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Knowledge of pediatricians in Rio de Janeiro, Brazil, about inhalation therapy in asthmatic children.

BACKGROUND: Despite the numerous guidelines on the diagnosis and treatment of asthma, there are data that indicate that general pediatrician's knowledge of the disease and its preferred treatment is limited, which may influence the quality of care given to asthmatic children. The purpose of this study was to describe pediatrician's knowledge of spacers and of concepts of chilhood asthma, as well as their prescribing habits concerning inhalation therapy, in the public health system of the city of Rio de Janeiro. METHODS AND RESULTS: A descriptive cross-sectional study was performed in a sample of 72 pediatricians from the public health system of Rio de Janeiro. A questionnaire was used to assess prescriptions for spacers, the reasons whay spacers were not used, the models employed, classification of asthma according to clinical severity and symptom frequency, recommendation for the correct spacer volume according to age group, and the concept of asthma as an inflammatory disease. Seventy percent (51/72) of the physicians did not routinely prescribe the spacer. The reasons given were as follows: a) lack of spacer availability in the public health system in 55 % (28/51); b) high cost in 57 % (29/51); c) the complexity of their use in 35 % (18/51); d) unwillingness to use aerosol type medication in 15 % (8/51), and e)lack of knowledge of their function and utilization in 59 % (30/51). Of the 30 % (21/72) who reported they regularly and routinely prescribed the spacer in daily practice, 48 % (10/21) stated that this routine prescription, even when indicated, was below 25 % of what was expected and makeshift models were preferred by 24 % (5/21) of the pediatricians. Six percent of the pediatricians chose the appropriate spacer volume according to age group, 62.5 % (45/72) reported that they classified asthma according to severity, 16 % (7/45) gave the correct answers when classifying asthma according to national consensus, and 22 % (16/72) considered asthma to be an inflammatory disease. CONCLUSIONS: The results of this study suggest that pediatrician's knowledge of inhalation therapy with dosed aerosol spacers and of asthma-related concepts in the public health system in Rio de Janeiro is limited. This may restrict the quality of care given to the asthmatic children in the city and suggests the need for training programs for the management of asthmatic children.

Adult↗

Systemic effects of high dose inhaled steroids: comparison of beclomethasone dipropionate and budesonide in healthy subjects.

BACKGROUND: Systemic absorption of inhaled corticosteroids may adversely influence the function of the hypothalamo-pituitary-adrenal axis, bone metabolism, and circulating leucocytes. These changes can be used to assess the safety of different types and modes of administration of these drugs. METHODS: The study was a randomised, double dummy, crossover design with nine healthy adults. It compared the effects of beclomethasone dipropionate and budesonide (given by metered dose aerosols with and without their respective large volume spacers (Volumatic and Nebuhaler) attached) on serum cortisol, 24 hour urinary free cortisol, and plasma osteocalcin concentrations, and circulating neutrophils and lymphocytes. Subjects inhaled the drug (1 mg) and matching placebo at 0900 and 2200 hours on each of six study days. Blood samples were taken hourly for six hours after the morning dose and at the end of the study period. RESULTS: All results were within the reference ranges. Both drugs caused similar reductions in serum cortisol four to six hours after inhalation. These changes were not affected by the use of a large spacer and did not persist at 24 hours. Use of spacers tended to increase the haematological effects of the steroids. Beclomethasone dipropionate inhaled through a Volumatic provoked a rise in circulating neutrophils compared with placebo although lymphocyte numbers were unaffected. Budesonide did not influence neutrophil numbers but did reduce circulating lymphocytes, numbers of which were further reduced when the Nebuhaler was used. There were no significant changes in plasma osteocalcin concentration or 24 hour urinary free cortisol excretion with budesonide, with or without a spacer. Beclomethasone dipropionate inhaled without a spacer reduced urinary cortisol and plasma osteocalcin at 24 hours; however, use of the Volumatic protected against these effects. CONCLUSIONS: Attaching a Volumatic reduces the systemic effects of 2 mg aerosol beclomethasone dipropionate on the hypothalamo-pituitary-adrenal axis and circulating osteocalcin concentrations. This study did not establish whether the Nebuhaler reduces the systemic effects of budesonide. When large spacers are used, 2 mg per day of beclomethasone dipropionate and budesonide seem to be equivalent in terms of unwanted effects.

Administration, Inhalation↗

Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of flow pattern.

