Infection in the cystic fibrosis lung

Published on April 2, 2014   52 min

A selection of talks on Respiratory Diseases

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My name is Stuart Elborn, I'm Professor of Respiratory Medicine at Queen's University, Belfast, and Director of the Center for Infection and Immunity. In this lecture, I'm going to describe some of the exciting new discoveries using second generation sequencing in identifying bacteria and other microorganisms in there airways of people with cystic fibrosis, and then go on to discuss some of the challenges that face us in cystic fibrosis care relating to the management of infection with antibiotics.
First of all, I'd like to orientate you around cystic fibrosis. This is the most common autosomal recessive disorder affecting Northwest Europeans that results in early death. It's a multi-system disorder because the genetic condition affects epithelial cells, and so all of our hollow organs are affected in this condition. The major part of the morbidity and mortality is in chronic sinopulmonary disease, with infection and inflammation in the airways resulting from bronchiectasis and progressive lung injury. This leads to respiratory failure. Other organ systems that are affected are the hepatobiliary system, the pancreatic ducts, the gastrointestinal tract, reproductive tracts in the vas deferens, and the endocrine pancreas is often also affected, probably as a result of pancreatic scarring rather than a primary defect, though there are some indications that there may also be some abnormalities of insulin metabolism.
Cystic fibrosis as a critical condition was reported by a number of clinicians in the first half of the 20th century, but it wasn't until the late 1940s that Anderson and colleagues described a number of children admitted during a heatwave in New York with severe electrolyte disturbances and connected these to the fibrocystic disease of the pancreas gland. Over the 1950s, the clinical condition of cystic fibrosis was much more clearly described, the diagnostic test using the concentration of chloride and sodium in the sweat was described. This sweat test has remained the pivotal diagnostic investigation for cystic fibrosis since then, with a sweat chloride concentration of greater than 60 million moles per liter being consistent with a diagnosis of cystic fibrosis. On this graph the highlights of some further interventions for cystic fibrosis are described. The red line indicates the median survival for people with cystic fibrosis over the last six or so decades. As you can see, the median survival for people with cystic fibrosis has risen from around five years in the early '60s to now being around 40 years. This progressive improvement has been due to the organization of cystic fibrosis care into specialist clinics, and the introduction of key therapies which have had an impact on the outcome. First of these was introduction of pancreatic enzyme replacement therapy to mitigate the effects of maldigestion due to pancreatic enzyme deficiency because of pancreatic fibrosis and a reduction in exocrine function. Subsequent key interventions were airway clearance, a range of antibiotics against Staphylococcus aureus and Pseudomonas aeruginosa, and drugs which improved mucus clearance such as DNase and hypertonic saline. In the last 20 years or so, antibiotics have been developed to be used by the inhaled route, particularly tobramycin, aztreonam, and colistin. These have also likely made a significant impact on improving survival. We now are in a new era in cystic fibrosis with a drug called ivacaftor which treats the basic defect in cystic fibrosis. It has transformative effect on key outcome measures such as lung function and frequency of pulmonary exacerbations. Cystic fibrosis centers throughout the world now collaborate to improve the quality of care delivered to people with cystic fibrosis and to conduct high quality clinical trials through the North American Therapeutic Development Network and the European Cystic Fibrosis Society Clinical Trials Network.