January - March 2003: 
Volume 16, Issue 1

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Respiratory problems in adults with cystic fibrosis
Cystic fibrosis is an autosomal recessive disorder characterized by the production of thick, viscous secretions in the respiratory and gastrointestinal tract, increased salt secretion by sweat glands, pancreatic insufficiency due to pancreatic duct obstruction with abnormal mucus, infertility in males and, occasionally, hepatic failure.1
Keywords: cystic fibrosis
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It is a fatal disease carrying a poor prognosis early on in life. Cystic fibrosis is more common in white people (5% carriage of the cystic fibrosis gene) with an incidence of 1 in 2500 births.2 The primary abnormality is defective sodium and chloride ion transport in the lumen of the airways with reduced secretion of the latter and enhanced reabsorption of the former, leading to decreased water content and, consequently, increased viscosity of the mucus secreted in the airways.3 The gene for cystic fibrosis, located on chromosome 7,4 was identified in 1989 and named CFTR (cystic fibrosis transmembrane conductance regulator). The most common mutation, ΔF508, occurs in 70% of cystic fibrosis chromosomes.1

The disease is typically diagnosed using the sweat test, with chloride levels >60 mEq/L in the patient's sweat being diagnostic; in cases of high clinical suspicion and negative sweat test results, genetic analysis or/and nasal potentials may be employed to confirm or exclude the presence of the disease.5 Less severe CFTR mutations have been associated with defects in a single organ system, e.g. late appearance of pulmonary disease, congenital bilateral absence of the vas deferens or idiopathic pancreatitis.6

Soon after delivery the majority of patients with cystic fibrosis will develop inflammatory infiltrations of the bronchi and obstruction of the airways with mucopurulent secretions, followed by a response involving migration of neutrophils and increased production of proteinases, resulting in respiratory tract infections.7-9 Sputum cultures initially reveal chronic colonisation with S. aureus and H. influenzae; in adolescence P. aeruginosa is also isolated. It is believed that bacterial colonisation is facilitated by recurrent viral infections, mainly in the winter months.10 The most common manifestations from the respiratory system include purulent expectoration or/and haemoptysis, shortness of breath, chest pain, and exercise intolerance. Imaging studies reveal lung hyperinflation and bronchiectasis of variable severity, presumably a result of recurrent infections and chronic inflammation. Spirometry usually demonstrates an obstructive pattern with low FEV1, and can be used to monitor the course of the disease and the progressive deterioration of pulmonary function. Arterial blood gas analysis and SaO2 measurements are useful in assessing the progression to respiratory failure, a feature of end-stage disease.

Regular intravenous antibacterial therapy is guided by sputum cultures and susceptibility reports and, in the adult patient, is almost exclusively aimed against P. aeruginosa. Chronic colonisation can be delayed by the administration of nebulised colistin combined with oral ciprofloxacin.11 Most intravenous antibiotic regimens are combinations of an antipseudomonal penicillin plus an aminoglycoside. Alternatively a cephalosporin, such as ceftazidime or cefepime, may be given instead of the penicillin. Other antipseudomonal antibiotics in use include aztreonam, carbapenems and colistin, the latter employed against multi-resistant strains.12 Ciprofloxacin is the only antibiotic that may also be given orally. For a number of years now cystic fibrosis patients have been treated with intravenous antipseudomonal antibiotics every three months, irrespective of pulmonary exacerbations; as a result, life expectancy has significantly increased.13 More recently, an inhaled tobramycin preparation without excipients (Tobi) is being administered between intravenous antibiotic courses.14 Daily drainage of bronchial secretions, proper nutrition, as well as the administration of pancreatic enzymes and fat-soluble vitamins in cases of pancreatic insufficiency, are as important interventions as antibacterial therapy. In addition, bronchodilators, mucolytic agents such as rhDNAse (Pulmozyme), corticosteroids, as well as diuretics when indicated, play an important role in day-to-day management. As a last therapeutic resort, lung or combined heart-lung transplantation has been employed with satisfactory results. Recent research is focusing on gene therapy, treatment with sodium reabsorption inhibitors (amiloride), chloride secretion inducing agents (UTP), anti-inflammatory agents, as well as on pharmacological treatments targeted towards the most common mutations.15

The main pulmonary complications of cystic fibrosis include atelectasis, pneumothorax (19% incidence rate), haemoptysis due to chronic inflammation and bronchiectasis, allergic bronchopulmonary aspergillosis, cor pulmonale and respiratory failure.16

At present 35% of affected individuals in developed countries survive into adulthood and average life expectancy in those countries has risen to 30 years. With appropriate use of antibiotics and other medications, as well as with the introduction of novel therapeutic agents currently under investigation, we can reasonably expect that the prognosis of this fatal disease will further improve in the years ahead.


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