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Pseudomonas aeruginosa (Pa) and Methicillin susceptible Staphylococcus aureus (MSSA) are the predominant bacteria found in the airways of people with cystic fibrosis (pwCF), significantly contributing to lung disease progression. While various factors influencing the initial acquisition (IA) of these pathogens are known, the impact of environmental conditions remains understudied. This epidemiological study assessed the risk of MSSA and Pa initial acquisitions in relation to seasonality and climatic zones among 1,184 French pwCF under 18 years old. The age at IA for Pa (Pa-IA) and MSSA (MSSA-IA) was estimated using the Kaplan-Meier method. Seasonality and climatic zones were analysed as risk factors using time-varying Cox regression models. The median age at MSSA-IA was notably earlier (2.0 years) than that at Pa-IA (5.1 years). MSSA-IA occurred increasingly younger in more recent birth cohorts, while the age at Pa-IA remained stable over time. The risk of Pa-IA was consistently higher in all seasons compared with spring, peaking in autumn (HR = 1.53), irrespective of climatic zones. In Oceanic and Continental climates, the highest risk for MSSA-IA was in winter (HRs = 1.45 and 1.20 respectively). In the Mediterranean climate, the risk of MSSA-IA was lower in winter compared to spring (HRs = 0.68 and 0.61 respectively), and the median age at MSSA-IA later than for Pa-IA. This study demonstrates that seasonality and meteorological factors may influence acquisition of MSSA and Pa in pwCF. These findings suggest that environmental factors play a role in pathogen acquisition dynamics in CF and could inform the development of preventive strategies., (© 2024. The Author(s).)

Background: Pseudomonas aeruginosa is a common pathogen that contributes to progressive lung disease in cystic fibrosis (CF). Genetic factors other than CF-causing CFTR (CF transmembrane conductance regulator) variations contribute ∼85% of the variation in chronic P. aeruginosa infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to P. aeruginosa infection., Materials and Methods: We conducted a genome-wide association study of chronic P. aeruginosa infection age in 1037 Canadians with CF. We subsequently assessed the genetic correlation between chronic P. aeruginosa infection age and lung function through polygenic risk score (PRS) analysis and inferred their causal relationship through bidirectional Mendelian randomisation analysis., Results: Two novel genome-wide significant loci with lead single nucleotide polymorphisms (SNPs) rs62369766 (chr5p12; p=1.98×10 -8 ) and rs927553 (chr13q12.12; p=1.91×10 -8 ) were associated with chronic P. aeruginosa infection age. The rs62369766 locus was validated using an independent French cohort (n=501). Furthermore, the PRS constructed from CF lung function-associated SNPs was significantly associated with chronic P. aeruginosa infection age (p=0.002). Finally, our analysis presented evidence for a causal effect of lung function on chronic P. aeruginosa infection age (β=0.782 years, p=4.24×10 -4 ). In the reverse direction, we observed a moderate effect (β=0.002, p=0.012)., Conclusions: We identified two novel loci that are associated with chronic P. aeruginosa infection age in individuals with CF. Additionally, we provided evidence of common genetic contributors and a potential causal relationship between P. aeruginosa infection susceptibility and lung function in CF. Therapeutics targeting these genetic factors may delay the onset of chronic infections, which account for significant remaining morbidity in CF., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Diffuse panbronchiolitis (DPB) is a rare, idiopathic inflammatory disease primarily diagnosed in East Asian populations. DPB is characterized by diffuse pulmonary lesions, inflammation of the respiratory bronchioles, and bacterial infections of the airway. Historically, sputum cultures reveal Pseudomonas aeruginosa in 22% of DPB patients, increasing to 60% after 4 years from disease onset. Although DPB patients have a known susceptibility to respiratory P. aeruginosa infections, as is observed in other chronic lung diseases such as cystic fibrosis (CF), the characterization of DPB P. aeruginosa strains is limited. In this study, we characterized 24 strains obtained from a cohort of DPB patients for traits previously associated with virulence, including growth, motility, antibiotic susceptibility, lipopolysaccharide structure, and genomic diversity. Our cohort of DPB P. aeruginosa strains exhibits considerable genomic variability when compared with isolates from people with cystic fibrosis chronically colonized with P. aeruginosa and acute P. aeruginosa infection isolates. Similar to CF, DPB P. aeruginosa strains produce a diverse array of modified lipid A structures. Antibiotic susceptibility testing revealed increased resistance to erythromycin, a representative agent of the macrolide antibiotics used to manage DPB patients. Differences in the O-antigen type among P. aeruginosa strains collected from these different backgrounds were also observed. Ultimately, the characterization of DPB P. aeruginosa strains highlights several unique qualities of P. aeruginosa strains collected from chronically diseased airways, underscoring the challenges in treating DPB, CF, and other obstructive respiratory disease patients with P. aeruginosa infections., Importance: Diffuse panbronchiolitis (DPB), a chronic lung disease characterized by persistent P. aeruginosa infection, serves as an informative comparator to more common chronic lung diseases, such as cystic fibrosis (CF). This study aimed to better address the interplay between P. aeruginosa and chronically compromised airway environments through the examination of DPB P. aeruginosa strains, as existing literature regarding DPB is limited to case reports, case series, and clinical treatment guidelines. The evaluation of these features in the context of DPB, in tandem with prevailing knowledge of P. aeruginosa strains collected from more common chronic lung diseases (e.g., CF), can aid in the development of more effective strategies to combat respiratory P. aeruginosa infections in patients with chronic lung diseases., Competing Interests: The authors declare no conflict of interest.

