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Large volume spacer devices and the influence of high dose beclomethasone dipropionate on hypothalamo-pituitary-adrenal axis function.

BACKGROUND: The systemic effects of the inhaled corticosteroid beclomethasone dipropionate are reduced if the drug is inhaled through a large volume spacer. Use of spacers may therefore permit higher doses to be given without causing hypothalamo-pituitary-adrenal suppression. METHODS: Randomised, double blind, double dummy, parallel group study was carried out in adults with chronic asthma to determine the dose of beclomethasone dipropionate causing hypothalamo-pituitary-adrenal suppression when the drug was administered by metered dose aerosol with and without a large volume spacer. After a four week run in taking 1.5 mg beclomethasone daily 50 patients underwent tests of hypothalamo-pituitary-adrenal function (measurement of 0900 h serum cortisol concentration and 24 hour urinary free cortisol excretion and the short tetracosactrin test). Six patients had hypothalamo-pituitary-adrenal suppression (results of at least two tests subnormal) and asthma was well controlled in six others. Thirty eight patients received increasing doses of beclomethasone with (group S) or without (group MDI) a 750 ml spacer. The daily dose was increased by 0.5 mg at monthly intervals until hypothalamo-pituitary-adrenal suppression developed or a dose of 5 mg/day was achieved. Asthma symptoms and peak expiratory flow were recorded daily. RESULTS: Twenty three patients completed the study, one (group S) reaching a dose of 5 mg beclomethasone dipropionate daily without hypothalamo-pituitary-adrenal suppression. Reasons for withdrawal were poor compliance (n = 10), the patient's decision (n = 3), and asthma that was too unstable (n = 2). "Intention to treat" analysis showed that the median dose of beclomethasone causing hypothalamo-pituitary-adrenal suppression was similar in the two groups (3.25 mg in S v 3.0 mg in MDI; 95% confidence interval (CI) for difference -1.0 to 1.0 mg). At 2 mg/day of beclomethasone most patients in both groups had well controlled asthma and there were no differences in symptoms or peak flow between the groups. Good control at this dose did not permit conclusions to be drawn about the efficacy of higher doses. CONCLUSIONS: There is wide interindividual variation in the dose of beclomethasone dipropionate causing hypothalamo-pituitary-adrenal suppression. Whether or not a spacer is used, doses higher than the currently accepted maximum of 2 mg/day can be taken by many adults with asthma without causing subnormal function of the hypothalamo-pituitary-adrenal axis. Whether these higher doses are more effective in controlling asthma remains to be established.

Asthma↗

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

OBJECTIVE: The delivery of bronchodilator drugs with metered-dose inhaler (MDI) and a spacer in mechanically ventilated patients has become a widespread practice. However, the various ventilator settings that influence the efficacy of MDI are not well established. The tidal volume (VT) during drug delivery has been suggested as one of the factors that might increase the effectiveness of this therapy. To test this, the effect of two different VT on the bronchodilation induced by beta 2-agonists administered with MDI and a spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) was examined. METHODS: Nine patients with COPD, mechanically ventilated on volume-controlled mode, were prospectively randomised to receive six puffs of salbutamol (S, 100 micrograms/puff) either with a VT of 8 ml/kg (normal VT, 582 +/- 85) or with a VT of 12 ml/kg (high VT, 912 +/- 137). With both modes inspiratory flow was identical. S was administered with 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 S by the alternative mode of administration. Static and dynamic airway pressures, minimum (Rint) and maximum (Rrs) inspiratory resistance, the difference between Rrs and Rint (delta R), static end-inspiratory respiratory system compliance (Cst,rs), intrinsic positive end-expiratory pressure (PEEPi) and heart rate (HR) were measured before and at 15, 30 and 60 min after S. RESULTS: S caused a significant decrease in dynamic and static airway pressures, PEEPi, Rint and Rrs. These changes were not influenced by VT and were evident at 15, 30 and 60 min after S. With normal and high VT, Cst,rs, delta R and HR did not change after S. CONCLUSIONS: We conclude that S delivered with an MDI and a spacer device induces significant bronchodilation in mechanically ventilated patients with COPD, the magnitude of which is not affected by at least a 50% increase in VT. These results do not support the VT manipulations when bronchodilators are administered in adequate doses during controlled mechanical ventilation.

