Serious asthma events with mometasone furoate plus formoterol compared with mometasone furoate.

BACKGROUND: The safety of long-acting ß-agonists added to inhaled corticosteroids for the treatment of persistent asthma has been controversial. OBJECTIVE: We sought to determine whether administering formoterol in combination with mometasone furoate increases the risk of serious asthma outcomes (SAOs) compared with mometasone furoate alone. This clinical trial is registered as NCT01471340. METHODS: We conducted a 26-week, randomized, double-blind trial in adolescent and adult patients (≥12 years) with persistent asthma in 35 countries with the primary objective of evaluating whether mometasone furoate-formoterol increases the risk of SAOs (adjudicated hospitalization, intubation, or death) compared with mometasone furoate alone. The key efficacy end point was asthma exacerbation (composite of hospitalization of ≥24 hours, emergency department visits of <24 hours requiring systemic corticosteroids, or use of systemic corticosteroids for ≥3 consecutive days). RESULTS: Among 11,729 patients (mometasone furoate-formoterol, n = 5,868; mometasone furoate, n = 5,861), a total of 81 SAOs, all asthma-related hospitalizations, were observed in 71 patients: 45 events from 39 patients receiving mometasone furoate-formoterol and 36 events from 32 patients receiving mometasone furoate. The hazard ratio for the first SAO in the mometasone furoate-formoterol versus mometasone furoate group was 1.22 (95% CI, 0.76-1.94; P = .411). Asthma exacerbation occurred in 1,487 patients: 708 receiving mometasone furoate-formoterol and 779 receiving mometasone furoate. The hazard ratio for the first asthma exacerbation in the mometasone furoate-formoterol versus mometasone furoate group was 0.89 (95% CI, 0.80-0.98; P = .021). CONCLUSIONS: The addition of formoterol to mometasone furoate maintenance therapy did not increase the risk of serious asthma-related events and reduced the risk of asthma exacerbation.

Effect of cetirizine on symptom severity and quality of life in perennial allergic rhinitis.

The effect of cetirizine on quality of life (QOL) in subjects with perennial allergic rhinitis (PAR) has been previously evaluated using generic instruments. While generic QOL tools are used across various conditions, disease-specific instruments evaluate the impact of treatment on areas that are affected by that particular condition. This study evaluated the effect of cetirizine on symptom severity and health-related QOL, using a disease-specific instrument, in adults with PAR. This randomized, double-blind, placebo-controlled study was conducted at 15 U.S. centers outside the pollen allergy season. After a 1-week placebo run-in period, qualified subjects aged 18-65 years with PAR were randomized to once-daily cetirizine 10 mg (n = 158) or placebo (n = 163) for 4 weeks. Change from baseline in total symptom severity complex (TSSC) and overall Rhinitis Quality of Life Questionnaire (RQLQ) scores were primary efficacy end points. Cetirizine produced significantly greater improvements in mean TSSC for each treatment week (p < 0.05) and for the entire 4-week treatment period (p = 0.005) compared with placebo. After 4 weeks, cetirizine-treated subjects reported significantly greater overall improvement in RQLQ scores compared with placebo-treated subjects (p = 0.004). After 1 week, cetirizine produced significant improvements in the nasal symptoms, practical problems, and activities RQLQ domain scores compared with placebo (p < 0.05). After 4 weeks, cetirizine-treated subjects reported significant reductions in these RQLQ domain scores and in emotion domain scores compared with placebo-treated subjects (p < 0.05). Cetirizine 10 mg daily produced significant improvements in symptom severity and allergic rhinitis-related QOL compared with placebo in adults with PAR.

Characterization of Moderate and Severe Asthma Exacerbations in the CAPTAIN Study.

BACKGROUND: Limited data exist on the relative impact of moderate and severe exacerbations on asthma control and impairment. OBJECTIVE: To explore data from the CAPTAIN trial to evaluate the relationship between first moderate or severe exacerbation and changes in lung function, symptoms, physical activity limitation scores, and short-acting ß2-agonist (SABA) usage to determine the clinical relevance of moderate events. METHODS: CAPTAIN was a phase IIIA 24- to 52-week, multicenter, international, randomized controlled trial evaluating efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in patients with uncontrolled asthma on inhaled corticosteroid/long-acting ß2-agonist. Outcomes reported include first postrandomization exacerbation event by severity (wk 1-52), frequency and duration of moderate and severe exacerbations, and time course of changes over ± 14-day peri-exacerbation period for lung function, symptoms, limitations, and SABA use. RESULTS: Of the intent-to-treat population (n = 2,436), 550 patients (23%) continued to 52 weeks. There were 529 moderate and 546 severe exacerbations. Lung function changes were similar, but symptom, physical activity limitation scores, and SABA use were higher, for severe versus moderate exacerbations. Lung function decline preceded increases in symptom, physical activity limitation scores, and SABA use, irrespective of exacerbation severity. Lung function variables, limitation scores, and SABA use returned to pre-exacerbation baseline after approximately 8 to 12 days for both exacerbation severities. CONCLUSIONS: Whereas severe events were associated with greater impact on symptoms, physical activity limitations, and SABA use, onset and time to resolution were generally similar for moderate and severe events. Both exacerbation severities represent clinically important deteriorations comprising clinical and functional changes.

Asthma control, cost and race: results from a national survey.

OBJECTIVE: Although interventions have been shown to alleviate symptoms in most patients suffering from asthma, only one-third of asthma patients have disease that is well-controlled. The purpose of this study is to investigate whether partly and uncontrolled asthmas are associated with increased costs for asthma-related healthcare utilization compared to well-controlled asthma and to determine whether these associations differed across racial groups. METHODS: We classified respondents from the Asthma Insights and Management survey into those with well-, partly and uncontrolled asthma and compared utilization of healthcare services and costs among these groups, as well as between whites and non-whites. RESULTS: Respondents categorized as having asthma that was not well-controlled reported lower income levels, higher rates of unemployment and more trouble paying for healthcare; similar results were found in analyses stratified by race. Patients whose asthma was partly or uncontrolled had greater use of asthma-related medications and medical services compared to patients whose asthma was well-controlled. Total unadjusted and adjusted costs were greater in patients whose asthma was classified as partly and uncontrolled. Similar results were found in analyses stratified on race. Across all levels of asthma control, non-whites had higher rates of utilization of emergency rooms and urgent care facilities and had greater rates of hospitalizations compared to whites. CONCLUSIONS: Our findings indicate that patients with asthma that is not well-controlled utilized more healthcare resources and had greater medical costs, despite lacking of health insurance which may suggest less access to care.

Associations of patient outcomes with level of asthma control.

BACKGROUND: Despite effective medications, asthma remains a significant burden to the US health care system. OBJECTIVE: To determine whether partly and uncontrolled asthma in respondents to the Asthma Insights and Management (AIM) survey was associated with adverse outcomes (such as visits to health care professionals and medication use) compared with well-controlled asthma. METHODS: The AIM survey, conducted in 2009, included 2,500 patients with asthma who were 12 years or older. We classified patients into levels of control and compared use of health care services and limitations of activities in patients whose asthma was well controlled vs those with partly and uncontrolled asthma. RESULTS: Patients who reported lower income and educational status and lacked health insurance were less likely to have had well-controlled asthma. Respondents with uncontrolled asthma were more likely to report ever use of oral steroids (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.9-3.2) and over-the-counter medicine (OR, 2.7; 95% CI, 2.0-3.7) compared with patients whose asthma was well controlled. Respondents with partly and uncontrolled asthma were also significantly more likely to report ever visiting physicians, specialists, or the emergency department or being hospitalized for asthma compared with those whose asthma was well controlled (ORs ranging from 2.1 to 5.6). Finally, respondents whose asthma was uncontrolled had increased odds (ORs ranging from 14 to 34) of reporting that asthma limited their activities compared with respondents whose asthma was well controlled. CONCLUSION: Patients with partly and uncontrolled asthma defined by international guidelines reported use of significantly more health care resources and greater limitations of their daily activities compared with patients whose asthma was well controlled.

The CHOICE survey: high rates of persistent and uncontrolled asthma in the United States.

BACKGROUND: Surveys have consistently shown that many patients with asthma do not have their disease well controlled. OBJECTIVES: The CHOICE (Comprehensive Survey of Healthcare Professionals and Asthma Patients Offering Insight on Current Treatment Gaps and Emerging Device Options) survey was designed to evaluate the current status of inhalation devices used in asthma treatment, but questions also were included about asthma severity and control. METHODS: A total of 1,000 patients with asthma were interviewed about their use of inhalation devices and asthma-related burden, medication use, and hospital/emergency care. Based on the responses to these questions, asthma severity and control were categorized using methods established in the Expert Panel Report III (EPR 3). RESULTS: Almost half (490) of the patients with asthma participating in the CHOICE survey were not using controller medications. Most of those not using controllers (79%) had persistent asthma; 47% had either mild or moderate persistent asthma. Of those on controllers (510), only 14.3% were well controlled. Acute care utilization was greater for patients with persistent asthma than those with intermittent asthma and for patients with not well and poorly controlled asthma than those with well-controlled asthma. CONCLUSION: The CHOICE survey is particularly pertinent clinically, because it demonstrates for the first time, using EPR 3 methods, the current extent of poor asthma control in the United States. This situation falls far short of national asthma management targets.

Safety and efficacy of fluticasone/formoterol combination therapy in adolescent and adult patients with mild-to-moderate asthma: a randomised controlled trial.

BACKGROUND: This study investigated the efficacy and safety of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol; flutiform®), administered twice daily (b.i.d.) via a single aerosol inhaler, compared with its individual components administered separately and placebo, in patients with mild-to-moderate asthma. METHODS: Patients aged ≥ 12 years were evenly randomised to 12 weeks of treatment with fluticasone/formoterol (100/10 µg b.i.d.), fluticasone (100 µg b.i.d.), formoterol (10 µg b.i.d.), or placebo, in this double-blind, parallel group, multicentre study. The three co-primary endpoints were: a) change in forced expiratory volume in the first second (FEV(1)) from morning pre-dose at baseline to pre-dose at week 12 for the comparison with formoterol; b) change in FEV(1) from morning pre-dose at baseline to 2 hours post-dose at week 12 for the comparison with fluticasone, and c) time to discontinuation due to lack of efficacy from baseline to week 12 for the comparison with placebo. Safety was assessed based on adverse events, clinical laboratory tests and vital sign evaluations. RESULTS: Statistically significant differences were demonstrated for all the three co-primary endpoints. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in pre-dose FEV(1) compared with formoterol (Least Squares (LS) mean treatment difference: 0.101 L; 95% Confidence Interval (CI): 0.002, 0.199; p = 0.045) and the change in pre-dose compared with 2 hours post-dose FEV(1) versus fluticasone (LS mean treatment difference: 0.200 L; 95% CI: 0.109, 0.292; p < 0.001). The time to discontinuation due to lack of efficacy was significantly longer for patients in the combination therapy group compared with those receiving placebo (p = 0.015). Overall, the results from multiple secondary endpoints assessing lung function, asthma symptoms, and rescue medication use supported the superior efficacy of the combination product compared with fluticasone, formoterol, and placebo. The fluticasone/formoterol combination therapy had a good safety and tolerability profile over the 12 week treatment period. CONCLUSIONS: Fluticasone/formoterol had a good safety and tolerability profile and showed statistically superior efficacy for the three co-primary endpoints compared to fluticasone, formoterol, and placebo, in adolescents and adults with mild-to-moderate asthma. EudraCT number: 2007-002866-36; US NCT number: NCT00393991.

Asthma management and control in the United States: results of the 2009 Asthma Insight and Management survey.

Past asthma surveys have shown suboptimal management and control of asthma in the United States. No major survey of asthma management has been conducted since the Third Expert Panel Report for the National Asthma Education and Prevention Program (NAEPP) guidelines on diagnosis and treatment of asthma (August 2007). This study was designed to report asthma management and control results from the Asthma Insight and Management survey of U.S. patients and physicians. A telephone-based survey was conducted during 2009 in 2500 patients with asthma, aged ≥12 years, and 309 physicians (104 allergists, 54 pulmonologists, 101 family practitioners, and 50 internists). Patients' asthma control perceptions (71% "completely controlled" or "well controlled") were inconsistent with their NAEPP control level as determined by self-reported symptoms (29% well controlled). Patients and physicians had low expectations for effective asthma management; patients considered asthma well managed if rescue medication was used three times per week (46%), urgent care visits occurred twice per year (67%), or emergency department visits occurred once per year (60%). Asthma-related syncope, seizure, intensive care unit admission, and intubation were associated with uncontrolled asthma based on NAEPP guidelines. Respiratory specialists (allergists/pulmonologists) implemented asthma management recommendations more than other physicians surveyed. However, only 22% of patients visited a specialist for usual asthma care and 48% had never visited a specialist. Despite detailed NAEPP guidance, asthma management and control in U.S. patients is unsatisfactory. Improved asthma control assessment (impairment and risk) and implementation of NAEPP management recommendations are needed to improve asthma control and outcomes.

Asthma burden in the United States: results of the 2009 Asthma Insight and Management survey.

Updated guidelines and new treatments for asthma have become available since the last major survey of asthma management in the United States was completed ∼11 years ago. The Asthma Insight and Management (AIM) survey was conducted to assess the current status of asthma burden in the United States. A geographically stratified screening of 60,682 households provided a national sample of 2500 patients with current asthma (2186 adults aged ≥18 years; 314 adolescents aged 12-17 years). A national sample of 1004 adults without current asthma was interviewed for comparison with the adult asthma population, and 309 asthma health care providers were surveyed for their opinions about the burden of asthma. Asthma prevalence in the United States was estimated at 8%. Twice as many adult asthma patients rated their health as "only fair," "poor," or "very poor," or experienced limitations in activity because of health problems, compared with the general population. Asthma also frequently caused negative emotional symptoms in patients. Most patients experienced asthma throughout the year (63%) and symptoms within the 4 weeks before the summer survey (68%). Overall, 41% of patients responded that asthma interfered with their/their child's life "some" or "a lot". During the year before the survey, 69% of patients experienced at least one severe asthma episode. Asthma burden in the United States remains high despite the availability of updated treatment guidelines and new therapies. Asthma care in the United States remains suboptimal, indicating the need for continued improvements in patient management.

Patient and physician asthma deterioration terminology: results from the 2009 Asthma Insight and Management survey.

Long-term achievement of asthma control is dependent in part on the use of mutually understandable asthma terminology in all verbal and written patient-physician communications. Using data from the Asthma Insight and Management (AIM) survey, the objective of this analysis is to provide a contemporary depiction of asthma deterioration terminology as used by current asthma patients and physicians in the United States. As part of the 2009 AIM survey, current asthma patients (≥12 years of age; weighted n = 2499) and physicians (n = 309) were queried about their recognition, understanding, and/or use of the terms "asthma attack," "asthma flare-up," and "asthma exacerbation" in telephone interviews. Nearly all patients had heard the term "asthma attack" (97%), but relatively few had heard the term "asthma exacerbation" (24%); 71% had heard "asthma flare-up." In contrast, physicians reported using the term "asthma attack" least (65%) and the term "asthma exacerbation" most (77%) when discussing asthma with their patients; 70% reported using "asthma flare-up." Among patients familiar with "asthma flare-up" and "asthma exacerbation" (n = 502), only 38% said that the terms mean the same thing; nearly all physicians (94%) said that the terms mean the same thing. Collectively, data from the AIM survey suggest that patients and physicians use different asthma deterioration terminology and, more importantly, that they do not necessarily understand each other's terms. Standardizing asthma deterioration terminology may help optimize asthma patient-physician communication to improve patient understanding of written asthma action plans and therefore, enhance patient outcomes.

Comparison of the Asthma in America and Asthma Insight and Management surveys: did asthma burden and care improve in the United States between 1998 and 2009?

Significant changes in asthma treatment guidelines and therapies occurred between the period of time in which the Asthma in America (AIA) and Asthma Insight and Management (AIM) surveys were conducted: 1998 and 2009, respectively. This study compares asthma burden and management in 1998 and 2009. Both surveys were telephone based and conducted across the United States. The AIA survey included 2509 patients with asthma (aged <1 year to 89 years old), 512 physicians, and 1000 adults from the general population. The AIM survey included 2500 patients (aged ≥12 years), 309 physicians, and 1090 adults from the general population. Patient responses were weighted to match the entire population of U.S. patients with asthma. The impact of asthma burden and care on the general population and on asthma patients was slightly lower or unchanged in the AIM survey versus the AIA survey. Acute care use (hospitalizations, emergency department visits, or other urgent care visits) was common in AIA (36%) and AIM (34%) surveys. Most physicians were aware of guidelines in AIA (90%) and AIM (96%), but fewer "always" followed them (AIA, 36%; AIM, 28%). Spirometry was often used to aid in diagnosis by asthma care specialists (AIA, 73%; AIM, 76%) but infrequently by nonsubspecialists (AIA, 27%; AIM, 38%). Most physicians prescribed inhaled corticosteroids (ICSs) for mild (AIA, 70%; AIM, 83%) or moderate (AIA, 89%; AIM, 83%) persistent asthma. In the AIM survey, 38% of specialists prescribed ICSs combined with a long-acting ß2-agonist for moderate asthma. The state of U.S. asthma care and clinical outcomes changed little from 1998 to 2009.

Patient satisfaction with a pressurized metered-dose inhaler with an integrated dose counter containing a fixed-dose mometasone furoate/formoterol combination.

INTRODUCTION: Inhaled delivery devices that are easy to use and facilitate dose tracking may lead to improved patient satisfaction and adherence. Patient satisfaction with a metered-dose inhaler (MDI) with an integrated dose counter containing a fixed-dose mometasone furoate/formoterol combination (MF/F MDI dose counter) was evaluated in subjects with persistent asthma or chronic obstructive pulmonary disease. METHODS: In this multicenter study (N = 272, age range: 12-92 years), subject experience and satisfaction with MDI devices was evaluated using baseline and poststudy surveys. Subjects responded to the baseline survey based on their previous MDI experience, then received MF/F MDI 100/10 µg with the integrated dose counter for 4 weeks before completing the poststudy survey. This evaluation was part of a broader study objective to assess performance of the MF/F MDI dose counter. RESULTS: At baseline, 52% of subjects reported being extremely satisfied with their previous MDI. After using the MF/F MDI dose counter, a relative increase of 43% in overall satisfaction was observed. Approximately 90% of subjects agreed the MF/F dose counter helped them track doses and was easy to use; >80% agreed the inhaler was of good quality and well designed. Subjects agreed the dose counter relieved anxiety about running out of medication (68%) or taking a subtherapeutic dose (65%). Nearly 80% of subjects had no reservations about the MF/F MDI dose counter, and most subjects stated they would request it from their physician (66%) and recommend it to a friend (75%). CONCLUSIONS: The MF/F MDI dose counter was found to be easy to use and have overall high patient satisfaction.

Twenty-six-week efficacy and safety study of mometasone furoate/formoterol 200/10 microg combination treatment in patients with persistent asthma previously receiving medium-dose inhaled corticosteroids.

Asthma is a heterogeneous condition characterized by reduced lung function, chronic inflammation, and periodic asthma deteriorations. This study was performed to evaluate the effect of mometasone furoate (MF)/formoterol (F) combination, 200/10 microg, administered twice daily (b.i.d.) on asthma deteriorations and pulmonary function in patients with asthma uncontrolled on medium-dose inhaled corticosteroid (ICS). After 2- to 3-week open-label run-in with MF 200 microg b.i.d., patients (>or=12 years) were randomized to 26 weeks of treatment with MF/F 200/10 microg, MF 200 microg, F 10 microg, or placebo b.i.d. Coprimary end points were time to first asthma deterioration (MF/F versus F) and bronchodilation, assessed by the area under the curve of the change in forced expiratory volume in 1 second 0-12 hours (FEV(1) AUC(0-12h); MF/F versus MF). A total of 781 patients were randomized. Treatment with MF/F 200/10 microg reduced asthma deteriorations and clinically judged deteriorations (i.e., deterioration resulting in emergency treatment, hospitalization, or treatment with additional excluded asthma medication [i.e., systemic corticosteroids]). The proportion of patients experiencing asthma deteriorations was MF/F, 30.4%; MF, 33.9%; F, 54.0%; placebo, 55.6% (p < 0.001, MF/F versus F and placebo). There was a sixfold reduction in clinically judged deteriorations with MF/F versus F and placebo (p < 0.001). Lung function improved more rapidly with MF/F than MF and placebo. Mean change from baseline FEV(1) AUC(0-12h) at week 12 was MF/F, 11.7% versus MF, 5.7%; F, 8.5%; and placebo, 3.9% (p < 0.001). Treatment-related AEs were rare and similar across groups. Treatment with MF/F 200/10 microg was effective in reducing the risk of asthma deteriorations. MF/F was safe and provided rapid and sustained bronchodilation in patients with asthma.

Serious Asthma Outcomes and Asthma Exacerbations with Maintenance on Inhaled Corticosteroid (Mometasone Furoate)/Long-Acting Beta Agonist (Formoterol) Combination Compared to Step Down to Mometasone Monotherapy.

BACKGROUND: Because of historical safety concerns with the use of long-acting ß-agonists (LABA) in asthma, step-down from inhaled corticosteroid (ICS)/LABA combination therapy to ICS monotherapy is recommended once asthma control is achieved. OBJECTIVE: To evaluate the benefit/risk question about whether patients with asthma who achieve disease control on fixed-dose ICS/LABA combination therapy, such as mometasone furoate/formoterol fumarate (MF/F), should continue with this therapy or be stepped down to ICS monotherapy, such as MF. METHODS: Using data from 8447 clinically stable patients with persistent asthma in the Safety Pharma Investigation of Respiratory Outcomes trial who had been receiving a stable dose of ICS/LABA for ≥4 weeks, this post hoc analysis evaluated the risk of serious asthma outcomes (SAOs) (adjudicated hospitalization, intubation, or death) and asthma exacerbation (AEX) (composite of hospitalizations ≥24 hours, emergency visits <24 hours requiring systemic corticosteroid, or systemic corticosteroid for ≥3 consecutive days) in participants randomized to remain on ICS/LABA (MF/F) or step down to ICS (MF) for 26 weeks. RESULTS: There was no significant difference in SAO risk among patients maintained on ICS/LABA with MF/F compared with those who stepped down from ICS/LABA to MF (hazard ratio [HR], 1.03 [95% confidence interval (CI): 0.61, 1.75], P = .913). The risk of AEX was significantly lower in patients maintained on ICS/LABA with MF/F compared with those who stepped down from ICS/LABA to MF (HR, 0.87 [95% CI: 0.78, 0.98], P = .020). CONCLUSIONS: In this post hoc analysis of a large clinical trial dataset, maintenance on ICS/LABA with MF/F is not associated with an increased risk of SAOs and also significantly reduces the risk of AEX compared with step-down from ICS/LABA to MF.

Management of patients with allergic rhinitis and asthma: literature review.

Allergic rhinitis (AR) and asthma are disorders of the airway characterized by inflammation of the respiratory mucosa. The presence of one disorder increases the likelihood that the other will also occur. As they are mechanistically intertwined, one can exacerbate the other when both conditions are present. In addition, comorbid AR and asthma have an additive impact on patients' health-related quality of life. The Allergic Rhinitis and its Impact on Asthma (ARIA) recommendations suggest that asthma patients should be evaluated for AR, and all AR patients should undergo tests for asthma. They also suggest that ideally, a combined strategy should be used to treat the upper and lower airway diseases. While treatment for AR includes antihistamines, intranasal glucocorticosteroids, antileukotrienes, and specific immunotherapy, data suggest that these treatment approaches may also improve asthma outcomes. This article reviews current clinical approaches to the diagnosis and management of patients with comorbid AR and asthma.

Intranasal mometasone furoate alleviates the ocular symptoms associated with seasonal allergic rhinitis: results of a post hoc analysis.

BACKGROUND: Burdensome symptoms of allergic rhinitis (AR) include nasal and ocular symptoms such as itching, tearing and redness. Intranasal corticosteroids are efficacious in the treatment of nasal symptoms of AR. OBJECTIVE: It was the aim of this study to determine the efficacy of the intranasal corticosteroid mometasone furoate nasal spray (MFNS) in relieving ocular symptoms associated with seasonal AR (SAR). METHODS: Ocular symptom data were analyzed for subjects >or=12 years of age, randomized to MFNS 200 mug q.d. (n = 176) or placebo (n = 177) in a placebo-controlled, double-blind clinical trial. Post hoc efficacy analysis assessed the mean change from baseline in subject-reported total ocular symptom scores (TOSS) averaged over the treatment period. RESULTS: Mean baseline TOSS was 4.91 for the MFNS group and comparable (5.05) for the placebo group - combined average for individual symptoms such as itching, tearing and redness ranged from 0 (no symptoms) to 9 (all symptoms, severe). Mean change from baseline in TOSS averaged over days 1-15 was -1.42 for the MFNS group and -0.94 for the placebo group (p = 0.02), for an observed treatment difference of 0.49 (statistical data rounded to 2 decimal positions). Improvement in individual symptoms (eye itching, tearing and redness) contributed to this treatment effect; the greatest improvement occurred with tearing, which decreased -0.52 from the baseline score 1.59 in the MFNS group and -0.31 from 1.67 in those receiving placebo (p < 0.01), for an observed treatment difference of 0.21. Treatment with MFNS was safe and well tolerated. CONCLUSION: MFNS is effective in reducing ocular symptoms of SAR, in addition to its established efficacy in reducing nasal symptoms of SAR.

The pathophysiology, clinical impact, and management of nasal congestion in allergic rhinitis.

BACKGROUND: Nasal congestion is a cardinal symptom of allergic rhinitis (AR). It is difficult to treat and is associated with decreased quality of life. OBJECTIVE: This article reviews the clinical features of nasal congestion, its complex pathophysiology in the context of AR, its clinical impact, and the strengths and weaknesses of available treatments. METHODS: Primary studies and reviews in the peer-reviewed, English-language literature were identified through searches of MEDLINE (1966-2008) and the Cochrane Library (1996-2008) using the terms nasal congestion, allergic rhinitis, pathophysiology, quality of life, and burden. Additional references were obtained by searching the reference lists of the identified articles. Abstracts from the 2006 and 2007 meetings of the American Academy of Allergy, Asthma, and Immunology were also searched. Pertinent articles were included in the review if they were recently published and patient-focused, and if their authors were recognized leaders in the field. RESULTS: A survey of 2355 patients with AR or their guardians found that almost half of respondents rated nasal congestion the most bothersome symptom; in a survey of 2500 adults with AR, 78% rated nasal congestion either extremely or moderately bothersome. Histamine and leukotrienes are major mediators of the allergic inflammation associated with nasal congestion, as indicated by reductions in nasal cross-sectional area in response to histamine challenge (P<0.001) and increases in nasal airway resistance in response to leukotriene challenge (P<0.05).Therapy for nasal congestion in AR is often hampered by limitations associated with the individual agents; for example, decongestants are effective in the control of nasal congestion, but their use is restricted by their adverse-event profiles. A meta-analysis of 16 controlled studies involving 2267 patients with AR found that intranasal corticosteroids provided significantly greater relief of nasal congestion than oral antihistamines (95% CI for combined standardized mean difference, -0.73 to -0.53). The results of several clinical trials have suggested that leukotriene-receptor antagonists may be associated with reduced nasal congestion; however, no agents in this class are currently approved for the treatment of nasal congestion in AR. CONCLUSION: There is a need for therapies that are well tolerated and effective in relieving nasal congestion in AR.

Efficacy and safety of fluticasone propionate/salmeterol 250/50 mcg Diskus administered once daily.

BACKGROUND: The twice daily administration of an inhaled corticosteroid (ICS) and long-acting beta(2)-agonist (LABA) has been shown to be effective in achieving asthma control. The once daily administration of an ICS/LABA may be a treatment option for some patients. OBJECTIVE: To assess the effectiveness of fluticasone propionate (FP)/salmeterol via a single inhaler (FSC) administered once daily compared with FP once daily, FSC twice daily, or placebo. METHODS: A 12-week, randomized, double-blind multicenter study conducted in 844 patients > or = 12 years of age who were symptomatic while using a short-acting beta(2)-agonist alone. Blinded treatments included: FSC 250/50 mcg once daily in the evening (FSC 250/50 QD), FP 250 mcg once daily in the evening (FP 250 QD), FSC 100/50 mcg twice daily (FSC 100/50 mcg BID), or placebo. All treatments were delivered via the Diskus device. RESULTS: All treatments demonstrated greater improvements in efficacy measures compared with placebo. Overall, the greatest improvements were observed in the patients receiving FSC, either once or twice daily, compared with the FP 250 QD group. The two FSC treatments were similar except that QD dosing did not maintain improvements in lung function for 24h compared with twice daily dosing. All treatments were well tolerated. No suppression of HPA axis, as assessed by 24-h urinary cortisol excretion, was observed in any of the active treatment groups. CONCLUSION: In patients symptomatic on a short-acting beta(2)-agonist alone, FSC 100/50 mcg BID was shown to provide better efficacy than a higher strength (FSC 250/50 mcg) administered once daily. However, a once daily regimen was effective and may be a valuable treatment option for some patients. Registered at (http://ctr.gsk.co.uk/welcome.asp) (SAS30022).

Rhinitis symptoms and comorbidities in the United States: burden of rhinitis in America survey.

OBJECTIVE: To assess the burden of nasal symptoms in the United States (U.S.) and the comorbid conditions associated with nasal symptoms. SUBJECTS AND METHODS: A self-administered screening questionnaire and follow-up survey was sent to targeted households from a representative sample of 15,000 households in the U.S. Subjects with comorbid asthma completed the Asthma Control Test (ACT). RESULTS: Out of 7024 evaluable subjects who responded, 3831 subjects were classified as rhinitis "sufferers." Individuals with active rhinitis symptoms were 1.5 to 4.5 times more likely to suffer from comorbid conditions including asthma, conjunctivitis, otitis media, sinusitis, eczema, food and insect bite allergies, migraine, and depression. Almost half of all respondents with moderate or severe rhinitis symptoms and comorbid asthma had poorly controlled asthma as defined by an ACT score of < or =19. CONCLUSIONS: A strong relationship exists between rhinitis symptoms and various comorbidities, including asthma, in the U.S. population. Poorly controlled rhinitis contributes to the public health burden of rhinitis and asthma.

Efficacy and tolerability of fluticasone propionate/salmeterol administered twice daily via hydrofluoroalkane 134a metered-dose inhaler in adolescent and adult patients with persistent asthma: a randomized, double-blind, placebo-controlled, 12-week study.

OBJECTIVE: This study compared the efficacy and tolerability of the combination of fluticasone propionate (FP) and salmeterol (SAL) delivered via a single hydrofluoroalkane (HFA) 134a metered-dose inhaler (MDI) with those of its 2 components alone delivered via a chlorofluorocarbon (CFC) MDI and placebo (PLA) delivered via HFA MDI in adolescent and adult patients with persistent asthma that was not controlled by medium doses (equivalent to FP 440-660 microg/d) of inhaled corticosteroids (ICSs). METHODS: This was a randomized, double-blind,placebo-controlled, parallel-group study consisting of a 2-week, single-blind, placebo run-in period followed by a 12-week, double-blind treatment period. Participants had to be > or =12 years of age and have a diagnosis of asthma requiring pharmacotherapy for at least 6 months before the study. Patients had to have used ICS therapy for > or =3 months before the study and at a consistent dose for the previous month. Lack of asthma control was defined as a forced expiratory volume in 1 second (FEV(1)) that was 40% to 85% of the predicted value. Patients could not enter the double-blind treatment period if they had 3 days when they required >12 puffs of rescue albuterol per day or >3 nighttime awakenings due to asthma that required treatment with albuterol during the 7 days before the randomization visit. Patients were randomized to receive one of the following treatments delivered via MDI twice daily for 12 weeks: FSC 220/42 microg HFA (2 inhalations of FSC 110/21 microg; 125 microg/21 microg ex-valve); FP 220 microg CFC (2 inhalations of FP 110 microg); SAL 42 microg CFC (2 inhalations of 21 microg); or 2 inhalations of PLA HFA. The primary efficacy end point for FSC versus FP was the mean area under the 12-hour serial FEV(1) curve relative to the prerandomization baseline (FEV(1) AUC(bl)). The primary efficacy end points for FSC versus SAL were the mean change from baseline in morning predose FEV(1) at end point and the probability of not being withdrawn from the study due to worsening asthma. Tolerability assessments included electrocardiograms, routine clinical laboratory tests, vital signs, oropharyngeal examinations, and physical examinations. Adverse events were assessed at each clinic visit. RESULTS: Thirty-two adolescent and 333 adult patients were randomly assigned to receive double-blind treatment. The treatment groups were comparable at baseline with respect to demographic characteristics (mean age, 38-41 years; white race, 78%-88%) and pulmonary function (mean percent predicted FEV(1), 68%-69%; mean asthma symptom score, 1.6 [scale 0-5]; and mean daily albuterol use, 3.1 puffs). After 12 weeks of treatment, the mean FEV(1) AUC(bl) was significantly greater in patients who received FSC compared with those who received FP, SAL, or PLA (7.0, 3.6, 5.3, and 1.4 L-h, respectively; all comparisons, P < or = 0.020). At end point, the mean change from baseline in morning predose FEV(1) for FSC was significantly greater than that for FP, SAL, and PLA (0.41, 0.19, 0.15, and -0.12 L; all comparisons, P < or = 0.001). During 12 weeks of treatment, 7% of patients receiving FSC were withdrawn due to worsening asthma, compared with 24% of patients receiving SAL and 54% of patients receiving PLA (P < 0.001); 11% of patients receiving FP were withdrawn due to worsening asthma. Treatment with FSC resulted in significant improvements in morning and evening peak expiratory flow compared with FP, SAL, and PLA (both, P < 0.001); need for rescue albuterol compared with FP and PLA (P < or =0.005); and asthma symptom scores compared with PLA (P < 0.001). The tolerability of FSC was similar to that of FP or SAL alone. The incidence of possibly drug-related adverse events was generally similar across treatment groups, and the most common (occurring in > or= 2% of patients) were headache (1%-4%), throat irritation (1%-2%), candidiasis of the mouth/throat (0%-2%), unspecified oropharyngeal plaques (0%-2%), and palpitations (0%-2%). CONCLUSIONS: In these adolescent and adult patients whose asthma was not controlled by medium doses of an ICS, FSC delivered via HFA 134a MDI (2 inhalations of 110/21-microg strength administered BID) was more effective in improving lung function than FP or SAL monotherapy or PLA. All treatments were well tolerated.