William R. Lincourt

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 ≤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 ≥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/m2, 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.

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 <or=19. RESULTS A total of 2429 children with a diagnosis of asthma (or caregivers) completed the survey. The prevalence of uncontrolled asthma was 46%. The prevalence of uncontrolled asthma was 35% in patients seen for a nonrespiratory complaint versus 54% in those seen for a respiratory complaint. Children seen for a non-respiratory-related complaint with uncontrolled asthma were more likely to have missed 1 or more school days in the previous 4 weeks compared with children with controlled asthma (53% vs 24%). CONCLUSIONS These findings highlight the impact of uncontrolled asthma not only in children seen for respiratory complaints, but also in those seen for nonrespiratory complaints. Pediatric care providers should consider evaluating asthma control on a regular basis regardless of the reason for the visit.

A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma

BACKGROUND Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few. OBJECTIVE We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 micrograms twice daily and 220 micrograms twice daily) with 2 doses of beclomethasone dipropionate (168 micrograms twice daily and 336 micrograms twice daily) in subjects with persistent asthma. METHODS Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards. RESULTS Fluticasone propionate treatment resulted in significantly (P </=.034) greater improvements in objective pulmonary function parameters than did beclomethasone dipropionate treatment and significantly greater reductions in daily albuterol use (P </=.010) and asthma symptoms (P </=.027). Both low-dose (88 micrograms twice daily) and medium-dose (220 micrograms twice daily) fluticasone propionate significantly increased FEV1 compared with higher doses of beclomethasone dipropionate (P =. 006). Low-dose and medium-dose fluticasone propionate improved FEV1 by 0.31 L (14%) and 0.36 L (15%), respectively, compared with improvements of 0.18 L (8%) and 0.21 L (9%) with low-dose and medium-dose beclomethasone dipropionate. The adverse event profiles were similar for both medications. CONCLUSION Fluticasone propionate provides greater asthma control at roughly half the dose of beclomethasone dipropionate, with a comparable adverse event profile.

Effects of the inhaled corticosteroids fluticasone propionate, triamcinolone acetonide, and flunisolide and oral prednisone on the hypothalamic-pituitary-adrenal axis in adult patients with asthma.

Two multicenter, randomized, double-masked, placebo-controlled, parallel-group studies were conducted in adult patients with mild-to-moderate persistent asthma to assess the effects of 4 weeks of treatment with inhaled corticosteroids on hypothalamic-pituitary-adrenal (HPA) axis function. The first study compared fluticasone propionate 100 and 500 microg twice daily, triamcinolone acetonide 300 and 500 microg twice daily, oral prednisone 10 mg every morning, and placebo. The second study compared fluticasone propionate 100 and 250 microg twice daily, flunisolide 500 microg twice daily, and placebo. Therapeutic doses of fluticasone propionate, triamcinolone acetonide, and flunisolide were found to be comparable to each other and to placebo in their lack of adrenal suppressive effects, based on mean plasma cortisol responses to 6-hour cosyntropin infusion. Prednisone produced significantly greater suppression of HPA-axis function than did any of the inhaled corticosteroids or placebo (P<0.001). Mean reductions from baseline in 8-hour area under the plasma concentration-time curve (AUC) and 8-hour peak plasma cortisol concentrations and the mean percentage of change from baseline in 8-hour AUC were significantly greater after treatment with triamcinolone acetonide 500 microg twice daily compared with placebo (P< or =0.042). These findings indicate that fluticasone propionate has no greater systemic effect than either triamcinolone acetonide or flunisolide at doses appropriate for patients with mild-to-moderate persistent asthma.

Assessment of asthma control in primary care

Abstract 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 ≥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† (ACT) and provided information including demographics, health behaviors, medical history, and asthma medication use. Uncontrolled asthma was defined as ACT score ≤19. † Asthma Control Test is a trademark of QualityMetric, Inc., Lincoln, RI, USA. 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.

Fluticasone propionate/salmeterol hydrofluoroalkane via metered‐dose inhaler with integrated dose counter: performance and patient satisfaction

Currently, patients have to keep track of doses to determine when to replace their metered‐dose inhalers (MDIs). This study evaluated the performance and patient satisfaction of a novel MDI with an integrated dose counter. In an open‐label study at 38 outpatient centres, patients ≥12 years old with asthma or chronic obstructive pulmonary disease (COPD) received two actuations of fluticasone propionate/salmeterol 125/25 μg (115/21 μg ex‐actuator) hydrofluoroalkane (ADVAIR® HFA) via MDI with counter twice a day until all 120 actuations were completed. Concordance between counter and diary recordings in patients who reported use of ≥90% of labelled actuations (completer population, n = 228) was high (discrepancy rate of 0.94%) and the incidence of device firing without changes in counter readings was low (0.13%). Mean expected actuations based on canister weights (114) were slightly lower than mean counter (121) and diary reported actuations (120). Upon study completion, 95% of patients were satisfied with the dose counter and 92% agreed it would help prevent them from running out of medication. Safety assessments (intent‐to‐treat population, n = 237) indicated that the drug was well tolerated. This integrated MDI counter may help patients maintain better disease control by enabling them to accurately track their medication supply.

Efficacy and safety of fluticasone propionate 250 μg 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.

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.

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.

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 oftentimes lead to emergency department visits in infants. Inhaled short-acting &bgr;2-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 &mgr;g (n = 43) or 360 &mgr;g (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-&mgr;g and 360-&mgr;g groups, respectively. Drug-related tachycardia (360 &mgr;g) and ventricular extrasystoles (180 &mgr;g) 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-&mgr;g and 360-&mgr;g 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 &mgr;g or 360 &mgr;g 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%.