Cystic fibrosis + bronchiectasis

What is Bronchiectasis?

Persistent or progressive, chronic, lung condition characterised by permanent dilation of the bronchi due to irreversible damage to the elastic and muscular components of the bronchial wall

Symptoms of bronchiectasis

• Persistent cough

• Large volumes of purulent sputum

• Dyspnoea

• Fatigue and reduced exercise tolerance

• Non-pleuritic chest pains present between exacerbations

• Haemoptysis

Signs of bronchiectasis

• Inspiratory coarse crackles, especially lower zones

• Wheeze

• High-pitched inspiratory squeaks

• Large airway rhonchi (low pitched snore-like sounds)

• NO SMOKING HISTORY 

Risk factors of bronchiectasis

Women > men

Increasing age

Recurrent and/or severe lower respiratory tract infection

COPD / asthma/CF

Pathophysiology of bronchiectasis

Persistent airway inflammation → bronchial wall oedema → increased mucus production

→ Inflammatory cells (neutrophils, T cells) recruited to the airways

→ Cytokines, proteases, and R.O.S destroy the airways

Bronchial damage leads to colonisation of the airways

** Cycle of colonisation and subsequent chronic inflammation leads to progressive airway damage and recurrent infection

What investigations do you carry out to diagnose brochesctasis

• High Resolution CT – gold standard → Signet ring sign: bronchus > accompanying pulmonary artery

• Sputum culture

• Chest x-ray: 

• Oxygen saturation levels

• Full blood count incl. WCC, CRP

• Spirometry – identify severity of airflow obstruction

Management of bronchiectasis

Treatment goal – prevent/slow down progression of disease

• Respiratory physiotherapy (airway clearance techniques)

• Mucolytic agents

• annual influenza vaccine 

• Antibiotics (for longer duration)

• Bronchodilators

• Pulmonary rehabilitation

• Lung resection surgery

What mutation leads to cystic fibrosis and how is the gene affected?

Autosomal recessive

deletion of phenoalynine in CFTR gene of Chromosome 7

• Misfolded CFTR protein synthesised in ER

• Protease-sensitive

• Readily degraded before entering Golgi complex

What is the role of the CFTR protein?

It is a Cl- transport protein found in the plasma membrane of epithelial cells → facilitates passive movement of Cl- across an electrochemical gradient

ATP binding and hydrolysis in the CFTR protein open and close a continuous ion channel

Pathophysiology of cystic fibrosis

Sweat glands: Impaired Cl- reabsorption → high salt sweat

Decreased Cl- secretion at the apical membrane → thickened, dehydrated secretions/mucus

Lungs: mucus plugging → colonisation → bronchiectasis 

decreased mucocilliary clearance

Pancreas: stagnant enzymes → auto-digestion → pancreatic insufficiency + diabetes mellitus

Liver: cholestasis → inflammation → fibrosis ± cirrhosis

Clinical manifestations of cystic fibrosis

salty sweat → increased risk of dehydration

nasal congestion and discharge 

nasal polyposis 

sinus infections

chronic bronchiecstasis 

male infertility: bilateral absence of vas deferens + reduced female fertility: abnormal cervical mucous

How do we test for cystic fibrosis

Antenatal testing (if high risk)
• Chorionic villus sampling (11-14 weeks)
• Amniocentesis (15-20 weeks)

Newborn blood spot screening
• Usually performed at day 5 of life
• Immunoreactive trypsinogen (IRT)

also need +ve sweat test: Cl- ≥ 60 mmol/L

Management of cystic fibrosis

Mucolytics:

• rhDNase (e.g. dornase alfa)

• Inhaled Hypertonic NaCl

• Inhaled mannitol dry powder

Chest physiotherapy

Airway clearance techniques

Regular monitoring:

• Respiratory secretion samples (sputum)

• Spirometry

• Chest x-ray

What are some lifestyle changes/ modifications recommended for patients with CF?

• Immunisations and vaccinations#

• No smoking/vaping

• Regular exercise

• Monitor BMI

• Glucose monitoring

• Monitoring blood tests (FBC/U&Es/CRP/LFTs/vitamin levels)

Targeted CF therapies

CFTR potentiators: Increases flow of Cl- ions through the mutant channel

+

CFTR correctors: Migrate misfolded CFTR protein to plasma membrane, partial restoration