Diagnosis Of Cystic Fibrosis Research Articles

Cystic fibrosis management in pediatric population—from clinical features to personalized therapy

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). In 1949, it's been identified as a monogenic disease and was thought to primarily affect individuals of Northern European descent. It was the most prevalent autosomal recessive disease that shortens life. With the availability of multiple testing methodologies nowadays, there is a chance to create novel and enhanced treatment options. Even in the absence of a high sweat chloride test (SCT) result, the discovery of two causal mutations is diagnostic for cystic fibrosis (CF). For a CF diagnosis, however, at least two positive E sweat chloride tests are still required. In order to achieve early and active intervention to manage cystic fibrosis (CF) and its comorbidities, treatment regimens for pediatric patients should be evaluated, improved, and closely monitored. New developments in the treatment of cystic fibrosis (CF) have led to the development of medications derived from molecules that target the pathogenetic pathway of the illness. These options are very efficient and allow pediatric patients to receive individualized care. However, in order to better direct patient care and enhance patient outcomes, it is crucial to research uncommon CF mutations, which can provide crucial information about the prognosis of the disease and the relationships between genotype and phenotype. To ensure the success of creating novel, safer, and more efficient treatment approaches, a deeper understanding of the pathogeny of the illness is required. In the age of customized medicine, genetic research will be essential to improving patient care and quality of life for those with uncommon mutations.

International Perspectives of Extended Genetic Sequencing When Used as Part of Newborn Screening to Identify Cystic Fibrosis.

There is increasing interest in using extended genetic sequencing (EGS) in newborn screening (NBS) for cystic fibrosis (CF). How this is implemented will change the number of children being given an uncertain outcome of CRMS/CFSPID (cystic fibrosis transmembrane conductance regulator (CFTR)-related metabolic syndrome/CF Screen Positive Inconclusive Diagnosis), probable carrier results, and the number of missed CF diagnoses. An international survey of CF health professionals was used to gather views on two approaches to EGS-specific (may reduce detection of CRMS/CFSID but miss some CF cases) versus sensitive (may increase detection of CRMS/CFSPID but avoid missing more CF cases). Health professionals acknowledged the anxiety caused to parents (and health professionals) from the uncertainty surrounding the prognosis and management of CRMS/CFSPID. However, most preferred the sensitive approach, as overall, identifying more cases of CRMS/CFSPID was viewed as less physically and psychologically damaging than a missed case of CF. The importance of early diagnosis and treatment for CF to ensure better health outcomes and reducing diagnostic odysseys for parents were highlighted. A potential benefit to identifying more children with CRMS/CFSPID included increasing knowledge to obtain a better understanding of how these children should best be managed in the future.

Diagnosis of Cystic Fibrosis Beyond Childhood in India

Abstract Cystic fibrosis (CF) is a life-limiting genetic condition with multisystemic manifestations. However, there are vast phenotypic as well as genotypic variations. This contributes to delay in diagnosis, especially in pancreatic-sufficient patients who may not manifest typical symptomatology. The last decade has witnessed significant breakthroughs in CF therapeutics. This in combination with early diagnosis through newborn screening, and aggressive supportive care can offer near-normal life expectancy for a majority of patients with CF (pwCF) worldwide. Even while addressing disparities in CF care around the world, it is crucial to train medical professionals to suspect and diagnose CF in children as well as in adults. Here, we share our experience of pwCF diagnosed beyond 16 years of age with an aim to highlight the clinical presentations in young adults, the need for screening family members of a newly diagnosed pwCF, and the negative effects of late diagnosis of CF.

