Infection prevention and control in cystic fibrosis: An update of a systematic review of interventions.

Preventing transmissible infection is a priority in cystic fibrosis (CF) care. This is an update of a systematic review of the evidence for infection prevention and control interventions in CF. Our full protocol can be found on PROSPERO (CRD42018109999).

Macrolide antibiotics (including azithromycin) for cystic fibrosis.

Background: Cystic fibrosis (CF) is a life-limiting genetic condition, affecting over 90,000 people worldwide. CF affects several organs in the body, but airway damage has the most profound impact on quality of life (QoL) and survival. Causes of lower airway infection in people with CF are, most notably, Staphylococcus aureus in the early course of the disease and Pseudomonas aeruginosa at a later stage.

Thinking outside the box: a review of gastrointestinal symptoms and complications in cystic fibrosis.

Introduction: Gastrointestinal (GI)-related symptoms, complications, and comorbidities in cystic fibrosis (CF) are common and research to reduce their burden is a priority for the CF community. To enable future research, this review aimed to summarize the range of GI symptoms, complications and comorbidities seen in CF, the underlying pathophysiology, and treatments.

Areas Covered: This was a rapid systematic review undertaken using the recommendations from the Cochrane Rapid Reviews Methods Group.

Nebulised hypertonic saline for cystic fibrosis.

Background: Hypertonic saline enhances mucociliary clearance and may lessen the destructive inflammatory process in the airways. This is an update of a previously published review.

Objectives: To investigate efficacy and tolerability of nebulised hypertonic saline treatment in people with cystic fibrosis (CF) compared to placebo or other treatments that enhance mucociliary clearance.

A refresh of the top 10 research priorities in cystic fibrosis.

In 2018 we published the James Lind Alliance (JLA) top 10 priorities for clinical research in cystic fibrosis (CF), chosen jointly by the patient and clinical communities. These priorities have led to new research funding. To establish whether priorities have changed with novel modulator therapies, we undertook an online international update through a series of surveys and a workshop.

Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis.

Background: Respiratory tract infections with Pseudomonas aeruginosa occur in most people with cystic fibrosis (CF). Established chronic P aeruginosa infection is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate.

Digital technology for early identification of exacerbations in people with cystic fibrosis.

Background: Cystic fibrosis (CF) is a life-limiting genetic condition affecting various organ systems including the gastrointestinal tract, endocrine system and especially the respiratory tract. Pulmonary exacerbations in CF result in increased symptoms, an acceleration in the rate of lung decline and an increased need for treatment. Early detection of infections or clinical worsening provides an opportunity for proactive treatment that may affect clinical outcomes.

Digital technology for monitoring adherence to inhaled therapies in people with cystic fibrosis.

Background: Improved understanding and treatment of cystic fibrosis (CF) has led to longer life expectancy, which is accompanied by an increasingly complex regimen of treatments. Suboptimal adherence to the treatment plan, in the context of respiratory disease, has been found to be associated with poorer health outcomes. With digital technology being more accessible, it can be used to monitor adherence to inhaled therapies via chipped nebulisers, mobile phone apps and web-based platforms.

Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis.

Background: Inhaled antibiotics are commonly used to treat persistent airway infection with Pseudomonas aeruginosa that contributes to lung damage in people with cystic fibrosis. Current guidelines recommend inhaled tobramycin for individuals with cystic fibrosis and persistent Pseudomonas aeruginosa infection who are aged six years or older. The aim is to reduce bacterial load in the lungs so as to reduce inflammation and deterioration of lung function.

Physical activity and exercise training in cystic fibrosis.

Background: Physical activity (including exercise) may form an important part of regular care for people with cystic fibrosis (CF). This is an update of a previously published review.

Objectives: To assess the effects of physical activity interventions on exercise capacity by peak oxygen uptake, lung function by forced expiratory volume in one second (FEV), health-related quality of life (HRQoL) and further important patient-relevant outcomes in people with cystic fibrosis (CF).

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis.

Background: Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections.

Short-acting inhaled bronchodilators for cystic fibrosis.

Background: Respiratory disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and many different therapies are used by people with CF in the management of respiratory problems. Bronchodilator therapy is used to relieve symptoms of shortness of breath and to open the airways to allow clearance of mucus. Despite the widespread use of inhaled bronchodilators in CF, there is little objective evidence of their efficacy.

Recombinant growth hormone therapy for X-linked hypophosphatemia in children.

Background: Conventional treatment of X-linked hypophosphatemia with oral phosphate and calcitriol can heal rickets, but it does not always raise serum phosphate concentrations significantly, nor does it always normalize linear growth. Some clinical trials suggest that combining recombinant human growth hormone therapy with conventional treatment improves growth velocity, phosphate retention, and bone mineral density, but some clinical trials suggest that it appears to aggravate the pre-existent disproportionate stature of such children. This is an updated version of a previously published review.

Exploring the challenges of accessing medication for patients with cystic fibrosis.

Reducing treatment burden in cystic fibrosis (CF) is the top research priority for patients and clinicians. Difficulty accessing medication is one aspect of treatment burden. We investigated this with an online survey available globally for patients with CF and healthcare professionals.

Rituximab for eradicating inhibitors in people with acquired haemophilia A.

Background: Acquired haemophilia A is a rare bleeding disorder caused by the development of specific autoantibodies against coagulation factor VIII. Standard treatment, usually steroids alone, or in combination with cyclophosphamide, aims to stop acute bleeds by using haemostatic agents to promote clotting. Rituximab may be an alternative approach to the treatment of acquired haemophilia by eradicating FVIII autoantibodies.

The measurement properties of tests and tools used in cystic fibrosis studies: a systematic review.

There is no consensus on how best to measure responses to interventions among children and adults with cystic fibrosis (CF). We have systematically reviewed and summarised the characteristics and measurement properties of tests and tools that have been used to capture outcomes in studies among people with CF, including their reliability, validity and responsiveness. This review is intended to guide researchers when selecting tests or tools for measuring treatment effects in CF trials.

Tyrosine supplementation for phenylketonuria.

Background: Phenylketonuria is an inherited disease for which the main treatment is the dietary restriction of the amino acid phenylalanine. The diet has to be initiated in the neonatal period to prevent or reduce mental handicap. However, the diet is very restrictive and unpalatable and can be difficult to follow.

Outcomes and endpoints reported in studies of pulmonary exacerbations in people with cystic fibrosis: A systematic review.

Background: There is no consensus about which outcomes should be evaluated in studies of pulmonary exacerbations in people with cystic fibrosis (CF). Outcomes used for evaluation should be meaningful; that is, they should capture how people feel, function or survive and be acknowledged as important to people with CF, or should be reliable surrogates of those outcomes. We aimed to summarise the outcomes and corresponding endpoints which have been reported in studies of pulmonary exacerbations, and to identify those which are most likely to be meaningful.

How can we relieve gastrointestinal symptoms in people with cystic fibrosis? An international qualitative survey.

Introduction: Relieving gastrointestinal (GI) symptoms was identified as a 'top ten' priority by our James Lind Alliance Priority Setting Partnership in cystic fibrosis (CF). We conducted an online survey to find out more about the effect of GI symptoms in CF.

Methods: We co-produced an online survey distributed to the CF community via web-based platforms.

What effective ways of motivation, support and technologies help people with cystic fibrosis improve and sustain adherence to treatment?

Introduction: "What effective ways of motivation, support and technologies help people with cystic fibrosis improve and sustain adherence to treatment?" was identified as one of the James Lind Alliance Priority Setting Partnership's top 10 research questions in cystic fibrosis (CF). Using electronic questionnaires, we aimed to gain a deeper understanding of this research priority.

Method: The work was led by the steering group representative of the UK CF community consisting of patients, carers and healthcare professionals (HCPs).

Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis.

Background: Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established.

Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis.

Background: Clinicians typically select the antibiotics used to treat pulmonary infections in people with cystic fibrosis based on the results of antimicrobial susceptibility testing performed on bacteria traditionally grown in a planktonic mode (grown in a liquid). However, there is considerable evidence to suggest that Pseudomonas aeruginosa actually grows in a biofilm (or slime layer) in the airways of people with cystic fibrosis with chronic pulmonary infections. Therefore, choosing antibiotics based on biofilm rather than conventional antimicrobial susceptibility testing could potentially improve response to treatment of Pseudomonas aeruginosa in people with cystic fibrosis.

Combination antimicrobial susceptibility testing for acute exacerbations in chronic infection of Pseudomonas aeruginosa in cystic fibrosis.

Background: Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis is usually chosen based on the results of antimicrobial susceptibility testing of individual drugs. Combination antimicrobial susceptibility testing assesses the efficacy of drug combinations including two or three antibiotics in vitro and can often demonstrate antimicrobial efficacy against bacterial isolates even when individual antibiotics have little or no effect. Therefore, choosing antibiotics based on combination antimicrobial susceptibility testing could potentially improve response to treatment in people with cystic fibrosis with acute exacerbations.