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Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance., Competing Interests: Declaration of competing interest Dr. Guimbellot reports consulting fees from Vertex Pharmaceuticals Incorporated, outside the submitted work. All other authors have no conflicts of interest to report., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: New York State (NYS) utilizes a three-tiered cystic fibrosis newborn screening (CFNBS) algorithm that includes cystic fibrosis transmembrane conductance regulator (CFTR) gene sequencing. Infants with >1 CFTR variant of potential clinical relevance, including variants of uncertain significance or varying clinical consequence are referred for diagnostic evaluation at NYS cystic fibrosis (CF) Specialty Care Centers (SCCs)., Aims: As part of ongoing quality improvement efforts, demographic, screening, diagnostic, and clinical data were evaluated for 289 CFNBS-positive infants identified in NYS between December 2017 and November 2020 who did not meet diagnostic criteria for CF and were classified as either: CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID) or CF carriers., Results: Overall, 194/289 (67.1%) had CFTR phasing to confirm whether the infant's CFTR variants were in cis or in trans. Eighteen complex alleles were identified in cis; known haplotypes (p.R117H+5T, p.F508del+p.L467F, and p.R74W+p.D1270N) were the most common identified. Thirty-two infants (16.5%) with all variants in cis were reclassified as CF carriers rather than CRMS/CFSPID. Among 263 infants evaluated at an NYS SCC, 70.3% were reported as having received genetic counseling about their results by any provider, with 96/263 (36.5%) counseled by a certified genetic counselor., Conclusion: Given the particularly complex genetic interpretation of results generated by CFNBS algorithms including sequencing analysis, additional efforts are needed to ensure families of infants with a positive CFNBS result have CFTR phasing when needed to distinguish carriers from infants with CRMS/CFSPID, and access to genetic counseling to address implications of CFNBS results., (© 2024 Wiley Periodicals LLC.)

Objective: To identify predictors of change in lung function and body weight during health care transition in cystic fibrosis (CF)., Methods: We conducted a retrospective cohort study using data from the CF Foundation Patient Registry and the web-based transition program CF RISE (Responsibility. Independence. Self-care. Education) for patients aged 16-25 years who transitioned to adult care from 2013 through 2019. We modeled change in forced expiratory volume in 1 second % predicted and weight using linear regression fit with generalized estimating equations. Predictors included gap in care (time between last pediatric and first adult outpatient visit), transition program engagement, and sociodemographic and medical factors., Results: Among 12 420 adolescents and young adults (AYAs), 3876 transitioned to adult care with a median gap in care of 7.6 months. Patients from CF centers with greater rates of CF RISE engagement had improved lung function and weight at their first adult outpatient visit. Coverage on a parent's insurance plan and absence of CF complications predicted increased lung function. History of a nonlung transplant and sinus disease predicted increased weight. Comorbid diabetes mellitus and gaps in care >3 months predicted decreased lung function with longer gaps in care associated with greater decrease. A gap in care of 6-9 months predicted decreased weight. Control variables including baseline forced expiratory volume in 1 second and weight, and exacerbation status were also statistically significant., Conclusions: Findings suggest 2 promising targets to improve transition of AYAs with CF: increasing AYA engagement in CF RISE and reducing gaps in care during the transition period., Competing Interests: Declaration of Competing Interest All phases of this study were supported by a National Institute of Nursing Research (NINR) grant, 1F31NR020141-01. K.M. also was supported by Agency for Healthcare Research and Quality (AHRQ) grant number T32HS000063 as part of the Harvard-wide Pediatric Health Services Research Fellowship Program. The NINR and AHRQ had no role in the design and conduct of the study. The first draft of the manuscript was written by K.M.; no honorarium or other compensation was received. The other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Cystic fibrosis (CF) is a systemic autosomal recessive condition characterised by progressive lung disease. CF pulmonary exacerbations (PEx) are episodes of worsening respiratory status, and frequent PEx are a risk factor for accelerated lung function decline, yet many people with CF (PwCF) go untreated at the time of decline. The goal of this quality improvement (QI) initiative was to improve recognition, treatment and follow-up of PEx in PwCF., Methods: Using the Model for Improvement, the Cystic Fibrosis Learning Network (CFLN) initiated a QI innovation laboratory (iLab) with a global aim to decrease the rate of lung function decline in PwCF. The iLab standardised definitions for signals of PEx using a threshold for decline in forced expiratory volume in one second (FEV 1 ) and/or changes in symptoms. The FEV 1 decline signal was termed FIES (FEV 1 -indicated exacerbation signal). Processes for screening