Pediatric Cystic Fibrosis Population Research Articles

Genetic and clinical factors influencing CF-associated liver disease: the impact of SERPINA1 variants and CFTR genotypes in Romanian pediatric cystic fibrosis patients.

Hepatic disease represents a significant complication in children with cystic fibrosis (CF), yet its relationship with specific genetic factors, including CFTR (Cystic fibrosis transmembrane conductance regulator) mutations and SERPINA1 alleles, is not well understood. This study aims to clarify these associations within a Romanian pediatric CF population. In this cross-sectional, prospective study, we examined 71 children with CF, comparing those with hepatic disease (n=25) to those without (n=46). We collected comprehensive clinical, biochemical, and genetic data, focusing on CFTR genotypes and SERPINA1 alleles. Key outcomes included the prevalence of hepatic disease in relation to specific genotypes, fibrosis markers, and liver function tests. The DF508/DF508 genotype was the most prevalent, occurring in 49% of the cohort. No significant associations were found between hepatic disease and specific CFTR genotypes or SERPINA1 alleles. However, children with hepatic disease exhibited significantly higher fibrosis scores (APRI and FIB-4), suggesting more advanced liver involvement. Additionally, a slight delay in CF diagnosis was observed in those with hepatic disease, though this difference did not reach statistical significance. This pioneering study in Romania underscores the complexity of hepatic disease in CF. While specific CFTR genotypes and SERPINA1 alleles were not significantly associated with hepatic complications, the findings emphasize the importance of early diagnosis and monitoring using fibrosis markers to identify children at risk for liver involvement.

P043 The oxygen pulse response during cardiopulmonary exercise testing in our paediatric cystic fibrosis population

P043 The oxygen pulse response during cardiopulmonary exercise testing in our paediatric cystic fibrosis population

P399 Child life interventions: caring for the pediatric cystic fibrosis population in the outpatient setting

P399 Child life interventions: caring for the pediatric cystic fibrosis population in the outpatient setting

Gastrointestinal Pathologies in Pediatric Patients With Cystic Fibrosis Undergoing Endoscopy: A Single-Center Retrospective Review Over 15 Years.

Introduction Previous studies have demonstrated an increased incidence of gastrointestinal (GI) pathologies, specifically celiac disease (CD) and eosinophilic esophagitis (EoE), in patients with cystic fibrosis (CF). However, there is minimal data available regarding endoscopic findings in pediatric patients with CF and GI mucosal disease. Methods A retrospective chart review was performed on patients with CF under 18 years of age who underwent esophagogastroduodenoscopy (EGD) or colonoscopy with biopsy over a 15-year period at our institution. Patient characteristics including assigned sex at birth, CF genetic mutations (if identified), and cystic fibrosis transmembrane conductance regulator (CFTR) modulator use were recorded.Data obtained at the time of biopsy included body mass index (BMI), indication for the procedure, exocrine pancreatic status, visual endoscopic findings, and histologic findings. Results A total of 72 patients with CF were included in the study. 24% (n=17) were found to have abnormal endoscopic biopsy results. EoE (13% of all patients, n=9) and CD (6% of all patients, n=4) were the most common GI diagnoses present on endoscopic biopsy. All 3 patients taking CFTR modulator medications at the time of endoscopy had normal biopsy results. Of the 17 patients found to have abnormal pathology results, 14 (82%) were taking proton-pump inhibitor (PPI) medication at the time of endoscopy. Conclusion This study highlights the probable increased frequency of GI disease in the pediatric CF population. These findings underscore the importance of maintaining a broad differential diagnosis while considering utilization of endoscopy with biopsy in pediatric patients with CF who have GI symptoms.

Prevalence of Scoliosis in Children and Adolescents with Cystic Fibrosis.

The prevalence of scoliosis in people with cystic fibrosis (CF) seems to be greater than in the normal population. Over the last two years, a screening for spinal deformities was carried out in patients with CF aged 5 to 18 years, followed up at the CF regional Centre in Parma (Italy). Forty-three patients (twenty-seven males, mean age: 11.8 ± 4.5 years) were enrolled in the study. Nine patients (20.9%) were diagnosed with scoliosis, with a mean Cobb angle of 20.8 ± 9.4 (12-38°). Five patients (11.6%) were diagnosed with a postural kyphosis attitude and one with pathological fixed kyphosis. All patients with scoliosis and postural kyphosis started daily physiotherapeutic scoliosis-specific exercises (PSSE). Compared to people without CF, the prevalence of scoliosis in our paediatric CF population seems to be higher and more present in males; the curves were thoracic and mostly right-sided. CF disease, hyposthenic postural attitude and sedentary lifestyle can contribute to the pathogenesis of this musculoskeletal alteration. Spinal deformities may negatively affect pulmonary function, resulting in disability, pain and a decreased quality of life. Since the prevention of musculoskeletal deformities is easier than restoration, in CF population targeted screening during growth and interventions, including regular physical exercise, are mandatory.

378 CFTR modulator therapy prescription rates in the pediatric cystic fibrosis population: a decade of care

378 CFTR modulator therapy prescription rates in the pediatric cystic fibrosis population: a decade of care

Evolving Nutritional Needs in Cystic Fibrosis.

The course of cystic fibrosis (CF) as a nutritional illness is diverging since the introduction of highly effective modulator therapy, leading to more heterogeneous phenotypes of the disease despite CF genetic mutations that portend worse prognosis. This may become more evident as we follow the pediatric CF population into adulthood as some highly effective modulator therapies (HEMT) are approved for those as young as 1 year old. This review will outline the current research and knowledge available in the evolving nutritional health of people with CF as it relates to the impact of HEMT on anthropometrics, body composition, and energy expenditure, exocrine and endocrine pancreatic insufficiencies (the latter resulting in CF-related diabetes), vitamin and mineral deficiencies, and nutritional health in CF as it relates to pregnancy and lung transplantation.

P329 Audit of change in weight and BMI centile in children on elexacaftor/tezacaftor/ivacaftor in the Liverpool paediatric cystic fibrosis population

There is emerging evidence of increasing weight gain and BMI centiles in both the paediatric and adult CF population taking elexacaftor/tezacaftor/ivacaftor (ETI).

The impact of telehealth based care on paediatric cystic fibrosis outcomes

In response to the COVID-19 pandemic telehealth utilisation amongst the Cystic Fibrosis (CF) population increased. Our aim was to assess the impact of CF telehealth clinics on CF outcomes. We conducted a retrospective chart review of patients seen in the CF clinic at the Royal Children's Hospital (Victoria, Australia). In this review we compared spirometry, microbiology and anthropometry in the year preceding the pandemic to during the pandemic, and to the first in-person appointment in 2021. 214 patients were included. First in-person FEV1 was median 5.4% below individuals’ best FEV1 in 12 months prior to lockdown and decreased by >10% in 46 (31.9%) patients. There were no significant findings with regards to microbiology or anthropometry. The reduction in FEV1 observed on return to in-person appointments highlights the importance of ongoing improvement of telehealth-based care along with continued face-to-face review for the paediatric CF population.

Trajectories of early growth and subsequent lung function in cystic fibrosis: An observational study using UK and Canadian registry data

BackgroundUnderstanding the pulmonary impact of changes in early life nutritional status over time in a paediatric CF population may help inform how to use nutritional assessment to guide clinical care. National registry data provides an opportunity to study patterns of weight gain over time at the level of the individual, and thus to gain detailed understanding of the relationship between early weight trajectories and later lung function in children with Cystic Fibrosis (CF). MethodsUsing data from the United Kingdom (UK) and Canadian CF Registries, a mixed effects linear regression model was used to describe children's weight and BMI z-score trajectories from age 1 to 5 years. The intercept (weight-for-age at age 1) and slope (weight-for-age trajectory) from this model were then used as covariates in a linear regression of first lung function measurement at age 6 years. ResultsIn both the UK and Canadian data, greater weight-for-age z-score at age 1 year and greater change in weight-for-age over time were associated with higher FEV1% predicted. A greater weight-for-age z-score at age 1 year was associated with a higher FEV1% predicted (UK: 3.78% (95% CI: 1.76; 4.70); Canada: 3.20% (95%CI: 1.76, 4.70)). These associations were reproduced for BMI z-scores and FVC% predicted. ConclusionsEarly weight-for-age, specifically at age 1 year, and weight-for-age trajectories across early childhood are associated with later lung function. This relationship persists after adjustment for potential confounders. Current guidelines may need to be updated to place less emphasis on a specific cut-off (such as the 10th percentile) and encourage tracking of weight-for-age over time.

What Is Most Suitable for Children With Cystic Fibrosis-The Relationship Between Spirometry, Oscillometry, and Multiple Breath Nitrogen Washout.

IntroductionIn cystic fibrosis (CF), pathological lung changes begin early in life. The technological progress currently gives many diagnostic possibilities. However, pulmonary function testing in children remains problematic.ObjectivesOur study aimed to correlate the results of impulse oscillometry (IOS) with those of multiple breath nitrogen washout (MBNW) in our pediatric CF population. We also compared those parameters between the groups with and without spirometric features of obturation.MethodsWe collected 150 pulmonary function test sets, including spirometry, IOS, and MBNW in patients with CF aged 12.08 ± 3.85 years [6–18]. The study group was divided into two subgroups: IA (without obturation) and IB (with obturation). We also compared Sacin, Scond, and oscillometry parameters of 20 patients aged 14–18 years who reached the appropriate tidal volume (VT) during MBNW.ResultsStatistical analysis showed a negative correlation between lung clearance index (LCI) and spimoetric parameters. Comparison of subgroups IA (n = 102) and IB (n = 48) indicated a statistically significant difference in LCI (p < 0.001) and FEV1z-score (p < 0.001), FEV1% pred (p < 0.001), MEF25z-score (p < 0.001), MEF50 z-score (p < 0.001), MEF75 z-score (p < 0.001), R5% pred (p < 0.05), and R20% pred (p < 0.01). LCI higher than 7.91 was found in 75.33% of the study group, in subgroup IB—91.67%, and IA−67.6%.ConclusionsLCI derived from MBNW may be a better tool than IOS for assessing pulmonary function in patients with CF, particularly those who cannot perform spirometry.

Comparison of Whole Genome Sequencing and Repetitive Element PCR for Multidrug-Resistant Pseudomonas aeruginosa Strain Typing

Hospital-acquired infections pose significant costly global challenges to patient care. Rapid and sensitive methods to identify potential outbreaks are integral to infection control measures. Whole-genome sequencing (WGS)-based bacterial strain typing provides higher discriminatory power over standard nucleotide banding pattern-based methods such as repetitive sequence-based PCR (rep-PCR). However, integration of WGS into clinical epidemiology is limited by the lack of consensus in methodology and data analysis/interpretation. In this study, WGS was performed on genomic DNA extracted from 22 multidrug-resistant Pseudomonas aeruginosa (MDR-PA) isolates using next-generation sequencing. Resulting high-quality reads were analyzed for phylogenetic relatedness using a whole-genome multilocus sequence typing (wgMLST)-based software program and single-nucleotide variant phylogenomics (SNVPhyl). WGS-based results were compared with conventional MLST and archived rep-PCR results. Rep-PCR identified three independent clonal clusters of MDR-PA. Only one clonal cluster identified by rep-PCR, an endemic strain within the pediatric cystic fibrosis population at Texas Children's Hospital, was concordantly identified using wgMLST and SNVPhyl. Results were highly consistent between the three sequence-based analyses (conventional MLST, wgMLST, and SNVPhyl), and these results remained consistent with the addition of 74 MDR-PA genomes. These WGS-based methods provided greater resolution for strain discrimination than rep-PCR or standard MLST classification, and the ease of use of wgMLST software renders it clinically viable for analysis, interpretation, and reporting of WGS-based strain typing.

Handgrip Strength and Pulmonary Function in the Pediatric Cystic Fibrosis Population

Identify indicators of nutrition status that predict pulmonary function within pediatric cystic fibrosis patients. In Cystic Fibrosis (CF), adequate nutrition promotes good pulmonary function and overall quality of life. Handgrip strength (HGS) has promise as an indicator for nutrition status and predictor of pulmonary function, with associations found in adult CF. The purpose of this study is to determine, in pediatric CF, if HGS is associated with pulmonary function, and if it is a better predictor compared to body mass index (BMI), the current nutrition measurement. This is a cross-sectional, retrospective chart review of 48 pediatric patients followed at the Nebraska Regional Cystic Fibrosis Center, Pediatric Program. Associations between HGS, BMI, and pulmonary function measures (FEV1, FVC) were assessed using linear regression and adjusted for age and sex. Significant associations were found between HGS and percent predicted forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) (β=1.347, p = 0.001 and β=1.278, p < 0.001, respectively). BMI was also significantly associated with percent predicted FEV1 and FVC (β=2.380, p = 0.033 and β=2.151, p = 0.027, respectively). HGS was found to have a significant association to pulmonary function, however BMI remains a strong predictor. These results support the continued use of BMI as a primary measurement for nutrition status in the CF population. HGS is a promising tool for clinic use and more research is needed to evaluate its efficacy within the pediatric CF population.

Evaluation of the health-related quality of life in Turkish cystic fibrosis patients.

Prolongation of life expectancy in cystic fibrosis (CF) to the fourth decade makes health-related quality of life (HRQOL) an important issue in this population. This study aims to evaluate the effects of clinical and socio-demographic characteristics of patients on different aspects of HRQOL in a pediatric CF population. We also intend to assess some measures of reliability and validity of the Turkish CF Questionnaire-Revised (CFQ-R) forms. Fifty-four CF patients and 46 parents / caregivers filled the appropriate CFQ-R forms. Disease severity was evaluated via modified Shwachman-Kulczycki (SK) scores, and additional clinical information was obtained from patient records. Forty-three percent (n=23) of patients were female, the mean age of patients being 13.3±3.96years. Self- and proxy-reported points showed a strong correlation (Spearman's rho>0.6) on more observable domains of HRQOL (e.g. physical functioning). No significant difference was found between sexes on any HRQOL domain. When compared between age groups, treatment burden appeared to worsen with age, while social functioning improved. All three forms of the CFQ-R Turkish version showed acceptable internal consistency reliability and convergence with disease severity measures. The CFQ-R showed a fair correlation with the Shwachman-Kulczycki score and the FEV1% value, which makes its longitudinal use possible in clinical practice. It is important to use self-reported evaluations as well as parent / caregiver-reported HRQOL evaluations, especially in young children. More studies are needed to assess the psychometric properties of Turkish CFQ-R forms.

Food Insecurity Increased During the COVID-19 Pandemic in a Pediatric Cystic Fibrosis Population but Was Not Associated With Weight or Pulmonary Function

ObjectivesThis study's purpose is to determine changes in household food security status and nutrition-related anthropometrics and pulmonary function of children with Cystic Fibrosis during the COVID-19 pandemic.MethodsThis retrospective study includede caregivers of children ages 2–18 years old with Cystic Fibrosis who had Ohio residency, a Forced Expiratory Volume in 1 second (FEV1) above 30% and consumed at least half of nutrient needs by mouth. After contacting all eligible households by phone, 30 subjects (50% response) enrolled. The validated 18 item Food Security survey module along with several supplemental questions was used to assess household food security status before and after the onset of the COVID-19 pandemic. A medical chart review collected demographics as well as weight (kg) and FEV1(%) for the visit closest to the start of the pandemic (Jan-Mar 2020) and themost current visit (July-Dec 2020). Change in weight was categorized as desirable/undesirable based on clinic standards for using the fiftieth percentile as desirable. A paired t-test was used to determine change in FEV1 since the pandemic. Changes in food security status in relation to change in weight and change in FEV1 were determined using Fisher's test and Welch's t-test, respectively.ResultsParticipants were caregivers of children who were 9.96 ± 5.02 years old, 56% female, and 83% Caucasian. Ten % of participants (n = 3) reported household food insecurity before the pandemic, which increased to thirty % (n = 9) after the pandemic. Fifty percent of participants (n = 15) experienced an undesirable weight gain (2.71 kg ± 6.32 kg; mean ± std dev). There was no change in FEV1 during the pandemic (−0.6% ± 9.02; P = .74). Changes in weight and FEV1 were not related to change in household food security status (P = 0.287 and P = .088 respectively).ConclusionsFood insecurity increased during the COVID-19 pandemic; however, it was not related to undesirable weight change or decrease in FEV1. The second part of this study will use semi-structured interviews to elucidate how families with children with cystic fibrosis coped with food insecurity during the pandemic.Funding SourcesPulmonary Division, Nationwide Children's Hospital, Columbus OH

Lung function in children with cystic fibrosis in the USA and UK: a comparative longitudinal analysis of national registry data

RationaleA previous analysis found significantly higher lung function in the US paediatric cystic fibrosis (CF) population compared with the UK with this difference apparently decreasing in adolescence and adulthood. However,...

Immunoglobulin G: A useful outcome marker in the follow-up of cystic fibrosis patients?

Background and MethodsHypergammaglobulinemia (hyper‐IgG) and hypogammaglobulinemia (hypo‐IgG) have been reported in patients with cystic fibrosis (CF). Although the clinical respiratory course is paradoxically different, depending on the IgG status, this association remains elusive. Therefore, we performed a longitudinal study to assess the annual evolution of IgG profiles in a cohort of pediatric patients with CF, from their diagnosis until 2016. We then compared clinical findings with the patients’ IgG status to determine whether IgG status could reflect the respiratory clinical course of patients with CF.ResultsAmong the 66 patients with CF that were aged between 12 months and 18 years in 2016 (mean age: 9.3 years [SD: 5.2]), hypo‐IgG was observed in 15.2% and no hyper‐IgG was identified. Longitudinal assessment since diagnosis revealed no hyper‐IgG but 33.3% of patients had at least one sample showing hypo‐IgG, among which two patients displayed persistent hypo‐IgG. The number of pulmonary exacerbations, duration of antibiotic therapy, and erythrocyte sedimentation rate were all lower in hypo‐IgG patients. No difference was observed for the genotype, chronic Pseudomonas aeruginosa or Staphylococcus aureus infection, and in the parameters of lung function.ConclusionThe IgG profile of pediatric patients with CF has changed over recent decades, particularly with regard to hyper‐IgG. In a significant portion of the pediatric CF population, hypo‐IgG is transient and only identifiable in longitudinal assessments. This study reinforces that hypo‐IgG patients paradoxically present a more favorable course of clinical status. Therefore, IgG levels could be a useful outcome marker in the follow‐up of patients with CF.

Glycated Hemoglobin as a First-line Screening Test for Cystic Fibrosis‒Related Diabetes and Impaired Glucose Tolerance in Children With Cystic Fibrosis: A Validation Study

