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OBJECTIVES In epidemiological studies, childhood asthma is usually assessed with questionnaires directed at parents or children, and these may give different answers. We studied how well parents and children agreed when asked to report symptoms of wheeze and investigated whose answers were closer to measurable traits of asthma. METHODS LuftiBus in the school is a cross-sectional survey of respiratory health among Swiss schoolchildren aged 6-17 years. We applied questionnaires to parents and children asking about wheeze and exertional wheeze in the past year. We assessed agreement between parent-child answers with Cohen's kappa (k), and associations of answers from children and parents with fractional exhaled nitric oxide (FeNO) and forced expiratory volume in 1 s over forced vital capacity (FEV1 /FVC), using quantile regression. RESULTS We received questionnaires from 3079 children and their parents. Agreement was poor for reported wheeze (k = 0.37) and exertional wheeze (k = 0.36). Median FeNO varied when wheeze was reported by children (19 ppb, interquartile range [IQR]: 9-44), parents (22 ppb, IQR: 12-46), both (31 ppb, IQR: 16-55), or neither (11 ppb, IQR: 7-19). Median absolute FEV1 /FVC was the same when wheeze was reported by children (84%, IQR: 78-89) and by parents (84%, IQR: 78-89), lower when reported by both (82%, IQR: 78-87), and higher when reported by neither (87%, IQR: 82-91). For exertional wheeze findings were similar. Results did not differ by age or sex. CONCLUSION Our findings suggest that surveying both parents and children and combining their responses can help us to better identify children with measurable asthma traits.

OBJECTIVE Exercise-induced respiratory symptoms (EIS) are common in childhood and reflect different diseases that can be difficult to diagnose. In children referred to respiratory outpatient clinics for EIS, we compared the diagnosis proposed by the primary care physician with the final diagnosis from the outpatient clinic and described diagnostic tests and treatments. DESIGN Observational study of respiratory outpatients aged 0-16 years nested in the Swiss Paediatric Airway Cohort (SPAC). PATIENTS We included children with EIS as main reason for referral. Information about diagnostic investigations, final diagnosis, and treatment prescribed came from outpatient records. We included 214 children (mean age 12 years, range 2-17, 54% males) referred for EIS. RESULTS The final diagnosis was asthma in 115 (54%), extrathoracic dysfunctional breathing (DB) in 35 (16%), thoracic DB in 22 (10%), asthma plus DB in 23 (11%), insufficient fitness in 10 (5%), chronic cough in 6 (3%), and other diagnoses in 3 (1%). Final diagnosis differed from referral diagnosis in 115 (54%, 95%-CI 46-60%). Spirometry, body plethysmography, and exhaled nitric oxide were performed in almost all, exercise-challenge tests in a third, and laryngoscopy in none. 91% of the children with a final diagnosis of asthma were prescribed inhaled medication and 50% of children with DB were referred to physiotherapy. CONCLUSIONS Diagnosis given at the outpatient clinic often differed from the diagnosis proposed by the referring physician. Diagnostic evaluations, management, and follow-up differed between clinics and diagnostic groups highlighting the need for evidence-based diagnostic guidelines and harmonised procedures for children seen for EIS. This article is protected by copyright. All rights reserved.

Background Lung disease can develop within the first year of life in infants with cystic fibrosis (CF). However, the frequency and severity of respiratory symptoms in infancy are not known. Methods We assessed respiratory symptoms in 50 infants with CF and 50 healthy matched controls from two prospective birth cohort studies. Respiratory symptoms and respiratory rate were documented by standardized weekly interviews throughout the first year. Infants performed multiple breath washout in the first weeks of life. Results We analyzed 4552 data points (2217 in CF). Respiratory symptoms (either mild or severe) were not more frequent in infants with CF (OR:1.1;95% CI:[0.76, 1.59]; p=0.6). Higher lung clearance index and higher respiratory rate in infants with CF were not associated with respiratory symptoms. Conclusions We found no difference in respiratory symptoms between healthy and CF infants. These data indicate that early CF lung disease may not be captured by clinical presentation alone.

BackgroundReferences from the Global Lung Function Initiative (GLI) are widely used to interpret children’s spirometry results. We assessed fit for healthy schoolchildren.MethodsLuftiBus in the school (LUIS) is a population-based cross-sectional study done from 2013-2016 in the canton of Zurich, Switzerland. Parents and children aged 6-17 years answered questionnaires about respiratory symptoms and lifestyle. Children underwent spirometry in a mobile lung function lab. We calculated GLI-based z-scores for FEV1, FVC, FEV1/FVC, and FEF25-75for healthy White participants. We defined appropriate fit to GLI references by mean values ±0.5 z-scores. We assessed if fit varied by age, body mass index, height, and sex using linear regression models.ResultsWe analysed data from 2036 children with valid FEV1measurements of which 1762 also had valid FVC measurements. The median age was 12.2 years. Fit was appropriate for children aged 6-11 years for all indices. In adolescents aged 12-17 years, fit was appropriate for FEV1/FVC (mean: -0.09; SD: 1.02) z-scores, but not for FEV1(mean: -0.62; SD: 0.98), FVC (mean: -0.60; SD: 0.98), and FEF25-75(mean: -0.54; SD: 1.02). FEV1, FVC, and FEF25-75z-scores fitted better in children considered overweight (means: -0.25, -0.13, -0.38) than normal weight (means: -0.55, -0.50, -0.55;p-trend: 1, FVC, and FEF25-75z-scores depended on both age and height (pinteraction: 0.034, 0.019, ConclusionGLI-based FEV1, FVC, and FEF25-75z-scores do not fit White Swiss adolescents well. This should be considered when using reference equations for clinical decision making, research and international comparison.Take home messageOur study suggests GLI-based FEV1, FVC, and FEF25-75z-scores over detect abnormal lung function in Swiss adolescents, and more so among slimmer adolescents, which has important implications for clinical care, research, and international comparisons.

