Beclomethasone Therapy Research Articles

P735 Comparative assessment of probiotics and standard therapies for mild to moderate ulcerative colitis: A systematic review and network meta-analysis

Abstract Background We performed a systematic review and network meta-analysis to compare probiotics to current therapies in the induction and maintenance of remission in ulcerative colitis (UC). Methods We systematically searched Medline, Embase, CENTRAL up to November 2018. We included randomised controlled trials (RCTs) in patients with mild to moderate UC that compared probiotics, sulfasalazine, mesalamine (low dose <2 g/day, standard dose ≥ 2 g/day), olsalazine, balsalazide, budesonide, budesonide MMX and beclomethasone either alone or in combination with topical therapy, to each other or placebo. We excluded trials where <50% of the population had extensive or left-sided colitis. Outcomes were remission (induction studies), relapse (maintenance studies) and discontinuation due to adverse events (tolerability). We conducted random-effects network meta-analysis and ranked treatments based on the surface under the cumulative ranking (SUCRA) probabilities. Results Forty-eight trials (probiotics 6 trials) of induction therapy and 30 trials (probiotics 6 trials) of maintenance therapy were included in the analysis. In studies with probiotics concomitant treatment, mainly mesalamine, were allowed. At induction, probiotics were not superior to placebo (OR 1.43; 95%CI 0.84–2.42) and they were inferior to combined oral and topical mesalamine therapy (OR 0.28; 95%CI 0.12–0.66) and combined mesalamine and beclomethasone therapy (OR 0.27; 95%CI 0.09–0.83). On SUCRA analysis, combination therapies (SUCRA 0.92 and 0.93) were ranked the highest followed by balsalazide (SUCRA 0.71), budesonide ΜΜΧ (SUCRA 0.68), standard dose mesalamine (SUCRA 0.52), beclomethasone (SUCRA 0.50), olsalazine (SUCRA 0.41), probiotics (SUCRA 0.29), low dose mesalamine (SUCRA 0.26) and sulfasalazine (SUCRA 0.23) in terms of inducing remission. Probiotics were well tolerated. At maintenance, probiotics (OR 0.35; 95%CI 0.19–0.62) and their combination with mesalamine (OR 0.38; 95%CI 0.15–0.99) had lower rate of relapse compared with placebo, but there were no differences when compared with other treatments. On SUCRA analysis, probiotics either alone or combined with mesalamine had comparable SUCRA values to standard dose mesalamine (SUCRA 0.59) and sulfasalazine (SUCRA 0.68). The combination of oral and rectal mesalamine was superior to placebo (OR 0.10; 95%CI 0.04–0.26) and all other treatments and it was ranked highest (SUCRA 0.99). Probiotics were ranked the best tolerated option in terms of discontinuation due to adverse events (SUCRA 0.80). Conclusion Probiotics are well tolerated but they are not effective in inducing remission in active UC. They may be effective when added to mesalamine therapy in preventing relapse of quiescent UC, but large, well-designed RCTs are needed.

Markers of Differential Response to Inhaled Corticosteroid Treatment Among Children with Mild Persistent Asthma

Inhaled corticosteroids are recommended as first-line therapy for children with mild persistent asthma; however, specific patient characteristics may modify the treatment response. Identify demographic, clinical, and atopic characteristics that may modify the inhaled corticosteroid treatment response among children enrolled in the Treating Children to Prevent Exacerbations of Asthma trial. Children aged 6 to 18 years with mild persistent asthma were randomized to 44 weeks of combined, daily, rescue, or placebo treatment. Daily treatment consisted of 40 μg of beclomethasone twice daily. Rescue treatment consisted of 40 μg of beclomethasone accompanying each symptom-driven albuterol actuation. Combined treatment consisted of both. Outcomes included time to first exacerbation and proportion of asthma control days. Fourteen baseline characteristics were selected for interaction testing on the basis of their clinical relevance. Two hundred eighty-eight children were randomized. Seventy-five percent were white, and 55% were male. As measured by time to first exacerbation, 4 characteristics identified children who received greater benefit from treatment: non-Hispanic ethnicity, positive aeroallergen skin test result, serum immunoglobulin E level of 350 K/μL or more, and history of oral corticosteroid use in the year before enrollment. As measured by asthma control days, 4 characteristics identified children who received greater benefit from treatment: male sex, positive aeroallergen skin test result, serum immunoglobulin E level of 350 K/μL or more, and incomplete run-in asthma control. Children with mild persistent asthma who have markers of atopic asthma or who have greater asthma burden may obtain greater benefit from beclomethasone therapy. Additional study is needed to confirm whether these markers can guide individualized therapy.

Rescue Use of Beclomethasone and Albuterol in a Single Inhaler for Mild Asthma

Treatment guidelines recommend the regular use of inhaled corticosteroids for patients with mild persistent asthma. We investigated whether the symptom-driven use of a combination of beclomethasone dipropionate and albuterol (also known as salbutamol) in a single inhaler would be as effective as the regular use of inhaled beclomethasone and superior to the as-needed use of inhaled albuterol. We conducted a 6-month, double-blind, double-dummy, randomized, parallel-group trial. After a 4-week run-in, patients with mild asthma were randomly assigned to receive one of four inhaled treatments: placebo twice daily plus 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler as needed (as-needed combination therapy); placebo twice daily plus 100 microg of albuterol as needed (as-needed albuterol therapy); 250 microg of beclomethasone twice daily and 100 microg of albuterol as needed (regular beclomethasone therapy); or 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler twice daily plus 100 microg of albuterol as needed (regular combination therapy). The primary outcome was the morning peak expiratory flow rate. In 455 patients with mild asthma who had a forced expiratory volume in 1 second of 2.96 liters (88.36% of the predicted value), the morning peak expiratory flow rate during the last 2 weeks of the 6-month treatment was higher (P=0.04) and the number of exacerbations during the 6-month treatment was lower (P=0.002) in the as-needed combination therapy group than in the as-needed albuterol therapy group, but the values in the as-needed combination therapy group were not significantly different from those in the groups receiving regular beclomethasone therapy or regular combination therapy. The cumulative dose of inhaled beclomethasone was lower in the as-needed combination therapy group than in the groups receiving regular beclomethasone therapy or regular combination therapy (P<0.001 for both comparisons). In patients with mild asthma, the symptom-driven use of inhaled beclomethasone (250 microg) and albuterol (100 microg) in a single inhaler is as effective as regular use of inhaled beclomethasone (250 microg twice daily) and is associated with a lower 6-month cumulative dose of the inhaled corticosteroid. (ClinicalTrials.gov number, NCT00382889 [ClinicalTrials.gov].).

Oral beclomethasone therapy for recurrent small bowel allograft rejection and intestinal graft-versus-host disease

INTESTINAL transplantation is an accepted therapy for short bowel syndrome in individuals with life-threatening complications of total parenteral nutrition (TPN). The primary problem preventing wider application of small bowel transplantation electively is the high levels of immunosuppression required to prevent rejection of the small bowel graft and the 20% incidence of graft loss due to rejection despite these high levels. Oral beclomethasone has been used experimentally in the treatment of inflammatory bowel disease and intestinal graft-versus-host disease (GVHD) associated with bone marrow transplantation. It acts primarily as a topical steroid without high levels of systemic absorption that would lead to adrenal suppression. There are currently no reports in the literature describing the use of beclomethasone in small bowel transplant recipients. The striking similarity between GVHD and acute small bowel allograft rejection histologically suggests beclomethasone may have a role in treating and preventing recurrent acute rejection. Herein we present the results of oral beclomethasone treatment in three small bowel transplant recipients who had multiple episodes of acute small bowel rejection and one with GVHD.

Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged > or = 6 years.

Montelukast is a leukotriene receptor antagonist administered orally once daily for treatment of chronic asthma in adults and children. A comprehensive analysis of safety data from double-blind, randomized, placebo-controlled trials with montelukast has not been previously reported. A pooled analysis of safety data from 11 multicentre, randomized, controlled montelukast Phase IIb and III trials and five long-term extension studies was performed. A total of 3386 adult patients (aged 15-85 years) and 336 paediatric patients (aged 6-14 years) were enrolled in the trials; 2031 adults received montelukast for up to 4.1 years, and 257 children received montelukast for up to 1.8 years. Summary statistics comparing incidences of adverse events among treatment groups were calculated. The overall incidence of clinical and laboratory adverse events among montelukast-treated patients, both adult and paediatric, was similar to that among patients receiving placebo. There were no clinically relevant differences in individual adverse events, including infectious upper respiratory conditions and transaminase elevations, between montelukast and placebo groups. Discontinuations due to adverse events occurred with similar frequencies during placebo, montelukast and inhaled beclomethasone therapy. No dose-related adverse effects of montelukast were observed in adults treated with dosages as high as 200 mg per day (20 times the recommended dose) for 5 months. This tolerability profile montelukast observed in clinical trials has been generally reflected in the post-marketing safety experience seen to date. These data indicate a tolerability profile for montelukast similar to placebo during both short-term and long-term administration, even at doses substantially higher than the recommended clinical dose of 10 mg once daily for adults and 5 mg once daily for children aged 6-14 years.

Adrenal function in premature infants during inhaled beclomethasone therapy

Objective: We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia does not cause adrenal suppression. Study design: Infants receiving ventilatory support with birth weights ≤1250 g and born at <33 weeks’ gestation, age 3 to 14 days, were enrolled in a multicenter randomized trial to study the efficacy and safety of beclomethasone therapy versus placebo for prevention of bronchopulmonary dysplasia. Adrenal function was assessed on study day 21 (± 2 days) by determination of basal and stimulated plasma cortisol levels. Initially, cortisol response was assessed with insulin-induced hypoglycemia test (IIHT) (n = 63) until an interim analysis revealed insignificant cortisol response in both study groups. Thereafter, cosyntropin stimulation was used (n = 85). Results: Beclomethasone therapy was associated with lower median basal cortisol levels (5 μg/dL beclomethasone, 6 μg/dL placebo, P = .04). IIHT revealed insignificant change in cortisol response within each group. Cortisol response to cosyntropin stimulation was similar for each group (17 μg/dL beclomethasone, 18 μg/dL placebo, P = .86). Conclusion: Beclomethasone therapy was associated with a small decrease in basal cortisol levels. There was no evidence of adrenal suppression in response to cosyntropin stimulation during beclomethasone therapy. Lack of cortisol response to hypoglycemia may reflect missed timing and/or decreased response of the premature infants’ hypothalamic-pituitary-adrenal axis to hypoglycemia. (J Pediatr 1999;135:65-70)

Effect of Beclomethasone Therapy on Tracheal Aspirate Interleukin-8 and Interleukin-1 Receptor Antagonist in Preterm Ventilated Infants at Risk for Bronchopulmonary Dysplasia (BPD)

Effect of Beclomethasone Therapy on Tracheal Aspirate Interleukin-8 and Interleukin-1 Receptor Antagonist in Preterm Ventilated Infants at Risk for Bronchopulmonary Dysplasia (BPD)

Cortisol Response in Premature Infants during Inhaled Beclomethasone Therapy† 984

Cortisol Response in Premature Infants during Inhaled Beclomethasone Therapy† 984

Early Inhaled Glucocorticoid Therapy for Prevention of Neonatal Chronic Lung Disease • 1629

Background: Systemic steroid therapy is widely used in treating infants at risk for chronic lung disease. Inhaled steroid therapy has potential advantages of direct delivery to the lung and fewer side effects.Methods:A multicenter, randomized, placebo-controlled, double-blind clinical trial was designed to test the hypothesis that early administration of inhaled beclomethasone would decrease the frequency of chronic lung disease with few systemic side effects. Infants <33 weeks gestation and <1251 grams birth weight still requiring assisted ventilation between days 3-14 of life were screened for enrollment. Infants were randomized to receive beclomethasone or placebo by metered dose inhaler and Aerochamber. Beclomethasone dose of 40 μg/kg/day was tapered over 4 weeks. Systemic steroid therapy was permitted if indicated. Outcome measures included frequency of chronic lung disease at age 28 days and at 36 weeks postconceptional age; death; frequency of systemic steroid therapy; duration of supplemental oxygen and mechanical ventilation. Occurrence of adverse effects, such as hyperglycemia, hypertension, infection, and decreased weight gain, were monitored. Results: 253 of 294 (86%) eligible infants were enrolled, randomized, and received either beclomethasone (n=123) or placebo (n=130). Baseline characteristics were similar between groups. Deaths by age 28 days: 7 beclomethasone v. 7 placebo. Deaths by 36 weeks postconceptional age: 11 beclomethasone v. 8 placebo. Among survivors, the study groups had similar frequency of chronic lung disease at age 28 days and 36 weeks postconceptional age. However, there was substantially less use of systemic steroid therapy in infants in the beclomethasone group v. placebo group at age 28 days and 36 weeks postconceptional age. The data also suggest that beclomethasone group had fewer days of supplemental oxygen and mechanical ventilation. There was no difference between groups with respect to death, systemic infection, blood glucose screens, blood pressures, weight gain, or ROP. Conclusion: Risk of chronic lung disease at age 28 days and 36 weeks postconceptional age was similar for infants treated with this regimen of early inhaled beclomethasone compared to placebo. Beclomethasone therapy resulted in less use of systemic steroid therapy. Increased used of systemic steroid therapy in the placebo group may have contributed to dampening detectable differences in chronic lung disease between the study groups.

Loratadine useful as an adjunct to intranasal beclomethasone therapy

Loratadine useful as an adjunct to intranasal beclomethasone therapy

A META-ANALYSIS OF THE EFFECT OF ORAL AND INHALED CORTICOSTEROIDS ON GROWTH

Meta-analytic integration supports the concern that there may be a small effect on growth with the use of oral corticosteroids (prednisone or other drugs). However, this technique also indicates that available studies of inhaled beclomethasone therapy do not show an association between its use and the adverse effect of diminished stature.

Intestinal calcium absorption and parathyroid hormone secretion in asthmatic patients on prolonged oral or inhaled steroid treatment

A secondary hyperparathyroidism resulting from decreased intestinal calcium (Ca) absorption has been proposed as a contributory factor to glucocorticoid-induced osteoporosis. Inhaled steroids do not usually suppress adrenal gland function unless daily doses above 1,500 microgram are used. A recent study, however, has shown a reduced total body calcium in patients on regular beclomethasone treatment. In theory, osteopenia in these patients could be due to a direct effect of inhaled steroids on bone or due to an impaired intestinal calcium absorption. In this study, Ca absorption and parathyroid hormone (PTH) secretion were evaluated in three groups: 1) asthmatics on continuous oral and inhaled steroid treatment (11.3 +/- 4.4, range 5-33.5 mg.day-1 prednisone and 660 +/- 265, range 400-1,600 microgram.day-1 beclomethasone, respectively); 2) asthmatics on regular beclomethasone therapy (585 +/- 210, range 400-1,200 microgram.day-1); and 3) healthy subjects. The prevalence of vertebral fractures was evaluated by a spinal X-ray. No differences were found in either Ca absorption or PTH serum levels between asthmatics and healthy subjects (analysis of variance-ANOVA). Vertebral fractures were significantly more frequent in patients from group 1 (14 of 25) than in those from group 2 (2 or 25). We conclude that both prolonged oral steroid treatment and inhaled steroids, at doses lower than 1,600 microgram.day-1 do not cause Ca malabsorption, and that hyperparathyroidism does not contribute to osteoporosis in these patients.

The inflammatory response in asthma exacerbation: changes in circulating eosinophils, basophils and their progenitors

Circulating eosinophils, basophils and eosinophil/basophil (Eo/B) progenitors were examined in 12 patients at the time of an exacerbation of asthma accompanied by sputum eosinophilia and after resolution of the exacerbation with inhaled corticosteroid treatment. Differential counts were performed and peripheral blood non-adherent mononuclear cells were cultured for 14 days in methyl-cellulose to determine the number of Eo/B and granulocyte-macrophage (GM) colonies without knowledge of the clinical conditions or findings. With resolution of the asthma exacerbation on beclomethasone therapy, there were significant falls in circulating eosinophils, basophils and Eo/B colonies whereas GM colonies were unchanged. To elucidate whether the observed changes could be due to systemic absorption or local action of inhaled corticosteroid, seven subjects with allergic rhinitis and no current evidence of lower airway inflammation (no symptoms of asthma and normal methacholine airway responsiveness) received 14 days' treatment with the same dose of inhaled beclomethasone or of placebo in a double-blind randomized cross-over study. No significant changes in airway function or in circulating cell counts were observed. The results suggest reduced production of eosinophils and basophils after the resolution of an exacerbation of asthma. This effect may be due to reduced levels of airway-derived eosinophil-basophil growth and differentiation factors.

Peroral Prednisolone in the Treatment of Middle-Ear Effusion in Children: A Double-Blind Study

Otitis media with effusion (OME) is one of the most important and, with respect to treatment, one of the most problematic of the common diseases of childhood. A variety of medical regimens and surgical procedures have been tried in the management of middle ear effusion. Conservative treatment has included long-term chemotherapy antihistamines, and decongestants, but definitive evidence that the clinical course of the disease is significantly shortened by any of these therapies has yet to be presented. Corticosteroid treatment has also been used both in allergic and nonallergic children. Evaluating the results of ampicillin and prednisone therapy in 160 children with OME, PERSICO et al. (1978) concluded that the steroid had a beneficial effect on Eustachian tube function. SCHWARTZ et al. (1980a) found that middle ear effusion cleared in 62S% of children with secretory otitis media as a result of treatment with 1 mg of prednisone per day. Following treatment with intranasal beclomethasone the middle ear effusion resolved in only 48% of children (SCHWARTZ et al., 1980b). A placebo-controlled trial by LINDHOLDT and KORTHOLM (1982) also failed to show a significant difference in favour of intranasal beclomethasone therapy. To obtain information on the role of prednisolone in the management of OME, we performed a clinical study in children with secretory middle ear effusion. The study was designed as a double-blind trial to compare the effects of prednisolone, sulfatrimethoprim and placebo. The outcome of therapy was assessed in a clinical follow-up of 2 months.

Effect of Inhaled Beclomethasone Dipropionate on Hypothalamic-Pituitary-Adrenal Axis Function in Children with Asthma

The hypothalamic-pituitary-adrenal axis was investigated in 15 asthmatic children treated with inhaled beclomethasone dipropionate (mean 490 micrograms/day) and 11 asthmatic control subjects receiving no corticosteroid therapy. Measurements of 24-h urinary free cortisol and 17 hydroxy corticosteroids, serum cortisol, response to ACTH, and the oral metyrapone test showed no significant difference between the two groups. All the patients' results were within normal limits, and carbohydrate metabolism, as shown by blood glucose and hemoglobin A1c, was not affected by beclomethasone therapy. Thus, in the above dose, inhaled beclomethasone does not cause suppression of the hypothalamic-pituitary-adrenal axis.

Beclomethasone in steroid-dependent asthma. Effective therapy and recovery of hypothalamo-pituitary-adrenal function

Beclomethasone dipropionate was administered by aerosol to 30 patients whose chronic bronchial asthma required oral corticosteroid therapy. During the initial 12 weeks of the trial, beclomethasone therapy could be discontinued in 12 of 16 patients in contrast to only one of 14 patients receiving the inert aerosol placebo. Patients receiving the placebo were then given beclomethasone, and prednisone therapy was discontinued in five more. During six months of observation, adrenal function improved and steroid toxic reactions decreased in patients in whom oral corticosteroid therapy had been discontinued. Beclomethasone aerosol was generally well-tolerated. Asymptomatic thrush developed in four patients and rhinitis developed in ten patients as prednisone therapy was discontinued.

Beclomethasone in Steroid-Dependent Asthma

Beclomethasone dipropionate was administered by aerosol to 30 patients whose chronic bronchial asthma required oral corticosteroid therapy. During the initial 12 weeks of the trial, beclomethasone therapy could be discontinued in 12 of 16 patients in contrast to only one of 14 patients receiving the inert aerosol placebo. Patients receiving the placebo were then given beclomethasone, and prednisone therapy was discontinued in five more. During six months of observation, adrenal function improved and steroid toxic reactions decreased in patients in whom oral corticosteroid therapy had been discontinued. Beclomethasone aerosol was generally well-tolerated. Asymptomatic thrush developed in four patients and rhinitis developed in ten patients as prednisone therapy was discontinued. (<i>JAMA</i>238:1508-1511, 1977)