J Pediatr Psychol. 2024 May 16:jsae034. doi: 10.1093/jpepsy/jsae034. Online ahead of print.

ABSTRACT

OBJECTIVE: Suboptimal nutritional adherence in adolescents with cystic fibrosis (awCF) has been associated with lower lung function. AwCF often have more independence in dietary decisions than younger children, yet little research has examined how adolescent decision-making relates to nutritional adherence. This study explored whether components of adolescent decision-making involvement facilitate enzyme and caloric adherence in awCF.

METHODS: 37 families participated and completed study procedures. AwCF and caregivers completed electronic surveys, including the Decision-Making Involvement Scale (DMIS). The DMIS evaluated awCF behaviors during nutrition-related decision-making/discussions with caregivers using DMIS subscales: Child Seek (asking for help/advice from caregivers), Child Express (awCF stating opinions) and Joint/Options (awCF participating in joint decision-making or caregiver providing options). AwCF completed 2, 24-hr diet recalls via videoconferencing/phone to estimate adherence. Chart reviews collected medical information. DMIS subscales were regressed onto enzyme and caloric adherence.

RESULTS: 43% of awCF met calorie recommendations; 48.6% took all enzymes as prescribed. Caloric adherence was positively correlated with adolescent- and parent-reported Child Seek (r = 0.53; r = 0.36) and adolescent-reported Joint/Options (r = 0.41). Per adolescent-report, the caloric adherence regression model was significant, with Child Seek contributing unique variance in caloric adherence (β = .62, p = .03). Parent-reported adolescent-decision-making involvement significantly predicted caloric adherence, but none of the subscales contributed unique variance. No other regressions were significant.

CONCLUSIONS: When awCF participated in nutrition-related discussions with a caregiver, especially with questions, caloric adherence was better. Future research should examine whether family factors influence these results. AwCF are encouraged to ask questions in nutrition discussions.

PMID:38752579 | DOI:10.1093/jpepsy/jsae034

Pediatr Pulmonol. 2024 May 15. doi: 10.1002/ppul.27041. Online ahead of print.

ABSTRACT

The aim was to gather an overview of the evidence of monoclonal antibody therapies in respiratory syncytial virus (RSV) prophylaxis in children. For this umbrella review of previous meta-analyses, we searched PubMed, Scopus, and Web of Science databases in August 2023. We included systematic reviews with meta-analyses of randomized controlled trials. One author extracted the data, and another author validated the data. We extracted all analyses focusing on clinical outcomes and comparing prophylaxis to placebo. Risk of bias in systematic reviews (ROBIS) tool was used to analyze the risk of bias in the included reviews. AMSTAR-2 was used to evaluate the quality of the included reviews. After screening of 323 abstracts and 22 full reports, a total of seven systematic reviews with meta-analyses were included. The risk of bias was rated to be low in four and high in three of these. Three reviews were of moderate quality, one low, and three very low quality according to AMSTAR-2 classification. Six of the meta-analyses were direct comparisons, and one was a network meta-analysis. Five of the reviews focused on palivizumab, one in nirsevimab, and one included all monoclonal antibodies. Six reviews focused on preterm neonates and consisted of 42 comparisons to placebo of which 21 showed efficacy, and 21 had no evidence of a difference. The positive effect was seen in all reviews against RSV infection and RSV hospitalization in palivizumab and nirsevimab groups compared to placebo. None of the mortality comparisons showed efficacy. One meta-analysis focused on cystic fibrosis patients and had eight comparisons, but it was underpowered to detect any results. The overall evidence from previous meta-analyses shows that monoclonal antibodies are effective in preventing RSV infections and RSV hospitalizations in preterm infants. However, no effect on mortality was seen in these studies. Evidence certainty has been ranked mainly from low to moderate.

PMID:38751021 | DOI:10.1002/ppul.27041

Pediatr Pulmonol. 2024 May 15. doi: 10.1002/ppul.27066. Online ahead of print.

NO ABSTRACT

PMID:38751016 | DOI:10.1002/ppul.27066

Sports Med Open. 2024 May 15;10(1):54. doi: 10.1186/s40798-024-00722-8.

ABSTRACT

BACKGROUND: This study aims to identify sports interventions for children and adolescents (CaA) with chronic diseases and evaluate their impact on physical, psychological, and social well-being. The findings of this study will contribute to our understanding of the potential benefits of sports interventions for CaA with chronic diseases and inform future interventions to promote their overall health and well-being.

METHODS: A systematic review was conducted in eight databases. This systematic review followed PRISMA guidelines and utilized a comprehensive search strategy to identify studies on sport-based interventions for CaA with chronic diseases. The review included randomized controlled trials and observational studies that focused on physical and psychosocial outcomes.

