Cystic Fibrosis And
Bronchiectasis
Cystic fibrosis (CF) is the primary cause of severe chronic lung
disease in children, although 90% of children now survive into their second
decade (Fig. 34a). CF is characterized by chronic bronchopulmonary infection
and airway obstruction (Fig. 34b) and by exocrine pancreatic
insufficiency with consequent effects on gut function, nutrition and
development. The key feature of CF is increased viscosity and subsequent
stasis of epithelial mucus. There is usually an increased salt content
of sweat. Figure 34c shows some associated disorders.
CF is an autosomal recessive trait that
is the most common genetic cause of morbidity and mortality in the white
population, with a prevalence of approximately 1 in 2000 live births; nearly 5%
of white people of European descent are heterozygous carriers. Prevalence is
far less in others, being approximately 1 in 17 000 for those of African
descent. CF is due to mutations in a gene on chromosome 7 encoding for the cystic
fibrosis transmembrane conductance regulator (CFTR), a cyclic adenosine
monophosphate (cAMP)-regulated epithelial chloride channel that can also alter
activity of other ionic transporters. Dysfunction of CFTR impairs epithelial
chloride, sodium and water transfer and thus causes reduced mucus hydration and
increased viscosity (Chapter 18). Over 800 mutations in the CFTR gene
have been described, but the most common, found in approximately 65% of
patients with CF, is deletion of the phenylalanine codon at position 508, the .6F508
mutation.
Clinical features
The lungs of neonates with CF are
often normal, but rapid development of respiratory symptoms, including
refractory cough and infections, is usual. CF patients nearly always have an
increased lung volume and finger clubbing (increased curvature of the
nail and loss of normal angle between nail and nail bed) (Chapter 19).
Recurrent bronchopulmonary infections, primarily as a result of defective mucus
clearance, are rarely cleared once established and eventually result in bronchiectasis
(see below), extensive lung damage and dysfunction. Spontaneous pneumothorax
(Chapter 35) and haemoptysis (spitting blood; Chapter 45) are not
uncommon. About 10% of neonates present with meconium ileus (failure to pass
meconium), which can cause death in the firs day of life; 20% of older patients
exhibit a similar ileal obstruction (meconium ileus equivalent, MIE).
Eighty-five percent of patients have steatorrhoea (high fat stools) as a result
of pancreatic insuff ciency. Some patients have only mild respiratory symptoms
for many years, but this is inevitably followed by a characteristic increase in
the frequency and severity of periods of exacerbation of symptoms (cough,
dyspnoea, loss of appetite). Eventually, severe restrictions in activity herald
the end-stage disease, followed by respiratory failure, hypoxaemia, pulmonary
hypertension and death.
Diagnosis
Several factors need to be taken into
account, including a family history of the disease and the presence of
typical respiratory and gastrointestinal disorders (Fig. 34c). A sweat
chloride or sodium concentration above 60 mmol/L is diagnostic when
coupled with such disorders, although approximately 1% of CF patients may have
normal sweat electrolytes. DNA analysis can detect known mutations (e.g. .6F508),
but is limited by the high number of unknown mutations. In later disease, chest
X-rays can detect bronchiectasis (see below). Neonates can be screened for CF
by blood immunoreactive trypsin, which can detect many, but not all cases.
Management
The primary objectives of treatment
are to control infection, promote mucus clearance and improve
nutrition. Early antibiotic therapy is crucial to inhibit progression of
the disease. Choice of antibiotic is determined following identificatio of
infecting organisms. The dosage should be higher in CF patients and the course
longer. Development of resistance is a key problem and is transferable;
segregation of patients is thus advisable. Adequate immunization for measles,
pertussis and influenz is important, as these organisms are particularly
dangerous in CF.
Clearance: Training by physiotherapists in postural drainage
(tip-ping the body so that the infected lobe is uppermost) is vital, coupled
with chest percussion to mobilize secretions to the upper airways where they
can be coughed up. Such treatment is prescribed one to four times a day.
Recently introduced therapies include inhalation of DNase, an enzyme that
breaks down DNA from dead cells, which contributes to mucus viscosity.
Inhalation of aerosolized saline may improve mucus hydration, as may blockade
of sodium reabsorption with amiloride or stimulation of chloride secretion with
nucleotide triphosphates. Cough should never be suppressed, as it is an
important method of clearance. Other therapies: Bronchodilators
(β-agonists) may improve lung function, and corticosteroids may assist
inflammatio in some patients. A potential therapy under intense investigation
is gene transfer of the normal CFTR gene. In end-stage respiratory disease, a
lung transplant should be considered.
Nutrition: Most patients with CF require pancreatic enzymes
with meals, supplemented with vitamins. High-calorifi foods should be advised.
Bronchiectasis
Bronchiectasis is an abnormal and permanent dilatation of
proximal (>2 mm) bronchi due to inflammatio and subsequent
destruction of the elastic and muscular components of their walls (Chapter 44).
It is normally associated with defects in mucociliary clearance (Chapter
18) and persistent respiratory infections. Onset is often in childhood,
following pulmonary infections complicating measles or pertussis. Since the
introduction of antibiotics, the most common cause of bronchiectasis is now CF (Fig.
34d), except in poorly resourced countries. Symptoms depend on the severity and
location of diseased bronchi, but commonly include persistent productive cough,
with large quantities of foul-smelling purulent sputum as the disease worsens.
Severity has been correlated with the volume of sputum produced, but not with
dyspnoea. Haemoptysis and recurrent pneumonia or abscesses are common;
haemoptysis is normally mild, but can become life-threatening, particularly in
CF patients. Fever, anaemia and weight loss may accompany the disease. Patients
often develop f nger clubbing, metastatic abscesses, respiratory failure and
amyloidosis. Chest X-rays and high-resolution computed tomography (HRCT) can
often detect the dilated and thickened bronchi (Chapter 45). Management is
similar to that for CF, although without the nutritional uirements.
