22nd February 2024

Bronchiectasis

Background

Bronchiectasis is defined as dilatation of the terminal bronchioles of more than 2mm, leading to inflammation and partial or complete obstruction by secretions. Inflammation consists of a combination of immune deficiency and persistent infection. This process is continuous and leads to a cycle of worsening pulmonary damage. The prevalence of bronchiectasis in the United Kingdom is approximately 210,000 to 300,000 cases. It is more commonly found amongst females compared to males, with 60% of diagnoses in patients above the age of 70. 

Pathophysiology 

The pathophysiology of bronchiectasis stems from two main processes: infectious insult and subsequent impaired drainage leading to airway obstruction.

The host immune response, led mainly through immune modulator cells (neutrophils) and elastases, in addition to oxidation radicals and inflammatory cytokines, leads to ulceration, inflammation and neovascularisation of airways. Other contributing factors include:

Neutrophil/Neutrophil elastase

The excess presence of neutrophil/neutrophil elastase has been noted in patients with features of bronchiectasis. Unopposed apoptosis, increased release of myeloperoxidase and phagocytosis have been characterised with stable bronchiectasis. Pregnancy-associated zone proteins (PZP) and intracellular neutrophil proteins are associated with infective exacerbation of bronchiectasis and indicate the presence of Pseudomonas aeruginosa. 

Vitamin D deficiency

Vitamin D has been correlated with exacerbation of bronchiectasis. Patients with Vitamin D deficiency are more likely to have Pseudomonas colonisation, worse exacerbations requiring hospitalisation and increased sputum expectancy.

References

• Chan SC, Leung VO, Ip MS, Shum DK. Shed syndecan-1 restricts neutrophil elastase from alpha1-antitrypsin in neutrophilic airway inflammation. Am J Respir Cell Mol Biol 2009; 41:620
• Chalmers JD, McHugh BJ, Docherty C, et al. Vitamin-D deficiency is associated with chronic bacterial colonisation and disease severity in bronchiectasis. Thorax 2013; 68:39.
• Pillarisetti N, Williamson E, Linnane B, et al. Infection, inflammation, and lung function decline in infants with cystic fibrosis. Am J Respir Crit Care Med 2011; 184:75

Aetiology 

There are numerous triggers for the onset of bronchiectasis. These include mechanical bronchial obstruction, immune deficiency, mucociliary clearance defects, lung parenchymal disease and repeated post-infected damage. Causes of bronchiectasis include:

Mechanical obstruction

• Foreign body ingestion
• Post tuberculosis 
• Tumour

Post-infective parenchymal damage

Recurrent bacterial infections including pertussis, measles, and aspiration pneumonia

Immune deficiency or overdrive

• Allergic bronchopulmonary aspergillosis
• Immunoglobulin deficiencies (IgA and IgG)
• HIV / malignancy

Mucociliary clearance defects

• Cystic fibrosis
• Kartagener Syndrome 
• Young syndrome

Kartagener syndrome is an autosomal recessive disorder characterised by situs inversus, bronchiectasis and chronic sinusitis. Symptoms manifest from A defect in the mucociliary escalator, resulting in patients with recurrent bacterial chest infections, otitis media, rhinosinusitis and infertility. Situs inversus is often identified on chest radiographs with dextrocardia seen as an incidental finding and does not have any clinical sequalae. Other signs of dextrocardia include ECG findings with positive P-wave and inverted T-wave in Lead I, tall R wave in aVR lead and poor R wave progression from Leads V1 – V6. 

Young syndrome is characterised by infertility due to azoospermia, rhinosinusitis and bronchiectasis. 

References

King PT. The pathophysiology of bronchiectasis. Int J Chron Obstruct Pulmon Dis. 2009;4:411-9. doi: 10.2147/copd.s6133. Epub 2009 Nov 29

Presentation

Symptoms

Exertional shortness of breath is commonly the earliest clinical manifestation. Other features include chest pain, fatigue, persistent cough, recurrent infections and loss of appetite. Psychological manifestations include depression, anxiety, loss of confidence and negative lifestyle impact. Patients with bronchiectasis are associated with increased hospitalisation episodes over the disease span, leading to an overall more sedentary lifestyle with reduced physical activity levels. 

Signs

Physical examination features include coarse inspiratory basal crackles, wheeze, finger clubbing, low body mass index and, in severe cases, features of right heart failure with hepatic congestion and peripheral oedema.

References

Alcaraz-Serrano V, Arbillaga-Etxarri A, Oscanoa P, Fernández-Barat L, Bueno L, Amaro R, Gimeno-Santos E, Torres A. Exacerbations and Changes in Physical Activity and Sedentary Behaviour in Patients with Bronchiectasis after 1 Year. J Clin Med. 2021 Mar 12;10(6):1190.

Diagnosis

Bronchiectasis should be suspected in individuals with recurrent purulent or mucopurulent sputum. Diagnosis is confirmed using results from laboratory tests, pulmonary function assessment and radiographic evidence. 

Investigations

• Raised inflammatory markers such as White Blood Cell (WBC) counts, in particular neutrophil count and c-reactive protein, are commonly associated with exacerbations of bronchiectasis. 
• Reduction in immunoglobulin profiles, such as IgG, IgM and IgA, are associated with bronchiectasis. Specific gene testing, such as the CFTR gene for cystic fibrosis, can also be linked with bronchiectasis. 
• Sputum culture: Pseudomonas colonisation is commonly associated with bronchiectasis exacerbation, requiring a longer duration of intravenous and oral antibiotics
• Rheumatoid factor: Bronchiectasis can be a feature of rheumatoid arthritis and is often associated with severe nodular disease.  
• Alpha 1 antitrypsin: A deficiency of alpha 1 antitrypsin is pathognomonic for COPD and helps differentiate bronchiectasis from COPD.

Pulmonary function tests

Spirometry is likely to show an obstructive pattern due to damage to the lung parenchyma from bronchiole dilatation and impairment of the mucociliary escalator, thereby causing a reduction of oxygen transfer and retention of carbon dioxide within the pulmonary capillary system. The patient will also have decreased Forced Expiratory Volume (FEV 1) as compared to Forced vital capacity (FVC), thus overall ratio of FEV1 / FEV <70 %.

Radiological evidence

Chest radiograph 

Most patients with bronchiectasis will have an abnormal chest radiograph. Although not diagnostic, common features include patchy lower zone opacification, linear atelectasis, and dilated and thickened airways (appearance of ‘tram lines’ / ring shadows).

Computed tomography (CT) 

High-resolution computed tomography (HRCT) is the gold standard imaging modality for confirming the diagnosis of bronchiectasis. Features of HRCT include:

• Airway dilatation can appear as a parallel / ‘tram line’ on chest X-ray. Dilated airways with accompanying pulmonary vessels can appear as  ‘signet rings’ on HRCT. Airway lumen dilatation of >1.5mm to adjacent pulmonary vessels is the classic diagnostic feature of bronchiectasis. 
• Smaller airways can present in a linear fashion, giving the appearance of a ‘tree in bud’ pattern on HRCT. 
• The distribution seen on HRCT  may be associated with different aetiologies of bronchiectasis:
  • The central (perihilar) pattern is more suggestive of allergic bronchopulmonary aspergillosis
  • Upper lobe distribution is significant for cystic fibrosis
  • Middle/lower lobe correlates with primary ciliary dyskinesis 
  • Lingula segment of the upper left lung with non-tuberculosis mycobacterium (NTM). 
• Airway visibility of 1cm around coastal pleural space or touching mediastinal pleura. 

References

• Hill AT, Sullivan AL, Chalmers JD, et al. British Thoracic Society Guideline for bronchiectasis in adults. Thorax 2019; 74:1.
• Riordan JR. Assembly or functional CFTR chloride channels. Annu Rev Physiol. 2005;67:701–718. 
• LeGrys VA, Yankaskas JR, Quittell LM, et al. Diagnostic sweat testing: the Cystic Fibrosis Foundation guidelines. J Pediatr 2007; 151:85.
• Aliberti S, Goeminne PC, O’Donnell AE, et al. Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations. Lancet Respir Med 2022; 10:298

Management

Bronchiectasis leads to irreversible damage to the lung parenchyma, so management is predominantly aimed at preventing and slowing further deterioration. Treatment strategies focus on treating the underlying condition and any other coexisting comorbidities. These range from risk factor modification and regular physiotherapy to treating acute exacerbation with antibiotics and, in rare cases, surgical intervention. 

General management

Bronchiectasis patients need to address risk factors such as smoking cessation, engaging in pulmonary rehabilitation and medication adherence. There is evidence that regular exercise reduces exacerbation episodes. Healthy dietary consumption, including sources rich in Vitamin D, is beneficial.  Regular annual immunisations against influenza and pneumococcus have also had a positive impact in reducing hospitalisations. 

Pulmonary rehabilitation

Pulmonary rehabilitation should be offered to individuals with limited exercise tolerance due to shortness of breath (Modified Medical Research Dyspnoea Scale >1). This should incorporate exercises for strengthening and conditioning, dietary advice, and behavioural and psychological therapies. Regular exercise with dietary input ensures muscle strengthening which aids in breathing improvement during exacerbation episodes. Regular gravity-assisted postural drainage are effective techniques in sputum burden relief.

Medical management 

First line antibiotic agents consist of Penicillins such as Amoxicillin (or Doxycycline for Penicillin allergic patients). Sputum samples are an important component of investigations for suspected bronchiectasis with Pseudomonas Aeuruginosa, which is commonly identified as a source of bacterial colonisation. These exacerbation episodes will require a longer duration of intravenous antibiotics (minimum 2 weeks)

For non-Pseudomonas Aeruginosa colonised patients, Macrolides such as Azithromycin / Erythromycin should be considered as first line. Alternatively, Doxycycline can be used for patients allergic to Macrolides. 

Chronic colonisation of Pseudomonas will require broad-spectrum intravenous options such as Piperacillin/Tazobactam. Planned administration of intravenous antibiotics can be considered if more than >5 exacerbation episodes per year despite other treatments. Prophylactic oral antibiotics such as Azithromycin (250mg three times a day) are a pragmatic dose for patients with chronic colonisation. 

References

• Lonni S, Chalmers JD, Goeminne PC, et al. Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity. Ann Am Thorac Soc 2015; 12:1764.
• Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 2003; 168:918.