Bronchiectasis

Question 1

What is bronchiectasis?

Answer 1

Bronchiectasis is the permanent dilation of bronchi due to the destruction of the elastic and muscular components of the bronchial wall.

• It is often caused as a consequence of recurrent and/or severe infections secondary to an underlying disorder.
• The majority of patients will present with a chronic cough and sputum production

Question 2

What is the aetiology of bronchiectasis?

Answer 2

Bronchiectasis has many different causes

The assessment and determination of an underlying aetiology determine the treatment as well as prognosis of this disease

• Post-infectious:
  
  • Prior childhood respiratory infections due to viruses (i.e., measles, influenza, pertussis)
  • Prior infections with Mycobacteria or severe bacterial pneumonia
  • Exaggerated response to inhaled Aspergillus fumigatus
• Immunodeficiency
  
  • Ig deficiency
  • HIV
• Genetic
  
  • Cystic fibrosis
  • Ciliary dyskinesia or immotile cilia syndrome with or without Kartagener’s syndrome (an autosomal-recessive condition characterised by the triad of ciliary dyskinesia, situs inversus, and chronic sinusitis)
  • Alpha-1-antitrypsin deficiency.
• Aspiration or inhalation injury.
• Connective tissue disorders
  
  • Rheumatoid arthritis
  • Sjogren’s syndrome.
• IBD
  
  • Ulcerative colitis
  • Crohn’s disease
• Focal bronchial obstruction:
  
  • Foreign body
  • ​Broncholith
  • Stenosis
  • Tumour
  • Adenopathy with extrinsic compression
• Other ​
  
  • Mounier-Kuhn’s syndrome (also known as tracheobronchomegaly, characterised by abnormal dilation of the trachea and main bronchi)
  • Williams-Campbell’s syndrome (also known as tracheomalacia, characterised by absence or weakness of bronchial cartilage, leading to bronchial collapse)
  • Yellow nail syndrome
  • Pulmonary sequestration
  • Ehlers-Danlos syndrome
  • Marfan’s syndrome
  • Young’s syndrome (a condition, believed to be genetic, characterised by obstructive azoospermia with normal sperm production plus chronic or recurrent sinus and lung infections).
• Idiopathic
  
  • 7-50% of cases

Question 3

What is the pathophysiology of bronchiectasis?

Answer 3

• The dilation and thickening of the bronchi seen in bronchiectasis are due to chronic inflammation elicited by the host response to micro-organisms colonising the airways. This persistent airway inflammation leads to the subsequent development of bronchial wall oedema and increased mucus production. Several inflammatory cells including neutrophils, T lymphocytes, and other immune effector cells are recruited to the airways and subsequently release inflammatory cytokines, proteases, and reactive oxygen mediators implicated in the progressive destruction of the airways.
• This initial insult to the airways by the primary infection leads to increased inflammation, resulting in bronchial damage, and serves as a nidus for subsequent colonisation of the airways. As a result, a vicious cycle ensues that predisposes to persistent bacterial colonisation and to a subsequent chronic inflammatory reaction that eventually leads to progressive airway damage and recurrent infections.
• The factors that predispose individuals with an initial infection to go on to develop bronchiectasis remain unclear.

Question 4

How is bronchiectasis classified?

Answer 4

Morphological classification: Reid classification of bronchiectasis

Cylindrical bronchiectasis:

• Bronchi enlarged and cylindrical in shape
• Normal tapering of airway as it traverses to the periphery is not present
• Distal airways end abruptly, owing to mucus plugging
• Fewer generations of bronchi than normal
• Parallel tram-track lines are seen on CXR or CT scan
• CT cross-section views reveal ‘signet ring’ appearance of the dilated bronchus and its accompanying vessel.

Varicose bronchiectasis:

• Irregular bronchi, with alternating dilation and constriction
• Bronchographic pattern resembles varicose veins.

Saccular or cystic bronchiectasis:

• Most severe form
• Commonly found in cystic fibrosis patients
• Bronchi are dilated, forming a cluster of round air-filled or fluid-filled cysts
• Only 25% of the normal number of bronchial subdivisions
• Degree of bronchial dilation increases proximal to distal
• Bronchial tree ends in blind sacs.
• more likely to be associated with Pseudomonas colonisation
• more sputum production than the other types.

