Limited role of children in transmission of SARS-CoV-2 virus in households-Immunological analysis of 26 familial clusters.

BACKGROUND: The impact of children on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains uncertain. This study provides an insight into distinct patterns of SARS-CoV-2 household transmission in case of pediatric and adult index cases as well as age-dependent susceptibility to SARS-CoV-2 infection. METHODS: Immune analysis, medical interviewing, and contact tracing of 26 families with confirmed SARS-CoV-2 infection cases have been conducted. Blood samples were analyzed serologically with the use of a SARS-CoV-2-specific IgG assay and virus neutralization test (VNT). Uni- and multivariable linear regression and mixed effect logistic regression models were used to describe potential risk factors for higher contagiousness and susceptibility to SARS-CoV-2 infection. RESULTS: SARS-CoV-2 infection could be confirmed in 67 of 124 family members. Fourteen children and 11 adults could be defined as index cases in their households. Forty of 82 exposed family members were defined as secondarily infected. The mean secondary attack rate in households was 0.48 and was significantly higher in households with adult than with pediatric index cases (0.85 vs 0.19; p < 0.0001). The age (grouped into child and adult) of index case, severity of disease, and occurrence of lower respiratory symptoms in index cases were significantly associated with secondary transmission rates in households. Children seem to be equally susceptible to acquire a SARS-CoV-2 infection as adults, but they suffer milder courses of the disease or remain asymptomatic. CONCLUSION: SARS-CoV-2 transmission from infected children to other household members occurred rarely in the first wave of the pandemic, despite close physical contact and the lack of hygienic measures.

SARS-CoV-2 Associated Pediatric Inflammatory Multisystem Syndrome With a High Prevalence of Myocarditis - A Multicenter Evaluation of Clinical and Laboratory Characteristics, Treatment and Outcome.

Introduction: Pediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 infection (PIMS -TS) comprises a new disease entity having emerged after the COVID-19 outbreak in 2019. Materials and Methods: For this multicenter, retrospective study children between 0 and 18 years with PIMS-TS between March 2020 and May 2021 were included, before availability of vaccination for children. Frequent SARS-CoV-2 variants at that period were the wildtype virus, alpha, beta and delta variants. Inclusion criteria were according to the PIMS-TS criteria, proposed by the Royal College of Pediatrics and WHO. Study aim was to review their clinical, laboratory and echocardiographic data with a focus on cardiac involvement. Results: We report 45 patients, median age 9 years, 64% male. SARS-CoV-2 antibodies were positive in 35/41 (85%). PIMS occurrence followed local COVID-19 peak incidence periods with a time lag. The most common symptoms at presentation were fever (98%), abdominal pain (89%) and rash (80%). Fever history of > 5 days was associated with decreased left ventricular function (p = 0.056). Arterial hypotension and cardiac dysfunction were documented in 72% patients, increased brain natriuretic peptide in 96% and increased cardiac troponin in 64% of the children. Echocardiography revealed mitral valve regurgitation (64%), coronary abnormalities (36%) and pericardial effusions (40%). Increased NT-proBNP was significantly associated with the need of inotropics (p < 0.05), which were necessary in 40% of the patients. Treatment comprised intravenous immunoglobulin (93%), systemic steroids (84%) and acetylsalicylic acid (100%; 26/45 started with high dosages). For insufficient response to this treatment, five (11%) children received the interleukin-1 receptor antagonist anakinra. All patients were discharged with almost resolved cardiac signs. Conclusion: Our analysis of non-vaccinated children with PIMS-TS demonstrates that a considerable number have associated myocarditis requiring intensive care and inotropic support. Most children showed adequate response to intravenous immunoglobulin and steroids and good recovery. Further evaluation of pediatric patients with COVID-19 associated diseases is required to evaluate the impact of new virus variants.

A Yersiniabactin-producing Klebsiella aerogenes Strain Causing an Outbreak in an Austrian Neonatal Intensive Care Unit.

