BACKGROUND:Cystic fibrosis (CF) is a genetic disease with increasing life expectancy due to advances in treatment. However, this increased life expectancy has led to new health challenges, especially diabetes. Nearly 25% of adults with CF develop diabetes, but only a minority receive endocrinology care. OBJECTIVE:This study aimed to co-design, implement, and evaluate a nested diabetes model of care (MOC) for adults with CF and diabetes in a single tertiary adult CF center in Australia. METHODS:We used several implementation frameworks to co-design the MOC with consumer and provider end-users. Following MOC implementation, we used database-driven analytics to evaluate changes in the primary clinical outcome (HbA1c) pre and post study at 1 year. A mixed methods approach was used to evaluate secondary clinical and non-clinical outcomes. RESULTS:The MOC promoted multidisciplinary collaboration and streamlined patient journeys, leading to high engagement. Thus, 76.7% of the entire CF cohort with confirmed diabetes was reviewed within the first year of operationalization. Engagement with the MOC was associated with a statistically significant decline in HbA1c (-0.54% vs +0.33%, p- value 0.004) and a 0.22% [95% CI 0.19 -0.32] per month increment in percent predicted forced expiratory volume (ppFEV1). CONCLUSION:Our co-designed MOC demonstrated high engagement as well as improving glycemic management and lung function in adults with CF and diabetes. Our approach to CF diabetes care may reduce the treatment burden in the order of initiating a new diabetes medication while concurrently enhancing end-user experiences of health care. SPANISH ABSTRACT:http://links.lww.com/IJEBH/A473.

BACKGROUND:People with cystic fibrosis (pwCF) are susceptible to chronic lung infections, particularly with Pseudomonas aeruginosa. During infection, a subset of patients develops cloaking antibodies specific to O-antigen lipopolysaccharide that impair complement-mediated bactericidal killing. These antibodies associate with worse disease, and their removal via plasmapheresis has been used as a successful treatment for multidrug-resistant P aeruginosa. Whether a similar mechanism of antibody-mediated serum resistance exists toward common polysaccharide antigen (CPA) lipopolysaccharide is unknown. METHODS:Forty-two serum samples and 63 matched P aeruginosa isolates were collected from pwCF. The titers of antibodies specific to CPA in patient sera were determined, and the ability of these antibodies to inhibit serum-mediated killing of P aeruginosa was assessed. RESULTS:Despite widespread anti-CPA antibodies, only 1 serum-strain pair showed evidence of complement inhibition. Patient serum IgG and IgA responses to CPA were elevated in 86% and 69% of sera, respectively. Furthermore, 69% of pwCF were colonized with CPA-expressing isolates. Despite the high prevalence of elevated anti-CPA antibodies, only 1 patient had antibodies capable of inhibiting complement killing of the cognate P aeruginosa. This isolate, CFP3A, had significantly higher expression of CPA than all other strains. Complement-mediated killing toward it was inhibited by anti-CPA antibodies in a titer-dependent manner. CONCLUSIONS:This investigation reveals that although antibody specific for CPA is prevalent in pwCF, it cannot inhibit complement killing of the majority of CPA-expressing strains. Thus, when Pseudomonas is treated by removal of cloaking antibodies, it is unlikely that CPA-specific antibodies will also need to be eliminated.

INTRODUCTION:Gastrostomies are used to support nutritional adequacy, growth and lung function in people with Cystic Fibrosis (CF). Adults with CF living with a gastrostomy face unique challenges due to the time and length of placement often being inserted in childhood and extending through to adulthood. In the era of CF modulator therapies removal of gastrostomies is increasingly being contemplated, and our aim was to understand experiences and perspectives of adults with CF who have lived with a gastrostomy. METHODS:This was a single-centre qualitative study in adults with CF who have lived with a gastrostomy. All semi-structured interviews were audio recorded, transcribed and analyzed inductively using grounded theory methodology. Data saturation was reached when no new codes emerged. Findings were summarized into major conceptual themes. Participant demographics and medical history were obtained. RESULTS:In total, thirteen participants completed semi-structured interviews. Analyzes revealed four main themes in adults with CF who have lived with a gastrostomy (1) Psychological (i.e. body image, embarrassment, isolating/social stigma, acceptance/adjustment), (2) Pain & physical concerns (i.e. general pain, hyper granulation, leaking), (3) Social (i.e. relationships and navigating social conversations), and (4) Functionality. CONCLUSION:Our study explored lived experiences of adults with CF and a gastrostomy. We found there was significant psychological and social impact of growing up with a gastrostomy, highlighting the need for clinicians to provide holistic support that addresses both physical and mental challenges of long-term gastrostomy care for adults with CF.

Abstract: Introduction: Cystic fibrosis (CF) lung disease is characterised by chronic infection, inflammation, and mucous hypersecretion. Airway clearance physiotherapy and mucoactive medication are effective, but burdensome components of disease management. The increasing availability of CFTR modulator therapies necessitates a re-evaluation of the role of established management strategies. This study explores self-reported airway clearance and inhaled medication use in adults with CF over a 12-month period following initiation of elexacaftor-tezacaftor-ivacaftor (ETI). Methods: This prospective cohort study enrolled participants who completed questionnaires on airway clearance practices, inhaled medication use and exercise participation at baseline and at 3-monthly intervals post-ETI for 12 months. Clinical parameters, including lung function, nutritional status, exercise capacity and sputum volume, were assessed throughout the study period. Results: Of the 132 participants who consented, 123 provided sufficient data for analysis. Airway clearance frequency and duration declined significantly, with 31.5% ceasing airway clearance. Salbutamol and hypertonic saline use also declined. Over the 12-month follow-up period, improvements were observed in lung function, body mass index (BMI), sputum volume and hospitalisation rates. Exercise duration remained unchanged, although improvements in modified shuttle walk distance were recorded. Lung function severity was associated with baseline sputum volume but not influenced by physiotherapy practices or response to ETI. Conclusion: Following initiation of ETI, there was a reduction in airway clearance and inhaled therapies without compromising improvements in lung function, nutrition, or exercise capacity in the first 12 months. These findings support re-evaluation of physiotherapy regimens in the context of CFTR modulator therapies.

BACKGROUND:Cystic fibrosis (CF) transmembrane conductance regulator modulators improve lung function, however, effects on cough frequency, physical activity, and sleep have not been assessed in clinical studies. METHODS:After a 12-week, phase 4 pilot feasibility study, we conducted a 13-week, phase 3b, open-label study in participants with CF aged ≥12 years previously naïve to elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) to assess the effects of ELX/TEZ/IVA on cough frequency, physical activity, and sleep using wearable cough monitors and actigraphy sensors (VX-445-126). RESULTS:In study VX-445-126 (N = 81), participants treated with ELX/TEZ/IVA experienced a 91.7% reduction in cough frequency (cough events per day) (95% CI, 89.2% to 93.6%; 241.3 coughs per day at baseline to 20.3 coughs per day) from baseline at the average of week 8 through week 12 (primary endpoint). Total steps per day (secondary endpoint) increased by 638 (95% CI, 298 to 977) at the average of week 8 through week 12. Time spent above sedentary physical activity per day, time spent on moderate-to-vigorous physical activity per day, and total mean activity count per day all increased from baseline at the average of week 8 through week 12 (other efficacy endpoints). While no changes in sleep activity patterns were observed in actigraphy data, patient-reported measures of sleep quality improved (other efficacy endpoints). ELX/TEZ/IVA was generally safe and well-tolerated. CONCLUSIONS:ELX/TEZ/IVA treatment led to a > 90% reduction in daily cough frequency, with sustained improvements in physical activity and better perceptions of sleep quality.

Cystic fibrosis (CF) is a multi-system genetic condition, and CF modulator therapies have transformed health outcomes promising improved longevity. Our aim was to co-design and implement a nested endocrine and metabolic model of care called CF Endocrine for adults with CF that aligned with consumer and healthcare provider priorities and addressed emerging service gaps in the post-modulator era. Using mixed-methods and implementation science methodologies, we designed and conducted surveys, audits and workshops to define service priorities and referral pathways and workflows. In total, 17% of adults attending our CF centre participated in the survey and reported lifestyle optimisation, weight management and diabetes prevention as leading consumer concerns. Four service arms were developed: (i) diabetes support, (ii) bone health, (iii) metabolic health and (iv) reproductive/sexual health. Providers showed strong alignment with consumer priorities and endorsed integration and feasibility of the new nested CF Endocrine service.

