The Infective Pulmonary Exacerbations in Cystic Fibrosis - an Ecological Perspective

Given the treatment burden and excess morbidity and mortality associated with acute infective exacerbations in cystic fibrosis, a clear understanding of the mechanisms involved in the origins of an infective exacerbation and the response to antibiotics is vital to improving long-term outcomes in CF.

This study will examine 3 areas of interest in CF exacerbations.

1. Bacterial biodiversity and its clinical significance 2. The role of bacteria which are able to rapidly mutate (hypermutators) 3. Inter-bacterial communication and its role in infective exacerbations

Study Hypothesis 1

Increased microbiological diversity represents a balanced community of bacteria. The presence of a diverse population of bacteria in CF infections therefore predicts a better outcome for treatment than when a population consists of a small number of more virulent organisms.

Study Hypothesis 2

Pseudomonas aeruginosa hypermutators can mutate much more often than ordinary Pseudomonas aeruginosa bacteria. Hypermutators are likely to grow better when the bacteria are under stress, such as during antibiotic treatment or during an infection. They are, however, weaker organisms because of the multiple mutations they have undergone. Their presence does not relate to clinical outcome but may be associated with the emergence of antibiotic resistance.

Study Hypothesis 3

Some Pseudomonas aeruginosa bacteria communicate with each other by secreting and responding to chemicals known as quorum sensing (QS)molecules. As well as affecting the behaviour of bacteria, these QS molecules can cause inflammation in the lung of CF patients. Selective growth of QS-producing organisms can trigger lung exacerbations in CF. If antibiotics kill this population of bacteria and QS molecule levels drop in the lung, patients recover from infection quickly. Failure to kill these bacteria with antibiotics allow QS molecule levels to remain elevated and patients to have prolonged infections.

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Infections Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

16 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Department of Cystic Fibrosis, NHLI, Imperial College,

London, SW3 6NP, United Kingdom

About this study

We will sequentially recruit patients attending our CF centre with an infective exacerbation of CF, who are chronically infected with Pseudomonas aeruginosa.

We will record spirometry, blood markers of inflammation, quality of life questionnaires and investigate sputum samples for:

Routine microbiology
Bacterial diversity using 16s RNA identification techniques
Relative abundance of P.aeruginosa hypermutators
Levels of quorum sensing molecules

These observations will be undertaken before commencing intravenous antibiotic therapy, on days 7, 10 and the last day of antibiotic therapy. Patients will also be reviewed one month after the end of antibiotic therapy where spirometry and a sputum sample will be collected for the above investigations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Confirmed diagnosis of Cystic Fibrosis
Chronic Pseudomonas aeruginosa
Symptoms and signs of infective exacerbation

Exclusion criteria

age under 16
unable to give consent or patients with significant mental health problems
co-existent active allergic bronchopulmonary aspergillosis requiring a change in steroid or antifungal therapy
a previous participant in this study

Sponsors and collaborators

Lead sponsor

Imperial College London

Other

Registry information

Important dates

Study start: 2011
Primary completion: 2012
First posted: Mar 1, 2011
Registry last updated: Mar 21, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed