BackgroundPeople with Cystic Fibrosis (CF) in the UK and elsewhere are increasingly surviving into adulthood, yet there is little research on the employment consequences of having CF. We investigated, for the first time in a UK-wide cohort, longitudinal employment status, and its association with deprivation, disease severity, and time in hospital.MethodsWe did a longitudinal registry study of adults with CF in the UK aged 20 to 40 (3458 people with 15,572 observations between 1996 and 2010), using mixed effects models.ResultsAround 50% of adults with CF were in employment. Male sex, higher lung function and body mass index, and less time in hospital were associated with improved employment chances. All other things being equal, being in the most deprived quintile was associated with a reduction of employment prevalence of 17.6 percentage points compared to the prevalence in the least deprived quintile. Having poor lung function was associated with a reduced employment prevalence of 7.2 percentage points compared to the prevalence for people with relatively good lung function. Acting synergistically, deprivation modifies the effect of lung function on employment chances – poor lung function in the least deprived group was associated with a 3 percentage point reduction in employment chances, while poor lung function in the most deprived quintile was associated with a 7.7 point reduction in employment chances.ConclusionsGreater deprivation, disease severity, and time in hospital are all associated with employment chances in adults with CF. Furthermore, our analysis suggests that deprivation amplifies the harmful association of disease severity on employment. Future studies should focus on understanding and mitigating the barriers to employment faced by people with CF.

The UK Cystic Fibrosis Registry is a national, secure, centralized database sponsored and managed by the Cystic Fibrosis Trust, with UK National Health Service (NHS) research ethics approval and consent from each person for whom data are collected. First established in 1995, it records longitudinal health data on all people with cystic fibrosis (CF) in England, Wales, Scotland and Northern Ireland, and to date has captured data on over 12,000 individuals.

If you are interested in using the CYFI dataset in the SAIL Databank, please contact SAIL via the website, along with also discussing your project with the Cystic Fibrosis Registry team for further advice via email at: registry@cysticfibrosis.org.uk

Diagnostics are key to the appropriate detection, treatment and management of many conditions and associated health implications. People with cystic fibrosis are susceptible to recurrent pulmonary infections that over time contribute to deterioration and degeneration of the lung. Launched in 2019, the Cystic Fibrosis (CF) Antimicrobial Resistance (AMR) Syndicate was formed to accelerate the translation and adoption of new CF antimicrobials and diagnostics to the clinic through collaboration (https://cfamr.org.uk/), bringing better treatment options to people with CF, faster. To catalyse the development of new diagnostics, the CF AMR Syndicate, together with the Newcastle NIHR HealthTech Research Centre (formerly Newcastle NIHR MIC), has worked with the wider community to understand the unmet diagnostic needs and develop a suite of Target Product Profiles (TPPs) for CF lung infection diagnostics. The intention of this is to drive diagnostic discovery, focusing efforts where they are needed the most. Although developed in the UK with input from UK based experts and people with CF, we intend for the impact of these TPPs to be global. This project involved three main phases, sandwiched between planning and management activities, and a dissemination strategy programme, all guided by an expert advisory group. Phase 1 involved a landscape analysis to identify and prioritise unmet diagnostic needs via multiple focus groups of clinical experts and people with Cystic Fibrosis (pwCF), as well as a scoping review of the diagnostic space and available diagnostic tests (https://doi.org/10.1016/j.resinv.2024.07.005). Phase 2 involved drafting the TPPs using existing literature and regulatory documentation, focus groups, one-to-one interviews with key opinion leaders (KoLs), and a web-based survey, to define ‘minimal’ and ‘optimal’ characteristics for each TPP. Phase 3 refined and validated the TPP content through additional interviews, a two-round modified Delphi exercise, and a virtual symposium. These data are from phase 2 of this study and are the outputs of expert and patient focus groups discussing the CF care pathway, positive and negative aspects of clinical care, unmet needs in CF, and the perspectives of pwCF and clinical teams on optimal and desired characteristics for diagnostic tests in CF. This patient-centric methodology builds upon the experience and network of MDC and CF Trust in the development of TPPs to guide CF antimicrobial therapeutic development. These early stakeholder focus groups went on to inform all subsequent diagnostic TPP development work, and laid the foundation for subsequent stakeholder elicitation regarding content and focus. Focus group topic guides are available at: https://doi.org/10.25405/data.ncl.26477263. The final TPP documents (and a report from the virtual symposium) are available at: https://cfamr.org.uk/therapeutic-tpp/.

The UK CF Registry is a centralised database of all 60 CF centres across the UK. Data are manually enterd in calendar years by CF clinical teams for the 99% of people with a diagnosis of CF who consent to their data being donated to the Registry. Data are entered onto a secure web-portal. For more information please see www.cysticfibrosis.org.uk/registry and 'Data Resource Profile: The UK CF Registry' published in the International Journal of Epidemiology (2018 Feb 1;47(1)9-10e).

The UK CF Registry is a centralised database of all 60 CF centres across the UK. Data are manually entered in calendar years by CF clinical teams for the 99% of people with a diagnosis of CF who consent to their data being donated to the Registry. Data are entered onto a secure web-portal. For more information please see www.cysticfibrosis.org.uk/registry and 'Data Resource Profile: The UK CF Registry' published in the International Journal of Epidemiology (2018 Feb 1;47(1)9-10e).

The airways of people with cystic fibrosis (CF) often harbor a diverse microbiota and in recent years, much effort has been invested in cataloguing these. In spite of providing a wealth of insight, this cataloguing tells us little about how the organisms interact with one another in the CF airways. However, such relationships can be inferred using the theoretical framework of the Lotka-Volterra (LV) model. In the current work, we use a generalized Lotka-Volterra model to interrogate the nationwide data collected and curated by the UK CF Registry. This longitudinal dataset (covering the period 2008–2020) contains annual depositions that record the presence/absence of microbial taxa in each patient, their medication, and their CF genotype. Specifically, we wanted to identify trends in ecological relationships between the CF microbiota at a nationwide level, and whether these are potentially affected by medication. Our results show that some medications have a distinct influence on the microbial interactome, especially those that potentially influence the “gut-lung axis” or mucus viscosity. In particular, we found that patients treated with a combination of antimicrobial agents (targeting the airway microbiota), digestive enzymes (assisting in the assimilation of dietary fats and carbohydrates), and DNase (to reduce mucus viscosity) displayed a distinctly different airway interactome compared with patients treated separately with these medications.

Diagnostics are key to the appropriate detection, treatment and management of many conditions and associated health implications. People with cystic fibrosis are susceptible to recurrent pulmonary infections that over time contribute to deterioration and degeneration of the lung. Launched in 2019, the Cystic Fibrosis (CF) Antimicrobial Resistance (AMR) Syndicate was formed to accelerate the translation and adoption of new CF antimicrobials and diagnostics to the clinic through collaboration (https://cfamr.org.uk/), bringing better treatment options to people with CF, faster.To catalyse the development of new diagnostics, the CF AMR Syndicate, together with the Newcastle NIHR HealthTech Research Centre (formerly Newcastle NIHR MIC), has worked with the wider community to understand the unmet diagnostic needs and develop a suite of Target Product Profiles (TPPs) for CF lung infection diagnostics. The intention of this is to drive diagnostic discovery, focusing efforts where they are needed the most. Although developed in the UK with input from UK based experts and people with CF, we intend for the impact of these TPPs to be global.This project involved three main phases, sandwiched between planning and management activities, and a dissemination strategy programme, all guided by an expert advisory group.Phase 1 involved a landscape analysis to identify and prioritise unmet diagnostic needs via multiple focus groups of clinical experts and people with Cystic Fibrosis (pwCF), as well as a scoping review of the diagnostic space and available diagnostic tests (https://doi.org/10.1016/j.resinv.2024.07.005).Phase 2 involved drafting the TPPs using existing literature and regulatory documentation, focus groups, one-to-one interviews with key opinion leaders (KoLs), and a web-based survey, to define ‘minimal’ and ‘optimal’ characteristics for each TPP.Phase 3 refined and validated the TPP content through additional interviews, a two-round modified Delphi exercise, and a virtual symposium.These data are from phase 2 of this study (the web based survey) and phase 3 (two-round Delphi exercise).The files are the survey data for each phase (anonymised)Plus the table of characteristics for one of the developed TPPs, explaining the content the table covered and the purpose and need for that characteristic to be defined and included in the TPP. As each TPP table differed slightly based on context and need, this table is based on TPP4, the most comprehensive TPP developed in this project (target product profile 4: non-tuberculous mycobacteria).These surveys went on to inform the wording and priority areas of the first and refined drafts of the TPP document.Focus group topic guides are available at: https://doi.org/10.25405/data.ncl.26477263.The final TPP documents (and a report from the virtual symposium) are available at: https://cfamr.org.uk/therapeutic-tpp/.

The SPADIS project aims at measuring the social participation of people living in Belgium with one of the following chronic diseases: cancer, diabetes, cystic fibrosis, neuromuscular disease, and HIV/AIDS. The researchers aimed to understand the personal and external barriers and facilitators of their social participation and to inform the relevant decision-makers. The project enriches existing databases with additional information at the individual level, concerning the socioeconomic status and position as well as self-reported outcomes and experience.

Background: The novel and highly effective CFTR modulator combination of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to improve lung function and body weight in people with Cystic Fibrosis (pwCF) carrying a F508del mutation. However, the impact of these modulators on gastrointestinal (GI) symptoms is relatively unknown. Therefore, the CFAbd-Score was developed and validated following FDA recommendations for development of a PROM including focus groups, multidisciplinary CF specialists, people with CF and their families. The aim of this study was to assess effects of ETI on GI symptoms using the CFAbd-Score.Methods: Gastrointestinal symptoms were prospectively assessed in pwCF using the CFAbd-Score before and up to 26 weeks during therapy. The CFAbd-Score was also administered to a healthy control (HC) group. The one-sided questionnaire includes 28 items grouped in five domains. Data analysis included calculation of scores with a weighting tool, developed according to FDA recommendations.Results: A total of 107 pwCF attended in four CF centres in Germany and four centres in the UK completed the CFAbd-Score on at least two occasions. Results were compared to those obtained from the questionnaire of 45 HCs. Despite differences in demographics, age and proportion of pancreatic insufficiency between German and UK patients, analyses based on linear mixed-effects models at week 24 of ETI therapy revealed that estimated marginal means (EMMs) of total CFAbd-Scores significantly reduced (mean ± SE: 14.9 ± 1.2→10.6 ± 1.4; p < 0.01). Also EMMs of all five domains significantly declined (“pain” 16.3 ± 1.6→10.2 ± 2.3, “GERD” 15.8 ± 1.8→8.2 ± 1.9, “disorders of bowel movement” 20.9 ± 1.5→16.0 ± 1.7, “disorders of appetite” 7.9 ± 1.1→2.6 ± 1.1 and “quality of life impairment” 10.1 ± 1.92→3.9 ± 1.9). However, during 24 weeks, CF participants’ symptoms mostly still did not reach the reference levels of HCs.Discussion: Using the CFAbd-Score, the first PROM specifically developed for assessment of CF-related abdominal symptoms, we demonstrate comprehensive improvements in GI symptoms after initiation of the highly effective modulator therapy ETI.

BackgroundLeptin (LEP) acts as a proinflammatory cytokine and may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to assess the quantitative difference in leptin status between CF patients and non-CF controls.MethodsIn this study, the researchers conducted systematic searches of various databases, such as PubMed, Excerpta Medica Database, Google Scholar, Web of Science, and the China National Knowledge Infrastructure. The data collected from the above databases were assessed using the Stata 11.0 and R 4.1.3 software. The correlation coefficients and the Standardized Mean Differences (SMD) were employed to assess the effect size. A combination analysis was also carried out with the help of either a fixed-effects or random-effects model. In addition, the single-cell sequencing GSE193782 dataset was obtained to determine the mRNA expression levels of LEP and leptin receptor (LEPR) in the bronchoalveolar lavage fluid, to verify the different leptin expression between the CF patients and healthy controls.ResultsA total of 919 CF patients and 397 controls from 14 articles were included in this study. CF patients and non-CF controls showed similar serum/plasma leptin levels. Gender, specimen testing, age, and study design were all taken into account for carrying out subgroup analyses. The results revealed no variations in serum/plasma leptin levels between the controls and CF patients in the various subgroups. Female CF patients exhibited higher leptin concentrations compared to male CF patients, and male healthy individuals showed lower leptin levels than female healthy participants. Aside from the fact that serum/plasma leptin appeared to be favorably linked to fat mass and BMI, the findings in this study also indicated that serum/plasma concentrations were not associated with Forced Expiratory Volume in the first second (FEV1). No statistically significant differences were observed in the leptin and leptin receptor mRNA expression levels between the healthy controls and CF patients. The leptin receptor and leptin expression levels in alveolar lavage fluid were low in various cells, without any distinctive distribution patterns.ConclusionsThe current meta-analysis indicated the absence of significant differences in leptin levels between CF patients and healthy individuals. Gender, fat mass, and BMI may all be correlated with leptin concentrations.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022380118.

Supplementary files for article "Understanding the lived experience of idiopathic pulmonary fibrosis and how this shapes views on home-based pulmonary rehabilitation in Delhi, India"Objectives: Pulmonary Rehabilitation (PR) is a high-impact intervention for individuals with idiopathic pulmonary fibrosis (IPF) but access is limited in India. PR barriers include distance to travel, lack of service provision and lack of healthcare professionals to deliver PR, thus it is disproportionate to the immense burden of IPF in India. We explored the lived experiences of people living with IPF, family caregivers (CGs) and healthcare workers (HCWs) as well as their views towards home-based PR (HBPR) in Delhi, India.Methods: A qualitative study using semi-structured interviews with individuals with IPF (n = 20), CGs (n = 10) and HCWs (n = 10) was conducted. Data were analysed using codebook thematic analysis.Results: Three major themes were generated: (i) Health impact, which included pathophysiological changes, range of symptoms experienced, disease consequences and impact of comorbidities; (ii) Disease management, which described strategies to control the progression and overall management of IPF, such as medications and exercises; (iii) Mode of Pulmonary Rehabilitation, which described perceptions regarding HBPR, comparisons with centre-based programmes, and how HBPR may fit as part of a menu of PR delivery options.Conclusion: People living with IPF, family caregivers and healthcare workers were positive about the potential implementation of HBPR and suggested the development of a paper-based manual to facilitate HBPR over digital/online approaches. The content of HBPR should be sensitive to the additional impact of non-IPF health issues and challenges of reduced interactions with healthcare professionals.©The Author(s) CC BY 4.0