Nebulised beclomethasone dipropionate suspension.

We compared nebulised beclomethasone dipropionate suspension against placebo in 16 children with moderately severe asthma in double blind crossover fashion. Three children withdrew due to deterioration while on placebo. Of the remaining 13, eight were better on beclomethasone and five on placebo. These trends in favour of nebulised beclomethasone were not significant and do not suggest that the suspension is as effective as inhaled powder or aerosol topical steroid formulation.     

Nebulised beclomethasone dipropionate in preschool asthma.

Twenty nine young children with severe recurrent asthma were given nebulised beclomethasone dipropionate or normal saline in a double blind manner over a six month period. Progress was monitored using diary score cards. Those receiving beclomethasone had lower symptom scores, had more symptom free days, and required less additional treatment with bronchodilator agents. The code needed to be broken more frequently if normal saline was used. Over the study period height and weight increases in the two groups were similar, and no serious side effects were noted.     

Respiratory problems 2 years after acute bronchiolitis in infancy.

We assessed the clinical progress of 55 children 2 years after admission to hospital with acute bronchiolitis and performed lung function tests on 40. During the 2 year follow up period 75% of the children had wheezed, 36% had 2 or more lower respiratory symptoms lasting more than 2 weeks, 33% had more than 100 days of lower respiratory symptoms, and 13% were readmitted to hospital with acute respiratory disease. In addition 60% of the children were hyperinflated on lung function tests. Many of the children with hyperinflation at the 2 year assessment had not been hyperinflated 1 year earlier, suggesting variable airways obstruction. Reversibility of airways obstruction was also assessed by response to nebulised salbutamol. Nine children had a fall greater than 15% in airways resistance after salbutamol and these children had the highest baseline airways resistances. Airways resistance was higher in the children with a family history of atopy.     

Respiratory problems 2 years after acute bronchiolitis in infancy

We assessed the clinical progress of 55 children 2 years after admission to hospital with acute bronchiolitis and performed lung function tests on 40. During the 2 year follow up period 75% of the children had wheezed, 36% had 2 or more lower respiratory symptoms lasting more than 2 weeks, 33% had more than 100 days of lower respiratory symptoms, and 13% were readmitted to hospital with acute respiratory disease. In addition 60% of the children were hyperinflated on lung function tests. Many of the children with hyperinflation at the 2 year assessment had not been hyperinflated 1 year earlier, suggesting variable airways obstruction. Reversibility of airways obstruction was also assessed by response to nebulised salbutamol. Nine children had a fall greater than 15% in airways resistance after salbutamol and these children had the highest baseline airways resistances. Airways resistance was higher in the children with a family history of atopy.     

Treatment of acute,episodic asthma in preschool children using intermittent high dose inhaled steroids at home.

In a double blind, controlled trial, the effect of high dose beclomethasone dipropionate (750 micrograms three times daily for five days) administered by metered dose inhaler and valved spacer, was compared with placebo, during 70 paired episodes of acute asthma in 24 preschool children. Treatment commenced at home at the first sign of an attack. Parents'' blind preference for active treatment was significant. Data from 17 pairs of treatment, however, were affected by interventions such as hospital admission or oral corticosteroid treatment. These events occurred similarly in active and control periods. An intrasubject comparison was made of diary scores from the 18 pairs of episodes in which no intervention occurred in either the active or placebo treatment. Both daytime and night symptoms over the first week of the attack were significantly reduced by active treatment. Intermittent high dose inhaled beclomethasone dipropionate is beneficial in modifying the severity of acute episodic asthma in preschool children able to use a spacer device.     

Osteocalcin, growth, and inhaled corticosteroids: a prospective study

OBJECTIVES: To determine the relationship between biochemical markers of bone metabolism and statural growth, and their suitability as surrogate markers of inhaled corticosteroid induced growth suppression. DESIGN: Randomised, double blind, placebo controlled comparison of inhaled beclomethasone dipropionate 200 micrograms twice daily as dry powder for six months. SETTING: Southampton. OUTCOME MEASURES: Serum osteocalcin, urinary deoxypyridinoline, and statural growth. SUBJECTS: 7 to 9 year old children with recurrent wheeze. RESULTS: There were no significant differences in serum osteocalcin between the beclomethasone dipropionate and placebo group measured at baseline or after three and six months' treatment, while deoxy-pyridinoline was significantly higher in the placebo treated children after three months. Growth was significantly decreased in the beclomethasone dipropionate group over the course of the study. Growth over the six months, both in those receiving beclomethasone dipropionate and those receiving placebo, was significantly correlated with serum osteocalcin measured at three months and six months. CONCLUSION: Although serum osteocalcin shows excellent correlation with growth, it is a poor marker for decreased growth associated with use of inhaled corticosteroids.     