and recognition of FIES and/or symptom changes, a treatment algorithm and follow-up in the presence of a signal were tested concurrently in multiple settings., Specific Aims: The specific aim is to increase the per cent of PwCF assessed for a PEx signal at ambulatory encounters and to increase the per cent of recommendations to follow-up within 6 weeks for PwCF experiencing a PEx signal., Results: FIES recognition increased from 18.6% to 73.4% across all teams during the iLab, and every team showed an improvement. Of PwCF assessed, 15.8% experienced an FIES event (>10% decline in FEV 1 per cent predicted (FEV 1 pp)). Follow-up within 6 weeks was recommended for an average of 70.5% of those assessed for FIES and had an FEV 1 pp decline greater than 5%., Conclusion: The CFLN iLab successfully defined and implemented a process to recognise and follow-up PEx signals. This process has the potential to be spread to the larger CF community. Further studies are needed to assess the impact of these processes on PwCF outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Peripherally inserted central catheters (PICCs) are used commonly to administer antibiotics to people with cystic fibrosis (CF), but their use can be complicated by venous thrombosis and catheter occlusion., Research Question: Which participant-, catheter-, and catheter management-level attributes are associated with increased risk of complications of PICCs among people with CF?, Study Design and Methods: This was a prospective observational study of adults and children with CF who received PICCs at 10 CF care centers in the United States. The primary end point was defined as occlusion of the catheter resulting in unplanned removal, symptomatic venous thrombosis in the extremity containing the catheter, or both. Three categories of composite secondary outcomes were identified: difficult line placement, local soft tissue or skin reactions, and catheter malfunction. Data specific to the participant, catheter placement, and catheter management were collected in a centralized database. Risk factors for primary and secondary outcomes were analyzed by multivariate logistic regression., Results: Between June 2018 and July 2021, 157 adults and 103 children older than 6 years with CF had 375 PICCs placed. Patients underwent 4,828 catheter-days of observation. Of the 375 PICCs, 334 (89%) were ≤ 4.5 F, 342 (91%) were single lumen, and 366 (98%) were placed using ultrasound guidance. The primary outcome occurred in 15 PICCs for an event rate of 3.11 per 1,000 catheter-days. No cases of catheter-related bloodstream infection occurred. Other secondary outcomes developed in 147 of 375 catheters (39%). Despite evidence of practice variation, no risk factors for the primary outcome and few risk factors for secondary outcomes were identified., Interpretation: This study affirmed the safety of contemporary approaches to inserting and using PICCs in people with CF. Given the low rate of complications in this study, observations may reflect a widespread shift to selecting smaller-diameter PICCs and using ultrasound to guide their placement., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Adolescents with cystic fibrosis (CF) and their parents must navigate changing roles and responsibilities within the family including transfer of disease management responsibilities., Aim/objective: The aim of this qualitative study was to explore how families share and transfer CF management responsibility from the perspectives of adolescents with CF and their parents., Methods: Guided by qualitative descriptive methodology, we purposively sampled adolescent/parent dyads. Participants completed two surveys measuring family responsibility (Family Responsibility Questionnaire [FRQ]) and transition readiness (Transition Readiness Assessment Questionnaire [TRAQ]) We conducted semistructured video or phone interviews, used a codebook to guide team coding and analyzed qualitative data using both content analysis and dyadic interview analysis., Results: Thirty participants (15 dyads) enrolled (7% Black; 33% Latina/o; 40% female; adolescent age 14.4 ± 2 years; 66% prescribed highly effective modulator therapy; 80% of parents were mothers). Parent FRQ and TRAQ scores were significantly higher than their adolescent indicating differing perceptions of responsibility and transition readiness. We inductively identified four themes: (1) CF management is a delicate balance (CF management is a routine which is easily disrupted), (2) Growing up and parenting under extraordinary circumstances (the burden of CF weighs on families as they navigate adolescence), (3) Differing Perceptions of risk and responsibility (adolescent and parent perceptions of treatment responsibility and the risks of nonadherence do not always align), and (4) Balancing independence and protection (families must weigh the benefits and risks of allowing adolescents increased independence)., Conclusions: Adolescents and parents demonstrated differing perceptions of CF management responsibility, which may be related to a lack of communication between family members about this topic. To help facilitate alignment of parent and adolescent expectations, discussion of family roles and responsibility for CF management should begin early during the transition process and be discussed regularly during clinic visits., (© 2023 Wiley Periodicals LLC.)

Purpose: The experience of healthcare transition from pediatric to adult care in cystic fibrosis (CF) remains poorly understood, particularly among racially and ethnically diverse adolescents and young adults (AYAs) with CF. The objective of this qualitative study was to explore the perspectives of a diverse sample of AYAs with CF at one urban academic medical center regarding healthcare transition., Design and Methods: Guided by qualitative descriptive methodology, we purposively selected AYAs who represented the pre and post transition experience: some AYAs had experienced the transition preparation program CF R.I.S.E. Demographic information and responsibility for self-management behaviors were collected using an online survey. Semi-structured video interviews were conducted following an iterative interview guide. A codebook directed inductive coding. QSR NVivo Version 12 software was used to organize the data., Results: 12 AYAs with CF were enrolled (25% female, 25% Black AYA, 33% Hispanic/Latina/o AYA, 50% White AYA; mean age 20.8 years). Three themes were identified: independent care of the whole self, preparing for change and the unknown and transition experiences vary., Conclusions: Not all participants experienced a smooth transition. Participants identified suggestions for the development of transition preparation interventions, specifically around involving AYAs in transition decisions and beginning transition preparation early in adolescence., Practice Implications: Participants expressed uncertainty about transition when they felt little control over the process or lacked sufficient information about adult care. Therefore, comprehensive early transition preparation for all AYAs with CF with a focus on involving AYAs in transition decisions is recommended., 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 © 2022 Elsevier Inc. All rights reserved.)

Rationale: Inhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and Pseudomonas aeruginosa airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill P. aeruginosa . This trial was done to test the effects of combining azithromycin with inhaled tobramycin on clinical and microbiological outcomes in people already using inhaled tobramycin. We theorised that those randomised to placebo (no azithromycin) would have greater improvement in forced expiratory volume in one second (FEV 1 ) and greater reduction in P. aeruginosa sputum in response to tobramycin., Methods: A 6-week prospective, randomised, placebo-controlled, double-blind trial testing oral azithromycin versus placebo combined with clinically prescribed inhaled tobramycin in individuals with cystic fibrosis and P. aeruginosa airway infection., Results: Over a 6-week period, including 4 weeks of inhaled tobramycin, the relative change in FEV 1 did not statistically significantly differ between groups (azithromycin (n=56) minus placebo (n=52) difference: 3.44%; 95% CI: -0.48 to 7.35; p=0.085). Differences in secondary clinical outcomes, including patient-reported symptom scores, weight and need for additional antibiotics, did not significantly differ. Among the 29 azithromycin and 35 placebo participants providing paired sputum samples, the 6-week change in P. aeruginosa density differed in favour of the placebo group (difference: 0.75 log 10 CFU/mL; 95% CI: 0.03 to 1.47; p=0.043)., Conclusions: Despite having greater reduction in P. aeruginosa density in participants able to provide sputum samples, participants randomised to placebo with inhaled tobramycin did not experience significantly greater improvements in lung function or other clinical outcomes compared with those randomised to azithromycin with tobramycin., Competing Interests: Competing interests: DN and NM-H, as part of their roles at the Cystic Fibrosis (CF) Foundation Therapeutics Development Network Coordinating Centre, provide consulting to industry sponsors who are developing new drug therapies for cystic fibrosis. Some of these sponsors are working to develop antimicrobial agents. PS and DN report grants from Vertex and Gilead Sciences outside of the published work. RG and GR-B report grants from Vertex outside of the published work. LS reports grants from Merck Co and