Administration, Inhalation↗

Variability of aerosol delivery via spacer devices in young asthmatic children in daily life.

Pressurized metered dose inhalers (pMDI) are widely used together with spacers for the treatment of asthma in children. However, the variability of daily medication dose for pMDI/spacer combinations is not known. Electrostatic charge is a potential source of dose variability. Metal spacers have no static charge. This study assessed and compared within-subject variability of aerosol delivery of metal and plastic spacers. This was a randomized, crossover study in children with stable asthma aged 1-4 (group I, n=17) and 5-8 (group II, n=16) yrs. In both groups the amount of drug delivered to the mouth by a metal spacer (Nebuchamber) and one of two plastic (polycarbonate) spacers, i.e. Babyhaler in group I and Volumatic in group II was measured. The metal and plastic spacers were tested at home in a randomized order for 7 days each, using budesonide (200 microg b.i.d.). Aerosol was collected on a filter positioned between spacer and facemask or mouth. Budesonide on the filter was assessed by high performance liquid chromatography. The mean filter dose for each child (mean+/-SD) during the 7 days was expressed as a percentage of the nominal dose. Within-subject variability was expressed as coefficient of variation (CV). Mean filter dose in group I was 41.7+/-10.1% for Nebuchamber and 26.0+/-4.0% for Babyhaler (p<0.001). Mean filter dose in group II was 50.2+/-9.2% for Nebuchamber and 19.4+/-7.2% for Volumatic (p<0.001). Mean CV in group I was 34% for Nebuchamber and 37% for Babyhaler (p=0.44). Mean CV in group II was 23% for Nebuchamber and 34% for Volumatic (p=0.003). There was substantial within-subject dose variability in aerosol delivery in children using a pMDI/spacer at home. This variability was lower for the metal than for the plastic spacer in children 5-8 yrs of age. The dose delivered to the mouth was about two-fold higher for the metal than the plastic spacer independent of age.

Aerosols↗

Inhalation treatment: errors in application and difficulties in acceptance of the devices are frequent in wheezy infants and young children.

The recent availability of small-volume spacers has facilitated the general use of inhaled treatment in infants. The purpose of this study was to evaluate any errors made by parents when using this new inhalation technique and the child's behavior during the inhalation. Ninety-four young children (61% boys) under 5 years of age were enrolled in the study. Inhalation treatment was recommended either by a general practitioner or by a pediatrician. Data concerning treatment regimens, the ability of parents to use the spacer and metered-dose inhalers (MDIs), and the acceptance of the devices, were collected by means of a demonstration and questionnaire. Unexpectedly, the doses, administration times, and duration of the treatments varied from one child to the next. No explanation or training in administering the treatment via the spacers was given to 12% and 47% of the parents, respectively. Fourteen per cent of parents did not shake the MDIs, 12% did not monitor the valves, and 22% allowed too short a time for inhalation. The lack of explanation increased the occurrence of errors in manipulation of the devices. The procedure was judged to be easy to follow by 78% of the parents, but the face mask was accepted with difficulty by 22% of the children. Repeated crying during administration of the treatment was observed in 38% of the patients, particularly the youngest. Crying influenced the acceptance of the face mask, reduced parental compliance, and made the use of the devices more difficult. Errors altering the efficiency of inhalation treatment in infants are frequent. Most of these errors could be avoided by spending more time to inform the parents about correct usage. Furthermore, repeated crying during inhalation is common in young children and this problem should to be taken into consideration in the evaluation of treatment.

Administration, Inhalation↗

Inhaled nedocromil sodium for persistent cough in children.

The efficacy of inhaled nedocromil sodium (NS) for children with a persistent cough was studied. Children aged 4-12 years with a persistent cough for >1 month were recruited and entered a 2-week baseline period during which an asthma diary was kept. Children with a cough score of >20 received inhaled NS via a spacer, 4mg qid for 2 weeks followed by 4mg bd for another 4 weeks. Twenty-two (42%) of 52 children recruited fulfilled treatment criteria. Four children were withdrawn from the study (2 developed wheezing and 2 were not compliant). The baseline cough score (29.1 +/- 13.6) improved after 2 weeks of treatment (15.2 +/- 9.3, p < 0.01) and improvement was sustained after 6 weeks (14.2 +/- 13.0, p = 0.01). Parents and patients had a more favourable perception of its efficacy compared to physicians (72% vs 50%, p = 0.01) Inhaled NS may be considered for treatment of persistent cough in children.

Administration, Inhalation↗

Systemic activity of inhaled and swallowed beclomethasone dipropionate and the effect of different inhaler devices.

Inhaled glucocorticoids such as beclomethasone dipropionate, which are used in the treatment of asthma, may be associated with systemic adverse effects. To determine whether any systemic absorption following the inhalation of beclomethasone was a result of drug being absorbed from the lung (inhaled fraction) or the gastrointestinal tract (swallowed fraction), we studied normal subjects after the inhalation or swallowing of 2 mg beclomethasone dipropionate. Systemic activity was assessed using early morning cortisol suppression. Both inhaled and swallowed fractions produced significant systemic activity, the degree of which depended on the inhaler device used. Systemic activity was greater using a dry powder inhaler (52%) than using a metered dose inhaler with a large volume spacer (28%). These findings suggest that to limit potential adverse effects from high-dose beclomethasone dipropionate it is better to use a metered dose aerosol with large volume spacer than a dry powder.

Administration, Inhalation↗

Aerosolized metaproterenol in the treatment of asthmatics with severe airflow obstruction. Comparison of two delivery methods.

The bronchodilator response to metaproterenol delivered by metered-dose inhaler (MDI) with a spacer device (Aerochamber [A]) and by jet nebulizer was studied in 44 asthmatic patients who presented to the emergency department with acute severe (FEV1 less than 50 percent predicted) airflow obstruction. The delivery method was randomized, double-blinded and placebo controlled. The A group received one puff of metaproterenol every five minutes for a total of three puffs (1.95 mg). The jet nebulizer group received 15 mg of metaproterenol by continuous nebulization over ten minutes. Only about 2.75 mg of the original 15 mg delivered by jet nebulizer was calculated to be available for inhalation due to the inefficiencies of the delivery system. The mean percentage of improvement in FVC and FEV1 in the A group was 33.5 and 49.0 percent, respectively. The mean percentage of improvement in FVC and FEV1 in the jet nebulizer group was 22.8 and 33.0 percent, respectively. There was no significant difference in the mean percentage of improvement values between the two groups. We were unable to demonstrate a difference in bronchodilator response to metaproterenol delivered by MDI-A and jet nebulizer in emergency department asthmatics with acute severe airflow obstruction.

Adult↗

The effect of inhaled corticosteroids on the urinary calcium to creatinine ratio in childhood asthma.

