Primary ciliary dyskinesia in Volendam: Diagnostic and phenotypic features in patients with a CCDC114 mutation.

Primary ciliary dyskinesia (PCD) is a heterogeneous disease, with impaired mucociliary clearance causing respiratory tract infections. A founding CCDC114 mutation has led to a relatively homogeneous and large Dutch PCD population in Volendam. Our aim was to describe their phenotype. Therefore, all Volendam PCD patients seen at the Amsterdam UMC were included in this study. Data were collected on lung function, microbiology, radiology, and ear-nose-throat (ENT) symptoms. A mixed effects model estimated lung function decline in %point per year (95% confidence interval [CI]). Thirty-three (60%) out of approximately 56 Volendam PCD patients were treated at our center and included in this study. Only 30% of patients had situs inversus. FEV1 declined in children (-1.43%/year, CI: -1.80/-1.05), but not in adults (0.01%/year, CI: -0.36/0.38). Pseudomonas aeruginosa was cultured in 21% of children and 60% of adults, respectively. Patients who have been infected at some point with P. aeruginosa had a steeper decline in FEV1 as compared to patients that have never been infected. Neonatal symptoms (79%) and ENT problems (94%) were common; fertility issues however, were not (11%) common. Compared to other PCD cohorts, the Volendam/CCDC114 patients have a moderately severe phenotype with lung function decline predominantly occurring in childhood.

Fitness to fly in the paediatric population, how to assess and advice.

The number of children on commercial aircrafts is rising steeply and poses a need for their treating physicians to be aware of the physiologic effects and risks of air travel. The most important risk factors while flying are a decrease in partial oxygen pressure, expansion of trapped air volume, low cabin humidity, immobility, recirculation of air and limited options for medical emergencies. Because on-board medical emergencies mostly concern exacerbations of chronic disease, the medical history, stability of current disease and previous flight experience should be assessed before flight. If necessary, hypoxia altitude simulation testing can be performed to simulate the effects of in-flight hypoxia. Although the literature on paediatric safety of air travel is sparse, recommendations for many different situations can be given. CONCLUSION: We present an overview of the most up to date recommendations to ensure the safety of children during flight. What is Known: • Around 65% of on-board medical emergencies are complications of underlying disease. • In children, the three most common emergencies during flight concern respiratory, neurological and infectious disease. What is New: • Although studies are scarce, some advices to ensure safe air travel can be given for most underlying medical conditions in children, based on physiology, studies in adults and expert opinions. • In former preterm infants without chronic lung disease, hypoxia altitude simulation testing to rule out in-flight desaturation is not recommended.

The Non-Invasive Detection of Pulmonary Exacerbations in Disorders of Mucociliary Clearance with Breath Analysis: A Systematic Review.

Background: Disorders of mucociliary clearance, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and bronchiectasis of unknown origin, are characterised by periods with increased respiratory symptoms, referred to as pulmonary exacerbations. These exacerbations are hard to predict and associated with lung function decline and the loss of quality of life. To optimise treatment and preserve lung function, there is a need for non-invasive and reliable methods of detection. Breath analysis might be such a method. Methods: We systematically reviewed the existing literature on breath analysis to detect pulmonary exacerbations in mucociliary clearance disorders. Extracted data included the study design, technique of measurement, definition of an exacerbation, identified compounds and diagnostic accuracy. Results: Out of 244 identified articles, 18 were included in the review. All studies included patients with CF and two also with PCD. Age and the definition of exacerbation differed between the studies. There were five that measured volatile organic compounds (VOCs) in exhaled breath using gas chromatography with mass spectrometry, two using an electronic nose and eleven measured organic compounds in exhaled breath condensate. Most studies showed a significant correlation between pulmonary exacerbations and one or multiple compounds, mainly hydrocarbons and cytokines, but the validation of these results in other studies was lacking. Conclusions: The detection of pulmonary exacerbations by the analysis of compounds in exhaled breath seems possible but is not near clinical application due to major differences in results, study design and the definition of an exacerbation. There is a need for larger studies, with a longitudinal design, international accepted definition of an exacerbation and validation of the results in independent cohorts.

Reduced lung function during childhood in identical twins with discordant fetal growth: a cohort study.

