Dr IP Kar Shun Simon
Consultant in Respiratory Medicine
Hong Kong Baptist Hospital
The British Thoracic Society (BTS) guidelines for bronchiectasis in adults recommend patients with or without chronic Pseudomonas aeruginosa infection, who experience three or more exacerbations per year, to receive treatments including long-term antibiotics.1 Globally, three large randomised clinical trials have shown the benefits of macrolides in reducing exacerbation frequency and sputum volume, as well as in increasing the duration before the first exacerbation requiring antibiotics.2-4
Dr Kar Shun Simon Ip – consultant in respiratory medicine at the Hong Kong Baptist Hospital – shares his experience in the management and prevention of bronchiectasis.
Q1: Please describe the aetiology and characteristics of patients with bronchiectasis in Hong Kong.
Bronchiectasis is quite a common disease in the Asia-Pacific, especially when diagnosis can be made readily with easy access to computed tomography (CT). However, there are no local prevalence or incidence data in Hong Kong; Prospective studies looking into the disease characteristics in our locality will be extremely valuable.
Bronchiectasis has a diverse aetiology, but most cases are idiopathic. While, some cases have post-tuberculous infection or post-pneumonic infection as the underlying cause; others may suffer from underlying conditions including gastroesophageal reflux disorder (GERD) and primary or secondary immunodeficiency. Bronchiectasis patients in Hong Kong are slightly different from their Western counterparts. For instance, patients in Hong Kong rarely suffer from allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis.
Bronchiectasis is characterised by repeated infections which destroy the airways – causing an irreversible dilatation of the bronchial trees. As a result, patients suffer from chronic cough and chronic sputum production, as well as haemoptysis in some cases. In fact, haemoptysis is the first presentation of bronchiectasis in some patients that I see in my clinic.
Q2: Given the similarities in clinical features of bronchiectasis and chronic obstructive pulmonary disease (COPD) – including inflamed and collapsible airways, and airflow obstruction5 – what is the diagnostic workup for bronchiectasis?
Radiology will be the first step. Tram line appearance on chest x-ray – representative of bronchial wall thickening is often difficult to pick up. As such, computed tomography (CT) is the preferred diagnostic tool. Classic findings include bronchoarterial ratio of greater than one and the lack of tapering of the airway.
For blood tests, full blood count and C-reactive protein (CRP) test are usually performed – these serve as inflammatory markers. Other tests such as serum IgG, IgM, and IgA are done to exclude immunodeficiency. Serum IgE test and specific IgE for Aspergillus can be performed, if necessary. Rheumatoid factor and antinuclear antibody tests can also be done for cases with clinical suspicion of associated autoimmune disease. We often perform sputum culture to identify bacterial, mycobacterial, and fungal infection; good sampling techniques are important to ensure good quality culture samples. As some patients with bronchiectasis may also have asthma and COPD, lung function test – particularly baseline spirometry – will be useful in ruling out airflow obstruction. On the other hand, for patients presented with haemoptysis or well localised disease, bronchoscopy will be useful in ruling out other bronchial diseases such as tumour and airway foreign bodies.
Q3: How are adult patients with bronchiectasis managed? What are the benefits of antimicrobial therapy?
Before we delve into bronchiectasis medication, it is worthwhile discussing airway clearance methods. Patients are often taught to perform airway clearance by a physiotherapist. Meanwhile, the therapeutic goals are: to manage exacerbations; long-term treatment aiming at reducing pulmonary exacerbations; and in some cases, to eradicate infections.
In the case of exacerbations, antibiotics are effective in reducing sputum volume and purulence – thus leading to clinical improvement. Antibiotics also reduce the microbial load and airway hyperresponsiveness. As such, the availability of previous sputum bacteriology results can be useful in guiding treatment, i.e. appropriate use of antibiotics. Intravenous (IV) antibiotics should be considered when patients are unwell. For instance, when patients have a fever or respiratory failure.
Long-term antibiotics should be considered in patients with stable bronchiectasis who experience three or more exacerbations per year. The benefit of antibiotic therapy is to aim for a reduction in exacerbation and therefore, reduction in hospitalisation. Treatment modalities largely depend on whether patients are colonised with Pseudomonas aeruginosa; patients with Pseudomonas aeruginosa colonisation are recommended to receive inhaled therapy such as colistin; whereas those non- Pseudomonas aeruginosa colonised patients are given macrolides such as azithromycin and erythromycin.
We have often emphasised the importance of Pseudomonas aeruginosa in bronchiectasis-related complications. Therefore, current guidelines recommend eradication treatment when this pathogen is newly isolated. The initial phase of the eradication treatment usually consists of an oral quinolone or IV antibiotics, followed by inhaled antibiotics. The total duration of treatment is three months.
Q4: What are the most common pathogens isolated in patients with bronchiectasis? How are antimicrobial therapies selected for the treatment of these patients?
The most important pathogens in the majority of patients with bronchiectasis are Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa; less commonly methicillin-sensitive Staphylococcus aureus (MSSA). Methicillin-resistant S. aureus (MRSA) can be isolated in some cases; non-tuberculous Mycobacterium (NTM) is also well described in patients with bronchiectasis. Therefore, the selection of antibiotics depends on the target pathogen.
Q5.: What are the differences between using respiratory quinolones versus other antibiotics? Is combination therapy used?
Patients with milder exacerbations can be managed in the outpatients setting. Amoxicillin/clavulanic acid or a second-generation cephalosporin is used to cover Haemophilus influenzae and Moraxella catarrhalis. Quinolones (oral ciprofloxacin or levofloxacin) are reserved as second-line treatment for these pathogens; these agents are most commonly indicated for the treatment of Pseudomonas aeruginosa infection.
In more severe cases, particularly patients with severe Pseudomonas aeruginosa infection, IV therapy is often used. This includes IV ceftazidime, IV piperacillin/tazobactam or IV meropenem – sometimes used in combination with gentamicin, tobramycin or colistin.
Q6: Are there any concerns around the emergence of antibiotic resistance with long-term antibiotics as maintenance management of clinically stable bronchiectasis? If so, what measures have been adopted to curb this problem?
Firstly, it is important to understand the rationale in using long-term antibiotics, i.e. for the treatment of patients with recurrent exacerbations. Therefore, it is crucial to define exacerbation when making treatment choice. Furthermore, it is also important to counsel patients on the use of long-term antibiotics and educate them on the potential side effects. The emergence of antibiotic resistance is almost inevitable. Therefore, treatment adherence is important – better treatment adherence reduces the emergence of antibiotic resistance.
Q7: Are patients with bronchiectasis at higher risk of the coronavirus disease 2019 (COVID-19) infection? If so, what preventive measures can be taken?
Theoretically, patients with bronchiectasis are at risk of any respiratory infections. Patients with underlying immunodeficiency are also at high risk of COVID-19 infection. Precautionary measures such as social shielding – not social distancing – is implemented in some countries, i.e. patients who are extremely vulnerable are advised not to leave their houses.