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Background: Patients with severe asthma often have uncontrolled disease and experience mood disorders, particularly anxiety and depression. The autonomic nervous system (ANS) plays an important role in asthma, mainly through the parasympathetic ANS system (PANS), which favors bronchoconstriction and mental health status., Objective: To evaluate the role of the activation of the PANS in uncontrolled asthma and related mood disorders., Methods: This was a proof-of-concept cross-sectional study that analyzed demographic and clinical variables reflecting asthma severity and control, lung function, inflammation (from induced sputum), evaluation of quality of life, and the risk for anxiety and depression according to validated questionnaires. The PANS analysis was conducted based on heart rate variability: SD of the difference between consecutive normal-to-normal (NN) intervals (SDNN), root mean square of the successive differences (RMSSD), percentage of consecutive NN intervals (pNN50), total power (TP), and respiratory-related power (Pr)., Results: A total of 30 patients with asthma were grouped according to asthma control and the risk for anxiety and depression; 10 patients with uncontrolled asthma compared with the patients with controlled asthma showed significant differences (P < .05) in SDNN (26.5 [8.2] vs 42.7 [29.7]), RMSSD (14.1 [6.5] vs 24 [20]), pNN50 (0.6 [1.5] vs 6.2 [11.8]), TP (0.0005 [0.00046] vs 0.0014 [0.00085]), and Pr (0.0003 [0.00025] vs 0.0007 [0.00060]) respectively. A total of 13 patients at risk for anxiety and depression compared with the patients without showed reduced values (P < .05) for SDNN (26.5 [7.9] vs 45.6 [31.3]), pNN50 (0.75 [1.4] to 7.12 [12.6]), TP (0.0005 [0.00048] to 0.0012 [0.0008]), and Pr (0.0003 [0.00027] to 0.0008 [0.00062])., Conclusion: Our results suggest that PANS activity is depressed in patients with uncontrolled asthma and common mood disorders such as depression and anxiety, and the evaluation of heart rate variability may be a useful means for follow-up of asthma control and related mood disorders., Competing Interests: Disclosures The authors have no conflict of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The concept of "remission" in asthma has been around for a long time and it has been a controversial topic. Despite the attempts of some studies to characterize this entity, the discussion continues. In the case of asthma there is still no clear definition, either in terms of its meaning or the parameters that should be included or whether it should be divided into clinical or complete remission. To help defining these controversial concepts, SEPAR has advocated the multidisciplinary working group REMAS (REMission in ASthma). Following the Delphi methodology and with the involvement of more than 120 specialists in asthma management, this group has arrived at a consensus on the definitions of remission in asthma and establishing the criteria and characteristics that will be of use in future studies evaluating the efficacy or effectiveness of treatments., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Evaluation of biologic therapy response is vital to monitor its effectiveness. Authors have proposed various response criteria including good responder, super-responder, non-responder, and clinical remission., Objectives: To ascertain the prevalence of response and clinical remission after long-term treatment (>6 months) of anti-IgE and anti-IL-5/IL-5Rα biologics, compare these results with existing criteria, and identify predictors for non-responders and clinical remission., Methods: A multicenter, real-life study involving severe asthma patients in Spain. Various outcomes were assessed to gauge response and clinical remission against established criteria., Results: The study included 429 patients, 209 (48.7%) omalizumab, 112 (26.1%) mepolizumab, 19 (4.4%) reslizumab and 89 (20.7%) benralizumab, with a mean treatment duration of 55.3±38.8 months. In the final year of treatment, 218 (50.8%) were super-responders, 173 (40.3%) responders, 38 (8.9%) non-responders, and clinical remission in 116 (27%), without differences among biologics. The short-term non-responders (<6 months) were 25/545 (4.6%). Substantial variations in response and clinical remission were observed when applying different published criteria. Predictors of non-response included higher BMI (OR:1.14; 95% CI:1.06-1.23; p<0.001), admissions at ICU (2.69; 1.30-5.56; p=0.01), high count of SAE (1.21; 1.03-1.42; p=0.02) before biologic treatment. High FEV 1 % (0.96; 0.95-0.98; p<0.001), a high ACT score (0.93; 0.88-0.99; p=0.01) before biologic treatment or NSAID-ERD (0.52; 0.29-0.91; p=0.02) showed strong associations with achieving clinical remission., Conclusion: A substantial proportion of severe asthma patients treated long-term with omalizumab or anti-IL5/IL-5Rα achieved a good response. Differences in response criteria highlight the need for harmonization in defining response and clinical remission in biologic therapy to enable meaningful cross-study comparisons., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: The definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes., Methods: We performed a multicentre prospective cohort study, including adult patients with asthma (N=512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A standardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm., Results: Four clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities., Conclusion: We defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Nowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR. Additionally, pathway enrichment analysis of deregulated miRNAs was conducted. We observed altered expression by the next-generation sequencing (NGS) of 11 miRNAs in serum, of which five (hsa-miR-148b-3p, hsa-miR-221-5p, hsa-miR-618, hsa-miR-941, and hsa-miR-769-5p) were validated by RT-qPCR, and three miRNAs in lung tissue (hsa-miR-144-3p, hsa-miR-144-5p, and hsa-miR-451a). The best multivariate logistic regression model to differentiate individuals with severe asthma, treated and untreated with OCS, was to combine the serum miRNAs hsa-miR-221-5p and hsa-miR-769-5p. Expression of hsa-miR-148b-3p and hsa-miR-221-5p correlated with FEV 1 /FVC (%) and these altered miRNAs act in key signaling pathways for asthma disease and the regulated expression of some genes ( FOXO3 , PTEN , and MAPK3 ) involved in these pathways. In conclusion, there are miRNA profiles differentially expressed in OCS-treated individuals with asthma and could be used as biomarkers of OCS treatment.

Objective: To collect perspectives and explore consensus for expert recommendations related to asthma control and the use of telemedicine among professionals who manage patients with asthma., Design: A Delphi-like questionnaire was designed to analyse the level of agreement about several recommendations formulated by an expert scientific committee about asthma control and the use of telemedicine with this purpose. A dedicated scientific committee validated the questionnaire, which included questions about the participants' profile and the use of technological tools at a personal level or in clinical practice. The experts expressed their agreement with a Likert-scale of 9 values: 1-3 was considered no agreement, 4-6 neutral, and 7-9 agreement. A rate ≥70% with the same answer was considered consensus. SITE: The questionnaire was programmed and distributed as an internet-based survey., Participants: A pre-selected sample of 75 experts with experience in telemedicine (pulmonology, allergology, family medicine, nursing and community pharmacy) responded to a Delphi-like questionnaire composed by six questions and 52 items., Interventions: Consultation was performed in two consecutive waves: the first wave was carried out from 12th of July to 8th of September of 2021; the second wave, from 25th of October to 12th of November of 2021., Main Measurements: Three questions about asthma control (actions for achieving or maintaining control of asthma at every visit, current problems that affect asthma control, and potential solutions to offset such problems), and three questions about the impact of telemedicine in asthma control (potential benefits of telemedicine, and potential reticence about telemedicine among both patients and healthcare professionals) were included., Results: From the 52 items inquired, 35 were agreed by consensus. The actions for achieving or maintaining control of asthma, the problems that affect asthma control, and their potential solutions were agreed by consensus. The potential benefits of telemedicine were validated by consensus. None of the potential reservations of patients about telemedicine were validated, while five out of 14 potential reservations of healthcare professionals were agreed by consensus., Conclusions: The COMETA consensus provides a current picture of the main problems for achieving asthma control, the benefits and the reservations about the use of telemedicine in the Spanish setting, and offers solutions. A wide interest in implementing telemedicine has been observed, although current limitations need to be overcome., (Copyright © 2022 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Two subsets of eosinophils have been described: resident eosinophils with homeostatic functions (rEOS) in healthy subjects and in patients with nonallergic eosinophilic asthma, and inflammatory eosinophils (iEOS) in blood and lung samples from patients with allergic asthma. We explored if it would be possible to identify different subsets of eosinophils using flow cytometry and the gating strategy applied to induced sputum. We conducted an observational cross-sectional single-center study of 62 patients with persistent allergic asthma. Inflammatory cells from induced sputum samples were counted by light microscopy and flow cytometry, and cytokine levels in the supernatant were determined. Two subsets of eosinophils were defined that we call E1 (CD66b-high and CD15-high) and E2 (CD66b-low and CD15-low). Of the 62 patients, 24 were eosinophilic, 18 mixed, 10 paucigranulocytic, and 10 neutrophilic. E1 predominated over E2 in the eosinophilic and mixed patients (20.86% vs. 6.27% and 14.42% vs. 4.31%, respectively), while E1 and E2 were similar for neutrophilic and paucigranulocytic patients. E1 correlated with IL-5, fractional exhaled nitric oxide, and blood eosinophils. While eosinophil subsets have been identified for asthma in blood, we have shown that they can also be identified in induced sputum.

