(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Body-Weight

Beclomethasone dipropionate administered by metered-dose inhaler to ventilated infants with early chronic lung disease was evaluated in a double-blind, placebo-controlled study to determine the feasibility and safety of administration. Patients selected for study were less than 1500 g birthweight, had previous radiographic evidence of respiratory distress syndrome with early changes of bronchopulmonary dysplasia (BPD), were greater than 2 weeks of age, and had failed attempts at extubation. The metered-dose inhaler was connected to the respirator circuit by an in-line spacer device and either saline placebo or beclomethasone was delivered for 7 days or until extubated. Beclomethasone was delivered in a dose calculated to be approximately 1 mg/kg/day in three divided doses. Nineteen infants were enrolled. Nine received placebo and 10 received beclomethasone. No adverse effects on blood pressure, heart rate, respiratory rate, ventilator settings, concentration or duration of oxygen therapy, incidence of retinopathy of prematurity (ROP) or infections, blood glucose, daily weight, or serum cortisol levels before and after adrenal stimulation tests were observed in the beclomethasone group compared with the placebo group. One infant in the placebo and six infants in the steroid group were extubated during the study period (p = 0.03). These data indicate that beclomethasone dipropionate may be administered safely to intubated neonates without adverse effects of hypertension, hyperglycemia, diminished weight gain, or adrenal suppression frequently seen with systemic steroid administration. Beclomethasone may enhance extubation in infants with early BPD, however, further data are required to substantiate this preliminary observation.

Topics: Anti-Inflammatory Agents; Bacterial Infections; Beclomethasone; Blood Glucose; Blood Pressure; Body Weight; Bronchopulmonary Dysplasia; Double-Blind Method; Feasibility Studies; Female; Glucocorticoids; Heart Rate; Humans; Hydrocortisone; Infant, Low Birth Weight; Infant, Newborn; Male; Nebulizers and Vaporizers; Oxygen Inhalation Therapy; Placebos; Respiration; Respiratory Distress Syndrome, Newborn; Retinopathy of Prematurity; Safety; Sodium Chloride; Ventilators, Mechanical

Following a short-term clinical trial reported elsewhere, beclomethasone dipropionate aerosol has been given to 15 children with asthma for between 2 1/2 and 3 years except for a short placebo period after the first year. Month-by-month records of wheezing, peak flow rate, and other treatments used are presented for the first 17 months, adrenocortical function tests are reported for the first 2 years, and growth is recorded for 2 1/2-3 years. The short-term clinical benefits of the treatment are confirmed in the longer term, adrenocortical function appears to be unchanged, and growth proceeds along expected lines. The main disadvantage seems to be worsening of eczema and allergic rhinitis in those children who have ceased using corticotrophin or oral steroids for the control of asthma. It is concluded that in the long term beclomethasone dipropionate aerosol provides safe and effective day-to-day control of asthma in children, although occasional recourse to systemic steroid therapy cannot be avoided. Oral candidasis has not been a clinical problem.

Topics: Adolescent; Adrenal Cortex Function Tests; Aerosols; Asthma; Beclomethasone; Body Height; Body Weight; Child; Clinical Trials as Topic; Cosyntropin; Female; Humans; Male; Methylprednisolone; Placebos; Rhinitis, Allergic, Seasonal

Beclomethasone dipropionate was found to be effective in reducing symptoms of asthma in children. There was no measurable influence on pulmonary function. An 18-month follow-up did not show untoward side effects on adrenal function, growth, serum electrolytes, and hepatic and renal functions with a dose of 100 mug three times daily. The treatment predisposes to the colonization with Candida albicans in the oropharynx.