In mechanically ventilated patients the flow pattern during bronchodilator delivery by metered-dose inhaler (MDI) could be a factor that might influence the effectiveness of this therapy. In order to test this the effect of two different inspiratory flow patterns on the bronchodilation induced by beta2-agonists administered via MDI and spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) was examined. Eighteen mechanically ventilated patients with COPD, were prospectively randomized to receive two (n=8, protocol A) or six (n=10 protocol B) puffs salbutamol (100 microg x puff(-1)) either under pressure control (decelerating flow pattern) or under volume control (square wave flow pattern). With both modes, tidal volume and inspiratory time were identical. Salbutamol was administered via an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud-enhancer spacer. After a 6-h washout, patients were crossed over to receive the same dose of salbutamol (200 or 600 microg, respectively in protocols A and B) by the alternative mode of administration. Static and dynamic airway pressures, minimum (Rint) and maximum (Rrs) inspiratory resistance and the difference between Rrs and Rint (deltaR) were measured before and at 15, 30 and 60 min after salbutamol. Independent of the dose, salbutamol caused a significant decrease in dynamic and static airway pressures, Rint and Rrs. These changes were not influenced by the inspiratory flow pattern and were evident at 15, 30 and 60 min after salbutamol. It is concluded that salbutamol delivered via metered dose inhaler and spacer device, induces significant bronchodilation in mechanically ventilated patients with chronic obstructive pulmonary disease, the magnitude of which is not affected by the inspiratory flow/time profile.

Adrenergic beta-Agonists↗

Comparative efficacy and safety of inhaled corticosteroids in asthma.

Current guidelines emphasize the efficacy of inhaled corticosteroids for anti-inflammatory activity in asthma, and recommend higher doses and earlier initiation of therapy than previous guidelines. Concern over possible side effects with long term use has prompted an evaluation of the available literature to determine the optimal dose that may be administered without fear that significant side effects might occur (e.g., growth retardation in children, adrenal suppression, reduction in bone mineral density, cataract formation). Regular treatment with the following drugs in adults and children, respectively, is unlikely to result in any clinically significant effects on the above parameters: beclomethasone dipropionate less than 1500 micrograms and 400 micrograms, budesonide less than 1600 micrograms and 400 micrograms, flunisolide less than 2000 micrograms and 1000 micrograms, fluticasone propionate approximately 500 micrograms and 200 micrograms, and triamcinolone acetonide less than 1600 micrograms and 1200 micrograms. Systemic effects are influenced by potency and bioavailability. Inhaled corticosteroids owe their favourable safety profile to a high topical to systemic potency ratio compared with that of oral corticosteroids. In terms of relative topical potency, fluticasone propionate is more potent than budesonide, which is more potent than beclomethasone dipropionate, which is more potent than flunisolide and triamcinolone acetonide. The delivery device has an important influence on the amount of drug reaching the patient. A spacer device attached to a metered dose inhaler or a Turbuhaler reduces oropharyngeal deposition and increases lung deposition. As a result, a dosage reduction may be possible, and local side effects of dysphonia and oral candidiasis may be reduced. Patients requiring continued high doses by the inhaled route should be monitored for systemic effects and be considered for osteoporosis prevention therapy if appropriate.

Administration, Inhalation↗

Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group.

The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone.

Acetates↗

The use of inhaled and related respiratory medications in Christchurch rest homes.

AIM: To describe the use of inhaled and related respiratory medications ('asthma medications') and associated management amongst Christchurch rest-home residents. METHODS: Fifty per cent of Christchurch rest homes were randomly selected. All residents on asthma medications, the rest-home managers, care-giving staff, and the residents' general practitioners were interviewed using specific questionnaires. RESULTS: All of the rest homes, residents using asthma medications and senior staff members participated. Seventy five per cent of caregivers and 73% of general practitioners took part. Asthma medications were used by 13% of 1416 rest-home residents. Eighty four per cent of these used a preventer medication, mostly inhaled steroids. Some daily doses exceeded current treatment guidelines. One third of residents using inhalers had an inadequate technique. Some staff and residents chose the wrong inhaler to manage 'shortness of breath'. Regular bronchodilator dosing, rather than 'as required', was common. Those using a spacer device usually had a good technique. Residents appreciated non-pharmacological strategies for breathlessness. Staff identified a need for clear written management plans. CONCLUSIONS: There were significant deficiencies in the staff and residents' knowledge of obstructive airways management and medications. Regular review of inhaler technique, greater use of spacers, and regular staff education may improve residents' respiratory management. Inhaled corticosteroids may be used in too high a dose. Inconsistent management of acutely deteriorating asthma/chronic obstructive pulmonary disease may be addressed by greater use of written management plans in residents' notes.

