Treatment of asthma in children with triamcinolone acetonide aerosol

Triamcinolone acetonide aerosol, 100 μg qid, was administered for 8 wk to 5 steroid-dependent asthmatic children and 10 who had not previously required continual corticosteroid treatment. Symptomatic control and pulmonary function improved in all 15 children despite discontinuation of oral corticosteroids in 3 of the steroid-dependent children. Determination of morning plasma cortisol concentrations disclosed no evidence of substantial adrenal suppression. Satisfactory symptomatic control has subsequently been maintained for 6 to 32 mo with doses of 100 μg bid to 300 μg qid without more extreme changes in plasma cortisol concentrations than were observed during the first 8 wk.     

A three- to five-year follow-up of the use of the aerosol steroid, beclomethasone dipropionate, in childhood asthma

Nineteen asthmatic children treated with the aerosol steroid, beclomethasone dipropionate, were followed 3 to 5 yr. Good control was maintained in all but one child throughout, although 73% have needed 1 or 2 wk of supplementary oral steroids per year for exacerbations. Growth has been along the percentile on which the child entered the study. No serious side effects have been encountered among 41 children treated between 1 and 5 yr with beclomethasone dipropionate. Seventeen percent needed prolonged alternate-day oral steroids, although all but one child did eventually return to good control with beclomethasone dipropionate.     

Effect of an inhaled corticosteroid on methacholine airway reactivity

Methacholine airway reactivity was studied in seven asthmatic patients before and at the end of 4 mo of beclomethasone dipropionate therapy, as well as in a control group. There was no statistically significant change in reactivity in either group, suggesting that a change in airway cholinergic receptor activity is not part of the mechanism of action of corticosteroids in asthma.     

High-dose inhaled steroids in the management of asthma A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function

Svendsen UG, Frølund L, Heinig JH, Madsen F, Nielsen NH, Weeke B. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.
The efficacy of budesonide (800 μg b.d.) and beclomethasone dipropionate (750 μg b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV₁ FVC, PEF or the histamine PC₂₀. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.     

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

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 μg beclomethasone per day. The latter ranged from 200 to 1, 800 μg. Only 4 patients were satisfactorily controlled without prednisone on 400 μg beclomethasone per' day or less. Seven needed extra intranasal beclomethasone to help control the nasal polyps which worsened after prednisone withdrawal. Suppression of plasma corlisol 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.     

Effect of beclomethasone dipropionate on basic fibroblast growth factor levels in induced sputum samples from asthmatic patients.

BACKGROUND: Airway remodeling in asthma refers to certain structural changes and is regulated by several growth factors. One molecule of potential relevance to these pathologic changes is basic fibroblast growth factor (bFGF). OBJECTIVES: To examine the relationship between bFGF levels and type III collagen synthesis in asthmatic airways and the effect of inhaled corticosteroid therapy on bFGF levels. METHODS: We simultaneously measured bFGF, vascular endothelial growth factor (VEGF), and procollagen type III peptide (P-III-P) levels in induced sputum samples from 17 asthmatic patients and 10 controls. Sputum induction was performed before and after 1 year of inhaled beclomethasone dipropionate therapy. RESULTS: Before beclomethasone dipropionate therapy, mean (SD) VEGF and bFGF levels were significantly higher in asthmatic patients (VEGF: 4270 [650] pg/mL; bFGF: 46.4 [20.0] pg/mL; P < .001 for both) than in controls (VEGF: 1730 [1140] pg/mL; bFGF: 6.0 [3.0] pg/mL). Although P-III-P was detected in none of the controls, P-III-P levels could be measured in all the asthmatic patients. No significant correlation was found between P-III-P and VEGF levels in asthmatic patients. However, a close correlation was found between bFGF and P-III-P levels in these patients (r = 0.84; P < .001). After 1 year of beclomethasone dipropionate therapy, VEGF levels were significantly decreased, whereas bFGF and P-III-P levels did not differ before vs after therapy. There remained a significant correlation between bFGF and P-III-P levels even after beclomethasone dipropionate therapy. CONCLUSIONS: A close correlation between bFGF and P-III-P levels was observed in asthmatic airways. However, corticosteroid therapy might not prevent airway remodeling via the bFGF-dependent pathway.     

Long-term corticosteroid effect on lymphocyte and polymorphonuclear cell function in asthmatics

The effect of long-term alternate-day steroid administration on lymphocyte and polymorphonuclear cell (PMN) functions was studied in 10 steroid-dependent adult asthmatic patients. The duration of alternate-day prednisone usage ranged from 3 to 12 yr with an average of 6.7 ± 3.6 yr. Maintenance steroid dosage at the time of study ranged from 20 to 50 mg on alternate days, averaging 31 ± 8 mg. Prednisone caused marked lymphopenia, suppression of phytohemagglutin (PHA) lymphocyte transformation and PMN adherence 4 hr after ingestion. By 24 hr these measurements returned to normal or higher. These effects appeared at all doses between 20 and 50 mg of prednisone. In contrast, there was no statistically significant suppression of the total leukocyte count, total and active erythrocyte (E) rosette-forming lymphocytes, serum immunoglobulin concentrations, polymorphonuclear cell (PMN) phagocytosis, or delayed skin reactivity. We conclude that the acute effects of prednisone on lymphocyte and PMN function are transient and return to normal levels by 24 hr. The continued administration of beclomethasone dipropionate by inhalation did not interfere with the recovery of the transient leukocyte abnormalities induced by oral prednisone.     

Adrenal cortical function after long-term beclomethasone aerosol therapy in early childhood

Ten asthmatic children were studied by tetracosactrin stimulation tests after receiving beclomethasone dipropionate aerosol (BDA) for periods of up to 12 months. Clinical improvement occurred in all children while receiving BDA. No change in adrenal function could be demonstrated by comparing the tetracosactrin stimulation tests before and after treatment with BDA.     

Methotrexate in steroid-dependent asthma: long-term results

Treatment of 21 steroid-dependent asthmatic patients with methotrexate (MTX) 15 mg/week was prospectively evaluated for a mean of 14.7 (SD 3.7) months. Before MTX, therapy consisted of a mean prednisone dose of 16.6 (SD 9.2) mg, in addition to inhaled beclomethasone/budesonide (mean daily dose 1157 (SD 330) μg) and bronchodilators. Thirteen patients were weaned from all regular systemic steroid therapy, a 50% or more reduction was achieved in four patients, and a less than 50% reduction in four patients. Abnormal liver function tests were noted in six of the 21 patients; this resolved despite continuation of MTX in five. In one patient, MTX was stopped because of symptoms as well as a fivefold rise in serum transaminases, and a speedy resolution was noted. Gastrointestinal side-effects were reported in six patients but were resolved in five with intramuscular MTX. There were no hematologic or pulmonary complications. We conclude that MTX appears to be both safe and efficacious as a steroid-sparing agent in most steroid-dependent asthmatic patients when taken over a long period.     

Beclomethasone dipropionate aerosol in the treatment of chronic bronchial asthma

In a double-blind, randomized study, 93 corticosteriod-independent patients with chronic bronchial asthma were treated with either beclomethasone dipropionate aerosol at 400 μg per day or its vehicle for 4 wk to determine and compare the effectiveness and safety of the preparations. Evaluations made before, at weekly intervals during, and 1 wk after treatment indicated that beclomethasone dipropionate aerosol was superior to its vehicle in improving FVC, FEV₁, FEF_25%–75%, and clinical signs and symptoms, and in the overall evaluations by both the investigators and the patients. Plasma cortisol levels measured at the end of the second and fourth weeks were not substantially different from those before treatment in either group. No significant side effects or abnormalities in laboratory results were noted.     

Steroid-dependent asthma treated with inhaled beclomethasone dipropionate in children.

The efficacy of beclomethasone diproprionate aerosal (BDA) was studied in 27 steroid-dependent asthmatic children. In the double-blind portion of the study BDA was found to be superior to placebo. The benefits of BDA therapy were sustained through the two-year, open-label portion of the study. Adverse effects were few and minor. Transfer from oral corticosteroid therapy to BDA was carried out uneventfully and was not associated with untoward effects.     

