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Biomedical subjects

J H Toogood

Publications and source records attributed to J H Toogood.

At least 37 records · Page 2Linked to original sources
PubMed1989

Bioequivalent doses of budesonide and prednisone in moderate and severe asthma.

We determined the relative antiasthmatic and systemic glucocorticoid potencies of inhaled budesonide (BUD) versus morning-dose oral prednisone (PRED) in 34 adult patients with asthma over a dose range extending from conventional to high and potentially toxic levels, 3.2 mg of BUD or 40 mg of PRED per day. Changes in symptom frequency and severity, FEV1, and peak expiratory flow rate were measured during a double-blind, double-dummy controlled, crossover protocol. The drugs proved equally effective, provided a sufficient dosage was administered. The dose required to eliminate recurrently disabling asthma relapses in these patients was about 2.0 mg of BUD per day or greater than 40 mg of PRED per day. On the average, BUD doses greater than or equal to 1.84 mg/day/70 kg adult (26.3 micrograms/kg/day) exhibited systemic effects on the 8 AM serum cortisol level and blood eosinophil count equivalent to greater than or equal to 15 mg of PRED per day. The latter doses are known to be associated with steroid-induced complications, such as osteoporosis. However, the level of systemic glucocorticoid activity produced by any particular dose of BUD in these patients was consistently much lower than that produced by the dose of PRED needed to achieve an equivalent level of antiasthmatic response. Thus, the use of high-dose inhaled BUD appears clinically reasonable and ethically acceptable in patients with severe asthma in whom the alternative is their continuing dependency on PRED.

Administration, Inhalation↗
PubMed1988

Effect of high-dose inhaled budesonide on calcium and phosphate metabolism and the risk of osteoporosis.

We investigated the effects of the antiasthmatic inhaled steroid budesonide at low and high dosage (0.6 and 2.4 mg/day) on calcium and phosphate metabolism (Ca, P) in 10 normal adults. Their endogenous production of cortisol dropped with budesonide treatment (p less than or equal to 0.0005), as did androgen production (p less than or equal to 0.003). This was associated with an increase in the renal tubular maximal reabsorption of Ca (p = 0.003) and P (p = 0.03), a decrease in the urinary output of Ca in the fasting morning state (p = 0.03), and an increase in serum P (p = 0.02). However, there was no change in the 24-h urinary excretion of Ca (p = 0.76) or P (p = 0.08) or the serum Ca level (p = 0.19). Similarly, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, parathyroid hormone, and urinary cAMP levels were not affected, indicating that absorption of Ca from the gut was not compromised. Thus, in contrast to the expected effects of oral steroid treatment, inhaled budesonide had no discernible short-term adverse effect on Ca or P metabolism under the conditions of this study, despite purposely using a dosage high enough to partially inhibit adrenocortical function. These data tend to support a broadening of the therapeutic role of budesonide, and possibly other inhaled steroid drugs, to include higher doses and more severe asthmatics. However, additional clinical and metabolic studies are needed to fully clarify the effects of high-dose inhaled steroid therapy on bone.

Absorption↗
PubMed1987

Beta-blocker therapy and the risk of anaphylaxis.

Beta-blocker therapy is associated with an increase in the severity and, possibly, the incidence of acute anaphylaxis. The population at risk consists of people with allergic conditions who are given a beta-blocker for an unrelated condition. Anaphylaxis under these conditions may be severe, protracted and resistant to conventional treatment because of the beta-adrenergic blockade. Severe or fatal attacks have been triggered by insect stings, the ingestion of allergenic foods or drugs, and injections of radiocontrast media, antisera or immunotherapy antigens. These occurrences are probably infrequent, but their incidence is unknown. At least two fatal cases have recently occurred in Canada. Clinical allergists, internists and family practitioners in particular should be aware of the need for aggressive and prolonged support in patients who experience anaphylaxis while receiving beta-blocker therapy and should report all such occurrences to the federal registry of adverse drug reactions. Allergy skin testing or immunotherapy is inadvisable in patients who take a beta-blocker orally or in the form of ophthalmic eyedrops. The list of relative contraindications to beta-blocker use should be extended to include susceptibility to recurrent anaphylaxis, whether it is idiopathic or due to an identifiable cause.

Adrenergic beta-Antagonists↗
PubMed1984

Use of spacers to facilitate inhaled corticosteroid treatment of asthma.

Budesonide, a topically active corticosteroid, was administered in doses of 400 and 1,600 micrograms/day to 35 asthmatic adults, using a standard inhalation device or a tube or cone spacer. The spacers reduced oropharyngeal candidiasis by an amount equivalent to a 90% reduction in drug dose (p = less than 0.005) and doubled the drug's overall antiasthmatic potency (delta FEV1, p = 0.05) without significantly increasing its overall effect on blood eosinophils (p = 0.14) or the A.M. serum cortisol (p = 0.12). Steroid-induced neutrophilia increased by an amount approximating that produced by an extra half tablet of prednisone per day (p = 0.002). Both the airways and systemic effects of the spacers were greater in patients who had small airways dysfunction present prior to the study. The data suggest an increase in intrapulmonary drug deposition during spacer treatment without a material shift in regional delivery within the lung. Spacers should be particularly useful for patients whose response to inhaled steroid is compromised by by dose-limiting oropharyngeal complications. They can also reduce drug costs. They should be used selectively in children until their effect on regional intrapulmonary drug deposition has been more clearly defined.

Administration, Topical↗
PubMed1984

Personal observations on the use of inhaled corticosteroid drugs for chronic asthma.

Topically active inhaled corticosteroid (IC) drugs are highly effective for chronic asthma. Formalized conceptions of "high, low or safe" dosages of these drugs may be less appropriate than one of "optimal dosage". It seems reasonable to formulate a specific goal of treatment, and then fit dosage to the individual needs and tolerances of the patient rather than to a conventionalized "safe" limit, based on averaged data from different and perhaps quite dissimilar subjects. The studies reviewed here illustrate some principles applicable to the effective use of IC drugs.

Aerosols↗
PubMed1984

Dosing regimen of budesonide and occurrence of oropharyngeal complications.

The influence of the dosing regimen on the occurrence of oropharyngeal complications during a trial of the anti-asthmatic aerosol steroid budesonide was assessed by systematically varying the daily dose (400, 800, 1,600 micrograms), dose frequency (b.i.d. vs. q.i.d.), and dosing schedule (AM vs. AM/PM). Dysphonia was infrequent and was not affected by any features of the treatment regimen. ;Its incidence was unrelated to that of candidiasis. The amount of oropharyngeal candidiasis on the other hand correlated strongly with the daily dose of budesonide and dosing frequency. B.i.d. treatment abolished the effect of increasing budesonide dose on candidiasis, and virtually eliminated any need for nystatin. A 24 h interval between doses (using an AM schedule), or two intervals of about 12 h were both effective in conserving antifungal host defences in the oropharynx. Temporary conversion to b.i.d. dosing can facilitate the control or prevention of thrush, especially when the risk is increased by concomitant antibiotic therapy, as was shown to be the case in these patients. A small, but statistically significant, deterioration in peak expiratory flow occurred during b.i.d. dosing. Thus, despite its ability to virtually eliminate the problem of recurring thrush, b.i.d. dosing should not be continued indefinitely. These considerations probably apply to other topically active steroids currently used to treat asthma.

Aerosols↗
PubMed1983

Tactics for clinical trials of therapy in patients with chronic asthma.

Asthma can be conceptualized as a disease system ranging from the molecular to the social level. It is important to monitor both subjective and objective indices appropriate to different parts of the system. Objective indices alone are not enough. It is also important to distinguish disability from symptom severity or frequency and pulmonary impairment. The personality of the patient or the duration of follow-up can profoundly affect the perceived outcome of a particular treatment. It is important in controlled trials, and also in clinical practice, to take these factors into account.

Asthma↗
PubMed1982

Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid, budesonide.

The influence of various dosing regimens on the response of asthmatic patients to aerosol steroid was investigated. Budesonide, a topically active corticosteroid like beclomethasone dipropionate, was given q.i.d. or b.i.d., in the morning or A.M./P.M., at doses of 400, 800, and 1600 micrograms/day. Each patient (n = 34) took every treatment combination for 2 wk. The antiasthmatic and systemic effects, measured by changes in peak expiratory flow rate (PEFR), blood eosinophils, and serum cortisol levels increased approximately linearly on log dose budesonide (p less than 0.0005). Systemic effects of the drug were nonsignificant at low dosage. At high dosage, morning dosing conserved hypothalamic-pituitary-adrenal function, but at the cost of a marginal reduction in efficacy (delta PEFR, p = 0.12). Having the dose frequency reduced the antiasthmatic potency of the drug, i.e., PEFR fell by an amount equivalent to approximately eightfold reduction in daily dosage (p = 0.002). This effect was not evident when asthma was in remission but became so with asthma in relapse. Overall, the q.i.d. A.M./P.M. regimen showed the best risk-benefit relationships. The data indicate (1) that reductions in dose frequency made with the hope of improving patient compliance and thus conserving the drug's long-term efficacy are likely to lead to the reverse effect, (2) that the clinician can conserve a better balance of risk vs benefit by titrating dosage in terms of puffs per dose rather than doses per day, and (3) that patients can increase the antiasthmatic efficacy of this aerosol steroid without any increase in drug costs (or apparent risk) by simply increasing dosing frequency. These therapeutic considerations probably apply to some or all of the other topically active steroids currently used to treat asthma.

Adrenal Cortex Hormones↗
PubMed1982

Efficacy of safety of concurrent use of intranasal flunisolide and oral beclomethasone aerosols in treatment of asthmatics with rhinitis.

Steroid-dependent, chronic asthmatic patients with severe rhinitis or nasal polyps are often candidates for treatment with intranasal topical corticosteroids, such as flunisolide. The possibility of additive adrenal suppression, when flunisolide, beclomethasone and prednisone are given together, has not previously been studied. The need to asses the risk is suggested by reports of additive adrenal suppression when aerosol and oral steroids are used together to treat asthma, and by the demonstrably higher systemic availability of aerosol steroid given intranasally rather than via the lung. We performed a double-blind, placebo-controlled crossover assessment of the efficacy and safety of 3 weeks of intranasal flunisolide spray treatment (300 micrograms/day) in nineteen steroid-dependent chronic asthmatic subjects, who also had nasal polyps or severe rhinitis. During the study, their doses of prednisone and beclomethasone, used for asthma, were held stable. Morning serum cortisol levels and 24-hr urinary-free cortisol excretion were essentially the same after the placebo, and the flunisolide treatments. The intranasal flunisolide improved their nasal symptoms significantly (P less than 0.05). Local complications were negligible. Given conventional steroid doses like those used in this study, there appears to be no important risk to endogenous adrenal function from combining the use of intranasal, flunisolide spray with administration of other steroids by other routes, when this is deemed clinically necessary. If higher doses are used, the possibility of some additive adrenal suppressive effect cannot be excluded.

Administration, Intranasal↗
PubMed1982

The addition of an aerosol anticholinergic to an oral beta agonist plus theophylline in asthma and bronchitis. A double-blind single dose study.

In two groups of patients, 15 with asthma and 15 with chronic bronchitis, the bronchodilator effects of ipratropium bromide, of fenoterol plus theophylline, and of the combination of the three drugs, were compared using a double-blind, single-dose, placebo-controlled format. Ipratropium bromide caused rapid bronchodilatation which was not significantly different in asthmatic patients and patients with bronchitis (delta FEV1 = .29 L in one hour in asthmatic patients, .18 L in patients with bronchitis). In contrast, fenoterol plus theophylline induced a considerably greater effect in asthmatic patients (delta FEV1 = .41 L in one hour) than in those with bronchitis (delta FEV1 = .07 in one hour). The use of the three drugs in combination compared with ipratropium bromide alone, or fenoterol plus theophylline alone, resulted in a significant additional bronchodilatation in asthmatic patients. In the patients with bronchitis, the triple combination was clearly superior to fenoterol plus theophylline. A similar trend was present in comparing the triple combination to ipratropium bromide, but the difference did not reach statistical significance. There was no evidence of synergism when ipratropium bromide was combined with fenoterol plus theophylline in that the total bronchodilator effect was approximately additive. Asthmatic patients and the physician were able to distinguish the triple combination from placebo. No such ability was demonstrated with respect to those with bronchitis. All three drugs were well tolerated. Side effects were mostly mild, and none was related to the use of ipratropium.

Administration, Oral↗
PubMed1982

Clinical use of spacer systems for corticosteroid inhalation therapy: a preliminary analysis.

This is a preliminary report on the first half of a study designed to assess the ability of two different spacer devices to improve the results of aerosol steroid treatment in chronic asthmatic patients given budesonide in low and high dosages. The spacers significantly reduced oropharyngeal candidiasis but did not affect dysphonia - possibly because the incidence of the latter was so low throughout the study. The spacers augmented the airway response to budesonide in these patients without materially increasing systemic absorption of the drug (assessed indirectly in terms of the change in blood eosinophil counts). Pretreatment with inhaled terbutaline did not significantly affect the performance of the spacers, either in terms of the airways responses or the amount of budesonide systemically absorbed. When used properly, these spacers can improve the cost effectiveness of aerosol steroid treatment. Since only adults were studied, it is not known whether these findings apply equally well to children with asthma.

Aerosols↗