Administration, Inhalation↗

Esophageal candidiasis as a side effect of inhaled fluticasone propionate dry powder: recovery by switching over to hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP).

BACKGROUND: Esophageal candidiasis is one of the local side effects of inhaled corticosteroid treatment, and it is difficult to prevent this condition. Our previous report indicated that the prevalence of esophageal candidiasis among patients treated with inhaled fluticasone propionate dry powder (FP-dp) reached up to 37% in Japanese patients. Although a reduction in the daily dose of inhaled FP-dp can eliminate this infection, it may lead to asthma not being well-controlled in these patients. OBJECTIVE: The aim of this study was to estimate whether switching to an equal daily dose of inhaled hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP), the oropharyngeal deposition of which is very low, can eliminate the infection without deterioration of asthma. METHODS: A total of 10 stable asthmatic patients with esophageal candidiasis, induced by inhaled FP-dp treatment (400 or 800 microg/ day), were enrolled in this study. A second upper GI endoscopy was performed, more than 1 month but less than 3 months after switching to an equal dose of inhaled HFA-BDP with a tube spacer device, Duopacer. The patients' medications were not changed during the study. RESULTS: Esophageal candidiasis was eliminated in 9 of the 10 patients. The degree of candidiasis reduced in another patient. The forced expiratory volume in 1 sec (FEV1.0) did not worsen during the study. CONCLUSION: Switching from FP-dp to HFA-BDP with Duopacer is useful in preventing esophageal candidiasis.

Administration, Inhalation↗

Normal diurnal variation in serum cortisol concentration in asthmatic children treated with inhaled budesonide.

BACKGROUND: Twenty-four-hour serum cortisol secretion is a sensitive parameter for the assessment of the pituitary-adrenal function of asthmatic children treated with inhaled corticosteroids. This study was undertaken to determine the effect of the long-term administration of inhaled budesonide on 24-hour cortisol production in young children with asthma. METHODS: We studied 11 children, aged 7 to 12 years, with severe perennial asthma. All had been receiving 100 micrograms of inhaled budesonide twice daily, administered with a spacer device, for 3 to 5 years. Serum cortisol concentration was measured at 8:00 A.M., 60 minutes after intravenous administration of 0.25 mg of corticotropin, and every 30 minutes for 24 hours in an open-design study. Urinary cortisol secretion was measured by 24-hour urine collection. All determinations were made with a radioimmunoassay kit. RESULTS: The individual morning serum cortisol concentration and the serum cortisol concentration at 60 minutes after corticotropin stimulation were within normal limits in all children. The 24-hour urinary cortisol excretion was also normal. The individual 24-hour serum cortisol concentration showed a normal pattern in all children, with no evidence of nocturnal suppression of serum cortisol concentration. CONCLUSION: Prolonged (3 to 5 years) administration of 200 micrograms/day of inhaled budesonide in young children with severe asthma does not impair pituitary-adrenal function, even according to the sensitive test for 24-hour serum cortisol secretion.

Administration, Inhalation↗

Albuterol delivery during noninvasive ventilation.

HYPOTHESIS: Albuterol delivered during noninvasive positive-pressure ventilation is affected by use of a nebulizer or metered-dose inhaler (MDI) and whether the leak port is in the hose or the mask. METHODS: A lung model that simulated spontaneous breathing at 20 breaths/min was used. A bi-level positive-airway-pressure ventilator (Respironics S/T30) was set for an inspiratory positive airway pressure of 15 cm H(2)O and an expiratory positive airway pressure of 5 cm H(2)O. The tidal volume delivered was 0.4 L. Two mask types were used: one in which the leak port was incorporated into the circuit, and another in which the leak port was incorporated into the mask. The nebulizer was filled with 4 mL, which contained 5 mg of albuterol, connected via a T-piece directly to the mask, and operated at 8 L/min for 15 min. For the MDI studies, a spacer was placed between the mask and the circuit, and an MDI was actuated into the spacer, either synchronized with the initiation of inhalation or during the exhalation phase (4 actuations separated by \G 15 s in each case). Albuterol was washed from the filter and measured with ultraviolet spectrophotometry. RESULTS: With the nebulizer, significantly more albuterol was delivered to the filter when the leak port was in the circuit (p = 0.001). Significantly more albuterol was delivered with the nebulizer than with the MDI (p < 0.001). The efficiency of albuterol delivery (percent delivered) was similar for nebulizer and MDI with the leak port in the circuit (p = 0.57), but better with the MDI with the leak port in the mask (p = 0.001). Albuterol delivery was significantly less when the MDI was actuated during exhalation (p = 0.001). CONCLUSIONS: Albuterol delivery with noninvasive positive-pressure ventilation was affected by the type of aerosol delivery device, by the location of the leak port, and by actuating the MDI at the proper time in the respiratory cycle.

Administration, Inhalation↗

Recovery of the ciliated epithelium following acute bronchiolitis in infancy.

BACKGROUND: Little is known about the longitudinal changes in the ciliated respiratory epithelium of infants following viral bronchiolitis. A study was undertaken to investigate the time required for the ciliated epithelium to return to normal following bronchiolitis in infants treated with inhaled steroids or placebo. METHODS: Thirty one previously healthy term infants were studied as part of a clinical trial to determine the effect of 12 weeks of treatment with inhaled fluticasone (FP) or placebo via a spacer device (17 FP, 14 placebo). Nineteen healthy children aged 0-6 years previously studied in our department were used as controls. Nasal biopsy specimens were taken from infants with bronchiolitis and ciliary beat frequency (CBF) was measured before treatment and repeated 3, 6, 12, and 24 weeks later. The epithelial ultrastructure was examined by transmission electron microscopy and a normal errors mixed model based on normal controls was used to examine the time for cilia to return to normal in bronchiolitic infants. RESULTS: The mean CBF of infants with bronchiolitis (in Hz) at weeks 0, 3, 6, 12, and 24 were 0.5 (n = 4), 10.9 (n = 4), 12.0 (n = 9), 11.9 (n = 8), and 12.1 (n = 7) in the placebo group and 10.6 (n = 6), 11.4 (n = 9), 8.8 (n = 8), 10.9 (n = 4), and 13.2 (n = 7) in the FP group. The time for the epithelial ultrastructure to normalise was as follows: epithelial integrity score (13.1 weeks), % ciliated cells with loss of cilia (14.0 weeks), and % epithelial cells with abnormalities in projection (16.7 weeks) or mitochondria (15.9 weeks). Inhaled steroids had no significant effects on CBF or epithelial ultrastructure. CONCLUSION: Ciliary loss and epithelial abnormalities persist on average for 13-17 weeks following acute bronchiolitis in infancy.

Acute Disease↗

Holding chambers versus nebulisers for inhaled steroids in chronic asthma.

BACKGROUND: Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the role of this mode of therapy in the treatment of chronic asthma is still unclear. OBJECTIVES: To assess the efficacy and safety of inhaled corticosteroids delivered via nebuliser versus holding chamber for the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted the authors of studies and pharmaceutical companies for additional studies and hand-searched the British Journal of Clinical Research, European Journal of Clinical Research and major respiratory society meeting abstracts (1997-1999). SELECTION CRITERIA: Randomised controlled trials comparing nebuliser to holding chamber in the delivery of inhaled corticosteroids for the treatment of chronic asthma. All age groups of patients were considered. Two reviewers assessed articles for inclusion; two reviewers independently assessed included studies for methodological quality. DATA COLLECTION AND ANALYSIS: One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses were undertaken using Review Manager 4.1 with MetaView 3.1. MAIN RESULTS: Two studies were selected for inclusion (63 subjects), both concerned adults. Methodological quality was variable. Due to design differences it was not appropriate to pool the studies. The single high quality study compared budesonide 2000-8000 mcg delivered via Pari Inhalier Boy jet nebuliser with inspiration-only inhalation to budesonide 1600 mcg via large volume spacer. The nebuliser delivery led to higher morning peak expiratory flow values (25 L/min p<0.01), higher evening values (30L/min, p<0.01), lower rescue beta2 agonist use and symptom scores compared to the holding chamber delivery. REVIEWER'S CONCLUSIONS: Budesonide in high dose delivered by the particular nebuliser used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 mcg via a large volume spacer. However, it is not clear whether this was an effect of nominal dose delivered or delivery system. Cost, compliance and patient preference are important determinants of clinical effectiveness that have not been assessed. Future studies are needed to evaluate the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebuliser/compressor compared to holding chamber. Moreover, further studies assessing these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulised corticosteroids.

