Exploring demographic and genetic correlates of hearing outcomes in children with primary ciliary dyskinesia: an observational study.

Objective: This retrospective observational study aimed to examine the associations among genetic mutations, demographic characteristics and hearing outcomes in children diagnosed with primary ciliary dyskinesia (PCD). By identifying potential predictors of adverse auditory outcomes, we hope to inform future approaches to clinical care and intervention.

Design: A total of 84 children, aged 1-17 years with confirmed PCD, underwent audiological assessments, including age-appropriate audiometry and tympanometry.

CF Tummy Tracker: A Cystic Fibrosis-Specific Patient-Reported Outcome Measure for Daily Gastrointestinal Symptom Burden.

Objective: To develop a cystic fibrosis (CF)-specific patient-reported outcome measure (PROM) to measure the daily burden of gastrointestinal symptoms for people with cystic fibrosis (pwCF) aged 12 years and older and address the lack of validated outcome measures for gastrointestinal symptoms in CF.

Patients And Methods: CF Tummy Tracker was developed through a 5-stage approach in accordance with regulatory guidance. This included development and refinement of a conceptual framework; item generation; refinement; reduction; selection; and initial PROM testing.

International consensus statement on routine blood testing in primary ciliary dyskinesia.

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by dysfunction of motile cilia. Symptoms include recurrent and chronic airway infections which can lead to deteriorating lung function and inflammatory destructive lung disease in the form of persistent atelectasis and bronchiectasis. Routine blood testing may be used as a tool for disease monitoring and management.

Sleep disordered breathing in children with primary ciliary dyskinesia.

https://bit.ly/3CBXTyj.

LONGITUDE: An observational study of the long-term effectiveness of elexacaftor/tezacaftor/ivacaftor in people aged ≥12 years with cystic fibrosis using data from the United Kingdom Cystic Fibrosis Registry - 2-year analysis.

Background: The cystic fibrosis (CF) transmembrane conductance regulator modulator (CFTRm) elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has demonstrated efficacy and safety in clinical trials and emerging observational studies in people with CF. This study evaluated the real-world impact of ELX/TEZ/IVA in a large cohort of people with CF in the UK.

Methods: LONGITUDE is an observational, registry-based cohort study using data from the UK CF Registry to evaluate outcomes of ELX/TEZ/IVA in people aged ≥6 years who initiated ELX/TEZ/IVA from August 2019.

Evaluating the correspondence between the EQ-5D-5L and disease severity and quality of life in adults and adolescents with cystic fibrosis.

Background: The EQ-5D is the recommended measure to capture health-related quality of life (HRQoL), recognised for use in health technology appraisal bodies. In order to assess whether it is appropriate to use the EQ-5D for making decisions about the cost-utility of treatments in cystic fibrosis (CF), this study assesses the performance of the EQ-5D-5L in adults and adolescents with CF.

Method: This was a cross-sectional observational survey study of patients with CF attending a single large CF centre.

Impact of COVID-19 infection on lung function and nutritional status amongst individuals with cystic fibrosis: A global cohort study.

Background: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF).

Methods: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021.

Demographic factors associated with within-individual variability of lung function for adults with cystic fibrosis: A UK registry study.

Background: Lung function is a key outcome used in the evaluation of disease progression in cystic fibrosis. The variability of individual lung function measurements over time (within-individual variability) has been shown to predict subsequent lung function changes. Nevertheless, the association between within-individual lung function variability and demographic and genetic covariates has not been quantified.

Combined approaches, including long-read sequencing, address the diagnostic challenge of HYDIN in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD), a disorder of the motile cilia, is now recognised as an underdiagnosed cause of bronchiectasis. Accurate PCD diagnosis comprises clinical assessment, analysis of cilia and the identification of biallelic variants in one of 50 known PCD-related genes, including HYDIN. HYDIN-related PCD is underdiagnosed due to the presence of a pseudogene, HYDIN2, with 98% sequence homology to HYDIN.

Pancreatic enzyme prescription following ivacaftor licensing: A retrospective analysis of the US and UK cystic fibrosis registries.

