Candidiasis and dysphonia complicating beclomethasone treatment of asthma

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.     

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.     

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.     

Adrenal function of children with bronchial asthma treated with beclomethasone dipropionate.

The function of the hypothalamic-pituitary-adrenal (HPA) axis was investigated in nine asthmatic children treated by inhalation of beclomethasone dipropionate (300 micrograms/day) for 12 weeks. The trial was designed as a prospective study. The 24-hour urinary free cortisol, serum cortisol, response to ACTH, and nocturnal serum cortisol followed by 20-minute sampling were measured before and after the study period. No significant changes were found, suggesting that inhaled beclomethasone, in a daily dose of 300 micrograms, does not cause suppression of the HPA axis.     

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

Jet-nebulized beclomethasone dipropionate in the management of bronchial asthma

The efficacy of jet nebulized beclomethasone dipropionate (BDP) in the management of asthma was evaluated in 18 children, 2-26 months old (mean 10 months). The children were selected on the basis of the severity of their symptoms and the lack of effect of conventional treatment. The effect of BDP was evaluated by comparing clinical data before and after the initiation of treatment. Fifteen of the 18 patients experienced a significant clinical improvement during treatment with BDP. BDP "nebulizer solution" is a valuable contribution to the management of severe asthma in young asthmatics.     

Effects of montelukast and beclomethasone on airway function and asthma control

BACKGROUND: Maintaining asthma control is a major objective of therapy. Traditionally, the effectiveness of asthma therapy has been judged primarily by its effect on airway function rather than on multiaspect asthma control. OBJECTIVE: An inhaled corticosteroid and a leukotriene receptor antagonist were compared to determine whether they provided equivalent effects, as judged by days of asthma control. METHODS: In a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, asthmatic patients (n = 782) with FEV(1) percent predicted values of between 50% and 85% and a weekly average beta-agonist use of more than 2 puffs per day were randomized to receive montelukast (10 mg daily), beclomethasone (200 microg twice daily), or placebo treatment for 6 weeks in a double-dummy fashion. We examined the distribution of the primary end point: percentage of days of asthma control. Secondary end points included FEV(1), albuterol use, occurrence of an asthma attack, asthma flare-up, rescue corticosteroid use, sustained asthma control, and adverse experiences. RESULTS: The percentage of days of asthma control was almost identical between the montelukast and beclomethasone groups (98% overlap in the distribution). Montelukast was at least equal to beclomethasone, and both were greater than placebo on the basis of frequency of asthma attacks, asthma flare-ups, and rescue corticosteroid use. Beclomethasone had a greater effect than montelukast and both treatments were better than placebo at improving FEV(1). CONCLUSIONS: Montelukast was as effective as beclomethasone, as judged by indices of clinical control other than FEV(1). When evaluating the outcome of montelukast therapy, FEV(1) might underestimate clinical effectiveness.     

A six-month, placebo-controlled comparison of the safety and efficacy of salmeterol or beclomethasone for persistent asthma.

BACKGROUND: There is a paucity of data comparing the long-term safety and efficacy of long-acting inhaled beta2-agonists versus low-dose inhaled corticosteroids in the treatment of asthma. OBJECTIVE: To compare the safety and efficacy of salmeterol xinafoate, beclomethasone dipropionate (BDP), and placebo over a 6-month treatment period in patients with persistent asthma. METHODS: Salmeterol (42 microg twice daily), BDP (84 microg four times daily), or placebo was administered via metered-dose inhaler to 386 adolescent and adult inhaled corticosteroid-naive patients in a randomized, double-blind, double-dummy, parallel-group study. Eligible patients demonstrated a forced expiratory volume in 1 second (FEV1) from 65% to 90% of predicted values. Pulmonary function, symptom control, frequency of asthma exacerbations, bronchial hyperresponsiveness (BHR) to methacholine challenge, and adverse events were assessed. RESULTS: There were few statistically significant differences between the two active treatments over 6 months of therapy. Asthma symptoms and lung function were significantly improved with both salmeterol and BDP compared with placebo (changes from baseline in FEV1 of 0.28 L (SE = 0.04) and 0.23 L (SE = 0.04), respectively, compared with 0.08 L (SE = 0.04); P < or = .014). There were no significant differences among the treatment groups with respect to the distribution of asthma exacerbations over time. Both salmeterol and BDP significantly reduced BHR compared with placebo (P < or = .033; changes from baseline of 1.29 (SE = 0.26) and 1.42 (SE = 0.24) doubling doses at 6 months, respectively, compared with 0.24 (SE = 0.29) doubling dose for placebo). No rebound effect in BHR was seen upon cessation of any of the three treatment regimens. There were no clinically important differences in the safety profiles among the three treatments. CONCLUSIONS: Both salmeterol and BDP are effective and well-tolerated when administered for 6 months to inhaled corticosteroid-naive patients with persistent asthma.     

Mometasone furoate: efficacy and safety in moderate asthma compared with beclomethasone dipropionate.

BACKGROUND: Mometasone furoate (MF) is a new inhaled glucocorticoid administered by dry powder inhaler (DPI). OBJECTIVE: MF-DPI was evaluated for safety and efficacy and compared with placebo DPI and beclomethasone dipropionate (BDP) administered by metered dose inhaler (MDI) in the treatment of patients with moderate persistent asthma. METHODS: Eligible patients (n = 227), 13 to 75 years of age, maintained on inhaled glucocorticoids before entering the trial, were randomized to receive: MF-DPI, 100 microg, twice daily, MF-DPI, 200 microg, twice daily, BDP MDI, 168 microg, twice daily, or placebo in a 12-week, multicenter, double-blind study. RESULTS: At endpoint, FEV1 (primary efficacy variable) significantly improved for all three active treatments compared with placebo (P < .01, all comparisons). The response to MF-DPI, 200 microg, twice daily treatment was approximately twice as large as the response to MF-DPI, 100 microg, twice daily or BDP MDI treatment, although the differences between these groups did not reach statistical significance. Secondary efficacy variables including PEFR, asthma symptoms, nocturnal awakenings, and albuterol use showed similar trends. The MF-DPI, 100 microg, twice daily and BDP MDI, 168 microg, twice daily treatment groups produced comparable results for all efficacy variables. CONCLUSIONS: MF-DPI, 100 microg and 200 microg, twice daily were well-tolerated and significantly improved lung function and symptom control in the treatment of patients with moderate persistent asthma. In this study, MF-DPI, 200 microg, twice daily seemed to be the most effective dosage.     

Disodium cromoglycate compared with beclomethasone dipropionate in juvenile asthma

In a double-blind controlled crossover trial of inhaled disodium cromoglycate and beclomethasone dipropionate in juvenile asthma, beclomethasone produced higher therapeutic scores but significantly so in only two indices–wheeze-free days and morning peak flow rates. Combined treatment offered no advantage over beclomethasone alone. No side-effects were noted. The findings confirm other studies of cromoglycate and a steroid aerosol (betamethasone 17-valerate) but disagree with the only other comparative trial of cromoglycate and beclomethasone, in which both were found equally effective.     

The superiority of combination beclomethasone and salbutamol over standard dosing of salbutamol in the treatment of chronic asthma

We studied the clinical effect of a combination aerosol containing salbutamol and beclomethasone dipropionate in comparison to doubling the standard dose of salbutamol from an inhaler. Fifty-seven patients completed the double-blind, crossover study. They were treated with either an aerosol of 100 micrograms beclomethasone dipropionate and 200 micrograms salbutamol or 400 micrograms salbutamol alone. Both regimens were administered four times a day for 4 weeks. The patients showed significant improvement in FEV1, PEFR, and symptom scores after treatment with beclomethasone dipropionate and salbutamol compared with pre-trial values and with treatment with double the dose of salbutamol. The patients demonstrated a clear preference for treatment with the combination of beclomethasone dipropionate and salbutamol. Regular treatment with beclomethasone dipropionate in addition to salbutamol as a combination inhaler provides much better control of asthma than merely increasing the dose of salbutamol in those patients poorly controlled on standard doses of inhaled bronchodilators.     

Comparison of roflumilast, an oral anti-inflammatory, with beclomethasone dipropionate in the treatment of persistent asthma

BACKGROUND: Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor with anti-inflammatory activity in development for the treatment of asthma. Roflumilast was compared with inhaled beclomethasone dipropionate (BDP) in patients with asthma. METHODS: In a double blind, double-dummy, randomized, noninferiority study, 499 patients (forced expiratory volume in 1 s [FEV1] = 50-85% predicted) received roflumilast 500 microg once daily or BDP 200 microg twice daily (400 microg/day) for 12 weeks. Lung function and adverse events were monitored. RESULTS: Roflumilast and BDP significantly improved FEV1 by 12% (270 +/- 30 ml) and 14% (320 +/- 30 ml), respectively (P < 0.0001 vs baseline). Roflumilast and BDP also significantly improved forced vital capacity (FVC) (P < 0.0001 vs baseline). There were no significant differences between roflumilast and BDP with regard to improvement in FEV1 and FVC. Roflumilast and BDP showed small improvements in median asthma symptom scores (-0.82 and -1.00, respectively) and reduced rescue medication use (-1.00 and -1.15 median puffs/day, respectively; P < 0.0001 vs baseline). These small differences between roflumilast and BDP were not considered clinically relevant. Both agents were well tolerated. CONCLUSIONS: Once daily, oral roflumilast 500 microg was comparable with inhaled twice-daily BDP (400 microg/day) in improving pulmonary function and asthma symptoms, and reducing rescue medication use in patients with asthma.     

Long-term use of oral beclomethasone dipropionate for the treatment of gastrointestinal graft-versus-host disease.

Treatment of severe acute and chronic gastrointestinal (GI) graft-versus-host disease (GVHD) with prolonged high-dose systemic corticosteroids has limited success and considerable toxicity. Beclomethasone dipropionate (BDP) is a potent topically active steroid. We treated 15 patients with acute (n = 2) or chronic (n = 13) GI GVHD refractory to systemic corticosteroids with 28-day courses of oral BDP (2 mg 4 times daily). Response was measured by the change in GI score (sum of 6 GI symptoms) as well as the ability to taper or discontinue systemic corticosteroids. Nine (60%) of 15 evaluable patients responded to BDP, including 3 complete responses (a GI score of 0 or 1 and discontinuation of systemic corticosteroids). Attempts to taper calcineurin inhibitor during BDP therapy were unsuccessful. The 2 patients with acute GVHD had no response to BDP. Responders received a median of 3 cycles (range, 1-20), compared with 1 cycle (range, 1-5) in nonresponders. Suppression of the hypothalamic-adrenal axis was seen in 2 of the 5 patients tested, but neither demonstrated clinically significant symptoms. We conclude that BDP is safe and effective for long-term treatment of chronic GI GVHD. Multiple courses may be necessary to achieve or maintain response in some patients, and prolonged BDP therapy is a feasible alternative to prolonged systemic corticosteroids.     

Efficacy of intranasal beclomethasone dipropionate in patients with perennial rhinitis and asthma

A Wright peak flow meter was used with a special mask for evaluating nasal blockage in a clinical drug study. The effect of beclomethasone dipropionate inhaled nasally was studied with PEFRn measurements twice a day in twenty-seven hospital patients with perennial rhinitis. Thirteen patients also had asthma. A statistically significant improvement in PEFRn values during the first 5 days of the active drug period was noted in both the rhinitis and rhinitis-asthma groups. In the rhinitis-asthma group the nasal blockage index, as calculated from the oral PEFR and PEFRn values, improved significantly during the second period of medication. Patients with rhinitis were found to have a tendency to fluctuating blockage according to the time of the day, the morning generally being poorer than the evening values. The fluctuation partially disappeared at the end of the period of active treatment, which also had a favourable effect on the bronchial obstruction of asthma patients when inhaled nasally, perhaps due to improved nasal respitatory function. The measurement of PEFRn values is, the authors believe, a useful method for measuring changes in nasal blockage of patients with rhinitis and asthma because of its simplicity and rapidity.     

A clinical comparison of aerosol and powder administration of beclomethasone dipropionate in asthma

A clinical comparison of conventional aerosol administration of beclomethasone dipropionate and insufflation as a powder using the ‘Rotahaler’ device in four doses of 100 μg each was made in thirty-seven cases. Each treatment was given for 4 weeks, the order being randomized. Symptom records, twice daily peak flow readings and records of bronchodilator and steroid dosage showed the powder to be as effective as the aerosol. In the physician's opinion the powder was preferable to the aerosol in some cases.     

Effects of inhaled beclomethasone dipropionate and alternate-day prednisone on pituitary-adrenal function in children with chronic asthma.

Two corticosteroid regimens, alternate-day prednisone and inhaled beclomethasone dipropionate, have been more acceptable than daily oral corticosteroids for treatment of chronic asthma. To compare the effect of these regimens on hypothalamic-pituitary-adrenal function, 20 children with asthma were evaluated while receiving 20 to 40 mg of prednisone on alternate mornings or 400 to 800 microgram per day of inhaled beclomethasone dipropionate in divided daily doses; seven children requiring only non-corticosteroid medication served as controls. Early-morning serum cortisol concentration, urinary free-cortisol excretion and the 11-desoxycortisol response to metyrapone were decreased to a similar degree among children receiving both corticosteroid regimens in comparison with the control patients and were lowest when alternate-day prednisone and inhaled beclomethasone dipropionate were given together. Thus, inhaled beclomethasone dipropionate appears similar to alternate-day prednisone in its effect on hypothalamic-pituitary-adrenal function when used alone; the effect is additive when the two are used together.