RESULTS: We screened 10,123 titles and abstracts, reviewed the full text of 622 records, and included 52 primary studies. A total of 2352 participants were assessed with an average of 45 ± 37 participants per study. Among the included studies involving CaA with chronic diseases with an age range from 3 to 18 years, 30% (n = 15) autism spectrum disorders, 21% (n = 11) cerebral palsy, 19% (n = 10) were attention deficit hyperactivity disorder, and 17% (n = 9) obesity. Other diseases included were cancer (n = 5), asthma (n = 1) and cystic fibrosis (n = 1). Interventions involved various sports and physical activities tailored to each chronic disease. The duration and frequency of interventions varied across studies. Most studies assessed physical outcomes, including motor performance and physical fitness measures. Psychosocial outcomes were also evaluated, focusing on behavioural problems, social competencies, and health-related quality of life.

CONCLUSION: Overall, sport-based interventions effectively improved physical and psychosocial outcomes in CaA with chronic diseases. Interventions are generally safe, and participants adhere to the prescribed protocols favorably. Despite that, there is little evidence that interventions are being implemented. Future studies should include interventions tailored to meet the common issues experienced by CaA with chronic conditions, providing a comprehensive understanding of the impact of sports interventions on those affected.

REGISTRATION: The methodology for this review was pre-determined and registered in the PROSPERO database (registration number: CRD42023397172).

PMID:38750266 | DOI:10.1186/s40798-024-00722-8

J Cyst Fibros. 2024 May 14:S1569-1993(24)00060-2. doi: 10.1016/j.jcf.2024.04.014. Online ahead of print.

ABSTRACT

BACKGROUND: The forskolin-induced swelling (FIS) assay measures CFTR function on patient-derived intestinal organoids (PDIOs) and may guide treatment selection for individuals with Cystic Fibrosis (CF). The aim of this study is to demonstrate the repeatability and reproducibility of the FIS assay following a detailed Standard Operating Procedure (SOP), thus advancing the validation of the assay for precision medicine (theranostic) applications.

METHODS: Over a 2-year period, FIS responses to CFTR modulators were measured in four European labs. PDIOs from six subjects with CF carrying different CFTR genotypes were used to assess the repeatability and reproducibility across the dynamic range of the assay.

RESULTS: Technical, intra-assay repeatability was high (Lin's concordance correlation coefficient (CCC) 0.95-0.98). Experimental, within-subject repeatability was also high within each lab (CCCs all >0.9). Longer-term repeatability (>1 year) showed more variability (CCCs from 0.67 to 0.95). The reproducibility between labs was also high (CCC ranging from 0.92 to 0.97). Exploratory analysis also found that between-lab percentage of agreement of dichotomized CFTR modulator outcomes for predefined FIS thresholds ranged between 78 and 100 %.

CONCLUSIONS: The observed repeatability and reproducibility of the FIS assay within and across different labs is high and support the use of FIS as biomarker of CFTR function in the presence or absence of CFTR modulators.

PMID:38749892 | DOI:10.1016/j.jcf.2024.04.014

J Cyst Fibros. 2024 May 14:S1569-1993(24)00064-X. doi: 10.1016/j.jcf.2024.05.002. Online ahead of print.

ABSTRACT

BACKGROUND: There is a paucity of knowledge on the longer-term effects of CF transmembrane conductance regulator (CFTR) modulator therapies upon the gut microbiome and associated outcomes. In a pilot study, we investigated longitudinal Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy on the gut microbiota, metabolomic functioning, and clinical outcomes in people with CF (pwCF).

STUDY DESIGN: Faecal samples from 20 pwCF were acquired before and then following 3, 6, and 17+ months of ETI therapy. Samples were subjected to microbiota sequencing and targeted metabolomics to profile and quantify short-chain fatty acid composition. Ten healthy matched controls were included for comparison. Clinical data, including markers of intestinal function were integrated to investigate relationships.

RESULTS: Extended ETI therapy increased core microbiota diversity and composition, which translated to gradual shifts in whole microbiota composition towards that observed in healthy controls. Despite becoming more similar over time, CF microbiota and functional metabolite compositions remained significantly different to healthy controls. Antibiotic treatment for pulmonary infection significantly explained a relatively large degree of variation within the whole microbiota and rarer satellite taxa. Clinical outcomes were not significantly different following ETI.

CONCLUSIONS: Whilst differences persisted, a positive trajectory towards the microbiota observed in healthy controls was found. We posit that progression was predominately impeded by pulmonary antibiotics administration. We recommend future studies use integrated omics approaches within a combination of long-term longitudinal patient studies and model experimental systems. This will deepen our understanding of the impacts of CFTR modulator therapy and respiratory antibiotic interventions upon the gut microbiome and gastrointestinal pathophysiology in CF.

PMID:38749891 | DOI:10.1016/j.jcf.2024.05.002

Transplant Proc. 2024 May 14:S0041-1345(24)00199-4. doi: 10.1016/j.transproceed.2024.03.034. Online ahead of print.

ABSTRACT

BACKGROUND: A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified for double organ liver-pancreas transplantation beyond typical indications. The respiratory symptoms of cystic fibrosis were moderate and well-treated. The patient was endangered mainly by liver insufficiency and recurrent hypoglycemia, which was due to the treatment of diabetes with high doses of insulin. Computed tomography showed mild bronchiectasis, cirrhotic liver, splenomegaly, and atrophy of the pancreas. Pseudomonas aeruginosa colonized the upper respiratory tract. Gastrointestinal complications were sufficient for the patient to be qualified for combined liver-pancreas transplantation.

METHODS: First, a standard hepatectomy was performed. The liver was transplanted orthotopically. Subsequently, the team performed pancreas transplantation through a separate incision. The donor's duodenum was anastomosed to the recipient's jejunum, close to the ligament of Treitz.

RESULTS: No serious complications were noted during the postoperative period. Transplanted organs started functioning without delay. The patient was discharged after 6 weeks in general good condition. Twenty months later, the patient felt well, and the grafts kept functioning properly.

CONCLUSION: Combined liver-pancreas transplantation in patients with CF restores exocrine and endocrine pancreatic function and minimizes the risk of life-threatening complications associated with liver insufficiency. Improvement of life quality coincides with the possibility of discontinuing insulin and pancreatic enzyme supplementation. The combination of liver and pancreas transplantation may prevent advanced pulmonary complications, extend the prognosis of survival, and improve the long-term life quality.

PMID:38749862 | DOI:10.1016/j.transproceed.2024.03.034

Cien Saude Colet. 2024 May;29(5):e17652022. doi: 10.1590/1413-81232024295.17652022. Epub 2023 Jun 30.

ABSTRACT

The complexities referred to in the search for "accuracy" in the diagnosis of cystic fibrosis (CF) point to reflections around "what is needed" in the current situation of "precision medicine". We analyzed the discourses of 19 social actors belonging to the community of specialists in cystic fibrosis, exploring the semantic meanings of the word "precision", and the barriers to diagnosis and innovations in therapeutics. We adopted the critical discourse analysis (CDA) of Norman Fairclough in order to achieve the discursive constructions around the integrality of care, the guarantee and equitable supply of basic social needs. Access was identified as an emic category when in the social arenas of dispute are health needs and the right to life.

PMID:38747779 | DOI:10.1590/1413-81232024295.17652022

Protein Sci. 2024 Jun;33(6):e5021. doi: 10.1002/pro.5021.

ABSTRACT

While nickel-nitrilotriacetic acid (Ni-NTA) has greatly advanced recombinant protein purification, its limitations, including nonspecific binding and partial purification for certain proteins, highlight the necessity for additional purification such as size exclusion and ion exchange chromatography. However, specialized equipment such as FPLC is typically needed but not often available in many laboratories. Here, we show a novel method utilizing polyphosphate (polyP) for purifying proteins with histidine repeats via non-covalent interactions. Our study demonstrates that immobilized polyP efficiently binds to histidine-tagged proteins across a pH range of 5.5-7.5, maintaining binding efficacy even in the presence of reducing agent DTT and chelating agent EDTA. We carried out experiments of purifying various proteins from cell lysates and fractions post-Ni-NTA. Our results demonstrate that polyP resin is capable of further purification post-Ni-NTA without the need for specialized equipment and without compromising protein activity. This cost-effective and convenient method offers a viable approach as a complementary approach to Ni-NTA.

PMID:38747394 | DOI:10.1002/pro.5021

ERJ Open Res. 2024 May 13;10(3):00880-2023. doi: 10.1183/23120541.00880-2023. eCollection 2024 May.

ABSTRACT

The 2023 European Respiratory Society Congress took place on a hybrid platform, with participants joining online and in-person in Milan, Italy. The congress welcomed over 20 000 attendees, bringing together exciting updates in respiratory science and medicine from around the world. In this article, early career members of Assembly 10 (Respiratory Infections) summarise a selection of sessions across a broad range of topics, including presentations on bronchiectasis, nontuberculous mycobacteria, tuberculosis, cystic fibrosis and coronavirus disease 2019.

PMID:38746858 | PMC:PMC11089386 | DOI:10.1183/23120541.00880-2023

ERJ Open Res. 2024 May 13;10(3):00065-2024. doi: 10.1183/23120541.00065-2024. eCollection 2024 May.

ABSTRACT

BACKGROUND: Significant progress in the field of cystic fibrosis (CF) has substantially extended the life expectancy of patients with CF (pwCF). Consequently, the population of adult pwCF has outnumbered paediatric patients in most developed countries. Ageing is a new factor that can contribute to disease complexity and can require adaptation of CF units. Therefore, the necessity for standardised, specialised and multidisciplinary care is imperative. Concerns arise regarding the adequacy of current healthcare, therapeutic and educational offerings.

METHODS: To address these concerns, a multinational survey was conducted to assess the current state of care in specialised multidisciplinary adult and paediatric CF units and identify areas for improvement. Responses were collected from 44 centres providing regular care to CF patients.

RESULTS: The survey unveiled considerable disparities in the availability of critical resources, including diagnostic access, supplementary testing, treatment modalities, transplant and transition programmes, and healthcare professionals' training.

CONCLUSION: This study underscores the urgent need to standardise care across these centres in order to minimise disparities in terms of available resources and training with a particular emphasis on adult pwCF who are becoming more numerous and showing different needs with ageing. The changing landscape of CF in adulthood will require constant monitoring to ensure proper adaptation of the current model of care.

PMID:38746857 | PMC:PMC11089383 | DOI:10.1183/23120541.00065-2024

Sci Data. 2024 May 14;11(1):495. doi: 10.1038/s41597-024-03327-8.

ABSTRACT

Single amino acid substitutions can profoundly affect protein folding, dynamics, and function. The ability to discern between benign and pathogenic substitutions is pivotal for therapeutic interventions and research directions. Given the limitations in experimental examination of these variants, AlphaMissense has emerged as a promising predictor of the pathogenicity of missense variants. Since heterogenous performance on different types of proteins can be expected, we assessed the efficacy of AlphaMissense across several protein groups (e.g. soluble, transmembrane, and mitochondrial proteins) and regions (e.g. intramembrane, membrane interacting, and high confidence AlphaFold segments) using ClinVar data for validation. Our comprehensive evaluation showed that AlphaMissense delivers outstanding performance, with MCC scores predominantly between 0.6 and 0.74. We observed low performance on disordered datasets and ClinVar data related to the CFTR ABC protein. However, a superior performance was shown when benchmarked against the high quality CFTR2 database. Our results with CFTR emphasizes AlphaMissense's potential in pinpointing functional hot spots, with its performance likely surpassing benchmarks calculated from ClinVar and ProteinGym datasets.

PMID:38744964 | DOI:10.1038/s41597-024-03327-8

Mol Genet Genomics. 2024 May 14;299(1):52. doi: 10.1007/s00438-024-02119-4.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a rare multi-systemic recessive disorder. The spectrum and the frequencies of CFTR mutations causing CF vary amongst different populations in Europe and the Middle East. In this study, we characterised the distribution of CF-causing mutations (i.e. pathogenic variants in the CFTR gene) in a representative CF cohort from the Kingdom of Bahrain based on a three-decade-long analysis at a single tertiary centre. We aim to improve CF genetic diagnostics, introduce of CF neonatal screening and provide CFTR modulator therapy (CFTRm).

METHODS: CFTR genotyping and associated clinical information were drawn from a longitudinal cohort. We sequenced 56 people with CF (pwCF) that had one or both CFTR mutations unidentified and carried out comprehensive bioinformatic- and family-based segregation analyses of detected variants, including genotype-phenotype correlations and disease incidence estimates. The study methodology could serve as a basis for other non-European CF populations with a high degree of consanguinity.

RESULTS: Altogether 18 CF-causing mutations were identified, 15 of which were not previously detected in Bahrain, accounting for close to 100% of all population-specific alleles. The most common alleles comprise c.1911delG [2043delG; 22.8%], c.2988+1G > A [3120+1G>A; 16.3%], c.2989-1G>A [3121-1G>A; 14.1%], c.3909C>G [N1303K; 13.0%], and c.1521_1523delCTT [p.PheF508del; 7.6%]. Although the proportion of 1st cousin marriages has decreased to 50%, the frequency of homozygosity in our pwCF is 67.4%, thereby indicating that CF still occurs in large, often related, families. pwCF in Bahrain present with faltering growth, pancreatic insufficiency and classical sino-pulmonary manifestations. Interestingly, two pwCF also suffer from sickle cell disease. The estimated incidence of CF in Bahrain based on data from the last three decades is 1 in 9,880 live births.

CONCLUSION: The most commonCF-causing mutations in Bahraini pwCF were identified, enabling more precise diagnosis, introduction of two-tier neonatal screening and fostering administration of CFTRm.

PMID:38744777 | DOI:10.1007/s00438-024-02119-4

J Clin Invest. 2024 May 14:e174500. doi: 10.1172/JCI174500. Online ahead of print.

ABSTRACT

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), a multiorgan disease that exhibits diverse metabolic defects. However, other than specific CFTR mutations, the factors that influence disease progression and severity remain poorly understood. Aberrant metabolite levels have been reported, but whether CFTR loss itself or secondary abnormalities (infection, inflammation, malnutrition, and various treatments) drive metabolic defects are uncertain. Here, we implemented comprehensive arteriovenous metabolomics in newborn CF pigs, and the results revealed CFTR as a bona fide regulator of metabolism. CFTR loss impaired metabolite exchange across organs, including disrupted lung uptake of fatty acids yet enhanced uptake of arachidonic acid, a precursor of pro-inflammatory cytokines. CFTR loss also impaired kidney reabsorption of amino acids and lactate and abolished renal glucose homeostasis. These and additional unexpected metabolic defects prior to disease manifestations reveal a fundamental role for CFTR in controlling multi-organ metabolism. Such discovery informs a basic understanding of CF, provides a foundation for future investigation, and has implications for developing therapies targeting only a single tissue.

PMID:38743489 | DOI:10.1172/JCI174500

mBio. 2024 May 14:e0060924. doi: 10.1128/mbio.00609-24. Online ahead of print.

ABSTRACT

Mycobacterium abscessus (Mab) affects patients with immunosuppression or underlying structural lung diseases such as cystic fibrosis (CF). Additionally, Mab poses clinical challenges due to its resistance to multiple antibiotics. Herein, we investigated the synergistic effect of dual β-lactams [sulopenem and cefuroxime (CXM)] or the combination of sulopenem and CXM with β-lactamase inhibitors [BLIs-avibactam (AVI) or durlobactam (DUR)]. The sulopenem-CXM combination yielded low minimum inhibitory concentration (MIC) values for 54 clinical Mab isolates and ATCC19977 (MIC50 and MIC90 ≤0.25 µg/mL). Similar synergistic effects were observed in time-kill studies conducted at concentrations achievable in clinical settings. Sulopenem-CXM outperformed monotherapy, yielding ~1.5 Log10 CFU/mL reduction during 10 days. Addition of BLIs enhanced this antibacterial effect, resulting in an additional reduction of CFUs (~3 Log10 for sulopenem-CXM and AVI and ~4 Log10 for sulopenem-DUR). Exploration of the potential mechanisms of the synergy focused on their interactions with L,D-transpeptidases (Ldts; LdtMab1-LdtMab4), penicillin-binding-protein B (PBP B), and D,D-carboxypeptidase (DDC). Acyl complexes, identified via mass spectrometry analysis, demonstrated the binding of sulopenem with LdtMab2-LdtMab4, DDC, and PBP B and CXM with LdtMab2 and PBP B. Molecular docking and mass spectrometry data suggest the formation of a covalent adduct between sulopenem and LdtMab2 after the nucleophilic attack of the cysteine residue at the β-lactam carbonyl carbon, leading to the cleavage of the β-lactam ring and the establishment of a thioester bond linking the LdtMab2 with sulopenem. In conclusion, we demonstrated the biochemical basis of the synergy of sulopenem-CXM with or without BLIs. These findings potentially broaden the selection of oral therapeutic agents to combat Mab.

IMPORTANCE: Treating infections from Mycobacterium abscessus (Mab), particularly those resistant to common antibiotics like macrolides, is notoriously difficult, akin to a never-ending struggle for healthcare providers. The rate of treatment failure is even higher than that seen with multidrug-resistant tuberculosis. The role of combination β-lactams in inhibiting L,D-transpeptidation, the major peptidoglycan crosslink reaction in Mab, is an area of intense investigation, and clinicians have utilized this approach in the treatment of macrolide-resistant Mab, with reports showing clinical success. In our study, we found that cefuroxime and sulopenem, when used together, display a significant synergistic effect. If this promising result seen in lab settings, translates well into real-world clinical effectiveness, it could revolutionize current treatment methods. This combination could either replace the need for more complex intravenous medications or serve as a "step down" to an oral medication regimen. Such a shift would be much easier for patients to manage, enhancing their comfort and likelihood of sticking to the treatment plan, which could lead to better outcomes in tackling these tough infections. Our research delved into how these drugs inhibit cell wall synthesis, examined time-kill data and binding studies, and provided a scientific basis for the observed synergy in cell-based assays.

PMID:38742824 | DOI:10.1128/mbio.00609-24

Int J Rheum Dis. 2024 May;27(5):e15185. doi: 10.1111/1756-185X.15185.

ABSTRACT

OBJECTIVES: This study aimed to unravel the complexities of autoimmune diseases by conducting a comprehensive analysis of gene expression data across 10 conditions, including systemic lupus erythematosus (SLE), psoriasis, Sjögren's syndrome, sclerosis, immune-associated diseases, osteoarthritis, cystic fibrosis, inflammatory bowel disease (IBD), type 1 diabetes, and Guillain-Barré syndrome.

METHODS: Gene expression profiles were rigorously examined to identify both upregulated and downregulated genes specific to each autoimmune disease. The study employed visual representation techniques such as heatmaps, volcano plots, and contour-MA plots to provide an intuitive understanding of the complex gene expression patterns in these conditions.

RESULTS: Distinct gene expression profiles for each autoimmune condition were uncovered, with psoriasis and osteoarthritis standing out due to a multitude of both upregulated and downregulated genes, indicating intricate molecular interplays in these disorders. Notably, common upregulated and downregulated genes were identified across various autoimmune conditions, with genes like SELENBP1, MMP9, BNC1, and COL1A1 emerging as pivotal players.

CONCLUSION: This research contributes valuable insights into the molecular signatures of autoimmune diseases, highlighting the unique gene expression patterns characterizing each condition. The identification of common genes shared among different autoimmune conditions, and their potential role in mitigating the risk of rare diseases in patients with more prevalent conditions, underscores the growing significance of genetics in healthcare and the promising future of personalized medicine.

PMID:38742742 | DOI:10.1111/1756-185X.15185

Epidemiol Prev. 2024 Mar-Apr;48(2 Suppl 2):1-41. doi: 10.19191/EP24.2.S2.031.

ABSTRACT

INTRODUCTION: Italian Cystic Fibrosis Registry (ICFR) collects data of patients with cystic fibrosis (CF) through the collaboration with Italian CF referral and support Centres (Italian law 548/93). It aims at analysing medium and long-term clinical and epidemiological trends, identifying healthcare needs at regional and national levels, contributing to healthcare programmes, and resource allocation. Italian data are also compared at international level through the collaboration with the European CF Registry for sharing epidemiological data on general aspects like CF epidemiology and specific topics such as the use of CFTR modulators.

OBJECTIVES: The purpose of this Report is to provide updated demographic and clinical data of the Italian FC population for the years 2021 and 2022, to contribute essential information for the implementation of projects aimed at improving the management of patients affected by this disease.

DESIGN: Analyses and results presented in this Report pertain to patients currently under care at Italian National Referral and Support Centres for Cystic Fibrosis and Paediatric Hospital 'Bambino Gesù' in the 2021-2022 period. Data were submitted by clinical Centres through a dedicated web-based software and underwent dual quality control (QC) measures: automated quantitative QC within the software and secondary QC at the European level before the integration into the European Cystic Fibrosis Registry. These measures ensure data completeness, accuracy, and longitudinal consistency with European core data.

SETTING AND PARTICIPANTS: A total of 27 CF Centres, including referral and support centres, as well as 'Bambino Gesù' Children's Hospital CF centre, submitted their data to ICFR for the years 2021-2022. Althourgh CF Centres in Verona and Messina do not use the ICFR software, their data are centrally collected and subsequently forwarded to the European Registry. Data from service centres in Treviso and Rovereto are transmitted via the Verona CF Centre. Data from Sardinia Centre are currently unavailable.

