Respiratory - Bronchiectasis

Question 1

What is bronchiectasis?

Answer 1

Abnormal and irreversible dilation of bronchi caused by bronchial wall damage resulting from infection and inflammation.

It is now relatively uncommon in Western countries due to the decline in predisposing childhood infections, particularly whooping cough and measles, but is still important in other parts of the world and in other predisposing circumstances.

Question 2

What is the pathogenesis of bronchiectasis?

Answer 2

Bronchiectasis can be caused by a number of underlying disease processes.

Impaired mucocilliary clearance leads to accumulation of secretions and obstruction.
Bronchial obstruction leads to collapse of lung tissue by absorption of air from the distal lung. Retained mucus becomes infected and inflammation extends into the bronchial wall.

Bronchial dilation occurs as the effects of inspiratory pressures transmitted to the damaged bronchi combine with distension due to retained secretions. Irreversible dilation develops with structural, inflammatory changes and fibrosis.

Question 3

What bacteria typically causes infection in CF and bronchiectasis patients?

Answer 3

Pseudomonas aeruginosa*

*Bronchial wall damage triggers epithelial regeneration, during which cells synthesise fibronectin and integrin. These receptors are used by the outer membrane protein of bacteria such as Pseudomonas as sites of bacterial adhesion.

Question 4

What is the aetiology of bronchiectasis?

Answer 4

A number of different disease processes cause bronchiectasis:

1) Severe infection: childhood pertussis, bacterial pneumonia, recurrent aspiration pneumonia, TB
2) Bronchial obstruction: foreign body, bronchial carcinoma, lymph node enlargement
3) Immunodeficient states: hypogammaglobulinaemia, immunodeficiency as a result of lymphoma, HIV
4) Allergic bronchopulmonary aspergillosis: CF, ciliary dysfunction, primary ciliary dyskinesia, Kartagener’s syndrome
5) Associated diseases: UC, RA

Question 5

What infections are associated with bronchiectasis?

Answer 5

Severe infections are one of the most common causes of bronchial wall damage and bronchiectasis.

In childhood, pertussis or measles are important causes (but these are declining as a result of vaccination). In adults, bronchiectasis can complicate necrotising pneumonia resulting from virulent organisms such as Strep pneumoniae, Staph aureus or Klebsiella pneumoniae.

TB is another important cause.

Question 6

How does bronchial obstruction cause bronchiectasis?

Answer 6

Bronchiectasis may develop in an area of lung obstructed by bronchial carcinoma. In children, inhalation of a foreign body may give rise to bronchial obstruction and distal bronchiectasis.

Lymph node enlargement as part of TB may compress a bronchus and give rise to bronchiectasis. This particularly occurs in the middle lobe.

Question 7

How do immunodeficiency states cause bronchiectasis?

Answer 7

Patients with congenital hypogammaglobulinaemia or selective immunoglobulin deficiencies usually present with recurrent respiratory tract infections in childhood. Sometimes the diagnosis is not established until adulthood when bronchiectasis may have developed.

Immunodeficiency may also arise secondary to malignancy such as lymphoma or myeloma. Patients with HIV are particularly susceptible to recurrent bacterial infections and bronchiectasis, and HIV testing should be offered where appropriate.

Question 8

What immunological investigations should patients with bronchiectasis receive?

Answer 8

Low levels of immunoglobulin predispose to recurrent chest infections which can cause bronchial wall damage and predispose to bronchiectasis.

All patients with bronchiectasis should have measurement of IgG, IgA and IgM globulins with serum electrophoresis. Baseline specific antibody levels to tetanus toxin and capsular polysaccharide of Strep pneumoniae and Haemophilus influenza type b should also be measured.

Question 9

What is the link between allergic bronchopulmonary aspergillosis and bronchiectasis?

Answer 9

Aspergillus fumigatus is an opportunistic fungi associated with a number of respiratory conditions (e.g. asthma, invasive aspergillosis (pneumonia), aspergilloma etc).

Allergic bronchopulmonary asperillgosis is intense bronchial inflammation with eosinophilia and high IgE levels in the blood. Eosinophilic infiltrates in the lung give rise to fleeting X ray shadows. Thick mucus plugs cause obstruction of small bronchi and give rise to bronchiectasis that is usually proximal.

Question 10

What is primary ciliary dyskinesia?

Answer 10

This is an autosomal recessive condition in which there is an abnormality in the ultrastructure of cilia throughout the body such that they do not beat in a coordinated fashion.

In the respiratory tract failure of ciliary function gives rise to otitis, sinusitis, and bronchiectasis. The tail of sperm is also a ciliary structure and males are subfertile.

Failure of ciliary function results in random organ rotation during embryonic development with about 50% of patients having dextrocardia or situs inversus. Ciliary dyskinesia + situs inversus = Kartagener’s syndrome.

Question 11

How is ciliary function investigated?

Answer 11

An estimate of ciliary function can be estimated by timing the nasal clearance of saccharin. This test is difficult to perform and a simple cold can disrupt ciliary clearance for up to 6 wks.

Patients with primary ciliary dyskinesia have low exhaled levels of NO. In men, sperm motility can be assessed by microscopy of seminal fluid.

Definitive diagnosis requires brush biopsy of nasal mucosa.

Question 12

In what group of patients with bronchiectatic symptoms should cystic fibrosis be investigated?

Answer 12

CF usually presents in early childhood with recurrent respiratory infections and failure to thrive due to pancreatic insufficiency. Most patients are detected by newborn screening. But there are 1700 CF genes and the clinical spectrum of the disease has been extended to include patients with less severe lung disease and normal pancreatic function. Some of these patients present with bronchiectasis in adulthood.

So, all children and adults up to the age of 40 should have sweat tests and gene analysis for CF.

The diagnosis of CF should also be considered in older patients wth persistent isolation of Staph aureus, progressive bronchiectasis or associated features of malabsorption, pancreatitis, nasal polyposis, or male infertility.

Question 13

What are the clinical features of bronchiectasis?

Answer 13

The cardinal feature of bronchiectasis is chronic cough productive of copious purulent sputum.

There is considerable variation in the severity of the disease and mild cases are often diagnosed as chronic bronchitis.

Haemoptysis is common and may occasionally be severe requiring embolisation of bronchial arteries to control bleeding.

Question 14

How are infective exacerbations of bronchiectasis characterised?

Answer 14

These may be associated with fever and pleuritic chest pain. Chronic severe bronchiectasis may also cause malaise, weight loss and halitosis (foul breath).

Coarse crackles may be audible over affected areas and clubbing is sometimes present. Systemic spread of infection (e.g. cerebral abscess) and secondary amyloidosis are now rare because of control of infection with antibiotics.

Question 15

What investigations should be performed in suspected bronchiectasis?

Answer 15

1) Sputum: MC&S
2) CXr: cystic shadows, thickened bronchial walls (tram tracks and ring shadows)
3) HRCT chest: to assess extent and distribution of disease
4) Spirometry: often shows obstructive defect, reversibility should be assessed
5) Bronchoscopy to locate site of haemoptysis, exclude obstruction and obtain samples for culture
6) Others: serum Ig; CF sweat test; Aspergillus precipitins or skin prick test

Question 16

What are the chest X-ray features of bronchiectasis?

Answer 16

The CXR can appear normal or non specific in mild to moderate bronchiectasis. HRCT is the more sensitive and gold standard.

CXR does however help to identify serious disease and therefore remains the first line investigation for suspicious symptoms such as persistant cough, profuse purulent sputum, and recurrent infection.

Characteristic X ray features include: ring opacities, tram tracks, cystic spaces, vascular crowding

• ring opacities: end-on bronchi with thickened walls appear as circular light grey densities with black centres, resembling “rings”
• tram tracks: side on dilated bronchi with thickened walls appear
• cystic spaces: these occur in cystic bronchiectasis
• crowding of pulmonary vascular markings: mucous obstruction of peripheral bronchi can cause atelectasis. The loss of lung volume brings the vascular markings closer together

Question 17

What are the HRCT features of bronchiectasis?

Answer 17

Dilated airways: airways larger than their accompanying vessels with a “signet ring” appearance and grape like clusters in more severely affected airways

Bronchial wall thickening.

Question 18

Describe an approach to the management of bronchiectasis?

Answer 18

1) Postural drainage: should be performed twice daily; physiotherapy may help with sputum expectoration and mucous drainage
2) Antibiotics: should be prescribed according to bacterial sensitivities. Patients known to culture Pseudomonas will require either oral ciprofloxacin or IV antibiotics; if > 3 exacerbations per year then consider long term antibiotics
3) Bronchodilators and inhaled steroids: (e.g. salbutamol and beclametasone, budesonide, fluticasone) may be useful in patients who demonstrate reversible airflow obstruction
4) Surgery: may be considered in localised disease or to control severe haemoptysis

Question 19

What is cystic fibrosis? What causes it?

Answer 19

This is a multisystem disease resulting from mutations (over 800) of a gene that codes for a chloride channel on epithelial membranes.

Specifically, CF is autosomal recessive and is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene on chromosome 7. This is a Cl- channel and the defect leads to a combination of defective chloride secretion and increased sodium absorption across airway epithelium. The changes in the composition of airway surface liquid predispose the lung to chronic pulmonary infections and bronchiectasis.

Question 20

How does the CF mutation affect the lungs?

Answer 20

In the bronchial mucosa, reduced chloride secretion and increased sodium reabsorption results in secretions of abnormal viscosity with reduced water content of the airway surface liquid. This disrupts mucociliary clearance and increases susceptibility to infections and inflammation.

Question 21

How does the CF mutation affect the gastrointestinal tract?

Answer 21

Pancreas: abnormal ion transport results in the plugging and obstruction of ductules with progressive destruction of the gland
- pancreatic enzymes fail to reach the intestine and this results in malabsorption of fats with steatorrhea and failure to gain weight.

• progressive destruction of the endocrine pancreas may cause diabetes

Gall bladder: abnormalities of bile secretion and absorption cause an increased incidence of gallstones and biliary cirrhosis

Intestine: sludging and desiccation of intestinal contents probably accounts for the occurence of meconium ileus (neonatal intestinal obstruction) and for the development of distal intestinal obstruction syndrome in older children and adults

Question 22

What are the clinical features of CF in neonates?

Answer 22

• failure to thrive
• meconium ileus
• rectal prolapse

Question 23

What are the clinical features of CF in children and young adults?

Answer 23

CF is a multisystem disease, some features are as follows:
1) Respiratory: cough; wheeze*; recurrent infections; bronchiectasis; pneumothorax; haemoptysis; respiratory failure; cor pulmonale

2) GIT: pancreatic insufficiency (DM, steatorrhoea); distal intestinal obstruction syndrome (meconium ileus equivalent); gallstones; cirrhosis
3) Other: male infertility; osteoporosis; arthritis; vasculitis; nasal polyps; HPOA

Signs on examination: cyanosis; finger clubbing; bilateral coarse crackles

*Progressive lung damage is associated with progressive airways obstruction. Cycle of infection and inflammation causes worsening lung damage with deteriorating airways obstruction and impairment of gas exchange

Question 24

How is CF diagnosed?

Answer 24

1) Sweat test: sweat sodium and chloride >60mmol/L; chloride usually > sodium
2) Genetics: screening for known common CF mutations should be considered
3) Faecal elastase: simple and useful screening test for exocrine pancreatic dysfunction

Question 25

How should CF be managed?

Answer 25

CF is best managed in a multidisciplinary team.
1) Chest: regular physio; antibiotics for infective exacerbations and prophylactically (PO or nebulised); mucolytics can be useful (e.g. DNase i.e. Dornase alfa 2.5mg daily nebulized); bronchodilators

2) GIT: pancreatic enzyme replacement; fat soluble vitamin supplements (A,D,E,K); ursodeoxycholic acid for impaired liver function
3) Other: treatment of CF related diabetes; screening for osteoporosis; fertility and genetic counselling; treating arthritis
4) Advanced lung disease: oxygen; diuretics; NIV; heart and lung transplantation

Question 26

What is the prognosis of CF?

Answer 26

Median survival is now approx. 40 years in the UK

Question 27

What is “cepacia syndrome”?

Answer 27

Burkholderia cepacia complex is a group of gram negative plant pathogens that cause onion rot. In the 1980s it became apparent that patients with cystic fibrosis were vulnerable to these bacteria and that infection could spread from patient to patient in an epidemic way. Especially among children with cystic fibrosis in close social contact at holiday camps for example.

The clinical course of patients with Burkholderia infection is very variable but some show an accelerated rate of decline in lung function and some develop a fulminant necrotizing pneumonia.