Osteocalcin,growth, and inhaled corticosteroids: a prospective study.

OBJECTIVES: To determine the relationship between biochemical markers of bone metabolism and statural growth, and their suitability as surrogate markers of inhaled corticosteroid induced growth suppression. DESIGN: Randomised, double blind, placebo controlled comparison of inhaled beclomethasone dipropionate 200 micrograms twice daily as dry powder for six months. SETTING: Southampton. OUTCOME MEASURES: Serum osteocalcin, urinary deoxypyridinoline, and statural growth. SUBJECTS: 7 to 9 year old children with recurrent wheeze. RESULTS: There were no significant differences in serum osteocalcin between the beclomethasone dipropionate and placebo group measured at baseline or after three and six months'' treatment, while deoxy-pyridinoline was significantly higher in the placebo treated children after three months. Growth was significantly decreased in the beclomethasone dipropionate group over the course of the study. Growth over the six months, both in those receiving beclomethasone dipropionate and those receiving placebo, was significantly correlated with serum osteocalcin measured at three months and six months. CONCLUSION: Although serum osteocalcin shows excellent correlation with growth, it is a poor marker for decreased growth associated with use of inhaled corticosteroids.     

Nebulized budesonide after hospitalization for recurrent bronchial obstruction in children younger than 18 months

A multi‐center, double‐blind, randomized dose–response study was performed to assess the effect of 3 months of treatment with two different doses of inhaled nebulized budesonide in children with acute recurrent bronchial obstruction (BO) causing hospitalization. Steroid‐naive children younger than 18 months were included when admitted to hospital because of BO for at least the second time, and were followed‐up monthly for 15 months. Forty‐five of 49 subjects (43 boys, 2 girls) (mean age 9.3 months upon inclusion) completed the study. Twenty‐four patients (20 boys, 4 girls) received nebulized budesonide 0.5 mg twice daily for 1 month followed by 0.25 mg daily for the next 2 months, whereas 25 children received 0.1 mg twice daily throughout the 3‐month treatment period. Outcome (number of BO episodes, time to first BO after start of treatment, and use of rescue medication), as well as height/length and weight, were assessed at the start of treatment and monthly for the following 3 months, as well as for 12 months after cessation of treatment (15 months in total). There was an overall tendency towards better symptom control (fewer episodes of acute BO during treatment and follow‐up, fewer hospital visits because of acute BO, lower clinical score during follow‐up, and less use of rescue medication during follow‐up) in the high‐dose treatment group vs. the low‐dose treatment group. However, the differences did not reach statistical significance for any of the outcomes. The only significant difference in effect between the groups was fewer children in the high‐dose group treated openly with nebulized budesonide during follow‐up. Length/height and weight gain did not differ significantly between the two treatment groups throughout the study. There was no significant dose‐dependent beneficial effect of 3 months of treatment with nebulized budesonide in infants and toddlers with at least two hospitalizations for acute bronchial obstruction.     

The effects of inhaled beclomethasone dipropionate on lung function and histamine responsiveness in recurrently wheezy infants.

Inhaled steroids improve pulmonary function and bronchial responsiveness in older asthmatics. Data from studies using subjective outcome measures to determine the effectiveness of inhaled steroids in infants with recurrent wheezing are equivocal. Therefore, this study tested the hypothesis that beclomethasone dipropionate improves pulmonary function, including bronchial responsiveness to histamine, in recurrently wheezy infants. The study was double blind, placebo controlled lasting nine weeks. After the first baseline week, pulmonary function was measured using the rapid thoracoabdominal compression technique and bronchial responsiveness assessed with a histamine challenge test. Infants were then randomly allocated to receive doses of placebo or beclomethasone dipropionate (100 micrograms/puff) from metered aerosols. Two puffs of test aerosol were administered twice daily for eight weeks via a large volume spacer fitted with a facemask. Symptoms were recorded daily and pulmonary function and bronchial responsiveness assessed at the end of the treatment period; 50 infants, median age 12 months (range 5 to 18 months), were recruited. Twenty three in the beclomethasone dipropionate group and 15 in the placebo group completed the study and had pairs of pulmonary function measurements. Three were probable treatment failures (one beclomethasone dipropionate, two placebo), three were possible treatment failures (placebo), and others were non-compliant with study protocol. Baseline variables were not significantly different between those infants who completed the study and those who did not. Beclomethasone dipropionate and placebo groups were similar in all respects at baseline. Lung function and symptoms improved for both groups of infants during the study. Bronchial responsiveness increased significantly in the placebo group but there were not statistically significant differences between groups for any of the other outcome measures. It is concluded that beclomethasone dipropionate (400 microgram daily) via a large volume spacer does not significantly improve lung function or symptoms in recurrently wheezy infants but might hav a beneficial effect on bronchial responsiveness.     

Beclomethasone dipropionate aerosol in treatment of hay fever in children.

Eighteen children suffering from hay fever were treated with intra-nasal beclomethasone dipropionate (400 mug/day) and an identical placebo aerosol in a double-blind cross-over trial. 17 of the children preferred the intranasal beclomethasone dipropionate, one had no preference, none preferred the placebo. The effect on the nasal symptoms was impressive. Symptom scores decreased, on average, to 12% and the number of antihistamine tablets taken to 18% of the pretreatment amount. Some beneficial effect on eye symptoms was also discernible, possibly due to an indirect influence from the nasal mucosa via the nasolacrimal reflex. Adrenal function was not affected. It was concluded that 400 mug beclomethasone dipropionate given intranasally daily for some weeks is an effective and safe treatment for hay fever in children.     

Inhaled corticosteroids during and after respiratory syncytial virus-bronchiolitis may decrease subsequent asthma

Respiratory syncytial virus (RSV) bronchiolitis in infancy can lead to bronchial hyper-reactivity or recurrent obstructive bronchitis. The aim of the present study was to determine whether the type of treatment has an influence on respiratory status after RSV bronchiolitis. The study involved 117 infants (mean age 2.6 months), who needed hospital treatment because of RSV bronchiolitis. The patients were divided randomly into three groups. All received the same symptomatic treatment. Group I children received symptomatic treatment only, group II children were treated for 7 days with inhaled budesonide, 500 µg three times per day, administered via a nebulizer. Group III children received nebulized budesonide, 500 µg twice per day for two months. Follow-up consisted of out-patient check-ups 2 and 6 months after the infection, and telephone contact two years after the infection. Statistically significant differences were seen between the groups. In group I 37% of the children had asthma, in group II 18%, and in group III 12%. According to the present study it seems that inhaled corticosteroid treatment during and after the acute phase of infant RSV bronchiolitis may have a beneficial effect on subsequent bronchial wheezing tendency.     

Intermittent treatment with high dose nebulized beclomethasone for recurrent wheezing in infants due to upper respiratory tract infection

BACKGROUND: To investigate if high dose inhaled beclomethasone dipropionate started early after upper respiratory tract infection (URTI) could reduce recurrent wheezing in infants. METHODS: Twenty-six ambulatory infants, 7-12 months of age, with recurrent wheezing during upper respiratory tract infection participated. All experienced at least three wheezing attacks. Those with underlying lung or systemic disease were excluded. Infants were divided into two groups in an open unblinded manner, until 13 patients had been recruited for each group. The groups were similar in risk factors for recurrent wheezing. Four treatment periods of 5 days were planned for group 1. The dose regimen was nebulized beclomethasone 400 mg by mask tid for 5 days. Treatment was started at the very first sign of URTI prior to any sign of wheezing. Group 2 did not receive any preventive treatment and constituted the control group. Symptoms scores were recorded. The number of emergency room visits, hospital admissions and short courses with oral steroids was also noted. RESULTS: Twelve infants completed 48 treatment periods. Five visited the emergency room, only one during beclomethasone therapy. Six received oral steroids, two receiving beclomethasone. No patient was admitted to the hospital. Symptom scores were significantly lower during beclomethasone treatment (p<0.05). No apparent adverse events were reported. CONCLUSIONS: The infant with recurrent wheezing during URTI is a therapeutic challenge. Most of these infants have prodromal symptoms for about 24 hours before wheezing starts. In the present study we observed favorable results, decrease in the number the child wheezed and the number of acute attacks, when high dose inhaled beclomethasone is administered during this critical time.     

