Inhaled glucocorticosteroids have now become first-line therapy for the treatment of chronic asthma in many countries. They are the most effective asthma therapy currently available, and numerous studies have documented their long-term efficacy in asthma control in adults and in children. Inhaled steroids suppress inflammation in asthmatic airways, although their precise molecular mechanism of action is not yet certain. It is likely that steroids affect the transcription of several steroid-responsive genes, and, of particular importance, they may inhibit cytokine gene transcription and cytokine effects, thereby reducing the chronic inflammation in asthmatic airways. Inhaled steroids are now used at a much earlier stage in asthma therapy, and there is a strong argument for their early introduction in both adults and children to prevent asthma morbidity and mortality and possibly the structural changes resulting from uncontrolled chronic inflammation, which may lead to irreversible airflow obstruction in so...

Efficacy and safety of inhaled corticosteroids in asthma

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.

https://www.jacionline.org/article/0091-6749(77)90051-3/pdf

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

Nocturnal adrenal suppression in asthmatic children taking inhaled beclomethasone dipropionate

BACKGROUND: High doses of inhaled corticosteroids are absorbed systemically and may cause long term side effects. As rinsing the mouth out after use and inhaling through a spacing device may reduce systemic absorption this has been further investigated. METHODS: Three crossover studies were carried out to assess the effect of budesonide given by dry powder inhaler (Turbuhaler) with and without mouth rinsing and beclomethasone dipropionate given by metered dose inhaler with or without a spacing device (Volumatic) on serum cortisol concentrations and urinary cortisol excretion in patients with asthma taking an inhaled corticosteroid. Each treatment period was two weeks with in a two week washout period. Serum cortisol concentrations at 0800 hours on day 14 and the 24 hour urinary excretion of cortisol were measured. In study 1 24 patients taking beclomethasone dipropionate 500 micrograms twice a day inhaled with (n = 10) or without (n = 14) a Volumatic spacing device were switched to a budesonide dry powder inhaler, 600 micrograms to be taken twice a day without mouth rinsing. In study 2 10 patients took budesonide 800 micrograms twice a day with and without mouth rinsing and without swallowing the rinsing water. In study 3 17 patients took budesonide 800 micrograms twice daily with mouth rinsing and beclomethasone dipropionate 500 micrograms twice daily with the spacing device and mouth rinsing. RESULTS: In study 1 no difference was seen between budesonide without mouth rinsing and beclomethasone dipropionate without a spacer: beclomethasone with spacer caused less suppression of cortisol (mean (SD) serum cortisol concentration: beclomethasone and spacer 487(148), budesonide 368(145) nmol/l). In study 2 mouth rinsing caused less suppression of morning serum cortisol concentrations (rinsing 440(63), no rinsing 375(56) nmol/1). In study 3 there was no difference in serum or urinary cortisol concentrations between twice daily beclomethasone dipropionate 500 micrograms inhaled by Volumatic spacer or budesonide by Turbuhaler 800 micrograms twice daily, both with mouth rinsing. Individual serum cortisol values were within the normal range in all patients except one in study 1. CONCLUSION: Systemic absorption of a corticosteroid inhaled from a metered dose inhaler is reduced by using a spacing device and that from a dry powder inhaler by mouth rinsing.

https://thorax.bmj.com/content/thoraxjnl/46/12/891.full.pdf

Effect of a volumatic spacer and mouth rinsing on systemic absorption of inhaled corticosteroids from a metered dose inhaler and dry powder inhaler.

Aerosol beclomethasone dipropionate: a dose-response study in chronic bronchial asthma

In a controlled trial 7 patients with airways obstruction were treated with beclomethasone by inhalation (2 mg/day) and then with prednisolone by mouth (20 mg/day), each for a period of 7 days. In 4 patients the airways obstruction was partially relieved by beclomethasone, but further improvement was recorded in 3 of these patients after subsequent treatment with prednisolone. There was evidence of impairment of hypothalamo-pituitary-adrenal (HPA) function following the administration of beclomethasone by inhalation in 5 of the 7 patients and of complete suppression in all 7 after subsequent treatment with prednisolone by mouth. It was concluded that beclomethasone by inhalation in a dose of 2 mg/day had no real advantage over prednisolone by mouth (20 mg/day) in the treatment of airways obstruction, in terms either of increase in FEV 1 or of preservation of normal HPA function. Limited experience with a smaller dose of beclomethasone (0·4 mg/day) by inhalation in an earlier uncontrolled trial suggested that this dose did not impair HPA function but was insufficient in most cases to relieve airways obstruction.

Beclomethasone dipropionate by inhalation in the treatment of airways obstruction.

A wet aerosol of 0.5 per cent salbutamol was administered for 3 minutes via a Bennett intermittent positive pressure ventilator driven by compressed air to 8 patients considered to be in status asthmaticus. Arterial blood gas analysis performed before and after salbutamol administration showed marked individual rises and falls in the partial pressure of oxygen with no predictable pattern of response. No dysrhythmia was observed on the E.C.G. but small changes of a non-specific nature occurred in the level of S-T segments and in the height of T-waves. It was concluded that in the dosage employed a salbutamol aerosol administered by I.P.P.V. produced no significant disturbance of myocardial function.

Y. F. J. Choo-Kang

Papers

Beclomethasone dipropionate by inhalation in the treatment of airways obstruction.

Salbutamol by intermittent positive pressure ventilation in status asthmaticus.