Objective: We aimed to explore the prevalence and predictive factors of sleep-disordered breathing (SDB) in patients with cystic fibrosis (pwCF) after lung transplantation (LTX)., Methods: We prospectively recruited adult pwCF who underwent LTX in our hospital from 2013 to 2022 and invited them for an attended overnight polysomnography (PSG) 1 year after transplantation. The apnea-hypopnea index (AHI) was the primary outcome, and SDB was defined as an AHI ≥ 5. Demographic, anthropometric, cardiometabolic, drug treatment, and pulmonary function variables were compared between pwCF with and without SDB. Multiple regression analysis was used to identify significant predictors of SDB. For a subset of participants who had available PSG before transplantation, sleep parameters were compared pre-post transplantation., Results: Sixty-two pwCF (31 females) were enrolled. Thirty participants had SDB, but only 11 of them had moderate-to-severe SDB (AHI ≥ 15). The average Epworth Sleepiness Scale (ESS) score indicated the absence of excessive daytime sleepiness. Older age (p < 0.001), male sex (p < 0.001), and smaller thoracic gas volume (p = 0.002) significantly predicted higher AHI. Comparison between pre- and post-transplantation polysomnographic data showed a significant increase in the percentage of slow wave sleep (p = 0.047), as well as a significant improvement in mean nocturnal oxygen saturation (p = 0.007). A statistically significant increase in the AHI was also observed (p = 0.047), but its clinical importance is uncertain (p = 0.476 for the increase in the ESS score)., Conclusions: We may conclude that SDB is prevalent in pwCF after LTX, but its severity is mild. Older male pwCF with greater improvement in lung hyperinflation after transplantation might be at risk for SDB and should be followed for symptoms or signs of sleep apnea., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Gastrointestinal (GI) complications are a significant source of morbidity for people with cystic fibrosis (PwCF). Historically, dietary recommendations in CF have focused on calories, typically emphasizing a high fat diet. The changing landscape of CF highlights the need to update this nutritional strategy. There is little research into how the quality of calories consumed by PwCF influences nutritional outcomes, GI symptoms, or likely contributors: intestinal inflammation and GI microbiology. We assessed the feasibility of a whole foods-based diet (WFD) and avoidance of ultra-processed foods, measuring safety/tolerability, adherence, and GI symptoms, as well as fecal measures of inflammation and microbiota among children with CF (CwCF) with GI symptoms., Methods: Single center, 4-week dietary intervention involving CwCF aged 5-14 years who screened positive on GI symptom questionnaire. Assessments included weight, symptom questionnaires and adverse events (AEs). Stool was analyzed for microbiota (16S rRNA) and calprotectin., Results: 108 children were pre-screened, 9 enrolled and 8 initiated and completed the study. There were no significant changes in weight and no AEs. PEDS-QL GI identified overall improvement in symptoms. Certain symptom domains (constipation, diarrhea, gas/bloating, stomach pain and hurt) demonstrated significant improvement on the WFD. Of two participants with abnormal fecal calprotectin at enrollment, both exhibited decreased values on WFD. There was no significant change in microbiota diversity., Conclusion: A WFD diet was feasible and safe in CwCF. There was improvement in GI symptom scores based on both parent and child assessments. Larger studies are needed to further investigate effects on intestinal inflammation and microbiota., Competing Interests: Conflict of interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: To resolve the epidemiology of airway infections with Burkholderia cepacia complex (Bcc) in patients with cystic fibrosis (pwCFs) over 40 years at a single treatment center., Methods: All Bcc and Burkholderia gladioli airway isolates were collected from pwCFs who presented at the cystic fibrosis outpatient and the lung transplantation clinics from 1983 to 2022., Results: The collection of 1205 strains is dominated by B. multivorans (56%), followed by B. cenocepacia (16%), B. stabilis (10%), and B. orbicola (9%). A total of 27 pwCFs experienced a single self-limiting episode of airway infection with Bcc. A total of 13 pwCFs were harboring Bcc for 1.7-13.6 years and 15 pwCFs were persistently infected with Bcc. A total of 16 Bcc-positive pwCFs received a lung transplant. Fatal post-transplant sepsis happened in one patient with B. multivorans, two with B. cenocepacia, and two with B. orbicola., Conclusions: After the first acquisition of Bcc, transient carriage was 2.7 times more frequent than persistent colonization. Infections with B. cenocepacia or B. orbicola confer a higher risk for post-transplant sepsis than an infection with B. multivorans., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Cystic Fibrosis is a multi-system disease, arising from a mutation of the cystic fibrosis transmembrane conductance regulator gene (CFTR). There is a lack of information regarding oral disease levels among people with cystic fibrosis. As part of an ongoing study assessing oral health in adults with cystic fibrosis at Cork University Dental School & Hospital, a systematic review of available literature was conducted to ascertain the caries experience of people with cystic fibrosis. The objective was to systematically present and evaluate the literature comparing caries experience between people with cystic fibrosis and people without cystic fibrosis., Methods: Five online databases were searched; Embase, Scopus, Web of Science Core Collection, Medline Ebsco and Cochrane Library. Studies that reported caries experience in people with cystic fibrosis were included in this review., Results: The initial search identified 1199 publications from online databases. Twenty-one studies were included for qualitative analysis. Fourteen studies reported a lower caries experience in children with CF compared to children without CF, five studies reported a higher caries experience in adults with CF, and two studies found inconclusive evidence regarding the association between caries experience and CF status. All studies had a risk of bias that may influence results., Conclusion: Despite a lack of complete unanimity between all studies, there is a general trend that children with cystic fibrosis have a lower caries experience than their healthy counterparts, whereas adults with cystic fibrosis have a higher caries experience. The review highlights the need for further studies involving adults with cystic fibrosis as the majority of studies primarily consist of paediatric populations., Clinical Significance: Dental practitioners should be aware that adults with cystic fibrosis have higher caries experience. Tailored approaches to dental care specific to cystic fibrosis individuals should be developed., Competing Interests: Declaration of competing interest I Dr Fiona O'Leary the corresponding author confirm on behalf of all authors that there have been no involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated. There was no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Respiratory infection is a major cause of disease severity in people with cystic fibrosis (PwCF). This project aimed to establish the CF community's opinion regarding cross infection (CI), nebuliser hygiene, antimicrobial resistance, personal impact of microbiological findings and the role of the microbiology laboratory., Methods: A questionnaire was completed anonymously (n = 280; PwCF (n = 128), parents (n = 123); friends/family/carers/charity personnel (n = 29)) from 13 countries. Readability scores (Flesch Reading Ease (FRE), Flesch Kincaid Grade Level (FKGL)) were determined for CI/IP&C information from six national CF charities and 21 scientific abstracts., Results: Respondents (72.5%) indicated knowledge of laboratory aspects of CF microbiology was important, however implications of microbiological findings on personal health/well-being were of higher importance (p < 0.0001). Cross infection/infection prevention & control (CI/IP&C) was of highest importance (95.6% respondents) with 27.3% indicating they were not given adequate information, particularly in older respondents (50 y+) (p = 0.006) versus young adults (16-29 y) and respondents from the Middle East versus N. America (p = 0.022) and Europe (p = 0.045). Responses highlighted how CI/IP&C health literacy could be enhanced. Respondents (77.3%), particularly females (p < 0.0001), indicated they would increase the frequency of nebuliser disinfection following guidance on infection risks/best practice, therefore an educational video was prepared. CI/IP&C readability scores (mean ± sd) from CF charities (FRE 52.5 ± 10.8; FKGL 9.7 ± 2.3) were more readable (p < 0.0001) than scientific abstracts (FRE 13.3 ± 11.1; FKGL 16.9 ± 2.3), however not meeting the targets (FRE≥60 and FKGL≤8)., Conclusion: There is a requirement for further CI/IP&C evidence-based guidance, policies/guidelines, education awareness, best practice in the home environment and multi-modal communication, enabling the CF community to make informed choices on lifestyle behaviours., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Cystic fibrosis (CF)-related diabetes (CFRD), characterized by partial to complete impaired insulin secretion, is the most common extra-pulmonary complication of CF. Actually, insulin is the only approved therapy for its management. Advanced hybrid closed loop (AHCL) systems are the gold standard therapy for type 1 diabetes and have been proposed for other insulin-dependent forms of diabetes, including CFRD. With AHCL systems, people with CFRD can better manage several typical disease-related issues, such as minimal insulin requirements, its variability due to exacerbations or concomitant steroid therapies, nutritional behaviors, the co-existence of CF complications as intestinal malabsorption or liver disease. SmartGuard, the AHCL system for Medtronic Minimed 780G, requires a minimum of 8 units per day to operate. In this paper, we expose a case of two young women with CFRD with total daily insulin requirements < 8 UI, using off-label SmartGuard system over a 3 years of follow-up period, suggesting an evaluation of its use also in people with minimal insulin needs, considering its beneficial impact in glucose control and quality of life., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background and Aims: It is not known why severe cystic fibrosis (CF) liver disease (CFLD) with portal hypertension occurs in only ~7% of people with CF. We aimed to identify genetic modifiers for severe CFLD to improve understanding of disease mechanisms., Approach and Results: Whole-genome sequencing was available in 4082 people with CF with pancreatic insufficiency (n = 516 with severe CFLD; n = 3566 without CFLD). We tested ~15.9 million single nucleotide polymorphisms (SNPs) for association with severe CFLD versus no-CFLD, using pre-modulator clinical phenotypes including (1) genetic variant ( SERPINA1 ; Z allele) previously associated with severe CFLD; (2) candidate SNPs (n = 205) associated with non-CF liver diseases; (3) genome-wide association study of common/rare SNPs; (4) transcriptome-wide association; and (5) gene-level and pathway analyses. The Z allele was significantly associated with severe CFLD ( p = 1.1 × 10 -4 ). No significant candidate SNPs were identified. A genome-wide association study identified genome-wide significant SNPs in 2 loci and 2 suggestive loci. These 4 loci contained genes [significant, PKD1 ( p = 8.05 × 10 -10 ) and FNBP1 ( p = 4.74 × 10 -9 ); suggestive, DUSP6 ( p = 1.51 × 10 -7 ) and ANKUB1 ( p = 4.69 × 10 -7 )] relevant to severe CFLD pathophysiology. The transcriptome-wide association identified 3 genes [ CXCR1 ( p = 1.01 × 10 -6 ) , AAMP ( p = 1.07 × 10 -6 ), and TRBV24 ( p = 1.23 × 10 -5 )] involved in hepatic inflammation and innate immunity. Gene-ranked analyses identified pathways enriched in genes linked to multiple liver pathologies., Conclusion: These results identify loci/genes associated with severe CFLD that point to disease mechanisms involving hepatic fibrosis, inflammation, innate immune function, vascular pathology, intracellular signaling, actin cytoskeleton and tight junction integrity and mechanisms of hepatic steatosis and insulin resistance. These discoveries will facilitate mechanistic studies and the development of therapeutics for severe CFLD., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: An adequate nutritional status in patients with cystic fibrosis correlates with higher survival and better pulmonary function. Body mass index (BMI) is an anthropometric indicator with independent association with pulmonary function, and it can hide alterations of nutritional status in cystic fibrosis., Objective: To determine the relationship of lung function with BMI and body composition parameters in children with cystic fibrosis in a Hight Complexity institution between 2015 and 2018., Materials and Methods: It was an observational study with analytical, cross-sectional, and retrospective scope, including 33 patients between 5 and 17 years old. Spearman's test was applied to evaluate correlation of FEV1 (forced expiratory volume in first second) with BMI and five body composition parameters by bioelectrical impedance using InbodyS10 equipment. Statistical significance was considered with p < 0.05., Results: Positive correlation was obtained between FEV1 and appendicular skeletal muscle mass between lung function and percentage of fat-free mass (p = 0.006) and phase angle (p = 0.001). Percent fat mass had a negative correlation with FEV1 (p = 0.007). BMI and fat free mass index did not correlate with lung function (p = 0.085)., Conclusions: Appendicular skeletal muscle mass correlated better than BMI with lung function in children with cystic fibrosis. It is recommended to perform anthropometric follow-up by BMI complemented with body composition study in children with cystic fibrosis. Analyses with larger populations are required to standardize its use., Competing Interests: Declaration of competing interest The authors have no conflicts of interest related to this article., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Objective: We hypothesized that the insulin-sensitizing adipokine adiponectin (ADP) is upregulated in cystic fibrosis (CF) related diabetes (CFRD) and underweight adults with CF. We aimed to assess correlations between glucose metabolism, body composition and ADP in CF., Methods: We performed a cross-sectional study among adults with CF at the Copenhagen CF Center. The study included a fasting level of ADP, an oral glucose tolerance test (OGTT), and a dual energy-x-ray absorptiometry scan., Results: In total, 115 patients were included of whom 104 had an OGTT performed. Glucose intolerance was not correlated with ADP in multivariable analysis, while increased hepatic insulin resistance (i.e., HOMA-IR) was correlated with reduced ADP levels. ADP declined by 4% (e β 0.96, 95% CI: 0.94, 0.98), 5% (e β 0.95, 95% CI: 0.93, 0.98), 9% (e β 0.91, 95% CI: 0.87, 0.95), and 83% (e β 0.17, 95% CI: 0.08, 0.37) for each one unit (kg/m 2 ) increase in body mass index, fat mass index, muscle mass index, and bone mineral content index, respectively., Conclusions: In CF, ADP was negatively correlated with hepatic insulin resistance as well as low fat, muscle, and bone mass, but not with glucose intolerance. This suggests that malnutrition leads to higher ADP levels in CF., Competing Interests: TA holds stocks in Novo-Nordisk A/S. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nielsen, Mikkelsen, Oturai, Krogh-Madsen, Katzenstein, Ritz, Pressler, Almdal, Mathiesen and Faurholt-Jepsen.)

