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Bronchodilator responsiveness in normal infants and young children.

UNLABELLED: Several studies have demonstrated that normal infants exhibit bronchoconstriction after inhalation of nonspecific agonists and that the induced airway narrowing can be reversed by the inhalation of a beta-agonist. However, there are very limited data on baseline airway tone and the airway response to a beta-agonist in this subject population. The purpose of our study was to evaluate in normal infants baseline airway responsiveness to the inhaled beta-agonist, albuterol, using changes in maximal expiratory flows. Forty-one healthy infant volunteers with no history of respiratory disease or recurrent wheezing (ages 5.4 to 141.4 wk) were studied. Maximal expiratory flow- volume curves were obtained at baseline and 10 min after inhalation of albuterol (n = 28) or placebo (n = 13) using a metered-dose inhaler with a spacer. The mean percent change was significantly greater (p < 0.05) in the albuterol versus placebo group for FEV(0.5) (2.2% versus -1.5%), FEF(75%) (10.6% versus -3.1%), and FEF(85%) (12.9% versus 0.5%). Six of 28 albuterol-treated infants demonstrated increases in FEF(75%) greater than two standard deviations from the mean change in FEF(75%) seen in the placebo group. These infants were younger and more frequently exposed to maternal smoking during pregnancy. We conclude that normal healthy infants have overall levels of baseline airway tone that are similar to that reported in adults and older children; however, among the infants we evaluated the response to an inhaled bronchodilator was greatest in the youngest infants and in those exposed to tobacco smoking. KEYWORDS: airway responsiveness; asthma; tobacco smoke; infant pulmonary function; bronchodilator

Administration, Inhalation↗

The effect of sodium cromoglycate on upper and lower respiratory symptoms in children born prematurely.

The aims of this study were to assess whether sodium cromoglycate (SCG) was an effective prophylaxis against both upper and lower respiratory tract signs and to determine factors which affected the site and magnitude of the response to SCG. Sixteen children born prematurely were entered into a randomised placebo-controlled trial at 15 months of age (range 4-31 months). The patients received, in random order, either 3 weeks' treatment with SCG (5 mg) or placebo, both given four times a day by inhalation via a spacer device. Parents were asked to record the occurrence and severity of their child's upper respiratory tract signs; sneezing and runny nose and lower respiratory tract signs; day and night time cough and wheeze. During the active compared to the placebo period there was an overall reduction of 47% and 53% in upper and lower respiratory tract signs, respectively. The magnitude of response to SCG as assessed by either the change in upper or lower respiratory tract signs was not significantly related to the patient's gestational or postnatal age, the occurrence of neonatal chronic lung disease, family history of atopy or the order in which the therapy was administered. We conclude that inhaled SCG may be a useful prophylaxis for both upper and lower respiratory tract signs for children born prematurely and less than 3 years of age.

Administration, Inhalation↗

Elevated plasma lactate level associated with high dose inhaled albuterol therapy in acute severe asthma.

BACKGROUND: Lactic acidosis is a recognised event in adult patients with status asthmaticus, particularly in the setting of intensive care. However, it has been infrequently studied in patients attending the emergency departments (ED). METHODS: We conducted a prospective and descriptive study to assess levels of lactate and effects on bronchodilator response in adult patients with acute severe asthma treated with high doses of albuterol in the ED. In total, 18 subjects (mean (SD) age 42.9 (2.7) years, FEV1 = 32.2 (10.9)% of predicted) who presented to an emergency department were enrolled in the study. All patients were treated with albuterol; four puffs (100 microg/puff) at 10 minute intervals, delivered by a pressurised metered dose inhaler into a spacer device over a 2 hour period. RESULTS: At the end of treatment, mean (SD) plasma lactate level (2.94 (2.1) mmol/l) was significantly higher (p = 0.001) than baseline. Of the 18 patients, nine (50%) showed lactate levels > or = 2.5 mmol/l (four patients presented values > 4 mmol/l); these patients had a shorter duration of attack prior to ED presentation (p = 0.01), a higher pretreatment heart rate (p = 0.005), a lower pretreatment SpO2 (p = 0.03), a lower pretreatment PO2 (p = 0.009), a higher pretreatment PCO2, and a lower pretreatment serum potassium (p = 0.005). However, there were no significant differences in the airway response between groups. CONCLUSIONS: This study confirmed previous observations that high lactate concentrations can develop during the first hours of inhaled beta agonist treatment. The presence of a previous hyperadrenergic state may predispose to the development of this condition. A significant improvement in lung function was associated with elevated lactate levels.

Acute Disease↗

Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of end-inspiratory pause.

The delivery of bronchodilators with a metered-dose inhaler (MDI) and a spacer in mechanically ventilated patients has become widespread practice. However, the various ventilator settings that influence the efficacy of MDI are not well established. Application of an end-inspiratory pause (EIP) 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 EIP on the bronchodilation induced by beta2-agonists administered with MDI and a spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) was examined. Twelve patients with COPD, mechanically ventilated on volume-controlled mode, were prospectively randomized to receive six puffs of salbutamol (100 microg x puff(-1)) either with or without EIP of 5 s duration. Salbutamol was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud-enhancer spacer. After a 6 h wash-out, patients were crossed over to receive salbutamol by the alternative mode of administration. Static and dynamic airway pressures, minimum (Rmin) and maximum (Rmax) airflow resistance, the difference between Rmax and Rmin (deltaR), static end-inspiratory respiratory system compliance (Cst,rs) and cardiac frequency (fc) were measured before and at 15, 30 and 60 min after salbutamol administration. Salbutamol caused a significant decrease in dynamic and static airway pressures, Rmin and Rmax. These changes were not influenced by application of EIP and were evident at 15, 30 and 60 min after salbutamol. With and without EIP, Cst,rs,deltaR and fc did not change after salbutamol. In conclusion, salbutamol delivered with a metered-dose inhaler and a spacer device induced significant bronchodilation in mechanically ventilated patients with chronic obstructive pulmonary disease, the magnitude of which was not affected by an end-expiratory pause of 5 s. These results do not support the use of end-inspiratory pause when bronchodilators are administered in adequate doses during controlled mechanical ventilation.

Aged↗

Reversing acute bronchoconstriction in asthma: the effect of bronchodilator tolerance after treatment with formoterol.

Continuous treatment with a short-acting beta2-agonist can lead to reduced bronchodilator responsiveness during acute bronchoconstriction. This study evaluated bronchodilator tolerance to salbutamol following regular treatment with a long-acting beta2-agonist, formoterol. The modifying effect of intravenous corticosteroid was also studied. Ten asthmatic subjects (using inhaled steroids) participated in a randomised, double-blind, placebo-controlled, cross-over study. Formoterol 12 microg b.i.d. or matching placebo was given for 10-14 days with >2 weeks washout. Following each treatment, patients underwent a methacholine challenge to induce a fall in forced expired volume in one second (FEV1) of at least 20%, then salbutamol 100 microg, 100 microg, and 200 microg was inhaled via a spacer at 5 min intervals, with a further 400 microg at 45 min. After a third single-blind formoterol treatment period, hydrocortisone 200 mg was given intravenously prior to salbutamol. Dose-response curves for change in FEV1 with salbutamol were compared using analysis of covariance to take account of methacholine-induced changes in spirometry. Regular formoterol resulted in a significantly lower FEV1 after salbutamol at each time point compared to placebo (p<0.01). The area under the curves (AUCs) for 15 (AUC0-15) and 45 (AUC0-45) min were 28.8% and 29.5% lower following formoterol treatment (p<0.001). Pretreatment with hydrocortisone had no significant modifying effect within 2 h of administration. It is concluded that significant tolerance to the bronchodilator effects of inhaled salbutamol occurs 36 h after stopping the regular administration of formoterol. This bronchodilator tolerance is evident in circumstances of acute bronchconstriction.

Acute Disease↗

Inhaler technique of outpatients in the home.

OBJECTIVE: Assess the role of evaluation, instruction, and use of spacers by patients using metered dose inhalers (MDIs) in the home. PATIENTS AND SETTING: Patients (age 64 +/- 15 y [mean +/- standard deviation]) receiving home visits by respiratory care practitioners for oxygen therapy had their inhaler technique checked. INTERVENTIONS AND MEASUREMENTS: A detailed acceptable/unacceptable check-off list was used with 172 patients to evaluate inhaler technique. Patients with poor technique were given instruction and their technique was reassessed. A subgroup of 43 patients was reevaluated on up to 3 visits. RESULTS: Only 18% of patients using MDIs without spacers were rated acceptable with the detailed check list. Instruction improved inhaler technique, but few patients with initially poor technique without spacers developed fully acceptable technique. Improvements made immediately following instruction were lost when patients were reevaluated months later. Few patients received spacers after they were recommended. Technique was markedly better with spacers. Most patients (76%) had initially proper technique with spacers, and most who had poor technique could learn and retain proper technique. CONCLUSIONS: Improper inhaler technique without spacers is very common among patients evaluated at home, and the majority of patients were unable to learn and retain proper technique. Most patients would benefit from using spacers with their inhalers. = 33 for first and second. = 26 for third. FRC = functional residual capacity. RV = residual volume. TLC = total lung capacity.¿., Fig. 3¿/PICK;0404f3;;;page;;;;yes;1¿ ¿/GRAPH;rk1000404003;comptd;;center;stack¿ ¿/CAPT;;;center;stack;2112n¿

Adult↗

The response of two different dosages of beclometasone dipropionate suspension for nebulization versus a standard dose of beclometasone dipropionate via a metered-dose inhaler on bronchoprovocation testing in adults with asthma.

The objective of this double-blind, randomized, placebo-controlled, parallel-group study was to compare the pharmacodynamic effects and safety of beclometasone dipropionate (BDP) given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 1-week run-in period, 40 patients, aged 18-60 years, with intermittent bronchial asthma were randomized to one of four treatment groups for 3 weeks (n = 10 in each group): beclometasone dipropionate (BDP) suspension for nebulization 1,600 microg day(-1) b.i.d. via a nebulizer, BDP suspension for nebulization 3,200 microg day(-1) b.i.d. via a nebulizer, BDP 800 microg day(-1) b.i.d. via a metered-dose inhaler (MDI) plus spacer, or placebo. At study end, comparable effects were reported for all active treatment groups on the primary pharmacodynamic endpoint of FEV1 in response to methacholine bronchial provocation testing, with a statistically significant improvement shown in the BDP 3,200 microg day(-1) suspension for nebulization group compared with pre-treatment for other parameters, including FEV1 and peak expiratory flow rates. All treatments were comparable. All treatments were equally well tolerated. No significant effects on cortisol levels were reported in any of the treatment groups.

Administration, Inhalation↗

Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial.

BACKGROUND: The value of azithromycin for treatment of acute bronchitis is unknown, even though this drug is commonly prescribed. We have investigated this question in a randomised, double-blind, controlled trial. METHODS: Adults diagnosed with acute bronchitis, without evidence of underlying lung disease, were randomly assigned azithromycin (n=112) or vitamin C (n=108) for 5 days (total dose for each 1.5 g). All individuals were also given liquid dextromethorphan and albuterol inhaler with a spacer. The primary outcome was improvement in health-related quality of life at 7 days; an important difference was defined as 0.5 or greater. Analysis was by intention to treat. FINDINGS: The study was stopped by the data-monitoring and safety committee when 220 patients had been recruited. On day 7, the adjusted difference in health-related quality of life was small and not significant (difference 0.03 [95% CI -0.20 to 0.26], p=0.8). 86 (89%) of 97 patients in the azithromycin group and 82 (89%) of 92 in the vitamin C group had returned to their usual activities by day 7 (difference 0.5% [-10% to 9%], p>0.9). There were no differences in the frequency of adverse effects; three patients in the vitamin C group discontinued the study medicine because of perceived adverse effects, compared with none in the azithromycin group. Most patients (81%) reported benefit from the albuterol inhaler. INTERPRETATION: Azithromycin is no better than low-dose vitamin C for acute bronchitis. Further studies are needed to identify the best treatment for this disorder.

Acute Disease↗

The effect of salbutamol on performance in elite nonasthmatic athletes.

The effect of salbutamol on performance was studied in seven male nonasthmatic highly trained (VO2max > or = 60 ml.kg-1 x min-1) cyclists. Salbutamol (S = 2 puffs = 200 micrograms) or placebo (P) was administered by metered-dose inhaler, through a spacer device, 20 min prior to testing in a double-blind, randomized cross-over design. Testing sessions on a cycle ergometer included the measurement of maximal oxygen uptake (VO2max), peak power, maximal heart rate, and pulmonary function. A timed sprint to exhaustion was performed after 45 min of exercise at 70% of VO2max, and a Wingate anaerobic test was used to measure total work and peak power. There was a nonsignificant decrease in VO2max (P = 63.5 +/- 3.2; S = 62.6 +/- 3.3 ml.kg-1 x min-1). No difference was found in peak power, maximum heart rate, endurance sprint time, Wingate peak power, or total work. After an anticipated baseline increase was taken into account, the pattern of change in FEV1 over time did not differ between salbutamol and placebo. It was concluded that a therapeutic dose of aerosol salbutamol does not have an ergogenic effect in elite nonasthmatic athletes, and it is therefore recommended that inhaled salbutamol continue to be permitted in international competition for individuals with exercise induced bronchospasm.

