High Prevalence of Suboptimal Peak Inspiratory Flow in Hospitalized Patients With COPD: A Real-world Study.

For optimal drug delivery, dry powder inhalers (DPIs) depend on the patient's peak inspiratory flow (PIF) and the internal resistance of the device to create turbulent energy and disaggregate the powder. A suboptimal PIF may lead to ineffective drug inhalation into the lungs. Our objective was to report the prevalence of suboptimal PIF in patients with COPD hospitalized for any reason using 1 or more DPIs. In this real-world, observational, single­site, retrospective study, PIF was measured for each DPI using the In-Check™ DIAL set to match the resistance of the DPI used by each patient. PIFs <60 and <30L/min were considered suboptimal for low to medium-high- and high-resistance DPIs, respectively. At initial hospitalization, the prevalence of suboptimal PIF was 44.6% in 829 patients (mean age, 71.7 years; 56.8% female); 21.2% were measured during admission for a COPD exacerbation. Suboptimal PIF percentages were 61.0% (38.1±9.5L/min [mean±standard deviation (SD)]) across low to medium-high-resistance DPIs and 17.2% (20.7±4.2L/min) for high-resistance DPIs. Overall, 190/829 patients had 1 or more 30-day all-cause readmission with 253 corresponding PIF measurements. For readmissions, suboptimal PIFs were observed in 49.5% (94/190) of patients. Suboptimal PIF percentages were 65.4% (38.4±9.2L/min) for low to medium-high-resistance DPIs and 19.8% (22.4±3.3L/min) for high-resistance DPIs. As the overall prevalence of suboptimal PIFs in hospitalized patients with COPD varied according to the specific internal resistance of the DPI, these findings may have clinical implications for inhaler selection.

Advancing the Patient EXperience (APEX) in COPD Registry: Study Design and Strengths.

The Advancing the Patient Experience (APEX) in Chronic Obstructive Pulmonary Disease (COPD) registry (https://www.apexcopd.org/) is the first primary care health system-based COPD registry in the United States. While its ultimate goal is to improve the care of patients diagnosed with COPD, the registry is also designed to describe real-life experiences of people with COPD, track key outcomes longitudinally, and assess the effectiveness of interventions. It will retrospectively and prospectively collect information from 3000 patients enrolled in 5 health care organizations. Information will be obtained from electronic health records, and from extended annual and brief questionnaires completed by patients before clinic visits. Core variables to be collected into the APEX COPD registry were agreed on by Delphi consensus and fall into 3 domains: demographics, COPD monitoring, and treatment. Main strengths of the registry include: 1) its size and scope (in terms of patient numbers, geographic spread and use of multiple information sources including patient-reported information); 2) collection of variables which are clinically relevant and practical to collect within primary care; 3) use of electronic data capture systems to ensure high-quality data and minimization of data-entry requirements; 4) inclusion of clinical, database development, management and communication experts; 5) regular sharing of key findings, both at international/national congresses and in peer-reviewed publications; and 6) a robust organizational structure to ensure continuance of the registry, and that research outputs are ethical, relevant and continue to bring value to both patients and physicians.

Development of the Advancing the Patient Experience in COPD Registry: A Modified Delphi Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is commonly managed by family physicians, but little is known about specifics of management and how this may be improved. The Advancing the Patient Experience in COPD (APEX COPD) registry will be the first U.S. primary care, health system-based registry following patients diagnosed with COPD longitudinally, using a standardized set of variables to investigate how patients are managed in real life and assess outcomes of various management strategies. OBJECTIVE: Gaining expert consensus on a standardized list of variables to capture in the APEX COPD registry. METHODS: A modified, Delphi process was used to reach consensus on which data to collect in the registry from electronic health records (EHRs), patient-reported information (PRI) and patient-reported outcomes (PRO), and by physicians during subsequent office visits. The Delphi panel comprised 14 primary care and specialty COPD experts from the United States and internationally. The process consisted of 3 iterative rounds. Responses were collected electronically. RESULTS: Of the initial 195 variables considered, consensus was reached to include up to 115 EHR variables, 34 PRI/PRO variables and 5 office-visit variables in the APEX COPD registry. These should include information on symptom burden, diagnosis, COPD exacerbations, lung function, quality of life, comorbidities, smoking status/history, treatment specifics (including side effects), inhaler management, and patient education/self-management. CONCLUSION: COPD experts agreed upon the core variables to collect from EHR data and from patients to populate the APEX COPD registry. Data will eventually be integrated, standardized and stored in the APEX COPD database and used for approved COPD-related research.

Add-on tiotropium versus step-up inhaled corticosteroid plus long-acting beta-2-agonist in real-world patients with asthma.

Background: A step-up approach (increasing inhaled corticosteroid [ICS] dose and/or add-on treatment) is recommended for asthma that is uncontrolled despite ICS plus long-acting beta-2-agonist (LABA) combination treatment. Understanding the impact of different treatment options on health outcomes can help guide treatment decision-making. Objective: To compare the effectiveness of add-on tiotropium 1.25 µg (two puffs once daily) versus an increased ICS plus LABA dose in a real-world cohort of patients with asthma initiated on ICS plus LABA. Methods: De-identified data from patients ages ≥12 years and with asthma who were initiated on ICS plus LABA, and then had tiotropium added (Tio group; index date) or an ICS plus LABA dose increased (inc-ICS group; index date) were collected from two medical and pharmacy claims data bases (2014-2018). To account for population/group differences, propensity score matching was performed. The primary end point was the exacerbation risk after the index date. Secondary end points included exacerbation rates 6 and 12 months postindex, health-care resource utilization, costs, and short-acting beta-2-agonist (SABA) refills 12 months postindex. Results: Overall, 7857 patients (Tio group, 2619; inc-ICS group, 5238) were included. The exacerbation risk was 35% lower in the Tio group than in the inc-ICS group (hazard ratio 0.65 [95% confidence interval, 0.43-0.99]; p = 0.044). Exacerbation rates in the Tio group also were significantly lower within 6 and 12 months postindex (64% and 73%, respectively). All-cause and asthma-related emergency department (ED) visits were 47% and 74% lower, respectively (p < 0.0001 for both), and all-cause and asthma-related hospitalizations were 48% (p < 0.01) and 76% (p < 0.001) lower, respectively, in the Tio group. Also, significantly fewer patients in the Tio group versus the inc-ICS group required SABA refills (56% versus 67%, p < 0.0001). Conclusion: Add-on tiotropium significantly decreased the risk and rate of exacerbations, decreased all-cause and asthma-related ED visits and hospitalizations, and reduced SABA refills compared with increasing the ICS plus LABA dose. The findings supported the use of add-on tiotropium for patients with uncontrolled asthma taking ICS plus LABA.

Effect of clinically significant thresholds of eosinophil elevation on health care resource use in asthma.

BACKGROUND: Blood eosinophil counts correlate with exacerbations, but there is a lack of consensus on a clinically relevant definition of eosinophil count elevation. OBJECTIVE: To analyze health care resource use among patients with elevated blood eosinophil counts defined at 150 cells/µL or greater and 300 cells/µL or greater. METHODS: Data on patients who received a diagnosis of asthma between 2007 and 2016 were extracted from EMRClaims + database. Patients were defined as having elevated eosinophil counts if any test result during 3 months before follow-up found blood eosinophil count of 150 cells/µL or more or 300 cells/µL or more. Hospitalizations, emergency department visits, outpatient visits, and associated costs were compared. With logistic regression, likelihood of hospitalization was assessed in the presence of eosinophil elevation. RESULTS: Among 3687 patients who met the study criteria, 1152 received a test within 3 months before the follow-up period, of whom 644 (56%) had elevated eosinophil counts of 150 cells/µL or greater and 322 (29%) had eosinophil counts of 300 cells/µL or greater. Overall, the mean (SD) number of hospitalizations for patients with elevated eosinophil counts vs the comparator was significantly greater (0.29 [0.92] vs 0.17 [0.57], P < .001 at ≥150 cells/µL and 0.30 [0.95] vs 0.18 [0.61] at ≥300 cells/µL, P = .001). The total mean cost was significantly greater for patients with elevated eosinophil counts (at ≥150 cells/µL: $10,262 vs $7149, P < .001 and at ≥300 cells/µL: $9966 vs $7468, P = .003). CONCLUSION: Patients with asthma incurred greater health care resource use when their blood eosinophil counts were elevated at 150 cells/µL or greater and 300 cells/µL or greater as measured within 3 months of follow-up.

Development of the International Severe Asthma Registry (ISAR): A Modified Delphi Study.

BACKGROUND: The lack of centralized data on severe asthma has resulted in a scarcity of information about the disease and its management. The development of a common data collection tool for the International Severe Asthma Registry (ISAR) will enable standardized data collection, subsequently enabling data interoperability. OBJECTIVES: To create a standardized list of variables for the first international registry for severe asthma via expert consensus. METHODS: A modified Delphi process was used to reach consensus on a minimum set of variables to capture in ISAR: the core variables. The Delphi panel brought together 27 international experts in the field of severe asthma research. The process consisted of 3 iterative rounds. In each round, all Delphi panel members were issued an electronic ISAR Delphi workbook to complete and return to the ISAR Delphi administrator. Workbooks and result summaries were anonymously distributed by the Delphi administrator to all panel members at subsequent rounds. Finalization of the core variable list was facilitated by 2 face-to-face meetings. RESULTS: Of the initial 747 selected variables, the Delphi panel reached a consensus on 95. The chosen variables will allow severe asthma to be assessed against patient demographics and medical history, patient-reported outcomes, diagnostic information, and clinical characteristics. Physician-reported outcomes such as nonadherence and information about treatment and management strategies will also be recorded. CONCLUSIONS: This is the first global attempt to generate an ISAR using a common set of core variables to ensure that data collected across all participating countries are standardized.

Association between blood eosinophil count and risk of readmission for patients with asthma: Historical cohort study.

BACKGROUND: Recent studies have demonstrated an association between high blood eosinophil counts and greater risk of asthma exacerbations. We sought to determine whether patients hospitalized for an asthma exacerbation were at greater risk of readmission if they had a high blood eosinophil count documented before the first hospitalization. METHODS: This historical cohort study drew on 2 years of medical record data (Clinical Practice Research Datalink with Hospital Episode Statistics linkage) of patients (aged ≥5 years) admitted to hospital in England for asthma, with recorded blood eosinophil count within 1 baseline year before admission. We analyzed the association between high blood eosinophil count (≥0.35x109 cells/L) and readmission risk during 1 year of follow-up after hospital discharge, with adjustment for predefined, relevant confounders using forward selection. RESULTS: We identified 2,613 eligible patients with asthma-related admission, of median age 51 years (interquartile range, 36-69) and 76% women (1,997/2,613). Overall, 835/2,613 (32.0%) had a preadmission high blood eosinophil count. During the follow-up year, 130/2,613 patients (5.0%) were readmitted for asthma, including 55/835 (6.6%) with vs. 75/1,778 (4.2%) without high blood eosinophil count at baseline (adjusted hazard ratio [HR] 1.49; 95% CI 1.04-2.13, p = 0.029). The association was strongest in never-smokers (n = 1,296; HR 2.16, 95% CI 1.27-3.68, p = 0.005) and absent in current smokers (n = 547; HR 1.00, 95% CI 0.49-2.04, p = 0.997). CONCLUSIONS: A high blood eosinophil count in the year before an asthma-related hospitalization is associated with increased risk of readmission within the following year. These findings suggest that patients with asthma and preadmission high blood eosinophil count require careful follow-up, with treatment optimization, after discharge.

Real-life effectiveness and safety of salbutamol Steri-Neb™ vs. Ventolin Nebules® for exacerbations in patients with COPD: Historical cohort study.

INTRODUCTION: Ventolin Nebules® (reference product; GlaxoSmithKline) was the first licensed nebulizer solution containing the rapid-onset, short-acting ß2-agonist salbutamol. Salbutamol Steri-Neb™ (comparator; Teva Pharmaceuticals, Inc.) has the same chemical composition as the reference product. This study evaluated whether the effectiveness of the comparator is non-inferior to the reference product alongside concomitant medications during real-life clinical management of COPD exacerbations. Safety in terms of adverse events (AEs) was also examined. METHODS: This matched (1:1) historical cohort study evaluated data from 2 UK primary care databases on patients prescribed the salbutamol comparator or reference. The study included a 1-year baseline period, starting 1 year before the index prescription date, and 1-year outcome period. Cohorts were matched for baseline COPD respiratory medications. The primary outcome was analysis of non-inferiority for the comparator versus reference product for the rate of moderate and severe COPD exacerbations. Non-inferiority was satisfied if the 95% confidence interval (CI) upper limit for mean differences in proportions between treatments was <15%. Secondary outcomes were examined through rate ratios (RR) of severe exacerbations and AEs. RESULTS: After matching, 1191 patients were included in each cohort. Adjusted upper 95% CI for the difference in proportion of patients experiencing moderate or severe exacerbations between comparator and reference groups was 0.032 (3.2%), demonstrating non-inferiority. No significant differences were observed in rates of moderate and severe exacerbations (RR: 1.00; 95% CI: 0.91, 1.10), severe exacerbations (RR: 0.76; 95% CI: 0.49, 1.17), or AEs (RR: 0.98; 95% CI: 0.78, 1.22) after adjusting for baseline confounders. No significant differences across cohorts were observed for rates of any AE or death. CONCLUSION: This matched cohort study of real-life management of COPD patients supports the salbutamol comparator as non-inferior to the reference product, providing an effective treatment alternative for COPD exacerbations. Comparator and reference safety profiles were similar.

Real-life effectiveness and safety of the inhalation suspension budesonide comparator vs the originator product for the treatment of patients with asthma: a historical cohort study using a US health claims database.

OBJECTIVE: The objective of this study was to determine whether the effectiveness of budesonide comparator is non-inferior to budesonide reference in the prevention of asthma exacerbations. Asthma-related hospitalizations and safety were also examined. METHODS: This study used a matched, historic cohort design. Data were drawn from the Clinformatics™ Data Mart US claims database and included a 1-year baseline, starting 1 year before the index prescription date, and a 1-year outcome period. Patients received budesonide comparator or reference treatment. The primary outcome was the rate of asthma exacerbations. Non-inferiority for budesonide comparator vs budesonide reference was established if the 95% confidence interval (CI) upper limit of mean difference in proportions between treatments was <15%. Secondary outcomes examined rate of asthma-related hospitalizations and adverse events (AEs). RESULTS: The budesonide comparator and reference-matched cohorts each included 3109 patients. The adjusted upper 95% CI for the difference in proportions of patients experiencing asthma exacerbations was 0.035 (3.5%), demonstrating non-inferiority. Cohorts did not significantly differ in the rate of asthma exacerbations (adjusted rate ratio [RR]=1.04, 95% CI: 0.95-1.14) or rate of asthma-related hospitalizations (adjusted RR=1.10, 95% CI: 0.99-1.24) after adjusting for baseline confounders. No asthma exacerbations occurred during the outcome period in 72.9% of budesonide comparator patients and 71.8% of budesonide reference patients. No asthma-related hospitalizations occurred in 77.9% of patients in the budesonide comparator cohort and 79.0% of patients in the budesonide reference cohort. The most frequent AEs were throat irritation (≤0.4% of patients) and hoarseness/dysphonia (0.02% of patients). AEs did not significantly differ between treatment cohorts. CONCLUSION: In this real-life study, non-inferiority of the budesonide comparator vs reference was met for the primary end point of asthma exacerbation rates. Asthma-related hospitalization and AE rates did not differ between the two treatment cohorts. The budesonide comparator is an effective and safe treatment alternative for asthma exacerbations.

Value of peripheral blood eosinophil markers to predict severity of asthma.

BACKGROUND: Asthma represents a significant clinical and economic burden to the US healthcare system. Along with other clinical manifestations of the disease, elevated sputum and blood eosinophil levels are observed in patients experiencing asthma exacerbations. The aim of this study was to evaluate the association between blood eosinophil levels and asthma severity defined using Expert Panel Report 3 guidelines. METHODS: Patients with asthma diagnosis between 2004 and 2011 were extracted from the EMRClaims+ database (eMAX Health, White Plains, NY) containing electronic medical records linked to insurance claims for over 675,000 patients. The date of first asthma diagnosis was defined as the 'index date'. Patients were required to have at least 1 peripheral eosinophil test (elevated defined as ≥ 400 cells/µL) in the 12 month 'assessment' period following the index date. We classified patients as those with mild asthma and moderate-to-severe asthma based on the pattern of medication use, as recommended by the 2007 National Institutes of Health Expert Panel Report. Logistic regression models were used to determine if patients with moderate-to-severe asthma had increased likelihood of an elevated peripheral eosinophil count, after accounting for demographics and comorbidities. RESULTS: Among 1,144 patients with an asthma diagnosis, 60 % were classified as having moderate-to-severe asthma. Twenty four percent of patients with moderate-to-severe asthma and 19 % of patients with mild asthma had an elevated peripheral eosinophil count (p = 0.053). Logistic regression showed that moderate-to-severe asthma was associated with 38 % increased odds of elevated eosinophil level (OR 1.38, 95 % CI: 1.02 to 1.86, p = 0.04). CONCLUSION: Patients with moderate-severe asthma are significantly more likely to have an elevated peripheral eosinophil count than patients with mild asthma.

Burden of asthma with elevated blood eosinophil levels.

BACKGROUND: Asthma is a common chronic condition with an economic burden of almost $56 billion annually in the US. Biologic markers like blood eosinophils, that help predict the risk of exacerbation could help guide more optimal treatment plans and reduce cost. The purpose of this study was to determine whether healthcare resource use and expenditures vary by eosinophil level among patients with asthma. METHODS: Patients with a diagnosis of asthma defined by ICD-9-CM code 493.xx between January 2004 and July 2011 were extracted from EMRClaims + database (eMAX Health, White Plains NY). Patients were classified as mild, moderate, or severe by medication use following diagnosis, based on recommendations of National Institutes of Health Expert Panel Report 3. Patients were classified as those with elevated eosinophils (≥400 cells/µL) and normal eosinophil level (<400 cells/µL). Patients were followed for resource use, defined as hospitalizations, ER visits and outpatient visit and associated costs were calculated to assess whether an economic difference exists between eosinophil groups. Non-parametric tests were used to compare resource use and associated cost between elevated and normal eosinophil groups. Multivariate modeling was performed to assess the contribution of eosinophil level on the likelihood of study outcomes among patients with severe asthma. RESULTS: Among the 2,164 patients meeting eligibility criteria, 1,144 had severity designations. Of these, 179(16 %) of patients had severe asthma of which 20 % (n = 35) had elevated eosinophils. Seventeen percent of patients with elevated eosinophils were admitted to the hospital during the follow-up period, significantly greater than patients with normal eosinophil levels (12 %; p = 0.011). Overall, compared to patients with normal eosinophil levels (n = 1734), patients with elevated eosinophil levels (n = 430) had significantly greater mean annual hospital admissions (0.51 vs. 0.21/year, p = 0.006) and hospital costs (2,536 vs. $1,091, p = 0.011). Logistic regressions showed that elevated eosinophil level was associated with 5.14 times increased odds of all cause admissions (95 % CI:1.76-14.99, p = 0.003) and 4.07 times increased odds of asthma related admissions (95 % CI: 1.26-13.12, p = 0.019). CONCLUSION: Eosinophil elevation was associated with greater healthcare resource use in patients with asthma.

A randomized, double-blinded, double-dummy efficacy and safety study of budesonide-formoterol Spiromax® compared to budesonide-formoterol Turbuhaler® in adults and adolescents with persistent asthma.

BACKGROUND: Budesonide and formoterol (BF) Spiromax® is a dry powder inhaler designed to deliver BF with maximum ease of use for patients with asthma or chronic obstructive pulmonary disease. METHODS: A phase 3b, 12-week, multicenter, double-blind, double-dummy, randomized, controlled trial in patients (≥12 years) with persistent asthma. PRIMARY OBJECTIVE: to demonstrate non-inferiority of twice-daily BF Spiromax 160/4.5 mcg to BF Turbuhaler® 200/6 mcg in change from baseline in weekly average of daily trough morning peak expiratory flow (PEF). Secondary endpoints included: Patient Satisfaction and Preference Questionnaire scores, change from baseline in evening PEF, trough forced expiratory volume in one second, percentage of symptom-free and rescue-free 24-hour periods, and safety. RESULTS: The analysis was based on the per-protocol population (BF Spiromax, n = 290; BF Turbuhaler, n = 284). The least squares mean change from baseline to week 12 in morning PEF was: BF Spiromax, 18.8 L/min and BF Turbuhaler, 21.8 L/min. Non-inferiority of BF Spiromax vs BF Turbuhaler was demonstrated (the lower limit of the 95% two-sided confidence interval was -9.02 L/min, which is greater than -15 L/min [the criteria specified for non-inferiority]). The mean difference in the total performance domains scores for BF Spiromax vs BF Turbuhaler were 0.248 at baseline and 0.353 at week 12 (both, p <0.001), indicating statistical superiority for BF Spiromax. No statistical or numerical differences were recorded in the total convenience domain score between the two devices. Scores for 'device preference' and 'willingness to continue' supported BF Spiromax at baseline and at week 12 (p = 0.0005 vs BF Turbuhaler). No significant between-group differences were observed in the other secondary efficacy endpoints. Both treatments were well tolerated, with no significant differences in adverse events or asthma exacerbations. CONCLUSIONS: This study demonstrates the non-inferiority of BF Spiromax vs BF Turbuhaler in patients (≥12 years) with asthma. More patients preferred the Spiromax device over Turbuhaler for its performance, and were willing to continue therapy with BF Spiromax beyond the 12-week study period. TRIAL REGISTRATION: NCT01803555; February 28, 2013.

Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study.

BACKGROUND: Elevated sputum eosinophil counts predict asthma exacerbations and responsiveness to inhaled corticosteroids but are impractical to measure in primary care. We investigated the relation between blood eosinophil count and prospective annual asthma outcomes for a large UK cohort. METHODS: This historical cohort study used anonymised medical record data to identify primary care patients with asthma aged 12-80 years with 2 years of continuous records, including 1 year before (baseline) and 1 year after (outcome) their most recent eosinophil count. Negative binomial regression was used to compare outcome exacerbation rates and logistic regression to compare odds of asthma control for patients with blood eosinophil counts of 400 cells per µL or less versus greater than 400 cells per µL, adjusting for age, sex, body-mass index, smoking status, and Charlson comorbidity index. The study is registered at ClinicalTrials.gov, number NCT02140541. FINDINGS: Overall, 20 929 (16%) of 130 248 patients had blood eosinophil counts greater than 400 cells per µL. During the outcome year, these patients experienced significantly more severe exacerbations (adjusted rate ratio [RR] 1·42, 95% CI 1·36-1·47) and acute respiratory events (RR 1·28, 1·24-1·33) than those with counts of 400 cells per µL or less. They also had significantly lower odds of achieving overall asthma control (OR 0·74, 95% CI 0·72-0·77), defined as limited reliever use and no asthma-related hospital attendance or admission, acute course of oral corticosteroids, or prescription for antibiotics. Exacerbation rates increased progressively with nine ascending categories of blood eosinophil count as compared with a reference category of 200 cells per µL or less. INTERPRETATION: Patients with asthma and blood eosinophil counts greater than 400 cells per µL experience more severe exacerbations and have poorer asthma control. Furthermore, a count-response relation exists between blood eosinophil counts and asthma-related outcomes. Blood eosinophil counts could add predictive value to Global Initiative for Asthma control-based risk assessment. FUNDING: Teva Pharmaceuticals.

Effect of inhalation profile and throat geometry on predicted lung deposition of budesonide and formoterol (BF) in COPD: An in-vitro comparison of Spiromax with Turbuhaler.

Successful delivery of inhalation medication to the lungs can be affected by the inhalation manoeuvre used. Conventional in-vitro testing of the emitted dose from a dry powder inhaler (DPI) uses a vacuum pump to simulate an inhalation. We have adapted this method by replacing the pump with patient inhalation profiles and an anatomical throat. Three anatomical throat sizes and three inhalation profiles were used. The profiles represented the 10th, 50th and 90th percentiles of peak inhalation flow and acceleration of flow from a population of 50 COPD patients inhaling through empty Spiromax and Turbuhaler devices. Combining the dose emission results for the three throat sizes, the mean (SD) budesonide fine-particle dose (FPD) from budesonide-formoterol Spiromax 320/9 µg was 78.91 (20.18), 79.91 (15.36) and 75.10 (19.91)µg and the total emitted dose (TED) of budesonide was 263.69 (40.74), 261.20 (21.65) and 261.61 (45.65)µg. Similarly, the FPD from 320/9 µg Turbuhaler was 22.45 (3.24), 52.20 (12.57) and 69.11 (75.10)µg with a TED of 143.80 (14.90), 149.50 (26.61) and 158.61 (43.04)µg. Spiromax showed greater consistency than Turbuhaler over a range of inspiratory flow profiles. The results demonstrate the value of this new method to assess the doses that patients receive during real-life use of their DPI.

Comparing the effectiveness of small-particle versus large-particle inhaled corticosteroid in COPD.

PURPOSE: Small airway changes and dysfunction contribute importantly to airway obstruction in chronic obstructive pulmonary disease (COPD), which is currently treated with inhaled corticosteroids (ICS) and long-acting bronchodilators at Global initiative for Obstructive Lung Disease (GOLD) grades 2-4. This retrospective matched cohort analysis compared effectiveness of a representative small-particle ICS (extrafine beclomethasone) and larger-particle ICS (fluticasone) in primary care patients with COPD. PATIENTS AND METHODS: Smokers and ex-smokers with COPD ≥ 40 years old initiating or stepping-up their dose of extrafine beclomethasone or fluticasone were matched 1:1 for demographic characteristics, index prescription year, concomitant therapies, and disease severity during 1 baseline year. During 2 subsequent years, we evaluated treatment change and COPD exacerbations, defined as emergency care/hospitalization for COPD, acute oral corticosteroids, or antibiotics for lower respiratory tract infection. RESULTS: Mean patient age was 67 years, 57%-60% being male. For both initiation (n=334:334) and step-up (n=189:189) patients, exacerbation rates were comparable between extrafine beclomethasone and fluticasone cohorts during the 2 year outcome period. Odds of treatment stability (no exacerbation or treatment change) were significantly greater for patients initiating extrafine beclomethasone compared with fluticasone (adjusted odds ratio 2.50; 95% confidence interval, 1.32-4.73). Median ICS dose exposure during 2 outcome years was significantly lower (P<0.001) for extrafine beclomethasone than fluticasone cohorts (315 µg/day versus 436 µg/day for initiation, 438 µg/day versus 534 µg/day for step-up patients). CONCLUSION: We observed that small-particle ICS at significantly lower doses had comparable effects on exacerbation rates as larger-particle ICS at higher doses, whereas initiation of small-particle ICS was associated with better odds of treatment stability during 2-years' follow-up.

Randomized controlled trial of desloratadine for persistent allergic rhinitis: correlations between symptom improvement and quality of life.

Allergic rhinitis (AR) symptoms can impart emotional, quality of life (QOL), and work productivity burdens, especially in persistent AR (PER). Desloratadine, an H1-receptor antagonist, has been shown to be effective against nasal and nonnasal AR symptoms and to improve QOL. Exploratory analyses were conducted to evaluate whether desloratadine-mediated symptom improvement correlated with improvements in QOL and productivity. The Aerius Control: Clinical and Evaluative Profile of Treatment 2 (NCT00405964) study was a 12-week, multinational, randomized, placebo-controlled prospective study of once-daily desloratadine at 5 mg in subjects with moderate-to-severe PER. Assessments included twice-daily symptom severity ratings (0 = none to 3 = severe; total and individual symptoms), sleep interference (morning [A.M.]), interference with activities of daily living (ADL; evening [P.M.]), the Rhinoconjunctivitis Quality of Life Questionnaire-Standardized version (baseline and days 29 and 85), and the Work Productivity and Activity Impairment-Allergy-Specific questionnaire (baseline and weekly). Pearson product-moment correlation statistics (r) were determined to assess correlations between symptom score improvements and QOL factors. All desloratadine-treated patients (n = 360) were included in this exploratory analysis. In the desloratadine-treated patients, all correlations tested were positive (all p < 0.0001). The highest coefficients were seen for the correlations between A.M./P.M. PRIOR total five-symptom score and interference with ADL (r = 0.72) and between A.M. NOW congestion and ADL interference (r = 0.69). Continuous daily treatment of moderate-to-severe PER with desloratadine at 5 mg/day significantly improved symptoms, which correlated positively, albeit moderately, with QOL benefits and reversal of functional impairments caused by PER.

Effects of intranasal mometasone furoate on itchy ear and palate in patients with seasonal allergic rhinitis.

BACKGROUND: Intranasal steroids relieve nasal symptoms and ocular itch in allergic rhinitis. Itchy ear and palate are also common and bothersome symptoms but have received little attention in clinical trials of allergic rhinitis. OBJECTIVE: To ascertain the efficacy of mometasone furoate nasal spray in alleviating itchy ear and palate in seasonal allergic rhinitis. METHODS: Data were pooled from 4 randomized, double-blind, placebo-controlled trials of mometasone furoate nasal spray, 200 µg/d. Participants rated ear and palate itching from baseline through treatment day 15 as follows: 0, none; 1, mild; 2, moderate; and 3, severe. RESULTS: A total of 962 study participants received mometasone furoate nasal spray or placebo. Baseline least squares mean itchy ear and palate score was 1.81 for participants receiving mometasone furoate nasal spray (n = 480) and 1.85 for participants receiving placebo (n = 482). Mometasone furoate nasal spray was associated with a greater decrease in itchy and ear palate score vs placebo during the 15-day study period (least squares mean change, -0.73 vs -0.45; P < .001). The difference reached significance on day 2 and persisted through day 15 (P ≤ .01 for each day). Results were similar in a subgroup of patients (n = 305) with moderate-to-severe symptoms at baseline. Adverse events with mometasone furoate nasal spray were similar to those observed in other studies of intranasal steroid therapy. CONCLUSION: These preliminary findings suggest that mometasone furoate nasal spray effectively treats itchy ear and palate in individuals with seasonal allergic rhinitis. Itchy ear and palate is a relevant end point for future clinical trials of allergic rhinitis.

Mometasone furoate nasal spray provides early, continuing relief of nasal congestion and improves nasal patency in allergic patients.