Insulin secretion is impaired in individuals with cystic fibrosis (CF), contributing to high rates of CF-related diabetes (CFRD) and substantially increasing disease burden. To develop improved therapies for CFRD, better knowledge of pancreatic pathology in CF is needed. Glucagon like peptide-1 (GLP-1) from islet α cells potentiates insulin secretion by binding GLP-1 receptors (GLP-1Rs) on β cells. We determined whether expression of GLP-1 and/or its signaling components are reduced in CFRD, thereby contributing to impaired insulin secretion. Immunohistochemistry of pancreas from humans with CFRD versus no-CF/no-diabetes revealed no difference in GLP-1 immunoreactivity per islet area, whereas GLP-1R immunoreactivity per islet area or per insulin-positive islet area was reduced in CFRD. Using spatial transcriptomics, we observed several differentially expressed α- and/or β-cell genes between CFRD and control pancreas. In CFRD, we found upregulation of α-cell PCSK1 which encodes the enzyme (PC1/3) that generates GLP-1, and downregulation of α-cell PCSK1N which inhibits PC1/3. Gene set enrichment analysis also revealed α and β cell-specific pathway dysregulation in CFRD. Together, our data suggest intra-islet GLP-1 is not limiting in CFRD, but its action may be restricted due to reduced GLP-1R protein levels. Thus, restoring β-cell GLP-1R protein expression may improve β-cell function in CFRD., (© 2024. The Author(s).)

Background: Haemophilus influenzae is prevalent within the airways of persons with cystic fibrosis (pwCF). H. influenzae is often associated with pulmonary exacerbations (PEx) in pediatric cohorts, but in adults, studies have yielded conflicting reports around the impact(s) on clinical outcomes such as lung function decline. Accordingly, we sought to discern the prevalence, natural history, and clinical impact of H. influenzae in adult pwCF., Methods: This single-centre retrospective cohort study reviewed all adult pwCF with H. influenzae sputum cultures between 2002 and 2016. From this cohort, persistently infected subjects (defined as: ≥2 samples with the same pulsotype and > 50% sputum culture-positive for H. influenzae in each year) were matched (1:2) to controls without H. influenzae. Demographic and clinical status (baseline health or during periods of PEx) were obtained at each visit that H. influenzae was cultured. Yearly biobank isolates were typed using pulsed-field gel electrophoresis (PFGE) to assess relatedness., Results: Over the study period, 30% (n = 70/240) of pwCF were culture positive for H. influenzae, of which 38 (54%) were culture-positive on multiple occasions and 12 (17%) had persistent infection. One hundred and thirty-seven isolates underwent PFGE, with 94 unique pulsotypes identified. Two (1.5%) were serotype f with the rest non-typeable (98.5%). H. influenzae isolation was associated with an increased risk of PEx (RR = 1.61 [1.14-2.27], p = 0.006), however, this association was lost when we excluded those who irregularly produced sputum (i.e. only during a PEx). Annual lung function decline did not differ across cohorts., Conclusions: Isolation of H. influenzae was common amongst adult pwCF but often transient. H. influenzae infection was not associated with acute PEx or chronic lung function decline., (© 2024. The Author(s).)

Central venous catheters including totally implantable venous access devices (TIVADs) have revolutionised the management of pulmonary infections and exacerbations in patients with cystic fibrosis (CF). While being better tolerated by the patient, these have allowed aggressive intravenous antibiotic therapies during recurrent hospitalisations. Given improvement in procedural strategies and operator experience, many patients with CF undergo lung transplants in the course of their disease nowadays. TIVADs can be associated with thrombosis leading to superior vena cava (SVC) obstruction and SVC syndrome which can pose a challenge, especially during the transplant surgery. We describe a case of successful management of SVC syndrome in a patient with CF undergoing a lung transplant, highlighting the strategies used to minimise risks associated with such a procedure., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The performance of a novel selective agar was evaluated against the performance of conventional mycobacterial cultures, i.e., a combination of the mycobacterial growth indicator tube (MGIT) with Löwenstein-Jensen (LJ), for the detection of nontuberculous mycobacteria (NTM) in sputum samples from people with cystic fibrosis (pwCF). Two hundred eighty-three sputum samples (231 fresh sputum and 52 spiked sputum) from 143 pwCF were collected. They were inoculated without prior decontamination on NTM Elite agar (30°C ± 2°C for 28 days) and inoculated on both MGIT and LJ (35°C-37°C for 6-8 weeks) after N-acetyl-L-cysteine-2% sodium hydroxide decontamination. NTM were identified by Matrix-Assisted Laser Desorption Ionization/Time of Flight Mass Spectrometry and/or PCR, and whole-genome sequencing. A total of 67 NTM were recovered overall by the combination of all culture media. NTM Elite agar allowed the recovery of 65 NTM (97%), compared to 22 for the conventional MGIT and LJ media combination (32.8%), including 22 NTM for MGIT (32.8%) and 3 NTM with the LJ medium (4.5%). For Mycobacterium abscessus complex, the sensitivity of NTM Elite agar was 95% compared with a sensitivity of 30% for the conventional MGIT and LJ media combination. Overall, 17.3% of cultures on NTM Elite agar were contaminated with other micro-organisms vs 46.3% on MGIT and 77% on LJ. This study shows that the novel selective agar (NTM Elite agar) significantly outperforms the conventional MGIT and LJ media combination in terms of sensitivity, selectivity, and ease of culture, without the requirement of an L3 laboratory.IMPORTANCENontuberculous mycobacteria (NTM) are significant pulmonary pathogens in patients with pre-existing structural lung conditions such as cystic fibrosis, bronchiectasis, or chronic obstructive pulmonary disease. Mycobacterium avium complex and Mycobacterium abscessus complex (MABSC) are the most frequently isolated organisms. Compared to the recommended culture method for NTM, which combines solid and liquid culture media, NTM Elite agar enables a faster/easier diagnosis and speeds up identification and susceptibility testing as the final reading is at 28 days instead of 6-8 weeks for the conventional mycobacterial cultures. In addition, for the NTM Elite agar, no decontamination stage before inoculation is necessary, unlike the conventional mycobacterial cultures. NTM Elite agar is derived from a formulation of medium adapted to rapidly growing mycobacteria (RGM). The medium enables the growth of RGM while suppressing other flora. It is supported with published clinical data showing the benefits of this medium., Competing Interests: J.G. is an employee of bioMérieux. The Newcastle upon Tyne Hospitals, UK, represented by John Perry, receive ongoing funding from bioMérieux, France, for the development and evaluation of culture media. UZ Leuven and Munster University Hospital received funding from bioMérieux, France, for the evaluation of NTM culture media.

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in cystic fibrosis (CF) by stabilizing the CFTR protein on respiratory epithelial surfaces. To determine the efficacy of CFTR modulators on sinonasal outcomes in patients with CF, we performed a meta-analysis of clinical trials to date that include functional and radiographic evidence of sinus disease., Methods: English full-text articles were searched in PubMed, Embase, and Scopus databases. Two reviewers screened articles and a third reviewer resolved disagreements. Articles were included if they reported functional or radiological sinonasal outcomes in patients with CF before and after CFTR modulator therapies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the risk of bias in non-randomized studies of interventions tool was used for quality assessment. The generic inverse variance method with random effects model was used for meta-analysis. Standardized mean difference (SMD) and mean difference (MD) were used as effect measurements., Results: Seven prospective and two retrospective studies representing 248 patients were included in this analysis. There was a significant improvement in sinonasal outcome test-22 scores on elexacaftor‒tezacaftor‒ivacaftor (MD = 12.80, [95% confidence interval, CI: 10.46‒15.13], p < 0.001, n = 222), with no heterogeneity detected (I 2  = 0%, p = 0.820). There was also a significant improvement in Lund‒Mackay scores (SMD = 1.25, [95% CI: 0.58‒1.91], p < 0.001, n = 88), with heterogeneity detected (I 2  = 67%, p = 0.030)., Conclusions: CFTR modulators improve functional and radiologic sinonasal outcomes. Given the utility of CFTR modulators, the treatment paradigm for CF-related chronic rhinosinusitis promises to evolve., (© 2024 ARS‐AAOA, LLC.)

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., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Introduction: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves lung function but its effect on mental health and sleep remains poorly understood. We report on mental health, sleep, and respiratory health outcomes of adolescents with CF commenced on ETI therapy, and monitored the prevalence of neuropsychiatric issues through the coronavirus disease 2019 pandemic., Methods: We conducted a prospective longitudinal study of 31 adolescents (aged 10-18 years) from July 2021 to October 2022. Data collected include demographics, Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Pediatric Daytime Sleepiness Scale (PDSS), Sleep Disturbance Scale for Children (SDSC) scores, and FEV 1 percent predicted. Twenty of 31 adolescents had data before and after ETI initiation. Mean differences (MD) in mental health, sleep, and respiratory health pre- and post-ETI therapy commencement were estimated using paired t-tests. The prevalence and trajectories of anxiety, depression, and sleep disturbance were described between the ETI epochs, and over the pandemic period., Results: FEV 1 improved following ETI therapy commencement (MD, 95% confidence interval [CI]: 7.1% (4.7%-9.6%) whereas PHQ-9, GAD-7, PDSS, and SDSC scores did not change significantly. Ten percent of participants developed new-onset anxiety/depression concerns and 10% developed new sleep concerns following ETI initiation., Conclusion: This is the first prospective longitudinal study of mental health and sleep changes after ETI commencement in adolescents with CF. Although respiratory outcomes improved, ETI did not improve anxiety, depression or sleep., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Aim: The relative contributions of insulin secretory defects and possible additional contribution of insulin resistance for the development of cystic fibrosis (CF)-related diabetes (CFRD) are poorly understood. We aimed to (a) determine which indices of insulin resistance predict progression to CFRD, and (b) to model the relative contributions of insulin secretory function and insulin resistance to predict the risk of CFRD., Materials and Methods: Three hundred and three individuals living with CF underwent a 2-h oral glucose tolerance test with blood sampling every 30 min at 12-24-month intervals until they developed CFRD or until the end of follow-up (up to 15 years). Indices of insulin resistance (e.g. Stumvoll) and insulin secretion were calculated from oral glucose tolerance test glucose and insulin measurements. CFRD-free survival was assessed by survival analysis., Results: Estimated insulin resistance showed associations with glucose homeostasis and risk of progression to CFRD. The CFRD-free survival was significantly different between quartiles of insulin resistance (p < 0.0001). When patients were subdivided according to both insulin resistance and insulin secretion (insulinogenic index), CFRD-free survival was significantly lower in those with combined lowest insulin secretion and highest insulin resistance (Stumvoll) indices (hazard ratio: 11.2; p < 0.0001). There was no significant difference when the same analysis was performed for the nine other indices., Conclusions: Insulin resistance is correlated with glucose homeostasis and the risk of progression to CFRD. Patients combining low insulin secretion and high insulin resistance had the greatest odds of developing CFRD over a 15-year period., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Endoscopic sinus surgery (ESS) is an established surgical option for cystic fibrosis (CF) patients with chronic rhinosinusitis that is refractory to conventional medical management. Objective and subjective evidence of benefit of ESS in this cohort of patients is currently conflicting in the literature., Methodology: A single center retrospective study was undertaken of all CF patients (transplanted and non-transplanted) over the age of 16 who underwent an ESS over a six-year period from 2015 to 2021. Patients on triple-therapy CFTR modulators were excluded. Data was collected on demographics, clinical management, and outcome measures. The objective outcome measures were lung function (%predicted FEV1), pulmonary exacerbations (total number of days of IV antibiotics- both ambulatory and in hospital). The subjective outcome measure was SNOT-22 scores pre and 6 months post-operatively. A minimally clinical important difference (MCID) in SNOT-22 scores of 9 points was used., Results: 55 patients were included in our study, with a median age of 31 and 53% females. Median Lund-Mackay scores for the cohort was 13 (3-24). There was a significant improvement in lung function at 1-year post-surgery, and a significant MCID reduction in SNOT-22 scores at 6 months post-surgery across the cohort. Sub-group analysis revealed a sustained MCID reduction in SNOT-22 scores in both lung-transplanted and native lung groups, and in patients with primary ESS or previous ESS. However, there was no post-operative pulmonary function improvement in lung transplanted patients and patients with previous ESS. There was no impact on the rate of pulmonary exacerbations across the cohort. 2 patients in the cohort died secondary to pulmonary disease., Conclusions: There was a demonstrated clinical and symptomatic benefit of ESS in CF patients in this study. Stricter guidelines for indications for ESS need to be established with regards to CF patients who will undergo ESS in the future.

Cystic fibrosis-related diabetes (CFRD), the most common comorbidity in cystic fibrosis (CF), leads to increased mortality by accelerating the decline in lung function. Scnn1b- Tg transgenic mice overexpressing the epithelial sodium channel β subunit exhibit spontaneous CF-like lung disease, including airway mucus obstruction and chronic inflammation. Here, we established a chronic CFRD-like model using Scnn1b- Tg mice made diabetic by injection of streptozotocin (STZ). In Ussing chamber recordings of the trachea, Scnn1b- Tg mice exhibited larger amiloride-sensitive currents and forskolin-activated currents, without a difference in adenosine triphosphate (ATP)-activated currents compared with wild-type (WT) littermates. Both diabetic WT (WT-D) and diabetic Scnn1b- Tg ( Scnn1b -Tg-D) mice on the same genetic background exhibited substantially elevated blood glucose at 8 wk; glucose levels also were elevated in bronchoalveolar lavage fluid (BALF). Bulk lung RNA-seq data showed significant differences between WT-D and Scnn1b -Tg-D mice. Neutrophil counts in BALF were substantially increased in Scnn1b- Tg-D lungs compared with controls ( Scnn1b -Tg-con) and compared with WT-D lungs. Lung histology data showed enhanced parenchymal destruction, alveolar wall thickening, and neutrophilic infiltration in Scnn1b- Tg-D mice compared with WT-D mice, consistent with the development of a spontaneous lung infection. We intranasally administered Pseudomonas aeruginosa to induce lung infection in these mice for 24 h, which led to severe lung leukocytic infiltration and an increase in pro-inflammatory cytokine levels in the BALF. In summary, we established a chronic CFRD-like lung mouse model using the Scnn1b -Tg mice. The model can be used for future studies toward understanding the mechanisms underlying the lung pathophysiology associated with CFRD and developing novel therapeutics. NEW & NOTEWORTHY We established a chronic CFRD-like mouse model using the Scnn1b -Tg transgenic mice overexpressing the epithelial sodium channel β subunit made diabetic by injection of streptozotocin. The results underscore the urgent need to develop novel therapeutics for CF lung disease.

Purpose: Pseudomonas aeruginosa is the predominant bacterial pathogen colonizing the cystic fibrosis (CF) lung. Mixed populations of nonmucoid and mucoid variants of P. aeruginosa have been isolated from the CF airway. While the association between mucoid variants and pulmonary function decline is well-established, their impact on inflammation and tissue damage in advanced CF lung disease remains unclear., Methods: This pilot study utilized 1 non-CF and 3 CF lung explants to examine lobar distribution, inflammation, and histopathology related to nonmucoid and mucoid P. aeruginosa infection. To study tissue damage, we developed a novel lung histopathology scoring system, the first applied to human CF lung biopsies, which is comprised of five indicators: bronchiolar epithelial infiltrate, luminal inflammation, peribronchial/bronchiolar infiltrate, peribronchiolar fibrosis, and alveolar involvement., Results: Mucoid P. aeruginosa variants were distributed throughout the CF lung but associated with greater concentrations of proinflammatory cytokines, IL-1β, TNF-α, IL-6, IL-8, and IFN-γ, and one anti-inflammatory cytokine, IL-10, compared to nonmucoid variants. CF lung explants exhibited higher histopathology scores compared to a non-CF lung control. In mixed-variant infection, nonmucoid constituents associated with increased bronchiolar epithelial infiltration, one indicator of histopathology., Conclusion: This pilot study suggests ongoing interplay between host and bacterial elements in late-stage CF pulmonary disease. Mucoid P. aeruginosa infection correlates with inflammation regardless of lung lobe, whereas nonmucoid P. aeruginosa is associated with increased inflammatory cell infiltration. The development of a novel lung histopathology scoring system lays the groundwork for future large-cohort investigations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The introduction of CFTR modulator drugs like elexacaftor-tezacaftor-ivacaftor (ETI) has transformed the management of cystic fibrosis (CF), significantly improving symptoms, lung function, and quality of life, while reducing reliance on intravenous antibiotics. However, respiratory exacerbations in the CFTR modulators era remain poorly understood from both pathophysiological and clinical perspectives. We present the case of a 20-year-old Caucasian woman with CF (F508del/L1077P) who, after three years of ETI treatment, experienced a severe episode of hemoptysis, despite being almost asymptomatic in the weeks leading up to admission, requiring bronchial artery embolization. Following ETI treatment, auscultatory findings and FEV 1 changes may be less significant, making the detection of respiratory exacerbation more challenging. This highlights the need for heightened vigilance in managing such cases and underscores the challenge of diagnosing and managing exacerbations in the era of modulators. Long term real-world studies are essential to comprehend the evolving course of the disease during ETI treatment., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: P. aeruginosa, a biofilm-forming bacteria, is the main cause of pulmonary infection in CF patients. We applied ZnO-np as a therapeutic agent for eradicating multi-drug resistance and biofilm-forming P. aeruginosa isolated from young CF patients., Methods: A total of 73 throat and sputum samples taken from young CF patients were inquired. ZnO-np was synthesized and characterized in terms of size, shape, and structure for anti-bacterial activity. The antibiotic susceptibility of isolates before and after the addition of 16 μg/ml of ZnO was evaluated using disc diffusion and microtiter methods, respectively. The gene expression level of QS genes was assessed after treatment with 16 μg/ml ZnO-np., Results: The optimum concentration of ZnO-np with a higher inhibitory zone was 16 μg/ml (MIC) and 32 μg/ml (MBC). All isolates were resistant to applied antibiotics, and about 45 % of isolates were strong biofilm-forming bacteria. After treatment with 16 μg/ml ZnO-np, all strains became susceptible to the applied antibiotic except for amikacin, which confers an intermediate pattern. About 63 % and 20 % of isolates were, respectively, non-biofilm and weak biofilm-forming bacteria following the addition of ZnO-np. Relative gene expression of gacA, lasR, and rhlR genes were downregulated significantly (P < 0.001). Although the retS did not have a significant reduction (P = 0.2) CONCLUSION: ZnO-np at a concentration of 16 μg/ml could significantly reduce the P. aeruginosa infection by altering the antibiotic susceptibility pattern and inhibiting biofilm formation. Due to their photocatalytic properties and their ability to penetrate the extracellular polysaccharide layer, ZnO nanoparticles can produce ROS, which increases their susceptibility to antibiotics. Nasal delivery of ZnO-np in the form of aerosol can be considered a potential strategy to decrease the mortality rate in CF patients at an early age., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This report describes the characterization of Burkholderia cenocepacia isolates belonging to sequence type (ST)-250, detected in eight patients with cystic fibrosis (CF) in Switzerland. We retrospectively analyzed 18 isolates of B. cenocepacia ST-250 isolated between 2003 and 2015 by whole-genome sequencing and evaluated clinical and epidemiological data. Single nucleotide polymorphism analysis of the B.°cenocepacia ST-250 lineage showed that the isolates from all patients cluster tightly, suggesting that this cluster has a recent common ancestor. Epidemiological investigations showed that six out of eight patients acquired B.°cenocepacia ST-250 in the years 2001-2006, where participation in CF summer camps was common. Two patients were siblings. Genomic relatedness of the B. cenocepacia ST-250 isolates supported transmission by close contact, however, a common source or nosocomial routes cannot be excluded. With respect to the fatal outcome in six patients, our study shows the importance of infection control measurements in CF patients with B.°cenocepacia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Mucor within the airways of immunocompromised patients often signifies an invasive life-threatening infection. However, its significance in immunocompetent patients with chronic lung diseases is less clear. We aimed to assess the clinical implication of mucor in airway-secretion cultures of these patients., Methods: A single-center retrospective cohort study was performed. Patients with cystic fibrosis (CF), primary ciliary dyskinesia (PCD) or non-CF/non-PCD bronchiectasis followed in our Pediatric Pulmonary Institute, with sputum or bronchoalveolar lavage cultures growing Mucorales molds in the years 2010-2022, were included. Demographic and clinical parameters such as body mass index and spirometry values (forced expiratory volume at 1 second) were collected and compared with values up to 12 months prior to and following the index (positive culture) visit., Results: A total of 27 patients of whom 22 (82%) patients were with CF, 3 with PCD (11%) and 2 (7%) with non-CF/non-PCD bronchiectasis were included. Median age was 21.8 (14.9-32.1) years, with forced expiratory volume at 1 second of 62.8% ± 21.9% at the index visit. None of the patients developed disseminated disease, none had clinical or radiological evidence of fungal disease and none required antifungal therapy. Throughout the 12 months prior to and following the positive cultures, no significant changes were noted in body mass index, forced expiratory volume at 1 second, frequency of pulmonary exacerbations, days of hospitalization or days of antibiotic treatment., Conclusions: Evidence of mucor in airway cultures of immunocompetent patients with chronic lung disease does not necessarily signify clinical deterioration nor suggests invasive fungal disease. Larger, long-term prospective studies are required to obviate the need for a thorough evaluation in these patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cystic fibrosis (CF) related diabetes affects up to half of all adults with CF and is associated with higher morbidity and mortality. Our aim is to codevelop an ideal model of care that integrates diabetes technology and better meets the needs of adults living with the condition to improve attendance, engagement, service satisfaction, and clinical outcomes., Methods: Using qualitative research methods, we evaluated disease perceptions, barriers, and enablers to optimal CF-related diabetes management and service delivery. Integration of continuous glucose monitoring (CGM) was also explored. An initial broad purposive consumer survey was followed by focus groups with end-users. Grounded theory approach was utilized with major problem areas identified then explored, coded, and grouped into requisites for an "ideal model of care" for adults living with CF-related diabetes., Results: Two key themes emerged (i) an ideal model of care consisted of a dual-specialty service co-led by endocrinology and CF physicians and supported by diabetes educator and CF dietitian with a goal to provide consistent and personalized diabetes management and (ii) CGM was acceptable for use in adults with CF-related diabetes with many perceived benefits and should be integrated into the model of care. Barriers to optimizing glycemic control included diet, finger-prick testing, reduced access to CGM, and pulmonary exacerbations. End-user feedback on CGM was overwhelmingly positive with regard to operability. CGM was also identified as a tool that could be used to engage, educate, and empower adults living with CF-related diabetes and facilitate constructive and personalized clinical decision-making by healthcare providers., Conclusion: For adults living with CF, a diagnosis of diabetes is associated with increased treatment burden. Our findings suggest an "ideal model of care" for CF-related diabetes would be co-led by endocrinology services integrated within a pre-existing CF service, incorporating CGM., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Introduction: Cystic fibrosis (CF) is commonly complicated by chronic rhinosinusitis (CRS). Despite highly effective management options, CRS in people with CF (PwCF+CRS) may be refractory to medical therapy, eventually requiring endoscopic sinus surgery. The impact of sinus surgery on pulmonary, quality of life (QOL), and other outcomes in PwCF+CRS in the expanding era of highly effective modulator therapy has not been fully elucidated. This study aims to determine if endoscopic sinus surgery can offer superior outcomes for PwCF+CRS when compared to continued medical treatment of CRS., Methods and Analysis: This multi-institutional, observational, prospective cohort study will enroll 150 adults with PwCF+CRS across nine US CF Centers who failed initial medical therapy for CRS and elected to pursue either endoscopic sinus surgery or continue medical treatment. To determine if sinus surgery outperforms continued medical therapy in different outcomes, we will assess changes in pulmonary, CF-specific QOL, CRS-specific QOL, sleep quality, depression, headache, cognition, olfaction, productivity loss, and health utility value after treatment. The influence of highly effective modulator therapy on these outcomes will also be evaluated. This study will provide crucial insights into the impact of endoscopic sinus surgery for PwCF+CRS and aid with development of future treatment pathways and guidelines., Ethics and Dissemination: This study has been approved by each institution's internal review board, and study enrollment began August 2019. Results will be disseminated in conferences and peer-reviewed journals., Trial Registration: This study was registered on ClinicalTrials.gov (NCT04469439)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JAA is a consultant for OptiNose and Medtronic; on a speaker panel GSK; on GlycoMira board and is an equity holder. PHH is a consultant for Stryker, Medtronic, Slate Therapeutics; and Equity ownership in Sound Health Systems. AJK is a consultant for Acclarent. ZMS is a consultant for OptiNose, Regeneron, SanofiGenzyme, and Lyra; and on Medical Directory for Healthy Humming. Unrelated to this work, NIC has received grant support from the Burroughs Welcome Fund, American Rhinologic Society, and the National Cancer Institute. In the last 36 months, CHG has received grants from the National Institutes of Health, the Cystic Fibrosis Foundation, the Federal Drug Administration unrelated to this work. CHG has received fees from Enterprise Therapeutics for providing clinical trial design advice. He received honoraria from Gilead Sciences to serve as grant review committee chair and from Vertex Pharmaceuticals for speaking at the UK LEAD conference. He served as a DSMB Chair for a trial supported by Novartis and the European Commission. He serves as the Deputy Editor of the Annals of the American Thoracic Society. CHG has stock in Air Therapeutics. JLTC reports personal financial relationships with commercial interests relevant to medicine within the past 3 years: As faculty in an institution that is part of the CF TDN, she have been site Pl on studies for Vertex, 4DMT, and Eloxx; she have done consulting/provided clinical trial design advice for Vertex and 4DMT; she served as Chair of a Data Monitoring Committee for AbbVie. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: she have received grant funding from the CFF and NIH. Professional Memberships include CFF Clinical Research Executive Committee; CFF TDN Sexual Health, Reproduction, and Gender Research Working Group (SHARING); ATS International Conference Committee Chair and Respiratory Health Awards Committee Member (Scientific Grant Review and Clinical Problems Programming Committee-complete); National Institutes of Health/National Heart, Blood, Lung Institute Clinical Trials Review Study Section. MTS receives funding from Cystic Fibrosis Foundation unrelated to this work. In the last 36 months, DMB has received grant support from CF Foundation related to this work as well as unrelated to this work. Unrelated to this work, DMB has received grant support from the International Society of Inflammation and Allergy of the Nose and the American Rhinologic Society, honoraria, and consulting fees from Amgen, on medicolegal cases, and at Garner Health (equity). CML, JLF, TEB, NIC, AEG, JCM, TLS have disclosed no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Pseudomonas aeruginosa is a multidrug-resistant pathogen causing recalcitrant pulmonary infections in people with cystic fibrosis (pwCF). Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been developed that partially correct the defective chloride channel driving disease. Despite the many clinical benefits, studies in adults have demonstrated that while P. aeruginosa sputum load decreases, chronic infection persists. Here, we investigate how P. aeruginosa in pwCF may change in the altered lung environment after CFTR modulation., Methods: P. aeruginosa strains (n = 105) were isolated from the sputum of 11 chronically colonized pwCF at baseline and up to 21 months posttreatment with elexacaftor-tezacaftor-ivacaftor or tezacaftor-ivacaftor. Phenotypic characterization and comparative genomics were performed., Results: Clonal lineages of P. aeruginosa persisted after therapy, with no evidence of displacement by alternative strains. We identified commonly mutated genes among patient isolates that may be positively selected for in the CFTR-modulated lung. However, classic chronic P. aeruginosa phenotypes such as mucoid morphology were sustained, and isolates remained just as resistant to clinically relevant antibiotics., Conclusions: Despite the clinical benefits of CFTR modulators, clonal lineages of P. aeruginosa persist that may prove just as difficult to manage in the future, especially in pwCF with advanced lung disease., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In this series of articles with comments and illustrations on the World Federation for Medicine and Biology (WFUMB) guidelines on contrast-enhanced ultrasound (CEUS) the topics of very rare focal liver lesions (FLL) are discussed. Improving the detection and characterization of the most common FLL are the main topics of these guidelines. The focus of this review is on the many manifestations of cystic fibrosis-related liver disease (CFLD). These include focal biliary fibrosis, liver cirrhosis, vascular manifestations with nodular regenerative hyperplasia and portal hypertension with or without cirrhosis. This article describes the diverse changes of liver involvement in cystic fibrosis and their appearance on ultrasound, duplex sonography, and contrast enhanced ultrasonography. This knowledge and the imaging should help to recognize liver manifestations in time and enable a correct interpretation of ultrasound images in CF in the corresponding clinical situation.

Purpose: To assess oral hygiene, gingivitis, and the association between them for adolescents with cystic fibrosis (CF) compared to nonCF controls. Methods: This was a cross-sectional study of adolescents with CF aged 12 to 17 years (n=27), compared to two non-CF control groups: Medicaid-enrolled adolescents with special health care needs (ASHCN; n=60) and healthy Medicaid-enrolled adolescents (n=185). Dental plaque was a proxy for oral hygiene, and gingival bleeding was a proxy for gingivitis. This study employed confounder-adjusted binomial logistic regression to compare outcomes between adolescents with CF and controls. Results: After adjusting for confounders, adolescents with CF had significantly poorer oral hygiene than controls (CF versus ASHCN odds ratio [OR] = 2.9, 95 percent confidence interval [95% CI] = 2.0 to 4.4, P<0.001; CF versus healthy OR = 1.7, 95% CI=1.3 to 2.2, P<0.001), but there was no significant difference in gingivitis (CF versus ASHCN OR=1.3, 95% CI=0.87 to 1.9, P=0.21; CF versus healthy OR = 0.80, 95% CI=0.60 to 0.99, P=0.04). Poor oral hygiene was significantly associated with gingivitis for all adolescents (CF OR=1.2, 95% CI=1.1 to 1.4, P<0.001; ASHCN OR = 1.8, 95% CI=1.6 to 2.0, P<0.001; healthy OR = 1.2, 95% CI=1.1 to 1.3, P<0.001). Conclusions: Adolescents with CF had poorer oral hygiene than non-CF controls but similar levels of gingivitis. Future efforts should identify factors that protect adolescents with CF from gingivitis.

Introduction: Malnutrition has always been a problem in CF (cystic fibrosis) patients; however, new treatments with CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators have led to weight gain, with some patients at risk of overweight and obesity., Objective: Our study aimed to analyze the evolution of BMI (body mass index) after one year of treatment with triple therapy and the factors associated with weight gain in CF patients undergoing treatment with triple therapy with CFTR protein modulators (ETI) (elexacaftor/tezacaftor/ivacaftor)., Methods: We conducted a prospective, observational, longitudinal, multicenter study in patients diagnosed with cystic fibrosis, aged 18 years or older, with at least one F508del allele and who underwent ETI therapy for at least one year, from 2020 to 2023. One hundred and eight patients from two cystic fibrosis units in Spain, Princess University Hospital of Madrid (74 patients) and Central University Hospital of Asturias (HUCA) (34 patients), were included. Demographic data, anthropometric data, lung function, and exacerbations were collected, comparing the data in the previous year to the start of therapy with the results after one year of treatment. Multivariant models were developed to account for repeated weight and BMI measurements, using a mixed effects model approach and accounting for possible modifying factors Results: One hundred and eight patients were included in the study, 58 men (53.7%) and 50 women (46.3%) with a mean age of 29.5 ± 9.4 years (18-59). Patient weight and BMI were recorded at baseline and at 3-month intervals during the study period. The weight increased from 59.6 kg to 62.6 kg and BMI increased from 21.9 kg/m 2 to 23.0 kg/m 2 after one year of treatment ( p < 0.0001 for both). The proportion of underweight individuals decreased after one year of ETI therapy, from 9.3% to 1.9%, while the proportion of overweight or obese individuals increased from 8.3% to 22.9 % at the same time ( p < 0.001). In relation to exacerbations, there is a significant increase in the number of patients who did not have any exacerbations after one year of treatment, which increased from 10.2% to 46.2% ( p < 0.001), while the number of patients who had >4 exacerbations decreased significantly, from 40.7% to 1.9% ( p < 0.001). FEV1% (forced expiratory volume) increased from 63.9 ± 20.9 to 76.8 ± 21.4 ( p < 0.001) and the VR/TLC (residual volume/total lung capacity) value decreased from 45.1 ± 10.9 to 34.9 ± 6.2 ( p < 0.001). The proportion with FEV1% > 80% increased from 23.1% before ETI therapy to 49.1% one year after ETI therapy. We performed multivariate mixed models to evaluate the evolution of BMI changes with time, accounting for repeated measures and for possible modifying factors. After the introduction of the triple therapy, patients included in the study had significant weight gain during the 12 months, and when including different covariates in the multivariate mixed model, we found that lower baseline BMI, lower baseline FEV1 and FVC (forced vital capacity), and higher VR/TLC value and higher number of exacerbations were associated with higher BMI changes over the study period., Conclusions: CF patients treated with triple therapy experience significant weight gain, increasing the proportion of overweight patients. CF patients who experienced greater weight gain were those with worse BMI at the start of treatment, as well as patients with worse lung function and a greater number of exacerbations in the year before starting ETI therapy.

Introduction: We are assisting to an increase in survival rates among individuals with cystic fibrosis (CF). Until now, renal involvement was a minority issue, but with the rise in life expectancy, we will likely see an increase in its prevalence. Our main objective was to assess renal function in CF and study risk factors associated with its deterioration., Methods: A cross-sectional, retrospective study was conducted, including adults with CF. Clinical, respiratory function, microbiological, blood and urine analysis, and major chronic treatments received were collected., Results: Eighty nine patients with a mean age of 35±12 years were analyzed. Mean serum creatinine levels were 0.8±0.2mg/dL. 10.6% had a glomerular filtration rate less than 90mL/min/1.73m 2 . No patient showed albuminuria. In multivariate model, only age was an independent risk factor for reduced glomerular filtration (OR: 0.344; 95%CI: 0.004-0.017; P=.002)., Conclusions: 11% of CF adults show decreased glomerular filtration, with age being the sole independent risk factor. Vigilance for this uncommon condition is crucial., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Cystic fibrosis (CF) is a genetic disorder characterized by chronic microbial colonization and inflammation of the respiratory tract (RT), leading to pulmonary exacerbation (PEx) and lung damage. Although the lung bacterial microbiota has been extensively studied, the mycobiome remains understudied. However, its importance as a contributor to CF pathophysiology has been highlighted. The objective of this review is to provide an overview of the current state of knowledge regarding the mycobiome, as described through NGS-based studies, in patients with CF (pwCF).Several studies have demonstrated that the mycobiome in CF lungs is a dynamic entity, exhibiting a lower diversity and abundance than the bacterial microbiome. Nevertheless, the progression of lung damage is associated with a decrease in fungal and bacterial diversity. The core mycobiome of the RT in pwCFs is mainly composed of yeasts (Candida spp., Malassezia spp.) and molds with lower abundance. Some fungi (Aspergillus, Scedosporium/Pseudallescheria) have been demonstrated to play a role in PEx, while the involvement of others (Candida, Pneumocystis) remains uncertain. The "climax attack" ecological model has been proposed to explain the complexity and interplay of microbial populations in the RT, leading to PEx and lung damage. NGS-based studies also enable the detection of intra- and interkingdom correlations between fungi and bacteria. Further studies are required to ascertain the biological and pathophysiological relevance of these correlations. Finally, with the recent advent of CFTR modulators, our understanding of the pulmonary microbiome and mycobiome in pwCFs is about to change., (© 2024. The Author(s).)

SUMMARYThis guidance presents recommendations for clinical microbiology laboratories for processing respiratory samples from people with cystic fibrosis (pwCF). Appropriate processing of respiratory samples is crucial to detect bacterial and fungal pathogens, guide treatment, monitor the epidemiology of cystic fibrosis (CF) pathogens, and assess therapeutic interventions. Thanks to CF transmembrane conductance regulator modulator therapy, the health of pwCF has improved, but as a result, fewer pwCF spontaneously expectorate sputum. Thus, the collection of sputum samples has decreased, while the collection of other types of respiratory samples such as oropharyngeal and bronchoalveolar lavage samples has increased. To optimize the detection of microorganisms, including Pseudomonas aeruginosa , Staphylococcus aureus , Haemophilus influenzae , and Burkholderia cepacia complex; other less common non-lactose fermenting Gram-negative bacilli, e.g., Stenotrophomonas maltophilia , Inquilinus , Achromobacter , Ralstonia , and Pandoraea species; and yeasts and filamentous fungi, non-selective and selective culture media are recommended for all types of respiratory samples, including samples obtained from pwCF after lung transplantation. There are no consensus recommendations for laboratory practices to detect, characterize, and report small colony variants (SCVs) of S. aureus , although studies are ongoing to address the potential clinical impact of SCVs. Accurate identification of less common Gram-negative bacilli, e.g., S. maltophilia , Inquilinus , Achromobacter , Ralstonia , and Pandoraea species, as well as yeasts and filamentous fungi, is recommended to understand their epidemiology and clinical importance in pwCF. However, conventional biochemical tests and automated platforms may not accurately identify CF pathogens. MALDI-TOF MS provides excellent genus-level identification, but databases may lack representation of CF pathogens to the species-level. Thus, DNA sequence analysis should be routinely available to laboratories for selected clinical circumstances. Antimicrobial susceptibility testing (AST) is not recommended for every routine surveillance culture obtained from pwCF, although selective AST may be helpful, e.g., for unusual pathogens or exacerbations unresponsive to initial therapy. While this guidance reflects current care paradigms for pwCF, recommendations will continue to evolve as CF research expands the evidence base for laboratory practices., Competing Interests: Lisa Saiman receives grant funding (provided to institution) from the U.S. CF Foundation and serves as a consultant to the CF Foundation. Valerie Waters receives grant funding from the U.S. CF Foundation and CF Canada. John J. LiPuma receives grant funding from the U.S. CF Foundation. Lucas R. Hoffman receives grant funding from the U.S. CF Foundation. Kevin Alby has no conflicts of interest to report. Sean X. Zhang receives grant funding from the U.S. CF Foundation. Yvonne C. Yau receives grant funding from the U.S. CF Foundation and CF Canada. Damian G. Downey receives grants from the CF Trust and U.S. CF Foundation. He receives support from the European CF Society and U.S. CF Foundation for travel to meetings. He is the Director of the European CF Society Clinical Trials Network. Isabelle Sermet-Gaudelus receives funding from the European Cystic Fibrosis Society and the UK Cystic Fibrosis Trust. Jean-Philippe Bouchara receives funding from Vaincre la Mucoviscidose, La Pierre Le Bigaut, Association Grégory Lemarchal, and Anjou Muco. Timothy J Kidd has no conflicts of interest to report. Scott C. Bell receives grant funding from the U.S. CF Foundation, the Australian National Health and Medical Research Council, and the Medical Research Future's Fund. A. Whitney Brown is an employee of the U.S. CF Foundation.

Background: Recurrent respiratory infections are a leading cause of morbidity and mortality in persons with Cystic Fibrosis (pwCF). Recently, the emergence of Nocardia species as a potential pathogen in CF has raised questions about its role and management, as its clinical significance and the optimal patient management remain unclear in current clinical practice. This review explores the clinical implications of Nocardia species in patients with Cystic Fibrosis (pwCF) through a comprehensive literature review. Key objectives include assessing its impact on lung function, identifying colonization risk factors, and evaluating an appropriate treatment., Methods: The literature review, conducted until June 30, 2023, from databases like MEDLINE, PubMed, Embase, and Cochrane, included 16 articles involving 89 pwCF with Nocardia species isolation according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline recommendations. Articles reporting Nocardia prevalence and symptoms based on original data in adult and paediatric pwCF were included. All the retrieved studies were observational ones, thus, they were categorized by study type as case report and case series., Results: Overall 89 pwCF and Nocardia species isolation were included: 42 children and 47 adults. Where reported, we found these main following bacterial species: Nocardia asteroides (35%, 23/64), Nocardia farcinica (21%, 14/64), Nocardia tranvalensis (13%, 8/64) and Nocardia cyriacigeorgica (11%, 7/64). A co-infection was reported in 85% of patients (61/72). Of patients whose lung function was reported before and after Nocardia isolation, 23% (16/68) showed a decline in FEV 1 . Above all, 82 patients were treated at least once after isolation of Nocardia strain. In 93% (77/82) of cases, treatment was started immediately upon isolation. Antibiotic treatment was performed per os or intravenously depending on the clinical condition of the individual patient. Nocardia eradication was attempted in only 32 cases out of 82, and 78% (25/32) of these patients were successfully eradicated after one or more courses of antibiotics. Death was reported in 3 patients, 2 of which were children., Conclusion: In general the isolation of the bacteria does not necessarily imply therapy, but patients need to be monitored closely to assess the possible occurrence of active infection. The treatment seems to be indicated in patients showing lung involvement with the possible appearance of pneumonia, pleural effusion, fever, cough, or a decrease in FEV 1 , as in the case that we described, or in patients undergoing pulmonary transplantation., (© 2024. The Author(s).)

Objectives: In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers., Design: All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was compared against non-transplanted pwCF and with all persons screened for suspected HEV infection from 2016 to 2022 in Alberta, Canada. Those with chronic HEV infection underwent genomic sequencing and phylogenetic analysis. Owing to their swine derivation, independently sourced pancreatic enzyme replacement therapy (PERT) capsules were screened for HEV., Results: HEV seropositivity was similar between transplanted and non-transplanted pwCF (6/29 (21%) vs 16/83 (19%); p=0.89). Relative to all other Albertans investigated for HEV as a cause of hepatitis (n=115/1079, 10.7%), pwCF had a twofold higher seropositivity relative risk and this was four times higher than the Canadian average. Only three chronic HEV infection cases were identified in all of Alberta, all in CF lung transplant recipients (n=3/29, 10.3%). Phylogenetics confirmed cases were unrelated porcine-derived HEV genotype 3a. Ninety-one per cent of pwCF were taking PERT (median 8760 capsules/person/year). HEV RNA was detected by RT-qPCR in 44% (47/107) of PERT capsules, and sequences clustered with chronic HEV cases., Conclusion: PwCF had disproportionate rates of HEV seropositivity, regardless of transplant status. Chronic HEV infection was evident only in CF transplant recipients. HEV may represent a significant risk for pwCF, particularly post-transplant. Studies to assess HEV incidence and prevalence in pwCF, and potential role of PERT are required., Competing Interests: Competing interests: SEC: reports grants from Bristol-Myers Squibb Canada, Gilead Sciences, Genfit, Allergan, Axcella Health, and Sequana Medical and personal fees from Intercept Pharmaceuticals, Eisai, Paladin Labs, AstraZeneca and Novo Nordisk outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cystic fibrosis (CF), an inherited autosomal recessive disorder, is linked with high morbidity and mortality rates due to bacteria, filamentous, yeast and black yeast-like fungi colonisation in the upper respiratory tract. Although Candida species are the most common fungi isolated from CF patients, azole-resistant Aspergillus fumigatus (ARAf) is a big concern for invasive aspergillosis. Notably, the exact prevalences of Aspergillus species and the prevalence of ARAf isolates among Iranian CF patients have yet to be previously reported and are unknown. We aimed to investigate the prevalence of ARAf isolates in CF patients among Iranian populations by focusing on molecular mechanisms of the mutations in the target gene., Methods: The 1 year prospective study recovered 120 sputum samples from 103 CF patients. Of these, 55.1% (86/156) yielded Aspergillus species, screened for ARAf using plates containing itraconazole (4 mg/L) and voriconazole (1 mg/L). According to the CLSI-M38 guidelines, antifungal susceptibility testing was performed using the broth microdilution method. In all phenotypically resistant isolates, the target of azole agents, the cyp51A gene, was sequenced to detect any possible single nucleotide polymorphisms (SNP) mediating resistance., Results: Of 120 samples, 101 (84.2%) were positive for filamentous fungi and yeast-like relatives, with 156 fungal isolates. The most common colonising fungi were Aspergillus species (55.1%, 86/156), followed by Candida species (39.8%, 62/156), Exophiala species (3.8%, 6/156) and Scedosporium species (1.3%, 2/156). Forty out of 86 (46.5%) were identified for section Fumigati, 36 (41.9%) for section Flavi, 6 (7%) for section Nigri and 4 (4.6%) for section Terrei. Fourteen out of 40 A. fumigatus isolates were phenotypically resistant. The overall proportion of ARAf in total fungal isolates was 9% (14/156). cyp51A gene analysis in resistant isolates revealed that 13 isolates harboured G448S, G432C, T289F, D255E, M220I, M172V, G138C, G54E and F46Y mutations and one isolate carried G448S, G432C, T289F, D255E, M220I, G138C, G54E and F46Y mutations. Additionally, this study detects two novel cyp51A single-nucleotide polymorphisms (I242V and D490E)., Conclusions: This study first investigated ARAf isolates in Iranian CF patients. Due to a resistance rate of up to 9%, it is recommended that susceptibility testing of Aspergillus isolates from CF patients receiving antifungal treatment be a part of the routine diagnostic workup. However, extensive multicentre studies with a high volume of CF patients are highly warranted to determine the impact of ARAf on CF patients., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

People with CF (pwCF) are at high risk for malnutrition, making nutritional management a critical aspect of CF care. Over the past several decades, optimal nutritional status for pwCF has been defined by body mass index (BMI) based on evidence linking suboptimal BMI to decreased lung function and life expectancy, although more recent changes in CF care may also bring changes to how nutritional health is defined. The historical focus on weight, BMI, and nutrition as key parts of multidisciplinary CF care starting at an early age places pwCF at increased risk for body image concerns and disordered eating. The landscape of CF care is evolving with the approval of highly effective modulator therapies (HEMT) and resulting improvements in growth; however, issues related to body image and eating remain important to consider, especially as past difficulties gaining weight may shift to discomfort with one's weight gain and/or physical appearance. This review aims to describe how body image concerns and disordered eating occur in pwCF across the lifespan; to discuss evidence-based approaches to addressing these concerns; and to identify future directions for research and clinical practice in assessing and treating eating disorders and body image concerns in this population., (© 2024 Wiley Periodicals LLC.)

Advances in treatment for cystic fibrosis (CF), including cystic fibrosis transmembrane conductor regulator (CFTR) modulators, have ushered in an era where patients with CF have much longer life expectancies. This shift in life expectancy demands increased attention to diseases of aging in patients with CF. A notable complication of CF is early-onset colorectal cancer (CRC), which is especially prevalent in patients with severe mutations and after transplant. CFTR acts as a tumor suppressor gene based on knockout models. Lack of CFTR expression promotes carcinogenic processes such as intestinal inflammation and deleterious gut microbiome changes. The consensus Cystic Fibrosis Foundation recommendations advocate treating this population as a high-risk group, using a colonoscopy-only screening strategy starting at age 40 in patients without transplant and at age 30 after transplant. Screening should be considered every 5 years if negative and every 3 years or sooner for patients with adenomatous polyps. Future research will determine the role of noninvasive CRC screening tools in this population, as well as the effects of CFTR modulators on the risk of developing CRC., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Advances in cystic fibrosis (CF) diagnostics and therapeutics have led to improved health and longevity, including increased body weight and decreased malnutrition in people with CF. Highly effective CFTR modulator therapies (HEMT) are associated with increased weight through a variety of mechanisms, accelerating trends of overweight and obesity in the CF population. Higher body mass index (BMI) is associated with improved pulmonary function in CF, yet the incremental improvement at overweight and obese BMIs is not clear. Improvements in pulmonary health with increasing BMI are largely driven by increases in fat-free mass (FFM), and impact of HEMT on FFM is uncertain. While trends toward higher weight and BMI are generally seen as favorable in CF, the increased prevalence of overweight and obesity has raised concern for potential risk of traditional age- and obesity-related comorbidities. Such comorbidities, including impaired glucose tolerance, hypertension, cardiac disease, hyperlipidemia, fatty liver, colon cancer, and obstructive sleep apnea, may occur on top of pre-existing CF-related comorbidities. CF nutrition recommendations are evolving in the post-modulator era to more individualized approaches, in contrast to prior blanket high-fat, high-calorie prescriptions for all. Ultimately, it will be essential to redefine goals for optimal weight and nutritional status to allow for holistic health and aging in people with CF., (© 2023 Wiley Periodicals LLC.)

Cystic Fibrosis (CF) is a complex disorder that requires multidisciplinary expertise for effective management. The GALAXY study estimated the prevalence of constipation to be about 25% among People with Cystic Fibrosis (PwCF), identifying it as one of the common gastrointestinal (GI) symptoms within this patient population. Quality of Life (QoL) assessments uncovered high patient dissatisfaction, highlighting the imperative need for enhanced treatment strategies. Similarly, Distal Intestinal Obstruction Syndrome (DIOS) is a unique condition exclusive to PwCF that, if left undiagnosed, can lead to considerable morbidity and mortality. Given the broad spectrum of differential diagnoses for abdominal pain, including constipation and DIOS, it is paramount for healthcare providers to possess a clear understanding of these conditions. This paper aims to delineate various differentials for abdominal pain while elucidating the pathogenesis, diagnostic criteria, and treatment options for managing constipation and DIOS in PwCF., (© 2024 Wiley Periodicals LLC.)

Background: Non-invasive and sensitive clinical endpoints are needed to monitor onset and progression of early lung disease in children with cystic fibrosis (CF). We compared lung clearance index (LCI), FEV 1 , functional and structural lung magnetic resonance imaging (MRI) outcomes in Swiss children with CF diagnosed following newborn screening., Methods: Lung function (LCI, FEV 1 ) and unsedated functional and structural lung MRI was performed in 79 clinically stable children with CF (3 - 8 years) and 75 age-matched healthy controls. Clinical information was collected throughout childhood., Results: LCI, ventilation and perfusion defects, and structural MRI scores were significantly higher in children with CF compared with controls, but FEV 1 was not different between groups. Lung MRI outcomes correlated significantly with LCI (morphology score (r = 0.56, p < 0.001); ventilation defects (r = 0.43, p = 0.001); perfusion defects (r = 0.64, p < 0.001), but not with FEV 1 . Lung MRI outcomes were more sensitive to detect impairments in children with CF (abnormal ventilation and perfusion outcomes in 47 %, morphology score in 30 %) compared with lung function (abnormal LCI in 21 % and FEV 1 in 4.8 %). Pulmonary exacerbations, respiratory hospitalizations, and increase in patient-reported cough was associated with higher LCI and higher structural and functional MRI outcomes., Conclusions: The LCI and lung MRI outcomes non-invasively detect even mild early lung disease in young children with CF diagnosed following newborn screening. Pulmonary exacerbations and early respiratory symptoms were risk factors for structural and functional impairment in childhood., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. P. Latzin reports the followind COIs: - Grants from Vertex and OM Pharma paid to the institution - Participation on data safety monitoring boards or advisory boards of Polyphor, Santhera DMC, Vertex, OM Pharma, Vifor, Sanofi Aventis - Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Vertex, Vifor, OM Pharma Jakob Usemann reports: Grants from - Swiss lung foundation - Palatin Foundation, Basel, Switzerland Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: - Vertex - Zurich Lung foundation Support for attending meetings and/or travel from Vertex Kathryn Ramsey reports: Support for the present manuscript form: -Swiss National Science Foundation Ambizione Research Grant (168173), paid to the institution Leadership or fiduciary role in other board, society, committee or advocacy group, unpaid Global Lung Initiative MBW Task Force Elisabeth Kieninger reports: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Sanofi-Aventis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Up to 90% of people with CF (pwCF) will have some form of hepatobiliary involvement. This manuscript aims to explore the different endovascular, endoscopic, radiological and surgical procedures available to diagnose and manage the most severe form of CF hepatobiliary involvement (CFHBI) known as advanced cystic fibrosis liver disease (aCFLD), seen in 10% of pwCF. These procedures and interventions include liver biopsy, hepatic venous pressure gradient measurement, gastrostomy tube placement to optimize nutrition, paracentesis, endoscopic variceal control of bleeding and portosystemic shunting before liver transplantation. By utilizing advanced diagnostic or surgical techniques, healthcare professionals of pwCF can more effectively manage patients with CFHBI and aCFLD and potentially improve patient outcomes., (© 2024 Wiley Periodicals LLC.)

Background: COMBAT-CF showed that children aged 0-3 years treated with azithromycin did clinically better than placebo but there was no effect on CT-scores. We reanalysed CTs using an automatic bronchus-artery (BA) analysis., Method: Inspiratory and expiratory CTs at 12 and 36 months were analysed. BA-analysis measures BA-diameters: bronchial outer wall (B out ), bronchial inner wall (B in ), artery (A), and bronchial wall thickness (B wt ) and computes BA-ratios: B out /A and B in /A for bronchial widening, B wt /A and B wa /B oa (bronchial wall area/bronchial outer area) for bronchial wall thickening. Low attenuation regions (LAR) were analysed using an automatic method. Mixed-effect model was used to compare BA-outcomes at 36 months between treatment groups., Results: 228 CTs (59 placebo; 66 azithromycin) were analysed. The azithromycin group had lower B wa /B oa (p = 0.0034) and higher B in /A (p = 0.001) relative to placebo. B out /A (p = 0.0088) was higher because of a reduction in artery diameters which correlated to a reduction in LAR., Conclusion: Azithromycin-treated infants with CF show a reduction in bronchial wall thickness and possibly a positive effect on lung perfusion., Competing Interests: Declaration of competing interest HAWMT reports grants from the Cystic Fibrosis Foundation, has a part time position as chief medical officer for Thirona, and Erasmus MC is expected to receive future license royalties for PRAGMA-CF. JPC is employee and shareholder at Thirona. SMS reports grants from the Cystic Fibrosis Foundation and National Health and Medical Research Foundation, and Telethon Kids Institute is expected to receive future license royalties for PRAGMA-CF. All other authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)