CF, Bronchiectasis, and OSA Flashcards
Cystic Fibrosis
Epidemiology
-
Most common AR genetic disease of Caucasians
- Northern European heritage most affected
- Other populations less frequent
- ~ 30,000 cases in US ⇒ 1 per 2k-3k live births
- Survival ↑↑↑ in last 30 years
- Median 39+ y/o
CFTR
Gene
“Cystic fibrosis transmembrane regulator”
- Codes for a chloride channel
- Found at apical cell surface of secretory organs
CFTR
Mutation
- AR genetic disease
- 1,500+ mutations identified so far
- Only 5 mutations found in > 1%
- Most common mutation ⇒ ∆F508
Cystic Fibrosis
Pathogenesis
Abnormal CFTR gene ⇒ absent, non-functioning, or hypo-functioning chloride channel.
Results in abnormal mucus which affects a variety of organs:
- Lungs ⇒ recurrent respiratory infections
-
Pancreas ⇒ exocrine pancreatic insufficiency (85%)
- Fat malabsorption
- Sweat glands ⇒ abnormally high sweat chloride
- Vas deferens ⇒ obstructive azospermia and male sterility
- Sinuses ⇒ recurrent sinus infections
CF
Diagnosis
-
Newborn screening ⇒ all 50 states
- Heelstick for trypsinogen
- Marker of pancreatic injury
- Sensitive but not specific
- Heelstick for trypsinogen
-
Sweat test ⇒ gold standard for diagnosis
- Sweat chloride > 60 mmol/L
- Genotype testing ⇒ for two most prevalent CF mutations
CF
Signs and Symptoms
- Pulmonary infection
- Pancreatic insufficiency
- ↑ Sweat Cl- levels
CF
Lung Disease
- Causes 95% of mortality and most of the morbidity in CF
-
Abnormal airway secretions become infected with bacteria shortly after birth
- Abx ↓ pathogen load
- Infection can never be completely eradicated
- Bacterial pathogens may change over time
Chronic respiratory infection or colonization ⇒ intermittent acute exacerbations ⇒ progressive decline in lung function ⇒ obstructive airways disease ⇒ ultimately respiratory failure
CF
Major Pathogens
- Pseudomonas aeruginosa ⇒ present in 85% of pts by adulthood
- Staph. aureus
- Hemophilus influenza
- Other gram negative organisms
CF
Treatment
Maintain aggressive airway clearance and a good pulmonary toilet.
- Chest physiotherapy
- Inhaled bronchodilators ⇒ SABA, LAMA, ICS
- Mucolytics ⇒ recombinant human DNAse
- Hypertonic saline 3%
-
± Suppressive antibiotics
- Oral ⇒ Azithromycin 3x/week
- Inhaled ⇒ nebulized tobramycin
- Nutritional support ⇒ pancreatic enzymes
- Aggressive weight management
- ± CFTR modulators
CFTR Modulators
New class of drugs that act to improve function of defective CFTR protein.
- Act directly on CFTR channel itself
- Major revolution in CF treatment
- Extremely expensive
- Need to monitor for side effects
Ivacaftor
- CFTR modulator drug
- At least one copy of G551D mutation
- Improved FEV1 by 10% compared to placebo
- Follow LFT’s and eye exam (cataract risk)
Lumacaftor-Ivacaftor
- CFTR modulator drug
- Homozygous for ∆F508 mutation
- Improved FEV1 by 3%
- Reduced exacerbations by 30-40%
- Monitor LFT’s and eye exam
- Side effects
- Chest pain
- Menstrual irregularities
CF
Acute Pulmonary Exacerbations
Defined as acute SOB, ∆ FEV1, ∆ sputum
Treatment
- Continue normal therapy
- Add abx against primary pathogens
- Mild exacerbation ⇒ can use PO
- Severe exacerbation ⇒ need IV
- Usually Pseudomonas aeruginosa
- Requires high-dose, double coverage
Advanced CF
Management
- Supplemental oxygen
- Non-invasive ventilation
- Lung transplantation ⇒ needs to be bilateral
Bronchiectasis
Definition
Chronic necrotizing infection of the bronchi and bronchioles leading to abnormal dilation.
- Dilation must be permanent
- Can be seen after abnormal healing of infection
- Can be part of CF or Kartegener’s syndrome
Bronchiectasis
Clinical Signs
- Severe, persistent cough
- Expectoration of copious amounts of foul-smelling, purulent sputum
- Fevers if pathogens present
- Symptoms start in childhood
- Later see hypoxia, hypercapnia, cor pulmonale
Bronchiectasis
Pathophysiology
- Early changes reversible
- Changes irreversible if
- Obstruction persists
-
Infection occurs, especially during growth
- Airways develop abnormally
- Infection ⇒ inflammation of bronchial wall ⇒ bronchial damage ⇒ weakening and further dilation
- Lower lobes affected bilaterally
- Most severe in distal bronchi
- Airways become dilated up to 4x normal
- Severe form associated with CF
Bronchiectasis
Histopathology
- Intense inflammatory exudate in bronchioles
- Desquamation and/or necrotizing ulceration of epithelium
- ± Squamous metaplasia of remaining epithelium
- Destruction of bronchial walls ⇒ ± lung abscess
OSA
Pathophysiology
-
Anatomical obstruction
- Nasal congestion
- Reduced airway size
- Physical obstruction
- Positional effects
-
Neuromechanical impairment
- Decreased airway tone
- Inappropriate timing of upper airway muscles during inspiration
OSA
Hypnogram
“Sleep study”
-
Definitions
- Apnea ⇒ cessation of airflow for 10 secs
- Hypopnea ⇒ 30% airflow, 4% desaturation
- Central ⇒ no effort or flow for 10 seconds
-
Apnea-Hypopnea Index (AHI)
- Mild ⇒ 5-15
- Moderate ⇒ 15-30
- Severe ⇒ > 30 events per hour