BACKGROUND: The use of inhaled corticosteroids (ICS) via spacers in childhood asthma is increasing. However, concern has been raised about its long-term impact. Hypercalciuria is a known adverse effect of treatment with systemic corticosteroids. The urinary calcium to creatinine ratio (UCa:Cr) is a simple, reliable and non-invasive tool for evaluation of hypercalciuria. AIM: To determine whether ICS can induce hypercalciuria in children with asthma. SETTING: Outpatient clinic in a referral hospital. METHODS: The UCa:Cr was determined in 25 children aged 3-6 years with mild-to-moderate persistent asthma before and after a 2-month course of inhaled budesonide 400 micrograms/day via an aerochamber. Children who had received oral corticosteroids, diuretics, antibiotics or theophylline were excluded. STATISTICS: Paired Student's t-test and Fisher's exact test. RESULTS: The mean UCa:Cr was similar in the children with asthma before and after 2 months' administration of budesonide (0.10 +/- 0.10 and 0.11 +/- 0.08, respectively; p = 0.601). The numbers of hypercalciuric children were two and five, respectively (p = 0.417). In 68% of patients, the UCa:Cr increased and in 16% the increase indicated hypercalciuria (UCa:Cr > 0.2). CONCLUSIONS: Although the treatment of childhood asthma with budesonide 400 micrograms/day via an aerochamber does not appear to be associated with hypercalciuria, the existence of a subgroup of patients in whom ICS may induce hypercalciuria is plausible. This needs to be further evaluated in a larger study.

Administration, Inhalation↗

Delivery of HFA and CFC salbutamol from spacer devices used in infancy.

The aim of the study was to compare the in vitro delivery of four salbutamol pressurized metered-dose inhalers (pMDIs) via the three spacer devices commonly used in European infants: Aerochamber-Infant, Babyhaler, and metallic NES-spacer. Emitted dose (ED) and fine particle dose (FPD, particles<5.8 microm) of each combination of spacer device and pMDI (chlorofluorocarbon-based Ventoline, Eolène, Spréor, and hydrofluoroalkane-based Airomir were measured respectively using unit dose sampling tubes (n=30 per combination) and an 8-stage cascade impactor (n=6 per group). The results were compared by analysis of variance and the Student-Newman-Keuls method. ED of Airomir was always greater than for Ventoline (P<0.05). FPD obtained with Ventoline was the lowest, with Eolène>Airomir=Spréor>Ventoline (P<0.05). Only Airomir produced a similar FPD with all three spacer devices. Chlorofluorocarbon-salbutamol pMDIs are not generics when used with spacer devices. The three spacer devices may be used interchangeably with Airomir.

Albuterol↗

Effects of inhaled corticosteroids on growth in asthmatic children: a comparison of fluticasone propionate with budesonide.

In asthmatic children inhaled corticosteroids are widely used. However, there are some concerns about the systemic adverse effects of these drugs, especially in the growing child. We performed this prospective study in order to compare the effects of 400 microg/day of budesonide (BUD) and 250 microg/day of fluticasone propionate (FP) on growth in prepubertal (aged 4-11.5 years), moderate persisting asthmatic children. One hundred patients (51 boys and 49 girls), who were randomized into two groups, were recruited for the study. The first group was treated with BUD, 2X 200 microg/day, and the second group was treated with FP, 2X 125 microg/day, by using a medium-size volume-spacer metered-dose inhaler. Growth in children with asthma who were treated by inhaled corticosteroids was calculated by growth velocity over a 12-month period. Comparisons between treatment groups were calculated by t-test and chi-square test. There were no significant differences between BUD and FP groups for sex, age, first height, and growth velocity. Moderate persisting, prepubertal asthmatic children treated with 250 microg/day of FP appeared to have no different linear growth than those children who received 400 microg/day of BUD.

Administration, Inhalation↗

Reversible airway obstruction: neurohumoral mechanisms and treatment. Lecture on asthma: clinical overview.

