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Bronchiectasis 

Bronchiectasis
Chapter:
Bronchiectasis
Author(s):

Stephen Chapman

, Grace Robinson

, John Stradling

, Sophie West

, and John Wrightson

DOI:
10.1093/med/9780198703860.003.0019
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date: 26 October 2021

Epidemiology, pathophysiology, and causes

Definition

Irreversible abnormal dilatation of one or more bronchi, with chronic airway inflammation. Associated chronic sputum production, recurrent chest infections, and airflow obstruction.

Epidemiology

Prevalence of bronchiectasis is unknown but is probably falling due to vaccinations and the improved and earlier treatment of childhood infections. However, the advent of HRCT scanning may now lead to the diagnosis of more subtle (and possibly subclinical) disease.

Pathophysiology

An initial (usually infectious) insult is needed to damage the airways. Disordered anatomy leads to 2° bacterial colonization, perpetuating inflammatory change and damaging the mucociliary escalator. This prevents bacterial clearance and leads to further airway damage. Major airways and bronchioles are involved, with mucosal oedema, inflammation, and ulceration. Terminal bronchioles become obstructed with secretions, leading to volume loss. A chronic host inflammatory response ensues, with free radical formation and production of neutrophil elastase, further contributing to inflammation. Bronchial neovascularization, with hypertrophy and tortuosity of the bronchial arteries (which are at systemic pressure), may lead to intermittent haemoptyses.

Aetiology

The causes of bronchiectasis are many and varied (see Table 19.1). In general, the aetiology is either a one-off infectious insult or an underlying immune deficiency. Determining the aetiology of the condition may lead to different management if, for example, the underlying cause is found to be CF, rather than an immune deficiency. The cause is idiopathic in around 50% of cases, and these are likely to be due to an (as yet unidentified) impairment in host defence.

Table 19.1 Causes of bronchiectasis

Genetic

CF

Congenital

Pulmonary sequestration

Post-infective

TB

Whooping cough (if infection in a localized area)

Severe pneumonia

NTM (see Bronchiectasis p. [link][link])—there is some debate as to whether the bronchiectasis seen in association with NTM (classically in elderly ♀) is caused or secondarily infected by NTM

Immune deficiency

2°—HIV, CLL, nephrotic syndrome

(Excessive immune response—ABPA) (see Bronchiectasis pp. [link][link])

Mucociliary clearance abnormalities

CF

1° ciliary dyskinesia (see Bronchiectasis pp. [link][link])

Kartagener’s syndrome

Young’s syndrome (bronchiectasis, sinusitis, and azoospermia, i.e. clinical features similar to those of CF)

Toxic insults

Aspiration

Inhalation (toxic gases, chemicals)

Mechanical insults

Foreign body aspiration

Extrinsic lymph node compression

Intrinsic (intraluminal) obstructing tumour

Associations

Bronchiectasis is associated with a number of systemic diseases, so cough and sputum production in these conditions should trigger referral to determine the cause:

RA (up to 35% of RA patients have bronchiectasis) (see Bronchiectasis pp. [link][link])

Connective tissue diseases, e.g. Sjögren’s syndrome, SLE (see Bronchiectasis p. [link])

Ulcerative colitis and Crohn’s disease (see Bronchiectasis p. [link])

Chronic sinusitis

Yellow nail syndrome

Marfan’s syndrome

The most important cause to exclude is CF (see Bronchiectasis p. [link]). Even relatively mild bronchiectasis diagnosed in middle age can be due to CF; this diagnosis will alter management, with:

  • Involvement of the multidisciplinary CF team

  • Attention to other potential problems, e.g. GI disease, diabetes

  • Inheritance (relevant to the rest of the family)

  • Fertility issues.

Consider investigations for CF (CFTR mutation screen and sweat test; see Bronchiectasis pp. [link][link]) if:

  • Predominantly upper lobe disease

  • Persistent S. aureus infection or Haemophilus influenzae or Pseudomonas aeruginosa colonization

  • Malnutrition ± malabsorption, diabetes

  • Family history of CF or bronchiectasis

  • Associated subfertility or infertility

  • Age <40 at presentation and no other cause for bronchiectasis identified.

Clinical features and diagnosis

Suspect bronchiectasis in a patient with recurrent episodes of ‘bronchitis’ over several years prior to presentation.

Diagnosis

is usually made clinically, with HRCT chest for confirmation.

Investigations are aimed at:

  • Confirming the diagnosis

  • Identifying a treatable underlying cause for the bronchiectasis (possible in about 50%)

  • Optimizing management to prevent exacerbations and lung damage.

