Objectives 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. Study design In a prospective longitudinal study, 18 children were sampled biweekly for respiratory pathogens, irrespective of respiratory symptoms. Polymerase chain reaction was performed for 13 respiratory pathogens. Episodes were defined “asymptomatic” if no symptoms of any respiratory tract illness were present between 1 week before and 1 week after sampling. Results A total of 230 samples were collected. In 56% of the symptomatic episodes, a pathogen was detected, compared with 40% of the asymptomatic episodes ( P = .03). Rhinovirus and coronaviruses were most prevalent in both symptomatic and asymptomatic episodes. In the youngest children, 9% of the pathogen-positive episodes were asymptomatic, compared with 36% in the oldest children ( P = .01). Multiple pathogens were found in 17% of the symptomatic episodes and in 3% of the asymptomatic episodes ( P = .02). Conclusions Respiratory pathogens are frequently detected in samples from children with no respiratory symptoms. Symptomatic cases occurred more often in younger children and with detections of more than 1 respiratory pathogen.
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.
A. fumigatus morbidity appears to be related to cystic fibrosis transmembrane conductance regulator-dependant function of the innate immune system. A. fumigatus-colonized patients have a lower lung capacity, more frequent hospitalizations and more prominent radiological abnormalities than noncolonized patients. Treatment with antifungal agents can be of value but has several drawbacks and a direct effect on lung function is yet to be shown.
A. fumigatus appears to have an important role in CF lung disease, not exclusive to the context of ABPA. However, a causal relationship still needs to be confirmed. Study observations and trends indicate a need to further elucidate the mechanisms of A. fumigatus interactions with the host innate immune system and its role in CF lung morbidity.
Different forms of dyadic coping are associated with positive outcomes in partner relationships, yet little is known about dyadic coping in parent-child relationships. The current research explored ...the association between parent-child dyadic coping and children’s quality of life in 12–18-year old children with a chronic disease (i.e., cystic fibrosis, autoimmune diseases, and children post-cancer treatment). In a sample of 105 parent-child dyads, self-reported forms of dyadic coping (i.e., stress communication, problem-oriented, emotion-oriented, and negative dyadic coping) and children’s quality of life were assessed. Children reported more stress communication and negative dyadic coping than their parents, while parents reported more problem-oriented dyadic coping and emotion-oriented dyadic coping than their children. More stress communication of the child was associated with more emotion-oriented dyadic coping and less negative dyadic coping of the parent. More negative dyadic coping of the child was associated with less stress communication, problem-oriented dyadic coping and emotion-oriented dyadic coping of the parent. Additionally, both children’s and parents’ negative dyadic coping were associated with lower self-reported pediatric quality of life and parents’ emotion-oriented dyadic coping was associated with higher pediatric quality of life. These findings emphasize that children and their parents mutually influence each other and that dyadic coping is associated with children’s quality of life. Theoretical and practical implications are discussed.
Background
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.
Methods
A retrospective study of children with a negative DBPCFC for peanut was performed. During follow‐up after DBPCFC, parents were systematically interviewed about the current diet, symptoms and problems during reintroduction, and reactions to peanut after the reintroduction period. Successful reintroduction was defined as eating peanut or products containing peanut as ingredient on a regular basis.
Results
Follow‐up data were obtained in 103 children with a negative peanut challenge. In 70 (68%) children, reintroduction was successful (54 children tolerated peanut, 16 children tolerated peanut as ingredient). Reintroduction failed in 33 (32%) children. Food refusal (45%) and peanut‐related symptoms (33%) were the most reported reasons. Risk factors for reintroduction failure were an elimination diet for more than three other foods (p = 0.019), a long elimination diet for peanut (p = 0.048) and peanut‐related symptoms at home (p = 0.002).
Conclusion
Reintroduction failure is a common problem in children after negative peanut challenge. To guide reintroduction and identify potential peanut‐related symptoms at home, careful follow‐up after negative DBPCFC is advised. When symptoms occur or persist, food challenge outcome needs to be reconsidered.
Display omitted
•Adolescents with various chronic diseases show enhanced aortic stiffness.•Enhanced aortic stiffness is associated with decreased LVGLS in these adolescents.•This may reflect adverse ...arterioventricular interaction.•Whether this impacts long-term cardiovascular outcomes requires further study.•Our data underscore the need for tailored cardiovascular follow-up programs.
The recent Cardiovascular Disease in Adolescents with Chronic Disease (CDACD) study showed enhanced aortic stiffness and wall thickness in adolescents with various chronic disorders. Enhanced aortic stiffness can increase left ventricular (LV) afterload and trigger a cascade of adverse arterioventricular interaction. Here, we investigate the relation between aortic changes and LV function in the CDACD study participants.
This cross-sectional study included 114 adolescents 12–18 years old with cystic fibrosis (CF, n = 24), corrected coarctation of the aorta (CoA, n = 25), juvenile idiopathic arthritis (JIA, n = 20), obesity (n = 20), and healthy controls (n = 25). Aortic pulse wave velocity (PWV), which reflects aortic stiffness, and aortic wall thickness (AWT) were assessed with cardiovascular magnetic resonance imaging (CMR). Echocardiography was employed to study conventional markers of LV function, as well as LV global longitudinal strain (LVGLS), which is an established (pre)clinical marker of LV dysfunction.
First, aortic PWV and AWT were increased in all chronic disease groups, compared to controls. Second, in adolescents with CoA, JIA, and obesity, echocardiography showed a decreased LVGLS, while LV dimensions and conventional LV function markers were similar to controls. Third, multivariable linear regression identified aortic PWV as the most important determinant of their decreased LVGLS (standardized β −0.522, p < 0.001).
The decreased LVGLS in several adolescent chronic disease groups was associated with enhanced aortic PWV, which might reflect adverse arterioventricular interaction. Whether the decreased LVGLS in the chronic disease groups could negatively impact their long-term cardiovascular outcomes requires further study.
Women with polycystic ovary syndrome (PCOS) have compromised cardiovascular health profiles and an increased risk of pregnancy complications. In order to evaluate potential consequences, we aim to ...compare the cardiovascular and metabolic health of the children from women with PCOS with a population-based reference cohort. We included children from women with PCOS between the age of 2.5 to 4 years (n = 42) and 6 to 8 years (n = 32). The reference groups consisted of 168 (3-4 years old) and 130 children (7-8 years old). In an extensive cardiovascular screening program, we measured anthropometrics and blood pressure (all children), heart function and vascular rigidity (young children), metabolic laboratory assessment and carotid intima thickness (old age-group). Results showed that young PCOS offspring have a significantly lower diastolic blood pressure (β = 2.3 95% confidence interval, CI: 0.5-4.0) and higher aortic pulse pressure (β = −1.4 95% CI: −2.5 to −0.2), compared to the reference population. Furthermore, a higher left ventricle internal diameter but a lower tissue Doppler imaging of the right wall in systole compared to the reference group was found. Older offspring of women with PCOS presented with a significantly lower breast and abdominal circumference, but higher triglycerides (β = −0.1 95% CI: −0.2 to −0.1), LDL-cholesterol (β = −0.4 95% CI: −0.6 to −0.1), and higher carotid intima-media thickness (β = −31.7 95% CI: −46.6 to −16.9) compared to the reference group. In conclusion, we observe subtle but distinct cardiovascular and metabolic abnormalities already at an early age in PCOS offspring compared to a population-based reference group, despite a lower diastolic blood pressure, breast, and abdominal circumference. These preliminary findings require confirmation in independent data sets.
Background Adolescents with chronic disease are often exposed to inflammatory, metabolic, and hemodynamic risk factors for early atherosclerosis. Since postmortem studies have shown that ...atherogenesis starts in the aorta, the CDACD (Cardiovascular Disease in Adolescents with Chronic Disease) study investigated preclinical aortic atherosclerosis in these adolescents. Methods and Results The cross-sectional CDACD study enrolled 114 adolescents 12 to 18 years old with chronic disorders including juvenile idiopathic arthritis, cystic fibrosis, obesity, corrected coarctation of the aorta, and healthy controls with a corrected atrial septal defect. Cardiovascular magnetic resonance was used to assess aortic pulse wave velocity and aortic wall thickness, as established aortic measures of preclinical atherosclerosis. Cardiovascular magnetic resonance showed a higher aortic pulse wave velocity, which reflects aortic stiffness, and higher aortic wall thickness in all adolescent chronic disease groups, compared with controls (
<0.05). Age (β=0.253), heart rate (β=0.236), systolic blood pressure (β=-0.264), and diastolic blood pressure (β=0.365) were identified as significant predictors for aortic pulse wave velocity, using multivariable linear regression analysis. Aortic wall thickness was predicted by body mass index (β=0.248) and fasting glucose (β=0.242), next to aortic lumen area (β=0.340). Carotid intima-media thickness was assessed using ultrasonography, and was only higher in adolescents with coarctation of the aorta, compared with controls (
<0.001). Conclusions Adolescents with chronic disease showed enhanced aortic stiffness and wall thickness compared with controls. The enhanced aortic pulse wave velocity and aortic wall thickness in adolescents with chronic disease could indicate accelerated atherogenesis. Our findings underscore the importance of the aorta for assessment of early atherosclerosis, and the need for tailored cardiovascular follow-up of children with chronic disease.
Growing up with a chronic disease comes with challenges, such as coping with fatigue. Many adolescents are severely fatigued, though its associated factors exhibit considerable interpersonal and ...longitudinal variation. We assessed whether PROfeel, a combination of a smartphone-based ecological momentary assessment (EMA) method using the internet, followed by a face-to-face dialogue and personalized advice for improvement of symptoms or tailor treatment based on a dynamic network analysis report, was feasible and useful.
Feasibility study in fatigued outpatient adolescents 12–18 years of age with cystic fibrosis, autoimmune disease, post-cancer treatment, or with medically unexplained fatigue. Participants were assessed at baseline to personalize EMA questions. EMA was conducted via smartphone notifications five times per day for approximately six weeks. Hereby, data was collected via the internet. The EMA results were translated into a personalized report, discussed with the participant, and subsequently translated into a personalized advice. Afterwards, semi-structured interviews on feasibility and usefulness were held.
Fifty-seven adolescents were assessed (mean age 16.2 y ± 1.6, 16% male). Adolescents deemed the smartphone-based EMA feasible, with the app being used for an average of 49 days. Forty-two percent of the notifications were answered and 85% of the participants would recommend the app to other adolescents. The personalized report was deemed useful and comprehensible and 95% recognized themselves in the personalized report, with 64% rating improved insight in their symptoms and subsequent steps towards an approach to reduce one's fatigue as good or very good.
PROfeel was found to be highly feasible and useful for fatigued adolescents with a chronic condition. This innovative method has clinical relevance through bringing a patient's daily life into the clinical conversation.
•Fatigued adolescents with a chronic condition could use insight in their symptoms.•Fatigue and associated factors were measured via ecological momentary assessments.•Data were analyzed with dynamic network analyses, leading to personalized feedback.•This combination of assessment and feedback (PROfeel), was feasible and useful.•This innovative method brings a patient's daily life into the clinical conversation.
Cystic fibrosis (CF) is a rare hereditary disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (
) gene. Recent therapies enable effective restoration of CFTR ...function of the most common F508del
mutation. This shifts the unmet clinical need towards people with rare
mutations such as nonsense mutations, of which G542X and W1282X are most prevalent. CFTR function measurements in patient-derived cell-based assays played a critical role in preclinical drug development for CF and may play an important role to identify new drugs for people with rare
mutations.
Here, we miniaturised the previously described forskolin-induced swelling (FIS) assay in intestinal organoids from a 96-well to a 384-well plate screening format. Using this novel assay, we tested CFTR increasing potential of a 1400-compound Food and Drug Administration (FDA)-approved drug library in organoids from donors with W1282X/W1282X
nonsense mutations.
The 384-well FIS assay demonstrated uniformity and robustness based on coefficient of variation and Z'-factor calculations. In the primary screen, CFTR induction was limited overall, yet interestingly, the top five compound combinations that increased CFTR function all contained at least one statin. In the secondary screen, we indeed verified that four out of the five statins (mevastatin, lovastatin, simvastatin and fluvastatin) increased CFTR function when combined with CFTR modulators. Statin-induced CFTR rescue was concentration-dependent and W1282X-specific.
Future studies should focus on elucidating genotype specificity and mode-of-action of statins in more detail. This study exemplifies proof of principle of large-scale compound screening in a functional assay using patient-derived organoids.
Epithelial ion and fluid transport studies in patient-derived organoids (PDOs) are increasingly being used for preclinical studies, drug development and precision medicine applications. Epithelial ...fluid transport properties in PDOs can be measured through visual changes in organoid (lumen) size. Such organoid phenotypes have been highly instrumental for the studying of diseases, including cystic fibrosis (CF), which is characterized by genetic mutations of the CF transmembrane conductance regulator (CFTR) ion channel. Here we present OrgaSegment, a MASK-RCNN based deep-learning segmentation model allowing for the segmentation of individual intestinal PDO structures from bright-field images. OrgaSegment recognizes spherical structures in addition to the oddly-shaped organoids that are a hallmark of CF organoids and can be used in organoid swelling assays, including the new drug-induced swelling assay that we show here. OrgaSegment enabled easy quantification of organoid swelling and could discriminate between organoids with different CFTR mutations, as well as measure responses to CFTR modulating drugs. The easy-to-apply label-free segmentation tool can help to study CFTR-based fluid secretion and possibly other epithelial ion transport mechanisms in organoids.
PDF