Racial inequities and rare CFTR variants: Impact on cystic fibrosis diagnosis and treatment

Cystic fibrosis (CF) has been traditionally viewed as a disease that primarily affects White individuals. The disorder results from mutations in the CF transmembrane conductance regulator (CFTR), with varying incidence of CF reported among Black, Indigenous, and People of Color (BIPOC). However, CF occurs among all races, ethnicities, and geographic ancestries, and BIPOC patients typically exhibit worse clinical outcomes. These populations are more likely to carry rare CFTR variants omitted from newborn screening panels, leading to disparities in care such as delayed diagnosis and treatment. In this study, we present a case-in-point describing an individual of Gambian descent identified with CF. Patient genotype includes a premature termination codon (PTC) (c.2353C > T) and previously undescribed single nucleotide deletion (c.1970delG), arguing against effectiveness of currently available CFTR modulator-based interventions. Strategies for overcoming these two variants will likely include combinations of PTC suppressors, nonsense mediated decay inhibitors, and/or alternative approaches (e.g. gene editing). Investigations such as the present study establish a foundation from which therapeutic treatments may be developed. Importantly, c.2353C > T and c.1970delG were not detected in the patient by traditional CFTR screening panels, which include an implicit racial and ethnic diagnostic bias as these tests are comprised of mutations largely observed in people of European ancestry. We suggest that next-generation sequencing of CFTR should be utilized to confirm or exclude a CF diagnosis, in order to equitably serve BIPOC individuals. Additional epidemiologic data, basic science investigations, and translational work are imperative for improving understanding of disease prevalence and progression, CFTR variant frequency, genotype-phenotype correlation, pharmacologic responsiveness, and personalized medicine approaches for patients with African ancestry and other historically understudied geographic lineages

International disparities in diagnosis and treatment access for cystic fibrosis.

Elexacaftor/tezacaftor/ivacaftor (ETI) has revolutionized cystic fibrosis (CF) treatment. However, previous research has demonstrated profound global disparities in diagnosis and treatment access. If unaddressed, these threaten to widen existing health inequities. Therefore, in this analysis we aimed to reappraise gaps and evaluate progress in diagnosis and treatment equity in high-income (HIC) versus low- and middle-income countries (LMICs). Estimates of the global CF population were made in 158 countries using patient registries, systematic literature searches, and an international survey of 14 CF experts. Estimates of the global burden of undiagnosed CF were made using epidemiological studies identified in literature searches and registry coverage data. The proportion of people receiving ETI was estimated using publicly available revenue data and a survey of 23 national drug pricing databases. 188,336 (163,421-209,204) people are estimated to have CF in 96 countries. Of these, 112,955 (60%) were diagnosed and 51,322 (27%) received ETI. The undiagnosed patient burden is estimated to be 75,381 people, with 82% in LMICs. ETI is reimbursed in 35 HICs, but only one LMIC. Four years after approval, there are 14,911 people diagnosed with CF who live in a country where ETI is inaccessible. This increases to 76,199 when including the estimated undiagnosed population. Equitable access to CFTR modulators must become a top priority for the international CF community. ETI costs up to $322,000 per year but could be manufactured for $5000 to allow access under a voluntary license. Given the extent of disparities, other mechanisms to improve access that circumvent the manufacturer should also be considered.

Prevalence, stability, and clinical significance of an isolated low FEV1 spirometry pattern in children.

In adults, an isolated low FEV1 pattern (an FEV1 below the lower limit of normal with a preserved FVC and FEV1/FVC) has been associated with the risk of developing airway obstruction. Our objective was to examine the prevalence, stability, and clinical significance of an isolated low FEV1 pattern in the pediatric population. We conducted a retrospective study of spirometries from children ages 6-21 years and categorized tests into spirometry patterns according to published guidelines and recent literature. In a subgroup of tests with an isolated low FEV1 pattern, we evaluated spirometry technique. We also examined the association of having a test with an isolated low FEV1 pattern with clinical markers of disease severity in a subgroup of children with cystic fibrosis (CF). The isolated low FEV1 pattern was uncommon across the 29,979 tests included (n = 645 [2%]). In the 263 children with an isolated low FEV1 pattern who had a follow-up test performed, the most frequent spirometry pattern at last test was normal (n = 123 [47%]). A primary diagnosis of CF was associated with increased odds of having at least one test with an isolated low FEV1 pattern (OR = 8.37, 95%CI = 4.70-15.96, p < .001). The spirometry quality in a subgroup of tests with an isolated low FEV1 pattern (n = 50) was satisfactory. In the subgroup of children with CF (n = 102), those who had a test with an isolated low FEV1 pattern had higher odds of using oral antibiotics in the last 12 months than those who had a normal pattern (OR = 3.50, 95%CI = 1.15-10.63, p = .03). The isolated low FEV1 pattern can occur repeatedly over time, usually transitions to a normal pattern, is not due to a poor spirometry technique, and could be clinically relevant in children with chronic lung diseases.

Correlation Between Lung Clearance Index (LCI) and Forced Expiratory Volume (FEV1) in Children with Cystic Fibrosis (CF): A Cross-Sectional Study

Background: The Lung Clearance Index (LCI) serves as a non-uniform ventilation index utilized for monitoring pulmonary function in patients with cystic fibrosis (CF). Lung Clearance Index exhibits higher sensitivity compared to forced expiratory volume in 1 second (FEV1) for early detection of lung disease and does not necessitate active patient cooperation, as required for FEV1 measured through spirometry. Presently, FEV1 is the standard parameter employed for monitoring lung function in CF patients. Objectives: The objective of this study was to assess the correlation between LCI and FEV1 in patients with cystic fibrosis. Methods: This cross-sectional study enrolled children aged 6 to 18 years with confirmed CF diagnosis, who were referred to the CF clinic at Children's Medical Center Hospital (Tehran, Iran). Participants completed consent forms and subsequently underwent pulmonary function tests. Lung Clearance Index was calculated using the exhaling-D device via the Multiple Breath Washout (MBW) method, followed by FEV1 assessment through spirometry. Results: The study included 52 patients with an average age of 12 years, among whom 52% were males. The mean ± standard deviation of FEV1 and LCI were 80.2% ± 25.3 and 8.9 ± 2.8, respectively. A significant inverse relationship was observed between these two parameters in the study (r = -0.49, P = 0.001). Conclusions: These findings further underscore the potential utility of LCI, which offers ease of administration and demonstrates high reliability and accuracy compared to FEV1 for monitoring pulmonary function in CF patients.

Family case of cystic fibrosis

Cystic fibrosis is an autosomal recessively inherited monogenic disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, located on the long arm of chromosome 7 (7q31.2). This mutation results in a disruption in the transport of sodium and chloride ions between intercellular fluid and the epithelial cells of the excretory ducts of the exocrine glands. This paper presents the description of a family case of cystic fibrosis involving two patients who have been under observation since birth and are sisters (patient A – 4 years 10 months, patient B – 1 year 11 months). In both patients, neonatal screening and sequential diagnosis of cystic fibrosis identified the DF508/CFTRdele2.3(21kb) mutation, the most prevalent among the Caucasian population in the Russian Federation. The primary concern in managing both patients is the correction of nutritional status and minimization of exacerbations of chronic bronchopulmonary inflammation. To determine the management strategy for these patients, a consultation was held with Dr. E.I. Kondratyeva, a leading cystic fibrosis expert and professor at the MGSC Institute, who serves as the head of the Scientific and Clinical Department of Cystic Fibrosis and the Department of Genetics of Respiratory System Diseases, an expert of the European Society for Cystic Fibrosis Committee on Diagnostics and Registry, and Deputy Chief for Scientific Work of Research Clinical Institute of Childhood of the Ministry of Health of the Moscow Region. The peculiarity of the presented clinical cases lies in the fact that within one family, with an interval of 3 years, two girls with severe disease were born. Early diagnosis was performed for both, which has allowed for the slowing down of the pathology's progression.

