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Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler® device, a high- or medium-high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases. Enhanced feature (slides, video, animation) (MP4 43768 kb).

Background: Selection of the most appropriate device for a switch from one inhaler to an equivalent product is known to have a major impact on clinical outcomes in patients with asthma or chronic obstructive pulmonary disease (COPD). Salmeterol/fluticasone propionate (S/F) Easyhaler® has been demonstrated to be therapeutically equivalent with a reference product. However, no data on real-life effectiveness are currently available for patients switching to S/F Easyhaler from another S/F inhaler. Methods: The aim of this prospective, open, multicenter, non-interventional study was to assess clinical effectiveness of propionate S/F Easyhaler in adult asthma and COPD patients switched from another inhaler. The primary endpoints were Asthma Control Test (ACT) and COPD Assessment Test (CAT). Secondary endpoints included assessments of patient satisfaction and preference and physician/nurse perception on S/F Easyhaler use. The study included three visits during a 12-week follow-up. Results: A total of 211 patients (160 with asthma; 51 with COPD) were included in the analyses. In patients with asthma, there was a statistically significant increase in the mean ACT score at week 12 (20.2 ± 3.9) compared with the baseline (18.6 ± 4.1), with a mean increase of 1.6 (±3.5) points ( p Conclusion: The results from this prospective real-life clinical study indicate better or at least similar treatment control of asthma and COPD after switching to S/F Easyhaler from another S/F inhaler. This study also shows that S/F Easyhaler was favored by the patients and that it is easy to teach, learn and use in a real-life setting. The reviews of this paper are available via the supplemental material section.

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler® device, a high- or medium–high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases. Enhanced feature (slides, video, animation) (MP4 43768 kb) Supplementary Information The online version contains supplementary material available at 10.1007/s41030-021-00174-5.

Josep Darbà,1 Meritxell Ascanio,2 Jörgen Syk,3– 5 Kjell Alving4 1Department of Economics, Universitat de Barcelona, Barcelona, Spain; 2BCN Health Economics & Outcomes Research, S.L., Barcelona, Spain; 3Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; 4Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden; 5Academic Primary Health Care Centre, Stockholm, SwedenCorrespondence: Josep DarbàDepartment of Economics, Universitat de Barcelona, Diagonal 696, Barcelona, 08034, SpainTel +34 934020110Fax +34 934039082Email darba@ub.eduObjective: To determine the economic impact of the fraction of exhaled nitric oxide (FeNO) in asthma diagnosis and management in primary care in Sweden.Methods: An economic model has been developed to determine the economic impact of the fraction of exhaled nitric oxide (FeNO) in asthma diagnosis and management in primary care in Sweden. The model includes the use and cost of commonly used tests, the associated outcomes and diagnostic accuracy. We compared FeNO with spirometry and reversibility testing, methacholine challenge test, allergy testing, and blood eosinophil count. One-way sensitivity analyses were performed to confirm the robustness of results.Results: Adding FeNO measurement in asthma diagnosis resulted in cost savings of SEK 672 per patient by the fourth year. The use of FeNO testing in asthma management proved to be a dominant strategy when compared with each other test except methacholine challenge test. Sensitivity analyses confirmed the robustness of the results.Conclusion: Introducing FeNO testing in clinical practice for the diagnosis and management of asthma in primary care in Sweden is less costly than standard methods while providing similar health benefits.Keywords: asthma, management, diagnosis, FeNO, exhaled nitric oxide, health economy

It is unclear if patients with COPD are at increased risk of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1, 2]. However, after contracting SARS-CoV-2, patients with COPD are at high risk of severe coronavirus disease 2019 (COVID-19), a condition associated with morbidity and mortality [3, 4]. Although studies have described COVID-19 cohorts and investigated COPD as a risk factor, studies investigating patients with COPD in relation to risks of COVID-19 remain rare. Approved by the Swedish Ethical Review Authority (2020-02777), the current study was based on the Swedish National Airway Register (SNAR), which includes a large, well-characterised cohort of patients with COPD [5]. In the cohort, patients who have been hospitalised or died from COVID-19 were identified, which afforded a unique opportunity to study predictors of severe COVID-19 in COPD., Older age, male sex, low educational level, symptom burden, degree of obstruction, underweight, obesity, comorbidity and prior COPD inpatient or secondary care predict severe COVID-19 in patients with COPD https://bit.ly/2VHZIEm

Introduction In real-life practice, asthma remains poorly controlled, with a considerable burden on patients’ quality of life. Budesonide/formoterol (B/F) Easyhaler® has demonstrated similar dose consistency, therapeutic equivalence, and equivalent bronchodilator efficacy to B/F Turbuhaler®, but no real-life comparisons are yet available in patients switching from B/F Turbuhaler® to B/F Easyhaler®. Methods The primary objective of this real-life, non-interventional, observational study was to show non-inferiority of asthma control when adult patients in Swedish primary care with persistent asthma switched from B/F Turbuhaler® to B/F Easyhaler®. At visit 1, baseline demographic and endpoint data were recorded, and eligible patients switched to B/F Easyhaler®. The study comprised a control visit (visit 2) and a concluding examination (visit 3) after 12 weeks. Asthma control was assessed using the Asthma Control Test (ACT). The mini-Asthma Quality of Life Questionnaire (AQLQ) and lung function test were performed, and participants and investigators answered questionnaires about ease-of-use and teaching. Results A total of 117 patients were enrolled in the on-treatment population; 81 (64.8%) were female. At visit 3, B/F Easyhaler® demonstrated non-inferiority to B/F Turbuhaler®; the mean difference in change from baseline ACT was statistically significant (18.9 vs. 20.7, respectively; p

Introduction: It has been suggested that change of inhaler may influence asthma control. However, meta-analyses indicate that all inhalers can achieve the same therapeutic effect if patients can apply the correct inhalation technique. Objective: The main aim of the study was to demonstrate non-inferiority of asthma control when switching inhaler from Symbicort Turbuhaler to Bufomix Easyhaler. Methods: This was an open, prospective, non-interventional, multicentre, single arm study. Adult asthmatics using Symbicort Turbuhaler regularly for at least six months were consecutively recruited from seven Swedish primary health care centres and switched to Bufomix Easyhaler with the same dose. Asthma Control Test (ACT), Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ) and spirometry were performed before switching inhalers and after 12 weeks. Check of inhaler technique was performed before switching and two weeks after switching according to the centres routine. Results: Altogether 125 patients were included and 117 completed the study. Five patients were lost to follow up and 3 due to adverse events. ACT mean score improved from 19.04 to 20.76 (p≤0.001, 95%CI 0.81-2.63) and Mini-AQLQ mean score improved from 5.44 to 5.78 (p≤0.001, 95%CI 0.18-0.49), neither of them considered as a clinically important improvement. Spirometry, FEV1 and FVC percent of predicted showed no statistically or clinically significant changes. Conclusion: Patients switching from Symbicort Turbuhaler to Bufomix Easyhaler had equivalent or better results regarding patient´s control of their asthma.

Chronic non-specific respiratory symptoms are difficult to manage. This trial aimed to evaluate the association between baseline fractional exhaled nitric oxide (FeNO) and the response to inhaled corticosteroids in patients with non-specific respiratory symptoms.In this double-blind randomised placebo-controlled trial, we enrolled undiagnosed patients, aged 18-80 years, with cough, wheeze, or dyspnoea and less than 20% bronchodilator reversibility across 26 primary care centres and hospitals in the UK and Singapore. Patients were assessed for 2 weeks before being randomly assigned (1:1) to 4 weeks of treatment with extrafine inhaled corticosteroids (QVAR 80 μg, two puffs twice per day, equivalent to 800 μg per day beclomethasone dipropionate) or placebo. Randomisation was stratified by baseline FeNO measurement: normal (≤25 parts per billion [ppb]), intermediate (25 tp40 ppb), and high (≥40 ppb). The primary endpoint was change in Asthma Control Questionnaire (ACQ7) mean score. We used generalised linear modelling to assess FeNO as a predictor of response, estimating an interaction effect between FeNO and treatment on change in ACQ7. We did our primary and secondary analyses in the per-protocol set, which excluded patients with non-completion of the primary endpoint, non-compliance to treatment (ascertained by patient report), and study visits made outside the predefined visit windows. This study is registered on ClinicalTrials.gov, number NCT02294279.Between Feb 4, 2015, and July 12, 2016, we randomly assigned 294 patients to extrafine inhaled corticosteroid treatment (n=148) or placebo (n=146). Following exclusions due to protocol violations, we analysed 214 patients (114 extrafine inhaled corticosteroids and 100 placebo). We observed a significant interaction between baseline FeNO and treatment group for every 10 ppb increase in baseline FeNO, with the change in ACQ7 greater in the extrafine inhaled corticosteroids group than in the placebo group (difference between groups 0·071, 95% CI 0·002 to 0·139; p=0·044). The most common adverse events were nasopharyngitis (18 [12%] patients in the treatment group vs 13 [9%] in the placebo group), infections and infestations (25 [17%] vs 21 [14%]), and respiratory, thoracic, and mediastinal disorders (13 [9%] vs 17 [12%]).FeNO measurement is an easy and non-invasive tool to use in clinical practice in patients with non-specific respiratory symptoms to predict response to inhaled corticosteroids. Further research is needed to examine its role in patients with evidence of other airway diseases, such as chronic obstructive pulmonary disease.Sponsored by OPRI with partial funding by Circassia and study drugs provided by TEVA.

Background Asthma is a chronic inflammatory respiratory disorder associated with reduced lung function and poor quality of life. The condition is also associated with poor self-rated health, a major predictor of objective health trajectories. Of biological correlates to self-rated health, evidence suggests a role for inflammatory cytokines and related sickness behaviours. However, this is mainly based on cross-sectional data, and the relation has not been investigated in patients with chronic inflammatory conditions. Objective To investigate inflammatory cytokines, lung function, sickness behaviour and asthma-related quality of life as determinants of self-rated health in patients with asthma, and to investigate if these variables co-vary over time. Methods Plasma cytokines (IL-5, IL-6), lung function (FEV1), sickness behaviour, asthma-related quality of life and self-rated health were assessed in 181 patients with allergic asthma aged 18–64 years in a one-year longitudinal study. Mixed effect regression models and Spearman’s correlation were performed to analyse the associations between repeated measurements. Results More sickness behaviour and poorer asthma-related quality of life were associated with poorer self-rated health (p’s

Background: Fractional exhaled nitric oxide (FeNO) can predict treatment response in asthma, but little is known of its utility in patients with non-specific respiratory symptoms (NSRS). Aims and objectives: To evaluate the association between baseline FeNO and response to treatment with inhaled corticosteroids (ICS) in patients with NSRS. Methods: This was a multi-centre randomised, placebo-controlled trial, carried out in UK and Singapore. It consisted of a 2-week assessment period to establish baseline measurements and a 4-week treatment period with either extrafine ICS (200 µ beclomethasone bid) or placebo. NIOX VERO (Circassia) was used to measure baseline FeNO. The primary endpoint was change in ACQ7 score (Asthma Control Questionnaire, 7 questions). Analysis was carried out in a Main Analysis Set (MAS), which contained all randomised patients who complied with their study treatment and completed follow-up within 6 weeks of randomisation, and in a Per Protocol (PP) set, which included all patients in the MAS but excluded protocol violations. Results: In the PP set (n=214), we found that higher baseline FeNO was associated with a greater treatment effect. Improvement of ACQ7 was 0.071 (95% confidence interval [CI], 0.002-0.139) greater in patients receiving extrafine ICS compared to patients receiving placebo, for every 10 ppb increase in baseline FeNO. The equivalent effect was not significant in the MAS set (n=259) (0.049; 95% CI, -0.012-0.110). Conclusions: FeNO measurement is a simple, near patient, quantitative and non-invasive diagnostic tool that could support treatment decisions for patients with NSRS. Further research is needed to establish a treatment paradigm.

Background Asthma is a chronic inflammatory respiratory disorder associated with reduced lung function and poor quality of life. The condition is also associated with poor self-rated health, a major predictor of objective health trajectories. Of biological correlates to self-rated health, evidence suggests a role for inflammatory cytokines and related sickness behaviours. However, this is mainly based on cross-sectional data, and the relation has not been investigated in patients with chronic inflammatory conditions. Objective To investigate inflammatory cytokines, lung function, sickness behaviour and asthma-related quality of life as determinants of self-rated health in patients with asthma, and to investigate if these variables co-vary over time. Methods Plasma cytokines (IL-5, IL-6), lung function (FEV1), sickness behaviour, asthma-related quality of life and self-rated health were assessed in 181 patients with allergic asthma aged 18-64 years in a one-year longitudinal study. Mixed effect regression models and Spearman's correlation were performed to analyse the associations between repeated measurements. Results More sickness behaviour and poorer asthma-related quality of life were associated with poorer self-rated health (p's

Introduction: Self-rated health (SRH) is a relevant measure of health as it can predict morbidity, mortality and health-care use. Studies have shown an association between poor SRH and elevated levels of circulating inflammatory cytokines. It is therefore interesting to learn more about the association between asthma, a chronic inflammatory disease with a recognised systemic component and SRH. Objectives: To compare SRH ratings in respondents with and without current asthma. A second aim was to compare SRH with quality-of-life ratings in the same groups. Methods: In 1995, we randomly selected 8200 persons ≥18 years from the population of Stockholm County, Sweden and mailed them a questionnaire. A total of 5355 persons (67.5%) responded. Respondents were divided in two groups, those with and those without current asthma. The groups were further divided by sex and age (18–44 and ≥45 years). SRH was measured with the question ‘How do you rate your general health status?’ and quality of life with the Gothenburg Quality of Life Instrument and the Ladder of Life. Results: Respondents with asthma rated their health significantly worse than did those without asthma, except women aged 18–44 years. SRH was associated at least as strong as quality of life to asthma with the advantage of being easier to apply (only one item). Conclusion: Information on SRH is easy to obtain and represents an important dimension of health status that potentially can be used as a complement to identify patients who need extra attention to manage their asthma and its consequences. Please cite this paper as: Syk J, Alving K and Unden A-L. Association between self-rated health and asthma: a population-based study. Clin Respir J 2012; 6: 150–158.

Introduction: The influence of the degree of immunoglobulin E (IgE) sensitisation on the fraction of expired nitric oxide (FENO) in asthma patients being treated with inhaled corticosteroids (ICS) is not well known. Objectives: To investigate the relationship between IgE sensitisation and FENO, and the effect of a step-up in ICS treatment on this relationship, in patients with allergic asthma. Methods: A primary health care centre recruited 20 non-smoking patients with perennial allergic asthma (18 years–50 years, six male) outside the pollen season. At every visit (0, 2, 4, 8 weeks), FENO was measured and an exposure questionnaire was completed. ICS dose was adjusted according to FENO (≥22 ppb prescribed increase in ICS). Quantitative analyses of serum IgE (eight common aeroallergens) confirmed allergy. Results: At baseline, FENO and the sum of IgE antibody titres for perennial allergens correlated significantly (r = 0.47, P = 0.04). After a step-up in ICS treatment, this correlation had disappeared. Nine patients had persistently elevated FENO at last visit (mean 35 ppb vs 16 ppb). This group was more frequently exposed to relevant allergens or colds (89% vs 27% of patients, P

Allergic asthma is a chronic inflammatory disorder with both local and systemic inflammation and is associated with elevated levels of IgE. Poor self-rated health has repeatedly been associated to inflammatory markers, but the nature of this relationship in states of chronic inflammatory disease in not known. Likewise, such findings largely rely on cross-sectional investigations. Here, we investigated the associations between self-rated health and levels of IgE over time in patients with asthma. Self-rated health and levels of IgE were assessed in 181 (87 women) non-smoking patients with allergic asthma aged 18–64 years in a one-year longitudinal study with two repeated measurements. All patients had a confirmed IgE sensitization to at least one airborne perennial allergen. Analyses of associations between repeated measurements were performed using mixed regression models and spearman’s correlations. Poor self-rated health was associated with higher levels of seasonal IgE ( p p p = 0.04). In conclusion, systemic levels of IgE in response to seasonal-, food and perennial allergens is a possible determinant of self-rated health in individuals with asthma.

Background Airway inflammation is the fundamental mechanism in asthma and can be measured non-invasively by means of fractional exhaled nitric oxide (FeNO). Both, The National Institute for Health and Care Excellence (NICE) diagnostics guidance 12 and British guideline on the management of asthma, are recommending the inclusion of FeNO testing as part of diagnosis in patients that have an intermediate probability of having asthma. Furthermore, FeNO testing is recommended as an option for monitoring response to corticosteroid treatment in patients with increased FeNO. However, there is a need for establishing routine data predictors for individuals with increased FeNO, to identify those that would benefit from FeNO measurement as a tool for aiding asthma diagnosis and monitoring treatment responsiveness. To provide a real-life predictive model for the identification of individuals at risk of asthma that have increased FeNO.

Atopic asthma is characterized by Th2 cytokine-driven inflammation of the airway mucosa, which is signaled by the fraction of exhaled nitric oxide (FENO).We tested whether an FENO-guided anti-inflammatory treatment algorithm could improve asthma-related quality of life and asthma symptom control, and reduce exacerbations in atopic asthmatics within primary care.Altogether, 187 patients with asthma and who were nonsmokers (age range, 18-64 years) with perennial allergy and who were on regular inhaled corticosteroid treatment were recruited at 17 primary health care centers, randomly assigned to 2 groups and followed up for 1 year. For the controls (n = 88), FENO measurement was blinded to both operator and patient, and anti-inflammatory treatment was adjusted according to usual care. In the active group (n = 93), treatment was adjusted according to FENO. Questionnaires on asthma-related quality of life (Mini Asthma Quality of Life Questionnaire) and asthma control (Asthma Control Questionnaire) were completed, and asthma events were noted.The Asthma Control Questionnaire score change over 1 year improved significantly more in the FENO-guided group (-0.17 [interquartile range {IQR}, -0.67 to 0.17] vs 0 [-0.33 to 0.50]; P = .045), whereas the Mini Asthma Quality of Life Questionnaire score did not (0.23 [IQR, 0.07-0.73] vs 0.07 [IQR, -0.20 to 0.80]; P = .197). The change in Asthma Control Questionnaire was clinically important in subpopulations with poor control at baseline (P = .03). Furthermore, the exacerbation rate (exacerbations/patient/y) was reduced by almost 50% in the FENO-guided group (0.22 [CI, 0.14-0.34] vs 0.41 [CI, 0.29-0.58]; P = .024). Mean overall inhaled corticosteroid use was similar in both groups (P = .95).Use of FENO to guide anti-inflammatory treatment within primary care significantly reduced the exacerbation rate and improved asthma symptom control without increasing overall inhaled corticosteroid use.

Allergic asthma is a chronic inflammatory disorder with both local and systemic inflammation and is associated with elevated levels of cytokines as well as exhaled fraction of nitric oxide (FeNO). Fatigue is a prominent symptom. Poor self-rated health has previously been associated to fatigue and inflammatory markers. However, it is not known if self-rated health is associated with fatigue and inflammation also in patients with asthma. Here, we investigated the associations between self-rated health, fatigue, inflammatory cytokines and FeNO in patients with asthma. Self-rated health, fatigue, levels of cytokines and FeNO were assessed in 184 (93 men, 91 women) non-smoking patients with allergic asthma aged 18–64 years in a one-year longitudinal study with five repeated measurements, two for cytokine levels. Analyses of associations between repeated measurements were performed using mixed regression models. More fatigue was associated with poor self-rated health in both men and women ( p p