Administration, Topical↗

Holding chambers versus nebulisers for inhaled steroids in chronic asthma.

BACKGROUND: Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the role of this mode of therapy in the treatment of chronic asthma is still unclear. OBJECTIVES: To assess the efficacy and safety of inhaled corticosteroids delivered via nebuliser versus holding chamber for the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted the authors of studies and pharmaceutical companies for additional studies and hand-searched the British Journal of Clinical Research, European Journal of Clinical Research and major respiratory society meeting abstracts (1997-1999). Date of last search August 2005. SELECTION CRITERIA: Randomised controlled trials comparing nebuliser to holding chamber in the delivery of inhaled corticosteroids for the treatment of chronic asthma. All age groups of patients were considered. Two reviewers assessed articles for inclusion; two reviewers independently assessed included studies for methodological quality. DATA COLLECTION AND ANALYSIS: One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses were undertaken using Review Manager 4.1 with MetaView 3.1. MAIN RESULTS: Two studies were selected for inclusion (63 subjects), both concerned adults. An additional small study including 14 children was identified for the 2005 update. Methodological quality was variable. Due to design differences it was not appropriate to pool the studies. The single high quality study compared budesonide 2000-8000 mcg delivered via Pari Inhalier Boy jet nebuliser with inspiration-only inhalation to budesonide 1600 mcg via large volume spacer. The nebuliser delivery led to higher morning peak expiratory flow values (25 L/min p<0.01), higher evening values (30L/min, p<0.01), lower rescue beta2 agonist use and symptom scores compared to the holding chamber delivery. AUTHORS' CONCLUSIONS: Budesonide in high dose delivered by the particular nebuliser used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 mcg via a large volume spacer. However, it is not clear whether this was an effect of nominal dose delivered or delivery system. Cost, compliance and patient preference are important determinants of clinical effectiveness that still require further assessment. Future studies are needed to evaluate the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebuliser/compressor compared to holding chamber. Moreover, further studies assessing these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulised corticosteroids.

Administration, Topical↗

Inhalation therapy in children with asthma.

Current consensus guidelines advocate the use of inhalation therapy for all children with asthma. In this paper, the published evidence on technical and practical aspects of inhalation therapy in children with asthma is reviewed. For children under 6 yr of age, nebulizers and metered dose inhaler (MDI)/spacer combinations can be used. Nebulizers are cumbersome, bulky, and difficult to operate. They require technical and hygienic maintenance. A number of studies has shown that nebulizers are no more effective in delivering bronchodilator therapy than MDI/spacer combinations. Thus, for young children with asthma, MDI/spacer combinations are the device of choice for inhalation therapy. Due to static charge, the output from plastic spacers is lower than that from metal spacers. Static charge on plastic spacers can be reduced by washing the spacer in detergent and allow it to drip dry. Most children aged 6 yr or over can use a dry powder inhaler (DPI) reliably. Modern DPIs require relatively low inspiratory flow rates for proper operation. Lung deposition from the Turbuhaler is twice as high as that from the Diskus, but the former device is slightly more difficult to operate than the latter. Many children with asthma have a poor inhalation technique. Because a reliable inhalation technique is the key to successful inhalation therapy, inhalation technique should be instructed carefully and checked repeatedly in every asthmatic child using an inhaler device.

Adolescent↗

Metered dose inhaler add-on devices: is the inhaled mass of drug dependent on the size of the infant?

