Long-term treatment with fluticasone propionate/salmeterol via Diskus improves asthma control versus fluticasone propionate alone.

This 52-week study was designed to assess the safety and efficacy of fluticasone propionate/salmeterol combination (FSC) 250/50 micrograms versus fluticasone propionate (FP) 250 micrograms in subjects with persistent asthma symptomatic on open-label FP 100 micrograms. The primary objective of this study was to show that FSC 250/50 micrograms was superior to FP 250 micrograms at increasing pulmonary function as measured by forced expiratory volume in 1 second over a 52-week treatment period. A secondary objective was to compare the rate of asthma attacks defined as (1) a sustained 2-day decrease in morning peak expiratory flow or increase in albuterol use for 2 consecutive days, (2) an asthma exacerbation requiring systemic corticosteroids, or (3) an unscheduled clinic or hospital visit for acute asthma symptoms. Three hundred six subjects received FSC 250/50 micrograms and 315 subjects received FP 250 micrograms. Both treatments were administered twice daily. Treatment with FSC 250/50 micrograms resulted in a significant improvement in lung function compared with FP 250 micrograms (p < 0.001). Additionally, treatment with FSC 250/50 micrograms resulted in a reduction in the rate of exacerbations of asthma (i.e., requiring systemic corticosteroids or unscheduled urgent care intervention) compared with FP 250 micrograms (0.170 versus 0.273, respectively; p = 0.017). There was no differentiation between treatments for less severe attacks of asthma. FSC 250/50 micrograms showed consistently greater improvement in lung function, symptom control, and decreased albuterol use. In addition, FSC 250/50 micrograms-treated subjects experienced fewer severe asthma exacerbations than subjects treated with FP 250 micrograms.

Assessing Primary Care Physician's Beliefs and Attitudes of Asthma Exacerbation Treatment and Follow-Up.

OBJECTIVE: The objective of this survey was to assess adult primary care physicians' and pediatricians' perceptions of asthma exacerbation management, including beliefs concerning the discharge of patients from the emergency department (ED) following asthma exacerbations. METHODS: This was a cross-sectional survey of primary care physicians (PCPs) treating adult or pediatric patients. Surveys were mailed to physicians and included questions on how PCPs define an exacerbation, how they are notified and how they followed-up with their patients who experienced exacerbations. RESULTS: A total of 189 physicians were targeted in this survey, with 124 (65%) returning a completed survey. The majority of physicians agreed that an exacerbation included worsening asthma requiring a course of oral corticosteroids (83%). However, >/=70% of physicians agreed that an exacerbation could also include events which did not require OCS. Overall, 71% of PCPs believed that the majority of their patients' asthma exacerbations were treated in the doctor's office with only 6% believing the majority were treated in the ED. Over 90% of PCPs surveyed said they scheduled a follow-up with their patients "all or most of the time" when notified of an ED visit for an asthma exacerbation. Of the adult PCPs surveyed, 20% said they were never notified when one of their patients received treatment in the hospital because of an asthma exacerbation, whereas only 10% of pediatricians said they were never notified. The majority of PCPs surveyed (79%) indicated that if a controller medication was warranted, the ED staff should initiate treatment at time of discharge. CONCLUSIONS: This study showed that healthcare providers may not share a common definition of an asthma exacerbation. In addition, most physicians believe that the majority of exacerbations are treated in their office or at home. Further, most agreed that if a controller medication was warranted, the ED or urgent care staff should initiate treatment.

Status of asthma control in pediatric primary care: results from the pediatric Asthma Control Characteristics and Prevalence Survey Study (ACCESS).

OBJECTIVE: To estimate the prevalence of uncontrolled asthma in pediatric patients with asthma visiting their primary care provider for any medical reason. STUDY DESIGN: This was a cross-sectional survey conducted at 29 pediatric care sites across the United States. Children age 4-17 years with self- or caregiver-reported asthma completed the Childhood Asthma Control Test (C-ACT) or the Asthma Control Test (ACT) and responded to demographic and health-related questions. Uncontrolled asthma was defined as a C-ACT or ACT score

Predictors of uncontrolled asthma in adult and pediatric patients: analysis of the Asthma Control Characteristics and Prevalence Survey Studies (ACCESS).

BACKGROUND: Despite the availability of effective asthma treatments and evidence-based management guidelines focusing on asthma control, many patients have asthma that is inadequately controlled. The objective of this analysis was to identify risk factors for uncontrolled asthma among adult and pediatric patients. METHODS: Two cross-sectional surveys assessing asthma control status were conducted between January 25 and May 2, 2008, among adult and pediatric patients with asthma. Participants completed a self-administered questionnaire including demographics, medical history, and current asthma medication use. In addition, participants completed either the Asthma Control Test (ACT) or Childhood ACT (C-ACT). Uncontrolled asthma was defined as a score of < or = 19 on the ACT or C-ACT. Multiple logistic regression was used to identify factors related to uncontrolled asthma. RESULTS: A sample of 64 primary care provider sites (35 for adults and 29 for pediatric patients) across the United States enrolled. One study enrolled 2238 adults (aged > or = 18 years) and the other 2429 children (aged 4-17 years) with asthma. The patients were visiting their health care provider for a scheduled appointment for any reason. The overall prevalence of uncontrolled asthma was 58% and 46% in adult and pediatric patients, respectively. Multivariate analysis identified predictors of uncontrolled asthma in both adults and children including self-reported asthma severity, lack of adherence, and recent history of cold, flu, or sinus infection. The predictors of uncontrolled asthma seen only in adults were less education, insurance status, current smoker, body mass index (BMI) >30 kg/m(2), and history of gastroesophageal symptoms. The predictors of uncontrolled asthma seen only in children were female aged 12-17 years, caregiver unemployment, and history of asthma exacerbation. CONCLUSIONS: A high proportion of patients with asthma seen in primary care settings are not well controlled. Recognition of specific predictors can signal who may be at higher risk of uncontrolled asthma and provide the opportunity for early interventions.

Repeat dosing of albuterol via metered-dose inhaler in infants with acute obstructive airway disease: a randomized controlled safety trial.

BACKGROUND: Airway obstruction and bronchial hyperactivity often times lead to emergency department visits in infants. Inhaled short-acting beta2-agonist bronchodilators have traditionally been dispensed to young children via nebulizers in the emergency department. Delivery of bronchodilators via metered-dose inhalers (MDIs) in conjunction with holding chambers (spacers) has been shown to be effective. STUDY OBJECTIVE: : Safety and efficacy evaluations of albuterol sulfate hydrofluoroalkane (HFA) inhalation aerosol in children younger than 2 years with acute wheezing caused by obstructive airway disease. METHODS: A randomized, double-blind, parallel group, multicenter study of albuterol HFA 180 microg (n = 43) or 360 microg (n = 44) via an MDI with a valved holding chamber and face mask in an urgent-care setting. Assessments included adverse events, signs of adrenergic stimulation, electrocardiograms, and blood glucose and potassium levels. Efficacy parameters included additional albuterol use and Modified Tal Asthma Symptoms Score ([MTASS] reduction in MTASS representing improvement). RESULTS: Overall, adverse events occurred in 4 (9%) and 3 (7%) subjects in the 180-microg and 360-microg groups, respectively. Drug-related tachycardia (360 microg) and ventricular extrasystoles (180 microg) were reported in 1 patient each. Three additional instances of single ventricular ectopy were identified from Holter monitoring. No hypokalemia or drug-related QT or QTc prolongation was seen; glucose values and adrenergic stimulation did not significantly differ between treatment groups. In the 180-microg and 360-microg groups, mean change from baseline in MTASS during the treatment period was -2.8 (-49.8%) and -2.9 (-48.4%), and rescue albuterol use occurred in 4 (9%) and 3 (7%) subjects, respectively. CONCLUSIONS: Cumulative dosing with albuterol HFA 180 microg or 360 microg via MDI-spacer and face mask in children younger than 2 years did not result in any significant safety issues and improved MTASS by at least 48%.

Assessment of asthma control in primary care.

OBJECTIVE: To determine the prevalence of uncontrolled asthma in patients who are visiting their primary care provider for any reason. RESEARCH DESIGN AND METHODS: This multisite, cross-sectional survey was conducted between January 25 and May 2, 2008. Participants aged > or =18 years were recruited from 35 primary care provider sites. Eligible participants presented to the office for any acute medical, routine, follow-up, or nonmedical reason; had a self-reported physician diagnosis of asthma; used medication to treat asthma in the past year; and had no history of COPD. They completed the Asthma Control Test dagger (ACT) and provided information including demographics, health behaviors, medical history, and asthma medication use. Uncontrolled asthma was defined as ACT score < or =19. RESULTS: The overall weighted prevalence of uncontrolled asthma in 2238 patients in primary care was 58% (95% confidence interval [CI], 0.56-0.60). Among asthma patients seeking care for a respiratory complaint, 72% (95% CI, 0.68-0.75) had uncontrolled asthma compared to 48% (95% CI, 0.45-0.51) of asthma patients presenting for a non-respiratory reason. CONCLUSIONS: At the population level, over half of patients with asthma under primary care management had uncontrolled asthma at the time of an office visit. Surprisingly, nearly 50% of patients with asthma who presented for office visits not associated with respiratory-related complaints had uncontrolled asthma. The study results may be influenced by a seasonal effect of upper respiratory infections and by the insurance status of the study respondents. However identifying patients with uncontrolled asthma is important and remains a challenge. Therefore, health care providers should consider evaluating asthma control on a regular basis, regardless of reason for visit.

Safety of daily albuterol in infants with a history of bronchospasm: a multi-center placebo controlled trial.

INTRODUCTION: Inhaled short-acting bronchodilators are recommended for the quick relief of bronchospasm symptoms in children including those less than five years of age. However, limited safety data is available in this young population. METHODS: Safety data were analyzed from a randomized, double-blind, parallel group, placebo-controlled multicenter, study evaluating albuterol HFA 90microg or 180microg versus placebo three times a day for 4 weeks using a valved holding chamber, Aerochamber Plus and facemask in children birth

Real-world assessment of a metered-dose inhaler with integrated dose counter.

Currently available metered dose inhalers (MDIs) do not track the remaining number of doses, indicating the need for a device that accurately monitors medication use. In an open-label study at 37 outpatient centers, patients > or =4 years old with asthma or chronic obstructive pulmonary disease requiring short-acting 32-agonists received two actuations of albuterol hydrofluoroalkane (HFA) [Ventolin HFA: GlaxoSmithKline], 90 microg twice daily, via a novel MDI with an integrated dose counter until all 200 actuations were completed. Concordance between counter readings, diary card-recorded actuations, and canister weights were measured in patients who completed > or =90% of the labeled actuations (n = 224). Adverse events and patient satisfaction were assessed in the intent-to-treat population (n = 268). In 43,865 recorded actuations, 333 counter versus diary discrepancies occurred (discrepancy rate of 0.76%), and 88% of discrepancies were by one to two actuations. Forty-seven percent of patients had no discrepancies. Incidence of the device firing without changes in counter readings was very low (0.09%). Mean expected actuations based on canister weights (184) were slightly lower than mean counter and diary-reported actuations (200 each). At baseline, 62% of patients reported anxiety about not knowing the quantity of medication remaining in their inhaler. On study completion, 92% expressed satisfaction with the dose counter and 92% agreed it would help prevent them from running out of medication. The adverse event profile showed that albuterol HFA was well tolerated. Integrated MDI counters are a useful and reliable tool for tracking a patient's medication supply.

Comparative efficacy and safety of low-dose fluticasone propionate and montelukast in children with persistent asthma.

OBJECTIVE: To evaluate efficacy, safety, health outcomes, and cost-effectiveness of fluticasone propionate (FP) versus montelukast (MON) in 342 children (6 to 12 years of age) with persistent asthma. STUDY DESIGN: Randomized, double-blind, 12-week study of treatment with FP inhalation powder 50 mug twice daily or MON chewable 5 mg once daily for 12 weeks. RESULTS: Compared with MON, FP significantly increased mean percent change from baseline FEV1 (forced expiratory volume in 1 second) (P=.002), morning PEF (peak expiratory flow) (P=.004), evening PEF (P=.020), and percent rescue-free days (P=.002) at end point, and it significantly reduced nighttime symptom scores (P <.001) and mean total (P=.018), and nighttime (P <.001) albuterol use. Withdrawals from the study were more frequent with MON (21%) than with FP (13%). Adverse events (69% vs 71%) and mean end point to baseline 12-hour urinary cortisol excretion ratios were similar. Parents and physicians were more satisfied with FP treatment than with MON (P=.006 and P=.016, respectively, at Week 12). Mean total daily asthma-related cost per patient in the FP group was approximately one-third of that in the MON group ($1.25 vs $3.49). CONCLUSION: FP was significantly more effective than MON in improving pulmonary function, asthma symptoms, and rescue albuterol use. Both therapies had similar safety profiles. Parent- and physician-reported satisfaction ratings were higher with FP treatment, and asthma-related costs were lower.

Evaluation of particle size distribution of albuterol sulfate hydrofluoroalkane administered via metered-dose inhaler with and without valved holding chambers.

BACKGROUND: Administration of inhaled medications via metered-dose inhaler (MDI) to pediatric patients younger than 4 years usually requires use of a holding chamber or spacer with an attached face mask. OBJECTIVE: To determine the particle size distribution and overall dose of albuterol from the albuterol sulfate hydrofluoroalkane delivered in conjunction with 2 US-marketed valved holding chambers (VHCs) compared with the dose delivered via MDIs without VHCs. METHODS: Cascade impaction methods with high-performance liquid chromatography were used to evaluate the fine particle mass (FPM) of albuterol administered without and with the use of 2 commercially available VHCs. RESULTS: Particle size distributions for the 2 VHCs and the control were similar. The mean FPM values for the 2 VHCs and the control were 32, 28, and 30 microg, respectively. Statistical comparison of the FPM shows a similar profile when differences from the albuterol hydrofluoroalkane without a spacer were evaluated. CONCLUSIONS: In vitro results obtained under these test conditions demonstrate that all the FPM values for the VHCs tested were within 15% of the control range, a difference that is unlikely to be clinically meaningful. These results do not warrant a change in the recommended dose of albuterol hydrofluoroalkane administered when using the VHCs tested. The use of an MDI in conjunction with a VHC provides a reasonable therapeutic approach for administration of albuterol hydrofluoroalkane to young children and other patients who have difficulty administering the MDI alone.

The relationship between health-related quality of life, lung function and daily symptoms in patients with persistent asthma.

It is generally believed that there is a direct correlation between asthma control and a patient's health-related quality of life (HRQL). Objective and subjective measures of asthma control are used interchangeably. A retrospective analysis from 8994 patients from 27 randomized, controlled clinical trials with persistent asthma was conducted to determine the degree of association which exists between objective (lung function) and subjective (symptoms, quality of life) measures. Assessments were made via forced expiratory volume in 1-second (FEV1), self-reported symptoms and the Asthma Quality of Life Questionnaire (AQLQ) overall scores. Baseline percent predicted FEV1 was weakly correlated with baseline symptom-free days (SFD) and baseline overall AQLQ scores (r=0.11 and 0.09, respectively; P <0.001). Changes in percent predicted FEV1 correlated weakly with changes in SFD but was more strongly correlated with changes in overall AQLQ scores (r= 0.26 and 0.38, respectively; P <0.001). Additionally, SFD at both baseline and endpoint were moderately correlated with overall AQLQ scores at baseline and endpoint (r=0.36 and 0.44; P <0.001). This study suggests that the impact of asthma on a patients' HRQL is not fully accounted for by objective measures such as lung function. Thus, HRQL data complements rather than duplicates results from traditional, objective assessments of asthma control.

Patient perceptions of an inhaled asthma medication administered as an inhalation powder via the Diskus or as an inhalation aerosol via a metered-dose inhaler.

OBJECTIVE: To evaluate patient preference, ease of use, and correctness of use of fluticasone propionate administered as inhalation powder via the Diskus (GlaxoSmithKline, Research Triangle Park, NC) and as inhalation aerosol administered via metered-dose inhaler (MDI). METHODS: In 154 patients 12 years of age and older with asthma and a history of MDI use, the Diskus and the MDI were compared in a randomized, open-label, 7-week crossover study. RESULTS: In patients who had used both devices, more found the Diskus easier to use (59%) and preferred it overall (60%) compared with the MDI (P < or = 0.025). Ninety-eight percent (for the MDI) vs 91% (for the Diskus) of patients were able to correctly perform all the maneuvers necessary to use the devices correctly by either viewing a single demonstration and/or reading the instructions for use. Ninety-four percent of all patients found it easier to tell the number of residual doses with the Diskus (P < 0.001), and 59% of patients indicated that they would most likely request the Diskus from their physician (P = 0.025). Compliance was significantly better with the Diskus; 91.1% of patients used the Diskus as directed compared with 78.6% for the MDI (P = 0.013). CONCLUSIONS: In patients exposed to both devices, the majority preferred the Diskus and found it easier to use compared with the MDI. Ninety-one percent of patients used the Diskus correctly with minimal training, and when given a choice, most indicated they would likely request the Diskus from their physicians. Together, these data indicate a significant level of acceptance of the Diskus device in this patient population.

Efficacy and safety of fluticasone propionate 250 microg administered once daily in patients with persistent asthma treated with or without inhaled corticosteroids.

BACKGROUND: Studies have shown fluticasone propionate (FP) 100, 200, and 500 microg administered once daily to be effective in the treatment of asthma. The efficacy of a once daily regimen of FP 250 microg has not been evaluated previously. OBJECTIVE: We sought to evaluate the efficacy and safety of inhaled FP 250 microg administered once daily in patients currently receiving inhaled short-acting beta-agonists (SABA) alone or inhaled corticosteroids (ICS). METHODS: In two separate studies, 408 patients in the SABA study and 401 patients in the ICS study were randomly assigned to receive FP 250 microg or placebo for 12 weeks through the Diskus device (GlaxoSmithKline, Research Triangle Park, NC) each morning. RESULTS: At the study endpoint, SABA patients treated with FP and placebo had mean increases in forced expiratory volume in 1 second from baseline of 0.23 +/- 0.03 L and 0.10 +/- 0.03 L, respectively (P < 0.001). ICS patients treated with FP had a mean increase of 0.08 +/- 0.02 L compared with a decrease in forced expiratory volume in 1 second of -0.08 +/- 0.03 L with placebo (P < 0.001). Changes of similar magnitude in morning peak expiratory flow rates were seen with FP in both the SABA and ICS studies. Fewer FP-treated ICS study patients were withdrawn from the study as a result of predetermined asthma stability criteria and, therefore, those patients had a greater probability of remaining in the study than placebo-treated patients (P < 0.001). CONCLUSIONS: FP 250 microg, once daily, produced greater improvements in pulmonary function and asthma symptom control than placebo. This new treatment regimen provides clinicians with an additional therapeutic option for patients with asthma previously treated with either beta2-agonists alone or ICS.