ObjectivesOur aims in this study were to document the screening rate for cystic fibrosis‒related diabetes (CFRD) in children followed at a cystic fibrosis (CF) clinic in Canada and to evaluate the accuracy of various glycated hemoglobin (A1C) cutoffs to screen for CFRD and impaired glucose tolerance (IGT) in a pediatric CF population. MethodsThe CFRD screening rate was calculated over a follow-up period of up to 8 years among children who attended the CF clinic between 1993 and 2018. Test performance of A1C at various thresholds ranging from 5.5% to 6.2% was compared with the oral glucose tolerance test (OGTT) as the reference method. Children with CF aged ≥10 years with an OGTT performed within 120 days of A1C measurement were included in the analysis. ResultsThe overall CFRD screening rate was 53.0%. A total of 256 children were included for the A1C performance analysis, of whom 8.6% had an OGTT-confirmed CFRD diagnosis. An A1C threshold of 5.8% demonstrated an optimal balance between sensitivity (90.9%) and specificity (60.7%) for CFRD screening, leading to a potential reduction of 56.3% of the annual required OGTTs. A1C demonstrated poor accuracy for identifying children with IGT. ConclusionsAn A1C threshold ≥5.8% allows for identification of children requiring further CFRD investigations, which may reduce the clinical burden of children with CF without compromising the ability of early CFRD diagnosis.

Impact of airway Exophiala spp. on children with cystic fibrosis

IntroductionIsolation of Exophiala species from sputum samples has become increasingly reported in Cystic Fibrosis (CF). However, the clinical significance of Exophiala spp. with regards to the paediatric CF population is unknown. MethodsA case control study was undertaken to compare CF children with and without chronic Exophiala spp. in their sputum samples. Demographic and clinical data were collected retrospectively for each case from the date of Exophiala isolation and for 12 months preceding isolation. Each case was compared to three age and year-matched controls. To determine the effect of Exophiala on clinical course, patients were then followed for 12 months post isolation. ResultsIn total, 27 of 244 eligible paediatric CF patients (11%) isolated Exophiala spp. on more than one occasion. There were no significant differences in the key clinical parameters: spirometry, mean number of intravenous (IV) antibiotic days and body mass index (BMI), between cases and controls (p = 0.91, p = 0.56 and p = 0.63 respectively). A higher proportion of cases isolated Candida spp. (67% vs 21%, p < 0.0001) and Aspergillus fumigatus (37% vs 26%, p = 0.37). There was no clinically significant difference in spirometry, mean number of IV antibiotic days and BMI in cases pre and post Exophiala spp. isolation. Posaconazole was the only drug used that successfully eradicated Exophiala. ConclusionDespite the frequent isolation of Exophiala spp. in this cohort, in most patients it is not associated with significant clinical deterioration. It does however seem to be associated with isolation of other fungi.

Utility of Mid‐Upper Arm Circumference in Diagnosing Malnutrition in Children With Cystic Fibrosis

Standardized diagnostic indicators for malnutrition using growth percentile z-scores (weight for length or body mass index [BMI]) and mid-upper arm circumference (MUAC) z-scores are being used in clinical practice; however, their application to the pediatric cystic fibrosis (CF) population is not well described. In this study, we aim to compare growth percentile z-scores and MUAC z-scores in diagnosing and classifying malnutrition in children with CF and assess the relationship between their degree of malnourishment and corresponding pulmonary function tests (PFTs). In this retrospective observational outpatient study of 49 pediatric CF patients, data were collected on baseline characteristics, anthropometrics, and PFTs over 12 months. Agreement in malnutrition diagnoses was quantified by Cohen κ statistics. Pearson test assessed the correlation between MUAC and BMI z-scores as well as PFTs and anthropometrics. Serial anthropometrics and PFTs were obtained and compared for a subset of patients (n = 28). Growth percentile and MUAC z-scores were positively correlated in diagnosing malnutrition (Pearson correlation r = 0.87), but MUAC z-scores identified more patients as malnourished compared with growth percentile z-scores (49% vs 12%, Cohen κ of 0.22 [95% CI, 0.04-0.40]). There was no significant relationship between anthropometrics and PFTs. MUAC z-scores increased significantly over time, but BMI z-scores did not show this trend. Our small-scale data suggest a promising role for MUAC z-scores in classifying malnutrition and in measuring changes in nutrition status over time in pediatric CF.