Bronchiesctasis and CF

What is bronchiectasis?

Irreversible dilation of the airway with chronic mucus retention and airway wall destruction.

Bronchiectasis: focal vs diffuse

Focal = localized to one region (e.g., obstruction). Diffuse = widespread (e.g., CF, PCD).

Classic symptoms of bronchiectasis

Chronic cough, recurrent infections, dyspnea, wheezing, hemoptysis, fatigue, weight loss.

Why does bronchiectasis cause recurrent infections?

Dilated airways trap mucus → impaired clearance → bacterial colonization → inflammation → further airway damage.

Common organisms in bronchiectasis

H. influenzae, Pseudomonas aeruginosa, S. pneumoniae, S. aureus.

Most common global cause of bronchiectasis

Tuberculosis.

Non‑CF bronchiectasis: Causes

Post infectious: TB

Anatomic: Foreign body, bronchial atresia/stenosis, carcinoid tumor, chronic aspiration, broncholithiasis, RML syndrome.

Immune-related Disease: Allergic bronchopulmonary aspergillosis (ABPA),

Non‑CF bronchiectasis: genetic causes

CF, primary ciliary dyskinesia, alpha‑1 antitrypsin deficiency.

Primary ciliary dyskinesia inheritance + pathophysiology

Autosomal recessive. Altered dynein formation of cilia rendering them ineffective

Most common Primary Cilary Dyskinesia gene defects

DNAI1 and DNAH5.

Classic triad of Kartagener syndrome(Situs inversus totalis)

Situs inversus, chronic sinusitis, bronchiectasis.

Why does PCD cause situs inversus?

Dysfunctional embryonic cilia disrupt left–right organ orientation. (cilia cause organs to flip)

Radiographic CXR findings of bronchiectasis

Tram‑tracking and peribronchial cuffing(bronchial wall thickening)

CT findings diagnostic of bronchiectasis

Lack of bronchial tapering» airway visibility to lung periphery, signet‑ring sign (bronchus > accompanying artery).

Signet‑ring sign

Bronchus diameter larger than adjacent pulmonary artery. Indicative of Bronchiectasis

Bronchiectasis workup: labs

A1AT level/genotype, CF testing, PCD genetic testing,

Bronchiectasis treatment pillars

Airway clearance, antimicrobial therapy, reduce inflammation, treat underlying cause.

Hypertonic saline role in treating Bronchiectasis and CF

Draws water into mucus → thins secretions → improves clearance.

Major complications of bronchiectasis

Hemoptysis(due to erosion of bronchial arteries), empyema, lung abscess, cor pulmonale(right sided HF).

Hemoptysis mechanism in bronchiectasis

Erosion of hypertrophied bronchial arteries due to chronic inflammation.

CF: inheritance pattern

Autosomal recessive.

CFTR gene location

Chromosome 7.

CFTR protein function

Chloride channel regulating Cl⁻ and Na⁺ transport across epithelial surfaces.

CF airway defect

Cl⁻ cannot exit airway epithelium → dehydrated mucus → impaired mucociliary clearance → infection/inflammation.

CF sweat gland defect

Cl⁻ cannot be reabsorbed → high sweat chloride.

Newborn CF screening test

Immunoreactive trypsinogen.

Most common CF mutation

ΔF508

ΔF508 pathophysiology in CF

Misfolded CFTR retained in RER → degraded → no membrane expression → no Cl⁻ transport.

CF‑PANCREAS Clinical Presentation

Chronic respiratory disease, Failure to thrive, Polyps, Alkalosis (hypochloremic), Neonatal meconium ileus, Clubbing, Rectal prolapse, Electrolyte abnormalities, Aspermia, Sputum pathogens.

Most common CF pathogens in children

Staphylococcus aureus.

Most common CF pathogens in adults

Pseudomonas aeruginosa.

Why is Pseudomonas dangerous in CF?

Accelerates lung function decline and increases mortality risk.

CF pancreatic insufficiency

Lack of digestive enzymes → malabsorption → failure to thrive.

CF airway clearance therapies

Chest physiotherapy, flutter valve, hypertonic saline, dornase alfa.

Dornase alfa mechanism

Mucolytic: Cleaves DNA in mucus → reduces viscosity.

CF anti‑inflammatory therapy

Chronic azithromycin.

CFTR modulators: potentiator

Ivacaftor (opens CFTR channel longer and wider).

CFTR modulators: correctors/stabilizers

Lumacaftor, tezacaftor, elexacaftor, vanzacaftor (improve trafficking»inc the number of gates).

CF exacerbation symptoms

↑ cough, ↑ sputum, hemoptysis, anorexia, ↓ exercise tolerance.

Major CF complications

Hemoptysis, ABPA, pneumothorax, cor pulmonale(right sided HF).

Difference between CF bronchiectasis and non‑CF bronchiectasis

CF is genetic, multisystem, with dehydrated mucus due to CFTR dysfunction

Why CF patients taste salty

High sweat chloride due to defective reabsorption.