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Find video protocols related to scientific articles indexed in Pubmed.
Allergies are associated with arterial changes in young children.
Eur J Prev Cardiol
PUBLISHED: 10-11-2014
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Inflammation is important in atherosclerosis development. Whether common causes of inflammation, such as allergies and infections, already exert this influence in early childhood is unknown. The objective of this study was to investigate the association between both allergies and infections with children's vasculature.
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Lack of long-term effects of high-dose inhaled beclomethasone for respiratory syncytial virus bronchiolitis: a randomized placebo-controlled trial.
Pediatr. Infect. Dis. J.
PUBLISHED: 09-03-2014
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Previously, we showed that high-dose early initiated inhaled corticosteroids during respiratory syncytial virus bronchiolitis partially and transiently prevents subsequent recurrent wheeze. Here, we study treatment effect on lung function at age 6.
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High-resolution CT can differentiate between alloimmune and nonalloimmune lung disease early after hematopoietic cell transplantation.
AJR Am J Roentgenol
PUBLISHED: 08-23-2014
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The purpose of this study was to develop a simple semiquantitative high-resolution CT (HRCT) scoring system to differentiate alloimmune-mediated lung syndromes (allo-LS) from other lung diseases early after hematopoietic cell transplantation. Allo-LS should be differentiated from other abnormalities, such as infections and toxicity, because they are life threatening and require prompt and specific treatment.
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Reintroduction failure after negative peanut challenges in children.
Pediatr Allergy Immunol
PUBLISHED: 08-18-2014
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A negative double-blind placebo-controlled food challenge (DBPCFC) should normally be followed by reintroduction of the food. However, reintroduction fails in a subset of children. The observed reintroduction problems could be due to refusal of the food that long has been avoided, to other behavioural/psychological factors or to false negative DBPCFC outcome. This study analyses the frequency, causes and risk factors for reintroduction failure in children after negative peanut DBPCFC.
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Decreased lung function precedes severe respiratory syncytial virus infection and post-respiratory syncytial virus wheeze in term infants.
Eur. Respir. J.
PUBLISHED: 07-03-2014
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It is unknown why respiratory syncytial virus (RSV) causes mild disease in some children and severe disease, requiring hospitalisation, in others. We aimed to assess whether diminished premorbid lung function in healthy term infants predisposes to hospitalisation during RSV bronchiolitis, and to post-RSV wheeze. In a prospective birth cohort study of unselected term healthy children, neonatal lung function was measured before the age of 2 months (n=2133). From birth through the first year of life, respiratory symptoms were recorded in a diary, and general practitioner consultations and hospitalisations were documented. In a subgroup (n=417) repeated nose and throat swabs were collected for PCR to detect RSV infections. Median neonatal respiratory system compliance (Crs) was significantly lower (41.2 versus 47.4 mL · kPa(-1), p=0.03) and resistance (Rrs) was higher (8.2 versus 6.3 kPa · s · L(-1), p=0.10) in hospitalised RSV patients (n=18) compared with nonhospitalised RSV-positive infants (n=84). Every 10 mL · kPa(-1) increase in Crs was associated with 55% less post-RSV wheeze (OR 0.56, 95% CI 0.35-0.90), and each kPa · s · L(-1) increase in Rrs was associated with 42% more post-RSV wheeze, which was only marginally explained by pre-RSV wheeze or severity of the RSV disease. This unselected birth cohort study shows for the first time that decreased lung function at birth predisposes to severe RSV disease, and to post-RSV wheeze.
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Prediction of mortality in adolescents with cystic fibrosis.
Med Sci Sports Exerc
PUBLISHED: 05-23-2014
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Lung function, nutritional status, and parameters of exercise capacity are known predictors of mortality in patients with cystic fibrosis (CF). The aim of the current study was to use these important parameters to develop a multivariate model to predict mortality in adolescent patients with CF.
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Respiratory tract infections and asthma control in children.
Respir Med
PUBLISHED: 04-18-2014
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Asthma control is considered the major goal of asthma management, while many determinants of control are difficult to modify. We studied the association between respiratory infection episodes (RTIs) of various types and asthma control.
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Impact of early daycare on healthcare resource use related to upper respiratory tract infections during childhood: prospective WHISTLER cohort study.
BMC Med
PUBLISHED: 02-20-2014
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Daycare attendance is an established risk factor for upper respiratory tract infections (URTI) and acute otitis media (AOM). Whether this results in higher use of healthcare resources during childhood remains unknown. We aim to assess the effect of first year daycare attendance on the timing and use of healthcare resources for URTI and AOM episodes during early childhood.
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Chronic inflammation and infection associate with a lower exercise training response in cystic fibrosis adolescents.
Respir Med
PUBLISHED: 02-01-2014
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Considerable heterogeneity among training-induced effects is observed in patients with cystic fibrosis (CF). We previously showed that longitudinal changes in exercise capacity in adolescents with CF were negatively associated with Pseudomonas aeruginosa (P. aeruginosa) colonization and total immunoglobulin G (IgG) levels, independent of age, pulmonary function and bodyweight. This is the first study investigating whether chronic inflammation and infection also associate with the exercise training response in adolescents with CF. Participants performed a home-based exercise training program for 12 weeks. Pulmonary function, anthropometrics, exercise capacity, markers of inflammation and P. aeruginosa colonization status were measured at baseline. Exercise training-induced changes in pulmonary function and exercise capacity were compared between patients with a low and high inflammation-infection status. Participants with CF with high total IgG levels and P. aeruginosa colonization improved significantly less from the exercise training program, with regard to maximal oxygen consumption. These observations support the hypothesis that chronic systemic inflammation and infection leads to devastating effects on skeletal muscles, hampering skeletal muscle tissue to improve from regular physical exercise. Data further suggest that patients with CF should preferentially be encouraged to engage in regular physical exercise when inflammation and infection status is low (e.g. at a young age).
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Increased risk of wheeze and decreased lung function after respiratory syncytial virus infection.
PLoS ONE
PUBLISHED: 01-01-2014
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A relationship between hospitalization for respiratory syncytial virus (RSV) bronchiolitis and asthma development has been suggested in case-control studies.
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Life-course of cardio-respiratory associations.
Eur J Prev Cardiol
PUBLISHED: 11-01-2013
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Several studies have shown that raised cardiovascular risk factors are associated with an impaired lung function in adulthood. Whether this association also exists in the young is unknown. Our aim was to study the relation between blood pressure and lung function from neonatal to elderly age.
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Lack of Long Term Effects of High Dose Inhaled Beclomethasone for RSV Bronchiolitis - A Randomized Placebo-Controlled Trial.
Pediatr. Infect. Dis. J.
PUBLISHED: 10-31-2013
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Previously we showed that high-dose early initiated inhaled corticosteroids during respiratory syncytial virus (RSV) bronchiolitis partially and transiently prevents subsequent recurrent wheeze. Here, we study treatment effect on lung function at age 6.
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Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients.
Cell Stem Cell
PUBLISHED: 10-21-2013
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Single murine and human intestinal stem cells can be expanded in culture over long time periods as genetically and phenotypically stable epithelial organoids. Increased cAMP levels induce rapid swelling of such organoids by opening the cystic fibrosis transmembrane conductor receptor (CFTR). This response is lost in organoids derived from cystic fibrosis (CF) patients. Here we use the CRISPR/Cas9 genome editing system to correct the CFTR locus by homologous recombination in cultured intestinal stem cells of CF patients. The corrected allele is expressed and fully functional as measured in clonally expanded organoids. This study provides proof of concept for gene correction by homologous recombination in primary adult stem cells derived from patients with a single-gene hereditary defect.
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Nasal nitric oxide levels and nasal polyposis in children and adolescents with cystic fibrosis.
JAMA Otolaryngol Head Neck Surg
PUBLISHED: 09-21-2013
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The counterintuitive decrease of exhaled nitric oxide (NO) levels in a severe inflammatory disorder like cystic fibrosis (CF) is only scarcely understood. Because NO is important in a variety of regulatory processes in the lung, including host defense, inflammation, and bronchomotor control, it is necessary to search for clarifying mechanisms.
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Can we predict severe reactions during peanut challenges in children?
Pediatr Allergy Immunol
PUBLISHED: 06-20-2013
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Limited and contrasting data are available about risk factors for severe reactions during double-blind, placebo-controlled food challenge (DBPCFC). Knowing these risk factors would help to improve safety precautions and choosing the best setting for challenge. We assessed whether we could determine predictors for positive and severe food challenge outcome (FCO) with regular available patient data in children suspected for peanut allergy.
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Inflammatory phenotypes underlying uncontrolled childhood asthma despite inhaled corticosteroid treatment: rationale and design of the PACMAN2 study.
BMC Pediatr
PUBLISHED: 06-10-2013
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BACKGROUND: The diagnosis of childhood asthma covers a broad spectrum of pathological mechanisms that can lead to similarly presenting clinical symptoms, but may nonetheless require different treatment approaches. Distinct underlying inflammatory patterns are thought to influence responsiveness to standard asthma medication.Methods/design: The purpose of the PACMAN2 study is to identify inflammatory phenotypes that can discriminate uncontrolled childhood asthma from controlled childhood asthma by measures in peripheral blood and exhaled air. PACMAN2 is a nested, case--control follow-up study to the ongoing pharmacy-based "Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects" (PACMAN) study. The original PACMAN cohort consists of children aged 4--12 years with reported use of asthma medication. The PACMAN2 study will be conducted within the larger PACMAN cohort, and will focus on detailed phenotyping of a subset of the PACMAN children. The selected participants will be invited to a follow-up visit in a clinical setting at least six months after their baseline visit based on their adherence to usage of inhaled corticosteroids, their asthma symptoms in the past year, and their age (>= 8 years). During the follow-up visit, current and long-term asthma symptoms, medication use, environmental factors, medication adherence and levels of exhaled nitric oxide will be reassessed. The following measures will also be examined: pulmonary function, exhaled volatile organic compounds, as well as inflammatory markers in peripheral blood and blood plasma. Comparative analysis and cluster-analyses will be used to identify markers that differentiate children with uncontrolled asthma despite their use of inhaled corticosteroids (ICS) (cases) from children whose asthma is controlled by the use of ICS (controls). DISCUSSION: Asthmatic children with distinct inflammatory phenotypes may respond differently to anti-inflammatory therapy. Therefore, by identifying inflammatory phenotypes in children with the PACMAN2 study, we may greatly impact future personalised treatment strategies, uncover new leads for therapeutic targets and improve the design of future clinical studies in the assessment of the efficacy of novel therapeutics.
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A functional CFTR assay using primary cystic fibrosis intestinal organoids.
Nat. Med.
PUBLISHED: 06-02-2013
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We recently established conditions allowing for long-term expansion of epithelial organoids from intestine, recapitulating essential features of the in vivo tissue architecture. Here we apply this technology to study primary intestinal organoids of people suffering from cystic fibrosis, a disease caused by mutations in CFTR, encoding cystic fibrosis transmembrane conductance regulator. Forskolin induces rapid swelling of organoids derived from healthy controls or wild-type mice, but this effect is strongly reduced in organoids of subjects with cystic fibrosis or in mice carrying the Cftr F508del mutation and is absent in Cftr-deficient organoids. This pattern is phenocopied by CFTR-specific inhibitors. Forskolin-induced swelling of in vitro-expanded human control and cystic fibrosis organoids corresponds quantitatively with forskolin-induced anion currents in freshly excised ex vivo rectal biopsies. Function of the CFTR F508del mutant protein is restored by incubation at low temperature, as well as by CFTR-restoring compounds. This relatively simple and robust assay will facilitate diagnosis, functional studies, drug development and personalized medicine approaches in cystic fibrosis.