Question 5

What are the risk factors for bronchiectasis?

Answer 5

• cystic fibrosis (the most common identifiable cause of bronchiectasis),
• immunodeficiency
• previous infections
• congenital disorders of the bronchial airways
• primary ciliary dyskinesia
• alpha-1 antitrypsin deficiency
• connective tissue disease
• inflammatory bowel disease
• aspiration or inhalational injury
• focal bronchial obstruction
• tall, thin, white females, aged 60 or over
  
  • Are at greater risk of pulmonary non-tuberculous mycobacteria (PNTM)-related bronchiectasis.
  • Mitral valve prolapse, scoliosis, and heterozygous cystic fibrosis transmembrane conductance regulator (CFTR) mutations have been found in greater frequency in these patients

Question 6

Summarise the epidemiology of bronchiectasis?

Answer 6

The prevalence worldwide is unknown due to the lack of standardised medical care and poor health care access in underdeveloped countries.

In the UK, the incidence is believed to be 1.06 to 1.3 per 100,000 population

Question 7

What are the presenting symptoms of bronchiectasis?

Answer 7

• cough
  
  • ​Occurs in 98% of patients and is the most common symptom of bronchiectasis
  • An acute exacerbation often presents as worsening of cough.
  • May be associated with large amounts of purulent sputum and, less commonly, haemoptysis.
  • worsen when lying flat/on one side
• sputum production
  
  • ​Daily sputum production is present in two-thirds of patients.
  • Bloody sputum is present in about 50% of patients and is usually mild
  • Sputum production will often increase during acute respiratory infections.
  • Sputum production will often increase during acute respiratory infections.
• dyspnoea
  
  • Present in majority of patients
  • especially with exertion.
  • Often correlates with severity of bronchiectasis on chest CT.
• fever​
• fatigue
  • A non-specific symptom
  • very common
  • An acute exacerbation often presents with fatigue.
• haemoptysis
  
  • ​Thought to originate from the bronchial arteries or bronchial-pulmonary anastomoses.
  • usually mild, but if severe - admit and consider bronchial artery embolisation.
• rhinosinusitis
  
  • Bronchiectasis due to a primary mucociliary clearance defect, such as primary ciliary dyskinesia or cystic fibrosis, will probably be accompanied by symptoms of rhinosinusitis.
• weight loss
  
  • A non-specific sign.
• wheezing
  
  • ​Present in 1/4 of pts
  • but more common in bronchiectasis patients who have concomitant asthma.

Question 8

What are the signs of bronchiectasis O/E?

Answer 8

• crackles O/A
  
  • ​most pts will have crackles
• high-pitched inspiratory squeaks O/A
  
  • ​commonly heard
• rhonchi O/A
  
  • commonly heard​

uncommon

• clubbing
  
  • quite rare

Question 9

Which rheumatoid condition has been associated with an increased prevalence of bronchiectasis?

Answer 9

The prevalence of bronchiectasis is increased in patients with rheumatoid arthritis compared with the general population.

• bronchiectasis symptoms may sometimes precede RA symptoms
• hence rheumatoid factor is checked

Question 10

What are the primary investigations for bronchiectasis?

Answer 10

imaging

• CXR
  
  • Findings are non-specific and often non-diagnostic,
  • but may show characteristic volume loss obscuring the underlying hemidiaphragm, tram lines, and tubular or ovoid opacities.
  • = may be normal or show obscured hemidiaphragm, thin-walled ring shadows with or without fluid levels, tram lines, tubular or ovoid opacities
• high-resolution chest CT
  
  • Recommended for all patients.
  • Shows dilation of bronchi with or without airway thickening.
  • = thickened, dilated airways with or without air fluid levels; varicose constrictions along airways; cysts and/or tree-in-bud pattern

bloods

• FBC
  
  • The WBC count will aid in determining the presence of a superimposed infection.
  • If the eosinophil count is high, an underlying allergic bronchopulmonary aspergillosis is possible.
• serum immunoglobulins
  
  • ​Functional assessment of immunoglobulins is performed by testing titres to Strep pneumo 23 serotypes in response to Pneumovax.
  • Immunoglobulin replacement reduces the frequency of infectious episodes and prevents further destruction of the airways.
  • = decreased IgG, IgM, and/or IgA with inappropriate titres to Pneumovax
• rheumatoid factor
  