Topics: Adrenal Cortex Function Tests; Asthma; Beclomethasone; Body Height; Body Weight; Child; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Respiratory Function Tests

Topics: Adrenal Cortex Hormones; Adrenal Glands; Aerosols; Asthma; Beclomethasone; Body Weight; Bronchitis; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone; Middle Aged; Substance-Related Disorders

Topics: 17-Ketosteroids; Administration, Topical; Adult; Aerosols; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Blood Pressure; Body Weight; Clinical Trials as Topic; Female; Humans; Hydrocortisone; Hydroxysteroids; Lung; Male; Middle Aged; Spirometry; Steroids; Substance-Related Disorders

Thirty-one chronic perennial asthmatics aged from 2(1/2) to 16 years were treated with beclomethasone dipropionate pressurized aerosols for up to 20 months. Of these, 16 patients dependent on oral corticosteroid or corticotrophin for up to 11 years were successfully transferred to this treatment, with one exception. Steroid withdrawal symptoms were slight. Loss of weight, disappearance of Cushingoid features, and resumption of growth indicated lack of systemic side effects. Fifteen others inadequately controlled on bronchodilators or disodium cromoglycate, were also effectively treated, and no clinical evidence of adrenal suppression was noted.

Topics: Administration, Oral; Administration, Topical; Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Body Weight; Child; Child, Preschool; Clinical Trials as Topic; Cromolyn Sodium; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Spirometry

In order to estimate predisposing activity of oral application of beclomethasone dipropionate (BDP)-containing mucoadhesive films for oral candidiasis, the effects of BDP on growth of Candida albicans were examined in vivo and in vitro. Murine neutrophils inhibited the mycelial growth of C. albicans in vitro, but this anti-Candida activity was clearly suppressed by the presence of 10(-6) M of BDP. In vitro, a BDP-release test showed that the amount of BDP released from BDP-containing films into the fluid phase increased in a time- and concentration-dependent manner and reached about 10-15% of the total amount of BDP in the film within 30 min. When the BDP-containing film was attached to the tongues of mice orally infected with C. albicans, oral infection by C. albicans deteriorated, but not as severely as in mice systemically immunosuppressed with prednisolone. Based on these findings, we also discuss the problems associated with the clinical application of BDP-film as an anti-inflammatory tool.

Topics: Administration, Oral; Animals; Beclomethasone; Body Weight; Candida albicans; Candidiasis, Oral; Glucocorticoids; Mice; Mice, Inbred ICR; Mycelium; Neutrophils; Tongue

We studied the effect of inhaled corticosteroids on the increase in bone mineral content in prepubertal children with asthma. Forty-eight asthmatic, prepubertal children receiving either inhaled beclomethasone dipropionate or budesonide were evaluated. Nine children of similar age not receiving inhaled steroids served as controls. The average age of corticosteroid-treated children was 7.8 +/- 2.4 years, and of control children, 8.4 +/- 2.1 years (NS). The average dose of inhaled corticosteroids in the treated children was 0.67 +/- 0.48 mg/m(2)/day, and they were followed over a 9-20-month period. Total bone mineral content (TBMC) was measured at baseline and after 9-20 months. A derived value for 12 months' TBMC was calculated, assuming that changes in TBMC were linear with the passage of time. The change in TBMC over a 12-month period was 264 +/- 68 mg for the corticosteroid-treated children and 330 +/- 84 mg for control children (P < 0.025). In a multiple regression analysis in which adjustments were made for the effects of age, height, and weight, the change in TBMC in corticosteroid-treated children was inversely related to the inhaled steroid dose/m(2)/day (P = 0.016). The increase in the lumbar vertebral bone mineral density in control children was also significantly greater than in the corticosteroid-treated children (P < 0.025). We conclude that inhaled steroids, at an average dose of 0.67 mg/m(2)/day, when used in the treatment of asthma reduce the acquisition of bone mineral in prepubertal children.

Topics: Absorptiometry, Photon; Administration, Inhalation; Administration, Topical; Adolescent; Age Factors; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Body Height; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Female; Follow-Up Studies; Glucocorticoids; Humans; Linear Models; Lumbar Vertebrae; Male; Puberty

Childhood asthma generally responds well to inhaled corticosteroids within the dosage range recommended by the manufacturers, but it is sometimes necessary to use higher doses--that is, above 400 micrograms/day--a practice which has become more widespread recently. Whereas the lack of adrenal suppression in children given inhaled corticosteroids in normal doses is well documented, little is known about the effects of higher doses.. The effects on adrenal function of high dose (above 400 micrograms/day) inhaled corticosteroids were evaluated by measuring cortisol concentration in the morning and performing a short tetracosactrin test in 49 children taking budesonide (mean age 9.2 years (range 4 to 16 years) and 28 children taking beclomethasone dipropionate (10.2 years (5 to 13 years)). Twenty three non-asthmatic children (8.9 years (4.9 to 13 years)) who were under investigation for short stature served as controls for the study.. Compared with controls mean basal cortisol concentration was lower in children taking budesonide and beclomethasone dipropionate (control 401 (26.8) nmol/l, budesonide 284 (22) nmol/l, beclomethasone dipropionate 279 (23.2) nmol/l). Sixteen of the 49 children taking budesonide had subnormal basal cortisol concentrations compared with seven of the 28 taking beclomethasone dipropionate. Mean stimulated cortisol concentrations were lower in children taking inhaled corticosteroids than in controls, with no difference between those taking budesonide or beclomethasone dipropionate.. Adrenal suppression occurs in some children who are given inhaled corticosteroids in doses greater than 400 micrograms/day. It may therefore be advisable to try alternative treatments before such doses are used.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex; Asthma; Beclomethasone; Body Height; Body Weight; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Female; Humans; Hydrocortisone; Male; Pregnenediones; Time Factors

Seven children from 3 to 14 years old with chronic steroid-dependent asthma were treated with methotrexate (MTX). Asthma in all of the patients had been poorly controlled for at least 2 years despite the use of oral theophylline and inhaled corticosteroids, cromolyn and albuterol. All presented with significant side effects as a result of chronic systemic steroid therapy. Five patients were atopic and had been unable to tolerate immunotherapy because of systemic reactions. Forced expiratory volume in 1 second and forced expiratory flow, mid-expiratory phase, improved in four patients after 4 to 6 months of treatment with doses of MTX ranging from 7.5 to 17.5 mg/wk. Three patients were able to discontinue their systemic corticosteroids. Laboratory values including complete blood cell count with differential and liver enzymes remained at baseline in all except one patient, who had transient elevation in alanine aminotransferase and aspartate aminotransferase. One patient experienced side effects sufficient to require discontinuation of MTX. It is concluded that MTX is effective for reducing the need for systemic corticosteroids and for improving pulmonary functions in some individuals. The benefits of MTX in this group of severe asthmatics appear to justify the potential risks involved in its use.

Topics: Adolescent; Albuterol; Asthma; Beclomethasone; Body Height; Body Weight; Child; Child, Preschool; Cromolyn Sodium; Female; Forced Expiratory Volume; Humans; Male; Maximal Expiratory Flow Rate; Methotrexate; Prednisone; Spirometry; Theophylline; Vital Capacity

The efficacy and side effects of the oral H1-antihistamine, astemizole, were compared with those of nasal beclomethasone in 158 adult birch-pollen allergic hay fever patients. 148 patients completed the 5-week, controlled trial which took place in Stockholm, May 1986, during the birch pollen season. Daily pollen counts were found to be at a rather low level throughout the study period. The effect and tolerability of both drugs were found to be excellent, although beclomethasone reduced nasal symptoms (sneezing, rhinorrhoea, blocked nose) significantly more effectively than astemizole. Eye symptoms were mild and equal in both groups. The results indicate that oral astemizole is an effective non-sedating antihistamine, though less so than nasal beclomethasone, in the treatment of nasal hay fever symptoms.