IntroductionCystic fibrosis transmembrane conductance regulator modulators (CFTRm), particularly elexacaftor/tezacaftor/ivacaftor (ETI), have transformed outcomes for people with cystic fibrosis (pwCF). However, access remains limited globally due to genotype-based eligibility and high medication cost. Pharmacokinetic manipulation using cytochrome P450 3A4 (CYP3A4) inhibitors has emerged as a potential strategy to extend ETI exposure in resource-constrained settings.CaseWe describe a 52-year-old female with CF (G542X/T1246I) whose genotype initially precluded subsidised ETI access in Australia. She experienced progressive clinical decline in 2024, with worsening bronchiectasis, recurrent Pseudomonas aeruginosa exacerbations, and a fall in ppFEV1 below 40%. Supported by in vitro evidence of T1246I responsiveness, she self-funded ETI, resulting in rapid symptomatic improvement, reduced sputum burden, and objective gains in lung function, sweat chloride, and weight. To improve affordability, azithromycin was replaced with clarithromycin, a potent CYP3A4 inhibitor, enabling a reduced ETI dosing schedule. Therapeutic drug monitoring demonstrated lower serum concentrations of all ETI components compared with full-dose therapy, yet clinical stability and improved quality of life were maintained, with no further exacerbations. Clarithromycin was selected due to its established safety profile and dual utility as macrolide therapy, avoiding the hepatotoxicity risk associated with azole antifungals.ConclusionThis report supports the potential for CYP3A4 inhibition to aid with personalised ETI dosing strategies, particularly in low and middle-income countries where CFTRm access remains limited. Further research is needed to define optimal manipulation strategies, understand inter-individual variability in CFTRm metabolism, and evaluate the feasibility of therapeutic drug monitoring in diverse healthcare settings.

INTRODUCTION:Burkholderia cepacia complex (BCC) comprises 25 species known to cause disease primarily in people with cystic fibrosis (pwCF). Isolation of BCC has major implications for infection control, eradication strategies, morbidity, and lung transplant eligibility. Although not considered part of the BCC, other Burkholderia species are known to cause respiratory disease in pwCF, namely Burkholderia gladioli and Burkholderia pseudomallei. The introduction of CFTR modulator therapy has improved pulmonary outcomes in pwCF, yet little is known about their impact on Burkholderia species acquisition, clearance, or long-term microbiological or clinical outcomes. METHOD:We reviewed the outcomes of pwCF infected with Burkholderia species (including BCC, B. gladioli, or B. pseudomallei) receiving care in a large CF centre over the past 15 years, spanning the introduction of CFTR modulator therapy. RESULTS:Forty-four pwCF cultured one of these organisms between 2010 and 2025. Ten had only a single isolation with 28 (63.6%) deemed to have chronic infection and 6 (13.6%) exhibiting transient infection defined by having only two positive cultures. Notably, no new Burkholderia species acquisitions occurred after commencement of elexacaftor/tezacaftor/ivacaftor (ETI). The longitudinal incidence rates of chronic infection with Burkholderia species showed a reducing trend from 2017-2025 with rates of spontaneous clearance following ETI appearing similar to background clearance rates prior to modulator therapy. CONCLUSION:These findings contribute to the evolving understanding of Burkholderia species in the modulator era. While ETI does not eliminate the risk of chronic infection, it may reduce acquisition and support clearance in a subset of pwCF.

Background The prevalence of infection with non-tuberculous mycobacteria (NTM) has been increasing in people with cystic fibrosis (pwCF) over the past 30 years. Emerging reports of beneficial effects of CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI), on the rates of NTM acquisition and persistence are encouraging. In this observational study, we evaluate the impact of the introduction of ETI on the prevalence of NTM infection within a cohort of pwCF living in sub-tropical Queensland, Australia.Methods We examined the impact of ETI introduction on rates of NTM isolation in pwCF attending an adult CF centre and two large regional clinics providing CF care. Data on NTM infection were collected for a minimum of 2 years pre- and post-initiation of ETI.Results In total, 271 (84.2%) were commenced on ETI with 33 (12.2%) of these pwCF isolating an NTM species on one or more occasion. The number of pwCF isolating Mycobacterium abscessus (Mabs) remained static across the 4-year period of analysis. However, there was a trend towards declining numbers of pwCF isolating either Mycobacterium intracellulare or other NTM species across the surveillance period.Conclusions ETI therapy was not associated with reduced rates of NTM isolation from sputum over the first 2 years of treatment. However, at a species level, two distinct patterns of change were seen with a trend towards a reduction in the isolation of M. intracellulare, while the rates of Mabs isolation remained unchanged. The reasons for this remain unclear at present but highlight the need for ongoing vigilance with screening for NTM in the setting of ETI therapy.

BACKGROUND:Early diabetes detection can enhance metabolic outcomes, reducing future risks and complications. Effective diabetes screening remains crucial in the post cystic fibrosis (CF) modulator therapy era whereby treatment with Elexacaftor/Tezacaftor/Ivacaftor (ETI) will lead to an aging CF population. Therefore, adults living with CF will be at increased risk of metabolic complications, specifically diabetes. The oral glucose tolerance test (OGTT) remains a key validated diagnostic tool for diabetes in this population; however, uptake has been historically low. AIM:This study aimed to evaluate and address barriers to the uptake of OGTT screening for CF-related diabetes from a clinician and service perspective. METHOD:This single center mixed methods study comprised a survey, solution mapping workshops, and database-driven analytics, incorporating both qualitative and quantitative analyses. The study was conducted in a hospital in Brisbane, Australia from 2017 to 2023. We hybridized the Theoretical Domains Framework and the Capability, Opportunity, Motivation, and Behaviour (COM-B) change model to identify clinician- and service-level barriers to OGTT uptake. OGTT uptake was assessed at three time-points: T0 (2018-2019) Baseline/Pre-implementation, T1 (2020-2021) Post-implementation, and T2 (2022-2023) Post-implementation and ETI. RESULTS:Three barriers to OGTT uptake were identified: (1) clinician capacity, (2) systematic processes, and (3) consumer engagement. Provider knowledge gaps on diabetes diagnostic criteria were addressed through education. A CF-related diabetes clinical pathway was developed and integrated into service procedures and clinical databases. Consumer engagement initiatives were implemented. In our cohort, OGTT screening significantly increased from 12.7% at T0 to 38.5% at T1 (p < 0.001), stabilizing at 33.5% at T2 (p < 0.001). CONCLUSIONS:OGTT screening significantly improved following the implementation of behavior-based solutions. Our findings indicate that addressing key barriers at a service level using a multifaceted interventional approach can change end-user perspectives and behavior. SPANISH ABSTRACT:http://links.lww.com/IJEBH/A405.

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. We found that clonal strains of Pseudomonas persist after elexacaftor-tezacaftor-ivacaftor treatment with the same "chronic" phenotypes that are just as clinically challenging in people with cystic fibrosis. We further identified commonly mutated bacterial genes that may drive future adaptation to the CFTR (cystic fibrosis transmembrane conductance regulator) modulated lung.

IntroductionThe Burkholderia cepacia complex encompasses a group of gram-negative opportunistic pathogens that cause chronic lung infections in people with cystic fibrosis. Distinct from other respiratory pathogens, Burkholderia causes a unique clinical disease in a subset of patients known as ‘cepacia syndrome’, fulminant pneumonia accompanied by bacteraemia and sepsis with a mortality rate of up to 75%. Due to the bacteraemia associated with this disease, the mechanisms that allow Burkholderia to resist the bactericidal effects of serum complement-depending killing are vital. Antibodies usually promote serum killing; however, we have described ‘cloaking antibodies’, specific for lipopolysaccharides that paradoxically protect serum-sensitive bacteria from complement-mediated lysis. Cloaking antibodies that protect Pseudomonas aeruginosa have been found in 24%–41% of patients with chronic lung diseases. The presence of these antibodies is also associated with worse clinical outcomes. Here, we sought to determine the relevance of cloaking antibodies in patients with Burkholderia infection.MethodsTwelve Burkholderia spp. were isolated from nine pwCF and characterised for susceptibility to healthy control serum. Patient serum was analysed for the titre of the cloaking antibody. The ability of the patient serum to prevent healthy control serum (HCS) killing of its cognate isolates was determined.ResultsWe found that several of the Burkholderia strains were shared between patients. Ten of the 12 isolates were highly susceptible to HCS killing. Four of nine (44%) patients had cloaking antibodies that protected their cognate strain from serum killing. Depleting cloaking antibodies from patient serum restored HCS killing of Burkholderia isolates.DiscussionCloaking antibodies are prevalent in patients with Burkholderia pulmonary infection and protect these strains from serum killing. Removal of cloaking antibodies via plasmapheresis, as previously described for individuals with life-threatening Pseudomonas infection, may be a useful new strategy for those with serious and life-threatening Burkholderia infection.