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The relationship between body growth and pulmonary function in children with cystic fibrosis.
Acta Paediatr.
PUBLISHED: 05-03-2013
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To measure the weight and height of children with cystic fibrosis (CF) from 2 to 10 years of age and to investigate the relationship between these parameters and forced expiratory volume in 1 sec (FEV1 ) beginning at 6 years of age.
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Optimal complement-mediated phagocytosis of Pseudomonas aeruginosa by monocytes is cystic fibrosis transmembrane conductance regulator-dependent.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 04-27-2013
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Cystic fibrosis (CF) is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and is characterized by chronic pulmonary infections. The mechanisms underlying chronic infection and inflammation remain incompletely understood. Mutant CFTR in nonepithelial tissues such as immune cells has been suggested to contribute to infection, inflammation, and the resultant lung disease. However, much controversy still exists regarding the intrinsic role of CFTR in immune cells, especially phagocytes. Therefore, we investigated CFTR expression and function in neutrophils and monocytes isolated from human peripheral blood. CFTR function was assessed by comparing non-CF and CF cells, before and after the chemical inhibition of CFTR. We found CFTR protein expression in monocytes, but this expression was limited or undetectable in neutrophils. Furthermore, the phagocytosis and intracellular killing of Pseudomonas aeruginosa was reduced in CF monocytes, and impaired phagocyte effector mechanisms were phenocopied in non-CF monocytes upon the pharmacological inhibition of CFTR. Reduced phagocytosis in CF monocytes relied on the complement-dependent opsonization of Pseudomonas aeruginosa, and was also observed in the context of latex particles labeled with purified C3b. In mechanistic terms, we observed that CFTR function in monocytes is required for the optimal expression of CD11b. We observed no role for CFTR in neutrophil-mediated phagocytosis. These data support an intrinsic role for CFTR in monocytes, and suggest that CFTR-dependent alterations in complement-mediated interactions between Pseudomonas aeruginosa and monocytes may contribute to enhanced susceptibility to infection in patients with CF.
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Human rhinovirus and wheezing: short and long-term associations in children.
Pediatr. Infect. Dis. J.
PUBLISHED: 04-16-2013
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Human rhinoviruses (HRVs) have been suggested to play a role in the development of childhood wheezing. However, whether HRV is causally related to the development of wheezing or HRV-associated wheeze is merely an indicator of disease susceptibility is unclear. Our aim was to study the role of HRV during infancy in the development of lower respiratory disease during infancy and childhood.
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Nocturnal Wheeze Measurement in Preschool Children.
Pediatr. Pulmonol.
PUBLISHED: 03-10-2013
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RATIONALE: Wheezing is a very common symptom in preschool children. Nocturnal wheezing is present in many asthmatic patients, due to enhanced airflow limitation overnight. We assessed the prevalence of nocturnal wheezing in young children and correlated this with respiratory system resistance and history of wheezing symptoms. METHODS: Using a continuous overnight recording of respiratory sounds we analyzed wheeze rate (ratio between wheezing time and recorded breathing time), oxygen saturation and heart rate during one night in 59 three-year-old children of an ongoing birth cohort study, the WHISTLER-project. We associated the nocturnal measurements with the patients history of wheezing symptoms and with measurement of respiratory system resistance (Rint). RESULTS: Analysis of wheeze rate was successful in 44 children. The overall wheeze rate of these children was low, with the highest wheeze rate of 0.63% measured by the tracheal sensor during expiration. In total, 21/44 children had a wheeze rate of ?5% during at least 1?min. There was no statistically significant difference in wheeze rate between the children with and without a history of wheezing. The wheeze rate of the tracheal sensor had a significant correlation with Rint (correlation coefficients of inspiration and expiration: 0.308 and 0.382, P-values 0.05 and 0.01, respectively). CONCLUSIONS: Overall, the wheeze rate in young children is low, but seems to increase over nighttime. Almost 50% of the children have sporadic wheeze during the night. Although higher nocturnal wheeze rates are related to increased respiratory system resistance, it is not related to clinical wheezing symptoms. Pediatr Pulmonol. 2013 9999:XX-XX. © 2013 Wiley Periodicals, Inc.
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Referrals for recurrent respiratory tract infections including otitis media in young children.
Int. J. Pediatr. Otorhinolaryngol.
PUBLISHED: 02-25-2013
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(a) To establish whether disease-related, child-related, and physician-related factors are independently associated with specialist referral in young children with recurrent RTI, and (b) to evaluate whether general practitioners (GPs) follow current guidelines regarding these referrals.
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Infection, inflammation and exercise in cystic fibrosis.
Respir. Res.
PUBLISHED: 02-17-2013
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Regular exercise is positively associated with health. It has also been suggested to exert anti-inflammatory effects. In healthy subjects, a single exercise session results in immune cell activation, which is characterized by production of immune modulatory peptides (e.g. IL-6, IL-8), a leukocytosis and enhanced immune cell functions. Upon cessation of exercise, immune activation is followed by a tolerizing phase, characterized by a reduced responsiveness of immune cells. Regular exercise of moderate intensity and duration has been shown to exert anti-inflammatory effects and is associated with a reduced disease incidence and viral infection susceptibility. Specific exercise programs may therefore be used to modify the course of chronic inflammatory and infectious diseases such as cystic fibrosis (CF).Patients with CF suffer from severe and chronic pulmonary infections and inflammation, leading to obstructive and restrictive pulmonary disease, exercise intolerance and muscle cachexia. Inflammation is characterized by a hyper-inflammatory phenotype. Patients are encouraged to engage in exercise programs to maintain physical fitness, quality of life, pulmonary function and health.In this review, we present an overview of available literature describing the association between regular exercise, inflammation and infection susceptibility and discuss the implications of these observations for prevention and treatment of inflammation and infection susceptibility in patients with CF.
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Apical CFTR expression in human nasal epithelium correlates with lung disease in cystic fibrosis.
PLoS ONE
PUBLISHED: 01-24-2013
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Although most individuals with cystic fibrosis (CF) develop progressive obstructive lung disease, disease severity is highly variable, even for individuals with similar CFTR mutations. Measurements of chloride transport as expression of CFTR function in nasal epithelial cells correlate with pulmonary function and suggest that F508del-CFTR is expressed at the apical membrane. However, an association between quantitative apical CFTR expression in nasal epithelium and CF disease severity is still missing.
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A novel fluorescent sensor for measurement of CFTR function by flow cytometry.
Cytometry A
PUBLISHED: 01-10-2013
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Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis. CFTR-dependent iodide transport measured by fluorescent quenching of ectopically expressed halide-sensitive yellow fluorescent protein (YFP) is widely being used to study CFTR function by microscopy or plate readers. Since YFP fluorescence in these systems is dependent on YFP expression levels and iodide concentration, differences in sensor expression level between experimental units are normalized at the start of each experiment. To allow accurate measurement of CFTR function by flow cytometry, we reasoned that co-expression of an iodide insensitive fluorescent protein would allow for normalization of sensor expression levels and more accurate quantification of CFTR function. Our data indicated that dsRed and mKate fluorescence are iodide insensitive, and we determined an optimal format for co-expression of these fluorescent proteins with halide-sensitive YFP. We showed using microscopy that ratiometric measurement (YFP/mKate) corrects for differences in sensor expression levels. Ratiometric measurements were essential to accurately measure CFTR function by flow cytometry that we here describe for the first time. Mixing of wild type or mutant CFTR expressing cells indicated that addition of approximately 10% of wild type CFTR expressing cells could be distinguished by ratiometric YFP quenching. Flow cytometric ratiometric YFP quenching also allowed us to study CFTR mutants associated with differential residual function upon ectopic expression. Compared with conventional plate-bound CFTR function assays, the flow cytometric approach described here can be used to study CFTR function in suspension cells. It may be further adapted to study CFTR function in heterologous cell populations using cell surface markers and selection of cells that display high CFTR function by cell sorting.
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The expert network and electronic portal for children with respiratory and allergic symptoms: rationale and design.
BMC Pediatr
PUBLISHED: 01-09-2013
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Data on baseline characteristics of children with asthma to predict individual treatment responses are lacking. We aimed to set up a data-collection system which can easily fill this gap in clinical practice.A web-based application was developed, named Portal for children with respiratory and allergic symptoms, hereafter called Electronic Portal (EP). It contains health- and disease-related questionnaires on respiratory- and allergic diseases. All patients, 1-18 years of age, with respiratory- and/or allergic complaints are invited to enter the EP before their first visit. By using the EP large amounts of data, gathered during routine patient care can be used for research purposes. This may help to further investigate the different treatment related asthma phenotypes and will be helpful to monitor risk factors for other atopic diseases and respiratory infections.
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Excess early postnatal weight gain leads to thicker and stiffer arteries in young children.
J. Clin. Endocrinol. Metab.
PUBLISHED: 01-02-2013
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Although early life growth pattern is associated with cardiovascular disease later in life, it is unknown whether vascular changes associated with excess early weight gain already occur in early childhood.
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Soluble Leukocyte-Associated Ig-Like Receptor-1 in Amniotic Fluid Is of Fetal Origin and Positively Associates with Lung Compliance.
PLoS ONE
PUBLISHED: 01-01-2013
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The soluble form of the inhibitory immune receptor leukocyte-Associated Ig-like Receptor-1 (sLAIR-1) is present in plasma, urine and synovial fluid and correlates to inflammation. We and others previously showed inflammatory protein expression in normal amniotic fluid at term. We hypothesized that sLAIR-1 is present in amniotic fluid during term parturition and is related to fetal lung function development. sLAIR-1 was detectable in all amniotic fluid samples (n=355) collected during term spontaneous deliveries. First, potential intra-uterine origins of amniotic fluid sLAIR-1 were explored. Although LAIR-1 was expressed on the surface of amniotic fluid neutrophils, LAIR-1 was not secreted upon ex vivo neutrophil stimulation with LPS, or PMA/ionomycin. Cord blood concentrations of sLAIR-1 were fourfold lower than and not related to amniotic fluid concentrations and placentas showed no or only sporadic LAIR-1 positive cells. Similarly, in post-mortem lung tissue of term neonates that died of non-pulmonary disorders LAIR-1 positive cells were absent or only sporadically present. In fetal urine samples, however, sLAIR-1 levels were even higher than in amniotic fluid and correlated with amniotic fluid sLAIR-1 concentrations. Second, the potential relevance of amniotic fluid sLAIR-1 was studied. sLAIR-1 concentrations had low correlation to amniotic fluid cytokines. We measured neonatal lung function in a convenient subset of 152 infants, using the single occlusion technique, at a median age of 34 days (IQR 30-39). The amniotic fluid concentration of sLAIR-1 was independently correlated to airway compliance (?=0.29, P=.001). Taken together, we show the consistent presence of sLAIR-1 in amniotic fluid, which originates from fetal urine. Concentrations of sLAIR-1 in amniotic fluid during term deliveries are independent from levels of other soluble immune mediators. The positive association between concentrations of amniotic fluid sLAIR-1 and neonatal lung compliance suggests that amniotic fluid sLAIR-1 may be useful as a novel independent marker of neonatal lung maturation.
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Effect of long-term voluntary exercise wheel running on susceptibility to bacterial pulmonary infections in a mouse model.