BACKGROUND: Yersiniabactin, a siderophore with a high affinity to iron, has been described as a potential virulence factor in Enterobacteriaceae. Klebsiella aerogenes is a Gram-negative rod known to cause invasive infection in very low birth weight infants but is an unusual pathogen to cause outbreaks in neonatal intensive care units (NICU). METHODS: We performed a retrospective analysis of all patients colonized with K. aerogenes in our NICU from September to December 2018. Each infant with an occurrence of K. aerogenes in any microbiological culture was defined as a case. Clinical data were taken from medical charts. K. aerogenes isolates were genotyped using whole-genome sequencing combined with core genome multilocus sequencing type analysis. Yersiniabactin production was evaluated by luciferase assay. RESULTS: In total 16 patients were colonized with K. aerogenes over the 3-month period and 13 patients remained asymptomatic or developed late-onset neonatal sepsis from another pathogen. Three patients developed necrotizing enterocolitis, 2 complicated by sepsis and 1 of them died. All symptomatic patients were premature infants with low birth weight. Genetic sequencing confirmed an outbreak with the same strain, all samples expressed the high-pathogenicity island, necessary for the production of yersiniabactin. Six exemplary cases were proven to produce yersiniabactin in vitro. CONCLUSION: This is the first report of an outbreak of a yersiniabactin-producing K. aerogenes strain causing invasive infection in preterm infants. We hypothesize that, due to improved iron uptake, this strain was associated with higher virulence than non-yersiniabactin-producing strains. Extended search for virulence factors and genetic sequencing could be pivotal in the management of NICU outbreaks in the future.

Associations Between Parental Occupational Balance, Subjective Health, and Clinical Characteristics of VLBW Infants.

Objective: Very low birthweight (VLBW) infants have an increased risk of mortality and frequently suffer from complications, which affects parental occupational balance. Occupational balance is the satisfaction with one's meaningful activities, which include everyday activities that people need to, want to, and are expected to do. In contrast to work-life balance, the construct of occupational balance addresses different activities equally and it applies to all persons, regardless of whether they are working or not. Parental occupational balance might be related to parents' and VLBW infants' health. Therefore, the objective of this study was to investigate associations between parental occupational balance, subjective health, and clinical characteristics of VLBW infants. Methods: A cross-sectional multicenter study was conducted in six Austrian neonatal intensive care units. Occupational balance and subjective health of parents of VLBW infants were assessed with six self-reported questionnaires. The following clinical characteristics of VLBW infants were extracted from medical records: gestational age, birthweight, Apgar scores, Clinical Risk for Babies II Score, and complications of prematurity. Spearman's rank coefficients were calculated. Results: In total, 270 parents, 168 (62%) female and their VLBW infants, 120 (44%) female, were included in this study. Parents' mean age was 33.7 (±6.0) years, mean gestational age of VLBW infants was 27 + 3 (±2) weeks. Associations between parental occupational balance, subjective health, and clinical characteristics of VLBW infants were identified (r s = 0.13 - 0.56; p ≤ 0.05), such as the correlation between occupational areas (r s = 0.22, p ≤ 0.01), occupational characteristics (r s = 0.17, p = 0.01), and occupational resilience (r s = 0.18, p ≤ 0.01) with bronchopulmonary dysplasia of VLBW infants. Conclusion: Occupational balance is associated with parents' and VLBW infants' health. Interventions to strengthen parental occupational balance might increase parental health and thereby also improve health and developmental outcomes of their VLBW infants.

Characterization of the antibody response to SARS-CoV-2 in a mildly affected pediatric population.

BACKGROUND: While children usually experience a mild course of COVID-19, and a severe disease is more common in adults, the features, specificities, and functionality of the SARS-CoV-2-specific antibody response in the pediatric population are of interest. METHODS: We performed a detailed analysis of IgG antibodies specific for SARS-CoV-2-derived antigens S and RBD by ELISA in 26 SARS-CoV-2 seropositive schoolchildren with mild or asymptomatic disease course, and in an equally sized, age- and gender-matched control group. Furthermore, a detailed mapping of IgG reactivity to a panel of microarrayed SARS-CoV-2 proteins and S-derived peptides was performed by microarray technology. The capacity of the antibody response to block RBD-ACE2 binding and virus neutralization were assessed. Results were compared with those obtained in an adult COVID-19 convalescent population. RESULTS: After mild COVID-19, anti-S and RBD-specific IgG antibodies were developed by 100% and 84.6% of pediatric subjects, respectively. No difference was observed in regards to symptoms and gender. Mounted antibodies recognized conformational epitopes of the spike protein and were capable to neutralize the virus up to a titer of ≥80 and to inhibit the ACE2-RBD interaction by up to 65%. SARS-CoV-2-specific IgG responses in children were comparable to mildly affected adult patients. CONCLUSION: SARS-CoV-2 asymptomatic and mildly affected pediatric patients develop a SARS-CoV-2-specific antibody response, which is comparable regarding antigen, epitope recognition, and the ability to inhibit the RBD-ACE2 interaction to that observed in adult patients after mild COVID-19.

FDA warning montelukast 03.2020-Statement of the Austrian working group of pediatric pulmonology and allergology.

Montelukast, a leukotriene receptor antagonist (LTRA) has been approved for use in Europe since 1998. Indications for use (from the age of 6 months) include mild to moderate asthma, seasonal allergic rhinitis with asthma, and the prevention of exercise-induced asthma episodes. The psychiatric side effects of montelukast have been known for the last 10 years; in the case of such symptoms benefits and risks should be considered. Due to potential life-threatening psychiatric adverse events, particularly suicide, a black box warning was issued. In this statement the Austrian working group of pediatric pulmonology and allergology advises that treatment with montelukast should be started only after critical evaluation. Treatment should be stopped on the occurrence of any neuropsychiatric side effects.

Development and validation of a self-reported questionnaire to assess occupational balance in parents of preterm infants.

BACKGROUND: Parents' meaningful activities (occupations) and occupational balance are relevant to neonatal care. Valid and reliable self-reported measurement instruments are needed to assess parents' occupational balance and to evaluate occupational balance interventions in neonatal care. The aims of this study were to develop a self-reported questionnaire on occupational balance in informal caregivers (OBI-Care) and to examine its measurement properties including construct validity and internal consistency. METHODS AND FINDINGS: A mixed method multicenter study design was employed. Items of the OBI-Care were created with parents of preterm infants based on qualitative research methods. Measurement properties were analyzed with quantitative data of parents of preterm infants. Construct validity was assessed by determining dimensionality, overall and item fit to a Rasch model, differential item functioning and threshold ordering. Internal consistency was examined by determining inter-item and item-total correlations, Cronbach's alpha and Rasch's person separation index. Fourteen parents participated in item creation. Measurement properties were explored in data of 304 parents. Twenty-two items, summarized in three subscales were compiled to the OBI-Care. Items showed an overall fit and except one item, an item fit to the Rasch model. There was no evidence of differential item functioning and all items displayed ordered thresholds. Each subscale had good values of person separation indices and Cronbach's alpha. CONCLUSIONS: The OBI-Care demonstrates construct validity and internal consistency and is thus a suitable measurement instrument to assess occupational balance of parents of preterm infants in neonatal care. OBI-Care is generic and can be applied in various health care settings.

Lessons from low seroprevalence of SARS-CoV-2 antibodies in schoolchildren: A cross-sectional study.

BACKGROUND: Children are discussed as hidden SARS-CoV-2 virus reservoir because of predominantly mild or even asymptomatic course of disease. The objective of this cross-sectional study in May-July 2020 was to assess the prevalence of SARS-CoV-2 antibodies and virus RNA in schoolchildren, consistent with previous infection by contact tracing. METHODS: School authorities approached parents for voluntary participation. Interested families were contacted by the study team. A nasal and oropharyngeal swab, a blood sample, and a questionnaire were employed. Primary endpoint was the frequency of SARS-CoV-2 real-time PCR (RT-PCR) and antibody-positive children. Antibody positivity was assessed by a highly sensitive first-line ELISA, and a neutralization assay and two other immunoassays as confirmatory assays. RESULTS: Of 2069 children (median age 13 years, IQR 10-15), 2 cases (0.1%) tested positive for SARS-CoV-2 RNA and 26 cases (1.3%) tested positive for specific antibodies. SARS-CoV-2-specific antibodies exhibited detectable virus-neutralizing activity in 92% (24 of 26 samples). Seropositivity was associated with a history of mild clinical symptoms in 14 children (53.8%), while 12 children (46.2%) remained asymptomatic. Among 13 seropositive children being tested concomitantly with their siblings, only one pair of siblings was seropositive. Contact tracing revealed adult family members and school teachers as potential index cases. CONCLUSION: In schoolchildren, the infection rate with SARS-CoV-2 is low and associated with a mild or asymptomatic course of disease. Virus spreading seemed to occur more likely in intergenerational contacts than among siblings in the same household. The presence of neutralizing SARS-CoV-2 antibodies in children may reflect protective adaptive immunity.

