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Miguel Angel Martinez-García,1,2 David Rigau,3 Miriam Barrecheguren,2,4 Alberto García-Ortega,1 Alexa Nuñez,2,4 Grace Oscullo Yepez,1 Marc Miravitlles2,4 1Pneumology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain; 2CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; 3Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; 4Pneumology Department, Hospital Universitari Vall d´Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainCorrespondence: Marc Miravitlles, University Hospital Vall d’Hebron, Department of Pneumology, Vall d’Hebron Barcelona Hospital Campus, Pg Vall d’Hebron 119-129, Barcelona, 08036, Spain, Email marcm@separ.esBackground: Chronic bronchial infection is frequent in chronic obstructive pulmonary disease (COPD), but the impact of the isolation of pathogenic bacteria, and in particular Pseudomonas aeruginosa (PA) in respiratory samples on the prognosis of COPD is unclear.Methods: We conducted a systematic review of prognostic studies including patients with isolation of PA in sputum in stable state or during exacerbations of COPD. The main outcomes were all-cause mortality, respiratory mortality, and number and severity of future exacerbations. Data were expressed as hazard ratio (HR) (95% confidence interval [CI]) whenever possible.Results: Of 2773 studies, eight were finally included (23,228 individuals). The mean age ranged from 65.5 to 73 years. Six studies reported data for all-cause mortality. The adjusted risk of death was almost double in patients with PA isolation (HR 1.95, 95% CI, 1.34 to 2.84; quality of evidence moderate). Patients with PA isolation showed a three times higher adjusted risk of readmission at 30 days after discharge (OR 3.60, 95% CI, 3.60 to 12.03, 1 study; quality of evidence very low), and more than double adjusted risk of death and hospitalization at two years (HR 2.80, 95% CI, 2.20 to 3.56, 1 study; quality of evidence very low).Conclusion: There is moderate certainty that the isolation of PA in sputum is associated with an adjusted increased risk of death in patients with COPD.Keywords: COPD, prognosis, outcomes, mortality, exacerbations, bronchial infection, bronchial colonization

Background: A major challenge in updating clinical guidelines is to efficiently identify new, relevant evidence. We evaluated the efficiency and feasibility of two new approaches: the development of restrictive search strategies using PubMed Clinical Queries for MEDLINE and the use of the PLUS (McMaster Premium Literature Service) database. Methods: We evaluated a random sample of recommendations from a national guideline development program and identified the references that would potentially trigger an update (key references) using an exhaustive approach. We designed restrictive search strategies using the minimum number of Medical Subject Headings (MeSH) terms and text words required from the original exhaustive search strategies and applying broad and narrow filters. We developed PLUS search strategies, matching Medical Subject Headings (MeSH) and Systematized Nomenclature of Medicine (SNOMED) terms with guideline topics. We compared the number of key references retrieved by these approaches with those retrieved by the exhaustive approach. Results: The restrictive approach retrieved 68.1 % fewer references than the exhaustive approach (12,486 versus 39,136), and identified 89.9 % (62/69) of key references and 88 % (22/25) of recommendation updates. The use of PLUS retrieved 88.5 % fewer references than the exhaustive approach (4,486 versus 39,136) and identified substantially fewer key references (18/69, 26.1 %) and fewer recommendation updates (10/25, 40 %). Conclusions: The proposed restrictive approach is a highly efficient and feasible method to identify new evidence that triggers a recommendation update. Searching only in the PLUS database proved to be a suboptimal approach and suggests the need for topic-specific tailoring. [ABSTRACT FROM AUTHOR]

Air pollution is one of the biggest environmental threats for asthma. Its impact is augmented by climate change. To inform the recommendations of the EAACI Guidelines on the environmental science for allergic diseases and asthma, a systematic review (SR) evaluated the impact on asthma-related outcomes of short-term exposure to outdoor air pollutants (PM2.5, PM10, NO 2 , SO 2 , O 3 , and CO), heavy traffic, outdoor pesticides, and extreme temperatures. Additionally, the SR evaluated the impact of the efficacy of interventions reducing outdoor pollutants. The risk of bias was assessed using ROBINS-E tools and the certainty of the evidence by using GRADE. Short-term exposure to PM2.5, PM10, and NO 2 probably increases the risk of asthma-related hospital admissions (HA) and emergency department (ED) visits (moderate certainty evidence). Exposure to heavy traffic may increase HA and deteriorate asthma control (low certainty evidence). Interventions reducing outdoor pollutants may reduce asthma exacerbations (low to very low certainty evidence). Exposure to fumigants may increase the risk of new-onset asthma in agricultural workers, while exposure to 1,3-dichloropropene may increase the risk of asthma-related ED visits (low certainty evidence). Heatwaves and cold spells may increase the risk of asthma-related ED visits and HA and asthma mortality (low certainty evidence)., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Limited number of studies have focused on the impact of pollen exposure on asthma. As a part of the EAACI Guidelines on Environment Science, this first systematic review on the relationship of pollen exposure to asthma exacerbations aimed to bridge this knowledge gap in view of implementing recommendations of prevention. We searched electronic iPubMed, Embase, and Web of Science databases using a set of MeSH terms and related synonyms and identified 73 eligible studies that were included for systemic review. When possible, meta-analyses were conducted. Overall meta-analysis suggests that outdoor pollen exposure may have an effect on asthma exacerbation, but caution is needed due to the low number of studies and their heterogeneity. The strongest associations were found between asthma attacks, asthma-related ED admissions or hospitalizations, and an increase in grass pollen concentration in the previous 2-day overall in children aged less than 18 years of age. Tree pollen may increase asthma-related ED visits or admissions lagged up to 7-day overall in individuals younger than 18 years. Rare data show that among subjects under 18 years of age, an exposure to grass pollen lagged up to 3 days may lower lung function. Further research considering effect modifiers of pollen sensitization, hay fever, asthma, air pollution, green spaces, and pre-existing medications is urgently warranted to better evaluate the impacts of pollen on asthma exacerbation. Preventive measures in relation to pollen exposure should be integrated in asthma control as pollen increase continues due to climate change., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP., Methods: The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations., Results: Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions., Conclusions: In these international guidelines, ERS, ESICM, ESCMID, and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment, and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Breast cancer clinical practice guidelines (CPGs) offer evidence-based recommendations to improve quality of healthcare for patients. Suboptimal compliance with breast cancer guideline recommendations remains frequent, and has been associated with a decreased survival. The aim of this systematic review was to characterize and determine the impact of available interventions to support healthcare providers' compliance with CPGs recommendations in breast cancer healthcare., Methods: We searched for systematic reviews and primary studies in PubMed and Embase (from inception to May 2021). We included experimental and observational studies reporting on the use of interventions to support compliance with breast cancer CPGs. Eligibility assessment, data extraction and critical appraisal was conducted by one reviewer, and cross-checked by a second reviewer. Using the same approach, we synthesized the characteristics and the effects of the interventions by type of intervention (according to the EPOC taxonomy), and applied the GRADE framework to assess the certainty of evidence., Results: We identified 35 primary studies reporting on 24 different interventions. Most frequently described interventions consisted in computerized decision support systems (12 studies); educational interventions (seven), audit and feedback (two), and multifaceted interventions (nine). There is low quality evidence that educational interventions targeted to healthcare professionals may improve compliance with recommendations concerning breast cancer screening, diagnosis and treatment. There is moderate quality evidence that reminder systems for healthcare professionals improve compliance with recommendations concerning breast cancer screening. There is low quality evidence that multifaceted interventions may improve compliance with recommendations concerning breast cancer screening. The effectiveness of the remaining types of interventions identified have not been evaluated with appropriate study designs for such purpose. There is very limited data on the costs of implementing these interventions., Conclusions: Different types of interventions to support compliance with breast cancer CPGs recommendations are available, and most of them show positive effects. More robust trials are needed to strengthen the available evidence base concerning their efficacy. Gathering data on the costs of implementing the proposed interventions is needed to inform decisions about their widespread implementation., Trial Registration: CRD42018092884 (PROSPERO)., (© 2023. European Union.)

This European Respiratory Society guideline is dedicated to the provision of good quality recommendations in lung cancer care. All the clinical recommendations contained were based on a comprehensive systematic review and evidence syntheses based on eight PICO (Patients, Intervention, Comparison, Outcomes) questions. The evidence was appraised in compliance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence profiles and the GRADE Evidence to Decision frameworks were used to summarise results and to make the decision-making process transparent. A multidisciplinary Task Force panel of lung cancer experts formulated and consented the clinical recommendations following thorough discussions of the systematic review results. In particular, we have made recommendations relating to the following quality improvement measures deemed applicable to routine lung cancer care: 1) avoidance of delay in the diagnostic and therapeutic period, 2) integration of multidisciplinary teams and multidisciplinary consultations, 3) implementation of and adherence to lung cancer guidelines, 4) benefit of higher institutional/individual volume and advanced specialisation in lung cancer surgery and other procedures, 5) need for pathological confirmation of lesions in patients with pulmonary lesions and suspected lung cancer, and histological subtyping and molecular characterisation for actionable targets or response to treatment of confirmed lung cancers, 6) added value of early integration of palliative care teams or specialists, 7) advantage of integrating specific quality improvement measures, and 8) benefit of using patient decision tools. These recommendations should be reconsidered and updated, as appropriate, as new evidence becomes available., Competing Interests: Conflict of interest: T.G. Blum reports an unrestricted grant from Stiftung Oskar-Helene-Heim (Berlin, Germany), through which staff support for the work of the current Task Force was provided. R.L. Morgan declares no competing interests. V. Durieux declares no competing interests. J. Chorostowska-Wynimko declares grants to the National Institute of Tuberculosis and Lung Diseases from Pfizer and to the Polish Respiratory Society from AstraZeneca; consulting fees from AstraZeneca, Pfizer, Amgen, Takeda, Merck Sharp & Dohme, Roche and Roche Diagnostica; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Pfizer, CelonPharma, Amgen, Takeda, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Roche Diagnostica and Amoy; support for attending meetings and/or travel from Bristol Myers Squibb, AstraZeneca, Merck Sharp & Dohme, Pfizer and Amgen; participation on a data safety monitoring board or advisory board for AstraZeneca, Pfizer, Takeda, Merck Sharp & Dohme, Roche and Roche Diagnostica, all in the 36 months prior to manuscript submission; and is Secretary General of the European Respiratory Society and a member of the Executive Committees of the Polish Respiratory Society and the Polish Coalition for Personalized Medicine. D.R. Baldwin declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bristol Myers Squibb, AstraZeneca, Roche and Merck Sharp & Dohme, all in the 36 months prior to manuscript submission. J. Boyd is an employee of the European Lung Foundation. C. Faivre-Finn reports research grants from AstraZeneca and Elekta; payment or honoraria for presentations from AstraZeneca; support for attending meetings and/or travel from Elekta and AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca and Merck Sharp & Dohme, all in the 36 months prior to manuscript submission. F. Galateau-Salle declares no competing interests. F. Gamarra declares no competing interests. B. Grigoriu declares support for attending meetings and/or travel from Roche and AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca, all in the 36 months prior to manuscript submission. G. Hardavella declares no competing interests. M. Hauptmann declares no competing interests. E. Jakobsen declares no competing interests. D. Jovanovic declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Merck Sharp & Dohme, Roche, Boehringer Ingelheim, WCBIP 2020 and AstraZeneca; payment for expert testimony relating to the health effects of air pollution from SO2 released by Serbia Zijin Copper mining and smelting complex and the two biggest Serbian power plants, all in the 36 months prior to manuscript submission; and is a member of the editorial boards of the Journal of Thoracic Disease and the AME Surgical Journal, and a committee member of the National Ecological Association (NEA), Serbia. P. Knaut declares no competing interests. G. Massard declares a speaker's fee from Pneumo Update Europe, in the 36 months prior to manuscript submission. J. McPhelim declares advisory board payments from AstraZeneca, Janssen-Cilag and Bristol Myers Squibb, all in the 36 months prior to manuscript submission. A-P. Meert declares no competing interests. R. Milroy declares no competing interests. R. Muhr declares no competing interests. L. Mutti declares no competing interests. M. Paesmans declares no competing interests. P. Powell is an employee of the European Lung Foundation. P.M. Putora declares research grants to their institution from AstraZeneca, Takeda and Bayer; and a speaker's fee from Janssen-Cilag, all in the 36 months prior to manuscript submission. J. Rawlinson declares travel/accommodation support from the BTOG to attend the annual meeting in Dublin as patient advocate/steering committee member; travel/accommodation support from the European Respiratory Society to attend a screening meeting in Barcelona (patient representative) and European Lung Foundation patient event at the European Respiratory Society Congress Madrid 2019; travel/accommodation support from the NCRI to attend a conference in Glasgow (consumer member); travel/accommodation support from the EORTC to attend the Patient Days event as a speaker and patient panel member; and has been a Non-Executive Director (lay member) at Sandwell and West Birmingham Clinical Commissioning Group, UK. A.L. Rich declares no competing interests. D. Rigau is a methodologist for the European Respiratory Society. D. de Ruysscher declares grants to their institution from AstraZeneca and BeiGene; payment to their institution for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca; and payment to their institution for participation on an advisory board from AstraZeneca, all in the 36 months prior to manuscript submission. J-P. Sculier declares no competing interests. A. Schepereel declares a research grant to their institution from Bristol Myers Squibb; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Bristol Myers Squibb and Leo Pharma; support for attending meetings and/or travel from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme and Roche; and payment for participation on a data safety monitoring board or advisory board from AstraZeneca, Bristol Myers Squibb and Merck Sharp & Dohme, all in the 36 months prior to manuscript submission. D. Subotic declares no competing interests. P. Van Schil declares consulting fees paid to their institution by AstraZeneca and Merck Sharp & Dohme; payment to their institution for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca; and travel expenses related to participation in data safety monitoring or advisory boards for the LungART Trial and the Pearls Trial, all in the 36 months prior to manuscript submission; and is the President-elect of the International Association for the Study of Lung Cancer and the Treasurer of the Belgian Association for Cardio-Thoracic Surgery. T. Tonia is a methodologist for the European Respiratory Society. C. Williams is an employee of the European Lung Foundation. T. Berghmans declares consulting fees from InhaTarget; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen; and participation on a data safety monitoring board or advisory board for Janssen and Roche, all in the 36 months prior to manuscript submission., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Purpose: Clinical practice guidelines (CPGs) have become fundamental tools for evidence-based medicine (EBM). However, CPG suffer from several limitations, including obsolescence, lack of applicability to many patients, and limited patient participation. This paper presents APPRAISE-RS, which is a methodology that we developed to overcome these limitations by automating, extending, and iterating the methodology that is most commonly used for building CPGs: the GRADE methodology., Method: APPRAISE-RS relies on updated information from clinical studies and adapts and automates the GRADE methodology to generate treatment recommendations. APPRAISE-RS provides personalized recommendations because they are based on the patient's individual characteristics. Moreover, both patients and clinicians express their personal preferences for treatment outcomes which are considered when making the recommendation (participatory). Rule-based system approaches are used to manage heuristic knowledge., Results: APPRAISE-RS has been implemented for attention deficit hyperactivity disorder (ADHD) and tested experimentally on 28 simulated patients. The resulting recommender system (APPRAISE-RS/TDApp) shows a higher degree of treatment personalization and patient participation than CPGs, while recommending the most frequent interventions in the largest body of evidence in the literature (EBM). Moreover, a comparison of the results with four blinded psychiatrist prescriptions supports the validation of the proposal., Conclusions: APPRAISE-RS is a valid methodology to build recommender systems that manage updated, personalized and participatory recommendations, which, in the case of ADHD includes at least one intervention that is identical or very similar to other drugs prescribed by psychiatrists., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

BACKGROUND. Homogeneous microscopic fat within adrenal nodules on chemical-shift MRI (CS-MRI) is diagnostic of benign adrenal adenoma, but the clinical relevance of heterogeneous microscopic fat is not well established. OBJECTIVE. This study sought to determine the prevalence of malignancy in adrenal nodules with heterogeneous microscopic fat on dual-echo T1-weighted CS-MRI. METHODS. We performed a retrospective study of adult patients with adrenal nodules detected on MRI performed between August 2007 and November 2020 at seven institutions. Eligible nodules had a short-axis diameter of 10 mm or larger with heterogeneous microscopic fat (defined by an area of signal loss of < 80% on opposed-phase CS-MRI). Two radiologists from each center, blinded to reference standard results, determined the signal loss pattern (diffuse, two distinct parts, speckling pattern, central loss, or peripheral loss) within the nodules. The reference standard used was available for 283 nodules (pathology for 21 nodules, ≥ 1 year of imaging follow-up for 245, and ≥ 5 years of clinical follow-up for 17) in 282 patients (171 women and 111 men; mean age, 60 ± 12 [SD] years); 30% (86/282) patients had prior malignancy. RESULTS. The mean long-axis diameter was 18.7 ± 7.9 mm (range, 10-80 mm). No malignant nodules were found in patients without prior cancer (0/197; 95% CI, 0-1.5%). Four of the 86 patients with prior malignancy (hepatocellular carcinoma [HCC], renal cell carcinoma [RCC], lung cancer, or both colon cancer and RCC) (4.7%; 95% CI, 1.3-11.5%) had metastatic nodules. Detected patterns were diffuse heterogeneous signal loss (40% [114/283]), speckling (28% [80/283]), two distinct parts (18% [51/283]), central loss (9% [26/283]), and peripheral loss (4% [12/283]). Two metastases from HCC and RCC showed diffuse heterogeneous signal loss. Lung cancer metastasis manifested as two distinct parts, and the metastasis in the patient with both colon cancer and RCC showed peripheral signal loss. CONCLUSION. Presence of heterogeneous microscopic fat in adrenal nodules on CS-MRI indicates a high likelihood of benignancy, particularly in patients without prior cancer. This finding is also commonly benign in patients with cancer; however, caution is warranted when primary malignancies may contain fat or if the morphologic pattern of signal loss may indicate a collision tumor. CLINICAL IMPACT. In the absence of prior cancer, adrenal nodules with heterogeneous microscopic fat do not require additional imaging evaluation.

In addition to recommendations for pharmacological treatment stratified for risk and phenotype, the new 2021 edition of the Spanish COPD Guidelines (GesEPOC 2021) proposes a personalized approach to treatable traits, defined as a characteristic (clinical, physiological, or biological) that can be identified by diagnostic tests or biomarkers, for which a specific treatment is available. Some treatable traits, such as malnutrition, sedentarism, emphysema or respiratory failure, can be treated with non-pharmacological therapies, and this was not covered in detail in the guidelines. This section of GesEPOC 2021 includes a narrative update with recommendations on dietary treatment, physical activity, respiratory rehabilitation, oxygen therapy, non-invasive ventilation, volume reduction, and lung transplantation. A PICO question with recommendations on the use of supplemental oxygen during exercise in COPD patients without severe hypoxemia is also included., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

The current health care models described in GesEPOC indicate the best way to make a correct diagnosis, the categorization of patients, the appropriate selection of the therapeutic strategy and the management and prevention of exacerbations. In addition, COPD involves several aspects that are crucial in an integrated approach to the health care of these patients. The evaluation of comorbidities in COPD patients represents a healthcare challenge. As part of a comprehensive assessment, the presence of comorbidities related to the clinical presentation, to some diagnostic technique or to some COPD-related treatments should be studied. Likewise, interventions on healthy lifestyle habits, adherence to complex treatments, developing skills to recognize the signs and symptoms of exacerbation, knowing what to do to prevent them and treat them within the framework of a self-management plan are also necessary. Finally, palliative care is one of the pillars in the comprehensive treatment of the COPD patient, seeking to prevent or treat the symptoms of a disease, the side effects of treatment, and the physical, psychological and social problems of patients and their caregivers. Therefore, the main objective of this palliative care is not to prolong life expectancy, but to improve its quality. This chapter of GesEPOC 2021 presents an update on the most important comorbidities, self-management strategies, and palliative care in COPD, and includes a recommendation on the use of opioids for the treatment of refractory dyspnea in COPD., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Although asthma is very common affecting 5-10% of the population, the diagnosis of asthma in adults remains a challenge in the real world that results in both over- and under-diagnosis. A task force (TF) was set up by the European Respiratory Society to systematically review the literature on the diagnostic accuracy of tests used to diagnose asthma in adult patients and provide recommendation for clinical practice.The TF defined eight PICO (Population, Index, Comparator, and Outcome) questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach, The TF utilised the outcomes to develop an evidenced-based diagnostic algorithm, with recommendations for a pragmatic guideline for everyday practice that was directed by real-life patient experiences.The TF support the initial use of spirometry followed, and if airway obstruction is present, by bronchodilator reversibility testing. If initial spirometry fails to show obstruction, further tests should be performed in the following order: FeNO, PEF variability or in secondary care, bronchial challenge. We present the thresholds for each test that are compatible with a diagnosis of asthma in the presence of current symptoms.The TF reinforce the priority to undertake spirometry and recognise the value of measuring blood eosinophils and serum IgE to phenotype the patient. Measuring gas trapping by body plethysmography in patients with preserved FEV 1 /FVC ratio deserves further attention. The TF draw attention on the difficulty of making a correct diagnosis in patients already receiving inhaled corticosteroids, the comorbidities that may obscure the diagnosis, the importance of phenotyping, and the necessity to consider the patient experience in the diagnostic process., Competing Interests: Conflict of interest: Dr. LOUIS reports grants and personal fees from GSK, grants and personal fees from AZ, grants and personal fees from Chiesi, grants and personal fees from Novartis, personal fees from Sanofi, outside the submitted work; . Conflict of interest: Dr. Satia reports grants and personal fees from GSK, personal fees from AstraZeneca, grants and personal fees from Merck, grants from ERS Respire 3 Marie Curie Fellowship, grants from E.J. Moran Campbell Early Career Award, outside the submitted work; . Conflict of interest: Dr. OJANGUREN reports grants and personal fees from ASTRAZENECA, personal fees and non-financial support from BOEHRINGUER-INGELHEIM, personal fees and non-financial support from CHIESI, grants, personal fees and non-financial support from NOVARTIS, personal fees from MSD, personal fees from PURETECH, grants and personal fees from SANOFI, personal