A prospective study of respiratory infection in asthmatic patients treated with beclomethasone dipropionate and sodium cromoglycate

A prospective study of forty adult asthmatic patients attending two chest clinics in the City of Liverpool was undertaken. All patients had reversible airways obstruction and were under treatment with either beclomethasone dipropionate or sodium cromoglycate. Satisfactory symptomatic control was achieved in both groups of patients on a subjective basis, but there was a statistically significant (P <0.001) reduction in the number of admissions to hospital in the treatment year compared to the preceding 12 months in the beclomethasone aerosol group. No increased incidence of lower respiratory tract infections or non-specific sore throats was found in either group studied. No cases of clinical oral Candida infection occurred in the beclomethasone aerosol treated patients. It is concluded that beclomethasone dipropionate in aerosol form is not only a safe and effective method for symptomatic control of adult bronchial asthma but is also economically worthwhile as a means of reducing hospital admissions in this vulnerable group of patients.     

Corticosteroid-sensitive lymphocytes are normal in atopic asthma

Corticosteroids, well known to increase susceptibility to infection, are often administered to atopic patients. Atopy may be associated with lymphocyte abnormalities and increased susceptibility to infections caused by intracellular organisms. We sought to determine whether atopic and nonatopic subjects respond in a similar manner to corticosteroids administered both systemically and locally. We compared the response of peripheral blood leukocytes of 15 atopic asthmatics and 10 nonatopic control subjects to prednisone or beclomethasone dipropionate. We determined leukocyte number, total eosinophil count, T-cell number, complement receptor lymphocyte number, and concanavalin A (Con A)- and phytohemagglutinin (PHA)-induced lymphocyte proliferation before and 5 hr after administration of 20 mg of prednisone orally or 336 jig of beclomethasone dipropionate by aerosol inhalation. Baseline values of the groups differed. The atopic asthmatic group had higher total eosinophil count, lower percent lymphocyte count, and slightly lower Con A- and PHA (high concentration) -induced lymphocyte proliferation. T-cell and complement receptor lymphocyte number were equivalent in both groups. Prednisone caused a profound eosinopenia, monocytopenia, T lymphopenia, depression of mitogen-induced lymphocyte proliferation, and increase in leukocyte number and complement receptor lymphocyte percent. Beclomethasone dipropionate was associated with little or no change in these parameters. We conclude that atopic asthma is not associated with a defect in corticosteroid-sensitive leukocyte populations and that beclomethasone dipropionate aerosol, as opposed to prednisone, does not alter peripheral blood mononuclear cell populations.     

Alpha-1 antitrypsin levels and prevalence of Pi variant phenotypes in asthmatic children

A total of 151 children with severe atopic bronchial asthma were screened for AAT levels by the STIC and RID methods. They were also phenotyped by the method of acid starch electrophoresis and crossed immunoelectrophoresis. The results were compared with those in a like control age group of children without known pulmonary problems. Both groups revealed similar incidences of AAT deficiency and 3% phenotype Z variants. The children with steroid-dependent severe asthma had a greater proportion of Z heterozygote variants than the non-steroid-dependent asthmatic and control population.     

Growth, pulmonary, and endocrine function in chronic asthma patients on daily and alternate-day adrenocorticosteroid therapy.

Growth, pulmonary, and adrenal-pituitary function were assessed in 20 steroid-dependent asthmatic children and adolescents while they were on daily prednisone therapy. The patients were then switched to equivalent daily methylprednisolone or twice equivalent alternate-day methylprednisolone for a 3-mo period, after which time studies were repeated. The steroid regimens were then crossed so that those patients taking daily methylprednisolone were switched to alternate-day therapy and the alternate-day therapy patients were switched to daily medication for another 3-mo interval, after which studies were repeated again. Abnormal growth, bone maturation, and cataracts were identified. Mean symptom scores at each evaluation were similar. Pulmonary function tests and shunt studies showed little difference between methylprednisolone and prednisone. Endocrine function tests showed a high incidence of disturbed pituitary and adrenal function. A 3-mo period of alternate-day therapy did not alter this.     