Wheeze and cough measurements at night in children with respiratory symptoms.

BACKGROUND: Nocturnal cough and wheeze are important symptoms when diagnosing any respiratory disease in a child, but objective measurements of these symptoms are not performed. METHODS: The aim of our study was to analyze the use of an automated detection system to assess breath sounds objectively in comparison to cough and wheeze questionnaires and to evaluate its feasibility in clinical practice. RESULTS: Forty-nine recordings of thirty-nine children were processed (asthma n = 13; cystic fibrosis n = 2; pneumonia n = 5; suspicion of habit cough n = 7; prolonged, recurrent or chronic cough n = 13), and cough and asthma scores were compared to the objective nocturnal recordings. Time for audio-validation of recordings took between 2 and 40 min (mean: 14.22 min, (SD): 10.72). Accuracy of the automated measurement was higher for cough than for wheezing sounds. Nocturnal cough readings but not wheeze readings correlated with some of the corresponding scores. CONCLUSION: To our knowledge this is the first study using a new device to assess nocturnal cough and obstructive breath sounds objectively in children with a wide variety of respiratory diseases. The assessment proved user friendly. We obtained additional information on nighttime symptoms, which would otherwise have remained obscure. Further studies to assess possible diagnostic and therapeutic benefits of this device are needed.

Does treatment guided by exhaled nitric oxide fraction improve outcomes in subgroups of children with asthma?

INTRODUCTION: Exhaled nitric oxide fraction (F ENO), a biomarker of eosinophilic airway inflammation, may be useful to guide asthma treatment. F ENO-guided treatment may be more effective in certain subgroups for improving asthma outcomes compared to standard treatment. METHODS: An individual patient data analysis was performed using data from seven randomised clinical trials (RCTs) which used F ENO to guide asthma treatment. The incidence of an asthma exacerbation and loss of control, and the time to first exacerbation and loss of control were described between five subgroups of RCT participants. RESULTS: Data were available in 1112 RCT participants. Among those not treated with leukotriene receptor antagonists (LTRA), but not among those who were treated with LTRA, F ENO-guided treatment was associated with reduced exacerbation risk (OR 0.68, 95% CI 0.49-0.94), longer time to first exacerbation (hazard ratio (HR) 0.76, 95% CI 0.57-0.99) and borderline reduced risk for loss of control (OR 0.70, 95% CI 0.49-1.00). Nonobese children, compared to obese children, were less likely to lose asthma control when treatment was guided by F ENO (OR 0.69, 95% CI 0.48-0.99) and time to loss of control was longer (HR 0.77, 95% CI 0.61-0.99). CONCLUSIONS: Asthma treatment guided by F ENO may be more effective in achieving better asthma outcomes for patients who are not treated with LTRA and who are not obese, compared to standard practice.

What is a clinically meaningful change in exhaled nitric oxide for children with asthma?

INTRODUCTION: Fractional exhaled nitric oxide (FE NO) may be a useful objective measurement to guide asthma treatment. What remains uncertain is what change in FE NO is clinically significant. METHODS: An individual patient data analysis was performed using data from seven randomized clinical trials which used FE NO to guide asthma treatment. The absolute and percentage intra-subject change in FE NO measurements over "stable" and also "unstable" 3-month periods were described. RESULTS: Data were available in 1112 randomized controlled trial participants and ≥1 stable period was present for 665 individuals. The interquartile range (IQR) and limits of agreement (LoA) for change in absolute FE NO among individuals whose initial FE NO was <50 parts per billion (ppb) were -7 to +9 ppb and -43 to +50 ppb, and for those with initial FE NO ≥50 ppb IQR was -29 to +17 ppb and LoA was -80 to +76 ppb. For percentage change in FE NO, the IQR and LoA for individuals whose initial FE NO was <50 ppb were -33% to +51% and -157% to +215%, and for those with initial FE NO ≥50 ppb were -33% to +35% and -159% to +192%. The variation in FE NO values for a stable period was similar irrespective of whether it was followed by a stable or unstable period. CONCLUSIONS: Over a 3-month period where FE NO is initially <50 ppb, a rise of <10 ppb or of <50% (based on IQR) is unlikely to be related to asthma. When FE NO is initially ≥50 ppb an percentage change of <50% (based on IQR) is unlikely to be asthma-related.

