Cystic fibrosis

Published on 05/05/2015 by admin

Filed under Internal Medicine

Last modified 22/04/2025

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105 Cystic fibrosis

Instruction

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

Salient features

History

• Cough with purulent and viscous expectoration

• Diabetes mellitus

• GI symptoms (steatorrhoea, failure to thrive in childhood, rectal prolapse, meconium ileus or distal intestinal obstruction)

• Heat stroke, salt depletion

• Sterility in men and decreased fertility in women.

Examination

• 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:

• Urine sugar
• Faecal fat
• Sweat sodium.

Remember: Cystic fibrosis is defined as the presence of a coherent clinical syndrome, plus either evidence of cystic fibrosis transmembrane conductor regulator (CFTR) dysfunction (an abnormal value for sweat chloride or nasal potential difference) or confirmation of cystic fibrosis-causing mutations on both alleles.

Diagnosis

This patient has bilateral coarse crackles, asthenia and foul fatty stool (lesion) caused by cystic fibrosis (aetiology) and requires continuous oxygen, indicating respiratory failure (functional status).

Questions

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

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

What are the clinical manifestations of this condition?

• Neonates: recurrent chest infections, failure to thrive, meconium ileus and rectal prolapse

• In childhood and young adults:

• Respiratory: infection, bronchiectasis (Fig. 105.1), pneumothorax, haemoptysis, nasal polyps, allergic bronchopulmonary aspergillosis, deterioration during and after pregnancy
• Cardiovascular: cor pulmonale. (see Fig. 102.1)
• GI: rectal prolapse, distal ileal obstruction (meconium ileus equivalent), cirrhosis, gallstones, intussusception
• Miscellaneous: male infertility, diabetes mellitus, hypertrophic pulmonary osteoarthropathy.
image

Fig. 105.1 Cystic fibrosis. There is slight overinflation and multiple thin-walled ring shadows in the right lung and the upper part of the left lung, reflecting cystic bronchiectasis. Some ring shadows contain air–fluid levels.

(With permission from Adam et al. 2008.)

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 shown to be useful, but there is 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.

Advanced-level questions

What is the inheritance in cystic fibrosis?

Autosomal recessive. On the long arm of chromosome 7 resides the gene encoding CFTR, a protein of 1480 residues that acts as a cyclic AMP-regulated chloride channel. This gene is carried by 1 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 (Δ508). This defect leads to a failure of the chloride channel to open in response to cyclic AMP. More than 175 other lesions in the cystic fibrosis gene are responsible for the disease in the remaining 30% of patients.

How is this condition diagnosed in infancy?

Immunoreactive trypsin (IRT) assay in dried blood in neonates. A very high IRT concentration suggests pancreatic injury consistent with (but not specific for) cystic fibrosis. This assay is useful for screening rather than diagnosis. Infants who have a high IRT concentration on initial testing undergo further assessment via a repeat IRT 1–3 weeks later (IRT/IRT), or by analysis of the initial blood spot for a specified group of CFTR mutations (IRT/DNA).

What do you know about sweat testing?

A sweat sodium concentration >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 electrochemical gradient from the cytoplasm to the lumen. In patients with cystic fibrosis, there is a defect in these channels that prevents this normal secretion. Simultaneously, there is a three-fold increase in the reabsorption 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 responsible?

Staphylococcus aureus, Haemophilus influenzae, Burkholderia cepacia and Pseudomonas aeruginosa. The last is associated with poor prognosis as this organism is almost impossible to eradicate.

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. Persistent or unexplained GI symptoms in these patients should be investigated carefully.

What is the lifespan in such patients?

The median age of survival is currently in the late 30s. It is possible that a child born today will have a median survival into the 50s.

What is the cause of death in cystic fibrosis?

Death occurs from pulmonary complications, such as pneumonia, pneumothorax or haemoptysis, or from 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 FEV1 is <30%. Thus the necessity for referral for transplantation can be anticipated about 1 year in advance of death.

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.

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 spillover of infected material from the recipient’s remaining lung.

What are the complications of lung transplantation?

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

What are the indications for a combined heart–lung transplantation?

The combined heart–lung transplantation has relatively few indications, the primary one being congenital heart disease with Eisenmenger syndrome.

What are the new methods of treatment available for cystic fibrosis?

• High-dose ibuprofen in patients with mild disease (FEV1 of at least 60% of the predicted value), taken consistently for 4 years, significantly slows the progression of lung disease without serious adverse effects.

• Aerosolized recombinant human DNAse (dornase-alpha), which is capable of degrading DNA in the bronchial secretion, has been shown to improve FEV1 by 20% when given by aerosol.

• Gene therapy: the gene is transferred in a ‘carrier’ (either in a cationic lipid envelope known as a liposome, or in an adenovirus). On transferring the gene for cystic fibrosis to the nasal epithelium using a cationic liposome, the deficit has been partly removed without provoking a local inflammatory response.

• Inhalation of hypertonic saline produces a sustained acceleration of mucus clearance and improved lung function. This treatment may protect the lung from insults that reduce mucus clearance and produce lung disease.

• Improvement of the hydration of secretion by:

• blocking the reabsorption of sodium from the airway lumen with amiloride
• stimulating the secretion of chloride with triphosphate nucleotides (of adenosine or uridine) through nucleotide receptors by a pathway independent of cylic AMP metabolism.

• 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 1 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 FEV1 <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.

• 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 considerable number will present with a pattern of disease in adult life that has not been recognized in the past as being caused by cystic fibrosis.

Quinton established that sweat ducts are impermeable to chloride in 1986.

Sir Magdi H Yacoub, contemporary Egyptian-born cardiothoracic surgeon, popularized cardiac transplantation in the UK at Harefield Hospital, London.

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

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