CF Children Research Articles

P156 Effects of lumacaftor/ivacaftor in CF children 2–6 years old: a case series

P156 Effects of lumacaftor/ivacaftor in CF children 2–6 years old: a case series

WS12.02 Erythrocyte essential fatty acid status and its association with breastfeeding, growth and early-onset lung disease in young children with cystic fibrosis

Objectives: Few studies have reported essential fatty acid (EFA) abnormalities, such as linoleic acid (LA,18:2n-6), linolenic acid (LN, 18:3n-3), and the pathological triene/tetraene (T/T) ratio, in very young children with CF. Additionally, little is known regarding docosahexaenoic acid (DHA, 22:6n-3) in the CF population. Our objectives are to characterize EFA profile and test the hypothesis that EFA insufficiency (EFAI) and deficiency (EFAD) are associated with suboptimal growth and early-onset lung disease in CF children in the first 3 years (yr) of life.

P171 Clinical experience with the introduction of a programme with CFTR modulators in a paediatric cystic fibrosis centre in Poland - a preliminary report

In 2022, Poland joined the elite group of countries where CFTR modulators (mCFTR) are reimbursed. The aim of this prospective study was the analysis of selected nutritional and pulmonary function parameters and their impact on patient health-related quality of life in CF children before and 3 months after the introduction of mCFTR therapy.

P384 Smoking prevalence in cystic fibrosis families is higher than in the Greek general population

Smoking has detrimental effects on lung health, especially in patients with chronic lung diseases. Recent studies have shown that CFTR mutation carriers that smoke are more likely to develop COPD. There is also evidence that smoking decreases CFTR function and interferes with the effectiveness of new CFTR modulators. The aim of the study was to determine how prevalent smoking is in parents of CF children and compare it to smoking prevalence in Greece.

Variability of the sweat test in children with Cystic Fibrosis previously CRMS/CFSPID: A retrospective monocenter experience

Some studies have evaluated the sweat test (ST) intra individual variability in CRMS/CFSPID. Here, we retrospectively evaluated this in a cohort followed at the CF center in Florence, Italy. We enrolled 37 CRMS/CFSPID and 37 CF children, born between 2011 and 2019. A total of 327 ST were retrospectively recovered, of which 17 (5.2%) were quantity not sufficient. After a median follow-up of 33.8 months (range 1.7–88.2), 11 (24.3%) became CF with at least two pathological sweat chloride (SC) values at a median age of 46.9 months (range 1.4–49). The coefficient of variation was 6.2% in CF patients and 32.5% in the CRMS/CFSPID that transitioned to CF (P<.001). Our data highlight a more variability of SC values in CRMS/CFSPID, especially in those that transitioned to a diagnosis of CF. Further studies are needed to understand whether it is correct to define an asymptomatic CRMS/CFSPID with pathological SC as CF.

Bacterial profile in children with early childhood caries

Early Childhood Caries (ECC) is the most common chronic infectious disease of childhood in the world, caused by the interaction of the host (oral cavity), substrate, microbes, and time. Bacteria as microbes that play a role in the formation of ECC have been widely studied. This study aims to determine the bacterial profile in children with ECC and to compare the oral microbial profiles in children with ECC and caries-free children (CF). Methods: This study uses a scoping review method. Article searches were performed on the PubMed, Science Direct, Cochrane, and Google Scholar databases, using the keyword and Boolean operator "(early childhood caries) AND (profile bacterial OR bacterial) AND (children)." The initial search obtained 1356 articles. All articles were then selected according to the inclusion and exclusion criteria using the PRISMA procedure to receive 14 articles. Results: Analysis of 14 articles showed that 11 articles reported that Streptococcus mutans had high levels of ECC in children. Other bacteria with lesser numbers were Provetella, Veillonella, S. wiggsae, S. sobrinus, Lactobacillus, Leptrotrichia shahii, and Leptrotrichia IK04. Neisseria, Streptococcus mitis, Streptococcus salivarius, and Leptotrichia buccalis were found in CF children. Other bacteria such as Hemophilus paraphrohaemolyticus HK411, Neisseria sicca 4320, Neisseria sp. oral clones AP132, Actinobacillus pleuro-pneumoniae MCCM 00189, and Streptococcus sp. ASCE06 oral clone was found in CF children but not in ECC children, while Lactobacillus sp C56 was found in half of ECC children and not in CF children. Conclusion: Streptococcus mutans levels in children with ECC are high, so they are assumed to be the main bacteria causing ECC. The bacterial profiles of ECC and CF children are different in species diversity. KEYWORDS: Early Childhood Caries, Bacterial, Children