Essential investigations

  • CXR sensitivity is only 50%, classically shows ‘ring shadows’ and ‘tramlines’—indicating thickened airways, and the ‘gloved finger’ appearance. Consolidation around thickened and dilated airways

  • HRCT chest is 97% sensitive in detecting disease. Typically shows airway dilatation to the lung periphery, bronchial wall thickening, and the airway appearing larger than its accompanying vessel (signet ring sign). Expiratory scans may be useful to demonstrate post-obstructive air trapping, indicative of small airways disease. If the bronchiectasis is localized to a single lobe, CT is useful to determine whether a central obstructing lesion is present. Contiguous 3mm slices are needed to exclude a central airway lesion if there is associated haemoptysis. Symptoms correlate with wall thickening and mucous plugging on CT scan. The radiological term ‘traction bronchiectasis’ refers to airway dilatation 2° to airway distortion, seen with chronic severe interstitial fibrosis. These patients rarely have clinical features of bronchiectasis

  • Lung function FEV1/FVC and flow-volume loop

  • Sputum microbiology Standard M, C, & S (including for atypical organisms), AFB, and Aspergillus

  • PFTs with reversibility testing

  • Immunoglobulins A, M, G

  • Aspergillus precipitins, Aspergillus-specific RAST, total IgE (see Bronchiectasis p. [link][link]).

Additional investigations

  • CFTR mutation screen and sweat test (see Bronchiectasis pp. [link][link])

  • Autoantibodies (ANA, RhF, dsDNA) if associated arthritis/connective tissue disease

  • Vaccination response to tetanus, H. influenzae, and pneumococcal antibodies if underlying immunosuppression suspected. If pneumoccoccal antibodies are low, arrange vaccination with Pneumovax, and repeat antibody testing 6 weeks later; failure to generate adequate pneumococcal antibody levels is suggestive of an immunodeficiency (e.g. IgG subclass deficiency), and referral to an immunologist may be required

  • Detailed immunological investigation (including neutrophil and lymphocyte function studies)

  • Skin tests/RAST to identify specific sensitizers (usually Aspergillus)

  • Bronchoscopy to exclude a foreign body if suggested by CT; obtain microbiological samples if unusual clinical presentation or failure to respond to standard antibiotics

  • Nasal brushings/biopsy (in tertiary centre) to assess ciliary beat frequency with video microscopy

  • Saccharin test The time for saccharin to be tasted in the mouth after deposition of a 0.5mm particle on the inferior turbinate of the nose. Normal is <30min. A poor man’s cilial function test

  • α‎1-AT levels if deficiency is suspected

  • Barium swallow/oesophageal imaging if recurrent aspiration suspected.

General management

The main aims of management of non-CF bronchiectasis are:

  • Treatment of any underlying medical condition

  • Prevention of exacerbations and progression of underlying disease by daily physiotherapy. The options for airway clearance include:

    • Active cycle of breathing technique—this involves breathing control with forced expiration (huffing) using variable thoracic expansion

    • Postural or autogenic drainage

    • Cough augmentation—using flutter valves/cough insufflator/high-frequency oscillation/positive pressure devices

    • Exercise regimes—important to prevent general deconditioning

    • The physiotherapist is also vital during admission for exacerbations to help clear tenacious sputum

    • Nebulized hypertonic saline may improve airway clearance, although there is no RCT data to support its use in non-CF disease

  • Reduction of bacterial load and prevention of 2° airway inflammation and damage with antimicrobial chemotherapy

  • Supportive treatment—treatment of associated airflow obstruction

  • Optimize nutrition

  • Refer for pulmonary rehabilitation if breathlessness limits activities of daily living

  • Refer for surgery if necessary—localized resection of affected area

  • Refer for transplantation if indicated.

Antimicrobial chemotherapy

  • This may be intermittent for exacerbations only (for mild disease) or long term for more severe disease. Antibiotics may be oral, nebulized, or IV

  • Regular sputum surveillance will ensure the likely colonizing organism is known

  • In vivo sensitivity may be different to in vitro sensitivity

  • Patients need a higher antibiotic dose and for a longer time period (usually 2 weeks) than people without bronchiectasis

  • Antibiotic treatment choice depends on the severity of the underlying disease

  • Treatment response is usually assessed by a fall in sputum volume and change to mucoid from purulent or mucopurulent sputum, with an improvement in systemic symptoms, spirometry, and CRP

  • Pseudomonas-colonized patients have more frequent exacerbations, worse CT scan appearances, and a faster decline in lung function.

Exacerbation treatment

An exacerbation is usually a clinical diagnosis, with an increase in sputum volume and tenacity and with discoloration. It may be associated with chest pain, haemoptysis and wheeze, and systemic upset—fevers, lethargy, and anorexia. The CRP is not always elevated. Treatment depends on the potential pathogens and resident flora. Nebulized bronchodilators and regular physiotherapy (as an inpatient or outpatient) may also be needed.

Exacerbation of mild bronchiectasis

  • Antibiotics for exacerbations only (tailored to the colonizing organism—review previous sputum microbiology)

  • Sputum samples should be sent for M, C, & S prior to starting antibiotics, but empirical treatment can be started whilst awaiting culture results

  • In the absence of prior positive microbiology, amoxicillin 500mg tds or clarithromycin 500mg bd for 14 days

  • Use a higher-dose oral regime, e.g. amoxicillin 1g tds for 2 weeks, especially if colonized with H. influenzae

  • A 2-week course of oral ciprofloxacin at 750mg bd if Pseudomonas aeruginosa colonized

  • If early relapse, with a return to purulent sputum within 6–8 weeks, consider a longer course of oral antibiotics, e.g. amoxicillin 500mg bd or doxycycline 100mg od. If treatment failure, change to appropriate IV antibiotics until clinical improvement.

Exacerbation of more severe bronchiectasis

Chronic suppressive antibiotics aim to prevent progression of disease by reducing bacterial load and preventing ongoing inflammation, thereby reducing morbidity and improving QoL.

  • Antibiotics are usually given for at least 2 days after the sputum has cleared—often for 2 weeks

  • If oral antibiotics fail, IV treatment is required. This may mean inpatient admission or could involve long-line insertion, patient education in self-administration of IV antibiotics, and involvement of a home care team.

First isolate of Pseudomonas aeruginosa

(See Bronchiectasis pp. [link][link].)

  • Initial treatment is a 4–6-week course of oral ciprofloxacin 500–750mg bd and concurrent nebulized colistin 1–2MU bd

  • If this fails and the patient still has Pseudomonas on sputum culture, there are several options—IV antibiotics, usually an anti-pseudomonal penicillin (minimum 2 weeks), a further 4 weeks of ciprofloxacin 750mg bd with nebulized colistin 2MU bd or 3 months nebulized colistin 2MU bd

  • Combination IV antibiotics are only needed if there is resistance to one or more anti-pseudomonal antibiotics. Aminoglycoside antibiotic drug levels need careful monitoring

  • Consider long-term therapy with daily nebulized colistin or gentamicin to reduce levels of Pseudomonas in colonized patients with frequent exacerbations.

Macrolide antibiotics

have both antibacterial and immunomodulatory properties and decrease mucous production, alter inflammatory mediator release, and inhibit Pseudomonas virulence factors and biofilm formation. Five small trials have reported beneficial effects of macrolides in bronchiectasis, with reduced sputum volume and improved lung function and symptoms. The drugs are well tolerated, though concerns have been raised about NTM resistance with long-term use (see Bronchiectasis pp. [link][link]). Azithromycin 250mg 3 times weekly or 500mg twice weekly (with LFT monitoring) are possible regimes. Warn patient about possible side effects of hearing loss and tinnitus.

Further management

  • Self-management plan Patients need an individual plan for exacerbations, which usually involves having a supply of home antibiotics

  • Treatment of associated airflow obstruction/wheeze with inhaled steroids and/or bronchodilators

  • There is no specific treatment for abnormalities of mucociliary function, although β‎2 agonists may enhance airway clearance

  • Nebulized hypertonic saline (7%) may aid sputum clearance

  • Acetylcysteine may reduce sputum viscosity

  • Annual influenza and pneumococcal vaccinations

  • Osteoporosis prophylaxis (if on long-term steroids)

  • Reflux treatment if aspiration

  • Immunoglobulin replacement therapy Patients found to have immunoglobulin deficiency should be referred to an immunologist for further assessment. IV immunoglobulin replacement therapy is usually given once or twice monthly, as a day case or weekly subcutaneous at home

  • NIV Hypercapnic ventilatory failure due to end-stage disease may need long-term nocturnal NIV. This can also be used as a bridge to transplantation

  • Surgery This is the only potential curative treatment, with resection of a single chronically infected lobe occasionally being of benefit. It is less commonly needed now, as the incidence of single lobe disease related to previous severe childhood pneumonia is falling.

  • Transplant is most commonly performed for CF bronchiectasis, but referral may be warranted for severe non-CF-related disease (see Bronchiectasis pp. [link][link])

  • Nebulized DNase (dornase alfa)—no evidence for the use of this in non-CF bronchiectasis; it is not recommended.

Complications of bronchiectasis

  • Infective exacerbation

  • Haemoptysis—small-volume haemoptysis (increasing during exacerbations) is common. Massive haemoptysis (usually from tortuous bronchial arteries around damaged lung) is a life-threatening emergency (see Bronchiectasis p. [link])

  • Pneumothorax

  • Respiratory failure

  • Opportunistic mycobacterial colonization

  • ABPA

  • Brain abscess (now very rare)

  • Amyloidosis.

Bronchiectasis and Aspergillus

  • ABPA—excessive immune response to environmental fungus Aspergillus (most commonly fumigatus species); may be the cause of bronchiectasis (suspect particularly if upper lobe disease), as mucus plugs become impacted in distal airways, causing airway damage and subsequent dilatation (see Bronchiectasis pp. [link][link])

  • Aspergilloma—Aspergillus may colonize a previously formed cavity. This is extremely difficult to treat. Most commonly, it causes systemic upset and haemoptysis (see Bronchiectasis pp. [link][link]).

Further information

Evans DJ, Bara A. Prolonged antibiotics for purulent bronchiectasis in children and adults. Cochrane Database Syst Rev 2009;2:CD001392. Bronchiectasis http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001392.pub2/abstract.Find this resource:

Guideline for non-CF bronchiectasis. Thorax 2010;65(Suppl. 1). Bronchiectasis http://www.brit-thoracic.org.uk/Portals/0/Guidelines/Bronchiectasis/non-CF-Bronchiectasis-guideline.pdf.Find this resource: