Bronchiectasis
Case Study
A 56 year old man was referred for respiratory assessment. He had been diagnosed with Chronic Obstructive Pulmonary Disease (COPD) previously. Despite therapy with inhaled long acting bronchodilators and steroids he was increasingly symptomatic. He was suffering six infective exacerbations per year requiring oral steroids and antibiotics. He was breathless on exertion.
On questioning his symptoms began 14 years previously. He had never smoked. He reported producing 25 mls of purulent sputum daily between exacerbations. He suffered measles and pertussis infections as a child.
Lung function testing showed mild obstruction with an FEV1 measured at 70% of predicted. Chest x-ray showed basal atelectasis. High Resolution CT scanning of chest showed bronchial wall thickening and dilation with the presence of “signet ring” changes. Sputum culture identified Pseudomonas aeruginosa. Blood testing showed a normal IgE and elevated IgG with no evidence of Aspergillus antibodies. Routine blood counts and inflammatory markers were normal.
A diagnosis of idiopathic bronchiectasis was made. Inhaled steroids were discontinued. The patient attended a respiratory physiotherapist for instruction and commenced daily autogenic drainage of secretions. Nebulised tobramycin was commenced. One year later the exacerbation frequency has reduced to one every six months. Spirometry is stable and the patient’s reported breathlessness has improved.
Introduction
Initially described by Laennec in 1819, bronchiectasis is a condition which occurs when there is abnormal dilatation of the airways. Mucous retention and frequently hypersecretion occurs causing a characteristic productive cough. Airway mucous in bronchiectasis is rich in inflammatory products and destructive enzymes. A viscous cycle of mucous secretion, airway infection and tissue damage ensues.
There are numerous causes of bronchiectasis. Cystic Fibrosis (CF) is generally considered and managed as a separate condition and is not considered further here. There are many similarities between bronchiectasis in adults and children; however this review focuses on the disease in adults
Successful immunisation programmes and improvements in public health have reduced the incidence of destructive childhood pulmonary infections. As a result it was thought that bronchiectasis was well on the way to becoming a rare, orphan lung disease in industrialised populations. However widespread use of High Resolution Computerised Tomographic (HRCT) scanning of the chest has meant that incidence is actually increasing in some areas. HRCT has replaced contrast bronchography as the gold standard diagnostic test. Prevalence figures vary, ranging from 4 to 272 cases per 100000 persons depending on the population studied. Prevalence is higher in women, those aged over 65 and amongst those with poor access to health care.
Presentation
Diagnosis is often preceded by several years of symptoms. Up to 90% of patients complain of cough which is generally but not ubiquitously productive. Other symptoms include; recurrent airway infections which are difficult to clear, breathlessness (80%), chest pains (30%) and haemoptysis (50%). Massive haemoptysis of more than 250 mL is uncommon. Occasionally patients present with systemic symptoms of malaise and weight loss. A history of severe childhood infection, particularly pertussis, should be sought.
Clinically finger clubbing is well described but rare. 70% of patients have coarse crackles on auscultation of the lung fields. Signs of airway obstruction are also common with wheeze present in one third of patients. Other signs of obstruction including a hyperinflated chest with reduced chest expansion are limited to severe disease. Signs of associated conditions such as rheumatoid arthritis or ulcerative colitis should be looked for.
Investigation
The purpose of testing is to confirm the diagnosis, identify any underlying cause and facilitate ongoing management. Common causes of bronchiectasis from a cohort of patients evaluated at the Royal Brompton Hospital, London are outlined in Table 1. A large proportion of the cases are idiopathic.
All patients should have sputum or respiratory tract specimens cultured on diagnosis and periodically thereafter. A chest x-ray is generally abnormal but often without specific pathognomonic features. High Resolution Computerised Tomography (HRCT) classically demonstrates signet ring changes where the internal bronchial diameter is greater than that of the adjacent artery. Other HRCT signs include; a lack of bronchial tapering where the bronchus is the same diameter as the parent branch for >2 cm, bronchi within 1 cm of costal pleura or bronchi abutting the mediastinal pleura. Bronchial wall thickening is a frequent but nonspecific appearance. Pus filled bronchi may have the appearance of pulmonary nodules.
Pulmonary function studies may show evidence of airway obstruction. This obstruction may be progressive with reductions in Forced Expiratory Volume (FEV1) of up to 50 mls per year. Those with P aeruginosa airway colonization, severe exacerbations and evidence of a systemic inflammatory response have a greater decline in lung function.
Bronchoscopy is useful in cases associated with foreign body aspiration or endobronchial obstruction. It is also useful for obtaining reliable microbiological cultures particularly in the absence of spontaneously expectorated samples. The presence of foam-laden macrophages in bronchoscopic samples indicates gastric aspiration as an aetiological factor.
Tests of immunological function should include; Aspergillus-specific IgE and IgG, serum immunoglobulins (IgG, IgA, IgM) and serum electrophoresis. Some units have replaced IgG subtype measurement with measurement of specific antibody levels to pneumococcal, haemophilus and tetanus antigens. If these are low they are repeated after vaccination.
The choice of investigation to identify gastric aspiration will depend on local protocols and may include one or more of; 24 hour oesophageal pH monitoring, barium studies or videofluoroscopy.
Occasionally testing for CF is appropriate for adults presenting with bronchiectasis particularly if there is associated male infertility, signs of malabsorption or combined sinopulmonary disease. Other tests which may be required include; saccharin test, exhaled nasal nitric oxide and nasal mucosal biopsy. Abnormalities of alpha-1-antitrypsin levels are seen in bronchiectasis more commonly than expected.
Management of Chronic Disease
The goal of therapy is to minimise the impact of infective exacerbations on quality of life and prevent deterioration of lung function.
Primary or underlying conditions such as allergic bronchopulmonary aspergillosis or gastroesophageal reflux should be effectively treated.
Smoking cessation support should be offered where appropriate. Regular exercise should be encouraged as tolerated. Pulmonary rehabilitation significantly increases exercise capacity in bronchiectasis. Inspiratory muscle training also improves exercise endurance and health-related quality of life but not as an adjunct to rehabilitation.
Physical therapy to clear the airways of mucous is a corner stone of chronic bronchiectasis management. All patients should have instruction on airway clearance techniques from a respiratory physiotherapist. Techniques such as huffing and active cycles of breathing should be utilised to clear airway secretions on a daily basis in those with productive cough. Postural drainage guided by HRCT images may also be utilised. Patients should be encouraged to complete their own airway clearance independently where possible – termed autogenic drainage.
Nebulised isotonic saline, hypertonic saline or bronchodilators may improve the efficacy of chest physiotherapy by increasing sputum yield, reducing viscosity and objectively easing sputum expectoration. Hypertonic saline (3% - 14%) is more effective than isotonic saline but may cause bronchoconstriction. Tolerability should be confirmed by administering the first dose under supervision with facilities in place to recognise and reverse acute bronchospasm. Sterile water nebulisation has also been studied but may also cause bronchoconstriction.
Non-invasive ventilation is a useful adjunct to physiotherapy particularly in those with severe disease. It reduces the fatigue associated with airway clearance increasing the length of time that can be tolerated. It may also allow the use of head down positions to facilitate postural drainage that may be otherwise intolerable because of breathlessness.
Oscillating positive expiratory pressure (PEP) devices such as the Acapella (photo) or the Flutter Valve devices have been demonstrated in a limited number of studies to be as effective as active cycle of breathing techniques. PEP devices should be used in conjunction with huffing and postural drainage. These devices appear to have high patient satisfaction over autogenic drainage alone.
Mucolytic agents such as acetylcysteine or mannitol have been insufficiently studied to allow recommendations for routine use. Nebulised recombinant DNAse which is effective in CF associated bronchiectasis is not recommended for non-CF bronchiectasis.
Inhaled steroids, bronchodilators, theophyllines and leukotriene antagonists are not indicated for bronchiectasis in the absence of associated conditions such as asthma.
One large clinical trial showed a frequency of 1.5 exacerbations per year in patients from North America, the United Kingdom, and Ireland who were receiving “usual” care for their bronchiectasis. Patients with more than three exacerbations per year may benefit from antibiotic prophylaxis. A thrice weekly regimen of azithromycin has been shown to reduce sputum production and exacerbation rates and also to improve a variety of quality of life measurements. Patients with chronic colonization with Pseudomonas aeruginosa may benefit from the prevision of nebulised antipseudomonal antibiotics directed by sensitivity results.
Management of Acute Exacerbation
Treatment of acute infective exacerbations of bronchiectasis can often be accomplished in the patient’s home (see panel). Attention must be paid to maintaining adequate oxygenation and ventilation. Physical and pharmacological measures to aid airway clearance should usually be increased.
Antibiotic treatment of exacerbations should be guided where possible by previous microbiological results from the patient. Antibiotic treatment should be preceded by further microbiological culture. Frequently encountered organisms include H influenzae P aeruginosa, Moraxella catarrhalis, Streptococcus pneumonia and S aureus. Mycobacteria are increasingly identified as either a causative or colonizing organism.
In the absence of previous microbiological data empiric therapy may include amoxicillin 500 mg three times a day or clarithromycin 500 mg twice daily (in patients who are penicillin-allergic) for 14 days. High-dose oral regimens (eg, amoxicillin 3g to 6 g per day in divided doses) may be required in patients with severe bronchiectasis who are not penicillin allergic, particularly those colonized with H influenzae. Patients improving on empiric antibiotics should not have their regimes altered on the basis of subsequent microbiology results alone. Failure to improve is a much better indicator of the need to change antibiotic regime.
Pseudomonas exacerbations may be treated by oral quinolones but care has to be exercised as resistance is frequently encountered following monotherapy of this organism. Exacerbations due to MRSA should be treated with two oral or one intravenous agent.
Intravenous therapy (see panel) should be considered for those too unwell to take oral therapy or who have failed to respond to a course of oral therapy. Exacerbations due to P aeruginosa are more likely to require intravenous therapy. Intravenous therapy is increasingly available in a domiciliary setting but should be reserved for those who are clinically stable.
Conclusion
Bronchiectasis, previously thought to be reducing in importance is becoming once again an important cause of respiratory morbidity. Diagnosis depends on clinical suspicion and the use of confirmatory imaging studies. Management requires coordinated physical and pharmacological therapies with prompt and sometimes extended treatment of infective exacerbations.
Panels
| When to Suspect a Diagnosis of Bronchiectasis in Adults |
|---|
| Chronic cough. |
| Daily sputum production. |
| Pseudomonas aeruginosa in the sputum. |
| A history of symptoms over many years. |
| No history of smoking. |
| Adults thought to have COPD, who do not smoke, or who have difficult exacerbations. |
| Unexplained haemoptysis (usually recurrent blood-streaked sputum). |
| Asthma, that responds poorly to treatment. |
| Indications for Specialist Referral |
|---|
| Diagnostic uncertainty |
| Chronic colonization with Pseudomonas aeruginosa, nontuberculous mycobacteria (NTM), or meticillin-resistant Staphylococcus aureus (MRSA). |
| Three or more infective exacerbations a year. |
| Bronchiectasis requiring long-term prophylactic antibiotics. |
| Bronchiectasis associated with rheumatoid arthritis, immune deficiency, inflammatory bowel disease, primary ciliary dyskinesia, and allergic bronchopulmonary aspergillosis. |
| Advanced disease. |
| Indications for Inpatient Management of Acute Exacerbation |
|---|
| Failed to respond adequately to oral therapy. |
| Unable to cope at home. |
| Respiratory rate more than 25 breaths per minute. |
| Signs of cardiorespiratory failure (such as marked breathlessness, rapid respiration, laboured breathing, cyanosis, worsening peripheral oedema, or oxygen saturation <93% on room air). |
| Temperature of 38°C or more. |
| Unable to take oral therapy. |
| Pleuritic pain severe enough to inhibit coughing and the clearing of secretions. |
Tables
| Cause | n (% of study population) | Age (SD) | No. males (% group) |
|---|---|---|---|
| Post infection | 52 (32) | 49 (16) | 17 (33) |
| Idiopathic | 43 (26) | 51 (14) | 15 (35) |
| Primary Ciliary Dyskinesia | 17 (10) | 36 (13) | 5 (29) |
| Allergic BronchoPulmonary Aspergillosis | 13 (8) | 54 (13) | 6 (46) |
| Immune deficiency | 11 (7) | 47 (18) | 1 (9) |
| Ulcerative colitis | 5 (3) | 48 (20) | 2 (40) |
| Young’s syndrome | 5 (3) | 56 (5) | 3 (60) |
| Pan bronchiolitis | 4 (2) | 46 (21) | 3 (75) |
| Yellow nail syndrome | 4 (2) | 55 (14) | 2 (50) |
| Mycobacterium infection | 4 (2) | 62 (20) | 0 (0) |
| Rheumatoid arthritis | 3 (2) | 65 (4) | 1 (33) |
| Aspiration | 2 (1) | 67 (13) | 1 (50) |
| Cystic fibrosis | 2 (1) | 41 (13) | 2 (100) |
| Total | 165 | 49 (16) | 58 (35) |
References
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NHS Clinical Knowledge Summaries (Bronchiectasis)
http://www.cks.nhs.uk/bronchiectasis
O’Donnell AE, Barker AF, Ilowite JS, et al.
Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I.
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Davies G, Wilson R.
Prophylactic antibiotic treatment of bronchiectasis with azithromycin.
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Anne E. O'Donnell
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