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Background: Due to the high transmissibility of SARS-CoV-2, accurate diagnosis is essential for effective infection control, but the gold standard, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), is costly, slow, and test capacity has at times been insufficient. We compared the accuracy of clinician diagnosis of COVID-19 against RT-PCR in a general adult population., Methods: COVID-19 diagnosis data by 30th September 2021 for participants in an ongoing population-based cohort study of adults in Western Sweden were retrieved from registers, based on positive RT-PCR and clinician diagnosis using recommended ICD-10 codes. We calculated accuracy measures of clinician diagnosis using RT-PCR as reference for all subjects and stratified by age, gender, BMI, and comorbidity collected pre-COVID-19., Results: Of 42,621 subjects, 3,936 (9.2%) and 5705 (13.4%) had had COVID-19 identified by RT-PCR and clinician diagnosis, respectively. Sensitivity and specificity of clinician diagnosis against RT-PCR were 78% (95%CI 77-80%) and 93% (95%CI 93-93%), respectively. Positive predictive value (PPV) was 54% (95%CI 53-55%), while negative predictive value (NPV) was 98% (95%CI 98-98%) and Youden's index 71% (95%CI 70-72%). These estimates were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while specificity, NPV, and Youden's index were similar between patients with and without chronic obstructive pulmonary disease (COPD), sensitivity was slightly higher in patients with (84% [95%CI 74-90%]) than those without (78% [95%CI 77-79%]) COPD., Conclusions: The accuracy of clinician diagnosis for COVID-19 is adequate, regardless of gender, age, BMI, and asthma, and thus can be used for screening purposes to supplement RT-PCR., (© 2023. The Author(s).)

Background: As the prevalence of dog allergy rises, component resolved diagnosis might improve the diagnosis, understanding of the clinical outcomes and the effectiveness of immunotherapy. Considering the paucity of data in adults, the current study characterized the patterns of sensitization to dog molecular allergens in an adult population., Methods: Data were derived from the West Sweden Asthma Study, a population-based and representative sample of adults from western Sweden. Of the 2006 subjects clinically examined, 313 participants sensitized to whole dog allergen extract were measured for specific immunoglobulin E (sIgE) levels to Can f 1, Can f 2, Can f 3, Can f 4, Can f 5 and Can f 6 using ImmunoCAP™. Polysensitization was defined as sensitization to ≥3 components. Overlapping sensitization was defined as having concomitant sensitization to at least two dog molecular allergen families (lipocalin, albumin or prostatic kallikrein)., Results: Of 313, 218 (70%) subjects tested positive to at least one dog allergen component. Sensitization to Can f 1 (43%) was the most common, followed by Can f 5 (33%) among molecular allergens, while sensitization to lipocalins (56%) was the most common among component families. Polysensitization was found in 22% of all participants and was more common in participants with than in those without asthma. Subjects with asthma were less likely to be monosensitized to Can f 5 than those without asthma. Subjects with asthma had higher IgE levels of Can f 3, Can f 4 and Can f 6 than those without asthma. Overlapping sensitizations also differed between those with asthma and allergic rhinitis and those without., Conclusion: Increased knowledge about the sensitization patterns of dog allergen components can aid in defining their role in asthma and rhinitis. In complex clinical cases of dog allergy, a detailed analysis of dog allergen components can provide additional information on the nature of sensitization., (© 2022 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Sensitization to allergen components has been linked to asthma in children, but studies in adults are lacking., Objective: To study the relation of sensitization to furry animal allergen components to risk of asthma, rhinitis, and markers of asthma severity in adults., Methods: From the West Sweden Asthma Study, a random population-representative sample of adults aged 16 to 75 years, 2006 participants were clinically examined; 1872 were analyzed for serum IgE level to a mix of aeroallergens. Those with an IgE level of more than 0.35 kU A /L to cat, dog, or horse allergen components were analyzed for specific cat (Felis domesticus [Fel d 1, Fel d 2, and Fel d 4]), dog (Canis familiaris [Can f 1, Can f 2, Can f 3, and Can f 5]), and horse (Equus caballus [Equ c 1]) allergen components. We defined monosensitization, double sensitization, and polysensitization (>2 components) patterns and applied cluster analysis to derive distinct sensitization clusters., Results: Sensitization to each allergen component, lipocalins, each sensitization pattern, and each sensitization cluster (nonsensitized, Fel d 1-driven sensitized, and multisensitized clusters) was associated with substantial increased risk of asthma, rhinitis, concomitant asthma and rhinitis, and Asthma Control Test-controlled asthma. Fel d 1, Can f 1, Can f 2, Can f 3, polysensitization, and multisensitized cluster were further associated with increased fractional exhaled nitric oxide and eosinophil levels, but with lower PD 20 methacoline (provocative dose of methacholine causing a 20% drop in FEV 1 ) values. There was no association with asthma exacerbations, FEV 1 predicted values, emergency visits or regular oral steroid use, and neutrophil levels., Conclusions: Sensitization to furry animal allergen components is an important predictor of asthma, rhinitis, and markers of asthma severity with increased blood eosinophils, fractional exhaled nitric oxide, and airway hyperreactivity., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: There are paucity of data on sensitization to furry animal allergen components in adults. Furry animals are major sensitizers and contributors to asthma burden in northern Europe and North America., Objective: To characterize sensitization patterns to furry animal allergen components in Swedish adults., Methods: Based on the West Sweden Asthma Study, a random population (n = 1103) and an asthma sample (n = 769) were tested for allergen sensitization using Phadiatop ® . Those with IgE ≥ 0.35 kU A /L were tested for cat (Fel d 1, 2, and 4), dog (Can f 1, 2, 3, and 5), and horse (Equ c 1) allergen component sensitization. We defined allergen component poly-sensitization patterns, identified data-driven sensitization clusters, described component sensitization overlaps, and assessed determinants of sensitization patterns., Results: The prevalence of allergen component sensitization ranged from 0.8% for Fel d 2 and Can f 3 to 8.9% for Fel d 1. The most common dog component was Can f 5 (3.6%); 2.1% were sensitized to Equ c 1. Those sensitized to Fel d 2 and Fel d 4 were commonly sensitized to Fel d 1. The most common dog component overlap was between Can f 1/Can f 2 and Can f 5. Mono-sensitization was 5.6%, double sensitization 1.5% and poly-sensitization 2.1%. Sensitization was always higher in the asthma than in the random sample. Three sensitization clusters were derived, namely non-sensitized (90% in random vs 66% in asthma sample); Fel d 1-driven sensitized (7% vs 19%); and multi-sensitized (3% vs 15%). Key determinants of sensitization were gender, age, raised on a farm, family history of allergy or asthma, smoking, and occupational exposure to dust or fumes., Conclusions & Clinical Relevance: Fel d 1 and Can f 5 are the most common cat and dog components sensitization in this adult Swedish population. Mono-sensitization is more common than poly-sensitization. This detailed characterization highlights the current distribution of furry animal allergen components in Swedish adults, and their impact on clinical outcomes of asthma will be further explored., (© 2019 John Wiley & Sons Ltd.)

Background: The prevalence of asthma severity is not well described at a population level., Objective: We sought to determine the prevalence of phenotypic signs of asthma severity among asthmatic patients in a general population and to describe risk factors for asthma severity., Methods: We performed an epidemiologic study conducted between 2008 and 2012 (West Sweden Asthma Study). A postal questionnaire was sent to a random population (n = 30,000) in west Sweden, with 18,087 responses. A total of 2,006 subjects were carefully phenotyped. Only subjects with "active asthma" (symptoms or medication in the last year, n = 744) were analyzed in this study to determine the degree of severity of the disease within an asthma cohort. Phenotypes of severity were calculated based on (1) multiple symptoms during the day despite ongoing use of asthma medications, (2) FEV 1 of less than 70% of predicted value, (3) daily or almost daily use of rescue medications, (4) nighttime symptoms once a week or more, and (5) oral corticosteroid use/emergency department visits. Asthmatic patients were grouped as having nonsevere disease, 1 sign of severity, or 2 or more signs of severity., Results: A total of 36.2% of asthmatic patients expressed at least 1 sign of asthma severity, and 13.2% had 2 or more signs. The group with 2 or more signs was older in age and had higher body mass index, a higher rate of tobacco smoking, and lower lung function. Bronchial hyperreactivity, airway inflammation, and sensitization were significantly different among the 3 groups. At a population level, the prevalence of asthma severity was 3.1% for 1 sign and 1.3% for at least 2 signs., Conclusion: More than 1 in 3 asthmatic patients show at least 1 sign of asthma severity. The phenotypes of asthma severity are highly diverse, which is important to consider when implementing personalized medicine in asthmatic patients., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Although asthma and chronic obstructive pulmonary disease (COPD) have been regarded as distinct conditions, emerging literature suggests that overlapping phenotypes, called asthma-COPD overlap (ACO), exists. The aim of this study was to describe prevalence, patient characteristics and morbidity of ACO., Methods: From a cross-sectional population sample, the West Sweden Asthma Study, subjects with suspected asthma, chronic bronchitis or COPD, and a random sample, were invited to clinical examinations. ACO was defined as doctor-diagnosed asthma, or clear clinical signs of asthma at examination, with a FEV 1 /FVC < 0.7., Results: Subjects were categorized as ACO (N = 181), COPD only (N = 89), asthma only (N = 651) or healthy (n = 1036) based on clinical examinations. Prevalence of ACO was 3.4% in the random sample (N = 1172) and 18.1% among asthmatics (N = 138) in the random sample. Subjects with ACO (mean age 59 years, 54% women) had an age and gender distribution in between asthma only (45 years, 63% women) and COPD only (62 years, 41% women). Ever-smoking was reported by 71%, 48% and 74% in the ACO, asthma only and COPD only groups, respectively. Subjects with ACO had worse lung function (mean FEV 1 % of predicted normal 76%) than asthma only (100%) and COPD only (87%) and reported more respiratory symptoms. Also respiratory related emergency visits were more common in ACO compared to asthma only and COPD only, respectively., Conclusions: ACO is present in 3.4% of the population and common among subjects with both asthma and COPD. Subjects with ACO had worse lung function and more symptoms than subjects with asthma or COPD only.

Background: Allergic and non-allergic asthma are viewed as separate entities, despite sharing similarities. The aims of this study were to determine differences in symptoms from the upper airways and the skin in allergic and non-allergic asthma. The secondary aims were to identify childhood risk factors and to compare quality of life in the two asthma groups., Methods: This cohort (age 17-76 years) consisted of 575 subjects with allergic or non-allergic asthma and 219 controls. The participants participated in an interview, spirometry, FeNO, skin prick test, and responded to the Mini Asthma Quality of Life Questionnaire., Results: Self-reported allergic rhinitis was significantly more common in both allergic and non-allergic asthma (82.3 and 40.7%) groups compared with the controls. The prevalence of chronic rhinosinusitis (CRS) was similar in both asthma groups. Eczema was significantly more common in both asthmatic groups (72.3 and 59.8%) than controls (47.0%) (p < 0.001 and p = 0.012). Severe respiratory infection in childhood and parental allergy were risk factors for both allergic and non-allergic asthma groups. Quality of life was significantly lower in non-allergic than allergic asthma groups (p = 0.01)., Conclusion: Concomitant symptoms from the upper airways and the skin were significantly more common in both allergic and non-allergic asthma. This indicates that non-allergic asthma has a systemic component with similarities to what is found in allergic asthma. There were similarities in the childhood risk factor pattern between the two types of asthma but asthma-related quality of life was lower in the non-allergic asthma group.

Background: B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive., Methods: A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors (CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of asthmatic patients and healthy controls., Results: Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40, CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics., Conclusion: Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation.

Increased awareness of asthma in society and altered diagnostic practices makes evaluation of data on prevalence change difficult. In most parts of the world the asthma prevalence seems to still be increasing. The increase is associated with urbanization and has been documented particularly among children and teenagers in urban areas of middle- and low-level income countries. Use of validated questionnaires has enabled comparisons of studies. Among adults there are few studies based on representative samples of the general population which allow evaluation of time trends of prevalence. This review focuses mainly on studies of asthma prevalence and symptoms among adults. Parallel with increased urbanization, we can assume that the increase in asthma prevalence in most areas of the world will continue. However, in Australia and North-West Europe studies performed, particularly among children and adolescents, indicate that the increase in asthma prevalence may now be leveling off.

Background: Epidemiologic data describing the association between allergic sensitization and asthma and allergic rhinitis in adults are scarce., Objective: To determine the prevalence and impact of specific sensitization to airborne allergens on asthma and allergic rhinitis among adults in relation to age., Methods: A random population sample (age 21-86 years) was examined with structured interview and analysis of specific IgE to 9 common airborne allergens. Of those invited, 692 (68%) subjects participated in blood sampling. IgE level of 0.35 U/mL or more to the specific allergen was defined as a positive test result., Results: Allergic sensitization decreased with increasing age, both in the population sample and among subjects with asthma and allergic rhinitis. In a multivariate model, sensitization to animal was significantly positively associated with asthma (odds ratio [OR], 4.80; 95% CI, 2.68-8.60), whereas sensitization to both animal (OR, 3.90; 95% CI, 2.31-6.58) and pollen (OR, 4.25; 95% CI, 2.55-7.06) was significantly associated with allergic rhinitis. The association between allergic sensitization and rhinitis was consistently strongest among the youngest age group, whereas this pattern was not found for asthma. The prevalence of allergic sensitization among patients with asthma decreased by increasing age of asthma onset, 86% with asthma onset at age 6 y or less, 56% at age 7 to 19 years, and 26% with asthma onset at age 20 years or more., Conclusions: Sensitization to animal was associated with asthma across all age groups; allergic rhinitis was associated with sensitization to both pollen and animal and consistently stronger among younger than among older adults. Early onset of asthma was associated with allergic sensitization among adults with asthma., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Inhaled glucocorticosteroids (ICS) are the mainstay of treatment in asthma. Fluticasone furoate (FF) is a novel, once-daily ICS asthma therapy. This study investigated the efficacy and safety of FF 50 mcg in patients with mild-to-moderate persistent asthma., Methods: A 24-week, multicenter, randomized, placebo-controlled and active-controlled, double-blind, double-dummy, parallel-group phase III study. Three hundred and fifty-one patients (aged ≥12 years; uncontrolled by non-ICS therapy) were randomized to treatment (1 : 1 : 1) with once-daily FF 50 mcg dosed in the evening, twice-daily fluticasone propionate (FP) 100 mcg or placebo. The primary endpoint was change from baseline in evening trough forced expiratory volume in 1 s (FEV1 ) at Week 24. Secondary endpoints were change from baseline in the percentage of rescue-free 24-h periods (powered endpoint), change from baseline in evening and morning peak expiratory flow, change from baseline in the percentage of symptom-free 24-h periods and number of withdrawals due to lack of efficacy., Results: Evening trough FEV1 at Week 24 was not statistically significantly increased with FF 50 mcg once-daily (37 ml [95% CI: -55, 128]; P = 0.430), but was with FP 100 mcg twice daily (102 ml [10, 194]; P = 0.030), vs placebo. No consistent trends were observed across other endpoints, including the powered secondary endpoint. No safety concerns were raised for either active treatment., Conclusions: FP 100 mcg twice daily improved evening trough FEV1 in patients with mild-to-moderate persistent asthma, but FF 50 mcg once daily did not demonstrate a significant effect. Secondary endpoints showed variable results. No safety concerns were identified for FF or FP., (© 2014 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Background: The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2-agonist vilanterol (VI) is under development for the treatment of asthma and chronic obstructive pulmonary disease., Objective: To compare the efficacy and safety of FF-VI and FF in patients (≥ 12 years old) with persistent asthma., Methods: In a randomized, double-blind, parallel-group study, patients (n = 609) (intent-to-treat population) received FF-VI 100-25 mcg, FF 100 mcg, or placebo once daily (evening) by using a dry powder inhaler for 12 weeks. Coprimary end points were change from baseline in trough FEV1 and serial (0-24 hours) weighted mean FEV1 (wmFEV(1)). Rescue-free 24-hour periods and safety also were assessed., Results: Placebo increased trough FEV1 (196 mL) and wmFEV(1) (212 mL) versus baseline. Compared with placebo, FF-VI and FF significantly improved trough FEV1 (172 mL [P < .001] and 136 mL [P = .002]), respectively, and serial wmFEV(1) (302 mL [P < .001] and 186 mL [P = .003]), respectively. Treatment differences between FF-VI and FF approached significance for serial wmFEV(1) (116 mL; P = .060) but not for trough FEV1 (36 mL; P = .405). The percentage of rescue-free 24-hour periods with FF-VI was 10.6% greater than FF and 19.3% greater than placebo. Statistically significant (P = .032) urinary cortisol suppression was observed with FF-VI (ratio, 0.82) relative to placebo, but not with FF. Adverse event and safety profiles were similar across treatment groups., Conclusions: Significant improvement in lung function was observed with FF-VI and FF versus placebo in patients with persistent asthma. Improvement of FEV1 when VI was added to FF was not significant. The high placebo response in evening trough FEV1 may have influenced the assessment of efficacy., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Asthma is a complex disease presenting with variable symptoms which are sometimes hard to control. The purpose of the study was to describe the prevalence of asthma symptoms, use of asthma medications and allergic sensitization in subjects with asthma. We also related those indices to the level of asthma control, lung function and in particular, cough., Methods: An extensive questionnaire was sent to randomly selected adults from the West Sweden region. Clinical examinations and interview were performed in a subset. Of the participants, 744 were defined as having an ongoing asthma - reported ever having asthma or physician diagnosed asthma and one of the following - use of asthma medications, recurrent wheeze or attacks of shortness of breath with or without wheeze in the last 12 months. A respiratory disease-free control group of 847 subjects was also described., Results: According to GINA guidelines, 40.6% of the asthmatics had partly controlled and 17.8% had uncontrolled asthma. Asthmatic subjects reported significantly more symptoms in the last 12 months than the control group - wheezing (79.4 vs 9.2%), shortness of breath (36.1 vs 2.5%), wheezing with shortness of breath (58.7 vs 1.3%). Important complaints were morning cough (42.5 vs 15.5%), cough with sputum production (36.1 vs 6.8%) and longstanding cough (32.5 vs 11.1%), which bothered two thirds of the uncontrolled and one third of partly controlled subjects. Asthma medications were used by 87.5% of the asthmatics, although around 30% of them who had insufficiently controlled disease used only short-acting beta-agonists. Asthmatics also had lower lung function, reacted to lower doses of methacholine that the controls and 13.6% of them had a FEV1/FVC ratio below 0.7. Allergic rhinitis was reported by 73.8% of the asthmatics and they were more frequently sensitized to several common allergens., Conclusions: Approximately 60% of asthmatics from this population-based study had insufficiently controlled asthma and persistent complaints, despite a high use of asthma medications. These self-reported symptoms were supported by clinical examination data. Increased cough frequency is an indicator of a more severe and difficult to control disease and should be considered when asthma is characterized.

Background: Fluticasone furoate (FF) is a novel, once-daily inhaled corticosteroid (ICS) that has been shown to improve lung function vs. placebo in asthma patients. This study evaluated the efficacy and safety of FF 50 mcg compared with placebo in asthma patients uncontrolled by non-ICS therapy., Methods: This 12-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study randomized 248 patients (aged ≥12 years) to once-daily FF 50 mcg administered via the ELLIPTA™a dry powder inhaler or placebo. The primary endpoint was change from baseline in pre-dose evening trough forced expiratory volume in one second (FEV1). Secondary endpoints were change from baseline in percentage of rescue-free 24-h periods (powered), evening and morning peak expiratory flow, symptom-free 24-h periods and withdrawals due to lack of efficacy. Other endpoints included Asthma Control Test™, Asthma Quality of Life Questionnaire and ELLIPTA ease of use questions. Safety was assessed throughout the study., Results: There was a significant difference in evening trough FEV1 between FF 50 mcg and placebo (treatment difference: 120 mL; p = 0.012). There was also a significant difference in rescue-free 24-h periods (11.6%; p = 0.004) vs. placebo. There were numerically greater improvements with FF vs. placebo for all remaining secondary endpoints. The incidence of adverse events was lower with FF (31%) than with placebo (38%); few were treatment-related (FF 50 mcg: n = 1, <1%; placebo: n = 4, 3%)., Conclusion: FF 50 mcg once daily significantly improved FEV1 and percentage of rescue-free 24-h periods experienced over 12 weeks vs. placebo, and was well tolerated., Trial Registration: www.clinicaltrials.gov, registration number: NCT01436071.

Background: Inhaled corticosteroids are a mainstay of therapy for persistent asthma, but suboptimal adherence with twice-daily use is widespread. Fluticasone furoate (FF) is a new inhaled corticosteroid (ICS) suitable for once-daily dosing in asthma. This study was performed to descriptively assess the efficacy and safety of two doses of FF, with no planned formal statistical hypothesis testing., Methods: This was a 24-week double-blind, multicentre, parallel-group study (NCT01431950). Patients aged ≥ 12 years with moderate-severe persistent asthma and uncontrolled on mid-high dose ICS were stratified by baseline FEV1 and randomised (1:1) to treatment with FF 100 μg or 200 μg once daily in the evening. The primary endpoint was change from baseline trough FEV1 after 24 weeks; secondary and other endpoints included peak expiratory flow (PEF) and rescue-free and symptom-free 24-hour periods over Weeks 1-24, and Asthma Control Test™ (ACT) score at Week 24. A pre-specified subgroup analysis of patients by randomisation strata was performed for the primary and selected secondary and other endpoints. Safety assessments included adverse events, laboratory and vital sign measurements, and change from baseline in 24-hour urinary cortisol at Week 24., Results: With FF 100 μg and 200 μg, least squares mean trough FEV1 improved from baseline by 208 mL and 284 mL, respectively, at Week 24; treatment difference: 77 mL (95% CI: -39, 192). Similar improvements from baseline in rescue- and symptom-free periods, and morning and evening PEF were observed in both groups. Patients were 42% more likely to be well-controlled (ACT score ≥ 20) with FF 200 μg than with FF 100 μg. Slightly more patients receiving FF 200 μg vs. FF 100 μg reported adverse events (63% vs. 59%) and events deemed treatment related (5% vs. <1%). Seven serious adverse events (FF 200 μg 4; FF 100 μg 3) were reported, none of which were deemed treatment related. No clinically relevant effects of either dose on 24-hour urinary cortisol were observed., Conclusion: Improvements from baseline in trough FEV1 were observed after 24 weeks of treatment with both doses of FF, with a numerically greater improvement in FEV1 observed in patients receiving FF 200 μg. Secondary endpoint findings were similar between groups. No safety concerns were identified during the study.

Background: Current maintenance therapies for asthma require twice-daily dosing. Vilanterol (VI) is a novel long-acting beta2 agonist, under development in combination with fluticasone furoate, a new inhaled corticosteroid (ICS). Findings from a previous 4-week study suggested that VI has inherent 24-hour activity and is therefore suitable for once-daily dosing. The study described here was a double-blind, double-dummy, randomised, placebo-controlled trial, the aim of which was to assess the efficacy of once-daily VI compared with placebo in patients with persistent asthma. The primary endpoint was change from baseline in 24-hour weighted mean forced expiratory volume in 1 second after 12 weeks of treatment vs. placebo. An active control arm received salmeterol (SAL) twice daily. All patients were maintained on a stable background dose of ICS., Results: Patients (n = 347) received VI, placebo or SAL (1:1:1). For the primary endpoint, substantial improvements in lung function were seen with VI (359 ml), SAL (283 ml) and placebo (289 ml). There were no statistically significant treatment differences between either the VI (70 ml, P = 0.244) or SAL (-6 ml, P = 0.926) groups and placebo. Both active treatments were well tolerated, with similarly low rates of treatment-related adverse events compared with placebo. No treatment-related serious adverse events occurred., Conclusions: This study failed to show a treatment difference between VI and placebo for the primary endpoint, in the presence of a placebo response of unforeseen magnitude. Because the placebo response was so large, it is not possible to draw meaningful conclusions from the data. The reason for this magnitude of effect is unclear but it may reflect increased compliance with the anti-inflammatory therapy regimen during the treatment period., Trial Registration: NCT01181895 at ClinicalTrials.gov.

Introduction: Asthma medication was increasingly used during the second part of the past century. There are few detailed data from population studies on use of asthma medication. The current study aimed to determine the use and determinants of asthma medication in West Sweden and to assess changes during the last two decades., Methods: From a random population sample participating in a survey on respiratory symptoms, 2000 individuals were randomly selected for clinical examinations and structured interviews, 1172 participated. All subjects reporting asthma (n = 1524) were also invited, and 834 participated. In total, 964 subjects with asthma participated. Asthma medication use was assessed in the general population and among two severity categories of asthma: multi-symptom asthma (MSA) and "other" asthma (having fewer symptoms). Current data, from 2010, was compared with data from 1992., Results: Asthma medication was used by 11% of the population, 4.4% used ICS with concurrent use of LABA, 3.3% used ICS without LABA, while 3.2% only used SABA. Compared with 1992, the prevalence of asthma medication use had increased with 54%, and use of ICS had increased from 1.5% to 7.7%., Conclusion: Subjects with MSA reported using asthma medication more frequently and at higher doses, and a higher proportion used ICS.A shift in asthma medication use has occurred since 1992, with increased use of ICS and decreased use of SABA only, implying better asthma control on a population level. Multi-symptom asthma should alert the treating physician to consider under-medication and/or poor treatment adherence., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Combination therapy with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) is recommended for patients with asthma symptomatic on ICS alone. However, there is ongoing debate regarding the risk-benefit ratio of using LABA in asthma., Objective: To evaluate the effect of the addition of a novel LABA, vilanterol (VI), to a once-daily ICS, fluticasone furoate (FF), on the risk of severe asthma exacerbations in patients with uncontrolled asthma., Methods: This randomised double-blind comparative study of variable duration (≥ 24-78 weeks) was designed to finish after 330 events (each patient's first on-treatment severe asthma exacerbation). 2019 patients with asthma aged ≥ 12 years with ≥ 1 recorded exacerbation within 1 year were randomised and received FF/VI 100/25 μg or FF 100 μg, administered once daily in the evening. The primary endpoint was time to first severe exacerbation; secondary endpoints were rate of severe asthma exacerbations per patient per year and change in trough evening forced expiratory volume in 1 s (FEV1) from baseline., Results: Compared with FF, FF/VI delayed the time to first severe exacerbation (HR 0.795, 95% CI 0.642 to 0.985) and reduced the annualised rate of severe exacerbations (rate reduction 25%, 95% CI 5% to 40%). Significantly greater improvements in trough FEV1 (p<0.001) were observed with FF/VI than with FF at weeks 12, 36, 52 and at endpoint. Both treatments were well tolerated with similar rates of treatment-related adverse events and on-treatment serious adverse events., Conclusions: Once-daily FF/VI reduced the risk of severe asthma exacerbations and improved lung function compared with FF alone, with good tolerability and safety profile in adolescents and adults with asthma currently receiving ICS., Clinicaltrialsgov No: NCT01086384.

The inhaled corticosteroid fluticasone furoate (FF) and the long-acting β₂ agonist vilanterol (VI) are in development as a combined once-daily therapy for asthma and chronic obstructive pulmonary disease. Our study objectives were to compare the efficacy and safety of once-daily FF/VI with FF alone and twice-daily fluticasone propionate (FP) in patients aged ≥12 years with moderate-to-severe persistent asthma. Patients (n=586) received FF/VI 200/25 μg or FF 200 μg once-daily (evening dosing), or FP 500 μg twice-daily for 24 weeks. Co-primary end-points were change from baseline in trough forced expiratory volume in 1 s (FEV₁) weighted mean (wm) 0-24 h serial FEV1. Secondary end-points included change from baseline in percentage of rescue-free 24-h periods, percentage of symptom-free 24-h periods and total Asthma Quality of Life Questionnaire (AQLQ). Safety assessments included adverse events, 24-h urinary cortisol excretion, vital signs and ECG. FF/VI significantly improved trough FEV1 and wmFEV₁ versus FF and FP. Significantly more rescue-free and symptom-free 24-h periods were reported with FF/VI versus FF. Treatment differences for AQLQ were not significant. Incidence of adverse events was similar across groups. No clinically significant differences were seen for 24-h urinary cortisol excretion, vital signs or ECG. FF/VI resulted in statistically greater improvements in lung function and symptomatic end-points versus FF, and was well tolerated in this asthma population.

Purpose: Poor adherence to medication treatment for asthma and allergic rhinitis could challenge a positive health outcome. Health-related quality of life (HRQL) is an important measure of health outcome. Both personality and gender could influence adherence and perceptions of HRQL. The purpose was to clarify the role of personality and gender in relation to adherence and HRQL in people with asthma and/or rhinitis., Data Sources: Participants (n = 180) with asthma and allergic rhinitis, selected from a population-based study, filled out questionnaires on the five-factor model personality traits--neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness--HRQL, and adherence to medication treatment. Data were statistically analyzed using t-tests, Mann-Whitney tests, bivariate correlations, and multiple regressions., Conclusions: Personality traits were associated with adherence to medication treatment in men. The influence of personality traits on HRQL also differed between men and women. These differences suggest that both a personality and gender perspective should be considered when planning care support aimed at improving adherence and HRQL in people living with asthma and/or allergic rhinitis., Implications for Practice: It is suggested that both a personality and gender perspective be taken into account in care support aimed at improving adherence and HRQL in people with asthma and allergic rhinitis., (©2013 The Author(s) ©2013 American Association of Nurse Practitioners.)

Inhaled corticosteroids (ICSs) improve asthma disease control; once-daily ICS administration may have advantages for patients. Our objective was to assess the efficacy and safety of the novel ICS fluticasone furoate (FF) over 24 weeks versus placebo. This was a 24-week double-blind, double-dummy, placebo- and active-controlled study (NCT01159912) of 343 asthma patients (≥12 years) not controlled by their current ICS. Patients were randomised (1:1:1) to FF100 μg, placebo (both administered once-daily [OD] via ELLIPTA™ dry powder inhaler in the evening) or fluticasone propionate (FP) 250 μg (administered twice-daily (BD) via DISKUS™/ACCUHALER™). Primary endpoint was change from baseline in pre-dose evening forced expiratory volume in 1s (FEV1) at Week 24; change from baseline in % rescue-free 24-h periods was a powered secondary endpoint. Adverse events (AEs) were assessed. FF100 μg OD and FP250 μg BD significantly improved pre-dose evening FEV1 compared with placebo at Week 24 (+146 ml [p = 0.009] and +145 ml [p = 0.011], respectively). Percentage of rescue-free 24-h periods was increased with FF100 μg OD (+14.8%) and FP250 μg BD (+17.9%) compared to placebo (both p < 0.001). On-treatment AEs were reported by 53% (FF100 μg OD), 42% (FP250 μg BD) and 40% (placebo) of patients. On-treatment severe asthma exacerbations were lower with FF100 μg OD (3%) and FP250 μg BD (2%) than placebo (7%). There was significant suppression of urinary cortisol at week 24 with FF100 μg OD (p = 0.030) and FP250 μg BD (p = 0.036) relative to placebo. FF100 μg OD, administered in the evening, achieves significant improvements in lung function and rescue inhaler use over 24 weeks, comparable to FP250 μg BD with similar safety profile., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult-to-treat asthma and severe treatment-resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment-resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult-to-control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult-to-control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Pharmacologically mediated bronchodilation is important in the management of asthma, and is primarily achieved with β₂-agonists. Novel compounds should preferably have a longer duration of action and a better systemic side effect profile than established alternatives at comparable peak bronchodilation. This single-dose crossover study was conducted to investigate and compare with formoterol the bronchodilatory and systemic effects, tolerability and safety of AZD3199, a novel ultra-long-acting β₂-agonist (uLABA)., Methods: Patients with asthma (n = 37) were randomized to receive AZD3199 (120, 480, 1920 µg), formoterol (9, 36 µg) or placebo inhaled via a Turbuhaler™. Bronchodilation was evaluated by maximum (E(max)) and average 22-26 h (E₂₂₋₂₆) forced expiratory volume in 1 second (FEV1). Serum potassium was evaluated by minimum (E(min)) and 0-4 h average (E(av)) determined from serial measurements. AZD3199 and formoterol were compared on the basis of relative dose potency. Adverse events, clinical laboratory tests and physical examinations were markers for safety and tolerability, with plasma AZD3199 as the indicator of drug exposure., Results: All active treatments dose-dependently increased E(max) and AZD3199 (480 and 1920 µg) and formoterol (36 µg) significantly increased E(₂₂₋₂₆) versus placebo. Relative dose potency between AZD3199 and formoterol was 50-fold on the microgram scale with respect to E max and 11-fold with respect to E(₂₂₋₂₆). Small, dose-dependent effects on potassium, heart rate and QTc were seen after administration of AZD3199 compared with placebo. These well-known dose-related class effects of β₂-agonists were mild. Notably, serum potassium suppression was less pronounced after AZD3199 compared with formoterol at similar bronchodilation. Overall, AZD3199 was well tolerated., Conclusions: AZD3199 480 µg and 1920 µg produced 24-hour bronchodilation. At comparable peak bronchodilator effect, AZD3199 was associated with a lower level of systemic side effects than formoterol. AZD3199 was well tolerated, with no safety concerns identified to preclude further investigation. ClinicalTrials.gov study identifier: NCT00736489.

Background: The combination of fluticasone furoate (FF), a novel inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting β2 agonist, is under development as a once-daily treatment of asthma and COPD. The aim of this study was to compare the efficacy of FF/VI with fluticasone propionate (FP)/salmeterol (SAL) in patients with persistent asthma uncontrolled on a medium dose of ICS., Methods: In a randomized, double-blind, double-dummy, parallel group study, 806 patients received FF/VI (100/25 μg, n = 403) once daily in the evening delivered through ELLIPTA (GlaxoSmithKline) dry powder inhaler, or FP/SAL (250/50 μg, n = 403) bid through DISKUS/ACCUHALER (GlaxoSmithKline). The primary efficacy measure was 0- to 24-h serial weighted mean (wm) FEV1 after 24 weeks of treatment., Results: Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (341 mL) and FP/SAL (377 mL); the adjusted mean treatment difference was not statistically significant (-37 mL; 95% CI, -88 to 15, P = 0.162). There were no differences between 0- to 4-h serial wmFEV1, trough FEV1, and asthma control and quality-of-life questionnaire scores. There was no difference in reported exacerbations between treatments. Both treatments were well tolerated, with no clinically relevant effect on urinary cortisol excretion or vital signs and no treatment-related serious adverse events., Conclusions: The efficacy of once-daily FF/VI was similar to bid FP/SAL in improving lung function in patients with persistent asthma. No safety issues were identified.

Background: The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2 agonist vilanterol (VI) is in development for asthma and chronic obstructive pulmonary disease., Objective: To assess the safety and tolerability of FF/VI over 52 weeks in patients with asthma., Methods: Patients (aged ≥12 years; on inhaled corticosteroid) were randomised (2:2:1) to FF/VI 100/25 µg or FF/VI 200/25 µg once daily in the evening, or fluticasone propionate (FP) 500 µg twice daily. Safety evaluations included adverse events (AEs), non-fasting glucose, potassium, 24-h urinary cortisol excretion, ophthalmic assessments, heart rate and pulse rate., Results: On-treatment AEs were similar across groups (FF/VI 66-69%; 73% FP). Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (6-7%) than FP (3%). Twelve serious AEs were reported; one (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p≤0.006), but not at Week 52 (ratios to FP were 1.05 [0.83 to 1.33] for FF/VI 100/25 µg and 1.09 [0.87 to 1.38] for FF/VI 200/25 µg). No clinically important changes in non-fasting glucose, potassium, QT interval corrected using Fridericia's formula (QTc[F]) or ophthalmic assessments were reported. Pulse rate (10 min post dose [Tmax], Week 52) was significantly increased with FF/VI versus FP (3.4 bpm, 95% CI 1.3 to 5.6; p=0.002 [FF/VI 100/25 µg]; 3.4 bpm, 95% CI 1.2 to 5.6; p=0.003 [FF/VI 200/25 µg]). Mean heart rate (24-h Holter monitoring) decreased from screening values in all groups (0.2-1.1 bpm FF/VI vs 5 bpm FP; Week 52)., Conclusions: FF/VI (100/25 µg or 200/25 µg) administered once daily over 52 weeks was well tolerated by patients aged ≥12 years with asthma. The overall safety profile of FF/VI did not reveal any findings of significant clinical concern. CLINICALTRIALS.GOV: NCT01018186.

Objective: To investigate respiratory symptoms and respiratory-related absence from work among Swedish health care workers (HCWs)., Methods: From a postal questionnaire study among a general Swedish working population (n = 12,186), we identified 2156 HCW (555 assistant nurses, 377 nurses, 109 physicians, and 1115 others), including 429 with mainly cleaning tasks (HCW-cleaning). The remaining respondents were classified as non-HCW. Multiple logistic regressions with 95% confidence intervals (CIs) were used to compare respiratory symptoms and respiratory-related absence from work between HCW and non-HCW, adjusting for potential confounders., Results: The prevalence of adult onset asthma was 4.3% in HCW and 3.0% in non-HCW (p = .003). Asthmatic symptoms during the past year were reported mainly by HCW-cleaning, 14.7%, in comparison to 8.3% among non-HCW (p < .0001). HCW had an increased odds ratio (OR) for asthmatic symptoms during the past year (OR 1.3, 95% CI (1.1-1.5)) and more prominent among assistant nurses (OR 1.5, 95% CI (1.1-2.0)) and HCW-cleaning (OR 1.9, 95% CI (1.4-2.5)). Respiratory-related absence from work in the past year was reported by 1.4% of non-HCW, 3.0% of HCW-cleaning, 2.9% of nurses, and 1.6% of assistant nurses. Taking smoking and age into account, there was still significantly increased respiratory-related absence from work in nurses (OR 2.0, 95% CI (1.1-3.8)) and in HCW-cleaning (OR 2.1, 95% CI (1.2-3.7))., Conclusions: HCW in Sweden, especially those with cleaning tasks, reported more respiratory symptoms and respiratory-related absence from work than the general working population. There is a need for longitudinal studies with detailed information on both occupational exposures and socioeconomic factors to explore what influences respiratory-related absence from work among HCW.

The role of T lymphocytes in pathogenesis of chronic inflammatory airway diseases - asthma and chronic obstructive pulmonary disease (COPD) has been emphasized in recent years: the importance of αβ T-cells (CD8+ and CD4+) has been widely described. A substantial fraction of γδ T-cells is a composite part of pulmonary T lymphocytes. Specific localisation of γδ T-cells in epithelium/mucosa-rich tissues implies their potential role in local inflammatory immune response, which occurs in chronic inflammatory airway diseases. An investigation was made of the T-lymphocyte subsets in induced sputum (IS), in bronchoalveolar lavage (BAL) and in peripheral blood from 20 patients with COPD (stages II-III; GOLD), 18 patients with asthma (persistent mild to moderate; GINA) and 14 healthy subjects. Relationship of γδ T-cells with lung function and smoking history was analysed. COPD patients had significantly higher numbers of CD8+T-cells in the airways of smokers compared to ex-smokers in the COPD group. A significant positive correlation was found between CD8+T-cells and pack-years of smoking. Differently, the COPD patients had significantly lower relative and absolute numbers of γδ T-cells in IS and in BAL compared to those from asthma or healthy subjects. The quantity of γδ T-cells negatively correlated with forced expiratory volume in 1 s and smoking (pack-years) only in COPD group. Our findings indicate a different local inflammatory response in COPD patients and in asthmatic groups. The reduced amount of γδ T-cells in IS and in BAL from COPD patients raises the hypothesis about their important role in pathogenesis of COPD., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Results of epidemiological studies are greatly influenced by the chosen methodology. The study aims to investigate how two frequently used questionnaires (Qs), with partly different layout, influence the prevalence of respiratory symptoms., Study Design and Setting: A booklet containing two Qs, the Global Allergy and Asthma European Network Q and the Obstructive Lung Disease in Northern Sweden Q, was mailed to 30,000 subjects aged 16-75years in West Sweden; 62% responded. Sixteen questions were included in the analysis: seven identical between the Qs, four different in set-up and five with the same layout but different wording. Comparisons were made using differences in proportions, observed agreement and Kappa statistics., Results:  Identical questions yielded similar prevalences with high observed agreement and kappa values. Questions with different set-up or differences in wording resulted in significantly different prevalences with lower observed agreement and kappa values. In general, the use of follow-up questions, excluding subjects answering no to the initial question, resulted in 2.9-6.7% units lower prevalence., Conclusion: The question set-up has great influences on epidemiological results, and specifically questions that are set up to be excluded based on a previous no answer leads to lower prevalence compared with detached questions. Therefore, Q layout and exact wording of questions has to be carefully considered when comparing studies., (© 2012 Blackwell Publishing Ltd.)

Background: Fluticasone furoate (FF) is an inhaled corticosteroid (ICS) with 24-hour activity in development as a once-daily treatment for the long-term management of asthma., Objective: To assess the efficacy and safety of 4 doses of once-daily FF administered using a dry powder inhaler in patients (≥12 years) with moderate asthma, uncontrolled on low-dose ICS (fluticasone propionate [FP] 200 μg/day or equivalent)., Methods: This double-blind, placebo-controlled, dose-ranging study randomized 622 patients to 1 of 6 treatments: FF (100, 200, 300, or 400 μg) once daily in the evening, FP 250 μg twice daily (active control), or placebo for 8 weeks. The primary endpoint was the change from baseline in predose evening forced expiratory colume in 1 second (FEV1) at week 8., Results: At week 8, relative to placebo, all doses of FF once daily and FP twice daily demonstrated significantly (P < .001) greater increases from baseline and greater than 200-mL increases in predose FEV1. There was no evidence of a dose-response relationship between FF doses. Improvement with once-daily FF was similar to or greater than that for twice-daily FP. Secondary efficacy endpoint findings generally supported the efficacy of FF 100 to 400 μg once daily, although statistically significant improvements versus placebo in symptom-free 24-hour periods were only reported for FF 400 μg. There were few withdrawals due to lack of efficacy. Oral candidiasis was reported in 0 to 4% of patients; 24-hour urinary cortisol excretion ratios were similar across active treatment groups and not significantly different from placebo., Conclusion: FF 100 to 400 μg once daily in the evening is effective and well tolerated in patients with asthma uncontrolled on low-dose ICS, with 100 μg and 200 μg, considered the most applicable doses in this asthma population., Trial Registration: clinicaltrials.gov Identifier: NCT00603278., (Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Current guidelines recommend adding a long-acting inhaled β(2)-agonist (LABA) to inhaled corticosteroids (ICS) in patients with uncontrolled asthma. This study evaluated the novel, once-daily LABA vilanterol trifenatate (VI) in asthma patients who remained symptomatic despite existing ICS therapy. The study involved a randomised, double-blind, placebo-controlled trial of VI (3, 6.25, 12.5, 25 and 50 μg), administered once daily in the evening by dry powder inhaler for 28 days, in asthma patients aged ≥ 12 yrs symptomatic on current ICS therapy. The primary end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV(1)); secondary end-points were weighted mean FEV(1), peak expiratory flow (PEF), symptom-/rescue-free 24-h periods, and safety. A significant relationship was observed between VI dose and improvements in trough FEV(1) (p=0.037). Statistically significant increases in mean trough FEV(1), relative to placebo, were documented for VI 12.5-50 μg (121-162 mL; p ≤ 0.016). Dose-related effects of VI were observed on weighted mean (0-24 h) FEV(1), morning/evening PEF, and symptom-/rescue-free 24-h periods. All doses of VI were well tolerated with low incidences of recognised LABA-related adverse events (tremor 0-2%; palpitations 0-2%; glucose effects 0-1%; potassium effects 0-<1%). Once-daily VI 12.5-50 μg resulted in prolonged bronchodilation of at least 24 h with good tolerability in asthma patients receiving ICS. Based on the overall efficacy and adverse event profile from this study, the optimum dose of VI appears to be 25 μg.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved., (© 2012 John Wiley & Sons A/S.)

Background: This randomized, double-blind, multicenter study was designed to evaluate the efficacy of inhaled once-daily fluticasone furoate (FF) administered in the evening in patients with persistent asthma not controlled by short-acting beta(2) agonists, and to determine the dose(s) suitable for further development., Methods: Of 1459 patients screened, 598 received one of six treatments: placebo, FF (25 μg, 50 μg, 100 μg or 200 μg) once daily each evening, or fluticasone propionate (FP) 100 μg twice daily for 8 weeks. The primary endpoint was change from baseline in pre-dose evening forced expiratory volume in 1 s (FEV(1))., Results: A dose-response effect was observed for once-daily FF 25-200 μg including (p < 0.001) and excluding placebo (p = 0.03). FF 50-200 μg once daily significantly increased FEV(1) from baseline (p < 0.05 vs placebo), by >200 mL for FF 100 μg and 200 μg. Significant improvements were also achieved for peak expiratory flow, and percentage symptom-free and rescue-free 24 h periods. The magnitude of effect was at least as good as twice-daily FP. Overall, once-daily FF was well tolerated with no systemic corticosteroid effects., Conclusion: FF 50-200 μg/day once daily in the evening demonstrated dose-related efficacy in asthma with 100-200 μg appearing to be the optimal doses for further evaluation. ClinicalTrials.gov: NCT00603382., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The immune process driving eosinophilic and non-eosinophilic asthma is likely driven by different subsets of T helper (Th) cells. Recently, in vitro studies and animal studies suggest that Th cell subsets displays plasticity by changing their transcription factor or by expressing multiple transcription factors. Our aim was to determine whether individuals with asthma and elevated circulating eosinophils express signs of different regulatory immune mechanisms compared with asthmatics with low blood eosinophils and non-asthmatic control subjects. In addition, determine the relationship between eosinophilia and circulating Th cell subsets., Methodology/principal Findings: Participants were selected from a random epidemiological cohort, the West Sweden Asthma Study. Immunophenotypes of fresh peripheral blood cells obtained from stable asthmatics, with and without elevated eosinophilic inflammation (EOS high and EOS low respectively) and control subjects, were determined by flow cytometry. No differences in the number of Th1 (T-bet), Th2 (GATA-3), Th17 (RORγt) or Treg (FOXP3) cells were observed between the groups when analysing each subset separately. However, in all groups, each of the Th subsets showed expression of additional canonical transcription factors T-bet, GATA-3, RORγt and FOXP3. Furthermore, by in vitro stimulation with anti-CD3/anti-CD28 there was a significant increase of single expressing GATA-3(+) and co-expressing T-bet(+)GATA-3(+) cells in the EOS high asthmatics in comparison with control subjects. In addition, T-bet(-)GATA-3(+)RORγt(+)FOXP3(+) were decreased in comparison to the EOS low asthmatics. Finally, in a group of control subjects we found that the majority of proliferating Th cells (CD4(+)CD25(+)Ki67(+)) expressed three or four transcription factors., Conclusions: The ability of human Th cells to express several regulatory transcription factors suggests that these cells may display plasticity in vivo.

Background: Fluticasone furoate (FF) is a novel inhaled corticosteroid with 24 h activity. FF is being developed as a once-daily treatment in combination with the long-acting β(2) agonist vilanterol trifenatate for asthma and chronic obstructive pulmonary disease., Objectives: To determine the optimal dose(s) of FF for treating patients with asthma., Methods: An 8-week multicentre, randomised, double-blind study. 627 patients with persistent moderate-to-severe asthma, symptomatic on medium-dose inhaled corticosteroid therapy, were randomised to placebo, FF 200, 400, 600 or 800 μg (once daily in the evening using a novel dry powder inhaler), or fluticasone propionate 500 μg twice daily (via Diskus™/Accuhaler™). The primary efficacy measure was mean change from baseline in pre-dose evening forced expiratory volume in one second (FEV(1)). Other endpoints included morning and evening peak expiratory flow, and rescue/symptom-free 24 h periods., Results: Each dose was significantly superior to placebo for the primary endpoint (p<0.001) with efficacy at least similar to that reported with fluticasone propionate. There was no dose-response relationship across the FF doses studied. Peak expiratory flow improved in all groups (p<0.001 vs placebo), and there were significant treatment effects on rescue/symptom-free 24 h periods with all active treatments. FF was generally well tolerated. The incidence of oral candidiasis was higher with FF 800 μg than placebo; pharmacokinetic and 24 h urinary cortisol analyses confirmed a higher systemic exposure of FF at this highest dose level., Conclusions: FF doses <800 μg have a favourable therapeutic index. The absence of an efficacy dose response suggests that 200 μg is an appropriate dose in patients with moderate persistent asthma. CLINICALTRIALS.GOV IDENTIFIER: NCT00603746.

Background: Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD) evening and twice-daily (BD) regimens of the novel inhaled corticosteroid fluticasone furoate (FF) in asthma patients., Methods: Patients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1) 40-85% predicted; FEV1 reversibility of ≥ 12% and ≥ 200 ml) were randomized to FF or fluticasone propionate (FP) regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough) FEV1; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs) and 24-hour urinary cortisol excretion were assessed., Results: The intent-to-treat population comprised 147 (FF) and 43 (FP) patients. On Day 28, pre-dose FEV1 showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml) to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml); all FF and FP regimens were significantly superior to placebo (p ≤ 0.02). AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02)., Conclusions: FF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose., Trial Registration: Clinicaltrials.gov; NCT00766090.

The application of proteomics to respiratory diseases, such as asthma and COPD, has been limited compared to other fields, like cancer. Both asthma and COPD are recognised to be multi-factorial and complex diseases, both consisting of clusters of multiple disease phenotypes. The complexity of these diseases combined with the inaccessibility and invasiveness of disease relevant samples have provided a hurdle to the progress of respiratory proteomics. Advances in proteomic instrumentation and methodology have led to the possibility to identify proteomes in much smaller quantities of biological material. This review focuses on the efforts in respiratory proteomics in relation to asthma and COPD, and the importance of identifying subgroups of disease entities to establish appropriate biomarkers, and to enhance the understanding of underlying mechanisms in each subgroup. Careful phenotype characterisation of patient subpopulations is required to make improvement in the field of heterogeneous diseases such as asthma and COPD, and the clusters of phenotypes are likely to encompass subgroups of disease with distinct molecular mechanisms; endotypes. The utilisation of modern advanced proteomics in endotypes of asthma and COPD will likely contribute to the increased understanding of disease mechanisms, establishment of biomarkers for these endotypes and improved patient care., (Copyright © 2011. Published by Elsevier B.V.)

The aim was to estimate the incidence rate of adult-onset asthma in relation to age, sex, smoking and occupational exposures. A random sample of 18,087 subjects aged 16-75 years was investigated using a respiratory questionnaire. Adult-onset asthma was defined as "physician-diagnosed" asthma with onset at or after 16 years of age. The subjects were asked about year of asthma diagnosis and year of starting and stopping smoking. Subjects with onset of asthma before 16 years of age and physician-diagnosed chronic obstructive pulmonary disease were excluded resulting in a study population of 15,761 subjects. Incidence-rates of adult-onset asthma were calculated and relative risks were assessed using Cox-regression models. During the observation period 1990-2008, 359 new cases of asthma occurred and the cumulative incidence for adult-onset asthma was 2.3%. The crude incidence rate was 1.4/1000 person-years (95% confidence interval 1.3/1000-1.6/1000), with significantly higher incidence rate among women than among men. The incidence rate of asthma during never-smoking years was similar to that during smoking years. The rate of asthma incidence decreased with increasing age. Occupational dust and fume exposure and being female were associated with increased risk of asthma. The attributable fraction for occupational exposure to gas, dust and fumes was 9.4% in the total group, 17.3% among men and 5.1% among women. The incidence rate of asthma was higher among women than among men, and the rate declined with increasing age. A substantial proportion of the new-onset asthma cases could be attributed to occupational exposures., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Asthma and rhinitis frequently coexist, but no population study has previously determined the relationship between nasal comorbidities and symptom expression and risk factors of asthma., Methods: In 2008, a postal questionnaire on respiratory health was sent to 30,000 randomly selected subjects aged 16-75 years in West Sweden; 29218 could be traced and 18,087 (62%) responded. The questionnaire included questions on asthma, rhinitis, chronic rhinosinusitis, respiratory symptoms and possible determinants., Results: Prevalence of allergic rhinitis in asthma was 63.9% and of asthma in allergic rhinitis 19.8%. Prevalence of chronic rhinosinusitis in asthma was 8.4% and of asthma in chronic rhinosinusitis 24.4%. Asthma subjects with chronic rhinitis, or chronic rhinosinusitis, had more symptoms of asthma and bronchitis than those without rhinitis (p < 0.001). There was an obvious trend of higher ORs for various environmental exposures including occupational exposure to dust, gases and fumes (OR 2.32 vs. OR 1.44), visible mould at home (OR 1.72 vs. OR 1.27) and water damage at home (OR 1.82 vs. OR 1.06) for asthma with chronic rhinosinusitis than for asthma with allergic rhinitis. Family history of allergy yielded a higher OR for asthma with allergic rhinitis than with asthma with chronic rhinosinusitis (OR 7.15 vs. OR 4.48)., Conclusion: Considerable overlap between asthma and nasal comorbidities was documented, confirming a close relationship between nasal disease and asthma. Allergic rhinitis, chronic rhinitis and chronic rhinosinusitis were associated with different risk factor patterns and symptom expression of asthma. Thus, different nasal comorbidities may reflect different phenotypes of asthma., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: There appears to be an obvious gap between a medical and patient adherence perspective. Deviating from a medication prescription could be regarded as fairly irrational, but with respect to patients' goals and/or concerns it could be seen as understandable. Thus, the aim was to elucidate adherence reasoning in relation to asthma medication., Methods: This was a qualitative study; data collection and analysis procedures were conducted according to Grounded Theory methodology. Eighteen persons, aged 22 with asthma and regular asthma medication treatment, were interviewed., Results: The emerged theoretical model illustrated that adherence to asthma medication was motivated by three foci, all directed towards a desired outcome in terms of a functional day as desired by the patient. A promotive focus was associated with the ambition to achieve a positive asthma outcome by being adherent either to the received prescription or to a self-adjusted dosage. A preventive focus was intended to ensure avoidance of a negative asthma outcome either by sticking to the prescription or by preventively overusing the medication. A permissive focus was associated with unstructured adherence behaviour in which medication intake was primarily triggered by asthma symptoms., Conclusions: As all participants had consciously adopted functioning medication tactics that directed them towards the desired goal of a functional day. In an effort to bridge the gap between a patient- and a medical adherence perspective, patients need support in defining their desired functionality and guidance in developing a person-based medication tactic.

Background: Fluticasone furoate (FF) is a novel long-acting inhaled corticosteroid (ICS). This double-blind, placebo-controlled randomized study evaluated the efficacy and safety of FF 200 mcg or 400 mcg once daily, either in the morning or in the evening, and FF 200 mcg twice daily (morning and evening), for 8 weeks in patients with persistent asthma., Methods: Asthma patients maintained on ICS for ≥ 3 months with baseline morning forced expiratory volume in one second (FEV(1)) 50-80% of predicted normal value and FEV(1) reversibility of ≥ 12% and ≥ 200 ml were eligible. The primary endpoint was mean change from baseline FEV(1) at week 8 in pre-dose (morning or evening [depending on regimen], pre-rescue bronchodilator) FEV(1)., Results: A total of 545 patients received one of five FF treatment groups and 101 patients received placebo (intent-to-treat population). Each of the five FF treatment groups produced a statistically significant improvement in pre-dose FEV(1) compared with placebo (p < 0.05). FF 400 mcg once daily in the evening and FF 200 mcg twice daily produced similar placebo-adjusted improvements in evening pre-dose FEV(1) at week 8 (240 ml vs. 235 ml). FF 400 mcg once daily in the morning, although effective, resulted in a smaller improvement in morning pre-dose FEV(1) than FF 200 mcg twice daily at week 8 (315 ml vs. 202 ml). The incidence of oral candidiasis was low (0-4%) and UC excretion was comparable with placebo for all FF groups., Conclusions: FF at total daily doses of 200 mcg or 400 mcg was significantly more effective than placebo. FF 400 mcg once daily in the evening had similar efficacy to FF 200 mcg twice daily and all FF regimens had a safety tolerability profile generally similar to placebo. This indicates that inhaled FF is an effective and well tolerated once-daily treatment for mild-to-moderate asthma., Trial Registration: NCT00398645.

Epidemiological questionnaires have failed to identify individuals with severe asthma. The extent of symptoms of asthma can, however, be easily established in epidemiology, by identification of multiple symptoms. We hypothesise that reporting of multiple symptoms of asthma reflects uncontrolled disease and is a sign of more severe asthma. The aims of the current study were, therefore, to determine the prevalence and determinants of multi-symptom asthma. A postal questionnaire was sent to 30,000 randomly selected individuals aged 16-75 yrs. A subgroup underwent clinical examinations. Multi-symptom asthma was defined as reported physician-diagnosed asthma, use of asthma medication, recurrent wheeze, attacks of shortness of breath and at least one additional respiratory symptom. The prevalence of multi-symptom asthma was 2.0%, and it was more common among females (2.4 versus 1.5%; p<0.001) and those with a body mass index >30 kg · m(-2). Multi-symptom asthmatics had lower forced expiratory volume in 1 s, higher exhaled nitric oxide fraction and more pronounced hyperresponsiveness. Family history of both asthma and allergy (OR 7.3), and occupational exposure to gas dust or fumes (OR 2.0) were also significant risk factors. Multi-symptom asthmatics comprise 2% of the general population; multi-symptom asthma is related to signs of more severe disease and could be used as an epidemiological marker of disease severity.

Background: Proteomic studies of respiratory disorders have the potential to identify protein biomarkers for diagnosis and disease monitoring. Utilisation of sensitive quantitative proteomic methods creates opportunities to determine individual patient proteomes. The aim of the current study was to determine if quantitative proteomics of bronchial biopsies from asthmatics can distinguish relevant biological functions and whether inhaled glucocorticoid treatment affects these functions., Methods: Endobronchial biopsies were taken from untreated asthmatic patients (n = 12) and healthy controls (n = 3). Asthmatic patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months) and new biopsies were obtained. Proteins extracted from the biopsies were digested and analysed using isobaric tags for relative and absolute quantitation combined with a nanoLC-LTQ Orbitrap mass spectrometer. Spectra obtained were used to identify and quantify proteins. Pathways analysis was performed using Ingenuity Pathway Analysis to identify significant biological pathways in asthma and determine how the expression of these pathways was changed by treatment., Results: More than 1800 proteins were identified and quantified in the bronchial biopsies of subjects. The pathway analysis revealed acute phase response signalling, cell-to-cell signalling and tissue development associations with proteins expressed in asthmatics compared to controls. The functions and pathways associated with placebo and budesonide treatment showed distinct differences, including the decreased association with acute phase proteins as a result of budesonide treatment compared to placebo., Conclusions: Proteomic analysis of bronchial biopsy material can be used to identify and quantify proteins using highly sensitive technologies, without the need for pooling of samples from several patients. Distinct pathophysiological features of asthma can be identified using this approach and the expression of these features is changed by inhaled glucocorticoid treatment. Quantitative proteomics may be applied to identify mechanisms of disease that may assist in the accurate and timely diagnosis of asthma., Trial Registration: ClinicalTrials.gov registration NCT01378039.

Aim: To explore the influence of personality traits and beliefs about medicines on adherence to treatment with asthma medication., Methods: Respondents were 35 asthmatic adults prescribed controller medication. They answered questionnaires about medication adherence, personality traits, and beliefs about medicines., Results: In gender comparisons, the personality traits "Neuroticism" in men and "adherence to medication" were associated with lower adherent behaviour. Associations between personality traits and beliefs in the necessity of medication for controlling the illness were identified. Beliefs about the necessity of medication were positively associated with adherent behaviour in women. In the total sample, a positive "necessity-concern" differential predicted adherent behaviour., Conclusion: The results imply that personality and beliefs about medicines may influence how well adults with asthma adhere to treatment with asthma medication.

Background: The increase in asthma prevalence until 1990 has been well described. Thereafter, time trends are poorly known, due to the low number of high quality studies. The preferred method for studying time trends in prevalence is repeated surveys of similar populations. This study aimed to compare the prevalence of asthma symptoms and their major determinants, rhinitis and smoking, in Swedish young adults in 1990 and 2008., Methods: In 1990 the European Community Respiratory Health Survey (ECRHS) studied respiratory symptoms, asthma, rhinitis and smoking in a population-based sample (86% participation) in Sweden. In 2008 the same symptom questions were included in the Global Allergy and Asthma European Network (GA(2)LEN) survey (60% participation). Smoking questions were however differently worded. The regions (Gothenburg, Uppsala, Umeå) and age interval (20-44 years) surveyed both in 1990 (n = 8,982) and 2008 (n = 9,156) were analysed., Results: The prevalence of any wheeze last 12 months decreased from 20% to 16% (p<0.001), and the prevalence of "asthma-related symptoms" was unchanged at 7%. However, either having asthma attacks or using asthma medications increased from 6% to 8% (p<0.001), and their major risk factor, rhinitis, increased from 22% to 31%. Past and present smoking decreased., Conclusion: From 1990 to 2008 the prevalence of obstructive airway symptoms common in asthma did not increase in Swedish young adults. This supports the few available international findings suggesting the previous upward trend in asthma has recently reached a plateau. The fact that wheeze did not increase despite the significant increment in rhinitis, may at least in part be due to the decrease in smoking.

Recent studies have associated osteopontin (OPN) with allergic inflammation; however, its role in human asthma remains unclear. The aim of this study was to measure OPN levels in the serum, bronchoalveolar lavage fluid (BALF) and bronchial tissue of healthy controls and asthmatics, identify cellular sources of OPN and examine possible correlations between OPN expression, disease severity and airway remodelling. Serum samples were obtained from 35 mild-to-moderate asthmatics, 19 severe asthmatics and 17 healthy controls in the steady state and in cases of exacerbation. Of these subjects, 29 asthmatics and nine controls underwent bronchoscopy with endobronchial biopsy and BALF collection. OPN expression was determined by ELISA and immunohistochemistry/immunofluorescence. Reticular basement membrane thickness and goblet cell hyperplasia were also determined. Serum and BALF OPN levels were significantly increased in all asthmatics in the steady state, whereas serum levels decreased during exacerbations. OPN was upregulated in the bronchial tissue of all patients, and expressed by epithelial, airway and vascular smooth muscle cells, myofibroblasts, T-lymphocytes and mast cells. OPN expression correlated with reticular basement membrane thickness and was more prominent in subepithelial inflammatory cells in severe compared to mild-to-moderate asthma. OPN expression is upregulated in human asthma and associated with remodelling changes, and its subepithelial expression correlates with disease severity.

It is increasingly clear that asthma is a complex disease made up of number of disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is possibly the greatest obstacle in understanding the causes of asthma and improving treatment and can explain the failure to identify consistent genetic and environmental correlations to asthma. Here we describe a hypothesis whereby the asthma syndrome is divided into distinct disease entities with specific mechanisms, which we have called "asthma endotypes." An "endotype" is proposed to be a subtype of a condition defined by a distinct pathophysiological mechanism. Criteria for defining asthma endotypes on the basis of their phenotypes and putative pathophysiology are suggested. Using these criteria, we identify several proposed asthma endotypes and propose how these new definitions can be used in clinical study design and drug development to target existing and novel therapies to patients most likely to benefit. This PRACTALL (PRACtical ALLergy) consensus report was produced by experts from the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)