PLoS ONE
PUBLISHED: 01-01-2013
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Regular moderate exercise has been suggested to exert anti-inflammatory effects and improve immune effector functions, resulting in reduced disease incidence and viral infection susceptibility. Whether regular exercise also affects bacterial infection susceptibility is unknown. The aim of this study was to investigate whether regular voluntary exercise wheel running prior to a pulmonary infection with bacteria (P. aeruginosa) affects lung bacteriology, sickness severity and phagocyte immune function in mice. Balb/c mice were randomly placed in a cage with or without a running wheel. After 28 days, mice were intranasally infected with P. aeruginosa. Our study showed that regular exercise resulted in a higher sickness severity score and bacterial (P. aeruginosa) loads in the lungs. The phagocytic capacity of monocytes and neutrophils from spleen and lungs was not affected. Although regular moderate exercise has many health benefits, healthy mice showed increased bacterial (P. aeruginosa) load and symptoms, after regular voluntary exercise, with perseverance of the phagocytic capacity of monocytes and neutrophils. Whether patients, suffering from bacterial infectious diseases, should be encouraged to engage in exercise and physical activities with caution requires further research.
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Parental smoking and vascular damage in their 5-year-old children.
Pediatrics
PUBLISHED: 12-26-2011
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The relation between smoke exposure in early life, the prenatal period in particular, and the vascular development of young children is largely unknown.
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Emergence and epidemic occurrence of enterovirus 68 respiratory infections in The Netherlands in 2010.
Virology
PUBLISHED: 10-19-2011
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Following an increase in detection of enterovirus 68 (EV68) in community surveillance of respiratory infections in The Netherlands in 2010, epidemiological and virological analyses were performed to investigate the possible public health impact of EV68 infections. We retrospectively tested specimens collected from acute respiratory infections surveillance and through three children cohort studies conducted in The Netherlands from 1994 through 2010. A total of 71 of 13,310 (0.5%) specimens were positive for EV68, of which 67 (94%) were from symptomatic persons. Twenty-four (34%) of the EV68 positive specimens were collected during 2010. EV68-positive patients with respiratory symptoms showed significantly more dyspnea, cough and bronchitis than EV68-negative patients with respiratory symptoms. Phylogenetic analysis showed an increased VP1 gene diversity in 2010, suggesting that the increased number of EV68 detections in 2010 reflects a real epidemic. Clinical laboratories should consider enterovirus diagnostics in the differential diagnosis of patients presenting with respiratory symptoms.
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CFTR expression analysis in human nasal epithelial cells by flow cytometry.
PLoS ONE
PUBLISHED: 08-23-2011
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Unbiased approaches that study aberrant protein expression in primary airway epithelial cells at single cell level may profoundly improve diagnosis and understanding of airway diseases. We here present a flow cytometric procedure to study CFTR expression in human primary nasal epithelial cells from patients with Cystic Fibrosis (CF). Our novel approach may be important in monitoring of therapeutic responses, and better understanding of CF disease at the molecular level.
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Asthma symptoms in pediatric patients: differences throughout the seasons.
J Asthma
PUBLISHED: 08-02-2011
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Seasonal variation in asthma has been widely recognized. The aim of this study was to describe seasonal patterns of asthma symptoms and asthma medication use in a cohort of pediatric asthma medication users and to study determinants of seasonal childhood asthma.
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Limited agreement between current and long-term asthma control in children: the PACMAN cohort study.
Pediatr Allergy Immunol
PUBLISHED: 07-13-2011
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Several studies have shown that predictors of asthma treatment outcomes differ depending on the definition of the outcome chosen. This provides evidence that different outcomes studied may reflect distinct aspects of asthma control. To assess predictors of asthma control, we need firm outcome phenotypes. The aim of this study was to investigate the association between measurements of current and long-term asthma control.
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Highly frequent infections with human rhinovirus in healthy young children: a longitudinal cohort study.
J. Clin. Virol.
PUBLISHED: 06-16-2011
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Human rhinoviruses (HRVs) are an important cause of respiratory tract infections.
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Reference values for paediatric pulmonary function testing: The Utrecht dataset.
Respir Med
PUBLISHED: 04-26-2011
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Since populations evolve, measurement protocols and equipment improve and analysis techniques progress, there is an ongoing need to reassess reference data for pulmonary function tests. Furthermore, reference values for total lung capacity and carbon monoxide diffusion capacity are scarcely available in children. We aimed to provide updated reference equations for most commonly used pulmonary function indices in Caucasian children.
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Intestinal obstruction syndromes in cystic fibrosis: meconium ileus, distal intestinal obstruction syndrome, and constipation.
Curr Gastroenterol Rep
PUBLISHED: 03-09-2011
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Meconium ileus at birth, distal intestinal obstruction syndrome (DIOS), and constipation are an interrelated group of intestinal obstruction syndromes with a variable severity of obstruction that occurs in cystic fibrosis patients. Long-term follow-up studies show that today meconium ileus is not a risk factor for impaired nutritional status, pulmonary function, or survival. DIOS and constipation are frequently seen in cystic fibrosis patients, especially later in life; genetic, dietary, and other associations have been explored. Diagnosis of DIOS is based on suggestive symptoms, with a right lower quadrant mass confirmed on abdominal radiography, whereas symptoms of constipation are milder and of longer standing. In DIOS, early aggressive laxative treatment with oral laxatives (polyethylene glycol) or intestinal lavage with balanced osmotic electrolyte solution and rehydration is required, which now makes the need for surgical interventions rare. Constipation can generally be well controlled with polyethylene glycol maintenance treatment.
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Comparison of height for age and height for bone age with and without adjustment for target height in pediatric patients with CF.
J. Cyst. Fibros.
PUBLISHED: 03-07-2011
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Height is a strong prognostic factor in cystic fibrosis (CF) and is usually compared to reference values of healthy children by expressing height as a z-score height-for-age (HFA). However, HFA does not take into account a potential delay in bone age (BA) and the genetic potential of the child and could therefore result in misclassification of short stature.
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Body fat distribution and early arterial changes in healthy 5-year-old children.
Ann. Med.
PUBLISHED: 03-01-2011
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It is unknown at what age overweight starts to takes its toll on the vasculature. We studied the relation between body size measures and vascular characteristics in healthy 5-year-old children.
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The association between breastfeeding and the cardiovascular system in early childhood.
Am. J. Clin. Nutr.
PUBLISHED: 02-10-2011
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Breastfeeding is suggested to have beneficial effects on childrens health and future health status. However, its cardiovascular effects in childhood and possibly later in life remain largely unclear.
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Asthma medication use in infancy: determinants related to prescription of drug therapy.
Fam Pract
PUBLISHED: 02-02-2011
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Little is known about factors that determine prescribing of asthma therapy in infancy.
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The influence of neonatal lung function on rhinovirus-associated wheeze.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 08-27-2010
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Several studies have shown that the occurrence of wheezing illnesses during the first year of life is associated with lower levels of lung function shortly after birth and before any respiratory illness. It has been suggested that reduced lung function early in life predisposes infants to wheezing during viral respiratory infections, but the association between neonatal lung function and subsequent confirmed viral infections has never been investigated.
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Controlled trial of cycled antibiotic prophylaxis to prevent initial Pseudomonas aeruginosa infection in children with cystic fibrosis.
Thorax
PUBLISHED: 08-20-2010
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Initial pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) is currently treated with intensive antibiotic therapy. At this stage, inflammation and tissue injury might have already occurred. Moreover, bacterial eradication is not always achieved. Prophylactic treatment against P aeruginosa seemed to have a preventive effect in retrospective studies. A study was undertaken to establish prospectively the effect of cycled prophylactic treatment on prevention of initial P aeruginosa infection in children with CF.
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Evaluation of interrupter resistance in methacholine challenge testing in children.
Pediatr. Pulmonol.
PUBLISHED: 02-23-2010
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Bronchial hyperresponsiveness (BHR) is a key feature of asthma and is assessed using bronchial provocation tests. The primary outcome in such tests (a 20% decrease in forced expiratory volume in 1?sec (FEV1 )) is difficult to measure in young patients. This study evaluated the sensitivity and specificity of the interrupter resistance (Rint ) technique, which does not require active patient participation, by comparing it to the primary outcome measure. Methacholine challenge tests were performed in children with a history of moderate asthma and BHR. Mean and individual changes in Rint and FEV1 were studied. A receiver operating characteristic (ROC) curve was used to describe sensitivity and specificity of Rint . Seventy-three children (median age: 9.2 years; range: 6.3-13.4 years) participated. There was a significant (P?
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Mechanical ventilation for respiratory failure in children with severe neurological impairment: is it futile medical treatment?
Dev Med Child Neurol
PUBLISHED: 01-18-2010
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To assess outcome for children with severe neurological impairment receiving invasive mechanical ventilation for respiratory failure.
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Upper and lower airway cultures in children with cystic fibrosis: do not neglect the upper airways.
J. Cyst. Fibros.
PUBLISHED: 01-04-2010
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Airways of cystic fibrosis (CF) patients are colonised with bacteria early in life. We aimed to analyse differences between results of simultaneously taken upper airway (UAW) and lower airway (LAW) cultures, to describe clinical characteristics of patients with positive versus negative cultures and to follow up the patients with P. aeruginosa positive UAW cultures.
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Respiratory pathogens in children with and without respiratory symptoms.
J. Pediatr.
PUBLISHED: 12-16-2009
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To investigate the occurrence of respiratory pathogens in samples from children with and without respiratory symptoms and to identify whether age and/ or coinfections modify the impact of respiratory pathogens on symptoms.
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Respiratory syncytial virus infection facilitates acute colonization of Pseudomonas aeruginosa in mice.
J. Med. Virol.
PUBLISHED: 10-27-2009
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Pseudomonas aeruginosa causes opportunistic infections in immunocompromised individuals and patients ventilated mechanically and is the major pathogen in patients with cystic fibrosis, in which it causes chronic infections. Epidemiological, in vitro and animal data suggest a role for respiratory virus infections in facilitating colonization and infection with P. aeruginosa. A study was undertaken to determine whether respiratory syncytial virus (RSV) infection could facilitate the initiation of an acute infection with P. aeruginosa in vivo. Balb/c mice were infected intranasally with P. aeruginosa, with and without simultaneous inoculation with RSV. Lung function measurements were undertaken using Whole Body Plethysmography and lungs were harvested 24 hr after inoculation. Mice exposed to RSV and P. aeruginosa showed 2,000 times higher colony-forming units (CFU) counts of P. aeruginosa in the lung homogenates when compared to mice which were only infected with P. aeruginosa and lung function changes were more severe in co-infected mice. Control mice receiving RSV alone showed no significant changes in lung function or cytokine production, and no inflammatory changes in the lung parenchyma. These results suggest that RSV can facilitate the initiation of acute P. aeruginosa infection without the RSV infection being clinically apparent. This could have implications for treatment strategies to prevent opportunistic P. aeruginosa lung infection.
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Pseudomonas aeruginosa genotype prevalence in Dutch cystic fibrosis patients and age dependency of colonization by various P. aeruginosa sequence types.
J. Clin. Microbiol.
PUBLISHED: 10-14-2009
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The patient-to-patient transmission of highly prevalent Pseudomonas aeruginosa clones which are associated with enhanced disease progression has led to strict segregation policies for cystic fibrosis (CF) patients in many countries. However, little is known about the population structure of P. aeruginosa among CF patients. The aim of the present cross-sectional study was to determine the prevalence and genetic relatedness of P. aeruginosa isolates from CF patients who visited two major CF centers in The Netherlands in 2007 and 2008. These patients represented 45% of the Dutch CF population. P. aeruginosa carriage in the respiratory tract was determined by standard microbiological culture techniques, and all phenotypically different isolates in the first specimens recovered in 2007 and 2008 were genotyped by multilocus sequence typing. A total of 313 (57%) of 551 patients whose samples were cultured carried P. aeruginosa. Two sequence types (STs), ST406 and ST497, were found in 15% and 5% of the patients, respectively, and 60% of the patients harbored a strain that was also found in at least two other patients. The risk ratios for carrying ST406 and ST497 were 17.8 (95% confidence interval [CI], 7.2 to 43.6) for those aged between 15 and 24 years and 6 (95% CI, 1.4 to 26.1) for those aged >25 years. ST406 and ST497 were not genetically linked to previously described epidemic clones, which were also not found in this CF population. The population structure of P. aeruginosa in Dutch CF patients is characterized by the presence of two prevalent STs that are associated with certain age groups and that are not genetically linked to previously described epidemic clones.
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Pharmacogenetics of anti-inflammatory treatment in children with asthma: rationale and design of the PACMAN cohort.
Pharmacogenomics
PUBLISHED: 08-12-2009
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To investigate the effects of genetic variation on treatment response to asthma medication in children and to identify (profiles of) SNPs that characterize response phenotypes.
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The impact of ambient NO on online measurements of exhaled and nasal NO: the PIAMA study.
Pediatr Allergy Immunol
PUBLISHED: 07-17-2009
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The guidelines of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) for standardized measurements of exhaled nitric oxide (NO) state that for online measurements the inhaled air should be free of NO. As it is not always possible to create an NO-free environment, inhalation through an NO-scrubber is used. To describe the relationship between ambient NO and measurements of fractional exhaled NO (FENO) and nasal NO (nNO) investigated according to the ATS-ERS guidelines in a large population of children. The present work makes use of data collected during the 8-yr follow-up of the Dutch PIAMA birth cohort study. FENO and nNO were measured in three hospitals in a total of 1005 children with a NIOX chemiluminescence analyser. In two hospitals, almost half of the measured ambient NO levels exceeded 5 p.p.b. Maximum levels were >100 p.p.b. in all hospitals. Despite its large variation, ambient NO did not have an effect on FENO, but it did have a significant impact on nNO in two of the three centres. The currently recommended technique including inhalation through an NO scrubber effectively deals with variable levels of ambient NO on FENO. In contrast, ambient NO has an effect on measurements of nNO.
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Respiratory pathogens in respiratory tract illnesses during the first year of life: a birth cohort study.
Pediatr. Infect. Dis. J.
PUBLISHED: 06-09-2009
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Respiratory virus infections are the most important trigger of respiratory illnesses in childhood. Data on the occurrence and the clinical impact of respiratory pathogens in the general population of infants are scarce. Therefore, we described the occurrence and clinical impact of respiratory pathogens in infants with respiratory tract infections during the first year of life.
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Respiratory symptoms in young infancy: child, parent and physician related determinants of drug prescription in primary care.
Pharmacoepidemiol Drug Saf
PUBLISHED: 04-29-2009
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Respiratory symptoms account for the majority of drug prescriptions in the first year of life. We investigated the influence of child, parent and physician factors on drug prescriptions for respiratory symptoms in primary care in infancy.
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Reduced neonatal lung function and wheezing illnesses during the first 5 years of life.
Eur. Respir. J.
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Studies of reduced neonatal lung function and wheezing illnesses during childhood show conflicting results. The aim of our study was to assess the association between resistance (Rrs) and compliance (Crs) of the respiratory system by using the single occlusion technique (SOT) and prospectively collected wheezing illnesses during the first 5 years of life in a large birth cohort. SOT was performed during natural sleep before the age of 2 months. Information about wheezing illnesses was collected from the electronic patient file. 549 infants had a successful SOT measurement and complete medical records. Every kPa·L(-1)·s(-1) increase in Rrs was associated with 10% more consultations in the first 3 years of life. Every 10 mL·kPa(-1) increase in Crs was associated with a 14% reduction in consultations in the first 3 years of life, 27% in the fourth to fifth years of life, and a lower probability of having asthma at the age of 5 years (OR 0.66). Children with late-onset or persistent wheezing had significant lower Crs values than their peers. An increased neonatal resistance is associated with more wheezing illnesses during infancy, while a reduced neonatal compliance is associated with more wheezing illnesses during the first 5 years of life, a late-onset or persistent wheezing phenotype, and asthma.
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Effects of Aspergillus fumigatus colonization on lung function in cystic fibrosis.
Curr Opin Pulm Med
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Aspergillus fumigatus is frequently isolated from cystic fibrosis (CF) patients and is notorious for its role in the debilitating condition of allergic bronchopulmonary aspergillosis (ABPA). Although CF patients suffer from perpetual microorganism-related lung disease, it is unclear whether A. fumigatus colonization has a role in causing accelerated lung function decline and whether intervention is necessary.
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Influence of obesity on nocturnal oxygen saturation in young children.
Eur. J. Pediatr.
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Obesity is increasing worldwide and it is accompanied by major health effects. In adults and school-aged children, obesity is associated with decreased respiratory function, which may lead to disturbed sleeping and subsequently difficulties in concentration and behavioural disorders. The evidence for the association between obesity and decreased respiratory function in younger children is scarce. To explore the association between body weight and nocturnal respiratory function in young children, 1 to 3 years old, nocturnal pulse oximetry was performed at home. Children with tonsillar hypertrophy were excluded. Percentage of time with oxygen saturation (SpO(2)) <95 % was measured and its association with body mass index (BMI) for age z scores was analysed. Pulse oximetric data of 51 children, including 18 children with a BMI for age above +2 standard deviations, were obtained for this study. Linear regression analysis, correction for gender and parental smoking, showed a positive association between the natural logarithm of SpO(2) <95 % and BMI for age z score [regression coefficient (?) 0.19, 95 % confidence interval 0.00-0.39]. Conclusion: In young children, higher body weight is associated with a decrease in nocturnal oxygen saturation.
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Azithromycin maintenance therapy in patients with cystic fibrosis: a dose advice based on a review of pharmacokinetics, efficacy, and side effects.
Pediatr. Pulmonol.
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Azithromycin maintenance therapy results in improvement of respiratory function in patients with cystic fibrosis (CF). In azithromycin maintenance therapy, several dosing schemes are applied. In this review, we combine current knowledge about azithromycin pharmacokinetics with the dosing schedules used in clinical trials in order to come to a dosing advise which could be generally applicable. We used data from a recently updated Cochrane meta analysis (2011), the reports of clinical trials and pharmacokinetic studies. Based on these data, it was concluded that a dose level of 22-30 mg/kg/week is the lowest dose level with proven efficacy. Due to the extended half-life in patients with CF, the weekly dose of azithromycin can be divided in one to seven dosing moments, depending on patient preference and gastro-intestinal tolerance. No important side effects or interactions with other CF-related drugs have been documented so far.
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Parental blood pressure is related to vascular properties of their 5-year-old offspring.
Am. J. Hypertens.
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Adolescent offspring of hypertensive parents have increased carotid intima media thickness (CIMT) and arterial stiffness compared with offspring of normotensives. We assessed whether systolic blood pressure (SBP) of both parents is associated with the vasculature of their offspring as early as in childhood.
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Excess early postnatal weight gain leads to increased abdominal fat in young children.
Int J Pediatr
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Background. Increased childhood weight gain has been associated with later adiposity. Whether excess early postnatal weight gain plays a role in childhood abdominal fat is unknown. Design. In the ongoing Wheezing Illnesses Study Leidsche Rijn (WHISTLER), birth cohort weight and length from birth to age 3 months were obtained. In the first 316 five-year-olds, intra-abdominal and subcutaneous fat were measured ultrasonographically. Individual weight and length gain rates were assessed in each child. Internal Z-scores of weight for length gain (WLG) were calculated. Multiple imputation was used to deal with missing covariates. Results. Per-1-unit increase in Z-score WLG from birth to 3 months, BMI, waist circumference, and subcutaneous fat were significantly higher; 0.51?kg/m(2), 0.84?cm, and 0.50?mm, respectively. After multiple imputation, a trend towards significance was observed for intra-abdominal fat as well (0.51?mm/SD). In the associations with 5-year adiposity, no interaction between postnatal Z-score WLG and birth size was found. Conclusion. Excess early postnatal weight gain is associated with increased general and central adiposity, characterized by more subcutaneous and likely more intra-abdominal fat at 5 years of age.
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Exhaled NO is a poor marker of asthma control in children with a reported use of asthma medication: a pharmacy-based study.
Pediatr Allergy Immunol
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A high fraction of nitric oxide in exhaled breath (FeNO) has been suggested to be a marker of ongoing airway inflammation and poorly controlled disease in asthma. The usefulness of FeNO to monitor asthma control is still debated today.
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Early life lung function and respiratory outcome in the first year of life.
Eur. Respir. J.
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Abnormal early life lung function is related to wheezing in childhood; however, data on the association with cough are not available. We determined the relationship between early life lung function and wheeze and cough during the first year of life, adjusted for other possible risk factors. Infants were participants of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function measurements were performed before the age of 2 months. Information on pre- and perinatal factors, general characteristics and anthropometrics were assessed by questionnaires. Follow-up data on respiratory symptoms were assessed by daily questionnaires. 836 infants had valid lung function measurements and complete follow-up data for respiratory symptoms at 1 yr of age. Multivariable Poisson analysis showed that higher values of respiratory resistance (R(rs)) and time constant (?(rs)) were associated with an increased risk for wheeze and cough during the first year of life. Higher values of respiratory compliance (C(rs)) were associated with a decreased risk for wheeze and cough. R(rs), C(rs) and ?(rs) measured shortly after birth were independently associated with wheeze and cough during the first year of life. As the strength of the relationships were different for wheeze and cough, they should be used as two separate entities.
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PPAR? as a therapeutic target in cystic fibrosis.
Trends Mol Med
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Cystic fibrosis (CF) is characterized by a proinflammatory pulmonary condition that may result from increased infections and altered intracellular metabolism in CFTR-deficient cells. The lipid-activated transcription factor peroxisome proliferator-activated receptor-? (PPAR?) has well-established roles in immune cell function and inflammatory modulation and has been demonstrated to play an important role in the heightened inflammatory response in CF cells. Here, we summarize current literature describing PPAR?-dependent alterations of CF cells and discuss the potential of PPAR? ligands for treating CF.
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Effect of endotoxin and allergens on neonatal lung function and infancy respiratory symptoms and eczema.
Pediatr Allergy Immunol
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Exposure to endotoxin and allergens in house dust has been found to be associated with childhood wheeze and asthma. Neonatal lung function is rarely examined in relation to this exposure.
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A prediction rule for food challenge outcome in children.
Pediatr Allergy Immunol
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In children with food-related symptoms, a food challenge is considered as the gold standard to diagnose allergy. If food allergy could be predicted by patient history and/or diagnostic tests, the number of time-consuming and sometimes risky food challenges could be decreased. We aimed to determine questionnaire and test-based characteristics, to predict the food challenge outcome (FCO) in children referred to a tertiary centre for the evaluation of food-related symptoms.
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Risk factors for Mycobacterium abscessus infection in cystic fibrosis patients; a case-control study.
J. Cyst. Fibros.
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Mycobacterium abscessus is a nontuberculous mycobacterium that is increasingly recognized as an opportunistic pathogen in cystic fibrosis (CF) patients. Factors that predispose CF patients to infection by this environmental bacterium remain unknown. In a case-control study of 22 CF patients with M. abscessus infection and 22 CF controls, we investigated risk factors for MAB infection as well as the positioning of MAB infection in relation to the other pathogens infecting CF patients. No clear risk factors were found; steroid treatment and CF related diabetes were equally common among cases and controls. M. abscessus disease affects CF patients of varying age, lung function and co-morbidities. Antimicrobial maintenance therapy did not prevent M. abscessus infection. A history of Stenotrophomonas maltophilia infection was significantly more frequent among cases than among controls and there may be a relation with Aspergillus fumigatus infection, or both may be signs of advanced lung damage that predisposes to MAB disease. The absence of clear risk factors and the omnipresence of MAB in the environment suggest that MAB infection in CF patients is a random event. Its symptoms and impact on lung function seem to warrant treatment.
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