Short-acting Beta Research Articles

Evaluation of asthma control by inhaled corticosteroids in general practice in Thailand.

Inhaled corticosteroid (ICS) is the main treatment of asthma but the clinical data of its efficacy is limited. This study aimed to evaluate the therapeutic efficacy of ICS alone or combined with controllers other than LABA for persistent asthma in Thailand. This cross-sectional study involved 1,206 patients with persistent asthma and was conducted at 38 hospitals across Thailand between May and November, 2009. Patients were enrolled if they were >12 years old, had persistent asthma, receiving ICS with/without controllers other than long-acting beta2-agonists (LABA) for at least 3 months, and smoked <10 packs-year. Of 1,206 patients, 78.4% were females, age 49.4 ± 13.8 years old, 89.3% were nonsmokers, the median duration of illness was 11 years, the median duration of ICS treatment was 20.4 months, and the mean dose of ICS was 738 ± 258 microgram per day. The top three medications prescribed in combination to ICS were short-acting beta2- agonist inhalers, theophylline, and short-acting beta2- agonist tablets. The mean Asthma Control Test (ACT) score was 19.2 ± 4.4. The percentage of successful asthma control (ACT ≥ 20) was 53.5% (95% CI: 50.7 to 56.3). The rate per patient per year of emergency room visits and all urgent health care visits were 0.98 and 1.28. In clinical practice, patients using ICS alone or combined with theophylline or short-acting b2 agonists had a low percentage of asthma control and a high number of urgent care visits. ICS either alone or combined with theophylline or short-acting b2 agonists is not sufficient.

Health-care utilization and costs with fluticasone propionate and fluticasone propionate/salmeterol in asthma patients at risk for exacerbations

Although studies have established that adding long-acting beta agonists (LABA) to inhaled corticosteroid (ICS) monotherapy among patients with inadequately controlled asthma is associated with better outcomes than increasing ICS dosage, outcomes with ICS versus fixed-dose ICS/LABA combination among patients with recent asthma exacerbation or frequent use of rescue medication are unavailable. This study was designed to compare health-care utilization/costs among patients with recent asthma exacerbation or frequent rescue medication use who received fluticasone propionate (FP) alone versus fixed-dose FP/salmeterol combination (FSC). A retrospective cohort study was conducted using a large health insurance data set. Patients with one or more claims with asthma diagnosis, two or more prescriptions for FSC (250/50- or 100/50-mg formulations) or FP (220- or 110-mg formulations), and one or more asthma exacerbations or five or more short-acting beta agonist (SABA) prescriptions within 1 year before initial receipt of study medications were included. Health-care utilization/costs and controller therapy compliance were compared for patients receiving FSC versus FP using multivariate regression analysis controlling for FP dose and baseline characteristics. A total of 7779 patients met inclusion criteria (5769, FSC, and 2010, FP) with comparable mean follow-up (FSC, 685 days; FP, 670 days; p = 0.151). Controlling for FP dosage and baseline characteristics, FSC patients had lower risks of asthma-related exacerbations, fewer SABAs and systemic corticosteroids, higher costs of asthma medications and total asthma-related health care, and lower total asthma-related health-care costs excluding study medication cost. In asthma patients with recent exacerbation or frequent SABA use, receipt of FSC reduced asthma-related exacerbation risks and rescue medication use versus receipt of FP.

Anesthetic management of peroral endoscopic myotomy for esophageal achalasia: a retrospective case series

Peroral endoscopic myotomy (POEM) is a newly developed, less invasive treatment for esophageal achalasia that requires general anesthesia under positive pressure ventilation. In this retrospective case series, we describe the anesthetic management of 28 consecutive patients who underwent POEM for esophageal achalasia. Anesthesia was maintained with sevoflurane and remifentanil under positive pressure ventilation through a tracheal tube. Retained contents in the esophagus were evacuated just before anesthesia induction to prevent regurgitation into the trachea. The POEM procedure was performed using an orally inserted flexible fiberscope. Elevation of end-tidal carbon dioxide after initiating esophageal carbon dioxide insufflation was observed in all patients and was treated by minute adjustments to the ventilation volume. Scopolamine butylbromide-induced tachycardia in one patient was treated with landiolol hydrochloride, which is a short-acting beta 1-selective blocker. Minor subcutaneous emphysema around the neck was observed in one patient. POEM was successfully completed, and tracheas were extubated immediately after the procedure in all patients. Our findings suggest that prevention of aspiration pneumonia during anesthesia induction, preparation for carbon dioxide insufflation-related complications, and treatment of scopolamine butylbromide-induced tachycardia play important roles in safe anesthesia management of POEM for esophageal achalasia.