BACKGROUND Nasal nitric oxide (nNO) measurement is recommended as a first line screening test for primary ciliary dyskinesia (PCD). While reliable velum- and non-velum-closure techniques exist for preschool children and older individuals, no data are available for neonates. AIMS To determine feasibility of nNO screening and nNO concentration in healthy newborns in the first week of life. METHODS Nasal NO was analyzed in tidal breathing during natural sleep using a CLD-88 sp NO analyzer (chemoluminescence sensor) and a NIOX MINO (electrochemical sensor). Test success and nNO concentration were determined and compared between the two devices. RESULTS Nasal NO was measured in 62 healthy neonates within the first week of life. Feasibility of nNO measurement was 100% for at least one nostril and 85.5% for both nostrils using the chemoluminescence device, but significantly lower with the electrochemical device (85.5% and 53.2%; p

Introduction Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe. Methods Structured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data. Results We interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals. Conclusion Substantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident., This study reveals enormous differences in therapy with biologicals for childhood severe asthma across Europe, and demonstrates the urgent need for harmonisation in medication choice, definition of therapy success and how/when to discontinue treatment https://bit.ly/3tnJMTY

Antibiotic eradication treatment is the standard-of-care for cystic fibrosis (CF) patients with early Pseudomonas aeruginosa (Pa)-infection; however, evidence from placebo-controlled trials is limited.This double-blind, placebo-controlled trial randomised CF patients7 years (N = 51) with early Pa-infection to tobramycin inhalation solution (TOBI 300 mg) or placebo (twice daily) for 28 days with an optional cross-over on Day 35. Primary endpoint was proportion of patients having throat swabs/sputum free of Pa on Day 29.On Day 29, 84.6% patients in the TOBI versus 24.0% in the placebo group were Pa-free (p 0.001). At the end of the cross-over period, 76.0% patients receiving TOBI in the initial 28 days were Pa-free compared to 47.8% receiving placebo initially. Adverse events were consistent with the TOBI safety profile with no differences between TOBI and placebo.TOBI was effective in eradicating early Pa-infection with a favourable safety profile in young CF patients.NCT01082367.

We assessed how prevalence estimates of cough in 6-17-year-olds vary depending on the question asked in the population-based Luftibus in the school (LUIS) study. 3427 parents answered three different questions on cough. The prevalence of parent-reported cough varied substantially depending on the question: 25% of parents reported cough without a cold, 11% dry night cough and 5% that their child coughs more than other children. There was only partial overlap with 3% answering yes to all questions. This suggests that the exact question used to assess cough strongly affects prevalence estimates and must be taken into account when comparing studies.

In epidemiological studies, childhood asthma is usually assessed with questionnaires directed at parents or children, and these may give different answers. We studied how well parents and children agreed when asked to report symptoms of wheeze and investigated whose answers were closer to measurable traits of asthma.LuftiBus in the schoolis a cross-sectional survey of respiratory health among Swiss schoolchildren aged 6-17 years. We applied questionnaires to parents and children asking about wheeze and exertional wheeze in the past year. We assessed agreement between parent-child answers with Cohen’s kappa (k), and associations of answers from children and parents with physiological measurements (i.e. FeNO and FEV1/FVC), using quantile regression.We received questionnaires from 3079 children and their parents. Agreement was poor for reported wheeze (k=0.37) and exertional wheeze (k=0.36). Median FeNO varied when wheeze was reported by children (19 ppb, IQR: 9-44), parents (22 ppb, IQR: 12-46), both (31 ppb, IQR: 16-55) or neither (11 ppb, IQR: 7-19). Median absolute FEV1/FVC was the same when wheeze was reported by children (84%, IQR: 78-89) and by parents (84%, IQR: 78-89), lower when reported by both (82%, IQR: 78-87) and higher when reported by neither (87%, IQR: 82-91). For exertional wheeze findings were similar. Results did not differ by age or sex.Our findings suggest that surveying both parents and children and combining their responses can help us to better identify children with measurable asthma traits.Take home messageThere is poor agreement between schoolchildren and their parents when reporting current wheeze. However, wheeze correlates best with lung function and FeNO when reported by both children and parents.

BackgroundExercise-induced breathing problems with similar clinical presentations can have different aetiologies. This makes distinguishing common diagnoses such as asthma, extrathoracic and thoracic dysfunctional breathing (DB), insufficient fitness, and chronic cough difficult.ObjectiveWe studied which parent-reported, exercise-induced symptoms (EIS) can help distinguish diagnoses of EIS in children seen in respiratory outpatient clinics.MethodsThis study was nested in the Swiss Paediatric Airway Cohort (SPAC), an observational study of children aged 0-17 years referred to paediatric respiratory outpatient clinics in Switzerland. We studied children aged 6-17 years and compared information on EIS from parent-completed questionnaires between children with different diagnoses. We used multinomial regression to analyse whether parent-reported symptoms differed between diagnoses (asthma as base).ResultsAmong 1109 children, EIS were reported for 732 (66%) (mean age 11 years, 318 of 732 [43%] female). Among the symptoms, dyspnoea best distinguished thoracic DB (relative risk ratio [RRR] 5.4, 95%CI 1.3-22) from asthma. Among exercise triggers, swimming best distinguished thoracic DB (RRR 2.4, 95%CI 1.3-6.2) and asthma plus DB (RRR 1.8, 95%CI 0.9-3.4) from asthma only. Late onset of EIS was less common for extrathoracic DB (RRR 0.1, 95%CI 0.03-0.5) and thoracic DB (RRR 0.4, 95%CI 0.1-1.2) compared with asthma. Localisation of dyspnoea (throat vs. chest) differed between extrathoracic DB (RRR 2.3, 95%CI 0.9-5.8) and asthma. Reported respiration phase (inspiration or expiration) did not help distinguish diagnoses.ConclusionParent-reported symptoms help distinguish different diagnoses in children with EIS. This highlights the importance of physicians obtaining detailed patient histories.Highlights boxWhat is already known about this topic?Experts suggest that information about the symptoms and their onset and duration can assist accurate diagnosis of children with exercise-induced respiratory problems, but no original studies have tested this. (29/35 words)What does this article add to our knowledge?Exercise-induced symptoms reported by parents and further information about their onset, triggers, and effects of treatment help differentiate diagnoses in children with exercise-induced respiratory problems. (25/35 words)How does this study impact current management guidelines?Our results emphasize the importance of taking detailed symptom histories of children with exercise-induced problems, and suggest which questions are most helpful.