fees from BIAL, personal fees from TEVA, grants and personal fees from GSK, outside the submitted work. Conflict of interest: Dr. SCHLEICH reports grants and personal fees from GSK, grants and personal fees from AstraZeneca, personal fees from Chiesi, outside the submitted work. Conflict of interest: Dr. Bonini has nothing to disclose. Conflict of interest: Ms Tonia reports acting as ERS Methodologist . Conflict of interest: Dr. Rigau reports and declares he worked as ERS methodologist until February 2020. Conflict of interest: Dr. ten Brinke reports institutional fees from Research Advisory Boards: GSK, Sanofi, TEVA, AstraZeneca, Boehringer Ingelheim , institutional fees from Lectures AstraZeneca, GSK ,TEVA, SanofiGenzyme, grants from AstraZeneca, GSK ,TEVA, outside the submitted work. Conflict of interest: Dr. Buhl reports personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Novartis, Sanofi, Roche and Teva, and grants to Mainz University Hospital from Boehringer Ingelheim, GlaxoSmithKline, Novartis and Roche, all outside the submitted work. Conflict of interest: Dr. Loukides has nothing to disclose. Conflict of interest: Dr. Kocks reports grants, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Boehringer Ingelheim, grants and personal fees from Chiesi Pharmaceuticals, grants and personal fees from GSK, grants and personal fees from Novartis, personal fees from MSD, grants and personal fees from TEVA, personal fees from COVIS, outside the submitted work; and Janwillem Kocks holds 72.5% of shares in the General Practitioners Research Institute. Conflict of interest: Dr. Boulet reports grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis, Sanofi-Regeneron, grants from AstraZeneca, GlaxoSmithKline. Merck, personal fees from Astra Zeneca, Novartis, GlaxoSmithKline, Merck, Sanofi-Regeneron, personal fees from AstraZeneca, Covis, GlaxoSmithKline, Novartis, Merck, Sanofi, grants and non-financial support from AstraZeneca, Covis, GlaxoSmithKline, Merck, Novartis, non-financial support from Chair of Global Initiative for Asthma (GINA) Board of Directors, President of the Global Asthma Organisation (Interasma) Conflict of interest: Dr. Bourdin reports grants, personal fees, non-financial support and other from GSK, grants, personal fees, non-financial support and other from Astra Zeneca, grants, personal fees, non-financial support and other from Boeringher Ingelheim, personal fees, non-financial support and other from Novartis, personal fees, non-financial support and other from Chiesi Farma, non-financial support and other from Teva, personal fees, non-financial support and other from Sanofi Regeneron, grants, personal fees, non-financial support and other from Actelion / Jansen, other from United Therapeutics, other from Pulsar, personal fees, non-financial support and other from Roche, from null, outside the submitted work. Conflict of interest: Courtney Coleman is an employee of European Lung Foundation. Conflict of interest: Dr. Needham has nothing to disclose. Conflict of interest: Dr. Thomas reports personal fees from GSK, personal fees from Boehringer Ingelheim , personal fees from Chiesi, outside the submitted work; . Conflict of interest: Dr. Idzko has nothing to disclose. Conflict of interest: Dr. Papi reports grants, personal fees, non-financial support and other from GlaxoSmithKline, grants, personal fees and non-financial support from AstraZeneca, grants, personal fees, non-financial support and other from Boehringer Ingelheim, grants, personal fees, non-financial support and other from Chiesi Farmaceutici, grants, personal fees, non-financial support and other from TEVA, personal fees, non-financial support and other from Mundipharma, personal fees, non-financial support and other from Zambon, personal fees, non-financial support and other from Novartis, grants, personal fees and non-financial support from Menarini, personal fees, non-financial support and other from Sanofi/Regeneron, personal fees from Roche, grants from Fondazione Maugeri, grants from Fondazione Chiesi, personal fees from Edmondpharma, outside the submitted work. Conflict of interest: Dr. Porsbjerg reports grants and personal fees from Astra Zeneca, grants and personal fees from GSK, grants and personal fees from Novartis, grants and personal fees from TEVA, grants and personal fees from Sanofi, grants and personal fees from Chiesi, grants from Pharmaxis, outside the submitted work; . Conflict of interest: Dr. Schuermans reports non-financial support from Free University of Brussels, outside the submitted work; . Conflict of interest: Dr. B. Soriano Conflict of interest: Dr. Usmani reports grants and personal fees from astra zeneca, grants and personal fees from boehringer ingelheim, grants and personal fees from chiesi, grants and personal fees from glaxosmithkline, personal fees from napp, personal fees from mundipharma, personal fees from sandoz, personal fees from takeda, grants from edmond pharma, personal fees from cipla, personal fees from covis, personal fees from novartis, personal fees from mereo biopharma, personal fees from orion, personal fees from menarini, personal fees from ucb, personal fees from trudell medical, personal fees from deva, personal fees from kamada, personal fees from covis, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

This article details the GesEPOC 2021 recommendations on the diagnosis and treatment of COPD exacerbation syndrome (CES). The guidelines propose a definition-based syndromic approach, a new classification of severity, and the recognition of different treatable traits (TT), representing a new step toward personalized medicine. The evidence is evaluated using GRADE methodology, with the incorporation of 6 new PICO questions. The diagnostic process comprises four stages: 1) establish a diagnosis of CES, 2) assess the severity of the episode, 3) identify the trigger, and 4) address TTs. This diagnostic process differentiates an outpatient approach, that recommends the inclusion of a basic battery of tests, from a more comprehensive hospital approach, that includes the study of different biomarkers and imaging tests. Bronchodilator treatment for immediate relief of symptoms is considered essential for all patients, while the use of antibiotics, systemic corticosteroids, oxygen therapy, and assisted ventilation and the treatment of comorbidities will vary depending on severity and possible TTs. The use of antibiotics will be indicated particularly if sputum color changes, when ventilatory assistance is required, in cases involving pneumonia, and in patients with elevated C-reactive protein (≥ 20 mg/L). Systemic corticosteroids are recommended in CES that requires admission and are suggested in moderate CES. These drugs are more effective in patients with blood eosinophil counts ≥ 300 cells/mm 3 . Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment., (Copyright © 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin or other manifestations. While glucocorticoids remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. Glucocorticoid-sparing alternatives are available. The presented treatment guidelines aim to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations., Methods: A European Respiratory Society Task Force committee composed of clinicians, methodologists and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations., Results: The Task Force committee delivered 12 recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac and neurologic disease as well as fatigue. One PICO question regarding small-fibre neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation., Conclusions: There are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment., Competing Interests: Conflict of interest: R.P. Baughman reports grants from Gilead, Genentech, Bayer, aTyr and Bellephron, grants and personal fees for consultancy from Novartis, personal fees for consultancy from Methial, grants and personal fees for consultancy and lectures from Mallinckrodt, grants and personal fees for lectures from Boehringer Ingelheim, outside the submitted work. Conflict of interest: D. Valeyre reports personal fees for advisory board work from Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: P. Korsten reports grants and personal fees from GlaxoSmithKline, personal fees from AbbVie, Pfizer, Chugai, Novartis Pharma, Sanofi-Aventis, Lilly and Gilead, outside the submitted work. Conflict of interest: A.G. Mathioudakis reports grants from Boehringer Ingelheim, outside the submitted work. Conflict of interest: W.A. Wuyts has nothing to disclose. Conflict of interest: A. Wells reports personal fees for lectures and advisory board work from Boehringer Ingelheim and Roche, during the conduct of the study. Conflict of interest: P. Rottoli has nothing to disclose. Conflict of interest: H. Nunes has nothing to disclose. Conflict of interest: E.E. Lower reports grants from Gilead, Genentech, Bayer and aTYR, grants and personal fees for consultancy from Novartis, outside the submitted work. Conflict of interest: M.A. Judson received grant support for his institution from Mallickrodt. Conflict of interest: D. Israël-Biet has nothing to disclose. Conflict of interest: J.C. Grutters has nothing to disclose. Conflict of interest: M. Drent has nothing to disclose. Conflict of interest: D.A. Culver reports grants and personal fees from aTyr, Mallinckrodt, Boehringer Ingelheim and Foundation for Sarcoidosis Research, personal fees from Roche, outside the submitted work. Conflict of interest: F. Bonella reports personal fees and non-financial support from Boehringer Ingelheim, Roche, Galapagos, BMS and Savara Pharma, outside the submitted work. Conflict of interest: K. Antoniou has nothing to disclose. Conflict of interest: F. Martone has nothing to disclose. Conflict of interest: B. Quadder has nothing to disclose. Conflict of interest: G. Spitzer has nothing to disclose. Conflict of interest: B. Nagavci acts as an ERS methodologist. Conflict of interest: T. Tonia acts as an ERS methodologist. Conflict of interest: D. Rigau acts as an ERS methodologist. Conflict of interest: D.R. Oullette reports grants from PCORI (Patient-Centred Outcomes Research Institute, US Federal) and Sanofi, outside the submitted work; and has provided expert witness work for venous thromboembolic disease., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Diagnosing asthma in children represents an important clinical challenge. There is no single gold-standard test to confirm the diagnosis. Consequently, over- and under-diagnosis of asthma is frequent in children., Methods: A task force supported by the European Respiratory Society has developed these evidence-based clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years using nine Population, Intervention, Comparator and Outcome (PICO) questions. The task force conducted systematic literature searches for all PICO questions and screened the outputs from these, including relevant full-text articles. All task force members approved the final decision for inclusion of research papers. The task force assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach., Results: The task force then developed a diagnostic algorithm based on the critical appraisal of the PICO questions, preferences expressed by lay members and test availability. Proposed cut-offs were determined based on the best available evidence. The task force formulated recommendations using the GRADE Evidence to Decision framework., Conclusion: Based on the critical appraisal of the evidence and the Evidence to Decision framework, the task force recommends spirometry, bronchodilator reversibility testing and exhaled nitric oxide fraction as first-line diagnostic tests in children under investigation for asthma. The task force recommends against diagnosing asthma in children based on clinical history alone or following a single abnormal objective test. Finally, this guideline also proposes a set of research priorities to improve asthma diagnosis in children in the future., Competing Interests: Conflict of interest: E.A. Gaillard reports consultancy work for Boehringer Ingelheim with money paid to the University of Leicester; investigator led research grants from Circassia, Gilead and Chiesi Ltd; research collaboration with Medimmune. Conflict of interest: C.E. Kuehni has nothing to disclose. Conflict of interest: S. Turner has nothing to disclose. Conflict of interest: M. Goutaki has nothing to disclose. Conflict of interest: K.A. Holden has nothing to disclose. Conflict of interest: C.C.M. de Jong has nothing to disclose. Conflict of interest: C. Lex reports other (lecture fee paid to institution) from Novartis, outside the submitted work. Conflict of interest: D.K.H. Lo has nothing to disclose. Conflict of interest: J.S. Lucas reports grants and non-financial support (provision of equipment) from Circassia, outside the submitted work. Conflict of interest: F. Midulla has nothing to disclose. Conflict of interest: R. Mozun has nothing to disclose. Conflict of interest: G. Piacentini has nothing to disclose. Conflict of interest: D. Rigau acts as ERS methodologist. Conflict of interest: B. Rottier has nothing to disclose. Conflict of interest: M. Thomas reports personal fees from GSK, Boehringer Ingelheim and Chiesi, outside the submitted work. Conflict of interest: T. Tonia acts as ERS Methodologist. Conflict of interest: J. Usemann reports personal fees from Vertex, outside the submitted work. Conflict of interest: O. Yilmaz reports non-financial support for meeting attendance from Abdi Ibrahim, other (lecture fees) from Novartis, outside the submitted work. Conflict of interest: A. Zacharasiewicz has nothing to disclose. Conflict of interest: A. Moeller has nothing to disclose., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Objective: To evaluate the impact of preoperative MRI in the management of Ductal carcinoma in situ (DCIS)., Methods: We searched the PubMed, EMBASE and Cochrane Library databases to identify randomised clinical trials (RCTs) or cohort studies assessing the impact of preoperative breast MRI in surgical outcomes, treatment change or loco-regional recurrence. We provided pooled estimates for odds ratios (OR), relative risks (RR) and proportions and assessed the certainty of the evidence using the GRADE approach., Results: We included 3 RCTs and 23 observational cohorts, corresponding to 20,415 patients. For initial breast-conserving surgery (BCS), the RCTs showed that MRI may result in little to no difference (RR 0.95, 95% CI 0.90 to 1.00) (low certainty); observational studies showed that MRI may have no difference in the odds of re-operation after BCS (OR 0.96; 95% CI 0.36 to 2.61) (low certainty); and uncertain evidence from RCTs suggests little to no difference with respect to total mastectomy rate (RR 0.91; 95% CI 0.65 to 1.27) (very low certainty). We also found that MRI may change the initial treatment plans in 17% (95% CI 12 to 24%) of cases, but with little to no effect on locoregional recurrence (aHR = 1.18; 95% CI 0.79 to 1.76) (very low certainty)., Conclusion: We found evidence of low to very low certainty which may suggest there is no improvement of surgical outcomes with pre-operative MRI assessment of women with DCIS lesions. There is a need for large rigorously conducted RCTs to evaluate the role of preoperative MRI in this population., Key Points: • Evidence of low to very low certainty may suggest there is no improvement in surgical outcomes with pre-operative MRI. • There is a need for large rigorously conducted RCTs evaluating the role of preoperative MRI to improve treatment planning for DCIS., (© 2021. The Author(s).)