E-learning within the European cystic fibrosis society - A multidisciplinary cross-sectional survey.

BACKGROUND: Continuing professional development (CPD) is a component of practice that spans all disciplines within cystic fibrosis (CF). E-learning resources theoretically represent flexible, low cost and time efficient methods of CPD. We aimed to explore European Cystic Fibrosis Society (ECFS) members' and CF health professional communities' current views, experiences and perceptions of e-learning and the ECFS education platform (ECFS-EP). METHODS: An online cross-sectional survey was developed by the ECFS Education Committee and circulated via the ECFS conference, emails and within the society subgroups between June and September 2023. RESULTS: 547 responses were received from 58 countries; 57 % of responders were ECFS members. A wide range of specialities were represented from the multidisciplinary team including 36 % clinicians. The majority of respondents (63 %) spent 6 or more hours a week on their professional education. Online platforms were used either weekly (34 %) or monthly (37 %); 54 % of respondents had used the ECFS-EP and this was rated favourably overall, specifically for content quality. Preferred formats for education were articles and medium length (15-30 min) webinars. CONCLUSIONS: This multidisciplinary cohort survey illustrates contemporary practice and opinion relating to e-learning and the ECFS-EP. Strengths include the high number of responses and the wide range of countries and specialities represented. Results suggest the ECFS-EP is valued and highlights priority topics, preferred formats and opportunities to optimise awareness. Results support continued provision and oversight of high quality education via an online platform. Continued success will rely on learning from user experience and feedback to inform future practice.

The gut microbiota in adults with cystic fibrosis compared to colorectal cancer.

BACKGROUND: Gut dysbiosis is implicated in colorectal cancer (CRC) pathogenesis. Cystic fibrosis (CF) is associated with both gut dysbiosis and increased CRC risk. We therefore compared the faecal microbiota from individuals with CF to CRC and screening samples. We also assessed changes in CRC-associated taxa before and after triple CF transmembrane conductance regulator (CFTR) modulator therapy. METHODS: Bacterial DNA amplification comprising V4 16S rRNA analysis was conducted on 84 baseline and 53 matched follow-up stool samples from adults with CF. These data were compared to an existing cohort of 430 CRC and 491 control gFOBT samples from the NHS Bowel Cancer Screening Programme. Data were also compared to 26 previously identified CRC-associated taxa from a published meta-analysis. RESULTS: Faecal CF samples had a lower alpha diversity and clustered distinctly from both CRC and control samples, with no clear clinical variables explaining the variation. Compared to controls, CF samples had an increased relative abundance in 6 of the 20 enriched CRC-associated taxa and depletion of 2 of the 6 taxa which have been reported as reduced in CRC. Commencing triple modulator therapy had subtle influence on the relative abundance of CRC-associated microbiota (n = 23 paired CF samples). CONCLUSIONS: CF stool samples were clearly dysbiotic, clustering distinctly from both CRC and control samples. Several bacterial shifts in CF samples resembled those observed in CRC. Studies assessing the impact of dietary or other interventions and the longer-term use of CFTR modulators on reducing this potentially pro-oncogenic milieu are needed.

Body mass index and nutritional intake following Elexacaftor/Tezacaftor/Ivacaftor modulator therapy in adults with cystic fibrosis.

BACKGROUND: Elexacaftor/Tezacaftor/Ivacaftor (ETI) modulator therapy is often associated with increased body mass index (BMI) in people with cystic fibrosis (CF). This is thought to reflect improved clinical stability and increased appetite and nutritional intake. We explored the change in BMI and nutritional intake following ETI modulator therapy in adults with CF. METHODS: Dietary intake, measured with myfood24®, and BMI were collected from adults with CF at baseline and follow-up as part of an observational study. Changes in BMI and nutritional intake in participants who commenced ETI therapy between time points were assessed. To contextualize findings, we also assessed changes in BMI and nutritional intake between study points in a group on no modulators. RESULTS: In the pre and post ETI threapy group (n = 40), BMI significantly increased from 23.0 kg/m2 (IQR 21.4, 25.3) at baseline to 24.6 kg/m2 (IQR 23.0, 26.7) at follow-up (p<0.001), with a median of 68 weeks between time points (range 20-94 weeks) and median duration of ETI therapy was 23 weeks (range 7-72 weeks). There was a significant decrease in energy intake from 2551 kcal/day (IQR 2107, 3115) to 2153 kcal/day (IQR 1648, 2606), p<0.001. In the no modulator group (n = 10), BMI and energy intake did not significantly change between time points (p>0.05), a median of 28 weeks apart (range 20-76 weeks). CONCLUSIONS: These findings tentatively suggest that the increase in BMI with ETI therapy may not simply be attributable to an increase in oral intake. Further exploration into the underlying aetiology of weight gain with ETI therapy is needed.

