Bronchiectasis

Bronchiectasis is a permanent dilatation and thickening of the airways, characterised by chronic cough, excessive sputum production, bacterial colonisation, and recurrent acute infections¹. It may be widespread throughout the lungs (diffuse) or more localised (focal). It is caused by chronic inflammation of the airways, and is associated with, or caused by, a large number of diseases. It may develop after lung infections, particularly in childhood and in association with underlying problems, such as immunodeficiency and cystic fibrosis.

Bronchiectasis can be classified into the following forms morphologically (all three forms may be present in the same patient):

• Cylindrical bronchiectasis: bronchi are enlarged and cylindrical.

• Varicose bronchiectasis: bronchi are irregular with areas of dilatation and constriction.

• Saccular or cystic: dilated bronchi form clusters of cysts. This is the most severe form of bronchiectasis and is often found in patients with cystic fibrosis.

The affected airways are inflamed and easily collapse. There is an impairment of airflow and drainage of secretions, leading to the accumulation of a large amount of mucus in the lungs. The mucus collects bacteria, predisposing to frequent and often severe lower respiratory tract infections. The severity of bronchiectasis used to be classified according to the volume of sputum produced but this has now largely been superseded by using the radiological appearance on CT scan.

Epidemiology

• A large study across 640 general practices in the UK published in 2012 found²:

  • Prevalence in 2011 in men was 227/100,000, and 309/100,000 in women.

  • Incidence increased each year between 2004 and 2011, from 18/100,000 person-years at risk, to 32/100,000 person-years at risk.

  • Prevalence was higher in women than in men.

  • Prevalence was higher in the older age groups (>60 years).

• It is estimated that around 1,000 people die each year from bronchiectasis in England and Wales³.

• The incidence varies between populations from 3.7/100,000 children in New Zealand to 52/100,000 adults in the USA. Features of bronchiectasis found in CXRs in the UK in the 1950s suggested a prevalence of 100/100,000⁴.

• Bronchiectasis can present at any age but increases with age and the highest prevalence is in older women⁵. Up to 70% of cases may be in women¹⁶.

Aetiology¹⁷

The disease is caused by chronic inflammation of the airways. It may therefore be caused by a large number of disorders which cause inflammation and infection, particularly conditions that facilitate infections, which therefore tend to be recurrent and more severe and so cause damage to the lungs. Up to 42% of cases develop post-infection. However, there is no identifiable underlying cause in about 50% of adults and 25% of children⁸.

• Post-infection - eg, childhood respiratory viral infections (measles, pertussis, influenza, respiratory syncytial virus), tuberculosis, bacterial pneumonia. Infection is the most common cause.

• Immunodeficiency, including HIV infection. Accounts for around 1-8% of cases. Always consider this as a cause in all ages, particularly if there have been serious, persistent or recurrent infections, or if with unusual or opportunist pathogens, or occurring at multiple sites⁴.

• Connective tissue diseases (3-6%) - eg, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, systemic lupus erythematosus (SLE), Ehlers-Danlos syndrome, Marfan's syndrome.

• Asthma.

• Allergic bronchopulmonary aspergillosis (1-7%).

• Gastric aspiration (up to 4%)

• Congenital defects. Genetic causes include cystic fibrosis (3-4%), Kartagener's syndrome (primary ciliary dyskinesia), alpha-1-antitrypsin deficiency, yellow nail syndrome.

• Bronchial obstruction by lymphadenopathy, tumour or inhaled foreign bodies.

• Inflammatory bowel disease.

Bronchial obstruction and bronchopneumonia are more likely to cause a focal bronchiectasis, whereas the other causes are more likely to result in diffuse disease. All conditions cause dilation of the airways (due to continued inflammation destroying their elastic and muscular structure) followed by poor mucus clearance, and bacterial colonisation of collected mucus. This then can progress, as chronic infection causes further inflammation in a cyclical fashion.

Smoking does not appear to be an independent risk factor but smoking cessation is important if the patient does smoke.

Presentation⁴

• The symptoms vary from intermittent episodes of expectoration and infection localised to the region of the affected lung to persistent daily expectoration of large volumes of purulent sputum.

• There may be associated nonspecific respiratory symptoms including dyspnoea, chest pain and haemoptysis. Bronchiectasis may progress to respiratory failure and cor pulmonale.

• Signs:

  • Coarse crackles are the most common finding in around 70%, heard in early inspiration and often in the lower zones. Area of crackles on auscultation corresponds poorly with localisation of bronchiectasis radiologically.

  • Large airway rhonchi are present in 44% (low-pitched snore-like sounds)¹.

  • Wheeze may be present in 34%.

  • Clubbing is found infrequently.

• All causes of bronchiectasis should be considered and assessed as appropriate.

Children

• Respiratory symptoms, especially cough and sputum production, should be assessed and recorded in all children with possible bronchiectasis.

• There should be a high index of suspicion for diagnosing bronchiectasis in children with chronic respiratory symptoms.

• Persistent lung crackles on auscultation indicate possible underlying bronchiectasis.

• Children should be assessed for bronchiectasis if they present with:
  

  • Chronic moist/productive cough, especially between viral colds or with positive bacterial cultures.

  • Asthma that does not respond to treatment.

  • A child with chronic respiratory symptoms and a single positive sputum culture for Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa, non-tuberculous mycobacteria or Burkholderia cepacia complex.

  • An episode of severe pneumonia, especially if there is incomplete resolution of symptoms, physical signs or radiological changes.

  • Pertussis-like illness failing to resolve after six months.

  • Recurrent pneumonia.

  • Persistent and unexplained physical signs or abnormalities on CXR.

  • Localised chronic bronchial obstruction.

  • Respiratory symptoms in children with structural or functional disorders of the oesophagus and upper respiratory tract.

  • Unexplained haemoptysis.

  • Respiratory symptoms with any clinical features of cystic fibrosis, primary ciliary dyskinesia or immunodeficiency.

Adult

• Assessment of symptoms in patients with bronchiectasis should include a record of both sputum purulence and estimated or measured 24-hour sputum volume when clinically stable.

• The number of infective exacerbations per annum should be noted including frequency and nature of antibiotic usage.

• Adults should be assessed for bronchiectasis if they present with:
  

  • Persistent productive cough, especially if any one of the following:
    

    • Young age at presentation.

    • History of symptoms over many years.

    • Absence of smoking history.

    • Daily expectoration of large volumes of very purulent sputum.

    • Haemoptysis.

    • Sputum colonisation with P. aeruginosa.

  • Unexplained haemoptysis or nonproductive cough.

  • Patients thought to have chronic obstructive pulmonary disease (COPD) may have bronchiectasis alone or as well as COPD and referral for investigation is appropriate if:
    

    • Management is not straightforward.

    • There is slow recovery from lower respiratory tract infections.

    • There are recurrent exacerbations.

    • There is no history of smoking.

Investigations¹⁴

Investigations are directed at identifying any underlying cause and to establish the severity of disease. In primary care, CXR is the main investigation, followed by referral to secondary care for confirmation by high-resolution computed tomography (HRCT), and then tests aimed at identifying a possible cause.

• Radiological investigations:
  

  • CXR: a baseline CXR should be done in all patients. Repeat CXRs need only be done if clinically indicated. CXR may be normal or show ring or tubular opacities, tramlines and fluid levels. CXR is abnormal in 90% of people with bronchiectasis, but there is not usually a diagnostic pattern. The main value is excluding other causes of symptoms.

  • The gold standard for diagnosis is HRCT of the chest. HRCT has a very high sensitivity and specificity for diagnosis and has now replaced bronchography.

  • HRCT features of bronchiectasis: bronchial wall dilation (internal lumen diameter greater than accompanying pulmonary artery or lack of tapering) is the characteristic feature; bronchial wall thickening is often also present although harder to define.

  • The severity of bronchiectasis on HRCT correlates with measures of airflow obstruction.

  • Routine repeat CXR or HRCT is not necessary; repeat imaging should be considered when there is clinical need. In cases of humoral immune deficiency, repeating HRCT at intervals may be necessary to detect asymptomatic progression.

• Sputum microbiology:
  

  • All children and adults with bronchiectasis should have an assessment of lower respiratory tract microbiology.

  • Respiratory tract specimens should be obtained in all patients with bronchiectasis. To maximise the chances of isolating H. influenzae and S. pneumoniae, specimens should reach the microbiology laboratory within three hours.

  • Persistent isolation of S. aureus (and/or P. aeruginosa in children) should lead to consideration of underlying bronchopulmonary aspergillosis or cystic fibrosis.

• Routine blood tests are nonspecific but may confirm the presence of infection or presence of any comorbidity. FBC may show raised white cell count (infection) or polycythaemia (in advanced cases).

• Immune function tests: the following should be measured in all patients:
  

  • Serum immunoglobulins (IgG, IgA, IgM) and serum electrophoresis.

  • Serum IgE, skin prick testing or serum IgE testing to Aspergillus fumigatus and aspergillosis precipitins.

  • All patients with bronchiectasis should be screened at presentation for gross antibody deficiency by routine measurement of serum IgG, IgA and IgM levels and serum electrophoresis.

  • Respiratory and immunology units should develop additional local protocols for screening assessment of humoral responses to specific antigens.

  • Measurement of baseline specific antibody levels against tetanus toxoid and the capsular polysaccharides of both S. pneumoniae and H. influenzae type b (or suitable alternative peptide and polysaccharide antigens).

  • Immunisation with appropriate vaccines followed by re-assay of individual specific antibody responses after 21 days where screening baseline levels are low.

• Further assessment of immune competence is recommended in the following circumstances:
  

  • Antibody screening investigations have demonstrated the presence of an antibody deficiency disorder.

  • In the presence of normal antibody screening test results where the following are present:
    

    • Clinical suspicion of immune deficiency (short stature, facial abnormality, cardiac lesions, hypocalcaemia, cleft palate, oculocutaneous telangiectasias, eczema, dermatitis, petechiae, manifestations of endocrinopathy, unexplained failure to thrive, enlargement or absence of lymphoid tissues, unexplained organomegaly, unexplained joint symptoms).

    • A family history of known or suspected immune deficiency.

    • Infections which are serious, involving a threat to life, or tissue destruction or which require/have required surgical intervention (eg, lobectomy, tonsillectomy, insertion of grommets, incision of boils), are persistent or recurrent despite multiple or prolonged courses of antibiotics, involve unusual/opportunistic micro-organisms or involve multiple sites (eg, sinuses or middle ear in addition to the bronchial tree).

• Gastrointestinal investigations:
  

  • There should be a low threshold for gastrointestinal investigations in children.

  • Gastric aspiration should be considered in patients following lung transplantation.

  • 24-hour pH monitoring for those suspected of having bronchiectasis secondary to gastrointestinal reflux or aspiration.

• Cystic fibrosis: all children and all adults up to the age of 40, presenting with bronchiectasis, should have investigations for cystic fibrosis.

• Tests for ciliary function:
  

  • Ciliary investigations should be considered in children with bronchiectasis when there is:
    

    • No other cause for bronchiectasis identified.

    • A history of continuous rhinitis since the neonatal period.

    • A history of neonatal respiratory distress.

    • Dextrocardia.

  • Ciliary investigations should be considered in adults only if there is a history of chronic upper respiratory tract problems or otitis media. Factors favouring investigation include:
    

    • Problems since childhood.

    • Childhood chronic otitis media.

    • Predominantly middle lobe bronchiectasis.

    • Infertility or dextrocardia.

  • For adults, the saccharin test and/or exhaled nasal nitric oxide (NO) may be used to screen out those not requiring detailed ciliary function tests⁹.

• Lung function tests:
  

  • In all children who are old enough (usually aged >5 years) forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and forced expiratory flow (FEF) 25-75% should be measured at initial assessment.

  • All adults with bronchiectasis should have measures of FEV1, FVC and peak expiratory flow (PEF).

  • Repeat assessment of FEV1, FVC and PEF should be made at least annually in those patients attending secondary care.

  • Patients with immune deficiency or primary ciliary dyskinesia should have measurements of FEV1, and FVC at least four times each year.

  • Measurement of lung volumes and gas transfer coefficient may help in the identification of other causes of airflow obstruction such as COPD or emphysema.

  • Reversibility testing may identify improvement in lung function after bronchodilators and should always be considered if airflow obstruction is identified, especially in young people.

  • Exercise tests have a role in investigating children in whom symptoms are out of keeping with lung function or HRCT measurements. In adults, exercise testing should be part of a pulmonary rehabilitation programme.

  • FEV1 and FVC should be measured before and after intravenous antibiotic therapy, as this may give objective evidence of improvement.

  • Spirometry and lung volumes should be measured in all patients before and after commencing long-term oral or nebulised antibiotic therapy.

• Bronchoscopy:
  

  • In children, bronchoscopy is indicated when bronchiectasis affects a single lobe, to exclude a foreign body. In some acutely ill patients it may achieve a useful microbiological result.

  • In adults with localised disease, bronchoscopy may be indicated to exclude proximal obstruction.

  • In adults, bronchoscopy and bronchoscopic sampling of the lower respiratory tract do not have a place in the routine investigation of patients with bronchiectasis.

  • For patients in whom serial testing of sputum does not yield microbiological information and who are not responding well to treatment, bronchoscopic sampling of lower respiratory tract secretions may be indicated.

  • Bronchoscopy is indicated if HRCT suggests atypical mycobacterial infection and sputum culture is negative.

  • Cytological examination of bronchoscopic specimens can provide evidence supporting gastric aspiration.

Differential diagnosis¹

• COPD.

• Asthma.

• Tuberculosis.

• Chronic sinusitis.

• Upper airway cough syndrome (postnasal drip).

• Cough due to gastrointestinal reflux.

• Pneumonia.

• Pulmonary fibrosis.

• Cancer of the lung.

• Inhaled foreign body.

Management⁴

Damaged lung cannot be repaired and so the basis of management is to prevent or at least slow down further deterioration. Management includes treatment of any underlying cause and any co-existing medical problems. Patients who should have regular follow-up in secondary care include:

• All children with bronchiectasis

• Patients with chronic P. aeruginosa, opportunistic mycobacteria or meticillin-resistant S. aureus (MRSA) colonisation.

• Deteriorating bronchiectasis with declining lung function.

• Recurrent exacerbations (three or more per year).

• Patients receiving prophylactic antibiotic therapy (oral or nebulised).

• Patients with bronchiectasis and associated rheumatoid arthritis, immune deficiency inflammatory bowel disease and primary ciliary dyskinesia.

• Patients with bronchopulmonary aspergillosis.

• Patients with advanced disease and those considering transplantation.

General management issues

• Maintain a healthy diet and physical exercise; ensure adequate energy intake to provide for increased energy demands.

• If the patient smokes this must be stopped and smoking cessation advice and help should be offered. Passive smoking should also be avoided.

• Immunisation against influenza and pneumococcus¹⁰¹¹.

Physiotherapy: airway clearance techniques and exercise

• All patients should be referred to a physiotherapist to be taught the airway clearance techniques available and, where possible, be encouraged to be independent with the chosen airway clearance technique. This should then be used on a daily basis for those with chronic productive cough, and on an intermittent basis for those with productive cough during exacerbations.

• A Cochrane review concluded more studies are needed to determine efficacy of different techniques in different situations¹².

• Modified gravity-assisted positions (no head-down tilt) should be offered where the conventional tipped position is contra-indicated or unacceptable to the patient.

• During an acute exacerbation or when the patient is more fatigued than usual, manual techniques may be offered as a part of an airway clearance technique regimen.

• Sterile water inhalation may be used before airway clearance to facilitate clearance. The use of nebulised normal or hypertonic saline prior to airway clearance could be considered to increase sputum yield, reduce sputum viscosity and improve ease of expectoration.

• Inhaled beta-2 agonists should be used prior to treatment to enhance sputum clearance.

• Non-invasive ventilation or intermittent positive pressure breathing may be used to augment tidal volume and reduce the work of breathing in those patients who are becoming fatigued and finding their standard airway clearance difficult.

• Pulmonary rehabilitation should be offered to individuals who have breathlessness affecting their activities of daily living.

Antibiotics for acute exacerbations¹³

An acute exacerbation of bronchiectasis is a sustained worsening of symptoms from a person's stable state.People with bronchiectasis should be educated so they know how to recognise an acute exacerbation. Signs to look out for include¹:

• Acute deterioration over a few days.

• Worsening cough.

• Increased sputum volume, viscosity or purulence.

• Increased wheeze, breathlessness or haemoptysis.

• Feeling systemically unwell.

If a person has an acute exacerbation:

• Send a sputum sample for culture and susceptibility testing.

• Offer an initial antibiotic based on the severity of symptoms, previous exacerbation and hospital admissions, the risk of developing complications, and previous sputum culture and susceptibility results.

• First-choice oral antibiotics for empirical treatment are amoxicillin, doxycycline or clarithromycin.

• The European Medicines Agency's Pharmacovigilance Risk Assessment Committee has recommended restricting the use of fluoroquinolone antibiotics following a review of disabling and potentially long-lasting side-effects, mainly involving muscles, tendons, bones and the nervous system. This includes a recommendation not to use them for mild or moderately severe infections unless other antibiotics cannot be used¹⁴.

• Review the choice of antibiotic when the results of sputum culture and susceptibility testing are available.

• Refer to hospital if there are any symptoms or signs suggesting a more serious illness or condition.

• Seek specialist advice if symptoms that are not improving with repeated courses of antibiotic treatment, the bacteria are resistant to oral antibiotics, or if the person cannot take oral medicines (in which case consider intravenous antibiotics at home or in the community, rather than in hospital, if appropriate).

Long-term antibiotics

• Patients having three or more exacerbations per year requiring antibiotic therapy or patients with fewer exacerbations that are causing significant morbidity should be considered for long-term antibiotics. Choice will be dictated by sensitivities and local microbiology advice from sputum test results.

• In the first instance, high doses should not be used, in order to minimise side-effects.

• The antibiotic regimen should be determined by sputum microbiology when clinically stable.

• Long-term antibiotics may result in antibiotic resistance in individual patients and alternative antibiotics should be chosen depending on sensitivity results.

• Some patients may respond to antibiotic treatment despite resistance to that drug in vitro. Antibiotics should only be changed if there is no clinical response.

Other drug treatment

• Bronchodilators: it is appropriate to assess patients with airflow obstruction for reversibility to beta-2 agonist and anticholinergic bronchodilators and to start treatment if lung function or symptoms improve on therapy.

• Likewise, theophylline and aminophylline are occasionally used if a trial of therapy has demonstrated improvement.

• The following are NOT recommended for bronchiectasis¹:

  • Corticosteroids - inhaled or oral - unless there is co-existent asthma.

  • Mucolytics.

  • Leukotriene receptor antagonists.

• Oxygen therapy:
  

  • The use of oxygen therapy may need to be considered.

  • Non-invasive ventilation can improve quality of life in some patients with chronic respiratory failure due to bronchiectasis.

Surgery

• Lung resection surgery may be considered in patients with localised disease in whom symptoms are not controlled by medical treatment¹⁵.

• Bronchial artery embolisation and/or surgery are first-line therapy for the management of massive haemoptysis.

• Lung transplantation may need to be considered for end-stage disease if pulmonary function is very poor with FEV1 below 30% of predicted.

Complications¹

• Repeated infection and deteriorating lung function.

• Empyema.

• Lung abscess.

• Pneumothorax from repeated coughing.

• Life-threatening haemoptysis.

• Respiratory failure.

• Right heart failure secondary to chronic respiratory disease.

• Amyloidosis (rare).

• Reduced quality of life - fatigue, embarrassment, anxiety and depression, urinary incontinence caused by cough.

Prognosis

• Before antibiotics, death would occur within five years but now, with aggressive therapy, the outcome is much better. However, there continues to be a significant reduction in life expectancy in patients with bronchiectasis⁴.

• 10% of adults with non-CF bronchiectasis die within 5-8 years of diagnosis, with the cause of death being respiratory in over half of those¹⁶¹⁷.

• Good nutrition to maintain an ideal body weight and regular vaccination correlate with improved survival¹⁸.

• Hypoxaemia, hypercapnia, degree of dyspnoea, and radiological extent of disease are closely correlated with mortality¹⁸.

• Chronic colonisation by P. aeruginosa, severe exacerbations, and systemic inflammation (raised C-reactive protein) are associated with disease progression in non-CF bronchiectasis¹⁹.