Examine the chest of this male patient who has had a good appetite, poor weight gain and foul fatty stool.



· Cough with purulent and viscous expectoration.

· Diabetes mellitus.

· Gastrointestinal symptoms (steatorrhoea, failure to thrive in childhood, rectal prolapse, meconium ileus or distal intestinal


· Heat stroke, salt depletion.

· Sterility in men and decreased fertility in women.


· Sputum is purulent.

· Patient is short of breath.

· Central cyanosis.

· Finger clubbing.

· Bilateral coarse crackles.

Proceed as follows:

Tell the examiner that you would like to check the following levels:

· Urine sugar.

· Faecal fat.

· Sweat sodium.


This patient has bilateral coarse crackles, asthenia and foul fatty stool (lesion) due to cystic fibrosis (aetiology) and requires

continuous oxygen indicating respiratory failure (functional status).


What are the chances of this male patient having a child?

Males are sterile owing to the failure of development of the vas deferens and epididymis.

What are the clinical manifestations of this condition?


Recurrent chest infections, failure to thrive, meconium ileus and rectal prolapse.

In childhood and young adults

· Respiratory: infection, bronchiectasis, pneumothorax, haemoptysis, nasal polyps, allergic bronchopulmonary aspergillosis,

deterioration during and after pregnancy.

· Cardiovascular: cur pulmonale.

· Gastrointestinal: rectal prolapse, distal ileal obstruction (meconium ileus equivalent), cirrhosis, gallstones, intussusception.

· Miscellaneous: male infertility, diabetes mellitus, hypertrophic pulmonary osteoarthropathy.

How would you treat steatorrhoea?

· Low-fat diet.

· Pancreatic supplements.

· H2-receptor antagonist.

How would you treat chest complications?

· Postural drainage.

· Antibiotics.

· Bronchodilators.

· Heart-lung transplantantion.

What is the role of physiotherapy?

Physiotherapy has been shown to be useful, but there remains considerable debate regarding the effectiveness of different

techniques including traditional postural drainage and percussion, forced expiratory technique, positive expiratory pressure masks,

autodrainage and flutter valves.


What is the inheritance in cystic fibrosis?

Autosomal recessive. On the long arm of chromosome 7 resides the gene coding for a 1480-amino-acid protein a cyclic

AMP-regulated chloride channel, now called the cystic fibrosis transmembrane conductor regulator (CFTR). The CFTR gene is

carried by I in 20 Caucasians and its incidence is about 1 in 2000 live births. There is a mutation on the long arm of chromosome 7

in 70% of patients. There is a deletion of the codon for phenylalanine at position 508 (A508; N Engl J Med 1990; 323:1517). This

detect leads to a failure of the chloride channel to open in response to cyclic AMP (Science 1992; 256: 774-9: N Engl d Med 1991;

325: 575-7). More than 175 other types of lesion in the cystic fibrosis gene are responsible for the disease in the remaining 30% of


How is this condition diagnosed in infancy?

lmmunoreactive trypsin assay in dried blood.

What do you know about sweat testing?

A sweat sodimn concentration over 60 mmol/l is indicative of cystic fibrosis. It identifies over 75% by the age of 2 years and about

95% by the age of 12 years. It is more difficult to interpret in older children and adults.

What is the basic defect in the airways of these patients?

The opening of chloride channels at the luminal surface of the airway epithelial cells in normal individuals allows the passive

transport of chloride along an electro-chemical gradient from the cytoplasm to the lumen. In patients with cystic fibrosis

there is a defect in these channels which prevents the normal secretion of chloride into the airway lumen. Simultaneously, there is a

three-fold increase in the reabsorp-tion of sodium from the airway lumen into the cytoplasm of the epithelial cell. As the movement of

water into airway secretions follows the movement of salt, it is believed that a decreased secretion of chloride into the airway lumen

and the increased reabsorption of sodium from the airway lumen combine to reduce water content and increase the viscosity and

tenacity of the airway secretions.

If the patient has persistent purulent cough, which organisms are usually


Staphylococcus aureus, Haemophilus influenzae, Burkholderia cepacia and Pseudomonas aeruginosa. The latter is associated with

poor prognosis as this organism is almost impossible to eradicate.

Which antibiotics are usually used to treat pseudomonal infections? Intravenous or aerosol carbenicillin and gentamicin in


What is the risk of cancer in patients with cystic fibrosis?

The overall risk of cancer is similar to that of the general population, but there is an increased risk of digestive tract cancers (N Engl

J Med 1995; 332: 494-9). Persistent or unexplained gastrointestinal symptoms in these patients ought to be investigated carefully.

What is the lifespan in such patients?

The median age of survival is currently in the early 30s. It is estimated that at least half of those with cystic fibrosis will be adults by

the year 2000.

What is the cause of death in cystic fibrosis?

Death occurs from pulmonary complications, such as pneumonia, pneumothorax or haemoptysis, or as a result of terminal chronic

respiratory failure.

What parameters can predict death in cystic fibrosis?

Prediction of death within 2 years can be made for 50% of the patients whose forced expiratory volume in 1 second (FEV1) is less

than 30%. Thus the necessity for referral for transplantation can be anticipated about 1 year in advance of death (N Engl J Med

1992; 326: l 187-91).

How would you manage a patient who has been accepted for transplantation ?

The aim is to sustain life by aggressive therapy with nocturnal oxygen, continuous intravenous antibiotics, enteral feeding,

respiratory stimulants and nasal intermittent positive pressure ventilation (Eur Respir J 1991; 4: 524-7).

If this patient requires lung transplantation, which type of transplantation is the treatment of choice?

Bilateral lung transplantation is necessary for patients with chronic bronchial infection such as cystic fibrosis (or bronchiectasis) to

avoid contamination of the donor lung by spill-over of infected material from the recipient's remaining lung (J Thorac Cardiovasc

Surg 1992; 103: 287-94).

What are the complications of lung transplantation?

Early post-transplantation lung oedema, infection and rejection (including obliterative bronchiolitis).

p class=MsoNormal style='text-align:left;mso-pagination:none;mso-layout-grid-align:

none;text-autospace:none;direction:ltr;unicode-bidi:embed'>What are the indications for combined

heart-lung transplantation? Combined heart-lung transplantation has relatively few indications, the primary one being congenital

heart disease with Eisenmenger syndrome.

What new methods of treatment are available?

· High-dose ibuprofen in patients with mild disease (FEVi of at least 60% of the predicted value), taken consistently for 4 years,

significantly slows the progression of lung disease without serious adverse effects (N Engl J Med 1995; 332: 848-54).

· Aerosolized recombinant human DNAse, which is capable of degrading DNA in the bronchial secretion, has been shown to

improve forced expiratory flow rates when given by aerosol (N Engl J Med 1994; 331: 637-42).

· Gene therapy: the gene is transferred in a 'carder' (either in a cationic lipid envelope known as a liposome (Nat Med1995; 1:

39-46), or in an adenovirus). On trans-ferdng the gene for cystic fibrosis to the nasal epithelium using a cationic liposome, the

deficit was partly restored without provoking a local inflammatory response.

· Improvement of the hydration of secretion:

- By blocking the reabsorption of sodium from the airway lumen with amiloride. -By stimulating the secretion of chloride with

triphosphate nucleotides (ATP or

uridine triphosphate) through nucleotide receptors by a pathway independent of cylic AMP metabolism (N Engl J Med 1991;


· Immunization to various components of Pseudomonas.

What advice would you give a patient with cystic fibrosis who wishes to become pregnant?

· The couple will be offered genetic counselling and the man will be offered testing to determine his genetic status. If he is a

carrier, chorionic villous sampling will be considered as the risk of the couple conceiving an infant with cystic fibrosis is I in 2

and they may wish to consider selective termination in the first trimester. The hazards of general anaesthesia (as lung function

is impaired) for termination of pregnancy will be brought to their attention. Termination of pregnancy either with spinal

anaesthesia or medications is an alternative.

· Women with severe disease will be informed that they may be unable to complete pregnancy and that their premature demise

may leave a motherless child.

· In women with an FEVj less than 60% of the predicted value there is an increased risk of premature delivery, an increased rate

of caesarean section, some loss of lung function and risk of respiratory complications, and early death of the mother (BMJ

1995; 311: 822-3).

· Pregnancy after heart-lung transplantation offers better health and increased longevity in the mother, but the risk of organ

rejection and exposure of the fetus to potentially teratogenic immunosuppressants means that pregnancy should not be

attempted by women with transplants.

What is the 'forme fruste' of cystic fibrosis?

Increasingly, with the availability of neonatal screening with immunoreactive trypsin and thorough diagnosis by genetic studies,

milder forms of disease have been recognized without the increase in sweat sodium. It is predicted that a con-siderable number of

patients will present with a pattern of disease in adult life that has not been recognized in the past as being due to cystic fibrosis.

<;ir 1~4nnrli 14 ¥nrn,,h rnnt~mnnrnn/ I:n~/ntinn-hnrn rarcllnthnrncir ~lirnpnn nt Hnr~fi~ld Hospital, London, popularized cardiac transplantation in the UK.

The first successful pregnancy in a woman with cystic fibrosis was reported in 1960.