BACKGROUND: Patients report nasal congestion as the most bothersome seasonal allergic rhinitis (SAR) symptom. Measurement of this symptom in previous research has largely been based on subjective patient ratings. This study was designed to measure efficacy, onset, and duration of action of the corticosteroid mometasone furoate nasal spray (MFNS) on nasal congestion using an environmental exposure chamber (EEC) and the objective assessment acoustic rhinometry (AcR). METHODS: In a randomized, double-blind, placebo-controlled study, ragweed-sensitive subjects were exposed to ragweed pollen (3500 ± 500 pollen grains/m(3)) in an EEC (day 1). Subjects rated instantaneous total nasal symptom score (TNSS), including NSS for congestion (NSS-C). Qualifying subjects received MFNS, 200 micrograms, or placebo and rated postdosing symptoms; a subset received MFNS, 200 micrograms, or placebo q.d. for 6 subsequent days, returning to EEC on day 8. Days 1 and 8 assessments included AcR, TNSS, and the Rhinoconjunctivitis Quality of Life Questionnaire developed for use in the EEC (RQOLQ-EEC). RESULTS: At day 1, hour 6, patients receiving MFNS (n = 155) reported significantly reduced congestion versus placebo (n = 155) per AcR and NSS-C after one dose, showing numerically superior TNSS change from baseline (p = NS). Among the subset who received 6 additional days of treatment, MFNS (n = 78) yielded significantly lower TNSS versus placebo (n = 77) before day 8 EEC entry and throughout 4-hour exposure (p < 0.05), except at 3.5 hours. AcR showed lower congestion with MFNS versus placebo before day 8 EEC exposure and at 24 and 26 hours after final dose (p < 0.05 for all). AcR and NSS-C correlated at multiple time points. Day 8 RQOLQ-EEC between-group scores were significantly different (p = 0.02) for practical problems. CONCLUSION: MFNS, 200 micrograms, showed onset of nasal congestion relief at 6 hours and duration of action beyond 24 hours postdosing. Objective and subjective assessments were correlated in subjects with maximal (placebo) or minimal (MFNS treatment) congestion symptoms; both assessments were correlated with improved QOL.

Intranasal mometasone furoate therapy for allergic rhinitis symptoms and rhinitis-disturbed sleep.

BACKGROUND: Allergic rhinitis (AR) and related nasal congestion cause rhinitis-disturbed sleep (RDS). Intranasal corticosteroids reduce nasal congestion and improve sleep quality in AR but have not been extensively studied in RDS. OBJECTIVE: To evaluate the efficacy of mometasone furoate nasal spray (NS) on nasal symptoms, nasal patency, sleep variables, quality of life, and daytime functioning in perennial AR (PAR) and concomitant RDS. METHODS: In this double-blind 4-week study, 30 adults with PAR and moderate RDS were randomized 2:1 to receive mometasone furoate NS, 200 microg, or placebo each morning. The primary end point was the apnea-hypopnea index. Secondary outcome measures included changes in total nasal symptom score (TNSS), nighttime symptom score, daytime peak nasal inspiratory flow, nighttime flow limitation index, Rhinoconjunctivitis Quality of Life Questionnaire-Standardized (RQLQ-S) score, Epworth Sleepiness Scale score, and Work Productivity and Activities Impairment-Allergy Specific (WPAI-AS) questionnaire score. Analysis of covariance was used for all efficacy end points. RESULTS: The apnea-hypopnea index at study end was not statistically significantly different between groups. However, mometasone furoate NS therapy significantly improved morning (P = .04) and evening (P = .01) TNSSs, morning (P = .049) and evening (P = .03) nasal obstruction/blockage/congestion, daily peak nasal inspiratory flow (P = .03), flow limitation index (P = .02), Epworth Sleepiness Scale score (P = .048), RQLQ-S score (P = .03), and 2 of 5 WPAI-AS domains. Among patients receiving mometasone furoate NS, TNSS improvements were significantly correlated with improved work- and non-work-related productivity. CONCLUSIONS: In patients with PAR and RDS, mometasone furoate NS use improved nasal symptoms, sleepiness, and impairment in daily activities. Correlated reduced nasal symptoms and improved performance suggest that improving AR symptoms with mometasone furoate NS administration can benefit sleep and daytime functioning.

Observational study comparing intranasal mometasone furoate with oral antihistamines for rhinitis and asthma.

AIMS: Retrospective database study comparing upper and lower airway-related outcomes for patients with rhinitis and co-morbid asthma receiving mometasone furoate--an intranasal corticosteroid with low systemic bioavailability--or an oral antihistamine. METHODS: 395 patients prescribed intranasal mometasone were matched on 10 demographic and respiratory-related criteria in a 1:2 ratio to 790 patients prescribed oral antihistamine. Asthma and rhinitis control were assessed over one year using predefined composite proxy measures. RESULTS: Asthma control was achieved by 309/395 (78.2%) versus 580/790 (73.4%; p=0.071) patients in the mometasone and antihistamine cohorts, respectively. Rhinitis control was achieved by 293 (74.2%) versus 539 (68.2%; p=0.035), respectively. The adjusted odds ratios for antihistamines, relative to mometasone, were 0.71 (95% CI, 0.52-0.98) for achieving asthma control and 0.74 (95% CI, 0.56-0.97) for achieving rhinitis control. CONCLUSIONS: Patients with rhinitis and co-morbid asthma initiating rhinitis therapy achieved significantly better upper as well as lower airway outcomes with intranasal mometasone than with oral antihistamine.