Childhood tuberculosis in Vienna between 2010 and 2016.

BACKGROUND: Tuberculosis (TB) has become a rare disease in developed countries. Austria is a low incidence country for TB with an incidence rate of 7.2/100,000 in 2016. The incidence of TB has shown a constant decline in Austria from 2008 (9.8/100,000) to 2015 (6.7/100,000) but recently stagnated in 2016 (7.2/100,000). In recent years migration to Austria from countries with high TB incidence rates has increased. Therefore, this study aimed to describe the recent epidemiology of childhood TB in Vienna. METHODS: Data of pediatric patients with active TB infections, who were hospitalized for further investigations or isolation precautions between 2010 and 2016 at the Wilhelminenspital, Austria's reference center for childhood tuberculosis, were retrospectively analyzed. Demographic and clinical data (symptoms, microbiology, radiology, immunology) were collected, compared and evaluated. RESULTS: A total of 127 patients with active tuberculosis were included in the study. The number of admissions varied between n = 7 in 2010 and n = 26 in 2016. There were two age peaks of infected children (0-5 years: n = 41 and 15-18 years: n = 45). In 35% of the cases one parent had active TB and was suspected to be the index case. In 36% the source of infection remained unknown. Compared to young children (<5 years), adolescents (15-18 years) showed proportionally more TB-related symptoms, such as cough (41% vs. 24%), fever (15% vs. 14%) and weight loss (22% vs. 0%). At the time of admission 51% of the young children and 33% of the adolescents were free of symptoms. Intrathoracic disease was found in 80.8%, extrathoracic disease in 19.2% and 11% of the cases were tuberculous lymphadenitis. Of the patients with intrathoracic TB 54% (n = 64) had a positive microbiological result (auramine staining, bacteriological culture, PCR). In young children hilar lymphadenopathy was the most frequent radiological finding (50%), whereas in adolescents lung infiltrates were most common (36%). The sensitivity of interferon-gamma release assays (IGRA) was 0.94 compared to 0.88 of the tuberculin skin test (TST). Both test methods showed moderate concordance (ϕ-coefficient = 0.48). CONCLUSION: A high number of asymptomatic children and adolescents with active TB were observed, which underlines the importance of efficient screening measures. Thorough history taking in all patients with TB is essential to maximize the effect of contact tracing. Overall, infection rates remained consistently low during the observation period.

Characteristics of cystic fibrosis-related diabetes: Data from two different sources the European cystic fibrosis society patient registry and German/Austrian diabetes prospective follow-up registry.

BACKGROUND: Standardized patient registries provide a unique basis to get insight into cystic fibrosis (CF)-related diabetes (CFRD), the most common comorbidity in CF. METHODS: A total of 3853 CFRD patients from the European CF Society Patient Registry (ECFSPR) and 752 from the German/Austrian diabetes prospective follow-up (diabetes patienten verlaufsdokumentation [DPV]) were studied. To adjust for age and sex, multivariable regression was used (SAS 9.4). RESULTS: DPV subjects were younger (26.5 [20.2-32.6] vs 28.3 [21.7-36.0] years, P < 0.001) and more often female (59.6 vs 50.9%, P < 0.001). In both registries, F508del homozygotes were most frequent, with higher proportion in DPV (80.9 vs 57.8%, P = 0.003). After adjustment, lung-transplantation (LTX) was more common in ECFSPR (18.9 vs 4.9%, P < 0.001), although duration since LTX (4.8 ± 0.2 vs 5.5 ± 0.7 years, P = 0.33) did not differ. In DPV patients without LTX, a lower BMI (19.6 ± 0.1 vs 21.0 ± 0.1 kg/m2 , P < 0.001), higher proportion of underweight (41.2 vs 20.2%, P < 0.001) and a tendency towards worse lung function (%FEV1 : 42.3 ± 4.2 vs 48.3 ± 0.5%, P = 0.16) were observed. CONCLUSIONS: Between both registries, demographic and clinical differences of CFRD were present. Besides different kind of data sources, diverse treatment structures between countries may play a role. The results may further indicate a more serious illness in patients treated in specialized diabetes clinics, documenting their data in DPV.

Change in FEV1 and Feno Measurements as Predictors of Future Asthma Outcomes in Children.

BACKGROUND: Repeated measurements of spirometry and fractional exhaled nitric oxide (Feno) are recommended as part of the management of childhood asthma, but the evidence base for such recommendations is small. We tested the hypothesis that reducing spirometric indices or increasing Feno will predict poor future asthma outcomes. METHODS: A one-stage individual patient data meta-analysis used data from seven randomized controlled trials in which Feno was used to guide asthma treatment; spirometric indices were also measured. Change in %FEV1 and % change in Feno between baseline and 3 months were related to having poor asthma control and to having an asthma exacerbation between 3 and 6 months after baseline. RESULTS: Data were available from 1,112 children (mean age, 12.6 years; mean %FEV1, 94%). A 10% reduction in %FEV1 between baseline and 3 months was associated with 28% increased odds for asthma exacerbation (95% CI, 3-58) and with 21% increased odds for having poor asthma control (95% CI, 0-45) 6 months after baseline. A 50% increase in Feno between baseline and 3 months was associated with 11% increase in odds for poor asthma control 6 months after baseline (95% CI, 0-16). Baseline Feno and %FEV1 were not related to asthma outcomes at 3 months. CONCLUSIONS: Repeated measurements of %FEV1 that are typically within the "normal" range add to clinical risk assessment of future asthma outcomes in children. The role of repeated Feno measurements is less certain because large changes were associated with small changes in outcome risk.

Estimating the age of p.(Phe508del) with family studies of geographically distinct European populations and the early spread of cystic fibrosis.

The high incidence of cystic fibrosis (CF) is due to the frequency of the c.1521_1523delCTT variant in the cystic fibrosis transmembrane conductance regulator (CFTR), but its age and origin are uncertain. This gap limits attempts to shed light on the presumed heterozygote selective advantage that accounts for the variant's high prevalence among Caucasian Europeans and Europe-derived populations. In addition, explaining the nature of heterozygosity to screened individuals with one c.1521_1523delCTT variant is challenging when families raise questions about these issues. To address this gap, we obtained DNA samples from 190 patients bearing c.1521_1523delCTT and their parents residing in geographically distinct European populations plus a Germany-derived population in the USA. We identified microsatellites spanning CFTR and reconstructed haplotypes at 10 loci to estimate the time/age of the most recent common ancestor (tMRCA) with the Estiage program. We found that the age estimates differ between northwestern populations, where the mean tMRCA values vary between 4600 and 4725 years, and the southeastern populations where c.1521_1523delCTT seems to have been introduced only about 1000 years ago. The tMRCA values of Central Europeans were intermediate. Thus, our data resolve a controversy by establishing an early Bronze Age origin of the c.1521_1523delCTT allele and demonstrating its likely spread from northwest to southeast during ancient migrations. Moreover, taking the archeological record into account, our results introduce a novel concept by suggesting that Bell Beaker folk were the probable migrating population responsible for the early dissemination of c.1521_1523delCTT in prehistoric Europe.

Increased severity of respiratory syncytial virus airway infection due to passive smoke exposure.

OBJECTIVE: Aim of this study was to analyze whether children with objectively measured second-hand cigarette smoke (SHS) exposure suffer from a more severe course of disease when hospitalized with lower respiratory tract infection (LRTI) due to respiratory syncytial virus (RSV). METHODS: This prospective study was conducted at the Department of Pediatrics, Wilhelminen-Hospital, Vienna, Austria in children aged below 1 year without a history of preceding lung disease and with acute symptoms of LRTI and a positive nasopharyngeal swab for RSV. On admission, urinary cotinine was measured as a marker of recent SHS and clinical severity of LRTI was assessed by oxygen saturation SpO2 and the "admission clinical severity score" (CSSA). Parents/caregivers were asked to complete a customized questionnaire assessing risks for SHS and demographic characteristics. RESULTS: After inclusion of 217 patients, data of 185 patients with a mean (SD) age of 106 days (80) were analyzed. Twenty-five patients (13.5%) were "cotinine-positive" (COT+) defined as a urinary cotinine level of ≥7 µg/L. SpO2 on admission was significantly lower in children recently exposed to SHS defined objectively by COT+ (94.8% ±2.0) in urine on admission compared to children not recently exposed (COT-) (96.8% ±3.0; P < 0.01). Disease severity, assessed via mean clinical severity score on admission (CSSA) for COT+ and COT- was 2.56 and 1.71, respectively (P = 0.03). CONCLUSIONS: Recent exposure to SHS was associated with lower O2 saturation and higher clinical severity score, measured by urine cotinine levels in children hospitalized for RSV infection under 1 year of age.