Posterior subcapsular cataracts in steroid-requiring asthmatic children

Slit-lamp examinations were performed on 24 children and adolescents with severe asthma, all of whom had received steroids for at least 365 days. Posterior subcapsular cataracts (PSCC) were detected in 7 (29.1%). None of the patients had been treated with beclomethasone. All 7 of the patients with PSCC were in the subgroup of 14 patients who had been on the highest doses of corticosteroid, 10 mg or more per day, for the longest period of time. The 7 children with PSCC were all below the fifth percentile for height and had fallen away from their normal growth curve. Of the 17 children in whom PSCC were not detected, only 1 was below the fifth percentile for height. It would seem from our results that the steroid-requiring asthmatic who is growth-suppressed is at an increased risk for developing PSCC. We have documented the reversal of PSCC in 2 children. Both of these children had been placed on beclomethasone, which allowed for the discontinuation of daily prednisone in one case and a reduction to less than 10 mg per day of prednisone in the other. The reversal occurred within 6 months of starting on beclomethasone.     

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

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.     

Extrapulmonary effects of maintenance corticosteroid therapy with alternate-day prednisone and inhaled beclomethasone in children with chronic asthma

Extrapulmonary effects of alternate-day prednisone and inhaled beclomethasone dipropionate therapy were examined in 24 and 32 children with asthma, respectively. Early morning serum cortisol values were significantly lower among patients receiving alternate-day prednisone than among patients receiving inhaled beclomethasone dipropionate and control subjects at 24 hours but not at 48 hours after an alternate-day prednisone dose. Urinary-free cortisol output during the second 24 hours of the alternate-day prednisone regimen were similar to values among patients receiving inhaled beclomethasone and were significantly lower than among control subjects for both groups. Mean heights among patients before being placed on maintenance corticosteroids were at the thirty-fifth percentile and were similar for both regimens. This was significantly lower than initial measurements for control subjects who, on average, were near the fiftieth percentile for both children with asthma not requiring maintenance corticosteroids and normal healthy Iowa children. Mean heights for both corticosteroid-treated groups remained at the thirty-fifth percentile after more than a 2-year average duration of follow-up. Heights of children with chronic asthma not requiring maintenance corticosteroids were initially significantly higher (fifty-first percentile) than the patients who subsequently required maintenance corticosteroids and increased significantly to the sixty-first percentile during a mean 2.7-year follow-up. Heights of healthy Iowa children remained near the fiftieth percentile during a mean 7-year follow-up. Disproportionate weight gain, although it was not consistently present, was significantly more likely with the alternate-day prednisone. Other extrapulmonary effects of the corticosteroid regimens appeared not to be of clinical importance during the time period of the study.     

Long-term effects of beclomethasone dipropionate on prednisone dosage in the corticosteroid-dependent asthmatic

The average prednisone dosage of 54 corticosteroid-dependent asthmatics was computed for one year prior to initiation of beclomethasone dipropionate. This was compared to the average prednisone dosage after nine months on the beclomethasone with progressive tapering of prednisone to either dose compatible with control of asthma or discontinuation. Beclomethasone was found clinically useful in the great majority of these patients because it permitted a significant decrease in dosage of prednisone, a change from daily to alternate-day prednisone, or discontinuation of prednisone after cautious tapering. The first two advantages were most evident in those asthmatics who initially required higher doses of oral steroids while the latter was evident in those requiring lower doses. Those patients whose prednisone dosage does not appear to be beneficially affected by the use of beclomethasone should be suspect as to adherence to proper medical dosage schedule.     

Once daily inhalation of budesonide in the treatment of chronic asthma: a clinical comparison

In a short-term, open cross-over clinical efficacy study, inhalation of budesonide 800 micrograms once daily was compared to inhalation of budesonide 400 micrograms twice daily and beclomethasone dipropionate 200 micrograms four times daily in 20 patients with stable steroid-dependent chronic asthma. Budesonide was inhaled through a spacer tube. The drugs were given in 3-week periods. Clinical symptoms, consumption of beta 2-agonists and peak flow were measured. In all but one patient, the reduced frequency of budesonide inhalations to only once daily has not given significantly different results compared with more frequent inhalations.