Background: Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists., Objective: To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe., Methods: Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States. Negative binomial models (incidence rate ratio [IRR] [95% CI adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations., Results: Across severities, 40.2% of patients were prescribed/possessed 3 or more SABA canisters/y. Per the Global Initiative for Asthma (GINA) 2018 definitions, steps 3 to 5-treated patients prescribed/possessing 3 or more versus 1 or 2 SABAs experienced more severe exacerbations (IRR 1.08 [95% CI 1.04‒1.13], U.S. Medicare; IRR 2.11 [95% CI 1.96‒2.27], Poland). This association was not observed in all step 1 or 2-treated patients (the Netherlands, IRR 1.25 [95% CI 0.91‒1.71]; U.S. commercial, IRR 0.92 [95% CI 0.91‒0.93]; U.S. Medicare, IRR 0.74 [95% CI 0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the U.S. datasets was attributable to the large patient population possessing fewer than 3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face health care provider encounters. In U.S. SABA monotherapy-treated patients, 3 or more SABAs were associated with more emergency/outpatient visits and hospitalizations (IRR 1.31 [95% CI 1.29‒1.34]). Most GINA 2 to 5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of 3 or more SABAs and severe exacerbations persisted (IRR 1.32 [95% CI 1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when U.K. SABA data were analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications., Conclusions: Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression., Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10 -5 ) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico., Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR T allele ) = 0.82, p = 9.05 × 10 -6 and replication: OR T allele  = 0.89, p = 5.35 × 10 -3 ) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR C allele  = 0.85, p = 3.10 × 10 -5 and replication: OR C allele  = 0.89, p = 1.30 × 10 -2 ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood., Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense., (© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

In this fifth phase of development, the contents of the Spanish Asthma Management Guidelines (GEMA), which include versions 5.0 and 5.1, have undergone a thorough review. The aim here is to set the main changes in context. These could be summarized as follows: DIAGNOSIS: new FE NO cut-off and severity classification based on treatment needed to maintain control; INTERMITTENT ASTHMA: a more restrictive concept and treatment extended to include a glucocorticoid/adrenergic combination as needed; MILD ASTHMA: glucocorticoid/adrenergic therapy as needed as an alternative in case of low therapeutic adherence to conventional fixed-dose steroids; SEVERE ASTHMA: readjustment of phenotypes, incorporation of triple therapy in a single inhaler, and criteria for selection of a biologic in severe uncontrolled asthma; OTHERS: specific scoring in childhood asthma, incorporation of certain organizational aspects (care circuits, asthma units, telemedicine), new sections on COVID-19 and nasal polyposis., (Copyright © 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction : Many patients sensitized to mites remain symptomatic and uncontrolled despite traditional treatment. Sublingual immunotherapy (SLIT) has demonstrated to reduce the symptoms of allergic rhinitis, the need for additional drug treatments, and to reduce the number of moderate and severe exacerbations in patients with allergic asthma caused by mites that had not been adequately controlled. Areas covered : After reviewing the most recent literature, a scientific committee composed by five pneumologists experts in asthma proposed 41 items that addressed the diagnosis of allergic asthma caused by mites, the role of house dust mite (HDM) SLIT tablet in the therapeutic plan and in the control of the disease, and the profile of patients with asthma candidates for this therapy. Through a modified Delphi method, the items were send to 106 pneumologists involved in asthma to be agreed. Expert opinion : The high degree of consensus reached by the panel of pneumologists shows the importance of HDM SLIT tablet in the treatment of allergic asthma caused by mites, particularly taking into account that they barely use this therapy because until now they did not have a registered treatment with solid evidence of efficacy and safety.

Introduction: Asthma with airway mucus hypersecretion is an inadequately characterized variant of asthma. While several studies have reported that hypersecreting patients may carry genetic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of those studies have been questioned for their numerous limitations and contradictory results., Objectives: (1) To determine the presence of genetic variants of the CFTR gene in patients with asthma with and without airway mucus hypersecretion. (2) To identify the clinical, inflammatory and functional characteristics of the asthma phenotype with airway mucus hypersecretion., Method: Comparative multicentre cross-sectional descriptive study that included 100 patients with asthma (39 hypersecretors and 61 non-hypersecretors). Asthmatic hypersecretion was defined as the presence of cough productive of sputum on most days for at least 3 months in 2 successive years. The patients were tested for fractional exhaled nitric oxide, spirometry, induced sputum cell count, total immunoglobulin E (IgE), peripheral blood eosinophil count, C-reactive protein, blood fibrinogen and blood albumin and underwent a skin prick test. Asthma control and quality of life were assessed by the Asthma Control Test and Mini Asthma Quality of Life questionnaires, respectively. Blood DNA samples were collected from the patients and next-generation sequencing using a MiSeq sequencer and the Illumina platform was used for the CFTR gene analysis., Results: Genetic differences were observed in the c.1680-870T>A polymorphism of the CFTR gene, significantly more evident in hypersecretors than in non-hypersecretors: 78.94% vs. 59.32% in the majority allele and 21.05% vs. 40.67% in the minority allele (p = 0.036). Clinically, asthma hypersecretors compared to non-hypersecretors were older (57.4 years vs. 49.4 years; p = 0.004); had greater asthma severity (58.9% vs. 23.7%; p = 0.005); experienced greater airway obstruction (FEV1/FVC% 64.3 vs. 69.5; p = 0.041); had poorer asthma control (60% vs. 29%; p = 0.021); had lower IgE levels (126.4 IU/mL vs. 407.6 IU/mL; p = 0.003); and were less likely to have a positive prick test (37.5% vs. 68.85%; p = 0.011)., Conclusion: The results suggest that patients with asthma and with mucus hypersecretion (1) may have a different phenotype and disease mechanism produced by an intronic polymorphism in the CFTR gene (NM&#95;000492.3:c.1680-870T>A), and (2) may have a poorer clinical outcome characterized by severe disease and poorer asthma control with a non-allergic inflammatory phenotype., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AC has received fees in the last three years for talks at meetings sponsored by Chiesi, Esteve Laboratories, GlaxoSmithKline, Novartis, Ferrer, Zambón and Boehringer Ingelheim, has received travel and attendance expenses for conferences from Novartis, Bial, Teva and FAES Farma and has received funds/grants for research projects from several state agencies and non-profit foundations and from AstraZeneca. EC reports non-financial support from Astrazeneca, personal fees from Boehringer-Ingleheim, personal fees and non-financial support from Chiesi, non-financial support from Novartis, non-financial support from Menarini, non-financial support from ALK, outside the submitted work. SB, EdR, ER, CM, NM, AP, SP, JG, AP, CC, JS and MB have no conflicts of interest to declare. VP has received fees in the last three years for talks at meetings sponsored by AstraZeneca, Boehringer-Ingelheim, MSD and Chiesi, has received travel and attendance expenses for conferences from AstraZeneca, Chiesi and Novartis, has acted as a consultant for ALK, AstraZeneca, Boehringer, MSD, MundiPharma and Sanofi, and has received funds/grants for research projects from several state agencies and non-profit foundations and from AstraZeneca, Chiesi and Menarini. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Asthma is managed by health professionals from different specialties. We aim to reach a consensus on the optimal use of inhaled therapy and the initial steps of asthma treatment, taking into account the opinions of the involved specialists., Methods: A modified Delphi approach was used. A scientific committee provided 52 controversial statements, which were submitted to primary care physicians, allergists, and pulmonologists. Discrepancies among specialties were evaluated., Results: A total of 209 specialists completed the questionnaire (20.2 ± 9.3 years of asthma management experience). A consensus was reached on 37 statements (71.1%), discrepancies among specialties were found in 14. The most recommended maintenance treatment for mild persistent asthma in adults/adolescents was low-dose-inhaled corticosteroids daily. MART (Maintenance and Reliever Therapy) was recommended as salvage treatment for moderate persistent asthma. Panelists agreed on the most frequent critical errors with pressurized Metered-Dose Inhalers or Dry-Powder Inhalers, and considered that Breath-Actuated Inhalers are a suitable option for all patients with the ability to inhale voluntarily., Conclusions: The experts endorse the main guidelines recommendations; however, do not fully agree on recent GINA recommendations about the treatment of the initial steps of the disease. The experts value positively the differential characteristics of BAI over other devices.

Objective: Adherence and inhaler technique are often suboptimal in asthma and chronic obstructive pulmonary disease (COPD). New inhalers have been developed to improve these determinants of treatment effectiveness. We assessed treatment adherence, satisfaction, and ease of use of DuoResp ® Spiromax ® among SPRINT study participants. Methods: The Phase IV SPRINT study was conducted in 10 European countries. Asthma and COPD patients were receiving a fixed-dose combination of inhaled corticosteroid (ICS) and long-acting β 2 -agonist (LABA), delivered via various inhalers including DuoResp Spiromax. DuoResp Spiromax users self-assessed adherence using the 8-item Morisky Medication Adherence Scale (MMAS-8 ® ), and ease of use and satisfaction using 10-point scales, during a single physician's office visit. Results: Of 1661 (asthma: n  = 1101; COPD: n  = 560) SPRINT study participants, 342 (asthma: n =  235; COPD: n =  107) received DuoResp Spiromax prior to inclusion. Overall, 72.5% of DuoResp Spiromax users reported medium or high adherence (MMAS-8 score ≥6). Mean (standard deviation [SD]) satisfaction score for DuoResp Spiromax was 8.9 (1.6). Almost all (98.8%) DuoResp Spiromax users were at least satisfied with their inhaler; 85.4% were very satisfied. Mean (SD) ease of use score for DuoResp Spiromax was 9.1 (1.3). Conclusions: Asthma and COPD patients using DuoResp Spiromax reported moderate-to-high medication adherence, were very satisfied with their inhaler and found it easy to use.

Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) - understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis., Competing Interests: Luis Perez de Llano declares to have received grants and/or fees for consultancy or speeches from Novartis, Astra-Zeneca, GSK, Teva, Boehringer-Ingelheim, Chiesi, Sanofi, Menarini, Mundipharma, and Esteve, and reports grants, personal fees, and non-financial support from AstraZeneca, TEVA, and Chiesi, personal fees and non-financial support from GSK, Novartis, Mundipharma and Boehringer, personal fees from Sanofi, other from Menarini, and personal fees from Esteve, BIAL, TECHDOW PHARMA, MSD, and ROVI S.A., outside the submitted work; Marc Miravitlles has received speaking fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, AstraZeneca, Menarini, Rovi, Bial, Zambon, CSL Behring, Grifols, and Novartis; consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Ferrer, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, pH Pharma, Novartis, and Grifols; and aid for research from GlaxoSmithKline and Grifols, and reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Novartis, GlaxoSmithKline, Gebro Pharma, Kamada, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Sanofi and Grifols, and grants from GlaxoSmithKline and Grifols, outside the submitted work. Rafael Golpe declares that he has received speaking or advisory fees, or economic aid to attend congresses from Astra-Zeneca, GSK, Novartis, Chiesi, Mundipharma, Menarini, TEVA, Grifols, Ferrer, Boehringer-Ingelheim, Rovi, and Gebro. Borja G Cosío declares he has received speaking or advisory fees, or economic aid to attend congresses from Astra-Zeneca, GSK, Novartis, Chiesi, Mundipharma, Menarini, TEVA, Boehringer-Ingelheim, and Rovi and reports personal fees from AstraZeneca, GlaxoSmithKline, Rovi, Boehringer-Ingelheim, Chiesi, Menarini, Rovi, Zambon, Grifols, Novartis, Ferrer, Gebro Pharma, and Laboratorios Esteve, during the conduct of the study. Francisco Javier Alvarez-Gutiérrez declares that in the last 3 years he has received fees for advisory work, lectures, or subsidies to attend congresses and scientific meetings from ALK, AstraZeneca, BIal, Boehringer-Ingelheim, Chiesi, GSK, Menarini, Mundipharma, Novartis, and TEVA. Carolina Cisneros has received speaking fees from AstraZeneca, GSK, TEVA, Menarini, Mundipharma, and Novartis; aid to attend congresses from Chiesi, TEVA, Menarini, and Mundipharma; and fees for advisory work from ALK, AstraZeneca, MundiPharma, TEVA, GSK, and Novartis, and reports grants, personal fees, and non-financial support from AstraZeneca, grants and personal fees from GSK and Novartis, personal fees and non-financial support from TEVA, Menarini, Chiesi and Mundipharma, and personal fees from ALK, outside the submitted work. Carlos Almonacid declares to have received funding in the last 5 years from Astra-zeneca, GSK, Novartis, Chiesi, Mundipharma, Menarini, and TEVA, by way of aid to attend congresses, or as speaking or consulting fees, and reports grants and personal fees from GSK and AstraZeneca, personal fees from ALK, Novartis, Chiesy, and Mundipharma, and non-financial support from Menarini, outside the submitted work. Eva Martinez-Moragon declares to have received funding in the last 5 years from Astra-zeneca, GSK, ALK, Novartis, Chiesi, Mundipharma, Menarini, and TEVA, by way of aid to attend congresses, as speaking fees, or participation in scientific consultancy. Francisco-Javier Gonzalez-Barcala has received speaking fees or research grants from ALK, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Gebro Pharma, GlaxoSmithKline, Laboratorios Esteve, Menarini, Mundipharma, Novartis, Rovi, Roxall, Stallergenes-Greer, and Teva, and reports speaker fees, consulting fees or research grants from ALK, Astra-Zeneca, Bial, Boehringer Ingelheim, Chiesi, Gebro Pharma, GlaxoSmithKline, Laboratorios Esteve, Menarini, Mundipharma, Novartis, Rovi, Roxall, Stallergenes-Greer and Teva. David Ramos-Barbón reports personal fees from GlaxoSmithKline, AstraZeneca, TEVA Pharmaceuticals, personal fees and non-financial support from Novartis and Chiesi, non-financial support from Boehringer-Ingelheim, and personal fees from BIAL Pharmaceuticals, outside the submitted work. Vicente Plaza declares to have received, in the last 3 years, fees for participating as speaker at meetings sponsored by AstraZeneca, Chiesi, and Novartis, and as a consultant from ALK, AstraZeneca, Bial, Boehringer, MundiPharma, and Sanofi; he received economic aid to attend congresses from AZ, Chiesi, and Novartis; and he received subsidies for research projects from AZ, Chiesi, and Menarini; and reports grants and personal fees from AstraZeneca and Chiesi, grants from Menarini, and personal fees from Sanofi, Mundipharma, Boehringer-Ingelheim, GlaxoSmithKline, and Merck, outside the submitted work. Jose Luis López-Campos has received fees, in the last 3 years, for giving lectures, scientific consultancy, participation in clinical studies, or writing papers for (alphabetical order): AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, Esteve, Ferrer, Gebro, GlaxoSmithKline, Grifols, Menarini, Novartis, Rovi, and Teva, and reports personal fees and non-financial support from AstraZeneca, grants, personal fees, and non-financial support from Boehringer, Chiesi, GSK, Grifols, Menarini, and Novartis, personal fees from CSL Behring, Esteve, and Ferrer, grants and personal fees from GebroPharma, and personal fees from Rovi and Teva, outside the submitted work. Ciro Casanova has received fees for giving lectures, scientific consultancy, participation in clinical studies, or writing papers for (alphabetical order): AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Esteve, Gebro, GlaxoSmithKline, Menarini, Novartis, Rovi, and Teva, and reports non-financial support from Astra-Zeneca, personal fees from Bial, Boehringer-Ingelheim, Chiesi, Esteve, and Novartis, personal fees and non-financial support from GSK, and grants and non-financial support from Menarini, outside the submitted work. Juan Luis Rodriguez Hermosa has received speaking fees from Boehringer Ingelheim and Gebro Pharma and reports personal fees from Boehringer Ingelheim, Grifols, Gebro, and Glaxo, outside the submitted work. Myriam Calle Rubio has received speaking fees from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, Menarini, and Novartis; and consulting fees from GlaxoSmith¬Kline, Gebro Pharma, and Novartis, and reports personal fees from Boehringer Ingelheim, Menarini, Novartis, Gebro, Glaxo, and AstraZeneca, outside the submitted work. JJ Soler-Cataluña declares to have received fees for giving lectures, scientific consultancy, or participation in clinical studies on behalf of Air Liquide, AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GSK, Menarini, Mundipharma, Novartis, Rovi, Sandoz, and Teva and reports grants and personal fees from AstraZeneca, Chiesi, and GSK, grants, personal fees, and non-financial support from Boehringer-Ingelheim and Novartis, and personal fees from Bial, Ferrer, Rovi, and Teva, outside the submitted work. Borja G Cosio reports grants and personal fees from AstraZeneca, Chiesi, and GSK, personal fees from Novartis, personal fees and non-financial support from Mundipharma, and grants from Menarini, Teva, Boehringer-Ingelheim, and Rovi, outside the submitted work. The rest of the authors declare they have no conflict of interests for this work. The rest of the authors declare they have no conflict of interests for this work., (© 2020 Pérez de Llano et al.)

Several modifiable factors leading to poor asthma control have been described. We aimed to determine the proportion of patients with inadequate treatment, adherence to it, or critical mistakes with inhaler technique, and their impact on asthma control. We conducted a cross-sectional multicenter observational study including asthma patients referred from primary to specialist care for the first time. Data collected were adequate prescription according to guidelines, treatment adherence, and disease control. Of the 1682 patients (age 45 ± 17 years, 64.6% men), 35.9% showed inadequate prescription, 76.8% low adherence, and 17% critical mistakes with inhaler technique, with significantly less critical mistakes among Easyhaler users versus other dry powder inhaler users (10.3 versus 18.4%; p < 0.05). Factors related to bad asthma control were inadequate prescription (OR: 3.65), non-adherence to treatment (OR: 1.8), and inhaler misuse (OR: 3.03). A higher number of risk factors were associated with a higher probability of having badly controlled asthma.

Background: Satisfaction with the inhaler is an important determinant of treatment adherence in patients with asthma and chronic obstructive pulmonary disease (COPD). However, few studies have compared these 2 groups to identify the factors associated with satisfaction with the inhaler., Objective: To assess and compare satisfaction with the inhaler in patients with asthma or COPD and to determine the variables associated with high inhaler satisfaction., Methods: A multicenter, cross-sectional study of 816 patients (406 with asthma and 410 with COPD) was conducted. Satisfaction was assessed with the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire. All participants completed the Test of Adherence to Inhalers and either the Asthma Control Test (ACT) or the COPD Assessment Test (CAT)., Results: Overall, the asthma group was significantly more satisfied with the inhaler (mean [standard deviation] FSI-10 scores: 44.1 [6.5] vs 42.0 [7.7]; P < .001) and more satisfied on most (7 of 10; 70%) items. Patients with asthma were significantly more satisfied with the inhaler regardless of the adherence level or the type of nonadherence pattern. Younger age, good disease control (ACT ≥20 or CAT ≤10), previous inhaler training, and absence of unwitting nonadherence were all independently and significantly associated with high inhaler satisfaction., Conclusions: Age, disease control, and training in inhalation technique all play a more significant role than the specific diagnosis in explaining satisfaction with the device in patients with asthma and COPD. These findings underscore the need to provide better training and more active monitoring of the inhalation technique to improve patient satisfaction, treatment adherence, and clinical outcomes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Most patients with nonallergic asthma have normal serum immunoglobulin E (IgE) levels. Recent reports suggest that total and aeroallergen-specific IgE levels in induced sputum may be higher in nonallergic asthmatics than in healthy controls. Our objective is to compare total and dust-mite specific (Der p 1) IgE levels in induced sputum in allergic and nonallergic asthmatics and healthy controls., Methods: Total and Der p 1-specific IgE were measured in induced sputum (ImmunoCAP immunoassay) from 56 age- and sex-matched asthmatics (21 allergic, 35 nonallergic) and 9 healthy controls. Allergic asthma was defined as asthma with a positive prick test and/or clinically-significant Der p 1-specific serum IgE levels., Results: Patients with allergic asthma presented significantly higher total and Der p 1-specific serum IgE levels. There were no significant between-group differences in total sputum IgE. However, Der p 1-specific sputum IgE levels were significantly higher (p = 0.000) in the allergic asthmatics, but without differences between the controls and nonallergic asthmatics. Serum and sputum IgE levels were significantly correlated, both for total IgE (rho = 0.498; p = 0.000) and Der p 1-specific IgE (rho, 0.621; p = 0001)., Conclusions: Total IgE levels measured in serum and induced sputum are significantly correlated. No significant differences were found between the differents groups in total sputum IgE. Nevertheless, the levels of Der p 1-specific sputum IgE levels were significantly higher in the allergic asthmatics, but without differences between the controls and nonallergic asthmatics. Probably due to the lack of sensitivity of the test used, but with the growing evidence for local allergic reactions better methods are need to explore its presence. The Clinical Trials Identifier for this project is NCT03640936., Competing Interests: AC. in the last three years received honoraria for speaking at sponsored meetings from AstraZeneca, Chiesi, Esteve Laboratories, Faes Farma, Ferrer, GlaxoSmithKline, Novartis, Teva, Zambon. Received help assistance to meeting travel from Bial, Novartis. Act as a consultant for AstraZeneca, Boehringer, GlaxoSmithKline, Novartis. And received funding/grant support for research projects from a variety of Government agencies and not-for-profit foundations, as well as AstraZeneca. EC has received funding to travel to and attend training activities from ALK, Menarini, Teva, AstraZeneca, Chiesi, Boehringer, and Novartis. LS, EM and declare no conflict of interests. JG has received funding to travel and attend to training activities from Menarini, Teva, AstraZeneca, Chiesi, GSK, Mundipharma, Boehringer. In the last three years, VP has received honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer-Ingelheim, Chiesi, GSK, and Novartis. VP has also received financial support to travel to meetings organized by Chiesi and Novartis. VP is a consultant for ALK, AstraZeneca, Boehringer, MundiPharma, and Sanofi. VP has also received funding/grant support for research projects from a variety of governmental agencies and not-for-profit foundations, as well as from AstraZeneca, Chiesi and Menarini.

Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m -2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day -1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day -1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries., Competing Interests: Conflict of interest: J.J.M.H. van Bragt has nothing to disclose. Conflict of interest: I.M. Adcock has nothing to disclose. Conflict of interest: E.H.D. Bel reports grants and personal fees from AstraZeneca, GSK and Novartis, grants from Teva, and personal fees from Boehringer Ingelheim, Sanofi/Regeneron, Vectura and Sterna, outside the submitted work. Conflict of interest: G-J. Braunstahl reports grants from GSK, Novartis, AstraZeneca and Chiesi, outside the submitted work. Conflict of interest: A. Ten Brinke reports institutional fees for research advisory boards and lectures from GSK, Teva and AstraZeneca, institutional fees for research advisory boards from Sanofi, Novartis and Boehringer Ingelheim, outside the submitted work. Conflict of interest: J. Busby has nothing to disclose. Conflict of interest: G.W. Canonica reports personal fees from A. Menarini, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Circassia, GSK, MSD, Novartis, Roche, Sanofi-Aventis and Teva, during the conduct of the study. Conflict of interest: H. Cao is an employee of Novartis, which is one of the funding pharmaceutical companies of SHARP. Conflict of interest: K.F. Chung has received honoraria for participating in advisory board meetings from GSK, AstraZeneca, Novartis, Merck, Boehringer Ingelheim and Teva regarding treatments for asthma and chronic obstructive pulmonary disease and has also been remunerated for speaking engagements. Conflict of interest: Z. Csoma has nothing to disclose. Conflict of interest: B. Dahlén reports advisory board membership for Teva, GSK and Sanofi, personal fees for lectures from AstraZeneca, outside the submitted work. Conflict of interest: E. Davin has nothing to disclose. Conflict of interest: S. Hansen has nothing to disclose. Conflict of interest: E. Heffler reports personal fees from AstraZeneca, Sanofi Genzyme, Teva, Novartis, GSK, Circassia and Nestle Purina, outside the submitted work. Conflict of interest: I. Horvath reports personal fees from AstraZeneca, Boehringer Ingelheim, GSK, Chiesi, Berlin-Chemie, Roche, MSD, CSL and Sager Pharma, outside the submitted work. Conflict of interest: S. Korn reports personal fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Teva and Roche, grants and personal fees from GSK and Novartis, during the conduct of the study. Conflict of interest: M. Kots is a full time Chiesi Famaceutici SpA employee, Global clinical development department. Conflict of interest: P. Kuna reports personal fees for lectures and advisory board work from AstraZeneca and Novartis, personal fees for lectures and nonfinancial support for meeting attendance from Berlin-Chemie, Menarini and Boehringer Ingelheim, outside the submitted work. Conflict of interest: N. Kwon is an employee of GSK. Conflict of interest: R. Louis reports grants and personal fees for advisory board work from GSK, AstraZeneca and Novartis, grants from Chiesi, outside the submitted work. Conflict of interest: V. Plaza reports grants, personal fees and nonfinancial support from Chiesi, grants and personal fees from AstraZeneca, personal fees from ALK, Mundipharma and Sanofi, grants from Menarini, outside the submitted work. Conflict of interest: C. Porsbjerg has nothing to disclose. Conflict of interest: D. Ramos-Barbon has nothing to disclose. Conflict of interest: L.B. Richards has nothing to disclose. Conflict of interest: S. Škrgat reports personal fees for lectures and scientific discussion at symposia from Teva and Boehringer, personal fees for lectures and advisory boards from AstraZeneca, Glaxo, Berlin-Chemie and Chiesi, outside the submitted work. Conflict of interest: J.K. Sont has nothing to disclose. Conflict of interest: S.J.H. Vijverberg has nothing to disclose. Conflict of interest: E.J. Weersink has nothing to disclose. Conflict of interest: V. Yasinska has nothing to disclose. Conflict of interest: S.S. Wagers reports consultancy fees from the European Respiratory Society, during the conduct of the study; consultancy fees from King's College Hospital NHS Foundation Trust, Academic Medical Research, AMC Medical Research BV, Asthma UK, Athens Medical School, Boehringer Ingelheim International GmbH, CHU de Toulouse, CIRO, DS Biologicals Ltd, École Polytechnique Fédérale de Lausanne, European Respiratory Society, FISEVI, Fluidic Analytics Ltd, Fraunhofer IGB, Fraunhofer ITEM, GSK R&D Ltd, Holland and Knight, Karolinska Institutet Fakturor, KU Leuven, Longfonds, National Heart and Lung Institute, Novartis Pharma AG, Owlstone Medical Ltd, PExA AB, UCB Biopharma SPRL, UCB Biosciences GmbH, Umeå University, University Hospital Southampton NHS Foundation Trust, Università Campus Bio-Medico di Roma, Universita Cattolica Del Sacro Cuore, Universität Ulm, University of Bern, University of Edinburgh, University of Hull, University of Leicester, University of Loughborough, University of Luxembourg, University of Manchester, University of Nottingham, Vlaams Brabant, Dienst Europa, Imperial College London, Boehringer Ingelheim, Breathomix, Gossamer Bio, AstraZeneca and CIBER, outside the submitted work. Conflict of interest: R. Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and Teva, consultation for Teva and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GSK; and is a co-founder and current consultant, and has shares in Synairgen, a University of Southampton spin out company. Conflict of interest: A.H. Maitland-van der Zee reports personal fees for participating in an advisory board from AstraZeneca and Boehringer Ingelheim, unrestricted research grants from Boehringer Ingelheim and GSK., (Copyright ©ERS 2020.)

Previous studies have found suboptimal control of symptom burden to be widespread among patients with asthma and chronic obstructive pulmonary disease (COPD). The Phase IV SPRINT study was conducted in 10 countries in Europe to assess asthma disease control and COPD symptom burden in patients treated with a fixed-dose combination (FDC) of inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs). SPRINT included 1101 patients with asthma and 560 with COPD; all were receiving treatment with an FDC of ICS/LABA, delivered via various inhalers. Data were obtained over a 3-month period, during a single routine physician's office visit. Asthma control was defined as Asthma Control Test (ACT) score >19. COPD symptom burden was assessed by COPD Assessment Test (CAT), with a CAT score <10 defining low COPD symptom burden. Among patients using any ICS/LABA FDC, 62% of patients with asthma had achieved disease control (ACT score >19) and 16% of patients with COPD had low symptom burden (CAT score <10).

Background: The minimum controlling dose of treatment must be established in patients with asthma, but the outcome of step-down is unpredictable., Objective: To identify factors associated with risk of control loss when stepping down asthma treatment and to develop a score to predict this risk., Methods: A prospective, multicenter study including adults with well-controlled asthma was performed. Treatment was stepped up or stepped down over a 12-month period to maintain asthma control. We determined associations between clinical and functional variables and step-down failure. Finally, we derived a score to predict loss of control in 1 cohort and validated it in an independent cohort., Results: The derivation cohort consisted of 228 patients; 218 completed at least 1 step-down episode and a total of 495 step-down episodes were evaluated. A medical-record documented postbronchodilator spirometry result of <70% forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (odds ratio [OR] = 2.08; 95% confidence interval [CI]: 1.26-3.43), current FEV 1 < 80% (OR = 1.80; 95% CI: 1.03-3.14), ≥1 severe exacerbation in the previous 12 months (OR = 2.43; 95% CI: 1.48-4.01), and Asthma Control Test score < 25 (OR = 2.30; 95% CI: 1.35-3.92) were independently associated with failure. The score showed an area under the curve of 0.690 (95% CI: 0.633-0.747; P < .05) in the derivation cohort and 0.76 (95% CI: 0.643-0.882; P < .001) in a validation cohort of 114 patients. A score <4.5 implies a low risk of failure (<20%), whereas a score >8 implies a high risk (>40%)., Conclusion: This score can facilitate the prediction of step-down failure before medication taper in patients with well-controlled asthma., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The preferences and opinions of patients are important when choosing the optimal inhaler device for asthma management. We compared patient satisfaction of three dry powder inhalers in patients with moderate to severe asthma., Methods: We selected a group of patients treated with Easyhaler TM (n = 164) and a second group of patients treated with Turbuhaler TM (n = 100) or Diskus TM (Accuhaler TM ) (n = 64) from the register of an observational, multicenter study. Data of patients were paired according to age, gender, and asthma severity. Patient satisfaction with the inhaler type was assessed with the specific 'Feeling of Satisfaction with Inhaler' (FSI-10) questionnaire., Results: Specific satisfaction with inhaler was statistically significantly higher with Easyhaler TM , as well as the percentage of patients with high satisfaction with inhaler. (FSI-10 score ≥43). Scores for Easyhaler TM were also statistically significantly better for individual FSI-10 items such as learning how to use, inhaler preparation, inhaler use, weight and size, and portability. There were no significant differences in asthma control (ACT, Mini-AQLQ) and adherence (TAI global score)., Conclusions: Specific satisfaction with inhaler was higher with Easyhaler TM in a homogeneous population of patients with moderate to severe asthma. However, the relationship between satisfaction with the inhaler and adherence and asthma control deserves more investigation.

Background: Asthma guidelines recommend considering patient preferences for inhaler choice. However, few studies have assessed the impact of patient satisfaction with an inhaler on adherence and health outcomes. Objective: To assess the impact of patient satisfaction with an inhaler on adherence and health outcomes in asthma. Methods: In a cross-sectional, observational, multicenter study, 778 patients with moderate or severe asthma and who were treated with maintenance inhalers completed a number of scales and questionnaires: the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire, the Treatment Satisfaction Questionnaire for Medication, the Test of Adherence to Inhalers (TAI), the Morisky-Green questionnaire, and the Asthma Control Test (ACT). Results: The study population was categorized according to a median FSI-10 score as high (49.4%) and low (50.6%) satisfaction with their inhaler. Logistic regression analysis showed that high specific satisfaction with an inhaler was associated with the younger age group (odds ratio [OR] 0.976 [95% confidence interval {CI} 0.965-0.987]); male gender (OR 1.725 [95% CI 1.187-2.507]); controlled asthma: ACT score ≥ 20 (OR 1.664 [95% CI 1.133-2.445]); high general satisfaction with treatment (OR 4.861 [95% CI 3.335-7.085]); high adherence to inhaler: TAI score ≥ 46 (OR 1.546 [95% CI 1.025-2.332]); nonsevere asthma (OR 1.056 [95% CI 0.648-1.721]); and no trouble with inhaler use (OR 0.401 [95% CI 0.174-0.922]). Conclusion: High patient satisfaction with an inhaler, irrespective of received medication, was related to adherence and asthma control. Our results pointed out the relevance of inhaler choice in inhaled therapy; these results could be useful for designing new strategies targeted to increase adherence in patients with asthma.

Background: It has been documented that anxiety and depression are prevalent in patients with asthma and are associated with greater frequency of exacerbations, increased use of health care resources, and poor asthma control., Objective: To examine the association of asthma diagnosis with symptoms of depression/anxiety and asthma control not only at baseline but also over a 6-month period of specialist supervision., Methods: We enrolled 3182 patients with moderate to severe asthma. All were evaluated with spirometry, the Asthma Control Test, and the Hospital Anxiety and Depression Scale at baseline and at 6 months. Treatments were decided by specialists according to published guidelines., Results: At baseline, 24.2% and 12% of the patients were diagnosed with anxiety and depression, respectively, according to the Hospital Anxiety and Depression Scale. After 6 months, anxiety and depression improved, affecting 15.3% and 8.1% of patients, respectively (P < .001); mean FEV 1 and asthma control also improved (FEV 1 from 81.6% ± 20.9% to 86% ± 20.8%; Asthma Control Test score from 15.8 ± 4.7 to 19.4 ± 4.4; both P < .001). Patients with anxiety and depression used significantly more health care resources and had more exacerbations. A multivariate analysis showed that patients with anxiety, depression, and lower FEV 1 (odds ratio, 0.20, 0.34, 0.62, respectively; P < .001) were independently associated with poor asthma control. A multiple linear regression analysis showed that anxiety had a nearly 4-fold greater influence over asthma control than depression (0.326/0.85 = 4.075)., Conclusion: Under standardized asthma care and after a specific visit with the specialist, patients present significant improvement in these psychological disorders and exhibit better asthma control and functional parameters., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Inefficient inhaler technique (IT) compromises the optimal delivery of medication. However, the IT knowledge of health care professionals (HCPs) has received scant attention., Objective: The objective of this study was to perform a systematic review of published reports assessing the IT proficiency of HCPs in using pressurized metered dose (pMDI) and dry powder (DPI) inhalers., Methods: Studies published between 1975 and 2014 that directly assessed the IT skills of HCPs were selected according to predefined selection criteria., Results: Data were extracted from 55 studies involving 6,304 HCPs who performed 9,996 tests to demonstrate their IT proficiency. Overall, the IT was considered correct in 15.5% of cases (95% confidence interval [CI], 12-19.3), decreasing over time from 20.5% (95% CI, 14.9-26.8) from the early period (defined as 1975-1995) to 10.8% (95% CI, 7.3-14.8) during the late period (1996-2014). The most common errors in the use of pMDIs were as follows: not breathing out completely before inhalation (75%; 95% CI, 56-90), lack of coordination (64%; 95% CI, 29-92), and postinhalation breath-hold (63%; 95% CI, 52-72). The most common errors using DPI were deficient preparation (89%; 95% CI, 82-95), not breathing out completely before inhalation (79%; 95% CI, 68-87), and no breath-hold (76%; 95% CI, 67-84)., Conclusions: HCPs demonstrated inadequate knowledge of the proper use of inhalers. The poor understanding of the correct use of these devices may prevent these professionals from being able to adequately assess and teach proper inhalation techniques to their patients., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to characterize the clinical, functional and inflammatory features of patients diagnosed diagnosed with ACO according to a new algorithm and to compare them with those of other chronic obstructive airway disease (COAD) categories (asthma and COPD)., Methods: ACO was diagnosed in a cohort of COAD patients in those patients with COPD who were either diagnosed with current asthma or showed significant blood eosinophilia (≥300cells/μl) and/or a very positive bronchodilator response (>400ml and >15% in FEV1)., Results: Eighty-seven (29.8%) out of 292 patients fulfilled the ACO diagnostic criteria (12.8% asthmatics who smoked <20 pack-years, 100% of asthmatics who smoked ≥20 pack-years, 47.7% of COPD with >200eosinophils/μl in blood and none with non-eosinophilic COPD). ACO, asthma and COPD patients showed no differences in symptoms or exacerbation rate. Mean pre-bronchodilator FEV1 in ACO and asthma were similar (1741 vs 1771ml), higher than in COPD (1431ml, p<0.05). DLCO was lower in ACO than in asthma (68.1 vs 84.1%) and similar to COPD (64.5%). Mean blood eosinophil count was similar in ACO and asthma (360 vs 305cells/μl) and higher than in COPD (170cells/μl). Periostin levels were similar in ACO to COPD (36.6 and 36.5IU/ml) and lower than in asthma (41.5IU/ml, p<0.05), whereas FeNO levels in ACO were intermediate., Conclusion: This algorithm classifies as ACO all smoking asthmatics with non-fully reversible airway obstruction and a considerable proportion of e-COPD patients, highlighting those who can benefit from inhaled corticosteroids., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of understanding of the underlying mechanisms. Determining systemic mediators may help clarify the nature of inflammation in patients with ACO., Objectives: We aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-α), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO., Methods: This is a cross-sectional study of patients aged ≥40 years with a post-bronchodilator forced expiratory volume in the first second/forced vital capacity <0.70 recruited from outpatient clinics in tertiary hospitals with a clinical diagnosis of asthma, COPD, or ACO. ACO was defined by a history of smoking >10 pack-years in a patient with a previous diagnosis of asthma or by the presence of eosinophilia in a patient with a previous diagnosis of COPD. Clinical, functional, and inflammatory parameters were compared between categories using discriminant and network analysis., Results: In total, 109 ACO, 89 COPD, and 94 asthma patients were included. Serum levels (median [interquartile range]) of IL-5 were higher in asthma patients than in COPD patients (2.09 [0.61-3.57] vs 1.11 [0.12-2.42] pg/mL, respectively; p =0.03), and IL-8 levels (median [interquartile range]) were higher in COPD patients than in asthma patients (9.45 [6.61-13.12] vs 7.03 [4.69-10.44] pg/mL, respectively; p <0.001). Their values in ACO were intermediate between those in asthma and in COPD. Principal component and network analysis showed a mixed inflammatory pattern in ACO in between asthma and COPD. IL-13 was the most connected node in the network, with different weights among the three conditions., Conclusion: Asthma and COPD are two different inflammatory conditions that may overlap in some patients, leading to a mixed inflammatory pattern. IL-13 could be central to the regulation of inflammation in these conditions., Competing Interests: Disclosure Dr Pérez de Llano reports grants from SEPAR, during the conduct of the study, and grants and personal fees from Novartis, Chiesi, AstraZeneca, and Pfizer, outside the submitted work. Dr Cosío reports grants from SEPAR, during the conduct of the study, and personal fees from AstraZeneca, grants from Boehringer Ingelheim, grants and personal fees from Novartis, Chiesi, Rovi, Menarini, and Esteve, outside the submitted work. Dr Izquierdo reports and has received funds for advisory boards and lectures from Almirall, AstraZeneca, Bayer, GlaxoSmithKline, Novartis, Pfizer, Boehringer Ingelheim, Takeda, Chiesi, and Menarini. Dr Soler-Cataluña reports grants from SEPAR, during the conduct of the study and grants and personal fees from AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Rovi, Menarini, and Esteve, outside the submitted work. Dr Miravitlles reports personal fees from Almirall, Boehringer Ingelheim, AstraZeneca, Chiesi, GlaxoSmithKline, Menarini, Teva, Grifols, and Novartis, outside the submitted work. The authors report no other conflicts of interest in this work.

Background: Bronchial hypersecretion is a poorly studied symptom in asthma. The aim of the study was to determine the specific characteristics of asthmatics with bronchial hypersecretion., Methods: A total of 142 asthmatics (21.8% men; mean age 49.8 years) were prospectively followed for one year. Mucus hypersecretion was clinically classified into two severity categories: daily sputum production and frequent expectoration but not every day. Clinical and pulmonary function variables associated with mucus hypersecretion were assessed by multiple logistic regression analysis., Results: Daily cough was recorded in 28.9% of patients and sputum production daily or most of the days in 52.1%. Patients with mucus hypersecretion had more dyspnoea, poorer asthma control and quality of life, had suffered from more exacerbations and showed anosmia associated with chronic rhinosinusitis and nasal polyposis more frequently. Factors associated to mucus hypersecretion were anosmia, one exacerbation or more in the previous year and FEV1/FVC <70% (AUC 0.75, 95% CI 0.66-0.85) for the first definition of hypersecretion, and anosmia, poor asthma control and age (AUC 0.75, 95% CI 0.67-0.83) for the second definition., Conclusions: Mucus hypersecretion is frequent in patients with asthma, and is associated with chronic upper airways disease, airway obstruction, poor asthma control and more exacerbations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose of Review: It has been estimated that adherence to inhaled medications in patients with asthma and chronic obstructive pulmonary disease (COPD) is around 50%. This low adherence rate increases morbidity and mortality of these disorders. The objective of this review was to update information on main questionnaires used in daily for assessing adherence to inhalers of patients with chronic respiratory diseases., Recent Findings: The test of the adherence to inhalers (TAI) is a recently developed and validated 12-item questionnaire to assess adherence to inhalers of aerosolized drugs in patients with asthma or COPD. The instrument can easily identify nonadherence, classify the level of adherence into good, intermediate and poor, and establish three nonadherence behaviour patterns of erratic, deliberate, and unwitting, which are useful for tailoring corrective measures., Summary: Adherence to inhaler devices may be underestimated with the use of validated self-report questionnaires as compared with other more sensitive methods. However, validated self-report questionnaires are more advantageous from a cost-effective perspective in clinical practice. The recently validated TAI is a reliable and homogeneous instrument to identify easily nonadherence and behavioural barriers to the use of inhalers in patients with asthma or COPD.

Introduction: Sexual limitations play an important role in the quality of life of patients with chronic diseases. Very limited information is available on the impact of asthma on the sexual functioning of these individuals., Materials and Methods: Cross-sectional, observational, multicenter study. Asthma patients and healthy individuals were recruited. All subjects participated in an interview in which demographic and clinical data were recorded, and completed the Goldberg Anxiety-Depression Scale (GADS) to evaluate the presence of concomitant psychiatric disease. Men also completed the International Index of Erectile Function (IIEF), and women, the Female Sexual Function Index (FSFI)., Results: A total of 276cases were included, comprising 172asthma patients (63 men and 109 women) with a mean age of 42 (±14) years, and 104 controls (52men and 51women) with a mean age of 39 (±12) years. Time since onset of asthma was 15 years and severity distribution was: 6.4% intermittent, 17.9% mild persistent, 47.4% moderate, and 28.2% severe. Disease was considered controlled in 57.7%, partially controlled in 28.2%, and uncontrolled in 14.1%. Women with asthma had greater sexual limitations than women in the control group, with a total FSFI score of 22.1 (±9) compared to 26.5 (±6.8), respectively (P<.005). Men with asthma had significantly more severe erectile dysfunction with a total IIEF score of 59.5 (±12.5) compared to 64.3 (±8.2) in male controls (P<.05). An association was also observed between sexual problems and poorer asthma control., Conclusions: Asthma is associated with a poorer sexual quality of life among patients. These results should arouse the interest of healthcare professionals in detecting and alleviating possible sexual limitations among their asthma patients in routine clinical practice., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Fibromyalgia can affect the control of asthma when both diseases are present in a single patient., Objectives: To characterize asthma in patients with concomitant fibromyalgia to assess whether fibromyalgia is an independent factor of asthma severity that influences poor asthma control. We also evaluated how dyspnea is perceived by patients in order to demonstrate that alterations in the perception of airway obstruction may be responsible for poor asthma control., Methods: This was a cross-sectional case-control multicenter study, in which 56 patients in the asthma and fibromyalgia group were matched to 36 asthmatics by sex, approximate age, and asthma severity level. All patients were women. Study variables included the Asthma Control Test (ACT), the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), the Nijmegen hyperventilation syndrome questionnaire, the Hospital Anxiety and Depression Scale, and perception of dyspnea after acute bronchoconstriction., Results: Although patients in both study groups showed similar asthma severity and use of anti-asthmatic drugs, patients in the asthma and fibromyalgia group showed lower scores on the ACT and MiniAQLQ questionnaires, and higher scores of anxiety and depression as well as hyperventilation compared to asthma patients without fibromyalgia. All these differences were statistically significant., Conclusions: Fibromyalgia in patients with asthma influences poor control of the respiratory disease and is associated with altered perception of dyspnea, hyperventilation syndrome, high prevalence of depression and anxiety, and impaired quality of life., Clinical Implications: Fibromyalgia may be considered a risk factor for uncontrolled asthma in patients suffering from asthma and fibromyalgia concomitantly.

Purpose: Rates of nonadherence to asthma treatment in Spain are between 24% and 76%, which results in poor disease control and increased health care costs. The main objective of this multidisciplinary consensus was to investigate the opinions of health professionals and patients regarding adherence to inhaled therapy in Spain. The results will help to identify the causes of nonadherence and to establish strategies to detect and correct the problem., Methods: This research was conducted by using a modified Delphi method organized into 2 rounds and involving a panel of 64 physicians, 16 nurses, and 10 community pharmacists. In addition, 70 patients with asthma completed a simplified 1-round survey, based on the Delphi questionnaire. The items proposed to reach a consensus included topics such as impact and causes of nonadherence, as well as strategies to improve adherence to treatment., Findings: Expert panelists reached a consensus on ~80% of the items proposed. They agreed that the lack of control in asthma has an important economic impact. The causes of nonadherence with more agreement were the patients' beliefs about treatment and the complexity of the inhalation devices. Panelists agreed that the most important strategies to improve adherence were modification of patients' beliefs, training of professionals in the management of adherence, and personalization of interventions. Most patients only agreed with items that referred to strategies to improve adherence., Implications: Although the problems, impact, causes, and interventions regarding nonadherence to asthma treatment are known, adequate monitoring of adherence to treatment is not performed. A multidisciplinary and personalized approach is necessary to control and improve adherence., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.)

Following a proposal by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), sponsor of the Spanish COPD Guidelines (GesEPOC) and the Spanish Guidelines on the Management of Asthma (GEMA), authors of both papers have unified the criteria for the diagnosis of asthma-COPD overlap syndrome (ACOS). This consensus defines ACOS as the presence in a given patient of three elements: significant smoking exposure, chronic airflow limitation and asthma. Diagnosis is confirmed when a patient (35years of age or older), smoker or ex-smoker of more than 10 pack-years, presents airflow limitation (post-bronchodilator FEV1/FVC<0.7) that persists after treatment with bronchodilators and inhaled corticosteroids (even after systemic corticosteroids in selected cases), and an objective current diagnosis of asthma (according to GEMA criteria). In cases in which the diagnosis of asthma cannot be demonstrated, marked positive results on a bronchodilator test (FEV 1 ≥15% and ≥400mL) or elevated blood eosinophil count (≥300eosinophils/μL) will also be diagnostic of ACOS. The opinion of another 33 experts who had not participated in the consensus was sought using a modified Delphi survey. Up to 80% of respondents gave a very positive opinion of the consensus, and declared that it was better than other previous proposals. The GesEPOC-GEMA consensus on ACOS provides a unique perspective of the diagnostic problem, using a simple proposal and a pragmatic diagnostic algorithm that can be applied at any healthcare level., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

We aimed to describe the differences and similarities between patients with chronic obstructive airway disease classified on the basis of classical diagnostic labels (asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD overlap (ACOS)) or according to the underlying inflammatory pattern (Th-2 signature, either Th-2-high or Th-2-low).We performed a cross-sectional study of patients aged ≥40 years and with a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio ≤0.7 with a previous diagnosis of asthma (non-smoking asthmatics (NSA)), COPD or ACOS, the latter including both smoking asthmatics (SA) and patients with eosinophilic COPD (COPD-e). Clinical, functional and inflammatory parameters (blood eosinophil count, IgE and exhaled nitric oxide fraction ( F eNO )) were compared between groups. Th-2 signature was defined by a blood eosinophil count ≥300 cells·μL -1 and/or a sputum eosinophil count ≥3%.Overall, 292 patients were included in the study: 89 with COPD, 94 NSA and 109 with ACOS (44 SA and 65 with COPD-e). No differences in symptoms or exacerbation rate were found between the three groups. With regards the underlying inflammatory pattern, 94 patients (32.2%) were characterised as Th-2-high and 198 (67.8%) as Th-2-low. The Th-2 signature was found in 49% of NSA, 3.3% of patients with COPD, 30% of SA and 49.3% of patients with COPD-e. This classification yielded significant differences in demographic, functional and inflammatory characteristics.We conclude that a classification based upon the inflammatory profile, irrespective of the taxonomy, provides a more clear distinction of patients with chronic obstructive airway disease., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Purpose of Review: The aims of the present review were to describe the heterogeneous nature of near-fatal asthma (NFA) and to summarize the distinctive phenotypes identified in this subtype of asthma., Recent Findings: Clinical, physiological, and histological studies have shown a large number of triggers, pathological mechanisms, and risk factors associated with NFA. Based on the demographic and clinical characteristics of the patients, the circumstances surrounding the asthma exacerbation and some distinctive features of the disease, several clinical profiles of asthma patients with NFA have been described. Recent data show new associations between some gene expression patterns and fatal asthma, as well as with some biological markers related to inflammatory or immunologic mechanisms in the airways. Also, the use of statistical methods, such as cluster analysis, allowed identifying and confirming different phenotypes of life-threatening asthma patients., Summary: NFA is a heterogeneous clinical entity, in which different patients' clinical profiles may coexist [e.g. rapid-onset NFA, NFA in patients with dyspnea hypoperception or sensitized to certain pneumoallergens (Alternaria alternata, soybean), NFA related to the menstrual cycle, brittle asthma]. Knowledge of these phenotypes as well as adequate and specific management strategies can reduce morbidity and mortality in patients suffering from NFA.

Purpose of Review: To illustrate the scant evidence and the shortcomings of the concept of 'asthma-COPD overlap syndrome' (ACOS) in terms of clinical utility., Recent Findings: Asthma and chronic obstructive pulmonary disease (COPD) are considered as two distinct and heterogeneous diseases. For many years, physicians have been aware that asthma and COPD can coexist in some patients. Recently, the term ACOS has been applied when a person has clinical features of both asthma and COPD. However, the lack of an accurate diagnosis has led to inconsistent data regarding reported prevalence, prognosis and therapeutics. Even today, it has not been possible to establish a phenotypic characterization of ACOS, although it is part of the overall complexity and heterogeneity of COPDs. No high quality data exist on which to base treatment recommendations for ACOS. Consequently, in clinical practice, treatment is extrapolated from the available evidence on asthma and COPD., Summary: The current concept of ACOS seems clinically irrelevant because it has no influence on the prognosis and treatment of these patients. The authors concluded that the term ACOS should be avoided in the case of patients with features of both asthma and COPD.

Differences between COPD and asthma may also differentially affect adherence to inhaled drugs in each disease. We aimed to determine differences in behaviour patterns of adherence and non-adherence to inhaled therapy between patients with COPD and patients with asthma using the Test of Adherence to Inhalers (TAI) questionnaire. A total of 910 patients (55% with asthma, 45% with COPD) participated in a cross-sectional multicentre study. Data recorded included sociodemographics, education level, asthma or COPD history, TAI score, the Asthma Control Test (ACT), the COPD Assessment Test (CAT) and spirometry. Asthma patients were statistically significant less adherents, 140 (28%) vs. 201 (49%), and the pattern of non-adherence was more frequently erratic (66.8% vs. 47.8%) and deliberate (47.2% vs. 34.1%) than COPD patients; however unwitting non-adherence was more frequently observed in COPD group (31.2% vs. 22.8%). Moreover, taking together all sample studied, only being younger than 50 years of age (OR 1.88 [95% CI: 1.26-2.81]) and active working status (OR 1.45 [95% CI: 1.00-2.09]) were risk factors for non-adherence in the multivariate analysis, while having asthma remained in the limits of the significance (OR 1.44 [95%CI: 0.97-2.14]). Even though non-adherence to inhalers is more frequently observed in asthma than in COPD patients and exhibited a different non-adherence patterns, these differences are more likely to be related to sociodemographic characteristics. However, differences in non-adherence patterns should be considered when designing specific education programmes tailored to each disease.

Background: Measurement of the fractional exhaled nitric oxide (FeNO) and eosinophils in induced sputum are noninvasive markers for assessing airway inflammation in asthma. The clinical usefulness of the correlation between raised FeNO and sputum eosinophilia is controversial. We aimed to examine dissociation between FeNO and sputum eosinophils in a clinical series of asthma patients and to determine whether dissociation between these noninvasive markers was associated with clinical and inflammatory differences in these patients., Methods and Findings: A total of 110 patients with asthma were included in a cross-sectional study. All of them were on maintenance treatment for asthma. All patients underwent the following on the same day: FeNO, induced sputum, spirometry, serum total IgE levels and skin prick test. The level of asthma control was determined by the Asthma control Test Questionnaire. In 46 (41.8%) patients, a discrepancy between FeNO and sputum eosinophil count was observed, of those, 34 (73.9%) had a FeNO <50 ppb and high eosinophil count, and were characterized by having a predominance of nonallergic asthma with bronchial eosinophilic inflammatory phenotype. Also, 12 (26.1%) patients had FeNO ≥50 ppb and sputum eosinophilia within the normal reference values, and were characterized by having a predominance of atopy with a paucigranulocytic inflammatory phenotype., Conclusions: A high percentage of patients with dissociation between results of FeNO and sputum eosinophils was observed. These patients showed differential clinical and inflammatory features.