RESULTS: The results section provides a comprehensive overview of various aspects of CF epidemiology and patient characteristics. 1.Demography: in 2021 and 2022, 5,977 and 6,077 CF patients were respectively included in the ICFR, with median ages of 23.3 and 23.7 years. The prevalence rates were 10.1 and 10.3 per 100,000 residents in Italy for the respective years, with males comprising 51.6% on average. The distribution by age showed a higher frequency among patients aged 7 to 35 years; adult patients constituted 63.5% on average in both years. 2. Diagnosis: most CF patients were diagnosed before the age of two (mean value 57.9%), with a significant percentage diagnosed in adult age (35.4% in 2021 and 25.6% in 2022). 3.New diagnoses: there were 113 new diagnoses in 2021 and 121 in 2022, with estimated incidences of 1 in 9,097 living births in 2021 and 1 in 6,232 in 2022. 4. Genetics: genetic analyses were conducted on 99.9% of patients, revealing CFTR gene mutations in over 98% of cases. The F508del mutation was the most common (44% of alleles in 2021), with 18% of patients having at least one "residual function" mutation. Gating mutations were present in 3.4% of Italian patients, while 20% had at least one-stop codon mutation. 5.Lung function: lung function, measured by percent predicted (pp)FEV1 (Forced Expiratory Volume in the first second) progressively declined before adulthood, with the majority of paediatric patients (92.8% in 2021 and 93.8% in 2022) maintaining a ppFEV1≥70%. 6.Nutrition: critical periods for nutrition were identified as the first 6 months of life and adolescence, with higher prevalence of malnourished male adolescents compared to females. Suboptimal BMI values were more common in adult females (28.7% in 2021 and 26.9% in 2022) compared to males (14.2% in 2021 and 12.6% in 2022). 7. Complications: CF-related liver disease without cirrhosis was prevalent in patients under 18 years (21.9% in 2021 and 21.2 in 2022), while CF-related diabetes was most frequent in adults (24.2%). 8.Transplantation: over the two-year period, 28 patients underwent double-lung transplantation, with median ages of 29.1 in 2021 and 35.3 in 2022, respectively. Median waiting times ranged from 9.4 to 11.6 months. 9.Microbiology: chronic Pseudomonas aeruginosa infection affected 37.2% of adult patients in 2021 and 36.0% in 2022, compared to 7.4% and 6.5% in paediatric patients. Staphylococcus aureus infection rates were 34.6% and 42.2% in 2021 among adults and 34.4% and 36.7% in 2022 among paediatric patients. 10. Mortality: a total of 34 patients died during the 2021-22 period (19 females, 15 males), with median ages at death of 43.7 years in 2021 and 46 years in 2022 (excluding transplanted patients).

CONCLUSIONS: The present Report is an update of the data published in the past years and summarizes the main epidemiological and clinical data regarding Italian CF subjects in the years 2021 and 2022. The number of patients registered in 2021 was 5,977, while in 2022 was 6,077. The population coverage estimates for 2022 to be around 97%. In 2020, 60.5% of patients were older than 18 years, in 2022 adult patients account for 63.5% of the Italian CF population. Over the years, therefore, an increase in the median age of Italian CF patients has been observed, reaching 23.7 years in 2022. The absolute number of new diagnoses per year remains substantially unchanged over the years (a total of 234 in the period under review). The median age at diagnosis in 2022 was 2.5 months, 62.6% of subjects are really diagnosed within the first year of life and almost 90% of them are diagnosed through neonatal screening. In 2022, almost all patients underwent genetic analysis (99.9%). Data collected confirm the great variability among Italian CF patients. As regards respiratory function, what is reported in previous reports is here confirmed, with an ever-increasing percentage of subjects under the age of 18 having normal respiratory function, moreover, less than 1% of paediatric patients has a severe lung function (ppFEV1<40). The marked improvement in this indicator in the adult population seems to be mainly due to the introduction from 2021 in Italy of therapy with highly effective CFTR modulators. At the same time, the close positive correlation between nutritional status and respiratory function is confirmed for the adult population. As regards chronic infection by Pseudomonas aeruginosa, in 2022, a reduction in the percentage of chronic infection is observed both among adults (36% vs 38.8% in 2020) and in paediatric patients (6.5% vs 7.6% in 2020). The most frequent complication in both paediatric and adult populations is liver disease (respectively, in 24.2% and 41.3% of subjects). In the two-year period, 34 patients died; their median age at death was between 43 and 46 years (transplant patients excluded); only two patients under the age of 18 died in the period 2021 and 2022, confirming once again that mortality in paediatric age is a rare event. The data presented in this Report shows how the register can be a national and international point of reference for CF patients and the scientific community, a tool for describing the Italian CF population over the years, and a starting point for planning epidemiological studies and clinical studies.

PMID:38742380 | DOI:10.19191/EP24.2.S2.031

Exp Clin Transplant. 2024 Apr;22(4):322-327. doi: 10.6002/ect.2024.0010.

ABSTRACT

Lung transplant is an effective method of treating patients with end-stage respiratory diseases, but problems such as the imbalance between the number of donor organs and the number ofrecipients needing organs still play a leading role. From a transplant point of view, a multiorgan donor is considered of greatest efficiency, so that all organs that can potentially be used should be transplanted. The combination of the vast geographical territory of Russia, the shortage of actual donors, and the relatively small number of transplant centers has led to the need to transport donor lungs by air over long distances. There were already precedents in the world for remote preservation of donor organs for transplant. In this study, we have described the unique experience of remote evaluation of donor lungs with their subsequent air transportation and transplantation, which is the first such description in Russia to our knowledge. The donor lungs for lung transplant were brought from medical institutions of the Samara region to Moscow. During remote evaluation, all information was transmitted to the transplant center by providing access to the automated information system "Organ Donation," which was used at that time by the service and contained all information about a potential donor in real time. The 2 transplant candidates had end-stage cystic fibrosis and severe respiratory failure; both patients underwent organ implantation from donors located outside their regions. In conditions of shortages of donor organs, long-distance transportation is a reasonable, feasible, and safe procedure.

PMID:38742326 | DOI:10.6002/ect.2024.0010

Pediatr Pulmonol. 2024 May 14. doi: 10.1002/ppul.27061. Online ahead of print.

ABSTRACT

INTRODUCTION: Obstructive sleep apnea (OSA) is common in children with cystic fibrosis (CF). Highly effective modulator therapies (HEMT) have led to improved sinopulmonary disease, but whether this translates to a lower frequency of OSA is unknown.

METHODS: We conducted a single center retrospective review of polysomnographic (PSG) data from 2012 to 2023 in patients aged 0-18 years with CF to assess frequency of OSA. Participants were classified based on HEMT status. Logistic regression was used to quantify the association between HEMT and OSA with p < .05 considered significant.

RESULTS: Forty-nine children underwent PSG during the study period. Ten percent were of non-White race and 24% were of Hispanic ethnicity. Twenty-one children (43%) were on HEMT. These children were older than those not on modulators (11.6 vs. 6.4 years; p = .0001) but no different with respect to gender, race, nutritional status, or lung function. Twenty-eight (57%) children had OSA. Odds of having OSA were higher in the HEMT group (odds ratio [OR] = 4.3; 95% confidence interval [CI]: 1.2-14.9; p = .02). Tonsillar hypertrophy was associated with an increased odds of having OSA independent of modulator status (OR: 6.6; 95% CI: 1.2-37.9; p = .03).

CONCLUSIONS: OSA is frequently diagnosed in the post-HEMT era in this large, racially diverse group of children with CF. Children on HEMT were older and more likely to have OSA as compared to those not on modulators but similar in nutritional status, lung function, and presence of upper airway pathology. Prospective studies are needed to further clarify the relationship between HEMT and OSA in children with CF.

PMID:38742253 | DOI:10.1002/ppul.27061

Orphanet J Rare Dis. 2024 May 13;19(1):197. doi: 10.1186/s13023-024-03207-9.

ABSTRACT

BACKGROUND: Rare diseases are often complex, chronic and many of them life-shortening. In Germany, healthcare for rare diseases is organized in expert centers for rare diseases. Most patients additionally have regional general practicioners and specialists for basic medical care. Thus, collaboration and information exchange between sectors is highly relevant. Our study focuses on the patient and caregiver perspective on intersectoral and interdisciplinary care between local healthcare professionals (HCPs) and centers for rare diseases in Germany. The aims were (1) to investigate patients' and caregivers' general experience of healthcare, (2) to analyse patients' and caregivers' perception of collaboration and cooperation between local healthcare professionals and expert centers for rare diseases and (3) to investigate patients' and caregivers' satisfaction with healthcare in the expert centers for rare diseases.

RESULTS: In total 299 individuals of whom 176 were patients and 123 were caregivers to pediatric patients participated in a survey using a questionnaire comprising several instruments and constructs. Fifty participants were additionally interviewed using a semistructured guideline. Most patients reported to receive written information about their care, have a contact person for medical issues and experienced interdisciplinary exchange within the centers for rare diseases. Patients and caregivers in our sample were mainly satisfied with the healthcare in the centers for rare diseases. The qualitative interviews showed a rather mixed picture including experiences of uncoordinated care, low engagement and communication difficulties between professionals of different sectors. Patients reported several factors that influenced the organization and quality of healthcare e.g. engagement and health literacy in patients or engagement of HCPs.

CONCLUSIONS: Our findings indicate the high relevance of transferring affected patients to specialized care as fast as possible to provide best medical treatment and increase patient satisfaction. Intersectoral collaboration should exceed written information exchange and should unburden patients of being and feeling responsible for communication between sectors and specialists. Results indicate a lack of inclusion of psychosocial aspects in routine care, which suggests opportunities for necessary improvements.

PMID:38741100 | DOI:10.1186/s13023-024-03207-9