Background: Relieving gastrointestinal symptoms is a research priority in cystic fibrosis. Emerging evidence highlights effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on gastrointestinal function, including pancreatic sufficiency. This study explores ivacaftor licensing and treatment on recorded pancreatic enzyme replacement therapy (PERT) prescription in the US and UK CF registries.

A grumbling concern: A survey of gastrointestinal symptoms in cystic fibrosis in the modulator era.

Background: Gastrointestinal symptoms in cystic fibrosis (CF) are common and intrusive to daily life. Relieving gastrointestinal symptoms was identified as an important research priority and previously explored in an international survey in 2018. However, following the widespread introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators in 2019, the landscape of CF treatment has changed.

Exploring the nature of perceived treatment burden: a study to compare treatment burden measures in adults with cystic fibrosis [version 1; peer review: 2 approved].

Background: Despite the importance of reducing treatment burden for people with cystic fibrosis (CF), it has not been fully understood as a concept. This study aims to quantify the treatment burden perceived by CF adults and explore the association between different validated treatment burden measures.

Methods: This is a cross-sectional observational study of CF adults attending a single large UK adult center.

Future therapies for cystic fibrosis.

We are currently witnessing transformative change for people with cystic fibrosis with the introduction of small molecule, mutation-specific drugs capable of restoring function of the defective protein, cystic fibrosis transmembrane conductance regulator (CFTR). However, despite being a single gene disorder, there are multiple cystic fibrosis-causing genetic variants; mutation-specific drugs are not suitable for all genetic variants and also do not correct all the multisystem clinical manifestations of the disease. For many, there will remain a need for improved treatments.

Trajectories of early growth and subsequent lung function in cystic fibrosis: An observational study using UK and Canadian registry data.

Background: Understanding the pulmonary impact of changes in early life nutritional status over time in a paediatric CF population may help inform how to use nutritional assessment to guide clinical care. National registry data provides an opportunity to study patterns of weight gain over time at the level of the individual, and thus to gain detailed understanding of the relationship between early weight trajectories and later lung function in children with Cystic Fibrosis (CF).

Methods: Using data from the United Kingdom (UK) and Canadian CF Registries, a mixed effects linear regression model was used to describe children's weight and BMI z-score trajectories from age 1 to 5 years.

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity.

Treatment Preference Among People With Cystic Fibrosis: The Importance of Reducing Treatment Burden.

Background: There is a growing consensus that the perspective of the patient should be considered in the evaluation of novel interventions.

Research Question: What treatment outcomes matter to people with cystic fibrosis (CF), and what trade-offs would they make to realize these outcomes?

Study Design And Methods: Adults attending a specialist CF center were invited to complete an online discrete choice experiment (DCE). The DCE required participants to evaluate hypothetical CF treatment profiles, defined by impact on lung function, pulmonary exacerbations, abdominal symptoms, life expectancy, quality of life, inhaled medicine usage, and physiotherapy requirement.

Factors associated with clinical progression to severe COVID-19 in people with cystic fibrosis: A global observational study.

Background: This international study aimed to characterise the impact of acute SARS-CoV-2 infection in people with cystic fibrosis and investigate factors associated with severe outcomes. Methods Data from 22 countries prior to 13 December 2020 and the introduction of vaccines were included. It was de-identified and included patient demographics, clinical characteristics, treatments, outcomes and sequalae following SARS-CoV-2 infection.

An Update on CFTR Modulators as New Therapies for Cystic Fibrosis.

Over the past decade there have been significant developments in the field of Cystic Fibrosis Transmembrane Regulator modulator drugs. Following treatment in patients with cystic fibrosis with common gating mutations using the potentiator drug ivacaftor, successive development of corrector drugs used in combination has led to highly effective modulator therapy being available to more than 85% of the cystic fibrosis population over 12 years of age in the form of elexacaftor/tezacaftor/ivacaftor. In this article, we review the evidence from clinical trials and mounting real-world observational and registry data that demonstrates the impact highly effective modulators have on both pulmonary and extra-pulmonary manifestations of cystic fibrosis.

Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes.

Methods: In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis.

Results: Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection.