European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16†years.

BACKGROUND: Diagnosing asthma in children represents an important clinical challenge. There is no single gold-standard test to confirm the diagnosis. Consequently, over- and under-diagnosis of asthma is frequent in children. METHODS: A task force supported by the European Respiratory Society has developed these evidence-based clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years using nine Population, Intervention, Comparator and Outcome (PICO) questions. The task force conducted systematic literature searches for all PICO questions and screened the outputs from these, including relevant full-text articles. All task force members approved the final decision for inclusion of research papers. The task force assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: The task force then developed a diagnostic algorithm based on the critical appraisal of the PICO questions, preferences expressed by lay members and test availability. Proposed cut-offs were determined based on the best available evidence. The task force formulated recommendations using the GRADE Evidence to Decision framework. CONCLUSION: Based on the critical appraisal of the evidence and the Evidence to Decision framework, the task force recommends spirometry, bronchodilator reversibility testing and exhaled nitric oxide fraction as first-line diagnostic tests in children under investigation for asthma. The task force recommends against diagnosing asthma in children based on clinical history alone or following a single abnormal objective test. Finally, this guideline also proposes a set of research priorities to improve asthma diagnosis in children in the future.

Paediatric cohort studies on lower respiratory diseases and their reporting quality: systematic review of the year 2018.

The paediatric respiratory research community uses cohort studies extensively. However, the landscape of these studies and their quality of reporting has not been assessed.We performed a systematic review of publications on cohort studies reporting on paediatric lower respiratory problems published in 2018. We searched MEDLINE and Embase and extracted data on study and journal characteristics. We assessed the number of items of the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) checklist that a random sample (100 papers) reported. We analysed factors associated with the STROBE score and with the most poorly reported items, using Poisson and logistic regression.Of the 21 319 records identified, 369 full-text articles met our inclusion criteria. Most papers studied asthma aetiology through birth cohorts and were based in Europe or North America. The reporting quality was insufficient: 15% reported the 22 STROBE items; median (interquartile range) score 18 (16-21). The most poorly reported items were sources of bias, sample size, statistical methods, descriptive results and generalisability. None of the study or journal factors were associated with the STROBE score.We need a joint effort of editors, reviewers and authors to improve the reporting quality of paediatric cohort studies on respiratory problems.

Diagnosis of asthma in children: findings from the Swiss Paediatric Airway Cohort.

INTRODUCTION: Diagnosing asthma in children remains a challenge because respiratory symptoms are not specific and vary over time. AIM: In 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. METHODS: We 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 (F eNO), 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). RESULTS: Among 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%. CONCLUSION: This 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.

Diagnosis of asthma in children: the contribution of a detailed history and test results.

INTRODUCTION: There are few data on the usefulness of different tests to diagnose asthma in children. AIM: We assessed the contribution of a detailed history and a variety of diagnostic tests for diagnosing asthma in children. METHODS: We studied children aged 6-16 years referred consecutively for evaluation of suspected asthma to two pulmonary outpatient clinics. Symptoms were assessed by parental questionnaire. The clinical evaluation included skin-prick tests, measurement of exhaled nitric oxide fraction (F eNO), spirometry, bronchodilator reversibility and bronchial provocation tests (BPT) by exercise, methacholine and mannitol. Asthma was diagnosed by the physicians at the end of the visit. We assessed diagnostic accuracy of symptoms and tests by calculating sensitivity, specificity, positive and negative predictive values and area under the curve (AUC). RESULTS: Of the 111 participants, 80 (72%) were diagnosed with asthma. The combined sensitivity and specificity was highest for reported frequent wheeze (more than three attacks per year) (sensitivity 0.44, specificity 0.90), awakening due to wheeze (0.41, 0.90) and wheeze triggered by pollen (0.46, 0.83) or by pets (0.29, 0.99). Of the diagnostic tests, the AUC was highest for F eNO measurement (0.80) and BPT by methacholine (0.81) or exercise (0.74), and lowest for forced expiratory volume in 1 s (FEV1) (0.62) and FEV1/forced vital capacity ratio (0.66), assessed by spirometry. CONCLUSION: This study suggests that specific questions about triggers and severity of wheeze, measurement of F eNO and BPT by methacholine or exercise contribute more to the diagnosis of asthma in school-aged children than spirometry, bronchodilator reversibility and skin-prick tests.

