Bronchiectasis: Causes

Pathogenesis (development of disease)

Repeated severe bronchial infections in childhood, such as pneumonias (lung infections), lead to remodeling of the structure of the bronchi. Bronchiectasis also often begins with narrowing (obstruction) of the bronchial tree, such as by foreign bodies or bronchial tumors. Ultimately, most triggers result in destruction of the respiratory ciliated epithelium and thus disruption of mucociliary clearance of the bronchi (self-cleaning of the bronchi). The ciliated epithelium consists of motile kinocilia that move in a coordinated fashion toward the pharynx (throat). They transport bronchial mucus and foreign bodies that have entered the airways, as well as microorganisms, out of the airways. As part of inflammatory processes, inflammatory cells infiltrate the surrounding parenchyma (“tissue”) of the bronchial epithelium. The tissue is destroyed and bulges in the form of saccular, spindle-shaped or cylindrical expansions occur. This disturbs the “mucociliary clearance” (self-cleaning mechanism of the bronchi), with the consequence of secretion retention (retention of secretion in the bronchi), which is an ideal breeding ground for infectious pathogens. In addition, the bronchial mucus can drain even more poorly due to the dilatations. A vicious circle (circulus vitiosus) develops.

Etiology (causes)

Biographic causes

  • Congenital (congenital) defects
    • Anatomic:
      • Marfan syndrome – genetic disorder that can be inherited in an autosomal-dominant manner or occur sporadically (as a new mutation); systemic connective tissue disorder that is most notable for tall stature, spider-limbedness, and hyperextensibility of the joints; 75% of these patients have an aneurysm (pathologic (abnormal) bulge in the arterial wall).
      • Scoliosis (S-shaped spine).
      • Tracheobronchomegaly – dilation of the trachea and large bronchi.
    • Other congenital disorders associated with impaired mucociliary clearance:
      • Agammaglobulinemia – X-linked immunodeficiency in which B lymphocytes cannot be fully formed due to a genetic defect; this causes increased susceptibility to infections in the ENT region as well as the lungs.
      • Alpha-1 antitrypsin deficiency – liver cells form the enzyme defective or in insufficient quantities; alpha-1 antitrypsin deficiency is associated with an increased risk of chronic obstructive pulmonary disease (COPD) in adults.
      • Defective ENaC protein – mutation in the ENaC gene resulting in a defective epithelial sodium channel; a hyperactive sodium channel occurs, leading to disruption of salt-water homeostasis (homeostasis = balance) at the respiratory mucosa (bronchial mucosa)
      • Hyper-IgE syndrome (HIES) – primary immunodeficiency clinically characterized by the triad of high serum IGE (> 2,000 IU/ml), recurrent staphylococcal skin abscesses, and recurrent pneumonias (pneumonia) with formation of pneumatoceles (abnormal accumulation of air in tissues)
      • Kartagener syndrome – congenital disease; triad of situs inversus viscerum (mirror image of the organs), bronchiectasis (synonyms: bronchiectasis; dilation of the bronchi) and aplasia (non-formation) of the paranasal sinuses; diseases without situs inversus are called primary ciliary dyskinesia (PCD).
      • Primary ciliary dyskinesia (PCD) (most common cause of non-CF bronchiectasis (not caused by cystic fibrosis)) – the movement of the cilia (cilia) is disturbed, resulting in decreased clearance of secretions → increased susceptibility to infection.
      • Selective IgA deficiency – most common genetic immunodeficiency; leads mainly to chronic recurrent (recurrent) infections of the respiratory tract.
      • Variable immunodeficiency syndrome (“Common variable immunodeficiency” (CVID)) – congenital immunodeficiency in which immunoglobulin synthesis, especially immunoglobulin G, is disproportionately low, resulting in increased susceptibility to infection, especially for bacterial infections of the respiratory tract and gastrointestinal tract (gastrointestinal tract).
      • Cystic fibrosis (CF) (synonym: cystic fibrosis).

Disease-related causes – acquired bronchiectasis.

  • Allergic bronchopulmonary aspergillosis (ABPA) – mixed allergic disease of the lungs (type I and type III allergy) triggered by molds of the tubular fungus genus Aspergillus.
  • Bronchial asthma
  • Chronic obstructive pulmonary disease (COPD)
  • Inflammatory bowel disease: Celiac disease (gluten-induced enteropathy) – chronic disease of the mucosa of the small intestine (small intestinal mucosa), which is based on hypersensitivity to the grain protein gluten.
  • Diffuse panbronchiolitis – chronic progressive (progressive) inflammation of the bronchioles.
  • Yellow fingernail syndrome (“yellow-nail syndrome”) – yellowish discolored nails; e.g. in chronic bronchitis, bronchiectasis (synonym: bronchiectasis), pleural effusion, sinusitis (sinusitis).
  • Fibrosis (pathological increase in connective tissue) – radiation fibrosis, pulmonary fibrosis, post-tuberculous fibrosis.
  • Immunological defects (secondary).
    • Chemotherapy
    • Immunosuppressive therapy
    • Tumor
  • Obstruction (narrowing) of the airway due to:
    • Benign (benign) tumors
    • Enlarged lymph nodes
  • Post-infectious – plays a role mainly in developing countries (most common cause); in industrialized nations, the rate of disease is declining due to the use of antibiotics and vaccination programs
  • Rheumatoid arthritis – inflammatory multisystem disease, usually manifested in the form of synovitis (inflammation of the synovial membrane).
  • Scoliosis (S-shaped spine) – sideways bending of the spine, with simultaneous rotation of the vertebrae, which can no longer be fully straightened.
  • Systemic lupus erythematosus (SLE) – systemic disease affecting the skin and connective tissue of the vessels, leading to vasculitides (vascular inflammation) of numerous organs such as the heart, kidneys or brain.
  • Tracheobronchial amyloidosis (most common form of pulmonary amyloidosis/deposits of amyloids (degradation-resistant proteins)).
  • Young syndrome – characterized by chronic bronchitis, sinusitis (inflammation of the sinuses) and azoospermia (absence of spermatozoa in semen); presumably inherited in an autosomal recessive manner

Other causes