Cystic Fibrosis Children Research Articles

FGF10 and Human Lung Disease Across the Life Spectrum.

Lung diseases impact patients across the lifespan, from infants in the first minutes of life through the aged population. Congenital abnormalities of lung structure can cause lung disease at birth or make adults more susceptible to chronic disease. Continuous inhalation of atmospheric components also requires the lung to be resilient to cellular injury. Fibroblast growth factor 10 (FGF10) regulates multiple stages of structural lung morphogenesis, cellular differentiation, and the response to injury. As a driver of lung airway branching morphogenesis, FGF10 signaling defects during development lead to neonatal lung disease. Alternatively, congenital airway abnormalities attributed to FGF10 mutations increase the risk of chronic airway disease in adulthood. FGF10 also maintains progenitor cell populations in the airway and promotes alveolar type 2 cell expansion and differentiation following injury. Here we review the cellular and molecular mechanisms linking FGF10 to multiple lung diseases, from bronchopulmonary dysplasia in extremely preterm neonates, cystic fibrosis in children, and chronic adult lung disorders. Understanding the connections between FGF10 and lung diseases may lead to exciting new therapeutic strategies.

Evaluation of Diagnosis and Management Plan of Diabetes Mellitus Related Cystic Fibrosis in Children

Background: Cystic fibrosis (CF) is a disease that occurs as a result of genetic mutations in cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR can be found in airways epithelial cells, intestine and cells with exocrine and exocrine function. CF is associated with variant complications, Cystic Fibrosis-Related Diabetes (CFRD) is considered as one of the most common complications of CF. Objective: In this review, we discussed the recent updates about Cystic Fibrosis-Related Diabetes (CFRD) diagnosis and management plan. Methods: PubMed database were used for articles selection. All relevant articles related to our review were chosen to cover the following topics: Cystic Fibrosis, Cystic Fibrosis Related Diabetes management, Cystic Fibrosis Related Diabetes diagnosis. We excluded other articles, which are not related to our objectives. Conclusion: CFRD can significantly worse the health condition of CF patients. However, with the recent advancement of management plans of CFRD, previous sex differences in mortality have disappeared and that the gap in mortality between CF patients with diabetes and CF patients without diabetes has considerably narrowed. Early diagnosis and early intervention also helped in improving the quality of CFRD patients and preventing the complications. This can be obtained by annual screening for DM among CF patients since 10 years of age using OGTT as recommended by ADA. The primary pathologic feature of CFRD is insulin insufficiency. It leads to increased breakdown of protein and fat. So, insulin replacement is the only recommended medical treatment and it has been shown to improve clinical outcomes. Oral diabetes agents are usually not recommended in CFRD.

Evaluation of Diagnosis and Management Plan of Diabetes Mellitus Related Cystic Fibrosis in Children

Background: Cystic fibrosis (CF) is a disease that occurs as a result of genetic mutations in cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR can be found in airways epithelial cells, intestine and cells with exocrine and exocrine function. CF is associated with variant complications, Cystic Fibrosis-Related Diabetes (CFRD) is considered as one of the most common complications of CF. Objective: In this review, we discussed the recent updates about Cystic Fibrosis-Related Diabetes (CFRD) diagnosis and management plan. Methods: PubMed database were used for articles selection. All relevant articles related to our review were chosen to cover the following topics: Cystic Fibrosis, Cystic Fibrosis Related Diabetes management, Cystic Fibrosis Related Diabetes diagnosis. We excluded other articles, which are not related to our objectives. Conclusion: CFRD can significantly worse the health condition of CF patients. However, with the recent advancement of management plans of CFRD, previous sex differences in mortality have disappeared and that the gap in mortality between CF patients with diabetes and CF patients without diabetes has considerably narrowed. Early diagnosis and early intervention also helped in improving the quality of CFRD patients and preventing the complications. This can be obtained by annual screening for DM among CF patients since 10 years of age using OGTT as recommended by ADA. The primary pathologic feature of CFRD is insulin insufficiency. It leads to increased breakdown of protein and fat. So, insulin replacement is the only recommended medical treatment and it has been shown to improve clinical outcomes. Oral diabetes agents are usually not recommended in CFRD.

Tele-Exercise as a Promising Tool to Promote Exercise in Children With Cystic Fibrosis.

Introduction: Cross-infection risk from contact exposure limits exercise opportunities in children with cystic fibrosis (CF). The purpose of this study is to evaluate the feasibility of a new live-streamed platform which delivered supervised and interactive group exercise sessions to CF children via digital devices while avoiding contact exposure.Methods: Ten CF children participated in a 6-week tele-exercise program. The program consisted of three 30-min sessions per week for a total of 18 sessions and included aerobic, resistance, and flexibility exercises. Sessions were streamed via a HIPAA compliant VSee telemedicine platform. Instructors and participants were able to interact in real-time online. Heart rate (HR) monitors were used to evaluate exercise intensity with a goal of moderate-vigorous physical activity ≥10 min, 70% of the sessions. System usability scale (SUS) and qualitative questionnaires were used to gauge participants' satisfaction and feedback.Results: On average participants attended 85% of the sessions. For the overall sessions participants exercise 21.1 ± 6.9 min at moderate-vigorous physical activity. Nine out of 10 participants used the exercise platform without parental guidance. Qualitative questionnaire and System Usability Scale (SUS) indicated that all participants enjoyed the tele-exercise program and highly rated the exercise platform 90.8 out of 100 (passing > 68).Conclusions: Tele-exercise platform is a promising new approach to promote exercise in children with CF. The online platform allows supervised virtual group exercise experience with optimal participation and no risk for cross-infection. This approach might prove to be useful in enhancing the use of exercise as therapy in children with CF.

Th17 cells in Bulgarian children with chronic obstructive lung diseases

Introduction and objectivesTh17 lymphocytes are now widely believed to be critical in various chronic pulmonary diseases. However, there is still a small number of investigations regarding children. We aimed to assess the percentage of Th17 lymphocytes and IL-17A in peripheral blood of children with chronic obstructive lung diseases. Patients and methodsWe included a total of 42 children: 20 with bronchial asthma (BA), 12 with cystic fibrosis (CF) and 10 healthy children without a history of allergies, aged 4–17 years. Th17 cells (CD3+CD4+CD161+CCR6+) were determined in peripheral blood by flow cytometry. The concentration of serum IL-17A was measured by ELISA. ResultsThe BA patients had a significantly higher percentage of Th17 (12.40±1.16%) compared to the CF children (7.64±0.87%, p=0.0035) and healthy (7.25±0.45%, p=0.008). Stratifying the BA group, we found higher levels of Th17 in patients with severe BA (p=0.03), whereas patients with moderate BA had Th17 cells close to those in CF and healthy children. We found that patients with better control of BA had Th17 closer to those with CF (p=0.98) than BA children with poor control (p<0.001) (post hoc, Bonferroni correction). CF patients with concomitant P. aeruginosa infection showed slightly higher percentages of Th17 cells than those without infection (8.08±3.09% vs. 6.25±2.42%, p=0.294). ConclusionsThe percentage of Th17 cells was significantly increased in the peripheral blood of children with severe BA compared to the children with moderate BA, which suggests that the former could possibly benefit from future target therapies.

Staphylococcus aureus Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection.

Staphylococcus aureus is a major cause of chronic respiratory infection in patients with cystic fibrosis (CF). We recently showed that Pseudomonas aeruginosa exhibits enhanced biofilm formation during respiratory syncytial virus (RSV) coinfection on human CF airway epithelial cells (AECs). The impact of respiratory viruses on other bacterial pathogens during polymicrobial infections in CF remains largely unknown. To investigate if S.aureus biofilm growth in the CF airways is impacted by virus coinfection, we evaluated S.aureus growth on CF AECs. Initial studies showed an increase in S.aureus growth over 24h, and microscopy revealed biofilm-like clusters of bacteria on CF AECs. Biofilm growth was enhanced when CF AECs were coinfected with RSV, and this observation was confirmed with S.aureus CF clinical isolates. Apical conditioned medium from RSV-infected cells promoted S.aureus biofilms in the absence of the host epithelium, suggesting that a secreted factor produced during virus infection benefits S.aureus biofilms. Exogenous iron addition did not significantly alter biofilm formation, suggesting that it is not likely the secreted factor. We further characterized S.aureus-RSV coinfection in our model using dual host-pathogen RNA sequencing, allowing us to observe specific contributions of S.aureus and RSV to the host response during coinfection. Using the dual host-pathogen RNA sequencing approach, we observed increased availability of nutrients from the host and upregulation of S.aureus genes involved in growth, protein translation and export, and amino acid metabolism during RSV coinfection.IMPORTANCE The airways of individuals with cystic fibrosis (CF) are commonly chronically infected, and Staphylococcus aureus is the dominant bacterial respiratory pathogen in CF children. CF patients also experience frequent respiratory virus infections, and it has been hypothesized that virus coinfection increases the severity of S.aureus lung infections in CF. We investigated the relationship between S.aureus and the CF airway epithelium and observed that coinfection with respiratory syncytial virus (RSV) enhances S.aureus biofilm growth. However, iron, which was previously found to be a significant factor influencing Pseudomonas aeruginosa biofilms during virus coinfection, plays a minor role in S.aureus coinfections. Transcriptomic analyses provided new insight into how bacterial and viral pathogens alter host defense and suggest potential pathways by which dampening of host responses to one pathogen may favor persistence of another in the CF airways, highlighting complex interactions occurring between bacteria, viruses, and the host during polymicrobial infections.

V232D mutation in patients with cystic fibrosis: Not so rare, not so mild.

The frequency of some Cystic Fibrosis (CF) Transmembrane Conductance Regulator gene (CFTR) mutations varies between populations. Genetic testing during newborn screening (NBS) for CF can identify less common mutations with low clinical expression in childhood and previously considered mild but not fully characterized, such as the mutation p.Val232Asp (c.695T > A). The aim of this study was to describe CF patients with the V232D mutation. We identify CF children with the V232D mutation detected by NBS and compare them with CF adults with this mutation whose diagnosis was prompted by clinical symptoms in the same period. We studied clinical, biochemical, spirometric, and prognostic features in both populations. NBS program tested 276,523 children during a period of 14 years (2003–2017) and identified 54 cases of CF. Six children (11%) had the V232D mutation. Over the same period, 5 adults (age 37.6 ± 16.29 years old) with symptoms of CF and this mutation were also diagnosed. Follow-up duration was mean 10.1 years for adults and mean 6.5 years for children. In the adult group, lung function was impaired at diagnosis in all patients (Forced Expiratory Volume1—FEV1—67.12% ± 13.09) and worsened in children tested during evolution (FEV1first: 113%; FEV1last: 64%). Pancreatic insufficiency was present in adult group, with recurrent pancreatitis in 1 present. Although with less clinical expression in children, V232D is associated with pulmonary and pancreatic involvement during adulthood and CF cannot be considered mild. This mutation is present in 11% of all patients diagnosed with CF in our region. Its inclusion in some NBS programs should be taken into account in order to improve the prognosis of affected children.

Pharmacoeconomic Assessment of the Application of Dornase Alfa in the Treatment of Lung Generation in Patients with Cystic Fibrosis

Introduction: Cystic fibrosis (CF) is an important medical and pharmaceutical, social and economic problem both in the whole world and in Ukraine. Effective and safe, well-grounded health technology (HT) is needed to increase the availability of highly qualified medical and pharmaceutical care to patients with CF in Ukraine for the purpose of survival rate, recovery and life expectancy of patients increasing. Materials and Methods: Taking into account the aforementioned goal of our study, we have conducted a pharmacoeconomic assessment of the dornase alfa usage in the treatment of pulmonary exacerbations in patients with CF. We included data for this outcome from trials lasting 1 month, 6 months and 2 years (dornase alfa n = 575, control n = 576)[9]. This yielded a risk ratio of 0.78 (95% confidence interval 0.62–0.96) in favor of dornase alfa. Results: It has been established that in the inhalation use of the dornase alfa (2.5 mg 1 time a day) in adults and children over 5 years ago, the absolute risk of pulmonary exacerbations in patients with CF was 19.5%, without dornase alfa - 25.2%. That is, in 195 patients form a thousand of CF’ patients who took dornase alfa, there were pulmonary exacerbations.[9] The frequency of pulmonary exacerbations in the treatment with dornase alfa per year was 1.25, and in non-dornase alfa – 3,13. Consequently, taking into account the data of the systematic review in the subsequent calculations, the annual period of use of the dornase alfa in the treatment of pulmonary exacerbations of patients with CF has been taken. It should be noted, that the total direct medical costs of the application of HT-1 (dornase alfa) in the treatment of pulmonary exacerbations in CF children aged 5–18 years have been in 2.7 times more comparing to the HT-2 (without dornase alfa). It has been established that the most cost-effective in the treatment of pulmonary exacerbations in children aged 5–18 years with CF is the use of HT-1. Direct medical costs for children aged 5–18 years with the use of HT-2 are 17% higher than with the use of HT-1. Thus, the use of HT-2 in children aged 5–1z8 years requires additional direct medical expenses of 245061.44 USD. Calculation of the coefficient of “lost opportunity” allowed to establish, in the course of the year, the use of dornase alfa in the treatment of patients with CF may additionally allows to treat almost 37 children diagnosed with CF. The BIA of direct medical expenses for the treatment of pulmonary exacerbations in patients with CF (for the predicted number of patients) for 2017–2021 has shown significant benefits of HT-1 (dornase alfa). Hence, in 2018, the total savings of budget funds will be 265 331.91 USD, in 2019–271 689.08 USD., in 2020–291 015.04 USD., and in 2021–310,340.99 USD (the average growth rate of budget savings for 2017–2021 will be 1.06). Discussion: There was not any study that describes pharmacoeconomic assessment of the application of dornase alfa in the treatment of lung generation in patients with CF for Ukraine’ conditions before. Conclusion: Consequently, pharmacoeconomic studies, conducted by us, allows to formulate a rational financial policy and promote the realization of the rights of the child patient with the CF for obtaining a pharmacotherapy that meets the modern international recommendations.

P102 First Aspergillus fumigatus seroconversion was associated with more severe disease in cystic fibrosis children

P102 First Aspergillus fumigatus seroconversion was associated with more severe disease in cystic fibrosis children

EPS2.05 Genotype/phenotype correlation in cystic fibrosis children with mutation 3272-16T > A

EPS2.05 Genotype/phenotype correlation in cystic fibrosis children with mutation 3272-16T > A

P171 How to give pancreatic enzyme in cystic fibrosis children with gastrostomy and unable to swallow opotherapy by mouth?

P171 How to give pancreatic enzyme in cystic fibrosis children with gastrostomy and unable to swallow opotherapy by mouth?

P184 Factors influencing total serum cholesterol in cystic fibrosis children and adolescents - preliminary data

P184 Factors influencing total serum cholesterol in cystic fibrosis children and adolescents - preliminary data

Respiratory syncytial virus prophylaxis in cystic fibrosis: the Canadian registry of palivizumab data (2005-2016).

Respiratory syncytial virus (RSV) may cause severe illness in cystic fibrosis (CF) children, but recommendations vary on prophylaxis. CARESS is a prospective registry of children who received palivizumab in 32 Canadian sites from 2005 to 2016. Demographic data were collected at enrollment and respiratory illness-related events recorded monthly. We reviewed respiratory illness hospitalization (RIH) and RSV hospitalization (RSVH) in CF children aged < 24months versus those prophylaxed for standard indications (SI; prematurity, chronic lung disease [CLD] and congenital heart disease [CHD]), and complex medical disorders (CM). Of 23,228 children analyzed, 19,452 (83.8%) were SI, 3349 (14.4%) were CM, and 427 (1.8%) were CF. CF children were more likely to be Caucasian, heavier at birth and enrollment, and less likely to have a sibling or live in crowded conditions. CF children were similar to the other groups in daycare attendance, history of atopy, and exposure to smoking. RIH incidences were 4.3% (premature), 13.8% CLD, 11.5% CHD, 11.7% CM, and 6.8% CF. RSVH incidence in CF children was similar to that in the SI and CM groups: 1.1, 1.5, and 2.0% groups respectively. Cox regression analyses showed that compared to CF children, the HRs for RSVH in SI (HR 2.0 95% CI 0.5-8.3, p = 0.3) and CM (HR 2.4, 95% CI 0.6-9.8, p = 0.2) did not differ. CF children are equally at risk for RSVH relative to those prophylaxed for other indications. Pending robust evidence from prospective trials, palivizumab could perhaps be considered in the interim, for young CF patients born early during the RSV season with evidence of serious lung disease.

Identification of Dermatoglyphic Patterns in Parents of Children with Cystic Fibrosis

Background Dermatoglyphics could assist in the diagnosis of congenital abnormalities. The aim of this study was to identify the dermatoglyphic patterns (finger print pattern type, total ridge count of each finger, a-b ridge count, and articulotrochanteric distance [ATD angles]) in the parents of cystic fibrosis children. Materials and Methods We recruited 75 parents of children with cystic fibrosis for the study group and 341 parents for the control group. We recorded finger print pattern type, total ridge count (TRC), a-b ridge count, and ATD angles of all participants. Then we identified any asymmetry between the right and left hands of each person and characteristics of parents in two genders. Chi-square analysis, Mann-Whitney U test, and Fisher's exact test were used for data analysis. Results We observed significant differences in a-b ridge count on the right hand (P=0.02), and mean total ridge count on the right digit I (P=0.05), right digit IV (P=0.03), and right digit V in the fathers of children with cystic fibrosis compared to the control group(P=0.02). Conclusion According to the results, we suggest that the dermatoglyphic traits of parents could be used as a simple, appropriate, and supplementary screening method in the diagnosis of children with CF. Nevertheless, we need lager studies to precisely confirm that dermatoglyphics is a reliable method in the diagnosis of CF.

Meropenem time above the MIC exposure is predictive of response in cystic fibrosis children with acute pulmonary exacerbations

Meropenem exposures from 15 children (8–17 years old) with cystic fibrosis (CF) acute pulmonary exacerbation were analyzed to define the pharmacodynamic threshold required for a positive response. The primary endpoint was the relative increase in forced expiratory volume in 1 s (↑FEV1) between pre- and posttreatment. Meropenem pharmacodynamic indices (fT > MIC, fAUC/MIC, fCmin/MIC) over the first 24 h were estimated for each participant based on their individual parameter estimates and the isolated pathogen with the highest meropenem MIC. Pseudomonas aeruginosa was the most common pathogen (n = 11/15). The mean ± SD ↑FEV1 was 18.8% ± 11.3% posttreatment. The mean (range) fT > MIC exposure was 63% (0–100%). An Emax model determined a significant relationship between fT > MIC and ↑FEV1 (r2 = 0.8, P < 0.0004). 65% fT > MIC was a significant predictor of response; the median (25th, 75th %) ↑FEV1 was 28.5% (22.2%, 31.7%) in those patients who achieved above 65% fT > MIC and 7.8% (1.1%, 12.6%) in those at or below 65% fT > MIC (P = 0.001). This is the first study in CF children to link meropenem exposure with a positive response as measured by ↑FEV1. Larger studies are required to confirm this exposure threshold.

Take care of children with cystic fibrosis

Cystic fibrosis (CF) is one of the life-threatening and an autosomal recessive hereditary disease, which may involve lung, digestive and reproductive systems.The occurrence of CF varied with race, and is common in European and American, while rare in Asian.But recently, with the progress of medical technology, more and more Chinese children with CF have been found.Lacking of experience in CF diagnosis may be the main cause of misdiagnosis in China.The aim of this review is to elaborate the pathogenesis, clinical characteristics, diagnosis and treatment of CF, in order to improve the ability of identifying CF for Chinese pediatrician.Early identification and intervention can improve the prognosis and prolong the life cycle of Chinese CF children. Key words: Cystic fibrosis; Diagnosis; Child

Young patients with cystic fibrosis demonstrate subtle alterations of the cardiovascular system

BackgroundAs life expectancy increases in patients with cystic fibrosis, it is important to pay attention to extra-pulmonary comorbidities. Several studies have shown signs of myocardial dysfunction in adult patients, but little is known about onset and development of these changes over time. In this prospective study, cardiac function in children with cystic fibrosis was compared to that of healthy children. Methods33 children, aged 3–12years, with cystic fibrosis were recruited from the Wilhelmina Children's hospital and 33 age-matched healthy children were selected from the WHISTLER study, a population-based cohort study. Measurements of lung function, arterial stiffness, and echocardiography (conventional measures and myocardial deformation imaging) were performed. ResultsThere were no differences in anthropometrics, lung function and blood pressure between the two groups. The cystic fibrosis children had a higher arterial stiffness compared to the healthy children (pulse wave velocity respectively 5.76±0.57m/s versus 5.43±0.61m/s, p-value 0.049). Using conventional echocardiographic parameters for right ventricular function, Tricuspid Annular Plane Systolic Excursion) and Tissue Doppler Imaging, cystic fibrosis children had a reduced right ventricular systolic function when compared to the healthy children. After adjustment for lung function, global strains of both right and left ventricles were significantly lower in the cystic fibrosis group than in healthy children (linear regression coefficient 1.45% left ventricle, p-value 0.022 and 4.42% right ventricle, p-value <0.01). Systolic strain rate of basal segment of the left ventricle, the mid segment of the right ventricle and the apical septum were significantly lower in the cystic fibrosis children than in healthy controls. ConclusionOur study suggests that already at a very young age, children with cystic fibrosis show an increased arterial stiffness and some signs of diminished both right and left ventricular function.

Early life growth patterns persist for 12 years and impact pulmonary outcomes in cystic fibrosis

BackgroundIn children with cystic fibrosis (CF), recovery from growth faltering within 2 years of diagnosis (Responders) is associated with better growth and less lung disease at age 6 years. This study examined whether these benefits are sustained through 12 years of age. MethodsLongitudinal growth from 76 children with CF enrolled in the Wisconsin CF Neonatal Screening Project was examined and categorized into 5 groups: R12, R6, and R2, representing Responders who maintained growth improvement to age 12, 6, and 2 years, respectively, and I6 and N6, representing Non-responders whose growth did and did not improve during ages 2–6 years, respectively. Lung disease was evaluated by % predicted forced expiratory volume in one second (FEV1) and chest radiograph (CXR) scores. ResultsSixty-two percent were Responders. Within this group, 47% were R12, 28% were R6, and 25% were R2. Among Non-responders, 76% were N6. CF children with meconium ileus (MI) had worse lung function and CXR scores compared to other CF children. Among 53 children with pancreatic insufficiency without MI, R12 had significantly better FEV1 (97–99% predicted) and CXR scores during ages 6–12 years than N6 (89–93% predicted). Both R6 and R2 experienced a decline in FEV1 by ages 10–12 years. ConclusionsEarly growth recovery in CF is critical, as malnutrition during infancy tends to persist and catch-up growth after age 2 years is difficult. The longer adequate growth was maintained after early growth recovery, the better the pulmonary outcomes at age 12 years.

Gas exchanges in children with cystic fibrosis or primary ciliary dyskinesia: A retrospective study

Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) both entail bronchiectasis and pulmonary impairment as measured using spirometry, during childhood. We aimed at looking whether blood gas exchanges progressed differently between CF and PCD children in a retrospective study of repeated measurements. Comparisons between groups (Wilcoxon-Mann-Whitney and Chi-squared tests) and a mixed linear model, adjusted for age, evaluated associations between diseases and PaO2, PaCO2, or PaO2-PaCO2 ratio.Among 42 PCD and 73 CF children, 62% and 59% had respectively bronchiectasis (P = 0.75). Spirometry and blood gases were similar at inclusion (PaO2 median [IQR] PCD −1.80 [−3.40; −0.40]; CF −1.80 [−4.20; 0.60] z-scores; P = 0.72). PaO2 and PaO2-PaCO2 ratio similarly and significantly decreased with age in both groups (P < 0.01) whereas PaCO2 increased more in CF (P = 0.02) remaining within the range of normal (except for one child).To conclude, gas exchange characteristics, similarly initially impaired in PCD and CF children, tended to less deteriorate with time in PCD children who could benefit from an early diagnosis.

Влияние дефицита витамина D на клинические проявления муковисцидоза у детей Московского региона

Влияние дефицита витамина D на клинические проявления муковисцидоза у детей Московского региона