Bill and Melinda Gates Foundation outside of the published work and payments for Data Safety Monitoring Board or Advisory Boards from Merck Co. Multiple authors have grant support or payments from the CF Foundation., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: People with cystic fibrosis (pwCF) may be at risk of complications from COVID-19 but the impact of COVID-19 on pwCF remains unknown., Methods: We conducted a multicenter retrospective cohort study to assess the impact of the COVID-19 pandemic first wave on pwCF in the New York metropolitan area (NY) from March 1, 2020 to August 31, 2020. Objectives were to determine (1) the prevalence of COVID-19 by PCR and IgG antibody testing, (2) the clinical characteristics of COVID-19, (3) delay in routine outpatient care, and (4) the effect on anxiety and depression in pwCF., Results: There were 26 COVID-19 cases diagnosed by PCR or antibody testing among the study cohort of 810 pwCF. The prevalence of COVID-19 by PCR (1.6%) and IgG antibody (12.2%) testing was low. 58% of cases were asymptomatic and 82% were managed at home. 8% were hospitalized and 1 person died. 89% of pwCF experienced delay in care. The prevalence of anxiety increased from 43% baseline to 58% during the pandemic (P<0.01). In post-hoc analysis, the proportion of patients with diabetes (38% versus 16%, P<0.01) and pancreatic insufficiency (96% versus 66%, P<0.01) were higher while CFTR modulator use was lower (46% versus 65%, P = 0.05) in pwCF who tested positive for COVID-19., Conclusions: The prevalence of COVID-19 among pwCF in NY during the pandemic first wave was low and most cases were managed at home. CFTR modulators may be protective. PwCF experienced delay in routine care and increased anxiety., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Rationale: Inhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and Pseudomonas aeruginosa airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill P. aeruginosa. This trial was done to test the effects of combining azithromycin with inhaled tobramycin on clinical and microbiological outcomes in people already using inhaled tobramycin. We theorised that those randomised to placebo (no azithromycin) would have greater improvement in forced expiratory volume in one second (FEV1) and greater reduction in P. aeruginosa sputum in response to tobramycin.Methods: A 6-week prospective, randomised, placebo-controlled, double-blind trial testing oral azithromycin versus placebo combined with clinically prescribed inhaled tobramycin in individuals with cystic fibrosis and P. aeruginosa airway infection.Results: Over a 6-week period, including 4 weeks of inhaled tobramycin, the relative change in FEV1 did not statistically significantly differ between groups (azithromycin (n=56) minus placebo (n=52) difference: 3.44%; 95% CI: -0.48 to 7.35; p=0.085). Differences in secondary clinical outcomes, including patient-reported symptom scores, weight and need for additional antibiotics, did not significantly differ. Among the 29 azithromycin and 35 placebo participants providing paired sputum samples, the 6-week change in P. aeruginosa density differed in favour of the placebo group (difference: 0.75 log10 CFU/mL; 95% CI: 0.03 to 1.47; p=0.043).Conclusions: Despite having greater reduction in P. aeruginosa density in participants able to provide sputum samples, participants randomised to placebo with inhaled tobramycin did not experience significantly greater improvements in lung function or other clinical outcomes compared with those randomised to azithromycin with tobramycin. [ABSTRACT FROM AUTHOR]

Pulmonary infections represent the major causes of morbidity and mortality in cystic fibrosis (CF). Here, we report a 3‐month‐old infant with pancreatic insufficient CF was hospitalized with positive RT‐PCR test for COVID‐19. He was treated successfully. Hypertonic saline can be hypothesized as a treatment regimen against COVID‐19 infection after further investigations. Children with CF have underlying lung disease that is associated with pulmonary exacerbation by viral infections. We also proposed that hypertonic saline might be considered as a therapeutic option for COVID‐19. [ABSTRACT FROM AUTHOR]