Efficacy of procaterol combined with inhaled budesonide for treatment of cough‐variant asthma

Procaterol, a selective, short-acting beta-2 adrenoceptor agonist, is effective in treating 'classical' asthma, but its efficacy for cough-variant asthma (CVA) is unknown. We evaluated the efficacy and safety of procaterol combined with budesonide for CVA. A prospective, randomized, double-blind, placebo-controlled, multicenter trial in China was conducted. One hundred and fifty-nine patients diagnosed with CVA (aged 18-75 years) were randomly divided into two groups to receive twice daily for 8 weeks, inhaled budesonide 100 μg plus either oral procaterol 25 μg or placebo. Primary and secondary efficacy variables were cough symptom severity scores and Leicester Cough Questionnaire (LCQ) life quality scores. Adverse events were also assessed. The budesonide/placebo and budesonide/procaterol groups contained 80 and 78 participants (one excluded for later diagnosis of eosinophilic bronchitis), respectively, with similar baseline characteristics. Daily cough score declined during treatment in both groups and was lower in the budesonide/procaterol group at 8 (0.44 vs 0.73) and 10 (0.36 vs 0.69) weeks (P < 0.05). Compared with the budesonide/placebo group, the proportion of patients with a reduction of 3 points or greater (66% vs 42%) and that of patients scoring 0 points (63% vs 51%) was higher in the budesonide/procaterol group for daily cough scores (P < 0.05). At 8 weeks, LCQ score improvement was superior in the budesonide/procaterol group (38.94 ± 19.24 vs 32.71 ± 18.92; P < 0.05). Procaterol combined with budesonide was well tolerated and effective at improving cough symptoms and quality of life in patients with CVA.

Cross-sectional assessment of exertional dyspnea in otherwise healthy children

Exertional dyspnea during sport at school in children with asthma or in otherwise healthy children is commonly attributed to exercise-induced asthma (EIA), but when a short-acting beta agonist (SABA) trial fails to improve symptoms the physician is often at a loose end. The aims were to prospectively assess the causes of exertional dyspnea in children/adolescents with or without asthma using a cardiopulmonary exercise test while receiving a SABA and to assess the effects of standardized breathing/reassurance therapy. Seventy-nine patients (12.2 ± 2.3 years, 41 girls, 49 with previously diagnosed asthma) with dyspnea unresponsive to SABA were prospectively included. Exercise test outcomes depicted normal or subnormal performance with normal ventilatory demand and capacity in 53/79 children (67%) defining a physiological response. The remaining 26 children had altered capacity (resistant EIA [n = 17, 9 with previous asthma diagnosis], vocal cord dysfunction [n = 2]) and/or increased demand (alveolar hyperventilation [n = 3], poor conditioning [n = 7]). Forty-two children who had similar characteristics than the remaining 37 children underwent the two sessions of standardized reassurance therapy. They all demonstrated an improvement that was rated "large." The degree of improvement correlated with % predicted peak V'O2 (r = -0.37, P = 0.015) and peak oxygen pulse (r = -0.45, P = 0.003), whatever the underlying dyspnea cause. It suggested a higher benefit in those with poorer conditioning condition. The most frequent finding in children/adolescents with mild exertional dyspnea unresponsive to preventive SABA is a physiological response to exercise, and standardized reassurance afforded early clinical improvement, irrespective of the dyspnea cause.

