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Recent clinical trials of as-needed fixed-dose combination of inhaled corticosteroid (ICS)/formoterol have provided new evidence that may warrant a reconsideration of current practice. A Task Force 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 Task Force defined two questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. The Task Force utilised the outcomes to develop recommendations for a pragmatic guideline for everyday clinical practice. The Task Force suggests that adults with mild asthma use as-needed ICS/formoterol instead of regular ICS maintenance treatment plus as-needed short-acting β 2 -antagonist (SABA) 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 option is suggested for adolescent patients as the balance is very close and data more limited. The Task Force 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., Competing Interests: Conflict of interest: A. Papi reports grants from Chiesi, AstraZeneca, GSK, Sanofi and Agenzia Italiana del Farmaco (AIFA), consulting fees from Chiesi, AstraZeneca, GSK, Novartis, Sanofi, Avillion and Elpen Pharmaceutica, lecture honoraria from Chiesi, AstraZeneca, GSK, Menarini, Novartis, Zambon, Munidpharma, Sanofi, Edmond Pharma, IQVIA, Avillion and Elpen Pharmaceuticals, and advisory board participation with Chiesi, AstraZeneca, GSK, MSD, Novartis, Sanofi, IQVIA, Avillion and Elpen Pharmaceuticals, outside the submitted work. I. Agache reports lecture honoraria from Stallergennes, Pfizer and Sanofi, and advisory board participation with Pfizer, outside the submitted work. E. Baraldi reports lecture honoraria from AstraZeneca and Sanofi, outside the submitted work. R. Beasley reports grants from AstraZeneca, Genentech and Health Research Council New Zealand, consulting fees, lecture honoraria, travel support and advisory board participation with AstraZeneca, Cipla, Avillion, Health Research Council New Zealand, CSL Seqirus and Teva, outside the submitted work; R. Beasley is also chair of the Asthma and Respiratory Foundation NZ adolescent and adult asthma guidelines, member of the GOLD Board, and consultant for GINA. G. Brusselle reports lecture honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Merck, Sharp & Dohme and Sanofi, outside the submitted work. C. Coleman is an employee of the European Lung Foundation. M. Gaga reports a role as Alternate Minister of Health, Greece, outside the submitted work. E. Melén has received consulting fees from ALK, AstraZeneca, Chiesi, Novartis and Sanofi, outside the submitted work. I.D. Pavord reports speaker fees from Aerocrine AB, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi and Teva, consultant fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi, Teva, Circassia, Dey Pharma, Genentech, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, RespiVert and Schering-Plough, payments for organisation of educational events from AstraZeneca, GSK, Regeneron Pharmaceuticals, Inc., Sanofi and Teva, international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Regeneron Pharmaceuticals, Inc., Sanofi, Teva and Napp Pharmaceuticals, and research grants from Chiesi, outside the submitted work. D. Peñate Gómez works as PMO Analyst at Asthma and Lung UK. A. Spanevello reports lecture honoraria, travel support and advisory board participation with Chiesi, AstraZeneca and GSK, outside the submitted work. T. Tonia acts as ERS methodologist. F. Schleich reports grants from GSK, AstraZeneca and Chiesi, lecture honoraria from GSK, AstraZeneca, Chiesi and Teva, and advisory board participation with GSK and AstraZeneca, outside the submitted work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

This document provides recommendations for monitoring and treatment of children in whom bronchopulmonary dysplasia (BPD) has been established and who have been discharged from the hospital, or who were >36 weeks of postmenstrual age. The guideline was based on predefined Population, Intervention, Comparison and Outcomes (PICO) questions relevant for clinical care, a systematic review of the literature and assessment of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. After considering the balance of desirable (benefits) and undesirable (burden, adverse effects) consequences of the intervention, the certainty of the evidence, and values, the task force made conditional recommendations for monitoring and treatment of BPD based on very low to low quality of evidence. We suggest monitoring with lung imaging using ionising radiation in a subgroup only, for example severe BPD or recurrent hospitalisations, and monitoring with lung function in all children. We suggest to give individual advice to parents regarding daycare attendance. With regards to treatment, we suggest the use of bronchodilators in a subgroup only, for example asthma-like symptoms, or reversibility in lung function; no treatment with inhaled or systemic corticosteroids; natural weaning of diuretics by the relative decrease in dose with increasing weight gain if diuretics are started in the neonatal period; and treatment with supplemental oxygen with a saturation target range of 90-95%. A multidisciplinary approach for children with established severe BPD after the neonatal period into adulthood is preferable. These recommendations should be considered until new and urgently needed evidence becomes available., Competing Interests: Conflict of interest: L. Duijts has nothing to disclose. Conflict of interest: E.R. van Meel has nothing to disclose. Conflict of interest: L. Moschino has nothing to disclose. Conflict of interest: E. Baraldi has nothing to disclose. Conflict of interest: M. Barnhoorn has nothing to disclose. Conflict of interest: W.M. Bramer has nothing to disclose. Conflict of interest: C.E. Bolton has nothing to disclose. Conflict of interest: J. Boyd is an employee of the European Lung Foundation. Conflict of interest: F. Buchvald has nothing to disclose. Conflict of interest: M.J. del Cerro has nothing to disclose. Conflict of interest: A.A. Colin has nothing to disclose. Conflict of interest: R. Ersu has nothing to disclose. Conflict of interest: A. Greenough reports grants and honoraria for lectures from MedImmune/Abbott, outside the submitted work. Conflict of interest: C. Gremmen has nothing to disclose. Conflict of interest: T. Halvorsen has nothing to disclose. Conflict of interest: J. Kamphuis has nothing to disclose. Conflict of interest: S. Kotecha has nothing to disclose. Conflict of interest: K. Rooney-Otero has nothing to disclose. Conflict of interest: S. Schulzke has nothing to disclose. Conflict of interest: A. Wilson has nothing to disclose. Conflict of interest: D. Rigau acts as ERS methodologist. Conflict of interest: R.L. Morgan has nothing to disclose. Conflict of interest: T. Tonia acts as ERS methodologist. Conflict of interest: C.C. Roehr has nothing to disclose. Conflict of interest: M.W. Pijnenburg has nothing to disclose., (Copyright ©ERS 2020.)

Breath tests cover the fraction of nitric oxide in expired gas ( F eNO ), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for F eNO , official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and F eNO , new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice., Competing Interests: Conflict of interest: T. Tonia acts as a methodologist for the European Respiratory Society. Further disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

The goal of asthma treatment is to obtain clinical control and reduce future risks to the patient. To reach this goal in children with asthma, ongoing monitoring is essential. While all components of asthma, such as symptoms, lung function, bronchial hyperresponsiveness and inflammation, may exist in various combinations in different individuals, to date there is limited evidence on how to integrate these for optimal monitoring of children with asthma. The aims of this ERS Task Force were to describe the current practise and give an overview of the best available evidence on how to monitor children with asthma. 22 clinical and research experts reviewed the literature. A modified Delphi method and four Task Force meetings were used to reach a consensus. This statement summarises the literature on monitoring children with asthma. Available tools for monitoring children with asthma, such as clinical tools, lung function, bronchial responsiveness and inflammatory markers, are described as are the ways in which they may be used in children with asthma. Management-related issues, comorbidities and environmental factors are summarised. Despite considerable interest in monitoring asthma in children, for many aspects of monitoring asthma in children there is a substantial lack of evidence., (Copyright ©ERS 2015.)

Chronic obstructive respiratory disorders such as asthma and chronic obstructive pulmonary disease often originate early in life. In addition to a genetic predisposition, prenatal and early-life environmental exposures have a persistent impact on respiratory health. Acting during a critical phase of lung development, these factors may change lung structure and metabolism, and may induce maladaptive responses to harmful agents, which will affect the whole lifespan. Some environmental factors, such as exposure to cigarette smoke, type of childbirth and diet, may be modifiable, but it is more difficult to influence other factors, such as preterm birth and early exposure to viruses or allergens. Here, we bring together recent literature to analyse the critical aspects involved in the early stages of lung development, going back to prenatal and perinatal events, and we discuss the mechanisms by which noxious factors encountered early on may have a lifelong impact on respiratory health. We briefly comment on the need for early disease biomarkers and on the possible role of "-omic" technologies in identifying risk profiles predictive of chronic respiratory conditions. Such profiles could guide the ideation of effective preventive strategies and/or targeted early lifestyle or therapeutic interventions., (©ERS 2014.)

Prematurity and its main respiratory complication, bronchopulmonary dysplasia (BPD), are potentially associated with lifelong respiratory morbidities and/or lung function abnormalities. The mechanisms behind these long-term respiratory problems are still unclear. We assessed airway oxidative stress in adolescents born very pre-term (≤ 32 gestational weeks) by measuring 8-isoprostane concentration in exhaled breath condensate (EBC). In addition, the study protocol included spirometry and measurement of exhaled nitric oxide fraction (F(eNO)). The study groups included 34 ex-pre-term adolescents with BPD, 18 ex-pre-term adolescents without BPD and 34 healthy controls born at term. Regardless of a history of BPD, the ex-premature adolescents had higher EBC 8-isoprostane levels (median (interquartile range) BPD 9.5 (7.3-12.2) pg·mL(-1); pre-term non-BPD 10 (8.1-16) pg·mL(-1)) than the controls (3.2 (1.9-6.5) pg·mL(-1)) (p<0.001). Forced expiratory volume in 1 s was lower in the BPD group (mean ± sd Z-score -2.1 ± 1.58) than in the pre-term non-BPD individuals (-1.13 ± 1.15), who showed in turn significantly lower values than the controls (0.18 ± 0.83; p<0.001). F(eNO) was similar in the three groups (p=0.55). Our data show that, after premature birth, evidence of oxidative stress in the airways may be detected into adolescence, suggesting that long-term respiratory abnormalities after pre-term birth may be associated with an ongoing airway disease and not just a stabilised structural lung damage.

There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided into medications used in lower doses for children with less severe asthma, and those used in other paediatric diseases but not for asthma (for example, methotrexate). In the first category are high-dose inhaled corticosteroids (ICS) (≤ 2,000 μg · day(-1) fluticasone equivalent), oral prednisolone, the anti-immunoglobulin (Ig)E antibody omalizumab, high-dose long-acting β(2)-agonists, low-dose oral theophylline and intramuscular triamcinolone. If peripheral airway inflammation is thought to be a problem, the use of fine-particle ICS or low-dose oral corticosteroids may be considered. More experimental therapies include oral macrolides, cyclosporin, cytotoxic drugs such as methotrexate and azathioprine, gold salts, intravenous infusions of Ig, subcutaneous β(2)-agonist treatment and, in those sensitised to fungi, oral antifungal therapy with itraconazole or voriconazole. Those with recurrent severe exacerbations, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both at the time of exacerbations can be considered. There is no evidence regarding which therapeutic option to recommend. Better evidence is required for all these treatment options, underscoring the need for the international and co-ordinated approach which we have previously advocated.

Assessment of problematic severe asthma in children should be performed in a step-wise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small, but challenging group of patients.

Asthmatic airways are characterised by enhanced oxidative stress, which can be studied by measuring biomarkers, such as 8-isoprostane. The aims of the present study were: 1) to measure the concentrations of 8-isoprostane in exhaled breath condensate (EBC) and urine of children with problematic and well-controlled asthma; 2) to compare the concentrations of 8-isoprostane measured by gas chromatographic/negative ion chemical ionisation mass spectrometry (GC/NICI-MS) and by an enzymatic immunoassay (EIA). We recruited 20 asthmatic allergic children, 13 with well-controlled asthma and seven with problematic asthma. They underwent exhaled nitric oxide measurements and spirometry, and both EBC and urine samples were collected. 8-isoprostane was measured in EBC by GC/NICI-MS and EIA. 8-isoprostane concentrations in EBC were significantly higher in children with problematic asthma than in children with well-controlled asthma (p = 0.01). An acceptable reproducibility emerged between GC/NICI-MS and EIA (coefficient of reproducibility 11.5 pg x mL(-1)). 8-isoprostane levels measured in urine did not correlate with those measured in EBC. We showed that 8-isoprostane in EBC was significantly increased in children with problematic asthma, suggesting a role for oxidative stress in this asthma phenotype. In addition we found an acceptable reproducibility of EIA compared to GC/NICI-MS, even if the latter method had higher accuracy.

Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

Measurement of fractional exhaled nitric oxide in exhaled air is an exciting innovative technique that gives new insights in to the pathophysiology of lung disease and asthma in particular, with many potential clinical applications. Careful standardisation of measurement techniques will facilitate the use of this new measurement in paediatric respiratory medicine: this Task Force was set up for this purpose. Methodologies, for use in all age groups, are already available and there are abundant questions relating to interpretation and application of fractional exhaled nitric oxide waiting to be addressed. Noninvasiveness and instantaneous results potentially make it a suitable monitoring instrument for use in children. Exhaled nitric oxide measurement has definitely found its way into clinical research in paediatric respiratory medicine. Evidence for clinically-useful applications is accumulating, and the merits of this new technique must now be demonstrated in larger studies, using standardised methodology in an appropriate setting.