Early detection of lung function decrements in children and adolescents with cystic fibrosis using new reference values.

Interpretation of lung function values in children with cystic fibrosis (CF) depends on the applied reference values. We hypothesize that differences between the new global lung function initiative (GLI) values and the formerly used Zapletal et al. values produce significantly different clinical results. We analyzed 3719 lung function measurements of 108 children and adolescents (n = 54 male; aged 6-18 years) with CF treated between September 1991 and July 2009. Data were analyzed in milliliters (ml) and % predicted (pred.) and interpreted using Zapletal and GLI reference values. Applying GLI compared to Zapletal resulted in significantly lower mean forced expiratory volume in 1s (FEV1)% pred. VALUES: Zapletal 86.6% (SD 20.6), GLI 79.9% (SD 20.3) and 32% (n = 497/1543) were misclassified as normal when using Zapletal. Despite showing no overall differences in FEV1 and forced vital capacity (FVC) between concomitant Pseudomonas detection (PA+) in n = 938 and Pseudomonas negative (PA-) (n = 2781) using either reference PA+ resulted in lower FEV1 and FVC values with increasing age; however, measurement of small airway obstruction with forced expiratory flow at 75% of FVC (FEF75) values - available for Zapletal -showed significant differences. Reassurance regarding lung function when using old reference values may occur with potential clinical significance. Discrepancies in lung function interpretation underline the importance of using uniform and best available reference values.

Cystic fibrosis in Austria.

Registry data for patients with cystic fibrosis (CF) are increasingly used to evaluate the natural history, for benchmarking of therapy and in order to identify eligible patients for clinical studies. So far, no data on frequency and clinical status of CF patients have been available for Austria on a national level. We collected data of CF patients treated 2014 in Austrian CF outpatient clinics by means of a European CF registry and on an individual search basis. A total of 773 CF patients with a median age of 18.9 years (SD 11.8 years) were seen in 13 centers (18-151 patients/center). Homozygous F508del mutation being the most common genotype was observed in 48.8% of patients. Mean age at diagnosis was 27 days. In 59% of all patients FEV1% predicted (Forced Exspiratory Volume in 1 second) was <80% and in 20% <50%. An average FEV1 predicted decline per year of 1.9% was observed between 6-18 years of age. Colonisation with Pseudomonas aeruginosa ranged between 12% and 69% in adult patients and in 0-16% in children with CF. Burkholderia cepacia complex species were present in a total of 29 samples (3.8%). Insulin therapy for diabetes was given in 14.5%. Liver involvement was reported in 36.3%. A wide variation of prescribed CF therapy was observed between centers. Data on CF patients living in Austria are now available and form a basis for clinical benchmarking as well as analyses from a public health perspective.

[New international reference values for spirometry: implications for clinical issues using a comparative analysis of a paediatric population]. / Neue internationale Referenzwerte für die Spirometrie--Implikation für die Praxis anhand einer vergleichenden Analyse eines pädiatrischen Patientenkollektivs.

BACKGROUND: The new lung function reference values of the global lung initiative (GLI) are recommended by most health societies. The aim of this study was to analyze FEV1- and FEV1/FVC-values from a German and Austrian patient group applying old and new reference values. RESULTS: A total of 215 Caucasian children (aged 5-17 years) were included. FEV1-values were significantly lower applying GLI reference values compared to Zapletal values (median 96.9 % pred. (87.3-105.2) versus 100.6 % pred. (quartile 91.5-111.4), p = 0.000), the median difference was 4.9 % (range -12.9 to 27.5) % pred. Differences correlated significantly with age and FEV1 in % predicted (Zapletal), p = 0.000 17/70 (24 %) patients with cystic fibrosis had FEV1-values <80% pred. applying Zapletal, in 25 (36 %) patients FEV1 was abnormal (z-score <1645) using GLI values; 3/145 asthmatics (2 %) had FEV1-Werte <80 % d.S. (Zapletal), 7/145 (5 %) z-scores <1645 (GLI). CONCLUSION: Differences between GLI-and Zapletal-reference values were considerable in pediatric asthma and CF-patients.