Cystic fibrosis is the most common autosomal recessive disease in Caucasians associated with early death. Unaffected carrier frequency is 1:25
Phe508del is the most common of over 1500 mutations
The gene encodes a transmembrane chloride conductance channel, the CFTR, which regulates chloride ion and water movements across the cell membrane CFTR is expressed throughout the body, and CF disease affects multiple systems, including major effects on the lung, pancreas and gastrointestinal systems. Pulmonary disease is the most important cause of death and disability, resulting from chronic progressive suppurative lung disease. Over- activation of the sodium (ENaC) channel in the lungs, caused by loss of CFTR- inhibition, results in dehydration of the airway surface fluid layer and consequent poor mucociliary clearance. Retained secretions encourage bacterial adherence, chronic neutrophillic infection, and a vicious cycle of infection, inflammation and tissue destruction.
Doring G., gulbins E. (2009) Cystic fibrosis and innate immunity: how chloride channels provoke lung disease. Cellular Microbiology Ch.2 diagnosis and process of care
Diagnosis is most common in those with recurrent respiratory and poor weight gain in the first year of life Those not diagnosed as newborns may present later in life with more subtle, but troublesome, respiratory infection CF is a clinical diagnosis, supported by an abnormal sweat chloride level on sweat testing Genetic analysis may help confirm a diagnosis of CF, but the very large number of mutations now identified make some genotype/ phenotype relationships difficult to predict. Newborn screening programmes generally test for raised immune reactive trypsin (IRT) on blood taken within the first week of life, with a subsequent test for CF gene mutations if IRT is elevated Patients with CF require regular review by health professionals trained in CF care Patients with CF may inadvertently share respiratory organisms and consideration should be given as how to minimize this risk during hospital contact Annual review is an important event in the care of patients with CF, enabling a multidisciplinary perspective on the rate of disease progression and plans made to slow this decline. Transition to adult services should begin in early teens, actively involve patients and parents, and provide plenty of opportunity for transfer of information across teams
Farrell P.M., Rosenstein B.J., White T.B., et al. (2008) Guidelines for diagnosis of cystic fibrosis in newborns through older adults: CF Foundation consensus report. J. Pediatrics Ch. 3 microbiology of CF lung disease
Bacterial lung infections are the predominant cause of restricted life expectancy of CF patients Eradication of bacteria chronically infecting the CF lungs is virtually impossible Bacteria adapt their genotype and phenotype to the specific lung environment CF lung infection involves a mixed growth of facultative and obligate anaerobes Anaerobic growth conditions induce Pseudomonas biofilm formation, reduce the efficacy of the human defence system, and impair the effectiveness of antibiotics Early therapy at the onset of infection offers the best chance of eradication Many organisms are either innately resistant to multiple antibiotics or are able to acquire resistance
Ch.4 management of stable CF lung disease
Aggressive treatment of specific lung infections improves prognosis Eradication of new Pseudomonas infection slows progression
Nebulized DNase improves lung function in some patients
Azithromycin and nebulized tobramycin can reduce the burden of infective exacerbations and improve lung function In advanced disease, oxygen and non- invasive ventilation may buy sufficient time for definitive treatment by lung transplantation.
Ch. 5 management of respiratory exacerbations
Early recognition and treatment of CF exacerbation is one of the modern CF care Diagnosis is essentially...