Limited cooperation and low tidal volumes in infants make aerosol therapy difficult. We measured the amount of drug delivered from two baby spacer devices especially developed for use in infants. Designed as a randomized crossover study, aerolized budesonide from a pressurized metered dose inhaler (pMDI) was collected in the inspiratory filter interposed between the face mask and the spacer in 13 infants aged from 2 to 19 months old. The study was performed in connection with pulmonary function testing with a plethysmograph, and the children were sedated with cloral hydrate. Two small-volume baby spacer devices were used: a Babyhaler spacer (GlaxoWellcome, Hertfordshire, UK) made of polycarbonate with a volume of 350 mL and a built-in dead space of 40 mL and a NebuChamber spacer (AstraZeneca, Lund, Sweden) made of stainless steel with a volume of 250 mL and no dead space. Budesonide delivery from the NebuChamber was significantly higher than from the Babyhaler: 38.2% (range, 28.3%-47.5%) of the nominal dose versus 12% (range, 3.3%-21.25%) of the nominal dose of 400 micrograms of budesonide (P = 0.002). The inhaled mass of budesonide from the Babyhaler correlated significantly with skin surface area (r = 0.68, P = 0.018), weight (r = 0.66, P = 0.019), height (r = 0.69; P = 0.017), tidal volume (r = 0.82; P = 0.004), and minute volume (r = 0.67; P = 0.019). No correlations were found between these variables and the inhaled mass of budesonide from the NebuChamber. The results indicate that the design of the NebuChamber spacer affords stable drug delivery in infants and that a large variability in the inhaled mass of drug may be found when infants are inhaling from different baby spacers.

Administration, Inhalation↗

Metered dose inhaler salbutamol treatment of asthma in the ED: comparison of two doses with plasma levels.

Two cumulative doses of salbutamol delivered by metered dose inhaler (MDI) with a pear-shaped spacer were compared (400 micrograms vs 600 micrograms at 10-minute intervals). Twenty-two patients (mean age 35.1 +/- 11.1 years) with acute exacerbation of asthma were randomly selected, in a double-blind fashion, to receive salbutamol delivered with MDI into a spacer device in 4 puffs at 10- minute intervals (100 micrograms or 150 micrograms per actuation) during 3 hours (1200 micrograms or 1800 micrograms each 30 minutes). Mean peak expiratory flow rate (PEFR) and forced expiratory volume in the first second (FEV1) improved significantly over baseline values for both groups (P < .001). Nevertheless, there were no significant differences between both groups for PEFR and FEV1 at any time point studied. A significant net reduction of heart rate was observed in the 400 microgram group (P < .01). On the other hand, a significant increase in heart rate was observed in the 600 microgram group (P < .001). The QTc interval did not show a significant prolongation, and the two groups presented moderate decreases of serum potassium levels. There was a significant dose-related increase (P = .027) in Sao2. Additionally, the 600 microgram group generated a serum glucose level increase from 0.85 +/- 0.12 mg/100 mL to 1.04 +/- 0.25 mg/100 mL (P = .02), with a higher incidence in 4 symptoms (tremor, headache, palpitations, and anxiety). These data support the notion that the treatment of acute asthma patients in the emergency department setting with salbutamol, 2.4 mg/h, delivered by MDI and spacer (4 puffs at 10-minute intervals) produces satisfactory bronchodilation, low serum concentration, and minimal extrapulmonary effects. However, an increase of 50% of the dose (600 micrograms at 10-minute intervals) produced a nonsignificant, slightly better therapeutic response but with greater side effects, probably related to higher salbutamol levels.

Adrenergic beta-Agonists↗

Clinical efficacy of nebulized drugs.

There is a mandatory need for effortless drug administration to young children since the prevalence among them of recurrent wheezing is a 15-20%. It is becoming increasingly evident that many of these children respond dramatically well to beta2-agonists and topical steroids; accordingly this sub-group of children should be treated as asthmatics. The dose of topical steroids is critical as opposed to that of beta2-agonists which are often administered in doses well above the minimal effective dose. Budesonide suspension has proven its efficacy in adults in a study of 21 patients with asthma treated with budesonide suspension delivered from a nebulizer activated during inspiration versus metered dose inhalation (MDI) via a large-volume spacer. Nebulized in this manner the suspension exhibited a dose-dependent effect, apparently equipotent to the MDI administration as evaluated from daily peak expiratory flow measurements and symptom scoring. Continuous nebulization of budesonide in 18 schoolchildren with bronchial asthma similarly showed a dose-dependent improvement of lung function and symptom score, though in a 1:2 potency ratio as compared to MDI administration, probably due to loss of nebulized aerosol during expiration. In a subsequent study of 23 young children unresponsive to beta2-agonist therapy, nebulized budesonide was without demonstrable effect. Recently, a study of 31 young children with steroid-dependent asthma demonstrated a significant improvement from continuous nebulization of budesonide 1mg twice daily. In conclusion, the efficacy of nebulized budesonide has been convincingly demonstrated in patients with reversible symptoms of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