Importance of Urine Dipstick in Evaluation of Young Febrile Infants With Positive Urine Culture: A Spanish Pediatric Emergency Research Group Study.

BACKGROUND AND OBJECTIVES: Guidelines from the American Academy of Pediatrics define urinary tract infection (UTI) as the growth of greater than 50,000 ufc/mL of a single bacterium in a urine culture with a positive urine dipstick or with a urinalysis associated. Our objective was to evaluate the adequacy of this cutoff point for the diagnosis of UTI in young febrile infants. METHODS: Subanalysis of a prospective multicenter study developed in RISeuP-SPERG Network between October 11 and September 13. To carry out the study, it was performed a comparison of analytical and microbiological characteristics of patients younger than 90 days with fever without focus, taking into account the results of urine dipstick and urine culture. RESULTS: Of a total of 3333 infants younger than 90 days with fever without focus which were included in the study, 538 were classified as UTI in accordance with American Academy of Pediatrics' guidelines. These patients were similar to those who had a positive urine dipstick and a urine culture yielding of 10,000 to 50,000 ufc/mL, and they were different from those who had a normal urine dipstick and a urine culture >50,000 ufc/mL, being focused on the isolated bacteria and blood biomarkers values. Forty-five invasive bacterial infections were diagnosed (5.9% of the 756 with a urine culture >10,000 ufc/mL). Half of the infants with a normal urine dipstick diagnosed with invasive bacterial infections were younger than 15 days. CONCLUSIONS: It might be inadequate to use a threshold of 50,000 cfu/mL to consider a urine culture as positive in young febrile infants given the fact that it would misdiagnose several UTIs.

Using a urine dipstick to identify a positive urine culture in young febrile infants is as effective as in older patients.

AIM: There is limited evidence about the diagnostic value of urine dipsticks in young febrile infants. The aim of this study was to determine whether urine dipsticks would identify positive urine cultures in febrile infants of less than 90 days of age. METHODS: This study was a subanalysis of a prospective multicentre study developed in 19 Spanish paediatric emergency departments belonging to the Spanish Paediatric Emergency Research Network. It focused on febrile infants of less than 90 days of age admitted between October 2011 and September 2013. A positive urine culture was defined as the growth of ≥ 50,000 cfu/mL of a single pathogen collected by a sterile method. RESULTS: We included 3401 patients, and 176 (12.8%) female patients and 473 (23.3%) males had a positive urine culture. The leucocyte esterase test showed a mean sensitivity of 82.1% and a mean specificity of 92.4%, with a greater mean negative predictive value for females than males (97.8 versus 94.1%) and a greater mean positive predictive value for males than females (79.4% versus 58%). CONCLUSION: The leucocyte esterase test showed the same accuracy in young febrile infants as previously reported findings for older children. It predicted positive urine cultures and also revealed important gender differences.

Blood Lactate Levels during Therapeutic Hypothermia and Neurodevelopmental Outcome or Death at 18-24 Months of Age in Neonates with Moderate and Severe Hypoxic-Ischemic Encephalopathy.

INTRODUCTION: Blood lactate levels in neonates with hypoxic-ischemic encephalopathy (HIE) vary, and their impact on neurodevelopmental outcome is unclear. We assessed blood lactate course over time in neonates with HIE during therapeutic hypothermia (TH) and investigated if blood lactate values were associated with neurodevelopmental outcome at 2 years of age. METHODS: This is a retrospective cohort study of neonates with HIE born between 2013 and 2019, treated at the University Children's Hospital Zurich. We recorded blood lactate values over time and calculated time until lactate was ≤2 mmol/L. Neurodevelopmental outcome was assessed at 18-24 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), and categorized as favorable or unfavorable. We investigated associations between blood lactate values and outcome using logistic regression and adjusted for Sarnat stage. RESULTS: 33/45 neonates (69%) had a favorable and 14 (31%) an unfavorable neurodevelopmental outcome. Mean initial lactate values were lower in the favorable (13.9 mmol/L, standard deviation [SD]: 2.9) versus unfavorable group (17.1 mmol/L, SD 3.2; p = 0.002). Higher initial and maximal blood lactate levels were associated with unfavorable outcome, also when adjusted for Sarnat stage (adjusted odds ratio [aOR]: 1.37, 95% CI: 1.01-1.88, p = 0.046, and aOR: 1.35, 95% CI: 1.01-1.81, p = 0.041, respectively). CONCLUSION: In neonates with HIE receiving TH, initial and maximal blood lactate levels were associated with neurodevelopmental outcome at 18-24 months of age, also when adjusted for Sarnat stage. Further investigations to analyze blood lactate as a biomarker for prognostic value are needed.

Evaluation of the Double-Tracer Gas Single-Breath Washout Test in a Pediatric Field Study.

BACKGROUND: The early life origins of chronic pulmonary diseases are thought to arise in peripheral small airways. Predictors of ventilation inhomogeneity, a proxy of peripheral airway function, are understudied in schoolchildren. RESEARCH QUESTION: Is the double-tracer gas single-breath washout (DTG-SBW) measurement feasible in a pediatric field study setting? What are the predictors of the DTG-SBW-derived ventilation inhomogeneity estimate in unselected schoolchildren? STUDY DESIGN AND METHODS: In this prospective cross-sectional field study, a mobile lung function testing unit visited participating schools in Switzerland. We applied DTG-SBW, fraction of exhaled nitric oxide (Feno), and spirometry measurements. The DTG-SBW is based on tidal inhalation of helium and sulfur-hexafluoride, and the phase III slope (SIIIHe-SF6) is derived. We assessed feasibility, repeatability, and associations of SIIIHe-SF6 with the potential predictors of anthropometrics, presence of wheeze (ie, parental report of one or more episode of wheeze in the prior year), Feno, FEV1, and FEV1/FVC. RESULTS: In 1,782 children, 5,223 DTG-SBW trials were obtained. The DTG-SBW was acceptable in 1,449 children (81.3%); the coefficient of variation was 39.8%. SIIIHe-SF6 was independently but weakly positively associated with age and BMI. In 276 children (21.2%), wheeze was reported. SIIIHe-SF6 was higher by 0.049 g.mol.L-1 in children with wheeze compared with those without and remained associated with wheeze after adjusting for age and BMI in a multivariable linear regression model. SIIIHe-SF6 was not associated with Feno, FEV1, and FEV1/FVC. INTERPRETATION: The DTG-SBW is feasible in a pediatric field study setting. On the population level, age, body composition, and wheeze are independent predictors of peripheral airway function in unselected schoolchildren. The variation of the DTG-SBW possibly constrains its current applicability on the individual level. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03659838; URL: www. CLINICALTRIALS: gov.

Phenotypic characteristics, healthcare use, and treatment in children with night cough compared with children with wheeze.