Short-term growth during treatment with inhaled fluticasone propionate and beclomethasone dipropionate.

Short-term lower leg growth was investigated with twice weekly knemometry measurements in 19 schoolchildren with mild asthma during treatment with daily doses of 200 micrograms fluticasone propionate, 400 micrograms, and 800 micrograms beclomethasone dipropionate from a dry powder inhaler. The design was a randomised, double blind, crossover trial. After a run in period of four days (period 1) the children were allocated to a sequence of active treatments in periods 2, 4, and 6. In periods 3 and 5 (wash out) placebo was given. All periods except the run in were two weeks long. The mean lower leg growth velocities during the wash out periods were 0.61 and 0.80 mm/week. Mean growth velocities during treatment with fluticasone propionate and low and high doses of beclomethasone dipropionate were 0.34, 0.09, and 0.06 mm/week respectively. Compared with fluticasone propionate, treatment with beclomethasone dipropionate 400 and 800 micrograms/day was associated with a statistically significant reduction in growth velocity.     

Short-term growth during treatment with inhaled fluticasone propionate and beclomethasone dipropionate

Short-term lower leg growth was investigated with twice weekly knemometry measurements in 19 schoolchildren with mild asthma during treatment with daily doses of 200 micrograms fluticasone propionate, 400 micrograms, and 800 micrograms beclomethasone dipropionate from a dry powder inhaler. The design was a randomised, double blind, crossover trial. After a run in period of four days (period 1) the children were allocated to a sequence of active treatments in periods 2, 4, and 6. In periods 3 and 5 (wash out) placebo was given. All periods except the run in were two weeks long. The mean lower leg growth velocities during the wash out periods were 0.61 and 0.80 mm/week. Mean growth velocities during treatment with fluticasone propionate and low and high doses of beclomethasone dipropionate were 0.34, 0.09, and 0.06 mm/week respectively. Compared with fluticasone propionate, treatment with beclomethasone dipropionate 400 and 800 micrograms/day was associated with a statistically significant reduction in growth velocity.     

Eosinophil cationic protein in nasal secretion and in serum and myeloperoxidase in serum in respiratory syncytial virus bronchiolitis: relation to asthma and atopy

Eosinophil cationic protein (ECP) in nasal secretions was determined in 34 infants with respiratory syncytial virus (RSV) bronchiolitis during the acute infection stage and one and six months later. ECP in serum was determined in 19 of these children at the same time. Myeloperoxidase (MPO) was determined in the same 19 children at the acute infection stage and after one month. All children were followed prospectively for two years after the infection with regard to the development of bronchial obstructive symptoms. Asthma, defined as three or more episodes of bronchial obstruction verified by a physician, developed in 18% of children and less severe obstructive symptoms in 29%. A screening test for food IgE antibodies in serum was performed six months and a skin prick test two years after the acute infection. Nasal ECP/albumin ratios after six months were significantly higher than during the acute RSV infection. MPO, but not ECP, levels in serum were significantly elevated at the time of acute infection compared with levels after one month. Nasal ECP/albumin ratios at the acute infection were compared to a control group of 27 infants with non-RSV upper respiratory tract infections and did not differ. It was not possible to predict, either from ECP/albumin ratios in nasal secretion or from ECP and MPO in serum, which children would develop asthma, other bronchial obstructive symptoms or positive IgE tests.     

Randomised controlled trial of budesonide for the prevention of post-bronchiolitis wheezing.

BACKGROUND: Previous studies suggest that recurrent episodes of coughing and wheezing occur in up to 75% of infants after acute viral bronchiolitis. AIM: To assess the efficacy of budesonide given by means of a metered dose inhaler, spacer, and face mask in reducing the incidence of coughing and wheezing episodes up to 12 months after acute viral bronchiolitis. METHODS: Children under the age of 12 months admitted to hospital with acute viral bronchiolitis were randomised to receive either budesonide or placebo (200 microg or one puff twice daily) for the next eight weeks. Parents kept a diary card record of all episodes of coughing and wheezing over the next 12 months. RESULTS: Full follow up data were collected for 49 infants. There were no significant differences between the two study groups for the number of infants with symptom episodes up to six months after hospital discharge. At 12 months, 21 infants in the budesonide group had symptom episodes compared with 12 of 24 in the placebo group. The median number of symptom episodes was 2 (range, 0-13) in those who received budesonide and 1 (range, 0-11) in those who received placebo. Because there is no pharmacological explanation for these results, they are likely to be caused by a type 1 error, possibly exacerbated by there being more boys in the treatment group. CONCLUSION: Routine administration of budesonide by means of a metered dose inhaler, spacer, and face mask system immediately after acute viral bronchiolitis cannot be recommended.     

Randomised controlled trial of budesonide for the prevention of post-bronchiolitis wheezing

BACKGROUND—Previous studies suggest that recurrent episodes of coughing and wheezing occur in up to 75% of infants after acute viral bronchiolitis.AIM—To assess the efficacy of budesonide given by means of a metered dose inhaler, spacer, and face mask in reducing the incidence of coughing and wheezing episodes up to 12 months after acute viral bronchiolitis.METHODS—Children under the age of 12 months admitted to hospital with acute viral bronchiolitis were randomised to receive either budesonide or placebo (200 µg or one puff twice daily) for the next eight weeks. Parents kept a diary card record of all episodes of coughing and wheezing over the next 12months.RESULTS—Full follow up data were collected for 49 infants. There were no significant differences between the two study groups for the number of infants with symptom episodes up to six months after hospital discharge. At 12 months, 21 infants in the budesonide group had symptom episodes compared with 12 of 24 in the placebo group. The median number of symptom episodes was 2 (range, 0-13) in those who received budesonide and 1 (range, 0-11) in those who received placebo. Because there is no pharmacological explanation for these results, they are likely to be caused by a type 1 error, possibly exacerbated by there being more boys in the treatment group.CONCLUSION—Routine administration of budesonide by means of a metered dose inhaler, spacer, and face mask system immediately after acute viral bronchiolitis cannot be recommended.     

Nebulised racemic adrenaline in the treatment of acute bronchiolitis in infants and toddlers

The effect of inhaled nebulised racemic adrenaline upon symptoms of acute bronchiolitis was investigated in 29 infants and toddlers aged 2-17.5 months by transcutaneous oxygen tension (TcPO2), oxygen saturation, transcutaneous carbon dioxide tension (TcPCO2), and clinical evaluation in a double blind placebo controlled study. Clinical score and TcPO2 improved significantly at 30, 45, and 60 minutes after inhalation of racemic adrenaline, with an increase in TcPO2 > or = 0.5 kPa in 72% of the children < 1 year of age. No significant improvement was observed after inhalation of placebo. No significant changes in heart rate or TcPCO2 were observed from before to after inhalation, but a small increase in mean systolic blood pressure was observed immediately and 45 minutes after racemic adrenaline inhalation. This study demonstrates that treatment with nebulised racemic adrenaline improved oxygenation and clinical signs in hospitalised children aged less than 18 months with bronchiolitis.     

Nebulised racemic adrenaline in the treatment of acute bronchiolitis in infants and toddlers.

The effect of inhaled nebulised racemic adrenaline upon symptoms of acute bronchiolitis was investigated in 29 infants and toddlers aged 2-17.5 months by transcutaneous oxygen tension (TcPO2), oxygen saturation, transcutaneous carbon dioxide tension (TcPCO2), and clinical evaluation in a double blind placebo controlled study. Clinical score and TcPO2 improved significantly at 30, 45, and 60 minutes after inhalation of racemic adrenaline, with an increase in TcPO2 > or = 0.5 kPa in 72% of the children < 1 year of age. No significant improvement was observed after inhalation of placebo. No significant changes in heart rate or TcPCO2 were observed from before to after inhalation, but a small increase in mean systolic blood pressure was observed immediately and 45 minutes after racemic adrenaline inhalation. This study demonstrates that treatment with nebulised racemic adrenaline improved oxygenation and clinical signs in hospitalised children aged less than 18 months with bronchiolitis.