1. Non–Cystic Fibrosis Bronchiectasis

1.1 Epidemiology

• Bronchiectasis is an abnormal dilation of the bronchi typically detected by CT scan.
• The median age at diagnosis is 50 years, though many patients have had symptoms for 10–20 years before confirmation.
• More prevalent in women (60% of cases).
• Estimated prevalence in industrialised countries: 1 in 1000 adults (higher in developing regions).
• With the widespread use of CT scans, bronchiectasis is increasingly identified as a complication of other chronic lung diseases (e.g. COPD, asthma).

1.2 Aetiology

• Bronchiectasis can be triggered by numerous causes (see table below), but in 30–50% of cases, no obvious aetiology is found (“idiopathic bronchiectasis”).
• The most common identifiable cause is previous severe lung infection.

Causes of Bronchiectasis

1.3 Risk Factors

1. History of severe lung infections (e.g. whooping cough, pneumonia).
2. Immunodeficiencies (e.g. primary immunoglobulin deficiency, secondary causes such as myeloma or HIV).
3. Structural lung abnormalities (e.g. obstructing lesions, previous tuberculosis stricture).
4. Chronic inflammatory airway diseases (e.g. COPD, asthma, allergic bronchopulmonary aspergillosis).
5. Ciliary dysfunction (e.g. primary ciliary dyskinesia).

1.4 Clinical Features

1.4.1 Symptoms

• Chronic productive cough with daily sputum production (mucoid, mucopurulent or purulent).
• Infective exacerbations: Increased sputum volume, viscosity, and purulence.
• Other common symptoms:
  • Minor haemoptysis
  • Malodorous breath
  • Fatigue and malaise
  • Dyspnoea on exertion
  • Wheeze
  • Musculoskeletal-type chest pain
• Coexisting chronic rhinitis/sinusitis is not uncommon.

1.4.2 Signs

• Finger clubbing in ~10% of cases.
• Focal crepitations (especially bibasally).
• In severe disease, signs of airway obstruction and possible type 2 respiratory failure in later stages.
• Major haemoptysis and amyloidosis can occur as complications.

1.5 Diagnostic Approach

1. Chest X-ray
   • May show bronchial wall thickening, ‘tramlines’ or ring shadows but can be normal in up to half of cases.
2. High-Resolution CT (HRCT) Scan
   • Gold standard: Demonstrates bronchial dilatation, lack of tapering bronchi, bronchial wall thickening.
   • May show cystic (saccular) changes, tree-in-bud pattern (small airway inflammation), and gas trapping if small airways are involved.
3. Pulmonary Function Tests
   • Often reveal obstructive impairment; used as a baseline to monitor progression.
4. Microbiological Assessment
   • Sputum culture: Identifies infecting organisms (e.g. Haemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus aureus).
   • Special tests for non-tuberculous mycobacteria where indicated.
5. Investigations for Aetiology
   • Immunoglobulin levels (IgG, IgA, IgM, subclasses, vaccine responses).
   • Tests for cystic fibrosis (sweat chloride, CFTR mutation analysis) in younger patients or predominantly upper lobe disease.
   • Evaluation for ABPA, HIV, ciliary dyskinesia, or rheumatological conditions as warranted by clinical presentation.

1.6 Immediate Management

• Typically, bronchiectasis is a chronic condition, so “immediate” management focuses on addressing acute exacerbations:

1. Antibiotic Therapy (typically 14 day duration)
   • Mild disease: Amoxicillin, doxycycline, or a macrolide (e.g. clarithromycin).
   • Moderate disease: Co-amoxiclav or doxycycline.
   • Severe disease: Broad-spectrum intravenous antibiotics (piperacillin/tazobactam; meropenem) if Pseudomonas is suspected or identified, or oral ciprofloxacin if sensitive.
2. Supportive Care
   • Adequate hydration.
   • Bronchodilators (β2-agonist ± inhaled steroids) if there is a significant reversible obstructive component.

1.7 Long-Term Management

1. Address Underlying Cause
   • Immunoglobulin replacement if Ig deficiency.
   • Surgery or bronchoscopic intervention for localised obstruction.
   • Anti-reflux measures for recurrent aspiration.
   • Anti-fungal / Corticosteroids for ABPA.
   • Antiretroviral therapy for HIV.
2. Airway Clearance and Physiotherapy
   • Lung clearance techniques taught by respiratory physiotherapists to reduce sputum load.
3. Chronic Antibiotic Prophylaxis
   • Consider if >3 exacerbations per year or evidence of progressive disease.
   • Examples: Low-dose daily amoxicillin, doxycycline, or co-amoxiclav; azithromycin (250–500 mg thrice weekly) for anti-inflammatory and antibacterial effects.
   • Nebulised antibiotics (e.g. colomycin, aminoglycosides) for patients chronically colonised with Pseudomonas aeruginosa.
4. Regular Sputum Cultures
   • Identifies resistant organisms (e.g. P. aeruginosa, non-tuberculous mycobacteria) and guides antibiotic choice.
5. Monitoring Lung Function
   • Follow-up spirometry to detect any progressive decline.

1.8 Prognosis / Complications

• Generally, non-CF bronchiectasis progresses slowly.
• Around 20% of patients may experience more rapid decline (FEV1 falling >50 mL/year), especially those with certain causes (e.g. ABPA, ciliary dyskinesia, non-tuberculous mycobacteria).
• Advanced disease can lead to respiratory failure (~15% mortality directly related to bronchiectasis).
• Other complications:
  • Major haemoptysis
  • Amyloidosis
  • Chronic colonisation with difficult pathogens (e.g. Pseudomonas).

