INTRODUCTION:
Cystic fibrosis (CF) is the most common lethal genetic disease in Caucasians, affecting 1 in 2500 births. It is caused by mutations of a gene (on chromosome 7) coding for a chloride channel – cystic fibrosis transmembrane conductance regulator (CFTR). The carrier rate of CF mutations is 1 in 25 and inheritance is autosomal recessive.
The most common mutation is ΔF508 but > 1000 mutations have been identified. The genetic defect causes increased sodium and chloride in sweat, and depletion of airway lining fluid, leading to chronic bacterial infection in the airways. The gut epithelium, pancreas, liver and reproductive tract are also affected.
Neonatal screening for CF is now routine in the UK. The diagnosis is confirmed by genetic testing and sweat electrolyte measurements.
CLINICAL FEATURES:
The lungs are normal at birth, but bronchiectasis develops in childhood. Staph. aureus is the most common childhood organism; however, in adulthood, increasing numbers are colonised with Pseudomonas aeruginosa. Recurrent exacerbations of bronchiectasis cause progressive lung damage, resulting ultimately in death from respiratory failure. Other clinical manifestations of the gene defect include intestinal obstruction, exocrine pancreatic insufficiency with malabsorption, diabetes and hepatic cirrhosis. Men with CF are infertile due to failure of development of the vas deferens.
MANAGEMENT & PROGNOSIS:
Regular chest physiotherapy is recommended. For exacerbations, Staph. aureus infection is often managed with oral antibiotics; IV treatment is usually needed for Pseudomonas spp. Resistant strains of Ps. aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia are a major problem. Aspergillus and ‘atypical mycobacteria’ are also frequently found (may be benign ‘colonisers’). Nebulised antibiotic therapy (Colomycin or tobramycin) is used to suppress chronic Pseudomonas infection. Nebulised recombinant human deoxyribonuclease (DNase) liquefies sputum, reduces exacerbations and improves pulmonary function in some patients. Regular macrolides (e.g. azithromycin) reduce exacerbations and improve lung function in patients with Pseudomonas colonisation.
In advanced disease, home oxygen and NIV may be necessary to treat respiratory failure. Ultimately, lung transplantation can produce dramatic improvements but is limited by donor organ availability.
Treatment of non-respiratory manifestations of CF: Malabsorption is treated with oral pancreatic enzymes and vitamin supplements. Increased calorie requirements of CF patients are met by supplemental feeding, including nasogastric or gastrostomy tube feeding if required. Diabetes eventually appears in ~25% of patients and often requires insulin. Osteoporosis should be sought and treated.
The prognosis of CF has improved greatly in recent decades, mainly because of better nutrition and control of bronchial sepsis. The median survival of patients with CF born in the 21st century is now predicted to be over 40 yrs.
THOSE ABOVE ARE COLLECTED FROM SOME BOOKS AND
WEBSITES..
(DAVIDSON’S ESSENTIALS OF MEDICINE)
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