Bronchiectasis and Cystic Fibrosis Overview

Bronchiectasis

• Bronchiectasis is a syndrome characterized by irreversible dilation and destruction of the bronchi, leading to inadequate mucus clearance and pooling of mucus in the airways.
• It's often associated with persistent microbial infections and inflammation.
• Bronchiectasis is divided into Cystic Fibrosis (CF) and non-CF forms.

Cystic Fibrosis

• Cystic Fibrosis (CF) is the most common genetic disease in the US, affecting approximately 1 in 3,000 white births.
• It's an autosomal recessive disorder with variable penetrance.
• The CF gene is located on the long arm of chromosome 7.
• The CF gene encodes the CF transmembrane regulator protein (CFTR).

CFTR Mutations

• CFTR mutations affect the function of the CFTR protein, causing it to not function properly or be produced in insufficient quantities.
• These mutations lead to various clinical consequences, with different mutation classes having different effects on CFTR function.
  • Class I: CFTR is not created.
  • Class II: CFTR is created, but misfolded and does not reach the cell surface.
  • Class III: CFTR is created and reaches the cell surface but does not function properly.
  • Class IV: The opening in the CFTR protein is faulty.
  • Class V: CFTR is created in insufficient quantities.

Lung Manifestations of CF

• In the lungs, CF causes changes in the mucus layer, including impaired mucociliary clearance, persistent bacterial infection, and increased inflammation (accumulation of cellular debris like DNA and elastase).
• These changes lead to airway obstruction and progressive lung dysfunction.
  • Different cell types, including goblet cells and inflammatory cells or proteins, are elevated or present in abnormally high amounts.
  • DNA and elastase are present in increased amounts.

Diagnostic Criteria for CF

• Elevated sweat chloride levels on two occasions.
• Identification of CFTR gene mutations.
• In vivo demonstration of characteristic abnormalities in ion transport across the nasal epithelium.
• One or more phenotypical features of CF
  • Sino-pulmonary disease
  • Characteristic GI or nutritional disorders
  • Obstructive azoospermia
  • Salt loss syndrome
• Sibling with CF
• Positive newborn screening

Classic and Non-Classic Cystic Fibrosis

• Classic CF is characterized by a lack of functional CFTR protein, resulting in more severe symptoms.
• Non-classic CF involves some functional CFTR protein, which provides a slight survival advantage but still presents with reduced lung function. – Different levels of inflammation, mucus production, and bacterial infection. – Different levels of pancreatic function. – Different sweat chloride values.

Prevalence of Respiratory Microorganisms in CF

• The prevalence of certain respiratory microorganisms, such as Pseudomonas aeruginosa, may exhibit trends over time in patients with CF.

Management of Bronchiectasis and CF

• General Management: Aims at maintaining lung function, improving quality of life, and clearing lung secretions.

  • Chest physiotherapy
  • Forced expiratory techniques
  • Mechanical vests
  • Flutter valves
  • Exercise training
  • Vaccination (influenza and pneumococcal)

• Specific Medications (CF):

  • DNase: Reduces viscosity of secretions.
  • Inhaled hypertonic saline: Used to treat thickened secretions.

• Antibiotic Therapy: Approaches include:

  • Chronic prophylaxis to prevent infection.
  • Conversion to culture negativity.
  • Palliation of acutely elevated signs and symptoms of infection.
  • Suppressing established infections.
    • Specifically, inhaled tobramycin or aztreonam are recommended in moderate-to-severe cases of CF respiratory dysfunction, while other treatments are not supported by adequate evidence.

• Macrolides:

  • Recent trials suggest benefits for non-CF bronchiectasis (reduced exacerbations, potential improved lung function and quality of life).

Pulmonary Complications

• Possible complications from bronchiectasis include:
  • Hemoptysis
  • Pneumothorax
  • Non-tuberculous mycobacterial infections
  • Respiratory failure (cor pulmonale)

Radiographic Findings

• Routine CXR (chest X-ray) may reveal findings such as tram tracks, hyperinflation, and ring shadows.
• HRCT (high-resolution computed tomography) is considered the gold standard, showing specific findings like internal bronchus diameter wider than adjacent artery and failure of bronchi to taper.

Bronchiectasis in Non-CF patients

• Inflammation and infection from different pathogens, like H. influenza, contribute to progression.
• Inflammatory response, such as PMNs (polymorphonuclear leukocytes) infiltration, also plays a role.

Diagnostic Testing

• Diagnostic tests might include CBC, immunoglobulins, spirometry, HRCT, and sputum cultures.
• Further tests such as Bronchoscopy, EM, BAL, and biopsies might be necessary in specific situations.

This quiz explores the characteristics of bronchiectasis, including its association with cystic fibrosis (CF). It covers the genetic aspects of CF, including the CFTR mutations and their clinical implications. Test your knowledge on this important respiratory syndrome and its genetic basis.