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

Air pollution exposure during pregnancy and lung function in childhood: The LUIS study.

BACKGROUND The adverse effects of high air pollution levels on childhood lung function are well-known. Limited evidence exists on the effects of moderate exposure levels during early life on childhood lung function. We investigated the association of exposure to moderate air pollution during pregnancy, infancy, and preschool time with lung function at school age in a Swiss population-based study. METHODS Fine-scale spatiotemporal model estimates of particulate matter with a diameter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) were linked with residential address histories. We compared air pollution exposures within different time windows (whole pregnancy, first, second, and third trimester of pregnancy, first year of life, preschool age) with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) measured cross-sectionally using linear regression models adjusted for potential confounders. RESULTS We included 2182 children, ages 6-17 years. Prenatal air pollution exposure was associated with reduced lung function at school age. In children aged 12 years, per 10 µg·m-3 increase in PM2.5 during pregnancy, FEV1 was 55 mL lower (95% CI -84 to -25 mL) and FVC 62 mL lower (95% CI -96 to -28 mL). Associations were age-dependent since they were stronger in younger and weaker in older children. PM2.5 exposure after birth was not associated with reduced lung function. There was no association between NO2 exposure and lung function. CONCLUSION In utero lung development is most sensitive to air pollution exposure, since even modest PM2.5 exposure during the prenatal time was associated with reduced lung function, most prominent in younger children

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

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 (FEV$_{1}$), forced vital capacity (FVC), FEV$_{1}$/FVC and forced expiratory flow for 25-75% of FVC (FEF$_{25-75}$) 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 FEV$_{1}$ 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 FEV$_{1}$/FVC z-scores (mean±sd -0.09±1.02), but not for FEV$_{1}$ (-0.62±0.98), FVC (-0.60±0.98) and FEF$_{25-75}$ (-0.54±1.02). Mean FEV$_{1}$, FVC and FEF$_{25-75}$ 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). FEV$_{1}$, FVC and FEF$_{25-75}$ z-scores depended on both age and height (p-interaction 0.033, 0.019 and <0.001, respectively). CONCLUSION: GLI-based FEV$_{1}$, FVC, and FEF$_{25-75}$ 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

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

Air pollution exposure during pregnancy and lung function in childhood: The LUIS study

BACKGROUND: The adverse effects of high air pollution levels on childhood lung function are well‐known. Limited evidence exists on the effects of moderate exposure levels during early life on childhood lung function. We investigated the association of exposure to moderate air pollution during pregnancy, infancy, and preschool time with lung function at school age in a Swiss population‐based study. METHODS: Fine‐scale spatiotemporal model estimates of particulate matter with a diameter <2.5 µm (PM$_{2.5}$) and nitrogen dioxide (NO$_{2}$) were linked with residential address histories. We compared air pollution exposures within different time windows (whole pregnancy, first, second, and third trimester of pregnancy, first year of life, preschool age) with forced expiratory volume in 1 s (FEV$_{1}$) and forced vital capacity (FVC) measured cross‐sectionally using linear regression models adjusted for potential confounders. RESULTS: We included 2182 children, ages 6−17 years. Prenatal air pollution exposure was associated with reduced lung function at school age. In children aged 12 years, per 10 µg·m$^{−3}$ increase in PM$_{2.5}$ during pregnancy, FEV$_{1}$ was 55 mL lower (95% CI −84 to −25 mL) and FVC 62 mL lower (95% CI −96 to −28 mL). Associations were age‐dependent since they were stronger in younger and weaker in older children. PM$_{2.5}$ exposure after birth was not associated with reduced lung function. There was no association between NO$_{2}$ exposure and lung function. CONCLUSION: In utero lung development is most sensitive to air pollution exposure, since even modest PM$_{2.5}$ exposure during the prenatal time was associated with reduced lung function, most prominent in younger children

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

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

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 (He) and sulfur-hexafluoride (SF6) and the phase III slope (SIIIHe-SF6) is derived. We assessed feasibility, repeatability, and associations of SIIIHe-SF6 with the potential predictors anthropometrics, presence of wheeze (i.e. parental report of ≥ 1 episode of wheeze in the prior year), FeNO, forced expiratory volume in the first second (FEV1), and FEV1/forced vital capacity (FVC). RESULTS In 1782 children, 5223 DTG-SBW trials were obtained. The DTG-SBW was acceptable in 1449 (81.3%) children, coefficient of variation was 39.8%. SIIIHe-SF6 was independently but weakly positively associated with age and BMI. In 276 (21.2%) children, wheeze was reported. SIIIHe-SF6 was higher by 0.049 g.mol.L-1 in children with wheeze as compared to those without and remained associated with wheeze after adjusting for age and BMI in a multi-variable 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