[Evaluation of the efficacy and safety of a combination drug containing ambroxol, guaifenesin, and levosalbutamol versus a fixed-dose combination of bromhexine/guaifenesin/salbutamol in the treatment of productive cough in adult patients with acute bronchitis].

AIM: To evaluate the efficacy and safety of a combination drug containing ambroxol, guaifenesin, and levosalbutamol, oral solution, versus Ascoril Expectorant, syrup (combination of bromhexine, guaifenesin, and salbutamol) in the treatment of productive cough in adult patients with acute bronchitis. MATERIALS AND METHODS: This open-label, randomized, phase III study included patients with acute bronchitis who had a productive cough with difficulty in sputum expectoration. 244 patients were randomized in a 1:1 ratio and received 10 mL of the study drug or reference drug 3 times daily for 2 weeks. After 7 and 14 days of treatment, the physician evaluated patient's subjective complaints and the efficacy of therapy. The primary endpoint was the proportion of patients with high and very high efficacy. RESULTS: The primary endpoint was reached by 70 (0.5738) patients in the study drug group and 54 (0.4426) in the reference drug group (p=0.04). The intergroup difference was 0.1311 [95% confidence interval: 0.0057; 0.2566]. The lower limit of the 95% confidence interval was above zero, which confirms the superiority of therapy with the study drug over therapy with Ascoril Expectorant. The proportion of patients with a 1-point total score reduction and with complete resolution of all symptoms according to the Modified Cough Relief and Sputum Expectoration Questionnaire after 7 and 14 days was numerically higher in the study drug group versus the reference drug group. There were no statistically significant differences between the groups in the incidence of adverse events. CONCLUSION: The efficacy of a new combination drug containing ambroxol, guaifenesin, and levosalbutamol in the treatment of productive cough in adult patients with acute bronchitis is superior to the efficacy of Ascoril Expectorant. The safety profiles of the study drug and the reference drug were comparable.

Case report: Paradoxical responses to short acting beta-agonists in a pediatric patient.

Introduction: Asthma is one of the most common airway diseases that nearly all pediatricians will encounter in their clinical practice. Using spirometry to compare a patient's forced expiratory volume in one second (FEV1) both pre- and post-bronchodilator administration is the ideal way to document a paradoxical bronchodilator response.Case Study: Here, we present a patient who experienced paradoxical responses to short acting beta-2 agonists (SABAs; albuterol and levalbuterol).Results: This patient responded to an anti-cholinergic agent (ipratropium bromide) with both subjective as well as objective response.Conclusion: This case highlights the need to include paradoxical response to SABAs in the differential of a patient with poorly controlled asthma. It also provides an example of successful treatment of a pediatric patient with a class of medications previously reserved for adults with chronic obstructive pulmonary disease.

Combined inhaled beta-agonist and anticholinergic agents for emergency management in adults with asthma.

