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.

The impact of plasma 25-hydroxyvitamin D on pulmonary function and exercise physiology in cystic fibrosis: A multicentre retrospective study.

Background: A 25-hydroxyvitamin D (25OHD) may exert immunomodulatory effects on respiratory health, which may translate to improvements in exercise physiology. Thus, we aimed to investigate whether plasma 25OHD is associated with lung function and aerobic fitness in people with cystic fibrosis (pwCF).

Methods: A multicentre retrospective review of pwCF (> 9 years old) attending the Royal Hospital for Sick Children (Edinburgh) or Wessex CF-Unit (Southampton) was performed between July 2017 and October 2019.

Lung function and microbiota diversity in cystic fibrosis.

Background: Chronic infection and concomitant airway inflammation is the leading cause of morbidity and mortality for people living with cystic fibrosis (CF). Although chronic infection in CF is undeniably polymicrobial, involving a lung microbiota, infection surveillance and control approaches remain underpinned by classical aerobic culture-based microbiology. How to use microbiomics to direct clinical management of CF airway infections remains a crucial challenge.

Circulating biomarkers of antioxidant status and oxidative stress in people with cystic fibrosis: A systematic review and meta-analysis.

Introduction: Oxidative stress may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to quantify CF-related redox imbalances.

Methods: Systematic searches of the Medline, CINAHL, CENTRAL and PsycINFO databases were conducted.

The implications of dysglycaemia on aerobic exercise and ventilatory function in cystic fibrosis.

Background: The development of cystic fibrosis (CF)-related diabetes (CFRD) in paediatric groups is associated with a reduced aerobic fitness. However, this has yet to be investigated in adults with more severe lung disease.

Methods: Cardiopulmonary exercise and glycaemic control tests were retrospectively analysed in 46 adults with CF (age: 26.

Cardiopulmonary exercise testing with supramaximal verification produces a safe and valid assessment of V̇o in people with cystic fibrosis: a retrospective analysis.

The validity and safety of using supramaximal verification (S) to confirm a maximal effort during cardiopulmonary exercise testing (CPET) in people with cystic fibrosis (CF) and/or those with severe disease has been questioned. Therefore, this study aimed to investigate these concerns in children, adolescents, and adults with mild-to-severe CF lung disease. Retrospective analysis of 17 pediatric and 28 adult participants with CF [age range: 9.

Contributions of Composition and Interactions to Bacterial Respiration Are Reliant on the Phylogenetic Similarity of the Measured Community.

Bacterial diversity underpins many ecosystem functions; however, the impact of within-species variation on the relationship between diversity and function remains unclear. Processes involving strain differentiation, such as niche radiation, are often overlooked in studies that focus on phylogenetic variation. This study used bacterial isolates assembled in two comparable microcosm experiments to test how species variation affected ecosystem function.

Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention.

Pulmonary symptoms in cystic fibrosis (CF) begin in early life with chronic lung infections and concomitant airway inflammation leading to progressive loss of lung function. Gradual pulmonary function decline is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs). Cumulatively, CFPEs are associated with more rapid disease progression.

Application of an Asthma Screening Questionnaire in Children with Sickle Cell Disease.

Asthma in sickle cell disease (SCD) patients is associated with elevated morbidity and mortality. Early detection and initiation of treatment may therefore lead to improved outcome. Utility of an asthma screening questionnaire to identify obstructive airway disease and physician diagnosed asthma in children with SCD at an outpatient setting as an effective, easy-to-administer screening tool has not previously been evaluated in this population.

Republished: Respiratory microbiota: addressing clinical questions, informing clinical practice.

Over the last decade, technological advances have revolutionised efforts to understand the role played by microbes in airways disease. With the application of ever more sophisticated techniques, the literature has become increasingly inaccessible to the non-specialist reader, potentially hampering the translation of these gains into improvements in patient care. In this article, we set out the key principles underpinning microbiota research in respiratory contexts and provide practical guidance on how best such studies can be designed, executed and interpreted.

A quality-of-life measure for adults with primary ciliary dyskinesia: QOL-PCD.

Primary ciliary dyskinesia (PCD) is characterised by chronic suppurative lung disease, rhino-sinusitis, hearing impairment and sub-fertility. We have developed the first multidimensional measure to assess health-related quality of life (HRQoL) in adults with PCD (QOL-PCD).Following a literature review and expert panel meeting, open-ended interviews with patients investigated the impact of PCD on HRQoL in the UK and North America (n=21).

Implications of multiple freeze-thawing on respiratory samples for culture-independent analyses.

Background: Best practice when performing culture-independent microbiological analysis of sputum samples involves their rapid freezing and storage at -80°C. However, accessing biobanked collections can mean that material has been passed through repeated freeze-thaw cycles. The aim of this study was to determine the impact of these cycles on microbial community profiles.

Respiratory microbiota: addressing clinical questions, informing clinical practice.

Over the last decade, technological advances have revolutionised efforts to understand the role played by microbes in airways disease. With the application of ever more sophisticated techniques, the literature has become increasingly inaccessible to the non-specialist reader, potentially hampering the translation of these gains into improvements in patient care. In this article, we set out the key principles underpinning microbiota research in respiratory contexts and provide practical guidance on how best such studies can be designed, executed and interpreted.

Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.

Background: Molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches.

Time between collection and storage significantly influences bacterial sequence composition in sputum samples from cystic fibrosis respiratory infections.

Spontaneously expectorated sputum is traditionally used as the sampling method for the investigation of lower airway infections. While guidelines exist for the handling of these samples for culture-based diagnostic microbiology, there is no comparable consensus on their handling prior to culture-independent analysis. The increasing incorporation of culture-independent approaches in diagnostic microbiology means that it is of critical importance to assess potential biases.

A relationship between growth behaviour and cystic fibrosis patient lung function identified in a metabolomic investigation.

Chronic polymicrobial lung infections in adult cystic fibrosis patients are typically dominated by high levels of . Determining the impact of growth on airway secretion composition is fundamental to understanding both the behaviour of this pathogen , and its relationship with other potential colonising species. We hypothesised that the marked differences in the phenotypes of clinical isolates would be reflected in the metabolite composition of spent culture media.

Complexity, temporal stability, and clinical correlates of airway bacterial community composition in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary function, leading to compromised airway clearance and chronic bacterial infection of the upper and lower airways. The compositions of these infections and the relationships between their characteristics and disease presentation are poorly defined. We describe here the first systematic culture-independent evaluation of lower airway bacteriology in PCD.

Interpreting infective microbiota: the importance of an ecological perspective.

Complex microbiota are being reported increasingly across a range of chronic infections, including those of the cystic fibrosis airways. Such diversity fits poorly into classical models of sterile tissue infections, which generally involve one species, and where microbe-outcome associations usually imply causality. It has been suggested that microbiota at sites of infection could represent pathogenic entities, analogous to individual species.

Reducing bias in bacterial community analysis of lower respiratory infections.

High-throughput pyrosequencing and quantitative PCR (Q-PCR) analysis offer greatly improved accuracy and depth of characterisation of lower respiratory infections. However, such approaches suffer from an inability to distinguish between DNA derived from viable and non-viable bacteria. This discrimination represents an important step in characterising microbial communities, particularly in contexts with poor clearance of material or high antimicrobial stress, as non-viable bacteria and extracellular DNA can contribute significantly to analyses.

Long-term cultivation-independent microbial diversity analysis demonstrates that bacterial communities infecting the adult cystic fibrosis lung show stability and resilience.

Background: Culture-independent analysis of the respiratory secretions of people with cystic fibrosis (CF) has identified many bacterial species not previously detected using culture in this context. However, little is known about their clinical significance or persistence in CF airways.

Methods: The authors characterised the viable bacterial communities in the sputum collected from 14 patients at monthly intervals over 1 year using a molecular community profiling technique-terminal restriction fragment length polymorphism.

Enhancing the utility of existing antibiotics by targeting bacterial behaviour?

The discovery of novel classes of antibiotics has slowed dramatically. This has occurred during a time when the appearance of resistant strains of bacteria has shown a substantial increase. Concern is therefore mounting over our ability to continue to treat infections in an effective manner using the antibiotics that are currently available.

Does bacterial density in cystic fibrosis sputum increase prior to pulmonary exacerbation?

Background: Cystic Fibrosis (CF) lung disease is characterised by an inexorable decline in lung function, punctuated by periods of symptomatic worsening known as pulmonary exacerbations (referred to here as CFPE). Despite their clinical significance, the cause of CFPE remains undetermined. It has been suggested that an increase in bacterial density may be a trigger, although this has not been shown empirically.

Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset.

Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated.