European Respiratory Journal 2024; 2400524; DOI https://doi.org/10.1183/13993003.00524-2024 BackgroundMultiple breath washout is a lung function test based on tidal breathing that assesses lung volume and ventilation distribution. The aim of this analysis was to use the Global Lung Function Initiative methodology to develop all-age reference equations for the multiple breath washout indices lung clearance index (LCI) and functional residual capacity (FRC). MethodsMultiple breath washout data from healthy individuals were collated from sites. Data were re-analysed using the latest software versions. Reference equations were derived using the lambda-mu-sigma (LMS) method using the generalised additive models of location shape and scale programme in R. The impact of equipment type, inert tracer gas, and equipment dead space volume on the derived reference ranges were investigated. ResultsData from 23 sites (n=3647 test occasions) were submitted. Reference equations were derived from 1581 unique observations from participants between the ages of 2 and 81?? years. Equipment type, inert tracer gas, and equipment dead space volume did not significantly affect the prediction equations for either LCI or FRC. Reference equations for LCI include age as the only predictor, whereas sex-specific reference equations for FRC included height and age. ConclusionsGlobal Lung Function Initiative reference equations for multiple breath washout variables provide a standard for reporting and interpretation of LCI and FRC.

European Respiratory Journal 2024; DOI: 10.1183/13993003.00725-2024 Abstract Background Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage, evaluation of antibodies against granulocyte macrophage colony stimulating factor (GM-CSF), genetic testing, and, eventually, lung biopsy. The management options are focused at removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis, and lung transplantation. The presented diagnostic and management guideline aim to provide guidance to physicians managing patients with PAP.  Methods A European Respiratory Society Task Force committee composed of clinicians, methodologists, and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of the evidence and strength of recommendations. The committee formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions, and two narrative questions to develop specific evidence-based recommendations.  Results The Task Force committee developed recommendations for five PICOs. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis, and lung transplantation. Also, the committee made recommendations regarding the use of GM-CSF antibody testing, diagnostic bronchoalveolar lavage (BAL) and biopsy based on narrative questions. In addition to the recommendations, the committee provided information on the hierarchy of diagnostic interventions and therapy.  Conclusions The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited.

European Respiratory Journal 2024; DOI: 10.1183/13993003.02307-2023 Abstract  The incidence of non-malignant pleural effusions (NMPE) far outweighs that of malignant pleural effusions (MPE) and is estimated to be at least 3-fold higher. These so called "benign" effusions do not follow a "benign course" in many cases, with mortality rates matching and sometimes exceeding that of MPEs. In addition to the impact on patients, healthcare systems are significantly affected, with recent US epidemiological data demonstrating that 75% of resource allocation for pleural effusion management is spent on NMPEs (excluding empyema). Despite this significant burden of disease, and by existing at the junction of multiple medical specialties, reflecting a heterogenous constellation of medical conditions, NMPEs are rarely the focus of research or the subject of management guidelines. With this ERS Taskforce, we assembled a multi-specialty collaborative across eleven countries and three continents to provide a Statement based on systematic searches of the medical literature to highlight evidence in the management of the following clinical areas: a diagnostic approach to transudative effusions, heart failure, hepatic hydrothorax, end stage renal failure, benign asbestos related pleural effusion, post-surgical effusion and non-specific pleuritis.

European Respiratory Journal 2024; DOI: 10.1183/13993003.00624-2024

European Respiratory Journal 2024; DOI: 10.1183/13993003.02160-2023

European Respiratory Journal 2024 63: 2300797; DOI: 10.1183/13993003.00797-2023 Background The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP.  Methods This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading of Recommendations, Assessment, Development and Evaluations). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations.  Results The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis.  Conclusions With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made.

European Respiratory Journal 2024; DOI: 10.1183/13993003.00335-2024   Respiratory symptoms are ubiquitous and impair health-related quality of life in people with respiratory disease. This European Respiratory Society (ERS) task force aimed to provide recommendations for symptomatic treatment in people with serious respiratory illness. The ERS task force comprised 16 members, including representatives of people with serious respiratory illness and informal caregivers. Seven questions were formulated, six in the "Population, Intervention, Comparison, Outcome" (PICO) format, which were addressed with full systematic reviews and evidence assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). One question was addressed narratively. An "evidence-to-decision" framework was used to formulate recommendations. To treat symptoms in people with serious respiratory illness, the task force suggests the use of graded exercise therapy (conditional recommendation, low certainty of evidence); and suggests the use of a multicomponent services, handheld fan and breathing techniques (conditional recommendations, very low certainty of evidence). The task force suggests not to use opioids (conditional recommendation, very low certainty of evidence); and suggests either administering or not administering supplemental oxygen therapy (conditional recommendation, low certainty of evidence). The task force suggests that needs assessment tools may be used as part of a comprehensive needs assessment, but do not replace patient centred care and shared decision making (conditional recommendation, low certainty of evidence). The low certainty of evidence, modest impact of interventions on patient-centred outcomes, and absence of effective strategies to ameliorate cough highlight the need for new approaches to reduce symptoms and enhance wellbeing for individuals who live with serious respiratory illness.

European Respiratory Journal 2024; DOI: 10.1183/13993003.01727-2023 Chronic graft-versus-host disease (cGvHD) is a common complication after allogeneic haematopoietic stem cell transplantation, characterised by a broad disease spectrum that can affect virtually any organ. Although pulmonary cGvHD is a less common manifestation, it is of great concern due to its severity and poor prognosis. Optimal management of patients with pulmonary cGvHD is complicated and no standardised approach is available. The purpose of this joint European Respiratory Society and European Society for Blood and Marrow Transplantation Task Force was to develop evidence-based recommendations regarding the treatment of pulmonary cGvHD phenotype bronchiolitis obliterans syndrome in adults. A multidisciplinary group representing specialists in haematology, respiratory medicine, methodology as well as patient advocates formulated eight PICO (Patient, Intervention, Comparison, Outcome) and two narrative questions. Following the ERS standardised methodology, we conducted systematic reviews to address these questions and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to develop recommendations. The resulting guideline addresses common therapeutic options (inhalation therapy, fluticasone-azithromycin-montelukast, imatinib, ibrutinib, ruxolitinib, belumosudil, extracorporeal photopheresis and lung transplantation), as well as other aspects of general management, such as lung functional and radiological follow-up and pulmonary rehabilitation, for adults with pulmonary cGvHD phenotype bronchiolitis obliterans syndrome. These recommendations include important advancements that could be incorporated in the management of adults with pulmonary cGvHD, primarily aimed at improving and standardising treatment and improving outcomes.

European Respiratory Journal 2024 63: 2300347; DOI: 10.1183/13993003.00347-2023 This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society and the European Society of Intensive Care Medicine. Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45?? mm on a visual analogue scale from 0 to 100?? mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

European Respiratory Journal 2023 61: 2202031; DOI: 10.1183/13993003.02031-2022AbstractNasal nitric oxide (nNO) is extremely low in most people with primary ciliary dyskinesia (PCD) and its measurement is an important contributor to making the diagnosis. Existing guidelines and technical standards focus on nNO measurements in older, cooperative children using chemiluminescence analysers. However, measurements of nNO in pre-school-age children (age 2-5?? years) may facilitate early diagnosis and electrochemical rather than chemiluminescence analysers are widely used. Pre-schoolers often need different methods to be employed when measuring nNO. Hence, a European Respiratory Society Task Force has developed this technical standard as the first step towards standardising sampling, analysis and reporting of nNO measured as part of the diagnostic testing for PCD in all age groups, including pre-school-age children. Furthermore, we considered both chemiluminescence and electrochemical analysers that are in use worldwide. There was a paucity of quality evidence for electrochemical analysers and sampling methods used in young children, and the Task Force proposes future research priorities to allow updates of this technical standard.

European Respiratory Journal 2023 61: 2300128; DOI: 10.1183/13993003.00128-2023AbstractBackground Screening for lung cancer with low radiation dose computed tomography (LDCT) has a strong evidence base. The European Council adopted a recommendation in November 2022 that lung cancer screening (LCS) be implemented using a stepwise approach. The imperative now is to ensure that implementation follows an evidence-based process that delivers clinical and cost-effectiveness. This European Respiratory Society (ERS) Task Force was formed to provide a technical standard for a high-quality LCS programme.Method A collaborative group was convened to include members of multiple European societies. Topics were identified during a scoping review and a systematic review of the literature was conducted. Full text was provided to members of the group for each topic. The final document was approved by all members and the ERS Scientific Advisory Committee.Results Topics were identified representing key components of a screening programme. The actions on findings from the LDCT were not included as they are addressed by separate international guidelines (nodule management and clinical management of lung cancer) and by a linked ERS Task Force (incidental findings). Other than smoking cessation, other interventions that are not part of the core screening process were not included (e.g. pulmonary function measurement). 56 statements were produced and areas for further research identified.Conclusions This European collaborative group has produced a technical standard that is a timely contribution to implementation of LCS. It will serve as a standard that can be used, as recommended by the European Council, to ensure a high-quality and effective programme.

European Respiratory Journal 2023; DOI: 10.1183/13993003.00442-2023AbstractFrailty is a complex, multidimensional syndrome characterised by a loss of physiological reserves that increases a person's susceptibility to adverse health outcomes. Most knowledge regarding frailty originates from geriatric medicine, however, awareness of its importance as a treatable trait for people with chronic respiratory disease (including asthma, COPD and interstitial lung disease) is emerging. A clearer understanding of frailty and its impact in chronic respiratory disease is a pre-requisite to optimise clinical management in the future. This unmet need underpins the rationale for undertaking the present work.This European Respiratory Society Statement synthesises current evidence and clinical insights from international experts and people affected by chronic respiratory conditions regarding frailty in adults with chronic respiratory disease. The scope includes coverage of frailty within international respiratory guidelines, prevalence and risk factors, review of clinical management options (including comprehensive geriatric care, rehabilitation, nutrition, pharmacological and psychological therapies), and identification of evidence gaps to inform future priority areas of research. Frailty is under-represented in international respiratory guidelines, despite being common and related to increased hospitalisation and mortality. Validated screening instruments can detect frailty to prompt comprehensive assessment and personalised clinical management. Clinical trials targeting people with chronic respiratory disease and frailty are needed.

European Respiratory Journal 2023 62: 2202053; DOI: 10.1183/13993003.02053-2022AbstractAirway clearance techniques (ACTs) are part of the main management strategy for patients with bronchiectasis. Despite being a priority for patients, accessibility, implementation and reporting of ACTs are variable in clinical settings and research studies. This European Respiratory Society statement summarises current knowledge about ACTs in adults with bronchiectasis and makes recommendations to improve the future evidence base. A task force of 14 experts and two patient representatives (10 countries) determined the scope of this statement through consensus and defined six questions. The questions were answered based on systematic searches of the literature. The statement provides a comprehensive review of the physiological rationale for ACTs in adults with bronchiectasis, and the mechanisms of action along with the advantages and disadvantages of each ACT. Evidence on ACTs in clinical practice indicates that the most frequently used techniques are active cycle of breathing techniques, positive expiratory pressure devices and gravity-assisted drainage, although there is limited evidence on the type of ACTs used in specific countries. A review of 30 randomised trials for the effectiveness of ACTs shows that these interventions increase sputum clearance during or after treatment, reduce the impact of cough and the risk of exacerbations, and improve health-related quality of life. Furthermore, strategies for reducing the risk of bias in future studies are proposed. Finally, an exploration of patients' perceptions, barriers and enablers related to this treatment is also included to facilitate implementation and adherence to ACTs.

European Respiratory Journal 2023 62: 2201519; DOI: 10.1183/13993003.01519-2022AbstractThis document updates the 2005 European Respiratory Society (ERS) and American Thoracic Society (ATS) technical standard for the measurement of lung volumes. The 2005 document integrated the recommendations of an ATS/ERS task force with those from an earlier National Heart, Lung, and Blood Institute workshop that led to the publication of background papers between 1995 and 1999 and a consensus workshop report with more in-depth descriptions and discussion. Advancements in hardware and software, new research and emerging approaches have necessitated an update to the 2005 technical standard to guide laboratory directors, physiologists, operators, pulmonologists and manufacturers. Key updates include standardisation of linked spirometry, new equipment quality control and validation recommendations, generalisation of the multiple breath washout concept beyond nitrogen, a new acceptability and grading system with addition of example tracings, and a brief review of imaging and other new techniques to measure lung volumes. Future directions and key research questions are also noted.

European Respiratory Journal 2023 62: 2300533; DOI: 10.1183/13993003.00533-2023AbstractBackground Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation.

European Respiratory Journal 2023; DOI: 10.1183/13993003.00370-2023 AbstractElevated levels of exhaled nitric oxide at a flow of 50?? mL·s−1 (FENO50) are an important indicator of Th2 airway inflammation and may aid clinicians in the diagnosis and monitoring of asthma. This study aimed to derive Global Lung Function Initiative reference equations and the upper limit of normal for FENO50.Available individual FENO50 data were collated and harmonised using consensus-derived variables and definitions. Data collected from individuals who met the harmonised definition of "healthy" were analysed using generalised additive models of location shape and scale (GAMLSS) technique.Data were retrospectively collated from 34 782 individuals from 34 sites in 15 countries, of whom 8022 met the definition of healthy (19 sites, 11 countries). Overall, height, age and sex only explained 12% of the between-subject variability of FENO50 (R2=0.12). The addition of NO device was a predictor of FENO50 and between-subject variability, such that the healthy range of values and the upper limit of normal varied depending on which device was used. The range of FENO50 values observed in healthy individuals was also very wide, and the heterogeneity was partially explained by the device used. The heterogeneity between sites remained within a sub-set of data where FENO50 was measured using the same device and a stricter definition of health (n=1027).Available FENO50 data collected from different sites using different protocols and devices was too variable to develop a single all-age reference equation. Further standardisation of NO devices and measurement is required before population reference values might be derived.

Recent clinical trials of as-needed fixed-dose combination of ICS/formoterol have provided new evidence that may warrant a reconsideration of current practice. A task force (TF) was set up by the European Respiratory Society to provide evidence-based recommendations on the use of as-needed ICS/formoterol as treatment for mild asthma. The TF defined two questions that were assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. The TF utilised the outcomes to develop recommendations for a pragmatic guideline for everyday clinical practice. The TF suggests that adults with mild asthma use as-needed ICS/formoterol instead of regular ICS maintenance treatment plus as-needed short-acting beta-2-antagonists (SABAs), and that adolescents with mild asthma use either as-needed ICS/formoterol or ICS maintenance treatment plus as-needed SABA (Conditional Recommendation; Low Certainty of Evidence). The recommendation for adults places a relatively higher value on the reduction of systemic corticosteroid use and the outcomes related to exacerbations and a relatively lower value on the small differences in asthma control. Either treatment options are suggested for adolescent patients as the balance is very close and data more limited. The TF recommends that adult and adolescent patients with mild asthma use as-needed ICS/formoterol instead of as-needed SABA (Strong Recommendation; Low Certainty of Evidence). This recommendation is based on the benefit of as-needed ICS/formoterol in mild asthma on several outcomes and the risks related to as-needed SABA in the absence of anti-inflammatory treatment. The implementation of this recommendation is hampered in countries (including European Union countries) where as-needed ICS/formoterol is not approved for mild asthma.

European Respiratory Journal 2023 62: 2202014; DOI: 10.1183/13993003.02014-2022 AbstractThere is increased awareness of palliative care needs in people with COPD or interstitial lung disease (ILD). This European Respiratory Society (ERS) task force aimed to provide recommendations for initiation and integration of palliative care into the respiratory care of adult people with COPD or ILD.The ERS task force consisted of 20 members, including representatives of people with COPD or ILD and informal caregivers. Eight questions were formulated, four in the Population, Intervention, Comparison, Outcome format. These were addressed with full systematic reviews and application of Grading of Recommendations Assessment, Development and Evaluation for assessing the evidence. Four additional questions were addressed narratively. An "evidence-to-decision" framework was used to formulate recommendations.The following definition of palliative care for people with COPD or ILD was agreed. A holistic and multidisciplinary person-centred approach aiming to control symptoms and improve quality of life of people with serious health-related suffering because of COPD or ILD, and to support their informal caregivers. Recommendations were made regarding people with COPD or ILD and their informal caregivers: to consider palliative care when physical, psychological, social or existential needs are identified through holistic needs assessment; to offer palliative care interventions, including support for informal caregivers, in accordance with such needs; to offer advance care planning in accordance with preferences; and to integrate palliative care into routine COPD and ILD care. Recommendations should be reconsidered as new evidence becomes available.

European Respiratory Journal 2023 61: 2200735; DOI: 10.1183/13993003.00735-2022 Background Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and while European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP.  Materials and methodology 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.

European Respiratory Journal 2022 59: 2102006; DOI: 10.1183/13993003.02006-2021