Prevalence and disparities in influenza vaccination among patients with COPD: A French nationwide population study

IntroductionDespite concordant international recommendations, many surveys found disappointing rates of influenza vaccination in at-risk populations, ranging from 23% in overall COPD population to more than 70% in more severe COPD subjects. Therefore, we assessed the proportion of French COPD patients non-vaccinated for influenza and their clinical and socio-demographic factors. Materiel and methodsThis was a national retrospective study based on the French health insurance database. We identified “diagnosed COPD”, defined as subjects hospitalized at least once in 2017 with a principal or associated diagnosis of COPD, and “suspected COPD” as those who were prescribed at least thrice long-acting bronchodilators (LAB), after exclusion of patients with a principal diagnosis or secondary associated diagnosis of asthma or cystic fibrosis, patients deceased before the influenza season and patients hospitalized in long-term or in palliative care unit. Multivariate logistic regression was used to assess the association between patients’ characteristics and the lack of influenza vaccination. ResultsFrom the national database, 1 474 396 subjects were identified as “suspected COPD” of whom 528 114 were excluded because of previous diagnosis of asthma or cystic fibrosis, and 350 566 as “diagnosed COPD”. Among the 1 296 848 patients included, 646 687 patients (53.3%) were vaccinated against influenza. Non-vaccinated subjects were significantly younger (62.1 vs 71.6 years old), more often women (47.9% vs 43.1%) and had fewer comorbidities assessed by Charlson's index (3.0 ± 2.2 vs 4.3 ± 2.1). Lack of vaccination was also associated with a lower LAB usage. Also, non-vaccinated subjects neither had severe exacerbation during the study period. Besides there was a significant heterogeneity in vaccination rate by geographic region, from 47% to 57%. In multivariate analysis, variables independently associated with the lack of influenza vaccination were female gender, younger age, fewer comorbidities and lower socio-economic level. ConclusionsThis study using the French exhaustive health insurance database shows that influenza vaccination among COPD patients remains dramatically low and must become a high-priority public-health strategy.

Abstract 1018: Characteristics and outcomes of patients with cystic fibrosis and pancreatic cancer: A population-based comparative analysis

Abstract Introduction: Advancements in diagnosis and treatment of cystic fibrosis (CF) has allowed improvement in overall survival which also in part explains the increasing incidence of malignancies among these patients, particularly, gastrointestinal cancers. Existing data related to the characteristics and outcomes of patients with CF and pancreatic cancer (PC) are limited to small case series. We sought to investigate the same using a large population-based database. Methods: We used TriNetX, a national database comprising approximately 74 million patients across 54 healthcare organizations in the United States. We retrospectively identified patients with CF who also had a diagnosis of PC (using ICD-10 codes). We then performed an age, sex and race-matched analysis to compare patients with CF+PC to patients with CF alone. To study the impact of CF diagnosis on PC-related outcomes, we performed a propensity matched analysis between cohorts of patients with CF+PC and patients with PC alone. Kaplan Meier estimates were used for survival analysis. A p-value of &amp;lt;0.05 was considered statistically significant. Results: We identified a total of 41,655 patients with CF, out of which 198 patients had a diagnosis of PC (0.48 %). A total of 180 patients were included in the propensity matched comparative analysis. Patients with CF and PC had a significantly higher prevalence of type 2 diabetes mellitus (42.8% vs 5.6%, p&amp;lt;0.001), hypertension (58.3% vs 5.6%, p&amp;lt;0.001) and hyperlipidemia (40% vs 5.6%, p&amp;lt;0.001) than patients with CF with no PC. No differences in the prevalence of liver cirrhosis were noted (8.9% vs 5.6%, p=0.22). Patients with PC and CF had a significantly lower prevalence of bronchiectasis (15.8% vs 28.7%, p=0.004). In a propensity matched analysis between patients with CF and PC and PC alone, CF did not impact survival among patients with resectable [HR=1.042 (0.35-3.11), p=0.79] or unresectable/advanced PC [HR=1.17 (0.62-2.22), p=0.09]. Conclusion: To our knowledge, this is the largest analysis investigating the characteristics and outcomes of patients with CF and PC. The prevalence of PC in patients with CF is higher than reported prevalence among general population. We found a significantly higher prevalence of diabetes, hypertension and hyperlipidemia and a significantly lower prevalence of bronchiectasis among patients with CF and PC. CF does not appear to impact overall survival among patients with resectable or unresectable or advanced PC. Our findings may inform risk prediction models for PC among patients with CF. Citation Format: Srija Manchkanti, Shiva J. Gaddam, Udhayvir S. Grewal. Characteristics and outcomes of patients with cystic fibrosis and pancreatic cancer: A population-based comparative analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1018.

Diversity of CFTR variants across ancestries characterized using 454,727 UK biobank whole exome sequences

BackgroundLimited understanding of the diversity of variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene across ancestries hampers efforts to advance molecular diagnosis of cystic fibrosis (CF). The consequences pose a risk of delayed diagnoses and subsequently worsened health outcomes for patients. Therefore, characterizing the spectrum of CFTR variants across ancestries is critical for revolutionizing molecular diagnoses of CF.MethodsWe analyzed 454,727 UK Biobank (UKBB) whole-exome sequences to characterize the diversity of CFTR variants across ancestries. Using the PanUKBB classification, the participants were assigned into six major groups: African (AFR), American/American Admixed (AMR), Central South Asia (CSA), East Asian (EAS), European (EUR), and Middle East (MID). We segregated ancestry-specific CFTR variants, including those that are CF-causing or clinically relevant. The ages of certain CF-causing variants were determined and analyzed for selective pressure effects, and curated phenotype analysis was performed for participants with clinically relevant CFTR genotypes.ResultsWe detected over 4000 CFTR variants, including novel ancestry-specific variants, across six ancestries. Europeans had the most unique CFTR variants [n = 2212], while the American group had the least unique variants [n = 23]. F508del was the most prevalent CF-causing variant found in all ancestries, except in EAS, where V520F was the most prevalent. Common EAS variants such as 3600G > A, V456A, and V520, which appeared approximately 270, 215, and 338 generations ago, respectively, did not show evidence of selective pressure. Sixteen participants had two CF-causing variants, with two being diagnosed with CF. We found 154 participants harboring a CF-causing and varying clinical consequences (VCC) variant. Phenotype analysis performed for participants with multiple clinically relevant variants returned significant associations with CF and its pulmonary phenotypes [Bonferroni-adjusted p < 0.05].ConclusionsWe leveraged the UKBB database to comprehensively characterize the broad spectrum of CFTR variants across ancestries. The detection of over 4000 CFTR variants, including several ancestry-specific and uncharacterized CFTR variants, warrants the need for further characterization of their functional and clinical relevance. Overall, the presentation of classical CF phenotypes seen in non-CF diagnosed participants with more than one CF-causing variant indicates that they may benefit from current CFTR modulator therapies.

Clinical outcomes at 9-10 years of age in children born with cystic fibrosis transmembrane conductance regulator related metabolic syndrome.

There are limited data on cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to analyze outcomes of infants with CRMS up to the age of 9-10 years using the CF Foundation Patient Registry (CFFPR). We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010 and 2020. We classified all patients based on the clinical diagnosis reported by the CF care center and the diagnosis using CFF guideline definitions for CF and CRMS, classifying children into groups based on agreement between clinical report and guideline criteria. Descriptive statistics for the cohort were calculated for demographics, nutritional outcomes, and microbiology for the first year of life and lung function and growth outcomes were summarized for ages 6-10 years. From 2010 to 2020, there were 8765 children with diagnosis of CF or CRMS entered into the CFFPR with sufficient diagnostic data for classification, of which 7591 children had a clinical diagnosis of CF and 1174 had a clinical diagnosis of CRMS. CRMS patients exhibited normal nutritional indices and pulmonary function up to age 9-10 years. The presence of respiratory bacteria associated with CF, such as Pseudomonas aeruginosa from CRMS patients ranged from 2.1% to 9.1% after the first year of life. Children with CRMS demonstrate normal pulmonary and nutritional outcomes into school age. However, a small percentage of children continue to culture CF-associated respiratory pathogens after infancy.