OBJECTIVES: Population-based studies of children with dry night cough alone compared with those who also wheeze are few and inconclusive. We compared how children with dry night cough differ from those who wheeze. METHODS: LuftiBus in the school is a population-based study of schoolchildren conducted between 2013 and 2016 in Zurich, Switzerland. We divided children into four mutually exclusive groups based on reported dry night cough (henceforth referred as "cough") and wheeze and compared parent-reported symptoms, comorbidities, exposures, FeNO, spirometry, and healthcare use and treatment. RESULTS: Among 3457 schoolchildren aged 6-17 years, 294 (9%) reported "cough," 181 (5%) reported "wheeze," 100 (3%) reported "wheeze and cough," and 2882 (83%) were "asymptomatic." Adjusting for confounders in a multinomial regression, children with "cough" reported more frequent colds, rhinitis, and snoring than "asymptomatic" children; children with "wheeze" or "wheeze and cough" more often reported hay fever, eczema, and parental histories of asthma. FeNO and spirometry were similar among "asymptomatic" and children with "cough," while children with "wheeze" or "wheeze and cough" had higher FeNO and evidence of bronchial obstruction. Children with "cough" used healthcare less often than those with "wheeze," and they attended mainly primary care. Twenty-two children (7% of those with "cough") reported a physician diagnosis of asthma and used inhalers. These had similar characteristics as children with wheeze. CONCLUSION: Our representative population-based study confirms that children with dry night cough without wheeze clearly differed from those with wheeze. This suggests asthma is unlikely, and they should be investigated for alternative aetiologies, particularly upper airway disease.

Prevalence of childhood cough in epidemiological studies depends on the question used: findings from two population-based studies.

BACKGROUND: Epidemiological studies use different questions to assess recurrent cough in children. In two independent population-based studies, we assessed how prevalence estimates of cough vary depending on the questions parents are asked about their child's cough and how answers to the different questions overlap. METHODS: We analysed cross-sectional data from two population-based studies on respiratory health: LuftiBus in the School (LUIS), conducted in 2013-2016 among 6- to 17-year-school children in the Canton of Zurich, Switzerland, and the 1998 Leicester Respiratory Cohort (LRC) study, UK where we used data from 6- to 8-year-old children from the 2003 follow-up survey. Both studies used parental questionnaires that included the same three questions on the child's cough, namely cough without a cold, dry cough at night and coughing more than others. We assessed how the prevalence of cough varied depending on the question and how answers to the different questions on cough overlapped. We also assessed how results were influenced by age, sex, presence of wheeze and parental education. RESULTS: We included 3457 children aged 6-17 years from LUIS and 2100 children aged 6-8 years from LRC. All respiratory outcomes - cough, wheeze and physician-diagnosed asthma - were reported twice as often in the LRC as in LUIS. We found large differences in the prevalence of parent-reported cough between the three cough questions. In LUIS, 880 (25%) parents reported cough without a cold, 394 (11%) dry night cough, and 159 (5%) reported that their child coughed more than other children. In the LRC, these numbers were 1003 (48%), 527 (25%) and 227 (11%). There was only partial overlap of answers, with 89 (3%) answering yes to all questions in LUIS and 168 (8%) in LRC. Prevalence of all types of cough and overlap between the cough questions was higher in children with current wheeze. CONCLUSION: In both population-based studies prevalence estimates of cough depended strongly on the question used to assess cough with only partial overlap of responses to different questions. Epidemiological studies on cough can only be compared if they used exactly the same questions for cough.

Age and body mass index affect fit of spirometry Global Lung Function Initiative references in schoolchildren.

Background: References from the Global Lung Function Initiative (GLI) are widely used to interpret children's spirometry results. We assessed fit for healthy schoolchildren. Methods: LuftiBus in the School was a population-based cross-sectional study undertaken in 2013-2016 in the canton of Zurich, Switzerland. Parents and their 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 forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow for 25-75% of FVC (FEF25-75) for healthy White participants. We defined appropriate fit to GLI references by mean values between +0.5 and -0.5 z-scores. We assessed whether fit varied by age, body mass index, height and sex using linear regression models. Results: We analysed data from 2036 children with valid FEV1 measurements, of whom 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 z-scores (mean±sd -0.09±1.02), but not for FEV1 (-0.62±0.98), FVC (-0.60±0.98) and FEF25-75 (-0.54±1.02). Mean FEV1, FVC and FEF25-75 z-scores fitted better in children considered overweight (-0.25, -0.13 and -0.38, respectively) than normal weight (-0.55, -0.50 and -0.55, respectively; p-trend <0.001, 0.014 and <0.001, respectively). FEV1, FVC and FEF25-75 z-scores depended on both age and height (p-interaction 0.033, 0.019 and <0.001, respectively). Conclusion: GLI-based FEV1, FVC, and FEF25-75 z-scores do not fit White Swiss adolescents well. This should be considered when using reference equations for clinical decision-making, research and international comparison.

