Clinical features and diagnosis of cystic fibrosis

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        <p><strong>Clinicalexamination</strong> of adolescents and adults
usually shows finger clubbing secondary to chronic respiratory
infection,retarded growth and development, and a hyperinflated chest with
coarse crackles and wheezes. Gynaecomastia isoccasionally seen, and there
may be hepatosplenomegaly and other signs of chronic liver disease.</p>
<p>The chest X-ray shows hyperinflated lungs and widespreadbronchiectasis
(parallel line and ring shadows, with multiple nodular opacities, mainly
in the mid and upperzones; the hila are usually prominent). Lung
functiontesting shows a progressive obstructive defect. The singlemost
important diagnostic test is the sweat sodium, whichis consistently
greater than 70mmol/L in children with thedisease and greater than
90mmol/L in affected adults,although the results in adults are less
reliable. Sputum bacteriology will often yield S. aureus, and later in
lifePs. aeruginosa becomes a major problem.</p>
<p>Haemophilusmay be an important pathogen, and patients
occasionallydevelop tuberculosis.Prenatal diagnosis can be achieved by
the measurementof elevated levels of enzymes such as alkaline phosphatase
in the amniotic fluid or by DNA analysis of chorionic villusbiopsies;
these techniques are only of value for 'at-risk'pregnancies. Neonatal
screening for immunoreactivetrypsin in the blood is simple and
inexpensive.The differential diagnosis includes hypogammaglobulinaemia,
immotile cilia syndromes, asthma, coeliac diseaseand Schwachman's
syndrome (pancreatic insufficiency,neutropenia, metaphyseal
chondrodysplasia, growth retardation and frequent infections).</p>
<p>The outlook for patients with cystic fibrosis has improved,and
predicted average survival for children born in the 1990s is now 40
years. These improvements have beenachieved by aggressive physiotherapy,
antibiotic treatment,pancreatic enzyme supplementation and
<p>The cornerstone of treatment of respiratory disease isregular chest
physiotherapy, particularly postural drainage.In the first year of life
prophylactic antistaphylococcal drugs may be helpful. Severe infective
exacerbations require intravenous antibiotics, usually
antipseudomonalagents (e.g. gentamicin, ceftazidime, piperacillin,
ciprofloxacin).As the disease progresses regular nebulized antibioticsare
of value. To facilitate home care, some patientswith repeated flare-up of
infection have indwelling centralvenous lines and administer their own
antibiotics. Bronchodilators,and occasionally oral corticosteroids, may
beuseful in patients with airflow obstruction. Pneumothoracesare not
uncommon and should be treated conservativelywhenever possible.</p>
<p>Malabsorption is treated by oralpancreatic enzyme supplements.
Abdominal emergenciesoccur, including adult meconium ileus equivalent,
intussusception,acute pancreatitis and bleeding from oesophagealvarices.
Diabetes is common. Adult patients willneed counselling about fertility,
as 98% of the males areinfertile (owing to maldevelopment of the vas
deferens)and for females pregnancy can be hazardous. Patients andtheir
family need constant moral, psychological and practicalsupport. Genetic
counselling of the parents of childrenwith cystic fibrosis and of the
patients themselves isessential.</p>
<p><strong>Gene therapy</strong></p>
<p>There are now many studies reporting gene therapy incystic fibrosis
patients. These have viral or non-viral vectorsto deliver CFTR-cDNA
topically to the nose or the lungsby aerosol or by liquid instillation.
Although in theory thetransfer of normal CFTR-cDNA into affected CF cells
inearly life should cause the production of enough normalCFTR to prevent
the clinical manifestations of cystic fibrosis,technical problems with
the vectors and the clinicalresponse have meant that gene therapy is not
yet curative.</p>
<p>In particular, the target cell type, the target airways (largeor
small) and the barrier created by viscous mucus areproving difficult to
overcome. Furthermore, it is not clearhow much CFTR mRNA is necessary to
get into cells toprevent disease. These topics are still the focus of
intensiveresearch and are likely to lead to important therapeutic
advances in the relatively near future.</p>
<p><strong>Lung transplantation in cystic fibrosis</strong></p>
<p>Lung transplantation programmes around the world now incorporate a
significant number of patients with cysticfibrosis. Transplantation is
reserved for those with the mostadvanced lung disease, and presents
special difficulties. Inparticular because of the level of infection
present the procedureis often complicated by postoperative sepsis,
andthis can be very difficult to manage.</p>
<p>Furthermore, previouspleural disease or tracheostomies can either be
contraindicationsor make the surgical techniques difficult.Live related
lobar donor transplantation has also been carried out, with mixed
success. Patients with cystic fibrosiswho have advanced liver disease
have had successfulliver transplantations in recent years.Clearly,
however, the best strategies for the treatment of cystic fibrosis and all
its complications are preventative,and in the long term it is in this
arena that the most successis likely.</p>        <!--INFOLINKS_OFF-->

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