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Dive into the research topics where John H. Toogood is active.

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Featured researches published by John H. Toogood.


The Journal of Allergy and Clinical Immunology | 1977

A graded dose assessment of the efficacy of beclomethasone dipropionate aerosol for severe chronic asthma

John H. Toogood; Neville M. Lefcoe; D.S.M. Haines; Barbara Jennings; N. Errington; L. Baksh; L. Chuang

In a 26-wk double-blind controlled study of 34 patients whose asthma had been poorly controlled despite oral steroids, valuable clinical and pulmonary function improvement was derived by adding beclomethasone aerosol to the prednisone regimen. The amount of improvement correlated linearly with beclomethasone dosage over the range 200 to 1,600 microng/day. These patients required relatively high dosage. Success in achieving asymptomatic status was only 26% with the conventional 400 microng/day and 60% at 1,600 microng/day. Oropharyngeal candidiasis was also dose-related but did not prohibit the use of high-dosage beclomethasone. Respiratory infections, physical signs, blood glucose, and electrolytes were unaffected by the drug. A dose-related suppression of cortisol secretion was demonstrated, but about 1/4 of the group had normal plasma cortisol even at 1,600 microng/day plus the oral prednisone. An individualized risk-benefit assessment seems a better basis for choosing an optimal beclomethasone regimen for each patient than adherence to a conventionalized fixed dosage of 400 microng/day. This requires definition of: (1) a specific goal of treatment in the individual patient and the beclomethasone dosage required to achieve it; (2) the adrenocortical functional response of that particular patient to the desired dose of beclomethasone; and (3) the presence and degree of any dose-limiting constraints such as preexisting complications of steroid use.


The Journal of Allergy and Clinical Immunology | 1980

Candidiasis and dysphonia complicating beclomethasone treatment of asthma.

John H. Toogood; Barbara Jennings; R.W. Greenway; L. Chuang

Abstract Oropharyngeal candidiasis and dysphonia were assessed in 34 asthma patients whose risk of local complications of aerosol steroid therapy was considered to be higher than usual because of the doses of beclomethasone used for treatment of asthma (1,080 ± 360 μg/day). Cultures and examinations of the oropharynx were collated with symptom and medication-use records over a period of 2 yr. Positive cultures for Candida were found in 40% of the group before starting beclomethasone. Colonization of the oropharynx, clinical thrush, and dysphonia each increased in direct relationship to the daily dose of beclomethasone over a range from 200 to 1,600 μg/day. However, at peak prevalence, clinical thrush affected only 13% of the total group, i.e., about one quarter of the number with asymptomatic oropharyngeal candidiasis. Thrush was not increased by occasional use of trimethoprim-sulfamethoxazole or erythromycin. Dysphonia was a more common symptom, affecting up to 50% of the group, and occasionally was severe or persistent. It was related to the aerosolized steroid and not to the Freon propellants. Chronic voice stress appeared to be an important contributing factor to its onset or persistence. Although dysphonia and thrush were both related to beclomethasone usage, they did not appear to be directly related to one another, and they required different treatments (voice rest and nystatin). These complications diminished in severity with time and did not limit beclomethasone dosage in any patient. Therefore, they need not preclude the long-term use of beclomethasone, even in high dosage when required.


The Journal of Allergy and Clinical Immunology | 1989

Bioequivalent doses of budesonide and prednisone in moderate and severe asthma

John H. Toogood; J. Baskerville; Barbara Jennings; Neville M. Lefcoe; S-A. Johansson

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.


The Journal of Allergy and Clinical Immunology | 1982

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

John H. Toogood; J. Baskerville; Barbara Jennings; Neville M. Lefcoe; S.A. Johansson

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 drugs 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.


The Journal of Allergy and Clinical Immunology | 1995

Bone mineral density and the risk of fracture in patients receiving long-term inhaled steroid therapy for asthma

John H. Toogood; J. Baskerville; A.E. Markov; Anthony B. Hodsman; Lawrence J. Fraher; Barbara Jennings; R.G. Haddad; D. Drost

To determine whether high-dose or prolonged inhaled steroid therapy for asthma increases a patients risk of osteoporosis and fracture, we measured bone density in 26 men and 43 women (41 postmenopausal, all of whom had received supplemental estrogen therapy) after treatment with an inhaled steroid for 10.1 +/- 5.5 years and oral prednisone for 10.7 +/- 9.7 years (mean +/- SD). Most had stopped receiving prednisone since commencing the inhaled steroid therapy. We found that bone densities (adjusted for age and sex to yield a z score) were lower in association with higher daily doses of inhaled steroid (p = 0.013 ANCOVA) and with the duration of past prednisone therapy (p = 0.032). Larger cumulative inhaled steroid doses were associated with higher bone densities (p = 0.002) and a reduction in the numbers of patients at risk of fracture. Bone density also increased with the amount of supplemental estrogen therapy (p = 0.058) and, at equivalent levels of inhaled and oral steroid use, women showed higher bone density z scores than did men. Women with a lifetime dose of inhaled steroid greater than 3 gm had normal bone density regardless of the amount of past or current prednisone use or the current dose of inhaled steroid. These data indicate that the daily dose, but not the duration, of inhaled steroid therapy may adversely affect bone density, and that estrogen therapy may offset this bone-depleting effect in postmenopausal women.


The Journal of Allergy and Clinical Immunology | 1991

Effects of dose and dosing schedule of inhaled budesonide on bone turnover

John H. Toogood; Barbara Jennings; Anthony B. Hodsman; J. Baskerville; Lawrence J. Fraher

To assess whether the use of larger than usual doses of inhaled steroid to treat severe asthma may adversely affect bone turnover and whether such an effect may be mitigated by altering the dose schedule, we investigated the effects of budesonide (BUD) on serum osteocalcin and the urinary output of hydroxyproline and calcium. Healthy adults were administered 1.2 or 2.4 mg of BUD per day (N = 40) or placebo (N = 8) in a crossover, double-blind comparison of morning versus diurnal dosing schedules for 1 month each. Both BUD doses reduced the 24-hour urinary free-cortisol output (p less than 0.001) and serum osteocalcin (p less than 0.001). The larger dose reduced the morning serum cortisol levels (p = 0.002). Neither dose increased the 8 AM urinary calcium or hydroxyproline output. Osteocalcin and plasma cortisol levels were higher on morning than on diurnal dosing (p = 0.01). The 24-hour urinary free-cortisol output was the same with either schedule (p = 0.96). Additional study is required to assess the clinical importance of the inhibitory effect of BUD on bone formation, as evidenced by the reduction in osteocalcin levels. Of concern is the possibility of serious bone complications resulting from the long-term use of inhaled steroid, particularly in growing children or patients in whom other risk factors for osteoporosis are present. The clinical advantage, if any, of morning dosing remains questionable.


The Journal of Allergy and Clinical Immunology | 1998

Side effects of inhaled corticosteroids

John H. Toogood

Inhaled corticosteroid (ICS) therapy carries less risk of complicating drug- or disease-related morbidity and mortality than that associated with other antiasthmatic drugs such as prednisone, theophylline, or beta2-agonist bronchodilators. Serious side effects are uncommon, but the risk increases with the daily dose. The degree of risk is most effectively minimized by ensuring each patient uses the smallest daily dose sufficient to maintain optimum control of their disease. Any patient in whom ocular symptoms develop while receiving ICS therapy should promptly be evaluated by an eye specialist. Growth velocity is commonly reduced during ICS therapy and should be monitored routinely. Bone metabolism may be affected by low or medium doses of ICS, but there is no evidence such doses cause osteoporosis or fracture. High-dose therapy may reduce bone density and increase the risk of fracture, particularly if other risk factors for osteoporosis are present. Research is needed to better define the impact of ICS therapy in children on height and peak bone density attained at maturity. Also, there is a need for practice guidelines specifically applicable to the prevention of bone loss during ICS treatment.


The Journal of Allergy and Clinical Immunology | 1989

High-dose inhaled steroid therapy for asthma

John H. Toogood

Only a small minority of patients with asthma have symptoms severe enough to require high-dose inhaled steroid therapy. Because they need more aggressive treatment, this group is disproportionately represented in tertiary care referral centers. Therapeutic effects are dose dependent, and the daily dose of steroid required to normalize pulmonary function far exceeds that for symptom relief. Studies show that, if titrated to minimum dose levels of each the combination of inhaled and oral steroids provides a better balance between antiasthmatic and systemic glucocorticoid activity compared with oral steroid alone. Also, rapidly metabolized inhaled steroids such as budesonide may be associated with a lower risk for the osteoporotic complications seen with long-term oral steroid use. However, high dose of inhaled steroids may lead to adrenocortical suppression and hence estrogen deficiency in postmenopausal women. Morning dosing may mitigate this effect. Oropharyngeal thrush may be prevented by lowering the dose frequency or using a spacer. During prolonged inhaled steroid therapy, patient compliance has proved an important determinant of outcome.


The Journal of Allergy and Clinical Immunology | 1978

Minimum dose requirements of steroid-dependent asthmatic patients for aerosol beclomethasone and oral prednisone☆

John H. Toogood; Neville M. Lefcoe; D.S.M. Haines; L. Chuang; Barbara Jennings; N. Errington; L. Baksh; M. Cauchi

In 34 steroid-dependent asthma patients who improved markedly during 2 mo of treatment when progressively larger doses of beclomethasone aerosol were added to their oral prednisone regimen, we subsequently reduced both steroids to ascertain the minimum dose of each needed to prevent recurrence of significant asthmatic disability. After 80 wk of follow-up, 15 patients had successfully terminated oral prednisone; 19 were better controlled with a combination of aerosol plus oral steroid than with either drug alone; all patients previously unable to convert to alternate-day prednisone did so successfully during the combined therapy. The minimum effective maintenance dosage varied greatly among these patients-the median values being 2.5 mg prednisone and 1,200 microgram beclomethasone per day. The latter ranged from 200 to 1,8000 microgram. Only 4 patients were satisfactorily controlled without prednisone on 400 microgram beclomethasone per day or less. Seven needed extra intranasal beclomethasone to help control the nasal polyps which worsened after prednisone withdrawal. Suppression of plasma cortisol levels, apparently attributable to the beclomethasone, persisted in most patients, but on the average this was no worse than before commencing this treatment and valuable clinical improvement accrued. There were no other important complications of the regimen. In most of these patients with severe chronic asthma, optimum control of the disease required combined aerosol-oral therapy and maintenance doses of beclomethasone higher than those usually recommended. In some patients, effective control of chronic asthma by beclomethasone treatment may require acceptance of some persisting suppression of adrenal function as a considered risk.


The Journal of Allergy and Clinical Immunology | 1981

A clinical trial of combined cromolyn/beclomethasone treatment for chronic asthma.

John H. Toogood; Barbara Jennings; Neville M. Lefcoe

Some patients with chronic asthma treated with beclomethasone aerosol (BA) derive significant symptom benefit, yet have persisting adrenal suppression due in part to their BA therapy. The daily dose of BA required is higher in patients with atopy. We therefore assessed the usefulness of ancillary treatment with cromolyn sodium (CS), a drug known to inhibit atopic asthma, to try to improve the balance of risk vs benefit in such patients. Thirty asthmatics, well controlled on high-dose BA (mean, 1,040 micrograms +/- 97 SE) but with morning cortisol levels averaging approximately 10 micrograms/dl, were allocated randomly to placebo or CS inhalant, used in addition to their regular BA and other asthma medications. After 4 wk, their BA dose was halved. Both groups were monitored for greater than 6 mo by daily symptom diaries and peak flows, and by spirograms and morning serum cortisol tests every 4 wk. Mean cortisol levels rose 27% after BA dose reduction (p less than 0.05) but asthma worsened. Risk-benefit assessments 20 wk after reducing the BA showed a general tendency for higher cortisol values to be coupled with worsening of the asthma symptoms and FEF25%-75%. The distributions of good, fair, and poor risk-benefit responses were the same in both CS and placebo-treated groups (p = 0.20). In other asthmatics who may have less associated bronchitis or small airways obstruction than these patients, CS might prove useful, but in these adult chronic asthmatics with this particular therapeutic problem, there was no discernible BA-sparing effect or other clinical advantage from adding CS to their established BA regimen.

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Barbara Jennings

University of Western Ontario

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J. Baskerville

University of Western Ontario

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Neville M. Lefcoe

University of Western Ontario

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Lawrence J. Fraher

University of Western Ontario

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Anthony B. Hodsman

University of Western Ontario

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L. Chuang

University of Western Ontario

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S.A. Johansson

University of Western Ontario

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D.S.M. Haines

University of Western Ontario

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N. Errington

University of Western Ontario

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A.E. Markov

University of Western Ontario

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