Asthma is an airway obstruction which is reversible, either spontaneously or in response to treatment. Repeated peak expiratory flow rate (PEFR) measurements, up to six times daily, allows this characteristic reversibility to be recognised, to guide diagnosis and therapy. Chronic asthmatics may eventually become relatively irreversible, and then appear similar to chronic bronchitics - unless an adequate history is taken. The commonest world-wide allergen is the fecal pellet of the house mite. Modern therapy of asthma starts with inhaled beta 2 agonists, but difficulty in using metered dose inhalers is helped by the 'spacer', or reservoirs (e.g. 'Nebuhaler'). Interaction between slow-release oral theophyllines and beta 2 agonists by inhalation maximises bronchodilatation but minimises tremor. High-dose ipratropium inhalation, as isotonic wet nebulisation with a beta 2 agonist, is useful in acute severe asthma. High doses of inhaled topical steroid are valuable in the difficult asthmatic, but pituitary adrenal suppression occurs if dosage exceeds 1,500 micrograms/day. Cromoglycate and a beta 2 agonist by inhalation can prevent exercise-induced asthma. Long-term oral steroids (never over 10 mg/day) are only used if inhaled therapy (+/- oral slow-release theophyllines) fails. Acute severe asthma needs parenteral steroid, parenteral beta 2 agonist, high-dose beta 2 agonist by inhalation, oxygen and hospital admission. Ventilation is increased in the acute severe asthmatic with hypoxia and low PCO2. In 90 asthmatic deaths surveyed in Britain, half had failed to realise the severity.

Administration, Topical↗

Early lung absorption profile of non-CFC salbutamol via small and large volume plastic spacer devices.

AIMS: To evaluate the lung dose of a non-CFC salbutamol metered dose inhaler (MDI) formulation via three commonly used plastic spacer devices, of both large and small volume, compared with the MDI used on its own. METHODS: Ten healthy volunteers were studied in a randomized single (investigator) blind crossover design. Single 1200 microg nominal doses of salbutamol from a non-CFC MDI (Airomir), as 12 sequential 100 microg puffs over 6 min, were delivered from the MDI alone and via two large volume spacer devices (Nebuhaler, Volumatic), and a small volume spacer (Aerochamber). All spacers were prewashed prior to each study day and mouth rinsing was performed after each drug sequence. Plasma salbutamol was measured at 5, 10, 15 and 20 min, with calculation of maximum (Cmax) and average (Cav) concentrations. This lung dose was assessed using the early lung absorption profile of salbutamol in the first 20 min after inhalation. RESULTS: Both of the large volume spacers, the Nebuhaler and the Volumatic, delivered significantly more salbutamol than the MDI alone. For Cav this amounted to a 2.07-fold difference (95% CI 1.48-2.90) between Nebuhaler vs MDI, and a 1.49-fold difference (95%CI 1.19-1.87) between Volumatic vs MDI. The Nebuhaler also produced greater deposition than either the Volumatic or the Aerochamber spacers; Nebuhaler vs Volumatic: 1.39-fold difference (95% CI 1.09-1.76), Nebuhaler vs Aerochamber: 1.63-fold difference (95% CI 1.20-2.21). There were no significant differences between the Aerochamber and the MDI alone. CONCLUSIONS: Using the early lung absorption profile, for administration of the same nominal dose, both of the large volume spacers (Nebuhaler and Volumatic) but not the small volume spacer (Aerochamber) delivered significantly more salbutamol than the MDI alone. The Nebuhaler also produced greater delivery than either the Volumatic or the Aerochamber spacer devices. Our results show that whilst lung delivery of non-CFC salbutamol MDI is improved by the use of a plastic spacer, there may be appreciable differences in performance, particularly between large and small volume devices.

Absorption↗

Comparison of inhaled terbutaline and terbutaline injection in treatment of acute asthmatic attacks in children.

Thirty asthmatic children, aged 4 to 13 years, 22 boys and 8 girls, were studied during acute asthmatic attacks. Each group of 15 children received either a 0.01 mg/kg subcutaneous injection of terbutaline or 2 puffs from terbutaline pressurized aerosol (0.25 mg/puff) inhaler through a 750-ml volumetric spacer. A slightly greater increase in PEFR following injection compared with inhalation throughout the 6 hours study period was observed. Significant increases in systolic blood pressure and pulse rate were observed only after injection. Therefore, it was concluded that inhaled terbutaline is safe and effective for treating children over 4 years of age with acute bronchospasm and has less cardiovascular side effects than injected terbutaline.