Albuterol↗

Bronchodilatation and the inspiratory flow volume curve.

The inspiratory flow volume curve is included in the spirometric tracing provided by most pulmonary function laboratories and is useful in assessing upper airway abnormalities. We analyzed the changes in peak inspiratory flow (PIF), forced inspiratory flow at 50% (FIF50), and forced inspiratory vital capacity (FIVC) that occur with bronchodilator challenge testing (3 puffs of a beta-agonist by metered-dose inhaler without a spacer device) in 145 consecutive patients. Fifty-five patients responded to bronchodilators with either a 12% or 200-mL change in FEV1 or FVC. All of these subjects produced forced expiratory maneuvers that fulfilled American Thoracic Society criteria or acceptability. The FIVC was the only inspiratory parameter that consistently showed a similar correlation to the bronchodilator responsiveness demonstrated by the FEV1 or FVC. With the reduction in air trapping, a 12% or 200-mL change in the FIVC is additional confirmatory evidence of bronchodilator responsiveness.

Adrenergic beta-Agonists↗

A comparison of inhaled fluticasone and oral prednisone for children with severe acute asthma.

BACKGROUND: Inhaled corticosteroids are effective in the treatment of children with asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in the management of severe acute disease. METHODS: We performed a double-blind, randomized trial involving 100 children five years of age or older who had severe acute asthma (indicated by a forced expiratory volume in one second [FEV1] that was less than 60 percent of the predicted value) and in whom the results could be evaluated. All were treated with an aggressive bronchodilator regimen and received one dose of either 2 mg of inhaled fluticasone through a metered-dose inhaler with a spacer or 2 mg of oral prednisone per kilogram of body weight. They were assessed hourly for up to four hours. RESULTS: The mean (+/-SD) base-line FEV1 as a percentage of the predicted value was 46.3+/-12.5 in the fluticasone group (51 subjects) and 43.9+/-9.9 in the prednisone group (49 subjects). The FEV1 increased by a mean of 9.4+/-12.5 percentage points in the fluticasone group and by 18.9+/-9.8 percentage points in the prednisone group four hours after therapy (P< 0.001). None of the children in the prednisone group had a reduction in FEV1 as a percentage of the predicted value from base line to four hours, as compared with 25 percent of those in the fluticasone group (P<0.001). Sixteen (31 percent) of the children treated with fluticasone were hospitalized, as compared with five (10 percent) of those treated with prednisone (P=0.01). CONCLUSIONS: Children with severe acute asthma should be treated with oral prednisone and not with inhaled fluticasone or a similar inhaled corticosteroid.

Administration, Inhalation↗

The effect of inhaled budesonide on symptoms, lung function, and cold air and methacholine responsiveness in 2- to 5-year-old asthmatic children.

We hypothesized that measurement of lung function (LF) and bronchial hyperresponsiveness (BHR) could serve as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids in asthmatic children aged 2 to 5 yr. We studied 38 children (mean age: 53 mo; range: 35 to 71 mo) with moderately severe asthma in a single-center, randomized, double-blind, parallel-group, placebo-controlled study involving 8 wk of treatment. Budesonide (BUD) 400 microgram twice daily was administered via a pressurized metered-dose inhaler and metal spacer device. Symptom scores (SSc) and use of short-acting beta(2)-agonist were monitored with diary cards. LF in awake children was measured as the specific airway resistance (sRaw), using whole-body plethysmography; as resistance by the interrupter technique (Rint); and as resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique. Cold air challenge (CACh) and methacholine challenge (MCh) were used to assess BHR. Children in the BUD group experienced significantly fewer night- and daytime symptoms (p < 0.05) and more symptom-free days (p < 0.05), but not nights (p = 0.07), than children in the placebo group. Daytime (p < 0.05) but not nighttime (p = 0.09) use of rescue medication and asthma exacerbation rates (3.7 versus 9.3 exacerbations/yr) (p = 0.006) were both in favor of BUD. LF measured with the Rint technique, Rrs5, and Xrs5 were significantly improved by BUD. BHR as measured by CACh improved significantly with BUD, whereas no improvement was found on MCh. In conclusion, inhaled BUD at a total dose of 800 microgram daily significantly improved SSc, asthma exacerbation rates, lung function, and BHR as assessed by CACh in asthmatic children aged 2 to 5 yr.