  • ​= positive rheumatoid factor may be detected
• serum HIV antibody
  
  • Recommended in all patients
  • Patients with HIV infection are predisposed to developing recurrent sinopulmonary infections and bronchiectasis, which is probably due to abnormal B-lymphocyte function

cytology

• sputum culture and sensitivity
  
  • ​Frequently, a pathogenic organism can be recovered in the sputum.
  • = gram-positive bacteria; gram-negative bacteria; non-tuberculous mycobacteria; fungi
  • aid Tx decisions to treat possible overlying infection
• serum alpha-1 antitrypsin phenotype and level
  
  • Referral for consideration of replacement therapy is suggested if abnormal phenotype or level.
  • The MM phenotype indicates patient is homozygous for the normal M allele
  • = possible abnormal phenotype or level

other

• sweat chloride test
  
  • An abnormal test is diagnostic for cystic fibrosis.
  • If abnormal or intermediate, cystic fibrosis transmembrane regulator protein (CFTR) gene mutation analysis should be done.
• Aspergillus fumigatus skin prick test
  
  • Recommended in patients with central bronchiectasis, asthma, and elevated IgE.
  • Further testing should include total serum IgE and Aspergillus fumigatus IgG precipitins.
  • = immediate cutaneous reactivity to antigen in bronchopulmonary aspergillosis
• nasal nitric oxide (NNO)
  
  • Recommended for patients with a high clinical suspicion of primary ciliary dyskinesia (PCD).
  • = low (<100 parts per billion) NNO level in primary ciliary dyskinesia; high NNO level excludes a diagnosis of PCD
• pulmonary function tests
  
  • Reduction of the FEV1 suggests the presence of infection or worsening bronchiectasis.
  • Spirometry recommended with most surgery visits.
  • = reduced FEV1, elevated RV/TLC

Question 11

How would you interpret the sweat chloride test results?

Answer 11

>60 mmol/L (>60 mEq/L) cystic fibrosis is likely

40 to 59 mmol/L cystic fibrosis is possible

<39 mmol/L cystic fibrosis is very unlikely

Question 12

What are tram lines?

Answer 12

seen on high res. CT scan in pts with bronchiectasis

Abnormal bronchial dilation is recognised as the lack of normal tapering of bronchi –> a tram line or flared appearance in the periphery of the lung;

more prominent when the bronchial walls are thickened.

Question 13

What is a tree in bud pattern?

Answer 13

seen in bronchiectasis pts on high res. CT

Affected small airways plugged by mucus appear as small, irregular, V- and Y-shaped markings 2 mm in size in the periphery of the lung (tree-in-bud pattern).

Question 14

What would fluid filled cysts seen on high res. CT indicate?

Answer 14

May show fluid-filled cysts; these represent superimposed infection and warrant a course of systemic antibiotics.

Question 15

What are some secondary investigations for bronchiectasis?

Answer 15

• bronchial biopsy and electron microscopy of cilia
  
  • Can be used to confirm a low nasal nitric oxide and, therefore, diagnose primary ciliary dyskinesia.
  • = abnormal ciliary beat motion and/or morphology in primary ciliary dyskinesia
• cystic fibrosis transmembrane regular (CFTR) protein gene mutation testing
  
  • If the sweat chloride test is abnormal, the patient should undergo CFTR gene mutation testing.
  • = positive in cystic fibrosis
• swallow study
  
  • Suggested to evaluate for chronic aspiration.
  • If a swallow study or pH monitoring suggests the presence of aspiration, referral to a gastroenterologist is recommended.
  • = may be abnormal in presence of chronic aspiration
• sputum pH monitoring
  
  • ​see above
• 6-minute walk test
  
  • Should be considered for patients at risk for desaturation with exercise.
  • Can be used to assess serial changes in functional capacity.
  • = reduced in those with significantly reduced lung function

Question 16

Explain the management plan for bronchiectasis

Answer 16

• Treatment for all patients involves maintenance therapy and treatment of acute exacerbations, with attention to the specific organism involved.
• For a select group of patients, surgery may be indicated.
• Patients with severe disease or a resistant organism (typically Pseudomonas) are likely to require IV antibiotics during acute exacerbations.
• For severe, progressive disease lung transplantation should be considered.
• The goal of treatment is to decrease baseline clinical symptoms of cough, sputum production, and dyspnoea, to improve quality of life, to decrease the number of acute exacerbations, and to prevent progression of airway damage.
• The particular organism present in the sputum, specifically Pseudomonas, and the frequency of exacerbations determine antibiotic treatment choices.
• Those with low risk of developing a Pseudomonas infection have few, if any, exacerbations and may require less maintenance therapy.

Question 17

What is the Tx plan for bronchiectasis?

Answer 17

• excercise and improved nutrition
  
  • pulmonary rehab
• Plus – airway clearance therapy
  
  • postural drainage, percussion, vibration, and the use of oscillatory devices.
• Adjunct – inhaled bronchodilator
  
  • ​salbutamol, ipatropium, tiotropium
• ​Adjunct – inhaled hyperosmolar agent
  
  • ​hypertonic saline inhaled + mannitol
  • helps reduce inflammatory mediators, improve sputum bacteriology, and improve quality of life scores
  • might cause chest tightness & wheeze in some - bronchodilator remedies
• Adjunct – long-term oral macrolide
  
  • ​azithromycin
  • therapeutic benefit in bronchiectasis patients with or without Pseudomonas​

Question 18

How does Tx differ for pts with high risk for / known chronic Pseudomonas infection?

Answer 18

also add an inhaled Abx:

• tobramycin / colistimethate sodium / gentamycin

Question 19

How does Tx differ for an acute exacerbation: mild to moderate disease?

Answer 19

short term oral Abx

• amoxicillin / clarithromycin / trimethoprim/sulfamethoxazole / ciprofloxacin / levofloxacin

Question 20

How does the Tx plan differ for

acute exacerbation: severe or not responding/resistant to oral antibiotics

Answer 20

short term IV Abx

• ciprofloxacin / cefepime / vancomycin / gentomycin

Question 21

What are some possible complications of bronchiectasis?

Answer 21

• massive haemoptysis
  
  • Massive, life-threatening haemoptysis (>250 mL/day) may occur.
  • Protection of the airway is achieved by reclining the patient on the side the bleeding is suspected. If needed, endotracheal intubation is recommended.
  • Breathing and circulation are monitored and supported as needed. Immediate referral to a thoracic surgeon and/or interventional radiologist is essential for bronchoscopy-guided haemostatic tamponade, bronchial artery embolisation, or surgical resection of the involved area
  • Haemoptysis is thought to originate from the bronchial arteries or bronchial-pulmonary anastomoses
• respiratory failure
  
  • A primary goal is to prevent or treat tissue hypoxia.
  • Treatment includes airway protection, supplemental oxygen, potentially mechanical ventilation, and treatment of the underlying cause.
• cor pulmonale
  
  • Early and effective treatment helps to prevent cor pulmonale.
  • If there is evidence of pulmonary hypertension, immediate referral to a pulmonologist and/or thoracic surgeon is optimal.
  • In the most severe cases, heart and lung transplantation may be necessary

Question 22

Summarise the prognosis of bronchiectasis

Answer 22

• Bronchiectasis is an irreversible condition.
• The typical disease course consists of periods of symptom control interrupted by periods of exacerbations.
• Bronchiectasis frequently co-exists with other respiratory disease, making it difficult to determine prognosis for bronchiectasis alone.
• Factors associated with a faster decline in lung function include more frequent severe exacerbations.
• Hypoxaemia, hypercapnia, dyspnoea, and radiographic extent of disease have been shown to correlate with mortality.
• Conversely, a higher BMI, regularly scheduled doctor visits, and vaccinations improve survival
• Pseudomonas species in the sputum of patients with bronchiectasis indicates more extensive lung disease and more severe impairment of pulmonary function than in patients without Pseudomonas species colonisation. Some studies have shown that Pseudomonas species colonisation is an independent factor associated with a faster decline in lung function

Question 23

Which factors have been found to predict mortality in moderate to severe bronchiectasis?

Answer 23

• Pseudomonas aeruginosa infection
• Male sex
• Advanced age
• Higher RV/TLC ratio
• Increased wall thickness on CT imaging
• Low activity level score as judged by St. George’s Respiratory Questionnaire.