2. Cystic Fibrosis

2.1 Epidemiology

• Most common fatal genetic disorder in Western countries.
• Prevalence: Approximately 1 in 2000–3000 newborn infants in Europe.
• Postnatal screening is now routine in several European countries, facilitating early diagnosis before symptoms become evident.

2.2 Aetiology

• Autosomal recessive mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene on chromosome 7.
• CFTR encodes a transmembrane chloride channel in the respiratory epithelium, exocrine glands, sweat ducts, etc.
• 1500 CFTR mutations identified, grouped by their effect on CFTR synthesis or function:
  • Defective or absent CFTR leads to reduced chloride transport, causing thick, sticky mucus.
• Over 70% of cases involve a mutation in amino acid 508 (ΔF508), leading to a misfolded protein with minimal function.

2.3 Risk Factors

• Because cystic fibrosis is genetically determined, the primary risk factor is carrying inherited mutations in the CFTR gene.
• There is a 1 in 25 carrier frequency among Caucasians.
• Children of two carriers have a 25% chance of inheriting the disease.

2.4 Clinical Features

2.4.1 Respiratory

• Progressive bronchiectasis with recurrent infective exacerbations.
• Excessively viscid mucus causes impaired mucociliary clearance, leading to chronic bacterial colonisation(e.g. Staphylococcus aureus, Pseudomonas aeruginosa).
• Predominant upper lobe involvement (as opposed to lower lobes in many non-CF bronchiectases).
• Respiratory failure (mainly Type 2) eventually occurs in severe or end-stage disease.

2.4.2 Systemic / Extra-Pulmonary

• Pancreatic insufficiency (affecting ~95%):
  • Malabsorption of fats and fat-soluble vitamins (A, D, E, K).
  • Steatorrhoea, low body weight, failure to thrive in children.
  • Glucose intolerance or diabetes (~25%).
• Meconium ileus in neonates (~10%), or bowel obstruction in older children/adults (meconium ileus equivalent).
• Male infertility (almost universal; congenital bilateral absence of vas deferens).
• Liver disease, gallstones (~10%), and cirrhosis (~5%).
• Chronic sinusitis, nasal polyps (~20%).
• Digital clubbing in >90%.
• Osteoporosis (~50%), vasculitic rashes, and reactive arthritis can also occur.

2.4.3 Age of Presentation

• Typically early childhood, sometimes detected in infancy via screening programmes.
• Milder CFTR mutations may present in adolescence or even adulthood.

2.5 Diagnostic Approach

1. Neonatal Screening
   • Blood spot tests for immunoreactive trypsin or direct CFTR genetic tests in some regions.
2. Sweat Chloride Test
   • Primary test: Elevated sweat chloride (>60 mmol/L) is indicative of cystic fibrosis.
3. Nasal Potential Difference Test
   • Measures abnormal ion transport across nasal epithelium.
4. Genetic Testing
   • Confirms specific CFTR mutations, including ΔF508, G551D, and others.

2.6 Immediate Management

In cystic fibrosis, “immediate” care often refers to addressing acute exacerbations or complications:

1. Antibiotic Therapy
   • Typically targets chronic respiratory pathogens, especially S. aureus or Pseudomonas aeruginosa.
   • Acute exacerbations may require intravenous routes if oral treatment fails or if resistant organisms are present.
2. Physiotherapy
   • Chest clearance techniques (e.g. flutter valve, active cycle of breathing) to mobilise secretions.
3. Supportive Measures
   • Oxygen therapy for hypoxia.
   • Nutritional support (high-calorie intake, supplementation for fat-soluble vitamins).

2.7 Long-Term Management

1. Airway Clearance and Mucolytics
   • Regular physiotherapy.
   • Nebulised hypertonic saline to reduce mucus viscosity.
   • DNase (dornase alfa) to break down DNA in sputum, improving clearance.
2. Antibiotic Prophylaxis
   • Flucloxacillin prophylaxis commonly used in childhood to reduce S. aureus colonisation.
   • Azithromycin (long-term, low dose) for anti-inflammatory and antibacterial effects.
3. Bronchodilators
   • Regular inhaled β2-agonists to relieve airway obstruction.
   • Consider inhaled steroids if there is an asthmatic component or allergic bronchopulmonary aspergillosis (ABPA).
4. Management of Extrapulmonary Manifestations
   • Pancreatic enzyme replacement for malabsorption.
   • Insulin for CF-related diabetes.
   • Supportive therapy (e.g. ursodeoxycholic acid for cholestasis, intravenous nutrition if needed).
5. CFTR Modulator Therapies
   • Ivacaftor for certain mutations (e.g. G551D) to increase chloride channel opening.
   • Combination correctors (e.g. lumacaftor–ivacaftor, tezacaftor–ivacaftor, elexacaftor–tezacaftor–ivacaftor) for ΔF508 and other specific mutations.
6. Specialist Multidisciplinary Care
   • Essential for coordinating respiratory, nutritional, and psychological support.
   • Gene replacement therapy under investigation but not yet mainstream.
7. Lung Transplantation
   • Considered in end-stage disease; can be curative for lung complications but does not address other systemic issues.

2.8 Prognosis / Complications

• Overall fatal disease: Slowly progressive respiratory failure is the usual cause of death.
• Median survival has improved from mid-20s (1970s) to the mid-40s currently.
• Lung transplantation offers a potential extension of life for selected patients.
• The emotional and practical burden is significant, affecting the patient and family due to daily treatments, repeated hospitalisations, and chronic decline.