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Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment. Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries. The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis. Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma.

Background: Although sensitization to indoor allergens is strongly associated with asthma, there are questions as to how this relates to asthma symptoms., Objective: We sought to study the relevance of IgE antibodies to cat and dog allergens in an area in which (1) the climate discourages cockroach, fungal, and mite growth and (2) dander allergens are known to be present in schools and houses without animals., Methods: IgE to 8 allergens was tested in 963 sera from a population-based study on 19-year-olds, and associations with asthma symptoms, diagnosis, and treatment were examined. In positive sera IgE to specific cat and dog allergens was also assayed., Results: IgE specific for animal dander had the highest prevalence and strongest relationship to asthma diagnosis. Furthermore, asthma severity, as judged by the frequency of symptoms and use of treatment, was directly associated with the titer of IgE antibodies to animal dander. Among the 103 subjects who had current asthma at age 19 years, 50 had asthma before age 12 years. Among those 50, the odds ratios for asthma related to any IgE antibodies to animal dander or high-titer IgE antibodies (≥17.5 IU/mL) were 9.2 (95% CI, 4.9-17) and 13 (95% CI, 6.9-25), respectively. In multivariable analysis IgE antibodies to Fel d 1 and Can f 5 were each associated with current asthma., Conclusion: High-titer IgE antibodies to cat and dog allergens were strongly associated with the diagnosis, severity, and persistence of asthma; however, a large proportion of patients with current asthma did not live in a house with a cat or dog., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders., Methods: The GA 2 LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires., Results: The mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis., Conclusion: Our study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma., Methods: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months., Results: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77)., Conclusion: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.

Achieving and maintaining optimal asthma control is a major asthma management goal advocated by the Global Initiative for Asthma (GINA). Recent evidence suggests that while asthma control is clearly achievable in most asthmatics, not all asthmatics attain optimal asthma control. The difficulty is compounded further because patients, physicians and regulatory bodies have different perceptions of what is meant by asthma control. The challenge therefore remains as to how best to assess asthma control and define management strategies to ensure that this control is achieved and maintained. Despite the availability of several patient-based tools for assessing asthma control, these are mostly employed in a research setting or in selected specialist clinics. A symptom-based treatment approach also may have its limitations because patients can be poor judges of disease symptoms and severity and under-estimation may lead to inadequate treatment of airway inflammation and airway hyperresponsiveness (AHR) when treatment is administered as on-demand reliever therapy, since the effect of treatment on these underlying features occurs over a longer time course. The clinical benefits of sustained maintenance treatment for at least 3 months has been documented in recent studies of salmeterol/fluticasone propionate combination, which have demonstrated correlations between reduction in airway inflammation/AHR and reduction in exacerbation rates. In view of the putative limitations of a purely symptom-based asthma management plan, we suggest that treatment should be focussed on management of all aspects of the disease rather than management of symptoms alone, with a practical approach being treatment for a minimum of 3 months with an optimal dose to ensure maximal effects are seen on asthma control, airway inflammation, lung function, and remodelling.

Three hundred and fifty-three asthmatic patients who remained symptomatic despite treatment with budesonide 800-1200 microg day(-1) (or equivalent) were randomized to a new combination therapy comprising salmeterol 50 microg and fluticasone propionate 250 microg (Seretide, Advair, Viani 50/250 microg) twice daily or budesonide 800 microg twice daily for 24 weeks. Patients kept daily records of their morning and evening peak expiratory flow (PEF), daytime and night-time symptom scores and daytime and night-time use of rescue salbutamol. Mean morning PEF increased by 451 min(-1) (baseline 361 l min(-1)) in the salmeterol/fluticasone propionate combination (SFC) group and by 19 l min(-1) (baseline 358 l min(-1)) in the budesonide group over the 24 weeks. The adjusted mean morning PEF over weeks 1 to 24 was significantly greater in the SFC group, despite the > three-fold lower corticosteroid dose (406 vs. 380 l min(-1); P < 0.001). A significantly greater improvement in evening PEF was also seen in the SFC group (adjusted mean 416 vs. 398 l min(-1); P<0.001). SFC also provided significantly better control of daytime symptoms and a significantly greater reduction in the requirement for rescue salbutamol compared with budesonide. These results demonstrate that SFC 50/250 microg twice daily is superior to budesonide 800 microg twice daily in the management of patients with moderate to severe asthma who are symptomatic on their existing dose of corticosteroid.

This multi-national, double-blind, randomized, parallel-group study compared the efficacy and tolerability of fluticasone propionate 500 microg twice daily propelled either by the non-chlorofluorocarbon (CFC) propellant, hydrofluoroalkane (HFA) 134a, or the CFC propellants 11 and 12 used in the established pressurized metered dose inhaler (pMDI). The study period was 12 months and involved 412 subjects with moderate to severe asthma (HFA 134a pMDI: n = 203; CFC pMDI: n = 209). For the first 3 months, subjects kept a daily record card and attended the clinic every 4 weeks. Thereafter, they kept daily diaries for 2 weeks before each clinic assessment, which were performed at the end of 6, 9 and 12 months. Mean morning peak expiratory flow (PEF) increased during the first week in both treatment groups. By the end of week 12 the adjusted mean increase from baseline in morning PEF was 21 and 23 l min(-1) in the HFA 134a and CFC pMDI groups, respectively, and this increase was maintained throughout the 12-month study period. Similar improvements were detected in other diary card parameters and in clinic lung function measurements. The two groups were shown to be clinically equivalent in terms of all efficacy variables and there were no differences in tolerability. There were few reports of low serum cortisol levels during the 12-month study period, and serum cortisol levels were similar at baseline and after 12 weeks and 12 months of treatment in the two groups. In conclusion, the new HFA 134a fluticasone propionate pMDI is as effective and safe as the established CFC fluticasone propionate pMDI when used at a dosage of 1 mg day(-1).

A study was done to compare the efficacy and safety of the coprescription of salmeterol 50 microgram twice daily or 100 microgram twice daily with beclomethasone dipropionate (BDP) 500 micrograms twice daily (SALM 50 and SALM 100) with BDP 1,000 microgram twice daily (BDP 1,000) in patients with asthma not controlled by BDP 500 microgram twice daily (or the equivalent). Following a run-in period, 738 patients at 72 centers were randomized to treatment for 24 wk in a double-blind, parallel-group study during which they maintained a daily record of peak expiratory flow rates (PEFRs) and symptom scores. At about 40 of the centers, bronchial hyperresponsiveness (BHR) to histamine was measured during and at 3 and 14 d after stopping treatment. Both groups taking salmeterol showed an improvement of more than 45 L/min in their morning PEFR and 30 L/min in their evening PEFR, compared with respective improvements of 16 L/min and 6 L/min in the group taking BDP 1,000. Both the SALM 50 and SALM 100 groups had a significantly increased percentage of symptom-free and rescue-free days and nights compared with the BDP 1,000 group, and there was no difference between the two salmeterol groups. None of the treatments altered BHR. Exacerbation rates did not differ among the three groups. We conclude that in this selected group of symptomatic patients taking BDP 500 micrograms twice daily, the addition of salmeterol provides better improvement in lung function and symptom control, without altering BHR or increasing exacerbation rates, than does doubling the dose of BDP.

In this 4-week, multicenter, double-blind, randomized, parallel group study, the dose-effect relationship of four doses of inhaled fluticasone propionate (50, 100, 200, and 400 micrograms twice daily) was investigated and compared with beclomethasone dipropionate, 200 micrograms twice daily. A total of 672 patients with moderate asthma currently receiving 1,000 micrograms/d or less of an inhaled steroid were recruited. The study demonstrated a significant dose-related improvement in lung function with fluticasone propionate. Linear dose-related increases were observed in morning (increase per doubling dose was 4.3 L/min; 95 percent confidence interval [CI], 1.8, 6.8 L/min; p = 0.001) and evening peak expiratory flow rate (PEFR) (increase per doubling dose was 3.0 L/min; 95 percent CI, 0.5, 5.5 L/min; p = 0.017), clinic lung function (at 4 weeks, increase in percent predicted PEFR per doubling dose = 1.1 percent; 95 percent CI, 0.2, 2.1 percent; p = 0.022; increase in percent predicted FEV1 per doubling dose = 1.1 percent; 95 percent CI, 0.3, 1.9 percent; p = 0.10:increase in percent predicted FVC per doubling dose = 1.3 percent, 95 percent CI, 0.5, 2.1 percent; p = 0.001), and the percentage of symptom-free days over days 1 to 14 of treatment (increase per doubling dose = 1.9, 95 percent CI, 0.0, 3.9; p = 0.048). There was also a dose-related reduction in extra bronchodilator usage (days 1 to 14 p = 0.002; days 15 to 28 p = 0.01). In addition, there was a significant decrease in diurnal variation with increasing doses of fluticasone propionate (decrease per doubling dose = 2.0 L/min, 95 percent CI, 0.4; p = 0.024). The number of asthma exacerbations was also reduced as the dose of fluticasone propionate increased. Fluticasone propionate was well tolerated, adverse events were few, and there was a similar incidence in all groups. Furthermore, there was no evidence of any hypothalamic pituitary adrenal axis suppression. The data from the study were consistent with other clinical studies that have shown fluticasone propionate to be more potent than beclomethasone dipropionate in terms of improvement in lung function. In conclusion, this study provided evidence of a dose-related improvement in asthma control for fluticasone propionate in the dose range 100 to 800 micrograms daily, in patients with moderate asthma.

Five hundred and eighty-five patients with moderate asthma, currently receiving 400-1000 micrograms day-1 of an inhaled corticosteroid, were treated for 6 weeks in a double-blind, randomized, parallel group study with either 500 micrograms day-1 fluticasone propionate as a dry powder via a Diskhaler inhaler, 500 micrograms day-1 fluticasone propionate via a pressurized inhaler or 1000 micrograms day-1 beclomethasone dipropionate via a pressurized inhaler. For all three treatment groups, mean morning and evening peak expiratory flow rates (PEFRs) increased within 1 week of the start of treatment. There were also improvements in clinic lung function, daytime and night-time asthma symptoms and a reduction in daytime and night-time rescue bronchodilator medication in all three groups. There were no statistically significant differences between the two formulations of fluticasone propionate in any of the efficacy parameters. Fluticasone propionate via the Diskhaler was significantly more effective than beclomethasone dipropionate over the 6 week study period in reducing diurnal variation (mean difference--4 l min-1, 95% CI--8 to 0 l min-1: P = 0.03). Fluticasone propionate via the Diskhaler produced a statistically significant improvement in night-time symptoms when compared to beclomethasone dipropionate whereas, beclomethasone dipropionate 1000 micrograms day-1 was statistically significantly more effective than both formulations of fluticasone propionate in improving daytime symptoms (P < 0.05). However, these statistical differences must be viewed together with the fact that very few patients recorded a score of 2 or more for both daytime or night-time symptoms. There was a similarly low incidence of adverse events with all three treatments with no evidence of hypothalamic pituitary adrenal (HPA)-axis suppression. The results of the 6-week comparative study showed that 500 micrograms day-1 fluticasone propionate whether administered via pressurized inhaler or Diskhaler is as effective and as safe as 1000 micrograms day-1 beclomethasone dipropionate administered via a pressurized inhaler in the treatment of moderate asthma. Over 12 months fluticasone propionate 500 micrograms day-1 via a pressurized inhaler was at least as effective and as well tolerated as beclomethasone dipropionate 1000 micrograms day-1.

Background: Salmeterol is a potent selective beta 2 agonist that has been shown to have a duration of action in excess of 12 hours. In this study salmeterol and salbutamol were compared over a three month period with a further extension of nine months., Methods: Three hundred and eighty eight patients with mild to moderate reversible airways obstruction (forced expiratory volume in one second (FEV1) > 50% predicted) were randomised to receive salmeterol (50 micrograms) twice daily or salbutamol (400 micrograms) four times daily, both by dry powder, in a double blind parallel group study. During the first three months detailed assessment of efficacy was made with recording of morning and evening peak expiratory flow rates (PEF), asthma symptoms, and bronchodilator use when necessary for the relief of symptoms. Patients continued in the study for a further nine months with the salbutamol dose reduced to 400 micrograms twice daily. Lung function was measured at the clinic and safety data were collected during this period., Results: Salmeterol produced a significantly higher mean morning PEF (mean difference compared with salbutamol 21 (95% CI 12-31) l/min), and a significant reduction in mean diurnal variation in PEF (from 30 l/min at baseline to 11 34 l/min at baseline to 32 l/min during salbutamol treatment). Salmeterol also reduced day and night symptoms and use of rescue bronchodilator. FEV1 increased with both salmeterol and salbutamol treatment over the 12 month treatment period. For both treatments the number of patients reporting exacerbations of asthma and the frequency of these exacerbations remained constant during the study. Thirty six patients in the salmeterol and 49 in the salbutamol group withdrew during the 12 months of the study., Conclusions: In this study salmeterol (50 micrograms twice daily) was more effective than salbutamol (400 micrograms four times daily) in the control of asthma over three months, and more effective than salbutamol (400 micrograms twice daily) over a further nine months. Neither salmeterol nor salbutamol was associated with any worsening of control of asthma.