Cystic Fibrosis-Related Gut Dysbiosis: A Systematic Review.

BACKGROUND AND AIMS: Cystic Fibrosis (CF) is associated with gut dysbiosis, local and systemic inflammation, and impaired immune function. Gut microbiota dysbiosis results from changes in the complex gut milieu in response to CF transmembrane conductance regulator (CFTR) dysfunction, pancreatic malabsorption, diet, medications, and environmental influences. In several diseases, alteration of the gut microbiota influences local and systemic inflammation and disease outcomes. We conducted a systematic review of the gut microbiota in CF and explored factors influencing dysbiosis. METHODS: An electronic search of three databases was conducted in January 2019, and re-run in June 2021. Human, animal, and in vitro studies were included. The primary outcome was differences in the gut microbiota between people with CF (pwCF) and healthy controls. Secondary outcomes included the relationship between the gut microbiota and other factors, including diet, medication, inflammation, and pulmonary function in pwCF. RESULTS: Thirty-eight studies were identified. The literature confirmed the presence of CF-related gut dysbiosis, characterized by reduced diversity and several taxonomic changes. There was a relative increase of bacteria associated with a pro-inflammatory response coupled with a reduction of those considered anti-inflammatory. However, studies linking gut dysbiosis to systemic and lung inflammation were limited. Causes of gut dysbiosis were multifactorial, and findings were variable. Data on the impact of CFTR modulators on the gut microbiota were limited. CONCLUSIONS: CF-related gut dysbiosis is evident in pwCF. Whether this influences local and systemic disease and is amenable to interventions with diet and drugs, such as CFTR modulators, requires further investigation.

Diabetes is associated with increased burden of gastrointestinal symptoms in adults with cystic fibrosis.

BACKGROUND: Individuals with diabetes mellitus (DM) are known to frequently experience gastrointestinal (GI) symptoms. In contrast, the impact of cystic fibrosis-related diabetes (CFRD) on accentuating GI symptoms in people with cystic fibrosis (pwCF) is unknown. We sought to examine this. METHODS: Abdominal symptoms were measured using the validated CF-specific GI symptom questionnaire - CFAbd-Score© - as part of a multicentre cohort study in pancreatic insufficient adults with CF, not on cystic fibrosis transmembrane conductance regulator (CFTR) modulators. The CFAbd-Score total score (0-100pts), its 5 domains, alongside nine specific GI symptoms associated with DM, were compared between the CFRD and non-CFRD groups. RESULTS: 27 (31%) and 61 (69%) participants with CF were recruited in the CFRD and non-CFRD groups respectively. Total CFAbd-Score and the two domains: gastroesophageal reflux disease and disorders of appetite were significantly higher in the CFRD group compared to the non-CFRD group (p<0.05), with the mean total CFAbd-Score being 25.4 ± 2.5 and 18.4 ± 1.5 in the CFRD and non-CFRD groups respectively. Among the nine GI symptoms commonly reported as elevated in DM, bloating and nausea were significantly more common in individuals with CFRD compared to those without (p<0.05). CONCLUSIONS: Individuals with CFRD overall, have a higher GI symptom burden, according to CFAbd-Scores. Specifically, they experience significantly more bloating and nausea. Close monitoring and further research is needed to better understand and manage GI symptoms in this group.

Dose adjustments of Elexacaftor/Tezacaftor/Ivacaftor in response to mental health side effects in adults with cystic fibrosis.

INTRODUCTION: Deterioration in mental health has been reported in a minority of individuals with cystic fibrosis starting elexacafor/tezacaftor/ivacaftor (ELX/TEZ/IVA). We report our experience of using sweat chloride and markers of clinical stability to titrate dose reduction with the aim of minimising adverse events and maintaining clinical stability. METHOD: Adults (n = 266) prescribed ELX/TEZ/IVA, were included. Adverse events, sweat chloride, lung function and clinical data were collected. RESULTS: Nineteen (7.1%) individuals reported anxiety, low mood, insomnia and "brain fog" with reduced attention and concentration span. Thirteen underwent dose reduction with sweat chloride remained normal (<30 mmol l-1) or borderline (30-60 mmol l-1) in six (46.2%) and seven (53.2%) cases respectively. Improvement or resolution of AEs occurring in 10 of the 13 cases. CONCLUSION: Dose adjustment of ELX/TEZ/IVA was associated with improvement in mental health AEs without significant clinical deterioration. Sweat chloride concentration may prove useful as a surrogate marker of CFTR function.

Average rate of lung function decline in adults with cystic fibrosis in the United Kingdom: Data from the UK CF registry.

BACKGROUND: Rate of change in lung function is used as a measure of disease progression and a predictor of mortality in individuals with cystic fibrosis (CF). The aim of this study was to determine the national rate of decline in percent predicted Forced Expiratory Volume in 1 second (ppFEV1) in adults in the UK accounting for age, sex and pancreatic status. METHODS: Data on ppFEV1 for adults with CF, excluding those post lung transplantation, was extracted from the UK CF registry between 2015 and 2017. Multilevel modelling was conducted to calculate the annual rate of change in ppFEV1 accounting for age, sex and pancreatic status. RESULTS: Overall annual ppFEV1 decline was -1.52% (95% CI: -1.66 to -1.38%) and -0.55% (95% CI: -0.86 to -0.23%) in pancreatic insufficient (PI) and sufficient (PS) adults respectively. In PI individuals, females had a greater rate of decline in ppFEV1. There were differences between age groups. The fastest rate of decline was observed in the 18-28 years group, declining -1.76% (95% CI: -2.06 to -1.46) and -1.61% (95% CI: -1.91 to -1.31) per year in PI females and males respectively. The pattern between the sexes and age categories was more inconsistent in the PS group. CONCLUSIONS: The average annual rates of decline in lung function in adults with CF in the UK are similar to reports from other large international cohorts. Pancreatic status has a marked impact on average rate of decline. Younger adults, especially females, have a faster rate of decline and need close monitoring.

Use of ceftazidime/avibactam for the treatment of MDR Pseudomonas aeruginosa and Burkholderia cepacia complex infections in cystic fibrosis: a case series.

BACKGROUND: The efficacy of antibiotic treatment in pulmonary and systemic infections in cystic fibrosis (CF) is limited by the increased prevalence of MDR strains of Pseudomonas aeruginosa and Burkholderia cepacia complex. Ceftazidime/avibactam is a new combination which, in vitro, appears to have good activity against MDR strains of P. aeruginosa and B. cepacia complex. METHODS: A retrospective analysis was performed including adult patients with CF who received at least one course of ceftazidime/avibactam owing to pulmonary exacerbations not responding to conventional antibiotic treatment. RESULTS: Treatment with ceftazidime/avibactam was associated with reduction in inflammatory markers and improvement in lung function. No episodes of acute kidney injury or elevation in transaminase were observed. CONCLUSIONS: Ceftazidime/avibactam appeared to be well tolerated and improved patients' outcomes. Further studies are needed to better assess the role of this new combination in CF.

Requirements and access needs of patients with chronic disease to their hospital electronic health record: results of a cross-sectional questionnaire survey.