Addition of a 5-lipoxygenase-activating protein inhibitor to an inhaled corticosteroid (ICS) or an ICS/long-acting beta-2-agonist combination in subjects with asthma

Objective:To investigate the clinical benefits of ‘add-on’ therapy with GSK2190915 in combination with the inhaled corticosteroid (ICS) fluticasone propionate (FP) and the ICS/long-acting beta 2 agonist (LABA) combination FP/salmeterol in asthmatic subjects.Methods:Both studies were cross-over, randomized, double-blind, double-dummy and placebo-controlled in subjects with a forced expiratory volume in 1 second (FEV1) best of >50 and ≤80% of predicted. Add-on to ICS: Subjects (n = 162) aged ≥12 years received FP 100 µg twice daily (BID) plus GSK2190915 100 mg once daily (QD); GSK2190915 300 mg QD; montelukast 10 mg QD; salmeterol 50 µg BID or placebo. Add-on to ICS/LABA: Female subjects (n = 145) aged ≥18 years received FP/salmeterol 250/50 µg BID plus GSK2190915 300 mg QD, montelukast 10 mg QD or placebo. In both studies, the primary endpoint was trough FEV1 at the end of the treatment period. Secondary endpoints included a range of objective and patient-reported measures of efficacy.Results:Add-on to ICS: There was no statistically significant difference in the primary endpoint between either dose of GSK2190915 (add-on to FP) and placebo. Nominally statistically significant increases were demonstrated for GSK2190915 300 mg add-on relative to placebo for mean morning peak expiratory flow (p = 0.049), percentage of symptom-free days (p = 0.035) and percentage of symptom-free 24 h periods (p = 0.030). Add-on to ICS/LABA: There were no statistically significant differences on the primary endpoint between treatment regimens. Nominally statistically significant decreases were demonstrated in daytime (p = 0.023), night-time (p = 0.041) and 24 h (p = 0.019) short-acting beta 2 agonist usage with FP/salmeterol + GSK2190915 300 mg vs. FP/salmeterol + placebo.Conclusion:There was no clinically significant improvement in the primary endpoint following GSK2190915 add-on treatment; however, improvements in a range of secondary endpoints and biomarker data provided evidence of pharmacological activity. Improvements in response to background treatment may have been a limitation in both studies.Trial registration:Clinicaltrials.gov identifiers: NCT01156792 and NCT01248975.

Combined inhaled anticholinergics and short-acting beta2-agonists for initial treatment of acute asthma in children

There are several treatment options for managing acute asthma exacerbations (sustained worsening of symptoms that do not subside with regular treatment and require a change in management). Guidelines advocate the use of inhaled short acting beta2-agonists (SABAs) in children experiencing an asthma exacerbation. Anticholinergic agents, such as ipratropium bromide and atropine sulfate, have a slower onset of action and weaker bronchodilating effect, but may specifically relieve cholinergic bronchomotor tone and decrease mucosal edema and secretions. Therefore, the combination of inhaled anticholinergics with SABAs may yield enhanced and prolonged bronchodilation. To determine whether the addition of inhaled anticholinergics to SABAs provides clinical improvement and affects the incidence of adverse effects in children with acute asthma exacerbations. We searched MEDLINE (1966 to April 2000), EMBASE (1980 to April 2000), CINAHL (1982 to April 2000) and reference lists of studies of previous versions of this review. We also contacted drug manufacturers and trialists. For the 2012 review update, we undertook an 'all years' search of the Cochrane Airways Group's register on the 18 April 2012. Randomized parallel trials comparing the combination of inhaled anticholinergics and SABAs with SABAs alone in children (aged 18 months to 18 years) with an acute asthma exacerbation. Two review authors independently assessed trial quality and extracted data. We used the GRADE rating system to assess the quality of evidence for our primary outcome (hospital admission). Twenty trials met the review eligibility criteria, generated 24 study comparisons and comprised 2697 randomised children aged one to 18 years, presenting predominantly with moderate or severe exacerbations. Most studies involved both preschool-aged children and school-aged children; three studies also included a small proportion of infants less than 18 months of age. Nine trials (45%) were at a low risk of bias. Most trials used a fixed-dose protocol of three doses of 250 mcg or two doses of 500 mcg of nebulized ipratropium bromide in combination with a SABA over 30 to 90 minutes while three trials used a single dose and two used a flexible-dose protocol according to the need for SABA.The addition of an anticholinergic to a SABA significantly reduced the risk of hospital admission (risk ratio (RR) 0.73; 95% confidence interval (CI) 0.63 to 0.85; 15 studies, 2497 children, high-quality evidence). In the group receiving only SABAs, 23 out of 100 children with acute asthma were admitted to hospital compared with 17 (95% CI 15 to 20) out of 100 children treated with SABAs plus anticholinergics. This represents an overall number needed to treat for an additional beneficial outcome (NNTB) of 16 (95% CI 12 to 29).Trends towards a greater effect with increased treatment intensity and with increased asthma severity were observed, but did not reach statistical significance. There was no effect modification due to concomitant use of oral corticosteroids and the effect of age could not be explored. However, exclusion of the one trial that included infants (< 18 months) and contributed data to the main outcome, did not affect the results. Statistically significant group differences favoring anticholinergic use were observed for lung function, clinical score at 120 minutes, oxygen saturation at 60 minutes, and the need for repeat use of bronchodilators prior to discharge from the emergency department. No significant group difference was seen in relapse rates.Fewer children treated with anticholinergics plus SABA reported nausea and tremor compared with SABA alone; no significant group difference was observed for vomiting. Children with an asthma exacerbation experience a lower risk of admission to hospital if they are treated with the combination of inhaled SABAs plus anticholinergic versus SABA alone. They also experience a greater improvement in lung function and less risk of nausea and tremor. Within this group, the findings suggested, but did not prove, the possibility of an effect modification, where intensity of anticholinergic treatment and asthma severity, could be associated with greater benefit.Further research is required to identify the characteristics of children that may benefit from anticholinergic use (e.g. age and asthma severity including mild exacerbation and impending respiratory failure) and the treatment modalities (dose, intensity, and duration) associated with most benefit from anticholinergic use better.

Risk of all-cause hospitalization in COPD patients initiating long-acting or short-acting beta agonist therapy

Objective:This retrospective claims study investigated the rates of all-cause hospitalization among chronic obstructive pulmonary disease (COPD) patients initiating treatment with short-acting beta agonists (SABA) or long-acting beta agonists (LABA).Methods:Data from the 5% national sample of Medicare enrollees for 2006–2008 were used. Patients initiating COPD therapy were identified as those with no COPD therapy for ≥ 6-months prior to initiating SABA or LABA (administered via dry-powder inhalers, metered-dose inhalers, or nebulizer) treatment. All patients were continuously eligible for Medicare Parts A, B, and D for 18 months. Those enrolled in Medicare Advantage, who had asthma, or were < 65 years old were excluded. Differences in the rates of all-cause hospitalizations and time to all-cause hospitalization during the 6-month follow-up period were examined, while adjusting for demographics, clinical indicators, and health service use.Results:Among 3017 COPD patients who met the inclusion criteria, 883 (30%) were LABA users and 2134 (70%) were SABA users. Overall, 21% of patients (16% [144/883] of LABA and 23% [492/2134] of SABA) had a hospitalization during the follow-up period. Mean time to hospitalization was 86 days for LABA vs 64 days for SABA patients (p < 0.05). The adjusted hazard ratio for hospitalization in a Cox proportional hazards model was 0.74 (95% CI = 0.62–0.90) for patients treated with LABA vs. SABA.Limitations:The analysis was adjusted for multiple background characteristics, but important measures of severity in COPD, such as measures of lung functioning, were not available and may have differed between patients treated with LABA or SABA.Conclusions:The results of this analysis indicate COPD patients initiating LABA treatment had a longer time to all-cause hospitalization and a 26% lower risk of hospitalization during the 6-months follow-up period compared to those initiating SABA therapy.

Review of the management of childhood asthma in Tasmania

To review the supply of medications to children with asthma and parent-reported management of childhood asthma in Tasmania and highlight evidence-practice gaps for future interventions. Participating pharmacies ran a software application that extracted data from dispensing records and helped to identify children with asthma. Parents of identified children were mailed a survey evaluating components of asthma management. Dispensing and survey data were analysed. A total of 939 children from 23 pharmacies were identified by the software and deemed eligible for inclusion. Surveys were received from 353 (37.6%) parents. In the past year, short-acting beta-2 agonists were supplied to 56.1% of the cohort, preventers to 76.5% (inhaled corticosteroids 52.3%; leukotriene receptor antagonists 31.3%; inhaled cromones 0.6%), long-acting beta-2 agonists (LABAs) to 25.7% and oral corticosteroids to 21.5%. Approximately half of the children receiving inhaled corticosteroids were concurrently receiving a LABA. Among children with indicators of inadequately controlled asthma, up to 73.7% of their parents reported that their asthma was adequately controlled, up to 38.2% did not possess an Asthma Action Plan, up to 36.8% were not regularly using a spacer and up to 22.8% had not received a preventer. These results indicate gaps in childhood asthma management, in particular, undersupply of preventers in high-risk patient groups, high supply of LABAs and insufficient spacer and asthma action plan usage. These areas should be targeted for interventions to improve childhood asthma management.

Development and Preliminary Validation of the Adult Asthma Adherence QuestionnaireTM

Asthma medication adherence is related to better asthma outcomes, but identification of suboptimal patient adherence behavior is not standardized in clinical settings. [corrected] The purpose of this study was to develop a practical questionnaire that reflects nonadherence risk and identifies potential adherence barriers. A questionnaire that included 20 potential adherence questions was completed by 420 adult patients with asthma who filled a prescription for an inhaled corticosteroid (ICS) and a short-acting beta agonist (SABA) in the previous 6 months. Questions without substantial floor or ceiling effects that were significantly related to self-reported low adherence or previous ICS canister dispensings were identified. Internal consistency reliability was tested by Cronbach α. Relationships of these questions to Asthma Control Test scores, future percent of days covered for ICS dispensings, and future asthma exacerbations and SABA dispensings were determined. Five final questions were identified: following "my medication plan," forgetting, not "needing" the medications, side effects, and cost. Low internal consistency reliability (<0.50) suggested items should not be summarized by a single score. All five questions were related to Asthma Control Test scores. Following the medication plan, forgetting, and not needing medication were significantly related to prospective percent of days covered. Side effects were related to subsequent SABA and oral corticosteroid dispensings, and cost was significantly related to oral corticosteroid dispensings. We identified five questions related to other measures of adherence and to asthma control that can be used clinically to identify patients at risk of nonadherence and the specific adherence barriers involved.

Dose-dependent anti-inflammatory effect of inhaled mometasone furoate/formoterol in subjects with asthma

A well-controlled study in patients with allergic asthma was warranted to assess dose-dependency between fractional concentration of exhaled nitric oxide (FeNO) and sputum eosinophils to a combination of an inhaled corticosteroid plus a long-acting β2-agonist. We sought to characterize the dose-dependency of mometasone furoate/formoterol (MF/F) using FeNO and sputum eosinophil percentage as surrogates of airway inflammation in subjects with allergic asthma. Following a 2-week, open-label run-in, 93 subjects (≥12y) using only short-acting beta agonist reliever medication as needed, were randomized to twice daily (BID) placebo; MF/F 100/10μg, 200/10μg, or 400/10μg (via pressurized metered-dose inhaler [MDI]); MF-MDI 200μg; or MF 200μg via dry powder inhaler (DPI) during a 2-week, double-blind treatment period. All active treatments demonstrated significant percentage reductions from baseline in FeNO compared with placebo at all time points (P≤0.034). At endpoint, mean MF/F treatment group FeNO reductions ranged from -35.3% to -61.4%. Sputum eosinophil percentage reductions from baseline were significant compared with placebo for the MF/F 200/10μg, MF/F 400/10μg, and MF-DPI 200μg groups at endpoint (P≤0.023). Escalating MF/F doses significantly reduced both FeNO (P≤0.001) and sputum eosinophil (P≤0.022) levels in a dose-dependent manner at all time points. All treatments were well tolerated; no serious adverse events were observed. All 3MF/F doses demonstrated pronounced, clinically meaningful, dose-dependent reductions in FeNO, with reduced sputum eosinophil levels for MF/F 200/10μg and MF/F 400/10μg. These findings suggest both inflammatory markers may be useful in assessing corticosteroid responsiveness in asthma patients, and perhaps identifying the same asthma subphenotype. Clinical Trials.gov: NCT00635882.

Long-Acting Beta-Agonists and their Association with Inhaled Corticosteroids in COPD

Inhaled bronchodilators, including beta(2)-agonists and antimuscaric receptor antagonists, are the mainstay of pharmacotherapy in chronic obstructive pulmonary disease (COPD). The short-acting beta(2)-agonists, including salbutamol, and fenoterol, have a rapid onset of action, a bronchodilating effect for 3-6 h and are used on demand. The long-acting beta(2)-agonists (LABAs), including salmeterol and formoterol, have 12-hour duration of action and are used with a twice-daily dosing regimen for long-term COPD treatment. Unlike salmeterol, formoterol has a rapid onset of action. Pharmacological characteristics required by novel inhaled LABAs include 24 h bronchodilator effect in vivo which would make them suitable for once daily administration (ultra-LABA), high potency and selectivity for beta(2)-adrenoceptors, rapid onset of action, low oral bioavailability (< 5%) after inhalation, and high systemic clearance. Indacaterol, which has been approved for long-term treatment of COPD in Europe and in the USA, has a 24-h duration of action and a once-daily dosing regimen. Newer ultra-LABAs, including olodaterol, vilanterol, milveterol, carmoterol, and abediterol, are in development. Combination with ICS (fluticasone/salmeterol, budesonide/formoterol, beclomethasone/formoterol) appears to provide an additional benefit over the monocomponent therapy, although the extent of this benefit is variable and often not clinically significant in all the endpoints assessed. In patients with COPD, treatment with ICS is associated with increased risk of pneumonia which should be carefully considered when assessing the risk/benefit ratio of ICS/LABA combinations. Subphenotyping of patients with COPD (e.g., frequent exacerbations, sputum eosinophilia, mixed asthma/COPD phenotype) might help identify those patients who are most likely to benefit from addition of ICS to bronchodilating treatment. Ultra-LABA/ long-acting muscarinic receptor antagonist (LAMA) combination treatment is under development and is likely to become a standard pharmacological strategy for COPD. Dual-pharmacology inhaled muscarinic antagonist-beta(2) agonist (MABA) molecules provide a new approach to the treatment of COPD.

Tratamento da exacerbação da asma na criança com inaladores pressurizados de dose controlada e câmara expansora: Dose segura e eficaz de Salbutamol

Aim and Objectives: Inhaled short-acting beta 2-agonists are the mainstay of treatment of acute asthma exacerbations. Salbutamol (also known as albuterol) is the most frequently used of these drugs in acute settings, however the recommended dose is still the subject of debate. The aim of this study is to determine the safe and effective dose of salbutamol delivered by a metered-dose inhaler with a spacer. Data sources: TRIP Database, National Guideline Clearinghouse, Guidelines Finder, The Cochrane Library, DARE, Bandolier, MEDLINE. Methods of the review: bibliographic search using the MeSH terms: Asthma/therapy and Albuterol/administration and dosage. The search was limited to articles published between January 2001 and 2011 in English, Spanish, French and Portuguese. The Strength of Recommendation Taxonomy of the American Family Physician Journal was used to assess the Level of Evidence. Results: Seven articles were evaluated including five guidelines and two clinical trials. The dose recommended by the guidelines was between two and ten puffs every 20 minutes. Each puff is equivalent to 100 µg of salbutamol by inhalation. In the clinical trials, the recommended doses are higher to those referred to by the guidelines. Adverse effects were not reported with these doses. Conclusions: There is some heterogeneity of the included studies. Some guidelines recommend two to four puffs, others two to six puffs, and others four to eight puffs at a time. The clinical trials report on higher doses, up 20 puffs per dose. The authors consider that it is safe to administer four to eight puffs per dose in the treatment of a child with a mild to moderate exacerbation of asthma (Strength of Recommendation B). Each dose should not be more than ten puffs (Strength of recommendation B).

Tolerability and Pulmonary Pharmacodynamic Effects During Treatment Initiation of Once-Daily Oral Fingolimod in Subjects With Moderate Asthma.