Acute Disease↗

Aerosol therapy: the special needs of young children.

Efficient aerosol therapy in young children is a challenge. The aerosol administration method requires special features, because young children can not perform an inhalation manoeuvre, breath usually through the nose and may be distressed during the administration. The prescribing clinician should be aware of the advantages and disadvantages of the different inhalation devices available, in order to select the proper device for each individual patient. For maintenance asthma therapy in young children the pressurized metered dose inhaler (pMDI) combined with spacer is the first choice for delivering aerosols. A facemask can be attached if a child is unable to breath through the mouth. A small leak of the facemask can reduce the dose delivered dramatically, therefore a good seal is crucial. Lung deposition can be improved by using a pMDI with extra-fine particles. However, even if the most optimal device is chosen, cooperation during administration remains the most important determinant for efficient drug delivery. During crying the dose to the lungs is minimal. Optimal aerosol delivery to the lungs of young children can be achieved with a good facemask seal, good cooperation of the child, with quiet breathing and an aerosol with small particles.

Administration, Inhalation↗

[High-dose inhaled beclomethasone in long-term management of chronic severe asthma--usefulness and dose-dependence].

We studied the usefulness of 18 weeks of therapy with two high doses of inhaled beclomethasone dipropionate (BDP) in the management of severe asthma in adults. The patients had asthma symptoms that had not been controlled by combination therapy with BDP (800 micrograms/day) and bronchodilators. They were divided into two groups. Patients in group A (n = 16) were treated with 1800 micrograms/day of BDP and bronchodilators. Patients in group B (n = 10) were treated with 1400 micrograms/day of BDP and bronchodilators. BDP was inhaled via a large spacer (Volumatic). Eleven patients in group A and 6 patients in group B had been given an oral steroid regularly before the study. Asthma symptom scores, peak expiratory flow (PEF), pulmonary function, bronchial reactivity to methacholine, the total amount of oral steroid, and adrenocortical function were recorded. Results. 1) Clinical characteristics before the start of the study did not differ between groups. 2) Asthma symptom scores decreased to a greater extent in patients who received the higher dose of BDP than in those who received the lower dose. 3) Only the higher dose of BDP significantly increased evening and morning % PEF, as measured 6 weeks and 8 weeks after the start of the treatment. 4) Only the higher dose of BDP significantly increased the FEV1 and the PC20 for methacholine. FVC did not increase. 5) Only the higher dose of BDP significantly decreased the total amount of oral steroid needed to control asthma. 6) Results of the rapid ACTH test indicated that neither dose of BDP suppressed adrenocoritical function. Furthermore, the serum cortisol level measured early in the morning increased to within the normal range in the three patients in whom oral steroid therapy could be reduced or stopped after treatment. These data indicate that 1800 micrograms of BDP per day is more effective than 1400 micrograms/day at the beginning of long-term management of severe chronic asthma in adults whose symptoms are not controlled with the combination of 800 micrograms/day BDP and bronchodilators. Therapy with a higher dose (at least 1600 micrograms/day) of an inhaled steroid is more useful and should be promptly begun to treat severe asthma.

Administration, Inhalation↗

Short-term growth and collagen turnover in asthmatic adolescents treated with the inhaled glucocorticoid budesonide.

Short-term lower leg growth, the insulin-like growth factor axis, and collagen turnover were assessed in 16 adolescents with asthma during treatment with inhaled budesonide, 800 micrograms/d, from a pressurized metered dose inhaler with a volume spacer. The design was a randomized double blind, placebo-controlled two-period crossover trial with treatment periods of 4 weeks and a 1-week wash-out. Lower leg growth was assessed by knemometry. Serum levels of insulin-like growth factor-I, insulin-like growth factor-binding protein-3, and the following markers of collagen turnover were evaluated: Serum markers of type I collagen formation and degradation; the carboxy-terminal propeptide of type I procollagen and the carboxy terminal pyridinoline cross-linked telopeptide of type I procollagen (ICTP), the serum marker of type III collagen formation; the amino-terminal propeptide of type III procollagen (PIIINP) and the urinary concentrations of the type I collagen degradation products pyridinoline (PYD) and deoxypyridinoline (DPD) cross-links. Mean lower leg growth velocity was suppressed from 0.51 mm/week during placebo to 0.18 mm/week during budesonide treatment (p < 0.001). No statistically significant effects on insulin-like growth factor-1, insulin-like growth faster-binding protein-3, or carboxy-terminal propeptide of type I procollagen were observed. ICTP and PIIINP were reduced with 2.3 and 2.5 micrograms/liter (p < 0.001 and p < 0.001, respectively) during budesonide treatment, urinary concentrations of PYD and DPD with 32.9 nmol/mmol creatinine (p < 0.005) and 6.8 nmol/mmol creatinine (p < 0.005), respectively. Significant correlations between lower leg growth velocity and ICTP, PIIINP, PYD, and DPD during placebo (p < 0.01, p < 0.05, p < 0.01, and p < 0.01) and budesonide (p < 0.05, p < 0.05, p < 0.05, and p < 0.05) periods were found. Short term lower leg growth suppression in adolescents treated with inhaled budesonide, 800 micrograms/d, reflects suppression of type I and III collagen turnover.

Administration, Topical↗

Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years.

The primary aim of this study was to quantify and compare bronchodilator responsiveness in healthy and asthmatic children aged 2 to 5 yr. The secondary aim of the study was to compare discriminative capacity (i.e., sensitivity, specificity, and predictive values of the reversibility test for the diagnosis of asthma) for each of the lung function tests applied in the study. Specific airway resistance (sRaw) as measured by whole-body plethysmography, respiratory resistance as measured with the interrupter technique (Rint), and respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5, respectively) as measured with the impulse oscillation technique were assessed before and 20 min after inhalation of terbutaline from a pressurized metered-dose inhaler via a metal spacer by 92 children (37 healthy controls and 55 asthmatic subjects). The study of healthy children followed a randomized, double-blind, crossover design, whereas the study of asthmatic children was open. Baseline lung function was significantly decreased in asthmatic children as compared with healthy control subjects as reflected by all techniques used in the study. sRaw, Rint, and Rrs5, but not Xrs5, improved significantly with terbutaline as compared with placebo in healthy control subjects. Lung function improved to a significantly greater extent in asthmatic children than in control subjects as reflected by all methods. sRaw provided the best discriminative power of such a bronchodilator response, with a sensitivity of 66% and specificity of 81% at the cutoff level of a 25% decrease in sRaw after bronchodilator administration. In conclusion, bronchodilator response measured by sRaw allows a separation of asthmatic from healthy young children. This may help define asthma in this clinically difficult-to-manage group of young wheezy children. The sensitivity and specificity of the other methods used in the study were less than those of sRaw.

Administration, Inhalation↗

The Chocuhaler: sweet deliverance in asthma management.

OBJECTIVE: To determine the characteristics of a new cocoa-based edible spacer device for the delivery of aerosol bronchodilator. DESIGN: In-vitro comparison of two spacer devices (standard and edible) and determination of bronchodilator response using the edible spacer. SETTING: A university children's hospital in Western Australia. SUBJECTS: Two volunteers with moderate asthma. RESULTS: Compared with a standard spacer, the edible spacer delivered significantly more bronchodilator in droplets of a size likely to enter the respiratory tract. A significant bronchodilator response occurred in two out of two subjects when salbutamol was inhaled orally via the chocolate spacer. No significant bronchodilator response occurred in either subject when the spacer was eaten at the end of the study. CONCLUSION: The chocolate spacer used in this study is a suitable device to deliver salbutamol by inhalation. However, there may be potential drawbacks of weight gain in some patients and meltdown in hot climates.

Administration, Inhalation↗