Background: Fetal growth restriction (FGR) can negatively affect lung development, leading to increased respiratory morbidity and reduced lung function later in life. Studies regarding the impact of FGR on lung function in singletons are influenced by genetic, obstetric, and maternal factors. To overcome these confounding factors, we aim to investigate lung function in identical twins with selective FGR (sFGR). Methods: Lung function assessments were performed in identical twins with sFGR born in our centre between March 1, 2002, and December 31, 2017, aged between 5 and 17 years. sFGR was defined as birthweight discordance ≥20%. Outcome measures consisted of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and transfer factor for carbon monoxide (DLCO) and were compared between the smaller and larger twin. Findings: Thirty-nine twin pairs performed spirometry of sufficient quality. Median gestational age at birth was 34.3 (interquartile range (IQR) 32.1-36.0) weeks with median birthweights of 1500 (IQR 1160-1880) grams and 2178 (IQR 1675-2720) grams for the smaller and larger twin, respectively. Smaller twins had significantly lower z-scores for FEV1 (-0.94 versus -0.41, p = 0.0015), FVC (-0.56 versus -0.06, p < 0.0001) and DLCO (-0.50 versus 0.00, p < 0.0001) compared to larger co-twins. Interpretation: Although being genetically identical, sFGR in identical twins is associated with a reduction in static and dynamic lung volume and a reduction in lung diffusion, even when taking the reduced lung volume into account. This indicates that adverse growth conditions in utero negatively affect lung development and function, potentially contributing to an increase in respiratory morbidities later in life. Funding: The Dutch Heart Foundation and The Bontius Foundation.

No Association Between Transient Hypothyroxinemia of Prematurity and Neurodevelopmental Outcome in Young Adulthood.

CONTEXT: Transient hypothyroxinemia of prematurity (THoP) has been associated with neurodevelopmental impairment in infancy and childhood. It is not known whether these relations persist into adulthood. OBJECTIVE: The objective was to examine whether there is an effect of THoP on intelligence quotient (IQ) score and motor functioning at a young adult age. DESIGN: This study was part of the 19-year follow-up of the Project On Preterm and Small-for-gestational-age birth (POPS) cohort, which included infants born very preterm (ie, <32 wk) and/or with a very low birth weight (ie, <1500 g). SETTING: This was a multicenter study. PATIENTS: There were 398 19-year-old participants of the POPS cohort, of whom 120 had THoP. EXPOSURE: T4 concentrations were obtained through the national neonatal screening program for congenital hypothyroidism. THoP was defined as a total T4 concentration < -3 SD of the daily mean (approximately 60 nmol/L). MAIN OUTCOME MEASURES: Main outcome measures were IQ and motor functioning, measured with the digital Multicultural Capacities Test-Intermediate Level and a revised version of Touwen's examination of minor neurological dysfunction, respectively. RESULTS: THoP was not associated with IQ score (mean difference, 0 [95% confidence interval, -3.8 to 3.8] points) or motor function (mean difference, 0.6 [95% confidence interval, -1.3 to 2.5] points) after adjustment for demographic and perinatal characteristics. CONCLUSIONS: No associations between THoP and neurodevelopmental outcome at age 19 years were found.

Mannose-binding lectin and the risk of HIV transmission and disease progression in children: a systematic review.

BACKGROUND: Mannose-binding lectin (MBL) can activate the complement system by binding to carbohydrates, such as those presented on the HIV virion surface. It is unclear whether genetically determined MBL deficiency is related to vertical HIV transmission and disease progression in HIV-infected children. METHODS: A literature search of Medline, Embase and Cochrane Central Register identified all relevant studies on MBL and HIV infection in children. We extracted information on the characteristics of the study group, method of MBL analysis, outcome definitions, follow-up and the risk estimates. The validity of each study was assessed. RESULTS: Nine studies were retrieved. Most were of good validity, but risk adjustment for confounders was missing in 6 studies. Age, treatment and outcome definitions differed between the study groups. In most of the studies, MBL deficiency was associated with an increased frequency of vertical HIV transmission and an increased speed of disease progression. In the 2 most valid studies, carriers of variant genes had an increased odds ratio for transmission and an increased relative hazard for disease progression and central nervous system impairment, especially in children <2 years of age. CONCLUSIONS: MBL deficiency is associated with an increased risk of vertical HIV transmission. How this risk relates to other factors that influence transmission is unclear. The association between HIV disease progression and MBL deficiency is most pronounced in children <2 years of age, probably due to immaturity of their adaptive immunity.