Agreement of parent- and child-reported wheeze and its association with measurable asthma traits.

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.

COVID-PCD: a participatory research study on the impact of COVID-19 in people with primary ciliary dyskinesia.

COVID-PCD is a participatory study initiated by people with primary ciliary dyskinesia (PCD) who have an essential vote in all stages of the research from the design of the study to the recruitment of participants, and interpretation and communication of the study results. COVID-PCD aims to collect epidemiological data in real-time from people with PCD throughout the pandemic to describe incidence of coronavirus disease 2019 (COVID-19), symptoms and course of disease; identify risk factors for prognosis; and assess experiences, wishes and needs. The study is advertised through patient support groups and participants register online on the study website (www.covid19pcd.ispm.ch). The study invites persons of any age from anywhere in the world with a suspected or confirmed PCD. A baseline questionnaire assesses details on PCD diagnosis, habitual symptoms and COVID-19 episodes that occurred before study entry. Afterwards, participants receive a weekly follow-up questionnaire with questions on incident severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, current symptoms, social contact behaviour and physical activity. Occasional thematic questionnaires are sent out focussing on emerging questions of interest chosen by people with PCD. In case of hospitalisation, patients or family members are asked to obtain a hospital report. Results are continuously analysed and summaries put online. The study started recruitment on April 30, 2020, and 556 people with PCD completed the baseline questionnaire by November 2, 2020. The COVID-PCD study is a participatory study that follows people with PCD during the COVID-19 pandemic, helps to empower affected persons, and serves as a platform for communication between patients, physicians and researchers.

Facemask Usage Among People With Primary Ciliary Dyskinesia During the COVID-19 Pandemic: A Participatory Project.

Objectives: Primary ciliary dyskinesia (PCD) is a rare genetic disease that causes recurrent respiratory infections. People with PCD may be at high risk of severe COVID-19 and protection against SARS-CoV-2 is therefore important. We studied facemask usage and problems reported in relation with their use among people with PCD. Methods: We used data from COVID-PCD, an international observational cohort study. A questionnaire was e-mailed to participants in October 2020 that asked about facemask usage. Results: In total, 282 participants from 27 countries were included (Median age 32 years; 63% female). In total, 252 (89%) wore facemasks everywhere in public, 13 (5%) wore facemasks in most places, and 17 (6%) did not wear facemasks in public. Half of the participants reported that it was uncomfortable to wear facemasks because of runny nose, cough, or difficulty breathing. Participants less often wore facemasks when there was no national requirement. Conclusion: Most people with PCD wore facemasks despite frequent respiratory problems related to their use. Facemask usage was most frequent in countries with a national requirement emphasizing the importance of nationwide policies mandating facemasks.

LuftiBus in the school (LUIS): a population-based study on respiratory health in schoolchildren.

Respiratory disease is common in children and strongly associated with lifestyle and environmental exposures. Thus, it is important to study the epidemiology locally. The LuftiBus in the School (LUIS) study 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 standardised 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 such as 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 1-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%) child 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.

Cigarette, shisha, and electronic smoking and respiratory symptoms in Swiss children: The LUIS study.

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 to 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 to 12-year-olds, 90/1905 (5%) had smoked occasionally (

Does high-flow oxygen reduce escalation of care in infants with hypoxaemic bronchiolitis?

Treatment failure leading to escalation of care occurred less often in infants with hypoxaemic bronchiolitis treated with high-flow oxygen than with standard oxygen therapy, but there were no differences in the proportion needing ICU transfer or intubation http://bit.ly/2F3rSi1.