OBJECTIVES: To identify patient's views on the functionality required for personalised access to the secondary care electronic health record (EHR) and their priorities for development. DESIGN: Quantitative analysis of a cross-sectional self-complete survey of patient views on required EHR functionality from a secondary care EHR, including a patient ranking of functionality. SETTING: Secondary care patients attending a regional cystic fibrosis unit in the north of England. PARTICIPANTS: 201 adults (106 (52.7%) males), median age 29 years (range 17-58 years), entered and completed the study. Inclusion criteria are as follows: a confirmed diagnosis of cystic fibrosis, aged 16 years and over, at the time of clinical stability. OUTCOME MEASURES: Quantitative responses within 4 themes; (1) value placed on aspects of the EHR; (2) access requirements to functions of the EHR; (3) views on information sent to the EHR and (4) patient feedback entered into the EHR. A ranked score for 15 functions of the EHR was obtained. RESULTS: Highest ratings (% reporting item as very important/important) were reported for access to clinical measures (lung function (94%), C reactive protein (84%), sputum microbiology (81%) and blood results (80%)), medication changes (82%) and lists (83%) and sending repeat prescription (83%) and treatment requests (80%), while sending symptom diaries was less so (62%). Email contact with clinicians was the most valuable communication element of the EHR (84% very important/important). Of 15 features of the EHR (1=most desirable to 15=least desirable), patients identified 'clinical measures' (2.62 (CI 2.07 to 3.06)), and 'access to medication lists' (4.91 (CI 4.47 to 5.44)), as highest priority for development and the ability to comment on errors/omissions (11.0 (CI 10.6 to 11.5)) or experience of care (11.8 (CI 11.4 to 12.2)) as lowest. CONCLUSIONS: Patients want extensive personal access to their hospital EHR, placing high importance on the viewing of practical clinical measures and medication management. These influence routine day-to-day care and are priorities for development.

The role of respiratory viruses in adult patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary exacerbation.

BACKGROUND: Respiratory viruses have become increasingly recognised as important agents in pulmonary exacerbations in infants and children with CF. The aim of this study was to determine the prevalence of respiratory viruses during acute pulmonary exacerbations in adults and compare the severity of these exacerbations with non-viral associated exacerbations. METHODS: This was a retrospective case control study. Viral throat swabs were taken from all patients presenting with an acute pulmonary exacerbation requiring intravenous antibiotic treatment over a 12 month period. RESULTS: There were 432 pulmonary exacerbations in 180 adults. A positive viral PCR in 42 exacerbations indicated a prevalence of 9.7%. The commonest virus isolated was rhinovirus (n = 29, 69%) with influenza A/H1N1 in seven patients (16.7%). Exacerbations associated with a positive viral PCR had a greater fall in lung function at presentation with higher levels of inflammatory markers. They received more days of intravenous antibiotics, showed less response to treatment and had a shorter time to next pulmonary exacerbation compared to matched controls. CONCLUSION: Viral associated pulmonary exacerbations in adults with CF are associated with more severe pulmonary involvement and respond less well to standard treatment.

Enteral tube feeding in adults with cystic fibrosis; patient choice and impact on long term outcomes.

BACKGROUND: Enteral tube feeding (ETF) has been evaluated in paediatric and mixed child and adult populations with cystic fibrosis, demonstrating positive outcomes from 6 months to 2 years post insertion. No studies have examined the longer term nutritional and clinical outcomes in an exclusively adult population with cystic fibrosis or compared the outcomes for those who meet standard criteria and opt to undertake or decline ETF. METHODS: Twenty three out of 380 patients attending the Leeds Regional Adult CF unit fulfilled the standard criteria for commencing ETF (CF Trust, 2002) between 2004 and 2008. Weight, BMI, FEV1, FVC, CFRD, and number of intravenous antibiotic treatment days were collected at 1 year pre baseline, at baseline, and at 1, 2, and 3 years post baseline for all these patients whether they accepted or declined ETF. RESULTS: Seventeen of the 23 patients agreed to accept a programme of ETF, two of whom died within the first year of ETF. In the remaining patients (n=15), weight increased by 19.5% from baseline (p<0.001), BMI increased to within the normal range and lung function stabilised. There was no reduction in the requirement for intravenous antibiotic treatment. The six patients who declined ETF had a decline in lung function and no weight gain. CONCLUSION: Supplemental enteral tube feeding improves clinical outcomes when administered over 3 years, resulting in significant weight gain, a normal BMI and stabilisation of lung function. It does not reduce intravenous antibiotic treatment days. In contrast those patients eligible for, but who declined ETF, showed a deterioration in lung function and a failure to gain weight and to achieve normal BMI status.