Results of a prospective open observational study of the use of dornase alfa as part of complex therapy for patients with cystic fibrosis

The article discusses results of a prospective observational study of long-term use of the biosimilar dornase alfa (Tigerase) (Generium, Russia) as part of complex therapy in patients with cystic fibrosis in real clinical practice.The aim was to analyze the outcomes of long-term use of the dornase alfa dornase alfa as part of complex therapy in patients with CF (protocol #DRN-CFR-N01).Methods. The study included patients (n = 165) aged 5 years and older from 11 centers for treatment of cystic fibrosis in the Russian Federation with a confirmed diagnosis of cystic fibrosis who were prescribed dornase alfa by their attending physician.Results. The analysis revealed that exacerbations of chronic pulmonary disease during the treatment with dornase alfa were observed in 29 (17.58%) patients included in the study. At the same time, there were no statistically significant changes in FEV1 and FVC (%) against baseline during the treatment in the study population. Adverse events related to the study drug were recorded in 9 (5.45%) patients.Conclusion. Biosimilar dornase alfa demonstrated a favorable efficacy and safety profile in routine clinical practice, which confirms the results of previously published studies.

Experience of correction of enzyme therapy in children with cystic fibrosis using computer systems and means of network communication

Justification. In recent years, great progress in the treatment of cystic fibrosis has been associated with the use of pathogenetic therapy (since 2012 - in world practice, since 2020 in the Russian Federation). Against the background of the use of which the nutritional status, the functional state of the lungs improves, but there is no complete restoration of the impaired functions of the organs, in particular, the external secretory function of the pancreas is restored only in young children with the timely appointment of targeted therapy The purpose of the study: to increase the effectiveness of correction of enzyme replacement therapy by an individualized approach. Methods. 140 children (boys - 81, girls - 59) with MV aged from 1 year to 18 years (average age 12.9±4.8 years) were examined. The study was conducted in 2022 in the Department of Cystic Fibrosis Scientific and «Research Clinical Institute of Childhood of the Ministry of Health of the Moscow Region» (clinical base of the scientific and clinical Department of Cystic fibrosis Research Center for Medical Genetic). Inclusion criteria - diagnosis of cystic fibrosis, chronic pancreatic insufficiency, severe. Exclusion criteria - short bowel syndrome, exacerbation of the disease. The doses of pancreatin per day were evaluated using the calculation method: units/g of fat in food and intestinal syndrome before and after correction using an algorithm of an individualized approach to calculating enzyme therapy. The observation period is 3 months Design: single-center, prospective, comparative Results. The study showed that the majority of 82 patients (59%) in the general group received less than 2000 U/g of fat, which is less than the reference values (2000-4000 U/g). The median daily dose was 1500 U / g of fat, which can be attributed to the peculiarities of dosing and the need for pancreatin in the Russian pediatric population of patients with cystic fibrosis. The results are consistent with the data of recent studies indicating an acceptable dosage range of pancreatin 1000-4000 units / g of fat in food. In the course of the study, an algorithm for individualized correction of enzyme replacement therapy was developed and the effectiveness of this approach was shown. Conclusion. When calculating pancreatin for the fat content in food, the dose was below the recommended values of 2000-4000 units / g and amounted to 1500 units / g, which indicated that it did not meet the needs of children in enzymes and required individual correction. This served as the basis for the development of an algorithm for individualized correction of enzyme replacement therapy. The effectiveness of this approach using computer technology (inpatient program for doctors and mobile version for patients), in the form of reduction / relief of intestinal syndrome, is shown. To increase compliance and to train parents to control diet and enzyme replacement therapy, it is advisable to use computer programs and mobile applications to calculate the diet and dosage of pancreatin for each meal.

Initial characteristics of cystic fibrosis in Algeria: Description of 34 pediatric cases.

Cystic fibrosis (CF) is a rare disease in Algeria, and its prognosis is poor in developing countries. The clinical and demographic knowledge of Algerian pediatric patients diagnosed with CF is incomplete due to the nonexistence of a national medical registry. Hence, the present study is the first Algerian multicentre study on CF. This retrospective study was conducted in western Algeria. Over 1 year, the study included all pediatric patients with a confirmed diagnosis of CF in the pediatric hospital of Oran. Patient characteristics, clinical manifestations, and the prescribed treatment were reported. Thirty-fourchildren (16 boys and 18 girls) participated in this study. Only 15 were diagnosed before the age of 6 months. The sweat chloride test was positive in all patients. Respiratory manifestations were found in all patients, chronic diarrhoea in 29 of them, and growth retardation in 10. Moreover, 25 (73.5%) had low to low intermediate socioeconomic levels. After diagnosis, respiratory complications marked the evolution of the 34 patients, withbronchial congestion observedin 33 of them, while 10 (29.4%) patients presented severe bronchopneumonia and 4 (11.8%) were affected by asthma. Consequently, three (8.8%) died at an average age of 9 years mainly because of respiratory failure. The prognosis of CF is poor in Algeria compared to other developed countries due to the longer diagnostic delay and limited therapeutic alternatives. This representative subset of Algerian pediatric patients with CF will serve as a reference for future studies on CF in Algeria.

Meconium Peritonitis in the Newborn with Cystic Fibrosis and Negative Neonatal Screening for Immunoreactive Trypsinogen: Clinical Case

Background. Meconium ileus is one of the manifestations of cystic fibrosis. It is characterized by intestinal obstruction with viscous meconium leading to perforation and peritonitis. The issues of early diagnosis of cystic fibrosis, management of newborns with meconium ileus and negative neonatal screening for immunoreactive trypsinogen (IRT), as well as IRT decrease causes and mechanisms in patients with meconium ileus require further study. Clinical case description. Routine ultrasound examination at the 33rd week of gestation has shown signs of colon obstruction and meconium peritonitis in the intrauterine child. Surgical treatment of peritonitis was performed urgently on the 1st day after birth. The child was on mechanical ventilation from the 1st day of life. The child has shown signs of intrahepatic cholestasis with direct hyperbilirubinemia (up to 100 μmol/L) and signs of hemorrhagic syndrome (bleeding from injection sites) on the 8th day of life. Negative IRT blood test was received (21.6 ng/mL, normal value &lt; 70 ng/mL) on the 10th day. The fecal elastase concentration was 45 μg/g (normal value &gt; 200 μg/g) (on the same day). Sweat tests were performed on the 21st and 23rd days of life. They have shown high levels of sweat chlorides (112 mmol/L in both samples, normal value — 30–59 mmol/L). The diagnosis of «cystic fibrosis» was established, thus, dornase alfa (dosage — 2.5 mg/day) was added to the therapy. Conclusion. Meconium ileus is one of the specific intestinal manifestations of cystic fibrosis and it commonly can be complicated with intestinal perforation in the intrauterine child with further peritonitis. Children with meconium ileus require sweat tests regardless the neonatal screening results.

The Future of Cystic Fibrosis Care: Exploring AI's Impact on Detection and Therapy

Abstract: Cystic Fibrosis (CF) is a fatal hereditary condition marked by thicker mucus production, which can cause problems with the digestive and respiratory systems. The quality of life and survival rates of CF patients can be improved by early identification and individualized therapy measures. With an emphasis on its applications in diagnosis and therapy, this paper investigates how Artificial Intelligence (AI) is transforming the management of Cystic Fibrosis (CF). AI-powered algorithms are revolutionizing CF diagnosis by utilizing huge genetic, clinical, and imaging data databases. In order to identify CF mutations quickly and precisely, machine learning methods evaluate genomic profiles. Furthermore, AI-driven imaging analysis helps to identify lung and gastrointestinal issues linked to cystic fibrosis early and allows for prompt treatment. Additionally, AI aids in individualized CF therapy by anticipating how patients will react to already available medications and enabling customized treatment regimens. Drug repurposing algorithms find prospective candidates from already-approved drugs, advancing treatment choices. Additionally, AI supports the optimization of pharmacological combinations, enhancing therapeutic results while minimizing side effects. AI also helps with patient stratification by connecting people with CF mutations to therapies that are best for their genetic profiles. Improved treatment effectiveness is promised by this tailored strategy. The transformational potential of artificial intelligence (AI) in the field of cystic fibrosis is highlighted in this review, from early identification to individualized medication, bringing hope for better patient outcomes, and eventually prolonging the lives of people with this difficult ailment.