In this review, the Paediatric Assembly of the European Respiratory Society (ERS) presents a summary of the highlights and most relevant findings in the field of paediatric respiratory medicine presented at the virtual ERS International Congress 2020. Early Career Members of the ERS and Chairs of the different Groups comprising the Paediatric Assembly discuss a selection of the presented research. These cover a wide range of research areas, including respiratory physiology and sleep, asthma and allergy, cystic fibrosis, respiratory infection and immunology, neonatology and intensive care, epidemiology, bronchology and lung and airway development. Specifically, we describe the long-term effect in lung function of premature birth, mode of delivery and chronic respiratory conditions such as cystic fibrosis. In paediatric asthma, we present risk factors, phenotypes and their progression with age, and the challenges in diagnosis. We confirm the value of the lung clearance index to detect early lung changes in cystic fibrosis. For bronchiectasis treatment, we highlight the importance of identifying treatable traits. The use of biomarkers and genotypes to identify infants at risk of long-term respiratory morbidity is also discussed. We present the long-term impact on respiratory health of early life and fetal exposures to maternal obesity and intrauterine hypoxia, mechanical ventilation hyperoxia, aeroallergens, air pollution, vitamin A deficient intake and bronchitis. Moreover, we report on the use of metabolomics and genetic analysis to understand the effect of these exposures on lung growth and alveolar development. Finally, we stress the need to establish multidisciplinary teams to treat complex airway pathologies., Highlights from the Paediatrics Assembly at the #ERSCongress 2020 https://bit.ly/3ptcnFr

BACKGROUND Multiple breath washout (MBW) is increasingly used in the clinical assessment of patients with cystic fibrosis (CF). Guidelines for MBW quality control (QC) were developed primarily for retrospective assessment and central overreading. We assessed whether real-time QC of MBW data during the measurement improves test acceptability in the clinical setting. METHODS We implemented standardized real-time QC and reporting of MBW data at the time of the measurement in the clinical pediatric lung function laboratory in Bern, Switzerland in children with CF aged 4-18 years. We assessed MBW test acceptability before (31 tests; 89 trials) and after (32 tests; 96 trials) implementation of real-time QC and compared agreement between reviewers. Further, we assessed the implementation of real-time QC at a secondary center in Zurich, Switzerland. RESULTS Before implementation of real-time QC in Bern, only 58% of clinical MBW tests were deemed acceptable following retrospective QC by an experienced reviewer. After implementation of real-time QC, MBW test acceptability improved to 75% in Bern. In Zurich, after implementation of real-time QC, test acceptability improved from 38% to 70%. Further, the agreement between MBW operators and an experienced reviewer for test acceptability was 84% in Bern and 93% in Zurich. CONCLUSION Real-time QC of MBW data at the time of measurement is feasible in the clinical setting and results in improved test acceptability. This article is protected by copyright. All rights reserved.

Background Early reports suggest that most children infected with severe acute respiratory syndrome coronavirus 2 (“SARS-CoV-2”) have mild symptoms. What is not known is whether children with chronic respiratory illnesses have exacerbations associated with SARS-CoV-2 virus. Methods An expert panel created a survey, which was circulated twice (in April and May 2020) to members of the Paediatric Assembly of the European Respiratory Society (ERS) and via the social media of the ERS. The survey stratified patients by the following conditions: asthma, cystic fibrosis (CF), bronchopulmonary dysplasia (BPD) and other respiratory conditions. Results In total 174 centres responded to at least one survey. 80 centres reported no cases, whereas 94 entered data from 945 children with coronavirus disease 2019 (COVID-19). SARS-CoV-2 was isolated from 49 children with asthma of whom 29 required no treatment, 19 needed supplemental oxygen and four children required mechanical ventilation. Of the 14 children with CF and COVID-19, 10 required no treatment and four had only minor symptoms. Among the nine children with BPD and COVID-19, two required no treatment, five required inpatient care and oxygen and two were admitted to a paediatric intensive care unit (PICU) requiring invasive ventilation. Data were available from 33 children with other conditions and SARS-CoV-2 of whom 20 required supplemental oxygen and 11 needed noninvasive or invasive ventilation. Conclusions Within the participating centres, in children with asthma and CF, infection with SARS-CoV-2 was well tolerated, but a substantial minority of children with BPD and other conditions required ventilatory support indicating that these latter groups are at risk from SARS-CoV-2 infection., Whereas children with asthma and CF seem not to be at increased risk of severe #COVID19, a minority of children with other respiratory diseases might be at increased risk and may benefit from being shielded https://bit.ly/3fiwUXp

Parental and children’s questionnaires are used to assess respiratory symptoms, but we know little about their validity against objective markers of asthma. We studied agreement between parent and child reported current wheeze in Swiss schoolchildren and its association with FeNO and FEV1. We analysed data from Luftibus in the school, a population-based survey of respiratory health in children done in the canton of Zurich. Parents completed a questionnaire at home, children at school. We analysed parent-child agreement on wheeze with Cohen’s kappa and the association of parent and child reported wheeze with FEV1% predicted (adjusting for age, sex) and FeNO (adjusting also for hay fever) with linear regressions. We received questionnaires from 3113 families (median age 12years, range 6-17). Prevalence of wheeze was similar when analysing children’s (9%) and parents’ (8%) questionnaires, but agreement was poor (kappa 0.37, 0.31-0.43). Wheeze was reported by the parent only in 128 families (4%), child only in 166 (6%) and both in 108 (4%). Children had higher median FeNO and lower mean FEV1% if both reported wheeze (FeNO 31.2; FEV1% 91.3) than parent only (FeNO 17.8; FEV1% 92.4), child only (FeNO 15.5; FEV1% 94.4) or none (FeNO 11.4; FEV1% 94.1). Wheeze was similarly associated with FeNO and FEV1% when using parents’ (FeNO 14.7, 95%CI 11.4-17.9; FEV1% -2.1, 95%CI -3.7 to -0.4) vs children’s answers (FeNO 12.5, 95%CI 9.6-15.4; FEV1% -0.7, 95%CI -2.2 to 0.9). Parent-child agreement on reported wheeze is poor, but both reports are similarly associated with objective markers of asthma. If parents and children both report wheeze, the probability that this reflects true asthma seems high. Method: Lunge Zurich

Introduction: Population-based studies on chronic cough in children are scarce. Little is known on how chronic cough varies by sex, age and presence or absence of wheeze, and its risk factors are unclear. Methods: In 2013-16, we conducted a field study on respiratory health among schoolchildren in the canton of Zurich, Switzerland (“Luftibus in the school”). Parents and children completed a questionnaire, and lung function tests were done in a mobile lab. In the questionnaire chronic cough was defined as cough lasting more than 3 weeks. We performed a multivariable logistic regression to identify factors associated with chronic cough. Results: We analysed data from 3395 children (age range 6-17 years, 50% girls), of which 319 (9%) reported chronic cough. The prevalence was 10% in girls, 8% in boys, 12% in 6-9 years old and 8% in older children. 73 (23%) of those with chronic cough reported also wheeze. Factors associated with chronic cough in the multivariable regression were: female sex (OR 1.5, 95%CI 1.1-2.0), younger age (OR:1.1, 95%CI 1.0-1.2), overweight (OR 1.5, 95%CI 1.1-2.1), active smoking (≥1/week) (OR 4.1, 95%CI 1.7-10.0), asthma (OR 2.6, 95%CI 1.8-3.9), rhinitis (OR 1.8, 95%CI 1.3-2.5) and otitis media (OR 1.9, 95%CI 1.3-2.7). We found no association with number of siblings, parental smoking, living on a farm, pets, hay fever and snoring. Conclusion: Chronic cough is frequent among schoolchildren in Switzerland, especially girls and younger children and associated with asthma and upper respiratory disease. Overweight and smoking are modifiable risk factors which could be addressed to reduce the burden of chronic cough. Funding: Lunge Zurich, SNF:32003B_162820

BackgroundSmoking is a major preventable cause of morbidity and mortality. We assessed smoking behaviour in 6-17-year-olds. In 13-17-year-olds, we studied risk factors for smoking and compared the frequency of respiratory problems between those who smoked and those who did not.MethodsWe used data from LuftiBus in the school, a school-based survey of the respiratory health of children carried out 2013-2016 in the canton of Zurich, Switzerland. Participants were asked about cigarette, shisha, and electronic smoking device (ESD) smoking, and respiratory symptoms and diseases. We studied the association between smoking and risk factors using logistic regression.ResultsWe included 3488 schoolchildren with data on active smoking. Five percent of the 6-12-year-olds (90 of 1905) had smoked occasionally (ConclusionSmoking of shishas and ESDs is popular among Swiss adolescents and often combined with smoking cigarettes. Structural smoking prevention strategies should include all forms of smoking including shishas and ESDs.

BACKGROUND Smoking habits in adolescents are changing. We assessed active smoking of conventional cigarettes, e-cigarettes and shishas in Swiss schoolchildren, studied risk factors and compared respiratory problems between smokers and non-smokers. METHODS We used data from LuftiBus in the school (LUIS), a school-based survey of respiratory health of children carried out 2013-2016 in the canton of Zurich, Switzerland. Participants were asked about use of cigarettes, shishas, and electronic smoking devices (ESD), and current respiratory symptoms. We studied associations between smoking and risk factors using logistic regression. RESULTS We included 3488 schoolchildren. Among 6-12-year-olds, 90/1905 (5%) had smoked occasionally (

IntroductionDiagnosing asthma in children remains a challenge because respiratory symptoms are not specific and vary over time.AimIn a real-life observational study, we assessed the diagnostic accuracy of respiratory symptoms, objective tests and two paediatric diagnostic algorithms (proposed by the Global Initiative for Asthma (GINA) and the National Institute for Health and Care Excellence (NICE)) in the diagnosis of asthma in school-aged children.MethodsWe studied children aged 5–17 years who were referred consecutively to pulmonary outpatient clinics for evaluation of suspected asthma. Symptoms were assessed by parental questionnaire. The investigations included specific IgE measurement or skin prick tests, measurement of exhaled nitric oxide fraction (FeNO), spirometry, body plethysmography and bronchodilator reversibility (BDR). Asthma was diagnosed by paediatric pulmonologists based on all available data. We assessed diagnostic accuracy of symptoms, tests and diagnostic algorithms by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC).ResultsAmong 514 participants, 357 (70%) were diagnosed with asthma. The combined sensitivity and specificity was highest for any wheeze (sensitivity=75%, specificity=65%), dyspnoea (sensitivity=56%, specificity=76%) and wheeze triggered by colds (sensitivity=58%, specificity=78%) or by exercise (sensitivity=55%, specificity=74%). Of the diagnostic tests, the AUC was highest for specific total airway resistance (sRtot; AUC=0.73) and lowest for the residual volume (RV)/total lung capacity (TLC) ratio (AUC=0.56). The NICE algorithm had sensitivity=69% and specificity=67%, whereas the GINA algorithm had sensitivity=42% and specificity=90%.ConclusionThis study confirms the limited usefulness of single tests and existing algorithms for the diagnosis of asthma. It highlights the need for new and more appropriate evidence-based guidance.

ObjectiveExercise-induced respiratory symptoms (EIS) are common in childhood and reflect different diseases that can be difficult to diagnose. In children referred to respiratory outpatient clinics for EIS, we compared the diagnosis proposed by the referring primary care physician with the final diagnosis from the outpatient clinic and described diagnostic tests performed and treatment prescribed after the diagnostic evaluation.DesignObservational study nested in the Swiss Paediatric Airway Cohort (SPAC), which includes respiratory outpatients aged 0-16 years.PatientsWe included children with EIS as main reason for referral. Information about diagnostic investigations, final diagnosis, and treatment prescribed came from outpatient records.Results214 were referred for EIS (mean age 12 years, 99 (46%) female). The final diagnosis was asthma in 115 (54%), extrathoracic dysfunctional breathing (DB) in 35 (16%), thoracic DB in 22 (10%), asthma plus DB in 23 (11%), insufficient fitness in 10 (5%), chronic cough in 6 (3%), and other diagnoses in 3 (1%). Final diagnosis differed from referral diagnosis in 115 (54%). Spirometry, body plethysmography and measurements of exhaled nitric oxide were performed in almost all; exercise-challenge tests in a third. 91% of the children with a final diagnosis of asthma were prescribed inhaled medication and 50% of children with DB were referred to physiotherapy.ConclusionsDiagnosis given at the outpatient clinic often differed from the diagnosis suspected by the referring physician. Diagnostic evaluation, management and follow-up were inconsistent between clinics and diagnostic groups, highlighting the need for diagnostic guidelines in children seen for EIS.Mandatory statements for Archives of Disease in ChildhoodWhat is already known on this topic (2-3 statements of max 25 words)Exercise-induced symptoms are common in childhood but not easy to diagnose because different diagnoses share similar clinical presentationsOnly few studies focused on children with exercise-induced symptoms and all have included selected groups of patients with difficult-to-diagnose problemsWhat this study adds (2-3 statements of max 25 words)Exercise-induced respiratory symptoms was the main reason for referral in one fifth of the children referred to paediatric respiratory outpatient clinics.Dysfunctional breathing is an under-recognised diagnosis; it was frequently diagnosed in the outpatient clinic (in 37%) but rarely suspected by the referring physician (6%)Diagnostic evaluation, management, and follow-up were inconsistent between clinics highlighting the need for diagnostic guidelines in children seen for EIS.

Early pulmonary infection and inflammation result in irreversible lung damage and are major contributors to cystic fibrosis (CF)-related morbidity. An easy to apply and noninvasive assessment for the timely detection of disease-associated complications would be of high value. We aimed to detect volatile organic compound (VOC) breath signatures of children with CF by real-time secondary electrospray ionisation high-resolution mass spectrometry (SESI-HRMS). A total of 101 children, aged 4–18 years (CF=52; healthy controls=49) and comparable for sex, body mass index and lung function were included in this prospective cross-sectional study. Exhaled air was analysed by a SESI-source linked to a high-resolution time-of-flight mass spectrometer. Mass spectra ranging from m/z 50 to 500 were recorded. Out of 3468 m/z features, 171 were significantly different in children with CF (false discovery rate adjusted p-value of 0.05). The predictive ability (CF versus healthy) was assessed by using a support-vector machine classifier and showed an average accuracy (repeated cross-validation) of 72.1% (sensitivity of 77.2% and specificity of 67.7%). This is the first study to assess entire breath profiles of children with SESI-HRMS and to extract sets of VOCs that are associated with CF. We have detected a large set of exhaled molecules that are potentially related to CF, indicating that the molecular breath of children with CF is diverse and informative., This is the first study to assess entire breath profiles of 101 children with SESI-HRMS. 171 molecules that are potentially related to CF were detected, indicating that the molecular breath profile of children with CF is diverse and informative. http://bit.ly/33nIeML

BACKGROUND Increased (abnormal) ventilation inhomogeneity in individuals with mild Cystic Fibrosis (CF) lung disease may become a treatable trait for small-molecule therapeutics improving Cystic Fibrosis Transmembrane Regulator (CFTR) function. The relationship between CFTR function and ventilation inhomogeneity is unknown. We aimed to identify and quantify increased ventilation inhomogeneity in relation to CFTR function. METHODS This was an international, multi-center, cross-sectional study. We collated data from individuals aged 3-25 years with minimal (CFTR-MF) or residual (CFTR-RF) function of a variety of CFTR genotypes and FEV1 ≥ 70% predicted. We measured lung function using nitrogen multiple-breath washout and spirometry. We compared lung clearance index (LCI) and FEV1 between individuals with CFTR-MF vs CFTR-RF using a mixed effects multi-variable linear regression model to account for study differences and a logistic model based on propensity-score matching to adjust for possible confounding. RESULTS We included 141 with CFTR-MF and 35 with CFTR-RF. LCI (> 1.96 z-score) was elevated in 71.6% individuals with CFTR-MF and in 40.0% with CFTR-RF. FEV1 (< -1.96 z-score) was reduced in 11.3% individuals with CFTR-MF and in 5.7% with CFTR-RF. The mean difference (95% CI) of LCI and FEV1 between CFTR-MF and CFTR-RF was 3.71 (1.63 to 5.79) and -0.40 (-0.83 to 0.02) z-score. The LCI differences were similar after adjustment for confounders and in individuals with normal FEV1. CONCLUSION Increased ventilation inhomogeneity is associated with less CFTR function. In individuals with mild CF lung disease, LCI can identify and quantify increased ventilation inhomogeneity, a candidate treatable trait.

INTRODUCTION Normalized phase III slope (Sn ) indices from multiple breath washout (MBW) estimate ventilation inhomogeneity. Alternate (*) protocols for Sn indices exist, however the utility of these outcomes in children with mild-to-moderate cystic fibrosis (CF) is unknown. METHODS We measured nitrogen MBW and spirometry in 135 children (43 controls) aged 4-18 years. We assessed validity, practicability, and reliability of Sn protocols. Outcomes included the ability to detect abnormal lung function, test agreement, measurement duration, intra-test repeatability, and quality. RESULTS Lung clearance index (LCI) was abnormal in 80 (87%), Scond in 55 (60%), Scond* in 17 (19%), Sacin in 10 (11%), Sacin* in 11 (12%), and FEV in 28 (30%). Alternate protocols reduced measurement duration. Agreement of indices to detect abnormal lung function was poor. The quality of analysis and repeatability deteriorated with the alternate technique compared to standard. CONCLUSION In children with mild-to-moderate CF lung disease, alternate protocols seem practical but clinimetric properties of standard Sn protocols are preferable.

SummaryRespiratory disease is common in children and strongly associated with lifestyle and environmental exposures. Thus, it is important to study the epidemiology locally. LuftiBus in the school (LUIS) was set up to assess the respiratory health of schoolchildren in the canton of Zurich, Switzerland.LUIS is a cross-sectional population-based study that was carried out 2013 to 2016. Children aged 6-17 years living in the canton of Zurich were eligible to participate. All schools in the canton were approached and the school head decided whether the school would participate and with which classes. Consenting parents answered a standardized questionnaire at home and assenting children completed a shorter questionnaire by interview at school. Trained technicians measured children’s lung function including spirometry, double tracer gas single-breath washout (DTG-SBW) and fractional exhaled nitric oxide (FeNO). Address histories of participants were geocoded to be linked with area-based socioeconomic measures and environmental exposures like spatiotemporal air pollution estimates for specific time periods and locations. A subgroup was seen again 12 months later using the same procedures to collect longitudinal data.The study included 3870 children at baseline and 655 at the one-year follow-up. Median age was 12.7 years; 281 (8%) had wheezed in the past year. At baseline we collected 3457 (89%) parental and 3546 (92%) children’s questionnaires, and 3393 (88%) FeNO, 3446 (89%) spirometry, and 1795 (46%) DTG-SBW measurements.LUIS is a rich resource of health-related data, with information on lung function, environmental exposures and respiratory health on Swiss schoolchildren.Take home messageLuftiBus in the school (LUIS) is a population-based study with detailed lung function data and rich information on respiratory health in Swiss schoolchildren.

SummaryBackground Respiratory muscle endurance (RME) training has been shown to increase exercise endurance and lung function in adults with cystic fibrosis (CF). We conducted an interventional study to investigate the effectiveness of RME training on CF-related health outcomes in children. Methods In a crossover trial, 22 children, aged 9–18 years, with CF performed 8 weeks of RME training and standard chest physiotherapy in a randomized sequence separated by a 1 week washout period. All children underwent training sessions using the RME training device before beginning the study. The primary outcomes were RME (in minutes) and exercise endurance (in minutes). Data were analyzed according to the intention-to-treat principle. Results Sixteen of 22 children (73%) completed the study. Study dropouts tended to be older with more advanced lung disease. After RME training, respiratory muscle endurance significantly increased by 7.03 ± 8.15 min (mean ± standard deviation, P

On-line analysis of exhaled breath offers insight into a person's metabolism without the need for sample preparation or sample collection. Due to its noninvasive nature and the possibility to sample continuously, the analysis of breath has great clinical potential. The unique features of this technology make it an attractive candidate for applications in medicine, beyond the task of diagnosis. We review the current methodologies for on-line breath analysis, discuss current and future applications, and critically evaluate challenges and pitfalls such as the need for standardization. Special emphasis is given to the use of the technology in diagnosing respiratory diseases, potential niche applications, and the promise of breath analysis for personalized medicine. The analytical methodologies used range from very small and low-cost chemical sensors, which are ideal for continuous monitoring of disease status, to optical spectroscopy and state-of-the-art, high-resolution mass spectrometry. The latter can be utilized for untargeted analysis of exhaled breath, with the capability to identify hitherto unknown molecules. The interpretation of the resulting big data sets is complex and often constrained due to a limited number of participants. Even larger data sets will be needed for assessing reproducibility and for validation of biomarker candidates. In addition, molecular structures and quantification of compounds are generally not easily available from on-line measurements and require complementary measurements, for example, a separation method coupled to mass spectrometry. Furthermore, a lack of standardization still hampers the application of the technique to screen larger cohorts of patients. This review summarizes the present status and continuous improvements of the principal on-line breath analysis methods and evaluates obstacles for their wider application.

Introduction: Studies done in the 1990s in Eastern Switzerland found that girls received less often treatment for asthma symptoms than boys despite similar symptoms. We reviewed this question in a recent survey. Methods: The Luftibus study collected information on respiratory symptoms by parent completed questionnaires in unselected school-aged children from the canton of Zurich, 2013-16. We investigated whether wheeze prevalence and asthma medication differed between girls and boys. Results: 3148 children participated, 1587 girls and 1561 boys, with median age of 12 years (IQR 10-14, range 6-16). 253 (8%) children reported current wheeze. The proportion decreased with age from 11% in 6-9 year olds to 8% in 13-16 year olds in boys while it increased with age from 5% (6-9year olds) to 9% (13-16year olds) in girls. 78 children (3%) had frequent wheeze (≥4 attacks/year). In the past year, among children who wheezed, 129 (51%), 52% girls and 51% boys, had used short-acting beta 2 agonists (SABA) and 94 (37%), 39% girls and 36% boys, were treated with inhaled corticosteroids (ICS). Among children with frequent wheeze only 45 (58%) and 27 (35%) used SABA and ICS respectively. Adjusting for frequency of attacks and number of asthma symptoms, there was no difference between boys and girls in the use of SABA (OR 0.95, 95%CI 0.54-1.7) and ICS (OR 0.93, 95%CI 0.53-1.7) overall. Among 6-9-year olds, boys received ICS less often than girls (OR 0.22, 95%CI 0.067-0.73). Conclusion: A significant proportion of schoolchildren with frequent wheeze did not use asthma medication in the past year. We found no evidence that girls received less treatment than boys. Funding: Lung League Zurich. SNSF (320030_162628)

BackgroundDiagnosing 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.MethodsA 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.ResultsThe 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.ConclusionBased 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.

OBJECTIVES: The aim of this study was to compare habitual physical activity between cystic fibrosis (CF) patients and healthy controls and to investigate possible predictors for reduced physical activity in CF patients. METHODS: Sixty-six patients with CF (3-44 years) and 65 healthy controls (3-55 years) were asked to wear an accelerometer (Actigraph GT1M) for 9 days (at least 10 hr/day). Physical activity was classified in five categories from very low to very strenuous. RESULTS: In general, there was no difference in physical activity between CF patients and healthy controls. However, young school-aged 6-13 years old children with CF spent less time with strenuous and very strenuous activity than healthy controls (adjusted difference in activity -0.43 (-0.69, -0.17)). Patients with very low lung function were significantly less active, but other CF-associated conditions did not affect physical activity. CONCLUSIONS: While we found similar levels of physical activity measured by accelerometry in patients with CF compared to healthy controls in general, young school-aged children showed less engagement in strenuous activities than their healthy counterparts. As the reduced physical activity in young school children was not likely to be explained by the disease state, strenuous physical activity may be enhanced by advocating exercise and sport. Pediatr Pulmonol. 2016;51:1020-1030. © 2016 Wiley Periodicals, Inc.

Chronic respiratory symptoms, such as cough, wheeze and dyspnoea, are common in children; however, most research has, with the exception of a few large-scale clinical cohort studies, been performed in the general population or in small, highly-selected samples. The Swiss Paediatric Airway Cohort (SPAC) is a national, prospective clinical cohort of children and adolescents who visit physicians for recurrent conditions, such as wheeze and cough, and exercise-related respiratory problems. The SPAC is an observational study and baseline assessment includes standardised questionnaires for families and data extracted from hospital records, including results of clinically indicated investigations, diagnoses and treatments. Outcomes are assessed through annual questionnaires, monthly symptom reporting via mobile phone and follow-up visits. The SPAC will address important questions about clinical phenotypes, diagnosis, treatment, and the short- and long-term prognosis of common respiratory problems in children. The cohort currently consists of 347 patients from four major hospitals (Bern, Zurich, Basel and Lucerne), with 70–80 additional patients joining each month. More centres will join and the target sample size is a minimum of 3000 patients. The SPAC will provide real-life data on children visiting the Swiss healthcare system for common respiratory problems and will provide a research platform for health services research and nested clinical and translational studies., The Swiss Paediatric Airway Cohort (SPAC) is a unique research platform for common respiratory problems in children http://ow.ly/Y1v030lDnji

Objective: To investigate efficacy and safety of enoxaparin for catheter-related arterial thrombosis in infants with congenital heart disease. Design: Prospective observational study. Setting: Pediatric Intensive Care and Cardiology Unit at the University Children's Hospital of Zurich. Patients: Acohort of 32 infants aged 0-12 months treated with enoxaparin for catheter-related arterial thrombosis from 2002 to 2005. Measurements: Dose requirements of enoxaparin, resolution of thrombosis by Doppler ultrasound, and bleeding complications. Results: Catheter-related arterial thrombosis was located in the iliac/femoral arteries in 31 (97%) infants and aorta in 1 infant, and was related to indwelling catheters and cardiac catheterization in 17 (53%) and 15 (47%) cases, respectively. Newborns required increased doses of enoxaparin to achieve therapeutic anti-FXa levels (mean 1.62 mg/kg per dose) compared with infants aged 2-12 months (mean 1.12 mg/kg per dose; p = 0.0002). Complete resolution of arterial thrombosis occurred in 29 (91%) infants at amean of 23 days after initiation of enoxaparin therapy. Partial or no resolution was observed in 1 (3%) and 2 (6%) infants, respectively, at amean follow-up time of 4.3 months. Bleeding complications occurred in 1 (3%) infant. Conclusion: Enoxaparin is efficient and safe for infants with congenital heart disease and catheter-related arterial thrombosis, possibly representing avalid alternative to the currently recommended unfractionated heparin

In this article, the group chairs of the Paediatric Assembly of the European Respiratory Society (ERS) highlight some of the most interesting findings presented at the 2017 ERS International Congress, which was held in Milan, Italy., A review of highlights from selected presentations from #ERSCongress 2017 by the @ERStalk Paediatric Assembly http://ow.ly/ixZj30jzlVy

We aimed at defining profiles of volatile organic compounds in exhaled breath from patients with cystic fibrosis (CF) using a novel real-time mass spectrometry technique. In this prospective matched case-control study, 30 patients with CF, and 30 healthy control subjects were matched one-to-one according to age, gender, and smoking state. We performed exhaled breath analysis by untargeted secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS). Patients with CF (mean age 26.0 ± 13.0 years) and controls (mean age 27.9 ± 14.0 years) were analyzed using SESI-HRMS. 49 exhaled breath features were found to be altered (p-value

Treatment of parapneumonic effusion in children remains controversial in the literature and in clinical practice. The aim of this study was to determine whether mutual consensus exists in the diagnosis and treatment of parapneumonic effusion in Central European countries. A questionnaire was sent to all directors of pediatric respiratory units in four adjacent Central European countries (Austria, France, Germany, Switzerland). The response rate was 61.8%. Responses reflected acceptable agreement regarding initial diagnostic procedures, as most centers performed chest X-ray and biological exams, followed by ultrasound, thoracocentesis, or computed tomography. However, antibiotic regimens were very heterogeneous, and the survey revealed complete lack of agreement on the indications and effusion volume threshold for invasive procedures, such as fibrinolytic instillation and thoracoscopy. In conclusion, apart from initial diagnostic procedures, this study showed a lack of mutual consensus among the four countries regarding the management of pediatric parapneumonic effusion. Multicenter prospective trials are clearly needed to acquire more evidence on the management of childhood parapneumonic effusion, enabling the development of evidence-based algorithms that could help to avoid unnecessary examinations with potential long-term side effects, such as radiation exposure at a young age.

