ABSTRACT
Cystic fibrosis is the most common lethal genetically inherited disease to affect Caucasian populations. The primary autosomal recessive genetic defect is carried by 1 in 25 of the population and affects 1 in 2500 newborn babies in the UK. For babies born in the 1990s with cystic fibrosis, a life expectancy of 40 years of age is now estimated. The genetic defect lies in the expression of a protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which is an anion channel expressed by epithelial cells. In the airways, the fact that the protein is either absent or defective leads to an imbalance in movement of water and electrolytes across the bronchial epithelium, leading to abnormal mucus gland secretions that are dehydrated and viscous. Such secretions invite infection; inevitably with Pseudomonas aeruginosa, an organism that has many immunoevasive properties and is hard to eradicate in this group of patients. A neutrophilic inflammatory response ensues. Mucus secretion from hyperplastic mucus glands is stimulated by neutrophil proteases, and self-amplifying cycles of infection and inflammation are initiated. Necrotic inflammatory cells, mainly neutrophils, release large amounts of DNA and actin, (high molecular weight polymers) in the airways that further contribute to increased mucus viscosity The mucociliary escalator is unable to clear the resulting tenacious secretions and daily chest physiotherapy becomes a necessity.