“If You Have CF, I Will Eat My Shoe”: Lived experiences and needs of individuals with adult-diagnosed cystic fibrosis

RATIONALE: Cystic Fibrosis (CF) is a genetic, multisystem disease 1 that can be diagnosed in both childhood and adulthood. Diagnosis of CF during childhood is well-documented in the literature, and there is substantial information available for the parents of children with CF. 2 However, there is less known about the experiences of those with adult-diagnosed CF coupled with limited to no tailored resources for those who receive a later CF diagnosis. 3 , 4 OBJECTIVES The current study examined the lived experiences and information needs of individuals with adult-diagnosed CF in Canada, as well as attitudes toward receiving CF-related education via the Internet. METHODS Eight individuals diagnosed with CF as adults (M age = 41.71, SD = 14.47) and 9 health care providers (HCP; M age = 45.35, SD = 7.91) completed a brief demographic questionnaire, consent form, and individual semi-structured interview either via Zoom or telephone. Thematic analysis was used to analyze the data collected for each participant group. MAIN RESULTS: Five major themes were generated from both participant groups: (1) CF information needs; (2) challenges; (3) emotions and coping; (4) health service needs; and (5) Internet-delivered resource considerations. CONCLUSIONS The findings highlight the unique experiences and challenges faced by those diagnosed with CF in adulthood. Information from the current study will be used alongside the empirical literature to inform the development of an evidence-based, Internet-delivered resource for this population.

Impact of elexacaftor/tezacaftor/ivacaftor on respiratory colonization in an adult cystic fibrosis clinic

BackgroundLittle research has been completed on the correlation between cystic fibrosis (CF) modulator therapy and its effect on respiratory cultures in CF patients. This study evaluated the effect of elexacaftor/tezacaftor/ivacaftor (ETI) on respiratory colonization with Pseudomonas aeruginosa. MethodsThis single center, IRB approved, retrospective chart review compared patient data two years immediately prior to ETI initiation with patient data two years post-initiation from January 2017-December 2022. Patients were included in the study if they were at least 18 years old with a diagnosis of CF and had at least one month of ETI dispensed, at least one sputum culture obtained, and were currently on ETI. Those who had not been seen since ETI initiation or received a bilateral lung transplant were excluded. The primary outcome was rate of patients with respiratory colonization post-ETI. Colonization was defined as two or more positive P. aeruginosa cultures in a 12-month period. Decolonization was defined as three consecutive negative P. aeruginosa cultures after previous colonization. Key secondary outcomes included average time to discontinuation of mucolytic therapy and relative risk of pulmonary exacerbation. ResultsA significant reduction (p<0.001) in colonization with P. aeruginosa was observed with 49 patients in the pre-ETI group compared to 25 in the post-ETI group meeting the definition of colonization (n=79). Average time to discontinuation of mucolytic therapy was 14 months (p=0.002). Relative risk of pulmonary exacerbation was 4.80 (p<0.001). ConclusionsETI use resulted in reduced colonization with P. aeruginosa, discontinuation of mucolytic therapy, and decreased frequency of pulmonary exacerbation.

Advances in the Study of Common and Rare CFTR Complex Alleles Using Intestinal Organoids.

Complex alleles (CAs) arise when two or more nucleotide variants are present on a single allele. CAs of the CFTR gene complicate the cystic fibrosis diagnosis process, classification of pathogenic variants, and determination of the clinical picture of the disease and increase the need for additional studies to determine their pathogenicity and modulatory effect in response to targeted therapy. For several different populations around the world, characteristic CAs of the CFTR gene have been discovered, although in general the prevalence and pathogenicity of CAs have not been sufficiently studied. This review presents examples of using intestinal organoid models for assessments of the two most common and two rare CFTR CAs in individuals with cystic fibrosis in Russia.