Biofilm accumulation and sucrose rinse modulate calcium and fluoride bioavailability in the saliva of children with early childhood caries

This study aimed at investigating the combined effect of biofilm accumulation and 20% sucrose rinse on the modulation of calcium (Ca2+), phosphate (Pi), and fluoride (F−) bioavailability in the saliva of children with early childhood caries (ECC). Fifty-six preschoolers of both genders were evaluated according to caries experience and activity: caries-free (CF, n = 28) and with ECC (n = 28) and then, submitted to biofilm intervention (biofilm accumulation). In each situation, saliva samples were collected before and five minutes after a 20% sucrose rinse to determine the concentrations of Ca2+, Pi, and F−. Calcium concentration was significantly lower in the biofilm accumulation situation compared to the situation of biofilm mechanical control (p ≤ 0.01), except for CF children after sucrose rinse. Biofilm accumulation increased salivary calcium concentration in children with ECC after sucrose rinse (p = 0.04), whereas mechanical biofilm control reduced it in both groups (p = 0.000). Phosphate concentration was influenced by mechanical control of biofilm in CF children (p = 0.03). The fluoride bioavailability was reduced by sucrose rinse and biofilm accumulation in CF and ECC children (p ≤ 0.002). In conclusion, the combined effect of biofilm accumulation and sucrose rinse modifies the bioavailability of calcium and fluoride in the saliva of children with early childhood caries.

Advanced but not mild liver disease is a predictor of decreased survival in children with cystic fibrosis, with far greater impact in females: A 27-year real-life cohort study

BackgroundImproved survival of children with CF has increased our need to understand the relevance of cystic fibrosis-associated liver disease (CFLD). We assessed the impact of liver disease and disease severity on the survival of children with cystic fibrosis. MethodsA real life, single center cohort study with 27 years follow up was conducted. Mild CFLD was diagnosed as children with abnormal serum liver function tests and abnormal ultrasound. Advanced CFLD was established by detection of cirrhosis or portal hypertension. A directed acyclic graph, Kaplan-Meier (KM) and Cox regression analysis were used to model survival. Results290 patients were enrolled, 48 (16.5%) had mild CFLD and 55 (19%) had advanced CFLD. Ten children with advanced CFLD and 1 with mild CFLD died. Based on the KM analysis, the mean (SE) overall survival age of all CF children was 29.1 years (0.50). The mean (SE) survival among females with advanced CFLD was 24.7 years (1.58) compared to 30.4 years (0.66) for females without advanced CFLD (p = 0.0027). Advanced CFLD was a predictor of decreased survival when adjusted for sex and diabetes (HR 2.54, 95%CI 1.05–6.15, p = 0.039). Mild CFLD was not associated with decreased survival. The effect of advanced CFLD on survival was mainly borne by females (HR = 6.37, 95%CI 1.62–25.06 vs. males, HR = 1.00, 95%CI 0.25–4.01). ConclusionAdvanced but not mild CFLD was associated with an increased risk of death when adjusted for sex and diabetes, and resulted in premature death in females with cystic fibrosis by approximately 6 years.

211: Heterogeneous ultrasound predicts high risk for the development of advanced liver disease in CF children: Final results of PUSH study

211: Heterogeneous ultrasound predicts high risk for the development of advanced liver disease in CF children: Final results of PUSH study

The role of mechanical control of biofilm in the salivary pH after sucrose exposure in children with early childhood caries

This quasi-experimental study sought to investigate if the mechanical control of biofilm (3-times-a-day) modifies the saliva’s ability to buffer the oral environment after 20% sucrose rinse (SR20%) in children with early childhood caries (ECC). Here, SR20% reduced the saliva’s pH in both groups and the mechanical control of biofilm had a greater effect on this parameter after SR20% in CF children. The mechanical control of biofilm evidenced a higher buffering capacity in CF children before SR20%, which was not observed after SR20%. Otherwise, the absence of mechanical control of biofilm showed that buffering capacity was comparable in the two groups before SR20%, whereas after SR20% the saliva’s buffering capacity of CF children was higher than ECC children. When biofilm was mechanically controlled, carbonic anhydrase VI activity did not change after SR20% whereas the absence of mechanical control of biofilm reduced this enzyme activity after SR20%. In conclusion, the mechanical control of biofilm did not change saliva’s ability to buffer the oral environment after SR20% in children with ECC. On the other hand, CF children appeared to regulate more effectively the saliva’s pH than ECC children while the absence of mechanical control of biofilm mediated their pH-modifying ability after SR20%.

An Increasing “Heavy” Burden: Child Obesity and Overweight

Introduction: Cystic fibrosis is a genetic condition with potential severe metabolic disturbances, with a high morbidity and mortality. We report the rates of liver damage( steatosis) and diabetes in Algerian children with cystic fibrosis, at diagnosis and during follow-up. Patients and methods: A cross-sectional, descriptive and retrospective study was carried out at the pneumo-allergology department at Canastel Hospital, Oran (Algeria) from 2000 to 2019 , encompassing all patients with a confirmed diagnosis of cystic fibrosis. Results: 51 patients files were collected (49% boys, mean age= 6.68 +/- 4.24 years) At admission, 10% of the children presented with clinical hepatomegaly and 14% had an increased liver volume on ultrasounds. Simultaneously, 6% of the CF children presented a hypertransaminasemia. During the follow- up, there were new cases of ultrasound-detected hepatomegaly (21.56%) and of elevated transaminases (9.8%). One case of diabetes associated with cystic fibrosis appeared in a 16- year-old boy. There was no pancreatitis reported in our cohort.Conclusion: Metabolic disorders are at the forefront in CF. In our Algerian pediatric cohort, more than one fifth of patients depicted at least one feature of hepatic steatosis. Diabetes occurred in only one adolescent patient (1.96%). Prompt recognition and nutritional management are essential steps to improve the “metabolic prognosis” of such high risk population.

IgA autoantibodies directed against self DNA are elevated in cystic fibrosis and associated with more severe lung dysfunction

Although extracellular host DNA (ecDNA) levels in CF airways were linked to airflow obstruction and recombinant DNAse therapy is beneficial for CF patients, it remains incompletely understood whether ecDNA also leads to an autoimmune response. Here we hypothesized that chronic presence of DNA in CF airways triggers the production of autoantibodies targeting host human DNA. We measured the levels of IgA autoantibodies recognising host double-stranded (ds) DNA in the blood and sputum samples of CF patients and only sera of controls subjects and patients suffering from rheumatoid arthritis and systemic lupus erythematosus (SLE) that served as non-CF, autoimmune disease cohorts. We found that concentrations of anti-dsDNA IgA, but not IgG, autoantibodies in the circulation were significantly elevated in adult CF patients compared to age-matched, control subjects. Systemic levels of anti-dsDNA IgA antibodies negatively correlated with FEV1% predicted, a measure of lung function, in CF patients. Anti-dsDNA IgA autoantibodies were also detected in CF sputa but sputum levels did not correlate with the degree of airway obstruction or sputum levels of DNA. We also found elevated autoantibody levels in CF children as 76.5% of CF patients younger than 10 years and 87.5% of CF patients 10–21 years had higher blood anti-dsDNA IgA levels than the highest value found in healthy control adults. Overall, our results detect elevated systemic anti-dsDNA IgA autoantibody levels in CF adults, teenagers and young children. We speculate that the appearance of an autoimmune response against host DNA in CF is an early event potentially contributing to disease pathogenesis. Highlights CF serum contains elevated levels of anti-dsDNA IgA, but not anti-dsDNA IgG, autoantibodies Anti-dsDNA IgA autoantibody levels in serum correlate with airflow obstruction in CF Anti-dsDNA IgA autoantibodies are detected in CF sputum but do not correlate with airflow obstruction Anti-dsDNA IgA autoantibodies are also elevated in the blood of the majority of CF toddlers and youth

Does synbiotic supplementation affect the quality of life in children with cystic fibrosis? A pilot randomized controlled clinical trial

BackgroundThere is no clinical trial that assesses the effect synbiotic supplementation on HRQOL in CF children. Considering the importance of HRQOL as an essential primary outcome and determinant of therapeutic benefit in chronic diseases like cystic fibrosis, the present clinical trial aimed to determine the efficacy of synbiotic supplementation on HRQOL in children with CF.MethodsIn the present double-blind randomized clinical trial, 40 CF children were randomly allocated to the two groups. The intervention group was supplemented with synbiotics supplements and the patients in the placebo group received maltodextrin for 6 months. Demographic data and information about antibiotic use were recorded using the questionnaire. The health-related quality of life was assessed using the Persian version of quality of life inventory questionnaires. Paired t-test and ANCOVA were used for statistical analysis.ResultsTotally, 36 participants completed the trial. The mean score of HRQOL was 76.34 ± 17.33. There were no significant differences between synbiotic and placebo groups regarding baseline demographic and quality of life characteristics. Compared with baseline values, the mean total score and subscores of quality of life did not change significantly after synbiotic and placebo supplementation (p > 0.05). Moreover, the results of ANCOVA showed that there were no significant differences between the two groups regarding the post-trial value of HRQOL total score and subscores.ConclusionAccording to results, six-month supplementation with synbiotic did not have a significant effect on the HRQOL in children with CF. However, further studies with larger sample sizes and using more disease-specific questionnaires are needed for a more precise conclusion.The protocol of the study was registered at Iranian registry clinical trials (Registration code: IRCT2017011732004N1; Registration date: 2017-02-14).

Quality of Life for Children with Cystic Fibrosis in Gaza Strip

Background: CF is a chronic, multisystem genetic disease with a wide variability in clinical severity. CF is a disease of exocrine gland function that involves multiple organ systems but chiefly results in chronic respiratory infections, pancreatic enzyme insufficiency, and associated complications in untreated patients. Many studies explained the lower QOL among adults with CF. in GS there is no previous studies concerned with measuring QOL among CF children Aim of the Study: The aim of this study was to assess the QOL among children with CF. Methodology: The study was descriptive, analytical and cross sectional studies. The study involves all 36 children with CF (less than 12 years old) who attained CF friends center; community based center in Gaza. The researchers uses the questionnaire which included demographic &amp; illness related variables and Quality of life domains (physical, emotional, social and school). Reliability coefficient for the questionnaire was good (Cronbach alpha =0.833). Results and Conclusion: About 61% of the study population were males and 39% were females. Approximately 47% of them were less than 9 years and 53% were more than 9 years. About 41.7% of the study population from Gaza, 25.0% from middle zone, 13.9% from Rafah, 11.1% from Khanyounis and 8.3% from North of Gaza. Housing classification was 38.9%, 33.3% and 27.8 % for property house, renting house and family house respectively. Most of their parents had low educational levels and the majority of them were unemployed and have a monthly income less than 1200 NIS. About 61% of them have another sibling with CF. the majority of them receive Creon at a regular basis. The most common disease associated with them was Respiratory problem with 43.2%, 38.3% had gastrointestinal disease, 14.8% had heart disease and 3.7% had Diabetes Mellitus. The overall perception of the children regarding QOL was low (55%). The social functions was the highest (61.6%), physical functions (55.2%), school function (50.6%), and emotional function (48.8%). The result presented below show that no significant difference in QOL between socio-demographic data (p-value &gt; 0.05) except the difference for QOL between age groups) p-value =0.001). Children older than 9 years old (2.95±0.3) have QOL more than children under nine years of age (2.53±0.4) and this difference was statistically significant as (P value = 0.02 &lt; 0.05). It is also clear that QOL in males are more than female but this difference was not statistically significant. There is a positive correlation with a highly significant difference between QOL and the 4 domains and between domains with each other. Social performance was high correlated with school performance (r = 0.706) while the lowest correlation was between physical and school performance with no significant (p-value =0.065). Recommendations: The study recommend the importance of initiating a program to enhance the QOL for children with CF and focusing on the emotional health for those children as it was the least one perceived.