The Effect of Sub-MIC ß-Lactam Antibiotic Exposure of Pseudomonas aeruginosa Strains from People with Cystic Fibrosis in a Desiccation Survival Model.

Prior to modern typing methods, cross-infection of P. aeruginosa between people with cystic fibrosis (CF) was felt to be rare. Recently a number of studies have demonstrated the presence of clonal strains of P. aeruginosa infecting people with CF. The aim of this study was to determine whether strains of P. aeruginosa demonstrated differences in resistance to desiccation and whether preincubation in subminimum inhibitory concentrations (MICs) of ß-lactam affected desiccation resistance. The experimental data were modelled to a first-order decay model and a Weibull decay model using least squares nonlinear regression. The Weibull model was the preferred model for the desiccation survival. The presence of a mucoid phenotype promoted desiccation survival. Preincubation with antibiotics did not have a consistent effect on the strains of P. aeruginosa. Meropenem reduced desiccation resistance, whereas ceftazidime had much less effect on the strains studied.

Cystic fibrosis co-existing with trisomy 21.

Previous reports of children with co-existence of cystic fibrosis and full trisomy 21 suggest a very poor prognosis, with the majority of cases dying in infancy and the oldest reported survivor being 6 years of age. We report the case of a young man with genetically confirmed trisomy 21 and homozygous for the F508del cystic fibrosis mutation. Despite the diagnosis of cystic fibrosis being delayed until the age of 2 years he has transitioned to adult services and is now 25 years of age. Currently he has poor lung function and a continuous ambulatory oxygen requirement.

An aerobiological model of aerosol survival of different strains of Pseudomonas aeruginosa isolated from people with cystic fibrosis.

Pseudomonas aeruginosa is a common and important pathogen in people with cystic fibrosis (CF). Recently epidemic strains of P. aeruginosa associated with increased morbidity, have been identified. The method of transmission is not clear, but there is evidence of a potential airborne route. The aim of this study was to determine whether different strains of P. aeruginosa isolated from people with CF were able to survive within artificially generated aerosols in an aerobiological chamber. Viable P. aeruginosa could still be detected up to 45min after halting generation of the aerosols. All of the strains of P. aeruginosa expressing a non-mucoid phenotype isolated from people with CF had a reduced ability to survive within aerosols compared to an environmental strain. Expression of a mucoid phenotype by the strains of P. aeruginosa isolated from people with CF promoted survival in the aerosol model compared to strains expressing a non-mucoid phenotype.

Acute Burkholderia cenocepacia pyomyositis in a patient with cystic fibrosis.

INTRODUCTION: Extra-pulmonary complications of Burkholderia cepacia complex (Bcc) infection in patients with cystic fibrosis are unusual. To the best of the authors' knowledge no case of pyomyositis secondary to Bcc infection has been reported previously. CASE PRESENTATION: We report a case of pyomyositis of the forearm caused by Bcc infection in a patient with CF. We also briefly discuss the management of pyomyositis. CONCLUSION: Pyomyositis is a potential extra-pulmonary complication of Bcc infection in patients with CF. A high index of clinical suspicion is required to make a prompt diagnosis. Final diagnosis may need MRI. An early diagnosis, aggressive medical therapy, multidisciplinary care and timely surgical intervention are all essential for proper management of this condition.

Nutritional decline in cystic fibrosis related diabetes: the effect of intensive nutritional intervention.

BACKGROUND: Reports indicate that nutritional and respiratory decline occur up to four years prior to diagnosis of cystic fibrosis related diabetes (CFRD). Our aim was to establish whether intensive nutritional intervention prevents pre-diabetic nutritional decline in an adult population with CFRD. METHODS: 48 adult patients with CFRD were matched to 48 controls with CF, for age, gender and lung pathogen status. Nutritional and other clinical indices were recorded at annual intervals from six years before until two years after diagnosis. Data were also analysed to examine the impact of early and late acquisition of CFRD. RESULTS: No important differences in weight, height, body mass index (BMI), lung function or intravenous treatment were found between groups in the six years prior to diagnosis, nor any significant deviation over time. In those who developed diabetes, use of overnight enteral tube feeding (ETF) was four times as likely at the time of diagnosis, compared to controls [ETF 43.8% (CFRD) v 18.8% (CF Controls), OR 4.0, CI 1.3 to 16.4, p=0.01]. Age at onset of CFRD played a significant role in determining the pre-diabetic clinical course. Younger diabetics with continued growth at study onset (n=17) had a lower BMI from 2 years prior to diagnosis compared to controls [BMI 18.9 kg/m(2) (CFRD) v 20.8 kg/m(2) (CF Controls), diff=1.9, CI -0.1 to 3.7 p=0.04]. The BMI of older diabetics (completed growth at study onset) was equal to that of controls throughout. CONCLUSION: Pre-diabetic nutritional decline is not inevitable in adults with CFRD, but is influenced by age of onset. In the group overall, those with CFRD are more likely to require ETF from 2 years prior to diagnosis. Despite intensive nutritional intervention, patients who continue to grow throughout the pre-diabetic years, show a level of nutritional decline absent in older adults.

Ten years of viral and non-bacterial serology in adults with cystic fibrosis.

Viral infections are associated with pulmonary exacerbations in children with cystic fibrosis (CF), but few studies have addressed the frequency in adults. This paper investigates the frequency and impact of viral infections in adults with CF receiving intravenous antibiotics. Pre- and post-treatment spirometry, inflammatory markers and antibody titres against influenza A, influenza B, adenovirus, respiratory syncytial virus, Mycoplasma pneumoniae, Chlamydia psittaci, and Coxiella burnetti were analysed over a 10-year period. Non-bacterial infections were identified in 5.1% of 3156 courses of treatment. The annual incidence of admissions per patient associated with viral infection was 4.9%. The presence of viral infection in association with a pulmonary exacerbation did not adversely affect lung function or inflammatory markers in the short term. Adults with CF have a lower incidence of respiratory viral infections associated with pulmonary exacerbations requiring intravenous antibiotics compared to children and infants with CF.

Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review.

The primary purpose of this systematic review was to produce an evidence-based review of the literature as a means of informing current clinical practice in the recognition, diagnosis and management of patients with suspected primary antibody deficiency. Randomized controlled trials (RCTs) were identified from a search of MEDLINE, EMBASE, The Cochrane Library, DARE (CRD website) and CINAHL by combining the search strategies with The Cochrane Collaboration's validated RCT filter. In addition, other types of studies were identified in a separate search of MEDLINE and EMBASE. Patients at any age with recurrent infections, especially in the upper and lower respiratory tracts, should be investigated for possible antibody deficiency. Replacement therapy with immunoglobulin in primary antibody deficiencies increases life expectancy and reduces infection frequency and severity. Higher doses of immunoglobulin are associated with reduced infection frequency. Late diagnosis and delayed institution of immunoglobulin replacement therapy results in increased morbidity and mortality. A wide variety of organ-specific complications can occur in primary antibody deficiency syndromes, including respiratory, gastroenterological, hepatic, haematological, neurological, rheumatological and cutaneous. There is an increased risk of malignancy. Some of these complications appear to be related to diagnostic delay and inadequate therapy. High-quality controlled trial data on the therapy of these complications is generally lacking. The present study has identified a number of key areas for further research, but RCT data, while desirable, is not always obtained easily for rare conditions. Few data from registries or large case-series have been published in the past 5 years and a greater focus on international collaboration and pooling of data is needed.