Cumulative Doses Of Salbutamol Research Articles

Bronchodilator responsiveness in children with asthma is not influenced by spacer device selection.

Spacer devices optimize delivery of aerosol therapies and maximize therapeutic efficacy. We assessed the impact of spacer device on the prevalence and magnitude of bronchodilator response (BDR) in children with asthma. Children with physician confirmed asthma and parentally reported symptoms in the last 12 months were recruited for this study. Each participant completed two separate visits (5-10 days apart) with spirometry performed at baseline and following cumulative doses of salbutamol (200, 400, 800, and 200 μg) delivered by either a small volume disposable spacer or a large volume multi-use spacer. Spacer type was alternated for each participant during each visit. The primary outcome was the effect of spacer type on bronchodilator responsiveness. The secondary outcome was to assess the relationships between spacer device, salbutamol dose and the proportion of children with a clinically relevant BDR. Thirty-two children (mean age 11.8 years) completed both visits. Change in lung function following bronchodilators was increased using the large volume spacer, for relative but not absolute increase in FEV1 [mean difference (95% confidence intervals): 1.28% (0.02, 2.54; P = 0.047) and 0.013 L (-0.01, 0.04; P = 0.288)], respectively. There was no observed difference in FVC by spacer type. Overall, 59% (n = 19) of children exhibited a clinically relevant BDR at 400 µg of salbutamol for any spacer and was independent of spacer type. Spacer device was not associated with clinically important differences in lung function following bronchodilator inhalation in children with asthma. At a recommended dose of 400 μg, some children with asthma may have their bronchodilator responsiveness misclassified.

Bronchodilation and safety of supratherapeutic doses of salbutamol or ipratropium bromide added to single dose GSK961081 in patients with moderate to severe COPD

BackgroundThere are few data on the bronchodilatory effects of adding short-acting bronchodilators (SABA) to maintenance, long-acting bronchodilator therapy. This study assessed the additional bronchodilation and safety of adding supratherapeutic doses of salbutamol (SALB) or ipratropium bromide (IPR) to the novel bi-functional molecule (or dual pharmacophore) GSK961081 400 μg (MABA 400) or 1200 μg (MABA 1200). MethodsThis randomised, double-blind, complete, crossover study in 44 patients with moderate to severe COPD, evaluated 6 treatments with a washout of at least 7 days between treatments: single doses of MABA 400 or MABA 1200 followed by cumulative doses of either SALB (3× 200 μg at 20 min intervals), IPR (20 μg, 20 μg and 40 μg at 20 min intervals) or placebo (PLA) (three doses at 20 min intervals) at 1 h, 12 h and 24 h post-MABA dose. The primary endpoint was maximal increase in FEV1, from pre-dose bronchodilator (SABA/PLA), measured 15 min after each cumulative dose of SALB, IPR or PLA. Systemic pharmacodynamics (potassium, heart rate, glucose and QTc), adverse events and systemic pharmacokinetics were also assessed. ResultsThe additional bronchodilatory effects at 12 h and 24 h for both SALB and IPR were of a similar magnitude and statistically significant relative to PLA; mean differences (SE) (L) following MABA 400 dosing: 0.139 (0.023) after SALB at 12 h; 0.123 (0.022) after SALB at 24 h; 0.124 (0.023) after IPR at 12 h; 0.141 (0.021) after IPR at 24 h; and after MABA 1200 dosing: 0.091 (0.023) after SALB at 12 h; 0.126 (0.022) after SALB at 24 h; 0.055 (0.023) after IPR at 12 h; 0.122 (0.022) after IPR at 24 h. Any additional bronchodilator effects at 1 h were small and not clinically significantly different from PLA. There were small, non-clinically significant increases in mean heart rate after both MABA doses plus SALB, and decreased potassium levels in four patients after MABA 1200 plus SALB (×3) or PLA (×1) were observed but overall all treatments were well tolerated and raised no significant safety signals. ConclusionThe additional bronchodilation achieved following supratherapeutic doses of SALB and IPR on top of single doses of MABA 400 or 1200 was comparable for the two agents and neither were associated with any clinically relevant systemic pharmacodynamic effects other than the small transient hypokalemic effect in a 3 out of 41 patients receiving additional high dose salbutamol and MABA 1200. Either short-acting bronchodilator could potentially be used as rescue medication on top of MABA therapy.

Theraputic Respponse Patterns of Severe Acute Asthma Patients to High and Cumulative Doses of Salbutamol

PURPOSE: Nebulized b2 adrenergic agonists are still the first line drugs for a rapid bronchodilatation & an easily adminstered drug during acute asthma attack. Purpose of this study is to assess theraputic response patterns of severe acute asthma patients to high and cumulative doses of salbutamol.

Clinical equivalence between salbutamol hydrofluoroalkane pMDI and salbutamol Turbuhaler TM at the same cumulative microgram doses in paediatric patients

This study aimed to demonstrate equivalent efficacy and safety between salbutamol delivered via the HFA134a pMDI (Hydrofluoroalkane 134a pressurised Metered Dose Inhaler) and the Turbuhaler™ dry powder inhaler in asthmatic children. This was a randomised, double-blind, double-dummy, placebo-controlled, crossover study in 10 asthmatic children aged 6–15 years who demonstrated at least 10% reversibility of FEV 1 after inhaling 400 μg of salbutamol. On 5 single study days subjects received either placebo or cumulative doses of 100, 200, 400 and 800 μg of salbutamol at 30 minute intervals. Both devices were placebo on one study day, while each device was active on two study days. FEV 1 was measured before and 20 minutes after each dose. Heart rate was measured before spirometry. Mean FEV 1 and heart rate at each time point and the area under the dose response time curve (AUC) were analysed using ANOVA. FEV 1 increased similarly after cumulative doses of salbutamol on each of the study days, irrespective of device. Mean treatment difference in AUC was 0.01L.min (95%CI –0.05 to 0.08L). Heart did not differ at any dose. It is concluded that salbutamol delivery from a HFA pMDI and Turbuhaler™ is equivalent on a microgram basis in asthmatic children for efficacy and safety.

Measurement of Inflammatory Mediators of Eosinophils and Lymphocytes in Blood in Acute Asthma: Serum Levels of ECP Influence the Bronchodilator Response

The aim of this study was to assess the relevance of immunoinflammatory markers on the response to short acting β₂-agonist in acute asthma exacerbation. Thus, we measured serum eosinophil cationic protein (ECP) levels and sIL-2R at acute exacerbation in 52 adult patients with atopic asthma, and assessed forced expiratory volume in 1 s (FEV₁) before and after the administration of aerosolized salbutamol. After a cumulative dose of salbutamol causing a 10% improvement in FEV₁ from baseline [CD10, i.e. cumulative doses of salbutamol (800 µg) causing an improvement in FEV₁ from baseline to 10%] the patients were divided into two groups: group A with CD <10 and group B with CD >10. The bronchodilator response, as defined by a ΔFEV₁ (percentage of predictive value of FEV₁) of ≧10 predictive value, was shown by 40% of the patients. After 200, 400 and 800 µg of salbutamol, significant differences of FEV₁ with respect to baseline values were, respectively, p = 0.049, 0.0039 and 0.0014. In contrast, no significant difference of the means of FEV₁ between the doses of salbutamol was observed. Significant differences of ΔFEV₁ between 200 and 400 µg (p = 0.0002) and between 200 and 800 µg (p < 0.0001) were observed, but not between 400 and 800 µg of salbutamol. There were significant correlations between baseline values of predictive FEV₁ and serum ECP levels (rho = –0.60, p < 0.0001) and sIL-2R levels (rho = –0.35, p = 0.01) respectively. Besides, a correlation between ΔFEV₁ and serum ECP levels (rho = –0.53, p < 0.0001) was observed, whereas no correlation was found between ΔFEV₁ and sIL-2R. By analyzing differences between the two groups (A and B) for serum ECP levels, sIL-2R and blood eosinophil count, a significant difference was found for serum ECP levels. We conclude that subjects with acute exacerbation of asthma show high serum levels of ECP and sIL-2R and, more interestingly, that the response to brochodilator was higher in patients with lower serum ECP levels.

Reproducibility of Bronchodilator Response for a Reservoir Dry Powder Inhaler Following Routine Clinical Use

The performance of dry powder inhaler (DPI) devices, particularly reservoir DPIs, may be influenced by environmental conditions. This study compared the bronchodilator efficacy and in vitro aerosol characteristics of salbutamol, delivered via a novel reservoir DPI (Clickhaler®) and a conventional pressurized metered-dose inhaler (MDI) before and after use of the DPI in clinical practice. Following a screening visit, patients received cumulative doses of salbutamol (100, 200, and 400 ug) via DPI or MDI on separate days in a double-blind, crossover design before and after a 4-week period, during which the DPI was used as the patients' first-line bronchodilator. Lung function responses (forced expiratory volume in 1 sec [FEV1], forced vital capacity [FVC], and peak expiratory flow [PEF]) to salbutamol delivered by DPI and MDI and in vitro aerosol characteristics were not significantly different before and after the period of DPI patient use. DPI performance, assessed in vivo and in vitro, is maintained following an extended period of patient use.

Therapeutic Response Patterns to High and Cumulative Doses of Salbutamol in Acute Severe Asthma

To examine the main therapeutic response patterns to high doses of salbutamol and to determine the factors that contribute to outcome in acute severe asthma. The emergency department (ED) of a large, urban hospital with primary and referral care responsibilities. One hundred sixteen consecutive patients with acute exacerbations of asthma were enrolled in the trial, using a prospective sequential design. All patients were treated with salbutamol delivered with a metered-dose inhaler into a spacer device in four puffs (400 microg) at 10-min intervals. The protocol involved 3 h of this treatment (1,200 microg each 30 min). A dose-response increase in pulmonary function was found, but only 70% improved sufficiently to be discharged. Of these, almost 70% required < or =2.4 mg of the drug within 1 h to reach the discharge threshold, whereas the remainder 30% need > or =3.6 mg. In 30% of subjects, salbutamol was ineffective. These patients were characterized by a more severe disease as judged by previous beta2-agonist use, larger duration of attack before ED visit, and a more severe obstruction at presentation. However, the most important predictors of outcome were peak expiratory flow rate (PEFR) as percent of predicted, PEFR as liters per minute, and PEFR variation over baseline value, all at 30 min. This study described two different therapeutic response patterns to salbutamol. Almost 70% of patients were sensitive to salbutamol (good response pattern), and in this group, 2.4 to 3.6 mg represents optimal treatment. In the remainder 30% of patients (poor response pattern), salbutamol in high doses had little effect. However, the outcome was not determined by the intensity of the initial symptoms or by the value of the presenting PEFR, but rather by the early (30 min) short-term response to treatment.