Fibrocyte accumulation in the lungs of cystic fibrosis patients

BackgroundCystic fibrosis (CF) patients develop severe lung disease including chronic airway infections, neutrophilic inflammation, and progressive fibrotic remodeling in airways. However, cellular and molecular processes that regulate excessive collagen deposition in airways in these patients remain unclear. Fibrocytes are bone marrow (BM)-derived mesenchymal cells that express the hematopoietic cell marker CD45, and mesenchymal cell markers and implicated in collagen deposition in several fibrotic diseases. It is unknown whether fibrocytes accumulate in the lungs of CF patients, so the current study evaluates the presence of fibrocytes in the fibrotic lesions of airways in explanted CF lungs compared to non-CF unused donor lungs (control). MethodsWe used immunofluorescence staining to determine if fibrocytes accumulate in explanted CF lungs compared to healthy donor lungs. Simultaneously, we evaluated cells collected by bronchoalveolar lavage (BAL) in CF patients using multi-color flow cytometry. Finally, we analyzed transcripts differentially expressed in fibrocytes isolated from the explanted CF lungs compared to control to assess fibrocyte-specific pro-fibrotic gene networks. ResultsOur findings demonstrate fibrocyte accumulation in CF lungs compared to non-CF lungs. Additionally, fibrocytes were detected in the BAL of all CF children. Transcriptomic analysis of fibrocytes identified dysregulated genes associated with fibrotic remodeling in CF lungs. ConclusionsWith significantly increased fibrocytes that show increased expression of pro-fibrotic gene transcripts compared to control, our findings suggest an intervention for fibrotic remodeling as a potential therapeutic target in CF.

Metabolomics profiling of tobacco exposure in children with cystic fibrosis

BackgroundInflammation is integral to early disease progression in children with CF. The effect of modifiable environmental factors on infection and inflammation in persons with CF is poorly understood. Our prior studies determined that secondhand smoke exposure (SHSe) is highly prevalent in young children with CF. SHSe is associated with increased inflammation, heightened bacterial burden, and worsened clinical outcomes. However, the specific metabolite and signaling pathways that regulate responses to SHSe in CF are relatively unknown. MethodsHigh-resolution metabolomics was performed on plasma samples from infants (n = 25) and children (n = 40) with CF compared to non-CF controls (n = 15). CF groups were stratified according to infant or child age and SHSe status. ResultsGlobal metabolomic profiles segregated by age and SHSe status. SHSe in CF was associated with changes in pathways related to steroid biosynthesis, fatty acid metabolism, cysteine metabolism, and oxidative stress. CF infants with SHSe demonstrated enrichment for altered metabolite localization to the small intestine, liver, and striatum. CF children with SHSe demonstrated metabolite enrichment for organs/tissues associated with oxidative stress including mitochondria, peroxisomes, and the endoplasmic reticulum. In a confirmatory analysis, SHSe was associated with changes in biomarkers of oxidative stress and cellular adhesion including MMP-9, MPO, and ICAM-1. ConclusionsSHSe in young children and infants with CF is associated with altered global metabolomics profiles and specific biochemical pathways, including enhanced oxidative stress. SHSe remains an important but understudied modifiable variable in early CF disease.

Sleep disturbance and sleep insufficiency in primary caregivers and their children with cystic fibrosis

BackgroundChronically ill children and their parents are at risk for sleep disorders and associated morbidity. Sleep disturbance prevalence and the relationships between parent and child sleep among children with CF are not well defined. Clarifying the presence and impact of sleep disturbances among pediatric CF patients and their parents could lead to improved health in this population. MethodsCross-sectional study assessing parent-reported sleep in ninety-one CF patients (mean age 8.8 years; 53.8% female) and their primary caregivers. Sleep sufficiency determined using American Academy of Sleep Medicine guidelines; correlation coefficients computed for sleep problem domains; stepwise multiple linear regression determined predictive models for sleep duration. ResultsParents reported concerns about their own sleep and that of their children. Night waking and daytime sleepiness were most common in parents; prolonged sleep latency was most common for children. Most parents and children had inadequate sleep duration. School-age children had the highest frequencies of overall sleep concerns and inadequate sleep. Most parent and child sleep problem domains were significantly associated, with large effects for similar parent and child problems. Stepwise multiple linear regression demonstrated that CF caregiver/patient sleep duration was significantly predicted by insomnia symptoms. ConclusionsMany CF children and their parents experience sleep difficulties including inadequate sleep duration, with presence of sleep problems in many families whose children with CF had normal lung function. These data suggest that sleep health should be a CF Care Model component and should be a health care focus for families of children with other chronic illness.

Three-axis accelerometer system for comparison of gait parameters in children with cystic fibrosis and healthy peers

BackgroundCystic Fibrosis (CF), affecting functional exercise capacity generally measured by submaximal exercise test such as 6min walk test, is a progressive, autosomal recessive and metabolic disorder. Three-axis accelerometers, which are used during gait, are an easy way to assess gait parameters in patients and healthy individuals. Gait parameters were significantly associated with clinical outcomes of COPD. However, the association between gait parameters and clinical outcomes in children with CF is unclear. Research questionDo clinical outcomes in CF have an important role in determining gait parameters?. MethodsTwenty-one CF and 21 healthy subjects participated in this case-control study. Body composition was evaluated using Tanita-BC 418. Respiratory and knee extension muscle strengths were assessed. Functional exercise capacity was evaluated using the 6-min walk test (6MWT). Spatiotemporal gait parameters were evaluated using a validated wireless inertial sensing device (G-Sensor, BTS Bioengineering S.p.A., Italy) during the 6MWT and 7-meter gait test. ResultsMIP, the distance of 6MWT, and stride length were significantly lower in the CF group compare to healthy children (p<0.05). Gait speed and functional exercise capacity, cadence and functional exercise capacity, quadriceps muscle strength, FEV1, fat-free mass were found to be correlated in CF patients (p<0.05). SignificanceThe aerobic capacity and gait parameters were affected in CF patients with mild disease severity in our study. Clinical outcomes were associated with gait parameters in CF patients. This is the first study to use the 3-axis accelerometer to evaluate functional exercise capacity and gait parameters of CF and healthy children. A three-axis accelerometer can be used to assess functional exercise capacity and gait parameters in CF patients at the clinics.

Glucose abnormalities detected by continuous glucose monitoring are common in young children with Cystic Fibrosis

It is not yet known whether continuous glucose monitoring (CGM) abnormalities persist in young children with CF. We evaluated longitudinal CGM results for children with CF < 10 years of age. We performed 3-day CGM at baseline, 12 months, and 24 months on 11 CF children (1 female) initially aged mean (SD) 3.8 (2.5) years. CGM analysis included (i) mean sensor glucose (SG), (ii) standard deviation (SD) for SG, (iii) peak SG and (iv)% time spent above a threshold of 7.8 mmol/L.Only three (3/11, 27%) had normal CGM at all time-points. Nearly three quarters of the participants (8/11, 73%) spent more than 4.5 percent time > 7.8 mmol/L at one time-point, five of whom had an elevated percent time on a subsequent test.Young children with CF have glucose abnormalities detected by CGM that fluctuate over time.

Utilizing centralized biorepository samples for biomarkers of cystic fibrosis lung disease severity

BackgroundCirculating biomarkers reflective of lung disease activity and severity have the potential to improve patient care and accelerate drug development in CF. The objective of this study was to leverage banked specimens to test the hypothesis that blood-based biomarkers discriminate CF children segregated by lung disease severity. MethodsBanked serum samples were selected from children who were categorized into two extremes of phenotype associated with lung function (‘mild’ or ‘severe’) based on CF-specific data and were matched on age, gender, CFTR genotype, and P. aeruginosa infection status. Targeted inflammatory proteins, lipids, and discovery metabolite profiles were measured in these serum samples. ResultsThe severe cohort, characterized by a lower CF-specific FEV1 percentile, had significantly higher circulating concentrations of high sensitivity C-reactive protein, serum amyloid A, granulocyte colony stimulating factor, and calprotectin compared to the mild cohort. The mild cohort tended to have higher serum linoleic acid concentrations. The metabolite arabitol was lower in the severe cohort while other CF relevant metabolic pathways showed non-significant differences after adjusting for multiple comparisons. A sensitivity analysis to correct for biased estimates that may result from selecting subjects using an extremes of phenotype approach confirmed the protein biomarker findings. ConclusionsCirculating inflammatory proteins differ in CF children segregated by lung function. These findings serve to demonstrate the value of maintaining centralized, high quality patient derived samples for future research, with linkage to clinical information to answer testable hypotheses in biomarker development.