BACKGROUND: Inhaled short-acting anticholinergics (SAAC) and short-acting beta2-agonists (SABA) are effective therapies for adult patients with acute asthma who present to the emergency department (ED). It is unclear, however, whether the combination of SAAC and SABA treatment is more effective in reducing hospitalisations compared to treatment with SABA alone. OBJECTIVES: To conduct an up-to-date systematic search and meta-analysis on the effectiveness of combined inhaled therapy (SAAC + SABA agents) vs. SABA alone to reduce hospitalisations in adult patients presenting to the ED with an exacerbation of asthma. SEARCH METHODS: We searched MEDLINE, Embase, CINAHL, SCOPUS, LILACS, ProQuest Dissertations & Theses Global and evidence-based medicine (EBM) databases using controlled vocabulary, natural language terms, and a variety of specific and general terms for inhaled SAAC and SABA drugs. The search spanned from 1946 to July 2015. The Cochrane Airways Group provided search results from the Cochrane Airways Group Register of Trials which was most recently conducted in July 2016. An extensive search of the grey literature was completed to identify any other potentially relevant studies. SELECTION CRITERIA: Included studies were randomised or controlled clinical trials comparing the effectiveness of combined inhaled therapy (SAAC and SABA) to SABA treatment alone to prevent hospitalisations in adults with acute asthma in the emergency department. Two independent review authors assessed studies for inclusion using pre-determined criteria. DATA COLLECTION AND ANALYSIS: For dichotomous outcomes, we calculated individual and pooled statistics as risk ratios (RR) or odds ratios (OR) with 95% confidence intervals (CI) using a random-effects model and reporting heterogeneity (I²). For continuous outcomes, we reported individual trial results using mean differences (MD) and pooled results as weighted mean differences (WMD) or standardised mean differences (SMD) with 95% CIs using a random-effects model. MAIN RESULTS: We included 23 studies that involved a total of 2724 enrolled participants. Most studies were rated at unclear or high risk of bias.Overall, participants receiving combination inhaled therapy were less likely to be hospitalised (RR 0.72, 95% CI 0.59 to 0.87; participants = 2120; studies = 16; I² = 12%; moderate quality of evidence). An estimated 65 fewer patients per 1000 would require hospitalisation after receiving combination therapy (95% 30 to 95), compared to 231 per 1000 patients receiving SABA alone. Although combination inhaled therapy was more effective than SABA treatment alone in reducing hospitalisation in participants with severe asthma exacerbations, this was not found for participants with mild or moderate exacerbations (test for difference between subgroups P = 0.02).Participants receiving combination therapy were more likely to experience improved forced expiratory volume in one second (FEV1) (MD 0.25 L, 95% CI 0.02 to 0.48; participants = 687; studies = 6; I² = 70%; low quality of evidence), peak expiratory flow (PEF) (MD 36.58 L/min, 95% CI 23.07 to 50.09; participants = 1056; studies = 12; I² = 25%; very low quality of evidence), increased percent change in PEF from baseline (MD 24.88, 95% CI 14.83 to 34.93; participants = 551; studies = 7; I² = 23%; moderate quality of evidence), and were less likely to return to the ED for additional care (RR 0.80, 95% CI 0.66 to 0.98; participants = 1180; studies = 5; I² = 0%; moderate quality of evidence) than participants receiving SABA alone.Participants receiving combination inhaled therapy were more likely to experience adverse events than those treated with SABA agents alone (OR 2.03, 95% CI 1.28 to 3.20; participants = 1392; studies = 11; I² = 14%; moderate quality of evidence). Among patients receiving combination therapy, 103 per 1000 were likely to report adverse events (95% 31 to 195 more) compared to 131 per 1000 patients receiving SABA alone. AUTHORS' CONCLUSIONS: Overall, combination inhaled therapy with SAAC and SABA reduced hospitalisation and improved pulmonary function in adults presenting to the ED with acute asthma. In particular, combination inhaled therapy was more effective in preventing hospitalisation in adults with severe asthma exacerbations who are at increased risk of hospitalisation, compared to those with mild-moderate exacerbations, who were at a lower risk to be hospitalised. A single dose of combination therapy and multiple doses both showed reductions in the risk of hospitalisation among adults with acute asthma. However, adults receiving combination therapy were more likely to experience adverse events, such as tremor, agitation, and palpitations, compared to patients receiving SABA alone.

A Cross-sectional Cohort Analyses Assessing Response to Levosalbutamol Bronchodilatory Cough Formulations in Outpatient Community Settings of India: 'BUS' analyses.

INTRODUCTION: Cough is significant health problem with greater implication for impaired quality of life. Acute and chronic cough due to infective (viral/bacterial), allergic conditions or bronchial asthma including cough variant asthma are often treated with combination of mucolytics, expectorants and bronchodilators. Bronchodilators reduces cough sensitivity, promotes clearance of cough secretions while reducing protrusive inflammatory mediator release. AIMS AND OBJECTIVES: To further understand the clinical utility and safety of Bronchodilatory cough formulations (BCF) containing Levosalbutamol in real world settings. MATERIAL AND METHODS: A prospective, cross sectional, cohort analyses (Bronchodilatory coUgh formulary Survey, BUS) assessing Levosalbutamol cough formulations utilization at 40 centers involving general and consultant physicians across India. RESULTS: Consecutive prescription records (n=1367) involving Levosalbutamol were collated for analyses. Baseline demographics included adults (21%) and children (79%) with mean age 11.1 yrs, male (60%) and female(40%). Levosalbutamol BCF was commonly prescribed for LRTI (69.7%), AECB (14.8%), Bronchial asthma (8.5%), Allergic rhinitis (5%). The predominant risk factors in both adults and children included smoking and allergic rhinitis respectively. In most cases cough severity was assessed utilizing Fisman scale score (0-4). Mean cough score improved from baseline score of 3 to 0.8 with parallel improvement in associated symptoms of wheeze and sputum. Antibiotics were prescribed in most of LRTI or acute exacerbation cases with purulent sputum. Side effects noted included tremor (1%), palpitation (0.9%), vomiting (0.7%) that were mild and transient in most cases with none requiring treatment withdrawal. In two cases (0.1%), further treatment with nebulization and antibiotics were provided. CONCLUSIONS: Levosalbutamol containing Bronchodilatory Cough formulation remains as safe and effective option for adults and children while managing acute or chronic cough primarily due to allergic rhinitis, bronchial asthma or COPD.

Usefulness Of Glucocorticoids In The Management Of Foreign Body Aspiration.

Foreign body aspiration can be a life-threatening emergency. An aspirated solid or semi-solid object may lodge in the larynx, trachea or other breathing airways. If the object is large enough to cause nearly complete obstruction of the airway, asphyxia may rapidly cause death. We report a 19-year old man admitted with right lower lobe pneumonia who spontaneously expelled a foreign body, one day after admission and glucocorticoids administration. Glucocorticoids should be considered in foreign body aspiration management because improvement of the inflammatory reaction may facilitate expontaneous expulsion or foreign body extraction

Comparative Efficacy of Levosalbutamol and Racemic Salbutamol in the Treatment of Acute Exacerbation of Asthma.

Asthma is a major noncommunicable disease (NCD), affecting both children and adults, and is the most common chronic disease among children. It is common in all ages and the prevalence is increasing in most countries, especially among children as because of urbanization. Multiple therapeutic modalities are available for management of acute asthma. The commonly used formulation is Racemic Salbutamol which contains equal amounts of both R and S isomers. Levosalbutamol contains only R isomer. The aim of the study was to compare the efficacy of levosalbutamol and racemic salbutamol for the treatment of acute exacerbation of asthma in children (5 to 15 years). A randomized double blind clinical trial was conducted in the Department of Paediatrics, Sylhet MAG Osmani Medical College Hospital, Sylhet, Bangladesh from October 2013 to March 2014. In this study randomization was done in two groups. Group A received nebulized levosalbutamol (LEV) and Group B received nebulized racemic salbutamol (RAC). The study parameters were respiratory rate (RR), heart rate (HR), oxygen saturation in room air (SpO2), PEFR, asthma score and serum K+ level. The results of treatment outcome were compared between two groups. After treatment the respiratory rate was 24.4±5.6 per minute versus 27.6±5.3 per minute (p<0.05); heart rate was 115.5±16.4 per minute versus 124.5±12.0 per minute (p<0.05); SpO2 was 97.2±1.8% vs 95.0±1.6% (p<0.05); PEFR was found 159.6±30.7L/min versus 143.8±27.1L/min (p<0.05) in the LEV and RAC group respectively. LEV is more effective than RAC in respect to significant improvement of asthma score. Regarding adverse events racemic salbutamol causes significant tachycardia. The study concluded that nebulized levosalbutamol is superior to racemic salbutamol in children in the treatment of acute exacerbation of asthma.

Levalbuterol vs. albuterol for hospitalized patients with COPD in China: cost-utility and budget impact analysis.

OBJECTIVES: For hospitalized patients with chronic obstructive pulmonary disease (COPD), albuterol and levalbuterol can both be used as relievers to alleviate bronchoconstriction. This study aimed to evaluate levalbuterol and albuterol's cost-utility and budget impact in hospitalized patients with COPD. INTERVENTIONS: A cost-utility analysis was used to evaluate the impact on the costs of nebulized levalbuterol verse albuterol in hospitalized patients with COPD. The decision tree model was employed to estimate the incremental cost per quality-adjusted life year in the admission setting. A budget impact model was used to examine the impact of budget on levalbuterol's entry into the Chinese market from the healthcare system's perspective. One-way sensitivity and probabilistic sensitivity analyses were performed to test the uncertainty of the parameters. RESULTS: The cost-utility results showed that levalbuterol saved ¥495.7 ($105.1) per hospitalization, while the budget impact analysis revealed a potential saving of ¥22.3 ($6.8) million in 3 years. The sensitivity analysis indicated that the results were robust to the changes in input parameter values. CONCLUSION: Levalbuterol is a cost-saving option for treating hospitalized patients with COPD in China.

Chronic obstructive pulmonary disease (COPD) is a common disease in China, with an increased financial burden over the years. Nebulized albuterol is the most commonly used short-acting beta2-agonist, often regarded as the initial bronchodilator to treat hospitalized COPD patients. Its R-isomer, levalbuterol, entered the Chinese market in 2019. The new intervention always impacts the expenditure of the health system. We built a cost-utility and budget impact model to analyze the difference between albuterol and levalbuterol. The cost-utility results showed that levalbuterol saved ¥495.7 ($105.1) per hospitalization compared with albuterol, while the budget impact analysis revealed a potential saving of ¥22.3 ($6.8) million in 3 years.

Clinical outcomes of levalbuterol versus racemic albuterol in pediatric patients with asthma: Propensity score matching approach in a medicaid population.

OBJECTIVE: Racemic albuterol and levalbuterol are used to treat acute episodes of asthma. The main objective of this study was to compare levalbuterol therapy to albuterol therapy on incidence rates of subsequent emergency department (ED) visits and hospitalizations. METHOD: We conducted a retrospective cohort study of asthmatic children who had pharmacy refills for levalbuterol/albuterol in the South Carolina Medicaid database in 2002-2011. Children receiving levalbuterol were matched to those receiving albuterol using propensity score matching technique. For ED visits and separately for hospitalizations, multivariable negative binomial regression was used to estimate the two group-specific incidence rates and the incidence rate ratio (IRR). RESULTS: A total of 8,172 asthmatic patients aged 2-18 years were identified in the South Carolina Medicaid database. During the 12-month follow-up period, the levalbuterol group had fewer asthma-related ED visits and hospitalizations: 939 (11.49%) children had asthma-related ED visits (levalbuterol: 8.76%; albuterol: 14.21%), and 89 (1.09%) children had asthma-related hospitalizations (levalbuterol: 1.07%; albuterol: 1.12%). Comparing the levalbuterol group to the albuterol group, the adjusted IRR estimate was 0.57 (95% confidence interval [CI], 0.49-0.65) for of asthma-related ED visits, and 0.93 (95%CI, 0.99-1.63) for hospitalizations. Children filling levalbuterol also had a lower IRR of all-cause ED visit (0.88; 95%CI, 0.82-0.95), but similar IRR of all-cause hospitalizations (1.08; 95%CI, 0.82-1.42). CONCLUSION: This observational study of children aged 2-18 demonstrated levalbuterol prescription fills were associated with reduced ED visits, but not hospitalizations. Additional research may be necessary to assess this association. Pediatr Pulmonol. 2017;52:516-523. © 2016 Wiley Periodicals, Inc.

Efficacy of Inhaled Levalbuterol Compared to Albuterol in Horses with Recurrent Airway Obstruction.

BACKGROUND: The (R)-enantiomer of racemic albuterol (levalbuterol) has bronchodilatory properties whereas the (S)-enantiomer causes adverse effects in human airways, animal models, and isolated equine bronchi. Levalbuterol is commercially available and improves pulmonary function of asthmatic patients with a longer duration of effect than albuterol. OBJECTIVE: To determine the dose at which inhaled levalbuterol produces maximal bronchodilatory effect (EDmax) and determine its duration of action in recurrent airway obstruction (RAO)-affected horses in comparison to racemic albuterol. ANIMALS: Nine horses with inducible and reversible RAO. METHODS: Randomized, crossover trial. Horses were challenged with moldy hay to induce airway obstruction. Horses were treated with nebulized albuterol or levalbuterol chosen randomly. Pulmonary function testing (PFT) was measured before and for up to 3 hours after bronchodilatation challenge. Maximum change in transpulmonary pressure (DPmax ) was measured to assess the dose effect and duration of action of each drug. After a 24 hours washout period, the bronchodilatation challenge was repeated with the second bronchodilator. RESULTS: The duration of effect was 60 minutes for albuterol and 120 minutes for levalbuterol. The dose of bronchodilator EDmax was not significantly different between albuterol and levalbuterol (EDmax = 125.0 [125-125 µg] and EDmax = 188 [125-188 µg] respectively; P = .068). The magnitude of bronchodilatation was not significantly different between the 2 treatments (61.1 and 59.9% decrease in DPmax for albuterol and levalbuterol respectively; P = .86). CONCLUSIONS AND CLINICAL IMPORTANCE: Levalbuterol is as effective a bronchodilator as albuterol; although levalbuterol lasts twice as long as albuterol, its duration of action is still too short to make it practical for RAO treatment.

Clinical outcomes and treatment cost comparison of levalbuterol versus albuterol in hospitalized adults with chronic obstructive pulmonary disease or asthma.

PURPOSE: Results of a prospective study comparing clinical outcomes and costs of levalbuterol versus albuterol therapy for exacerbations of asthma or chronic obstructive pulmonary disease (COPD) are presented. METHODS: In a single-center open-label study, selected adults hospitalized for asthma or COPD exacerbations over a 21-month period were randomly assigned to receive levalbuterol 1.25 mg three times daily (n = 55) or albuterol 2.5 mg four times daily (n = 57); dosage reductions and other respiratory therapies were permitted. Study outcomes included scheduled and rescue nebulizations, total treatment costs, hospital length of stay, and change in heart rate from baseline. RESULTS: The numbers of scheduled nebulizations were similar in the levalbuterol and albuterol groups (mean ± S.D., 19.6 ± 13.4 versus 20.7 ± 14.4; p = 0.692), as were the numbers of rescue nebulizations (mean ± S.D., 0.7 ± 1.4 versus 0.8 ± 2.0; p = 0.849). The mean change from baseline in heart rate did not differ significantly between groups. Mean total treatment costs per patient were significantly greater with the use of levalbuterol ($8003, bootstrap 95% confidence interval [CI], $6628-$9379) versus albuterol ($5772, bootstrap 95% CI, $5051-$6494; p = 0.006). Hospital length of stay was significantly greater in the levalbuterol group (mean ± S.D., 8.5 ± 5.2 days versus 6.8 ± 3.6 days with albuterol use; p = 0.040). CONCLUSION: Clinical outcomes were similar with the use of levalbuterol versus albuterol for exacerbations of COPD or asthma. On average, patients receiving levalbuterol had longer and more costly hospital stays.