Fingolimod, a first-in-class sphingosine 1-phosphate receptor modulator, is the first approved oral therapy for relapsing multiple sclerosis (MS). While treatment initiation of clinical dose of fingolimod (0.5 mg) does not affect pulmonary function, supra-therapeutic doses (≥5.0 mg) increased airway resistance. The aim of this double-blind, placebo-controlled, parallel group, 10-day study was to measure the effect of fingolimod on pulmonary function in otherwise healthy patients with moderate asthma. Subjects (n = 36) were randomized into four cohorts that received either fingolimod 0.5, 1.25, 2.5 mg, or placebo once daily for 10 days. Subjects in placebo and fingolimod 0.5 mg groups did not differ in FEV1 AUEC0-6 h , FEF25-75% AUEC0-6 h , or in short-acting beta (β) 2 agonists (SABA, rescue bronchodilator) use. Subjects on higher doses of fingolimod showed a mild reduction in FEV1 AUEC0-6 h and FEF25-75% AUEC0-6 h and a significant sixfold increase in SABA use versus placebo. One subject had moderately severe, acute exacerbation of asthma after receiving the first dose of fingolimod 1.25 mg that quickly responded to inhaled SABA. The observed safety profile was consistent with previous reports. These results provide reassurance that moderately asthmatic MS individuals can start on fingolimod 0.5 mg therapy with minimal effects on pulmonary function and SABA use.

Reversibility of the Pulmonary Function Based on the Partial Flow-volume Curve Predicts the Efficacy of Bronchodilator Therapy for Treating Chronic Cough

Partial expiratory flow-volume curves have the potential to detect mild bronchoconstriction because they are not affected by the modulatory effects of deep inspiration. The aim of this study was to investigate the relationship between the efficacy of bronchodilator therapy (BDT) in treating the cough and to assess the increase in the expiratory flow of the partial flow-volume curve at 40% above the residual volume level (PEF40) caused by treatment with a short-acting beta-2 agonist (SABA) in patients with chronic nonproductive cough. We measured the reversibility of PEF40 caused by a SABA in 42 patients with chronic nonproductive cough at visit 1 (day 0). The patients received BDT for six days. The visual analogue scale (VAS) was used to assess the efficacy of BDT in treating coughing at visit 2 (day 7) (0 mm, 'no cough;' 100 mm, 'no change in coughing'). Reversibility of the PEF40 was correlated (r=0.690, p<0.001) with the VAS score determined at visit 2 and was higher in the patients with cough variant asthma (CVA) (44.9 ± 18.3%) than in those with atopic cough (13.4 ± 10.4%) (p<0.01). Reversibility of the PEF40 predicted the efficacy of BDT in patients with chronic nonproductive cough and helped to identify patients with CVA.

Treatment With Formoterol Fumarate Inhalation Solution (FFIS) Among COPD Patients With High Use of Nebulized Short Acting Beta 2-Agonists (SABAs

Treatment With Formoterol Fumarate Inhalation Solution (FFIS) Among COPD Patients With High Use of Nebulized Short Acting Beta 2-Agonists (SABAs

Longitudinal FEV1 dose–response model for inhaled PF-00610355 and salmeterol in patients with chronic obstructive pulmonary disease

The objective of this work was to characterize the dose-response relationship between two inhaled long-acting beta agonists (PF-00610355 and salmeterol) and the forced expiratory volume in one second (FEV1) in order to inform dosing recommendations for future clinical trials in patients with chronic obstructive pulmonary disease (COPD). This meta-analysis of four studies included 8,513 FEV1 measurements from 690 patients with moderate COPD. A longitudinal kinetic-pharmacodynamic (K-PD) model was developed and adequately described changes in FEV1 measurements over time, including circadian patterns within a day, as well as changes in FEV1 measurements elicited from administration of PF-00610355 or salmeterol. The fine-particle dose, the amount of drug present in particles small enough for lung delivery, was used as the exposure measure for PF-00610355. Greater reversibility following administration of a short-acting beta agonist during run-in was associated with increased FEV1 response to long-acting beta agonists (through an increased maximal response, E(max)). Simulations were conducted to better understand the response to PF-00610355 relative to placebo and salmeterol. The results of the simulations show that once daily fine-particle doses of 28.1μg versus placebo have a moderate probability of providing an average improvement above 100mL at trough. The 50μg fine-particle dose, on the other hand, has a greater than 0.78 probability of achieving a 120mL improvement versus placebo at trough. From an efficacy perspective and assuming a fine-particle fraction of 25% for the Phase 3 formulation; 100 and 200μg once daily nominal doses would be of interest to investigate in future Phase 3 trials.

PRS49 All-Cause 30-Day Readmissions for Matched Inpatients with Copd Receiving Nebulized Short-Acting or Long-Acting Beta Agonists

PRS49 All-Cause 30-Day Readmissions for Matched Inpatients with Copd Receiving Nebulized Short-Acting or Long-Acting Beta Agonists

Chapter 15: Lessons learned from clinical trials of asthma

The preponderance of clinical data suggest that inhaled corticosteroids (ICSs) are the preferred therapy for the long-term management of asthma, whereas oral or parental corticosteroids and short-acting beta(2)-adrenergic agonists remain the mainstay treatment of acute exacerbations. Allergen and tobacco avoidance are tenets to the practice of allergy-immunology and are beneficial in the treatment of asthma. Failure to avoid animal danders or fungi to which a patient with asthma is allergic is a risk factor for a fatal attack. First introduced in the 1970s, ICSs are the mainstay of pharmacotherapy to control airway inflammation and bronchial hyperresponsiveness in children and adults with asthma. ICSs reduce symptoms, exacerbations, hospitalizations, and deaths while improving quality of life and lung function. When used in combination with an ICS, essentially all clinical trials have indicated that long-acting beta(2)-adrenergic agonists are effective and safe. Leukotriene modifiers (LTMs) are effective in the treatment of persistent asthma, exercise-induced asthma, and aspirin-induced asthma but, in general, are less efficacious than ICSs when used as monotherapy to control asthma symptoms. Nevertheless, some patients respond to LTMs better than ICSs so a personalized approach to asthma pharmacotherapy is recommended. Not only is conventional (subcutaneous) allergen immunotherapy effective in patients with allergic asthma, immunotherapy (subcutaneous or sublingual) administered for rhinoconjunctivitis in children has been shown to reduce the development of asthma.

Regular treatment with formoterol for chronic asthma: serious adverse events.

Epidemiological evidence has suggested a link between beta(2)-agonists and increases in asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta(2)-agonists are safe. The aim of this review is to assess the risk of fatal and non-fatal serious adverse events in trials that randomised patients with chronic asthma to regular formoterol versus placebo or regular short-acting beta(2)-agonists. We identified trials using the Cochrane Airways Group Specialised Register of trials. We checked websites of clinical trial registers for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol. The date of the most recent search was January 2012. We included controlled, parallel design clinical trials on patients of any age and severity of asthma if they randomised patients to treatment with regular formoterol and were of at least 12 weeks' duration. Concomitant use of inhaled corticosteroids was allowed, as long as this was not part of the randomised treatment regimen. Two authors independently selected trials for inclusion in the review. One author extracted outcome data and the second author checked them. We sought unpublished data on mortality and serious adverse events. The review includes 22 studies (8032 participants) comparing regular formoterol to placebo and salbutamol. Non-fatal serious adverse event data could be obtained for all participants from published studies comparing formoterol and placebo but only 80% of those comparing formoterol with salbutamol or terbutaline.Three deaths occurred on regular formoterol and none on placebo; this difference was not statistically significant. It was not possible to assess disease-specific mortality in view of the small number of deaths. Non-fatal serious adverse events were significantly increased when regular formoterol was compared with placebo (Peto odds ratio (OR) 1.57; 95% CI 1.06 to 2.31). One extra serious adverse event occurred over 16 weeks for every 149 people treated with regular formoterol (95% CI 66 to 1407 people). The increase was larger in children than in adults, but the impact of age was not statistically significant. Data submitted to the FDA indicate that the increase in asthma-related serious adverse events remained significant in patients taking regular formoterol who were also on inhaled corticosteroids.No significant increase in fatal or non-fatal serious adverse events was found when regular formoterol was compared with regular salbutamol or terbutaline. In comparison with placebo, we have found an increased risk of serious adverse events with regular formoterol, and this does not appear to be abolished in patients taking inhaled corticosteroids. The effect on serious adverse events of regular formoterol in children was greater than the effect in adults, but the difference between age groups was not significant.Data on all-cause serious adverse events should be more fully reported in journal articles, and not combined with all severities of adverse events or limited to those events that are thought by the investigator to be drug-related.