Aerosol Beclomethasone Dipropionate: A Dose-Response Study in Chronic Bronchial Asthma

Gaddie, J; Reid, I. W.; Skinner, C; Petrie, G.; Sinclair, D.J.M.; Palmer, K.N.V.

doi:10.1016/s0140-6736(73)90788-5

Cited by 125 publications

(34 citation statements)

References 7 publications

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“…A similar misinterpretation of results occurred in the 1973 study of Gaddie et al [51] where a post-ACTH stimulation plasma cortisol, after 28 days of 1,600 Ìg/day of BDP, was 27.9 Ìg/dl (770 nmol/l) -more than double the pretest level. This was taken to be indicative of 'impairment of adrenal function' because it was statistically different from the stimulated cortisol output with the 400 Ìg/day dose (33.5 Ìg/dl; 920 nmol/l).…”

Section: Discussionmentioning

confidence: 56%

“…One of the earliest studies of BDP safety [51] to use ACTH stimulation testing demonstrated a lack of clinically significant effect on the HPA axis of 1,600 Ìg/ day of aerosol administration in an adult population (see also below). The present survey, however, confirms the conclusions of Palmer with more certainty and with firmer data.…”

Section: Discussionmentioning

confidence: 99%

“…Equivalent results -which ignore dose-response characteristics -are misinterpreted as defining potency relationships. More than 20 years ago, Gaddie et al [51] at one of the leading clinical investigation units in the United Kingdom established in a study of 15 adult chronic asthmatics (with moderate-to-severe disease) that increasing the daily dose of BDP from 400 to 1,600 Ìg/day in 28-day increments of 400 Ìg resulted in no further improvement in FEV 1 and FVC. At the FDA's Pulmonary-Allergy Drugs Advisory Committee review of the FP submission [58], it was pointed out by the manufacturer that a dose of 100 Ìg twice daily of FP will 'produce approximately three quarters of the maximum efficacy' to be obtained with this treatment.…”

Section: Discussionmentioning

confidence: 99%

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Hypothalamic-Pituitary-Adrenal Axis Suppression and Inhaled Corticosteroid Therapy

Chrousos

Harris

1998

Neuroimmunomodulation

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In the first part of this two-part review it was noted that inhaled corticosteroids had become the mainstay of treatment for chronic asthma and yet the effects of long-term use of these compounds on the hypothalamic-adrenal-pituitary (HPA) axis were largely being determined by testing methods of limited reliability, especially by morning plasma cortisol measurements. It was established in our examination of the published literature and in our presentation of current knowledge of the structure and function of the HPA axis that safe, accurate and discriminating techniques to assess the functional status of the HPA axis were available. It was concluded that two state-of-the-art tests that have been insufficiently used were the ACTH stimulation test and measurement of the 24-hour integrated serial plasma cortisol concentrations. These two tests can detect adrenal suppression before the appearance of clinical effects. For part 2 of this review we conducted an exhaustive search of the English language clinical and pharmacological literature on the use of inhaled corticosteroids from 1988 until the present time to identify studies in which one or both of these testing methods have been used. We present our analysis of this limited number of studies to determine what accurately can be known of the HPA axis safety profile of three of the most commonly used and investigated inhaled corticosteroids – beclomethasone dipropionate, budesonide and fluticasone propionate. The first finding of significance was that only 50 reports were identified in which information on the HPA axis safety effects of orally inhaled steroids in asthma patients or in clinical pharmacological studies met our inclusion requirements. By analysis of the data presented in these reports we were able to reach the following conclusions: (1) inhaled corticosteroids administered chronically, and prudently, within recommended dose ranges do not endanger the functioning of the HPA axis, (2) the increasing tendency to use higher doses of inhaled corticosteroids on the assumption that there are clear dose-response benefits and no adverse HPA axis effects from long-term high-dose regimens is misguided and not supported by reliable published information, (3) the corollary – that higher corticosteroid potencies (as measured, for example, by skin-blanching activity) can have greater therapeutic effect in lung tissue without greater concomitant systemic activity – is a flawed concept, and (4) the limited clinical and pharmacological data support our part 1 conclusions that discriminating techniques to assess the functional HPA axis status should be an integral part of the drug development process and that further HPA axis function studies are required on existing inhaled corticosteroids – if they lack a rigorous testing history or long-term record of clinical safety.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Hypothalamic-Pituitary-Adrenal Axis Suppression and Inhaled Corticosteroid Therapy

Chrousos

Harris

1998

Neuroimmunomodulation

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“…No other biochemical changes were detected in any patient after 6 months' treatment on the higher dose. Gaddie et al (1973) failed to demonstrate any improvement in respiratory function on increasing the dose of beclomethasone dipropionate in 15 patients. The likeliest explanation for this finding is that these patients had already achieved their maximum increase in respiratory function at the lowest dose used (400 tg daily).…”

Section: Resultsmentioning

confidence: 89%

Experience with the use of a corticosteroid aerosol.

Chatterjee¹

1977

Brit J Clinical Pharma

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1. In 48 patients with chronic asthma who had been receiving treatment with beclomethasone dipropionate aerosol (BDA) at a daily dose of 400 microgram for several years, observations were made on the effect of increasing the dose to 800 microgram daily for 6 months. 2. There was subjective improvement in 37 of the 48 patients, but the only objective evidence of improvement was a slight reduction in airways resistance. 3. The higher dose of BDA did not produce impairment of pituitary‐ adrenal function or an increase in the incidence of oropharyngeal candidiasis.

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“…15 Poor dose-response relationship with inhaled steroid therapy regarding symptom control or oral steroid-sparing effect has been reported in other studies. 16,17 Dahl et al have reported a dose-dependent effect of graded doses of inhaled fluticasone (100-800 µg/day) in patients with asthma but the mean increases in morning peak expiratory flow rates (PEFR) observed were small, possibly because of the chronicity of the asthma, with patients whose mean baseline FEV 1 was approximately 70% of the predicted value. 18 In this study, there was a plateau response observed regarding the reduction in the number of exacerbations achieved at the dose of 400 µg/day.…”

Section: Early Introduction Of Inhaled Steroid Therapymentioning

confidence: 99%

The role of new asthma treatments

Chung

1998

Allergology International

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Aerosol Beclomethasone Dipropionate: A Dose-Response Study in Chronic Bronchial Asthma

Cited by 125 publications

References 7 publications

Hypothalamic-Pituitary-Adrenal Axis Suppression and Inhaled Corticosteroid Therapy

Hypothalamic-Pituitary-Adrenal Axis Suppression and Inhaled Corticosteroid Therapy

Experience with the use of a corticosteroid aerosol.

The role of new asthma treatments

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