BACKGROUND Lung clearance index (LCI), a marker of ventilation inhomogeneity, is elevated early in children with cystic fibrosis (CF). However, in infants with CF, LCI values are found to be normal, although structural lung abnormalities are often detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package. AIM Our aim was to challenge the validity of these software algorithms. METHODS We compared multiple breath washout (MBW) results of current software algorithms (automatic modus) to refined algorithms (manual modus) in 17 asymptomatic infants with CF, and 24 matched healthy term-born infants. The main difference between these two analysis methods lies in the calculation of the molar mass differences that the system uses to define the completion of the measurement. RESULTS In infants with CF the refined manual modus revealed clearly elevated LCI above 9 in 8 out of 35 measurements (23%), all showing LCI values below 8.3 using the automatic modus (paired t-test comparing the means, P

Vitamin D has immunomodulatory properties in the defence against pathogens. Its insufficiency is a widespread feature of cystic fibrosis (CF) patients, which are repeatedly suffering from rhinovirus (RV)-induced pulmonary exacerbations.To investigate whether vitamin D has antiviral activity, primary bronchial epithelial cells from CF children were pre-treated with vitamin D and infected with RV16. Antiviral and anti-inflammatory activity of vitamin D was assessed. RV and LL-37 levels were measured in bronchoalveolar lavage (BAL) of CF children infected with RV.Vitamin D reduced RV16 load in a dose-dependent manner in CF cells (10−7 M, pRV replication in primary CF bronchial cells was reduced by vitamin D through the induction of LL-37. Clinical studies are needed to determine the importance of an adequate control of vitamin D for prevention of virus-induced pulmonary CF exacerbations.

Bronchiectasis in children may be the result of chronic or repeated episodes of environmental insults, probably superimposed on a background of genetic vulnerability or increased susceptibility. The majority of children with bronchiectasis suffer from an underlying disorder, see Fig. 21.1.

Aspergillus bronchitis (AB) in the absence of allergic bronchopulmonary aspergillosis (ABPA) has recently been described as new entity in cystic fibrosis (CF) patients. We identified 16 CF individuals (age range 8 – 39 yrs, 69% females) with AB in 2016 (prevalence 2.3%). 8 subjects had no sensitization to Aspergillus fumigatus (AF), whereas 8 subjects showed mild sensitization (specific IgE AB occurs in all age groups including subjects with normal lung function and patients sensitized to AF without ABPA. Patients typically experience clinical signs of pulmonary exacerbation but may show stable lung function. Unsuccessful treatment with antibiotics, evidence of AF in lower airways, and endobronchial casts in BALF with AF hyphae are criteria for AB and should induce antimycotic treatment.

Introduction: In adults with Ehlers-Danlos Syndrome (EDS), a group of monogenic disorders affecting connective tissues, obstructive sleep apnea (OSA) is highly prevalent. The prevalence of OSA in children with EDS is unknown. Objectives. The aim of this prospective cross-sectional study was to compare the prevalence of OSA in pediatric EDS patients and healthy controls. Methods: Children with EDS (n=24), age 6 to 18, were recruited from the Children`s Hospital Zurich. 1-to-1 matching to healthy controls according to sex, age, ethnicity, and Z-score BMI was conducted. Participants completed home respiratory polygraphy and questionnaires (Sleep-Related-Breathing-Disorder Scale (SRBD), Epworth-Sleepiness-Score (ESS), Child Health Questionnaire (CHQ-PF28)). American Academy of Sleep Medicine (AASM) criteria were applied for OSA diagnosis (obstructive apnea-hypopnea-index (OAHI) ≥1/h). Conditional logistic regression was used to compare prevalence and to adjust for possible confounding. Results: OSA was found in 42% of pediatric EDS patients and in 13% of matched controls (OR 4.5 [95% CI 0.97–20.83]; p=0.054). The median OAHI was higher in EDS patients than in controls (0.77/h [Interquartile range 0.19-1.76] vs 0.24/h [0.0-0.60], p Conclusion: OSA is highly prevalent in school-aged children with EDS. Whether treatment of OSA also improves symptoms in these patients remains to be proven.

Background: Unlimited physical activity is one of the key issues of asthma control and management. We investigated how reliable reported exercise-related respiratory symptoms (ERRS) are in predicting exercise-induced bronchoconstriction (EIB) in asthmatic children. Methods: In this prospective study, 179 asthmatic children aged 7 - 15 years were asked for specific questions on respiratory symptoms related to exercise and allocated into two groups according to whether they complained about symptoms. Group I (n = 134) consisted of children answering “yes” to one or more of the questions and group II (n = 45) consisted of children answering “no” to all of the questions. Results: Sixty-four of 179 children showed a positive exercise challenge test (ECT). There was no difference in the frequency of a positive test between children in group I (n = 48) and group II (n = 12) (P = 0.47). The sensitivity of a positive report for ERRS to predict a positive ECT was only 37%, with a specificity of 0.72. Conclusion: According to current guidelines, the report or lack of ERRS has direct consequences on treatment decisions. However, the history of ERRS did not predict EIB and one-third of asthmatic children without complaints of ERRS developed EIB during the ECT. This raises the question of the need for objective measures of bronchial hyperresponsiveness (BHR) in pediatric asthma management. J Clin Med Res. 2017;9(5):410-415 doi: https://doi.org/10.14740/jocmr2935w