Topics: Administration, Oral; Adolescent; Adult; Astemizole; Beclomethasone; Benzimidazoles; Body Weight; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Rhinitis, Allergic, Seasonal

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.

Topics: Administration, Inhalation; Adolescent; Asthma; Beclomethasone; Blood Cell Count; Body Height; Body Weight; Candidiasis; Cataract; Child; Female; Growth; Hematocrit; Hemoglobins; Humans; Hydrocortisone; Immunoglobulins; Male; Prednisone

Height and weight were measured every six months in a long term prospective study of 66 children with chronic perennial asthma for a mean 13.1 years. There was no evidence of growth retardation on entry into the study. Growth developed along normal lines in all 66 children until about 10 years, and in 35 of these children growth continued along normal lines throughout the whole period of follow up. Thirty children showed the physiological decelerating growth velocity pattern seen in children with delay in the onset of puberty, and one child had an early menarche. The tendency for delay in the onset of puberty was significant for both boys and girls and was noted to be independent of severity of asthma. Once puberty finally began in these children, complete catch up growth resulted in the attainment of the predicted adult height. Long term prophylactic inhalation of beclomethasone dipropionate in 26 children in a dosage up to 600 mcg/day before puberty and 400 mcg/day during puberty was shown not to affect growth. It is concluded that asthma had no direct influence on growth in height but was associated with delay in the onset of puberty. The pre-adolescent physiological deceleration of growth velocity that occurs in these children gives the impression of growth retardation.

Topics: Asthma; Beclomethasone; Body Height; Body Weight; Child; Chronic Disease; Cromolyn Sodium; Female; Growth; Humans; Male; Prednisolone; Prospective Studies; Puberty, Delayed; Time Factors

Mechanical ventilation of the newborn is now widely used in neonatal intensive care. The oro-tracheal route of intubation is simpler, but for long-term ventilation has been considered unstable. A method of fixation of oro-tracheal tubes is described which overcomes this instability. Five hundred consecutive ventilated infants were intubated by the oro-tracheal route and the tube was fixed by the method described. Of the 500 ventilated infants, 213 died without being extubated. Of the 287 survivors, 44 developed a degree of post-extubation stridor. No surviving infant developed clinical evidence of subglottic stenosis and in almost 200 postmortem examinations laryngeal narrowing was not identified. The method of oro-tracheal fixation described is stable and may reduce the incidence of subglottic stenosis.

Topics: Beclomethasone; Body Weight; Humans; Infant, Newborn; Infant, Premature; Intubation, Intratracheal; Laryngostenosis; Respiration, Artificial; Respiratory Sounds

Excellent clinical results were obtained in 85 patients with chronic asthma who took corticosteroids (mostly triamcinolone) on a long-term basis for periods varying from one to 26 years. There was a minimum of side-effects, none serious; the most discomforting were ecchymosis and a tendency to easy bruising. The results of this and previous studies have convinced the author that corticosteroids, if judiciously used, are the most valuable adjunct we have in the treatment of acute and chronic asthma.

Topics: Acne Vulgaris; Adrenal Cortex Hormones; Asthma; Beclomethasone; Betamethasone; Body Weight; Dose-Response Relationship, Drug; Ecchymosis; Edema; Hirsutism; Humans; Prednisone; Triamcinolone

Topics: Administration, Oral; Adult; Aged; Beclomethasone; Blood Glucose; Blood Pressure; Body Weight; Eosinophils; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Pituitary-Adrenal Function Tests; Prednisolone; Respiratory Function Tests; Respiratory Therapy

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.

Topics: Administration, Oral; Adolescent; Aerosols; Asthma; Beclomethasone; Body Height; Body Weight; Child; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Steroids; Time Factors

Topics: Adrenal Gland Diseases; Adult; Asthma; Beclomethasone; Body Weight; Humans; Hydrocortisone; Male; Prednisolone; Substance Withdrawal Syndrome