major focus of this review is the mechanistic actions of Zn and its candidate intracellular targets. In particular, we examine the cytoprotective functions of Zn which suppress major pathways leading to apoptosis, as well as the more direct influence of Zn on the apoptotic regulators, especially the caspase family of enzymes. These two mechanisms are closely related since a decline in intracellular Zn below a critical threshold level may not only trigger pathways leading to caspase activation but may also facilitate the process by which the caspases are activated. Studies by our laboratory in airway epithelial cells show that Zn is co-localized with the precursor form of caspase-3, mitochondria and microtubules, suggesting this Zn is critically placed to control apoptosis. Further understanding the different pools of Zn and how they interact with apoptotic pathways should have importance in human disease.
OBJECTIVES: The present study aims to describe the use of health services by children with asthma, and examine disease-specific, parental and sociodemographic variables associated with different levels of health-service utilization. METHODS: Parents of 135 children attending an emergency room (ER) completed questionnaires measuring the children's asthma symptoms, and sociodemographic and psychological variables. Parents were contacted monthly for 6 months to document the number of planned and unplanned visits to hospital and community health-care services for asthma. RESULTS: At least one further unplanned visit to the ER was made by 37% of children, while 62% made at least one unplanned visit to a general practitioner (GP). Fifty-five per cent made planned review visits to a GP, 30% to paediatricians and 5% to hospital clinics. After controlling for the level of asthma symptoms, parental anxiety and parental perceptions of children's vulnerability were associated with unplanned GP visits (P = 0.05 and P = 0.01, respectively); a planned review visit and the child being admitted to hospital for the index attack were associated with unplanned ER visits (P = 0.05 and P = 0.004, respectively). CONCLUSIONS: Children with asthma more frequently attend GP services than hospital services for both planned and unplanned asthma management. Different variables predict the unplanned use of GP and ER services. Understanding these differences is imperative if children and families are to make the most effective use of health services.
INTRODUCTION: The National Asthma Campaign (NAC) was formed in 1990 as a coalition of the key professional organizations concerned with asthma and its management in Australia. It has conducted multifaceted educational activities targeting health care professionals, people with asthma, and the general public. Between November 1991 and March 1993, an educational mass media campaign was developed to inform people about new approaches to preventive asthma therapy and how people with symptoms of asthma should talk to their doctor or pharmacist about new management and monitoring strategies. Evaluation was based on McGuire's communication/persuasion model for assessing the impact of mass media campaigns. METHODS: Four serial cross-sectional population surveys of persons over the age of 18 years were conducted in four major Australian cities using structured telephone interviews. Information was sought on asthma campaign awareness and knowledge or use of appropriate asthma management practices. RESULTS: There was an increasing trend in awareness of asthma messages in the media and of appropriate message recall across the two-year period. Knowledge about the need to use preventive therapy for asthma improved significantly. Among those with asthma there was a significant upward trend in the proportion who discussed asthma with their doctor or pharmacist and who used peak flow meters and written asthma management plans. CONCLUSIONS: The net impact of the NAC and other activities has been an increase in awareness about asthma in Australia. These campaigns relied on the relatively nonselective medium of television to raise awareness and to start to change attitudes to asthma. The challenge is to build on these trends to further reduce morbidity and mortality due to asthma.