Administration, Inhalation↗

Effect of age on bronchodilator response in acute severe asthma treatment.

STUDY OBJECTIVES: This study was designed to evaluate the effects of age on bronchodilator response to salbutamol in patients with acute severe asthma in the emergency department. SUBJECTS AND METHODS: Sixty-four sequential patients (mean age, 34.2+/-10.7 years) with acute asthma were enrolled in the trial. Using age as a major criterion, we divided the sample in two groups: the young one (age < or = 35 years, n=30) and the older (> 35 years, n=34). All patients were treated with salbutamol delivered with metered-dose inhaler into a spacer device, in a dose of four puffs every 10 min (100 microg per actuation) during 3 h. RESULTS: Mean FEV1 improved significantly over baseline values for both groups (p=0.001). At final disposition, the mean percent of predicted FEV1 was 55.1+/-16.3% in the young group and 58.0+/-20.9% in the older group. There were no significant differences between both groups for FEV1 percent response at any point studied. A significant increase in heart rate over baseline was seen in the older group (p=0.001). Older patients also presented a higher incidence in nausea and tremor. Young and older patients with acute asthma achieved equivalent bronchodilation response to salbutamol. CONCLUSIONS: We concluded that age is not a predictor of response to beta-agonists.

Acute Disease↗

Systemic activity of inhaled topical steroid in toddlers studied by knemometry.

The short-term linear growth rate of the lower leg in toddlers was measured and evaluated in order to study the possible effect of inhaled budesonide on this factor in toddlers with mild recurrent wheezing. The short-term linear growth rate of the lower leg was measured weekly using a hand-held knemometer. Eighteen toddlers aged 13-36 months (mean 27 months) with a history of recurrent wheezing requiring inhaled topical steroids, but without need of regular medication during the months prior to the study, were studied. The children were randomized blindly through three consecutive treatment periods of four weeks with placebo or budesonide in daily doses of 200 micrograms and 800 micrograms administered as a pressurized aerosol inhaled via a spacer with a face mask. Twenty-nine percent (median) of the nominal dose was delivered at the mouth of the children. Three children were withdrawn because of exacerbations and one because of non-compliance. The precision of the measurement procedure was 51 microns/day. The mean growth rate during placebo, low-dose and high-dose steroid treatment was 92 microns/day, 114 microns/day and 46 microns/day respectively. The growth rate during the high-dose treatment was suppressed significantly compared to placebo treatment (95% CI -76 microns/day to -17 microns/day), whereas the growth rate during low-dose steroid treatment was indistinguishable from placebo treatment (95% CI -7 to +52 microns/day). In conclusion, measurement of short-term linear growth rate by knemometry in toddlers is a fast and gentle method with a high level of precision.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Importance of the inhalation device on the effect of budesonide.

Two hundred and forty one children with chronic perennial asthma, who had been treated with budesonide via a metered dose inhaler with a spacer device (Nebuhaler), had their normal dose of budesonide reduced by 50% to determine if they had been overtreated. Within three weeks, asthma control deteriorated in 126 patients to such an extent that budesonide had to be increased to the normal dose. After stabilising their asthma, these children were enrolled in a randomised, double blind, double dummy, parallel study, performed to compare the effect of budesonide via Nebuhaler with that of half the dose of budesonide via Turbuhaler. The study started with a two week run-in during which patients were treated with their normal dose of budesonide via Nebuhaler. After run-in, 64 children were randomised to treatment with their normal budesonide treatment and the remaining 62 children to treatment with half their normal dose via Turbuhaler for nine weeks. Throughout the study, patients recorded asthma symptoms, peak flow measurements, and beta 2 agonist use in a diary. Pulmonary function tests, exercise tests, and 24 hour urine sample collections were performed at hospital visits during run-in and the study period. Apart from beta 2 agonist use, which was significantly lower for patients on Turbuhaler treatment than on Nebuhaler treatment, there were no differences between the groups in any of the parameters studied during run-in or during the study period. Furthermore, there was no trend of deterioration in asthma control when the dose of budesonide was reduced by 50% when Turbuhaler was the inhalation device. It is concluded that budesonide via Turbuhaler is more effective than via Nebuhaler in the treatment of asthma. Based on this finding, attempts should be made to reduce the dose of budesonide when patients are switched from Nebuhaler to Turbuhaler treatment.

Administration, Inhalation↗

Systemic effects of inhaled corticosteroids on growth and bone turnover in childhood asthma: a comparison of fluticasone with beclomethasone.

Inhaled steroids are frequently used in childhood asthma, but concerns based on limited objective evidence remain, regarding long-term side-effects. In this study the systemic effects of standard doses of inhaled steroids in childhood asthma were assessed, comparing beclomethasone dipropionate (BDP) with fluticasone propionate (FP). The study was prospective, randomized and double-blind. Twenty-three steroid-naive children with moderately severe asthma, aged 5-10 yrs, were allocated either BDP (400 microg x day(-1) or FP (200 microg x day(-1)) using a metered-dose inhaler with a spacer. Asthma control was assessed at regular intervals over 20 months. Fasting morning blood and overnight urine samples were collected for estimation of serum cortisol, serum 1-carboxyterminal telopeptide (ICTP), serum osteocalcin and urine deoxypyridinoline (DPD). Bone mineral density (BMD) was measured at each visit. None of the markers of bone turnover showed any change during the study period. BMD increased at normal rates with age. Serum cortisol significantly decreased on BDP, but not on FP. A significant difference in growth rates was found between the groups, with a slower rate of growth towards the end of the observation period in the BDP group. In conclusion when taken in a relatively modest dose over a period of time, beclomethasone dipropionate had significant effects on the hypothalamic-pituitary-adrenal axis and statural growth in childhood asthma. These systemic effects were not seen with an equipotent dose of fluticasone propionate.

Administration, Inhalation↗

Bronchodilator response in asthmatic children is significantly reduced when measured immediately after methacholine challenge.

AIM: Airway responses to a bronchodilator (BDR) and to methacholine are frequently measured in the assessment of childhood asthma and in pulmonary research. For practical reasons, we wondered whether it would be possible to obtain a reliable BDR immediately after completion of a methacholine challenge test. To this end, we compared BDR with and without a preceding methacholine challenge. METHODS: The BDR was measured twice in random order on consecutive days in 24 asthmatic children with methacholine hyperresponsiveness. It was calculated as the change in forced expiratory volume in one second (FEV1) before and 20 min after inhaling 800 microg of salbutamol (metered dose inhaler with a spacer), expressed as a percentage of the predicted value (deltaFEV1%pred). On one day BDR was measured immediately after completing a methacholine challenge, on the other day without any preceding challenge. RESULTS: Mean(SD) baseline FEV1%pred was not significantly different between test days [98.6(14.2)% and 98.1(13.8)%, respectively, p=0.53]. The geometric mean provocative dose of methacholine producing a 20% fall in FEV1 (PD20) was 56.2 microg (range 10.3-306.2 microg). The mean (SEM) BDR without preceding methacholine challenge was 10.8(1.4)%, while after preceding methacholine challenge it was 5.2(1.5)% (mean difference 5.6%, 95% CI 3.0%-8.1%, p<0.001). Mean(SEM) postbronchodilator FEV1%pred was 109.4(3.0)% without and 103.4(2.7)% with preceding methacholine challenge (mean difference 6.0%, 95% CI 3.5%-8.6%, p<0.001). CONCLUSION: A preceding methacholine challenge significantly reduces BDR in asthmatic children. Therefore, a BDR, measured immediately after completing a methacholine challenge, cannot be used as a substitute for a separate bronchodilator test.

Administration, Inhalation↗

Effectiveness of budesonide aerosol in ventilator-dependent preterm babies: a preliminary report.

The aim of this randomized, double-blind, placebo-controlled trial was to assess the short-term effect of a topical glucocorticoid (budesonide 600 mu g twice daily) vs. placebo administered by metered dose inhaler (MDL) and spacer (Aerochamber MV15) directly into endotracheal tube of intubated infants for 7 days. Twenty preterm infants (mean birthweight, 1,030 g; mean gestational age, 27.3 weeks)who still needed assisted ventilation at 14 days of age were randomly assigned to receive budesonide (n=9) or placebo (n=11) and completed the study. The primary outcome was the need for mechanical ventilation after 7 days of treatment. Other outcome variables included ventilator settings, blood gases, serum cortisol levels, and bronchoalveolar lavage inflammatory cell counts. No ventilated infant was extubated during the study period. The treatment group showed significant improvements in mean peak inspiratory pressure, ventilator efficiency index, and (A-a) oxygen difference. There were no changes in the placebo group. Serum cortisol levels and bronchoalveolar lavage cell counts did not change significantly during study period. There was no difference in side effects between the groups. This trial demonstrates that topical budesonide administered by MDL and Aerochamber produces clinical improvement in ventilated preterm infants, without glucocorticoid side effects.

Administration, Inhalation↗