Bronchiectasis Flashcards
What is bronchiectasis?
- Chronic infection/inflammation –> if inflammation does not resolve there is airway wall remodeling via proteases –> floppy/dilated bronchi (irrev) –> fail to effectively clear secretions –> chronic airway infection, excessive bronchial secretions and chronic, productive cough
- Can be local or diffuse depending on cause
5 Normal Host Innate Resp Defenses
1- Secreted Anti-Microbial Proteins- Lactoferrin, lysozyme, defensins, collectins, secretory IgA
2- Mucus Blanket (gel layer) - Contains mucins that bind pathogens then cleared by mucociliary elevator
3- Airway Surface Liquid Beneath Mucus Blanket (sol layer) - Reservoir of anti-microbial proteins, fluid layer allows normal mucociliary clearance
4- Synchronous Ciliary Activity - Clears mucus w/ bound pathogens
5- Alveolar Macrophages - Phagocytosis in airspace
3 Symptoms that Differentiate Bronchiectasis from Other Obstructive Diseases
- Clubbing
- Nasal polyps, nasal inflammation
- Mid-inspiratory crackles
10 General Causes of Bronchiectasis
LOCAL
1- Acute Broncho-pulmonary Infection - Pertussis, measles, staph aureus, Klebsiella, hemophilus, Tb, histoplasmosis
2- Bronchial Obstruction - Aspiration, neoplasms (adenoma or carcinoma), chronic obstructive lung disease (asthma, alpha-1-trypsin def, dilation/scars on top of path) adenopathy (Tb, sarcoidosis)
SYSTEMIC
3- Cilia Abnormality - Immotile Cilia Syndrome (w or w/o Kartagener’s), ciliary dyskinesia
4- Defect in Airway Surface Fluid - CF
5- Immunodeficiencies - IgA def, IgG def, chronic granulomatous disease or HIV
6- Anatomic Defects - Cartilage def, relapsing polychondritis, bronchomalacia, amyloidosis, pulmonary sequestration
7- Irritant Inhalation - ammonia, talc, smoke, detergents
8- Lung Transplant Rejection
9- Obliterative bronchiolitis
10- Allergic fungal response - ABPA (from Aspergillosis)
Treatment (7)
- Airway Hygiene - reduce mucus obstruction
- chest physical therapy, postural drainage, chest wall oscillator
- Bronchodilators - inc ciliary beat frequency and dec airway hyper-reactivity
- Abx
- Used during acute infectious exacerbation
- Many pts ultimately get infected w/ Pseudomonas (creates biofilm so hard to penetrate) but tobramycin and aztreonam used to slow progression (inhaled abx)
- May alternate on and off to prevent resistance
- Mucolytics - hypertonic saline/osmotically active agents
- Vaccination - for flu and pneumococcus b/c inc risk
- Resp Support - later in disease may need BiPaP
- Transplant
Pulmozyme
- recombinant human DNase to dec mucus viscosity in CF b/c mucus of CF has neg-charged DNA stuck in it
5 Classes of CFTR Mutations
- I - premature STOP
- II - misfolds and targeted for degradation (includes common deltaF508 - over 70% cases)
- III - full length protein makes it to cell membrane but defective
- IV - full length protein makes it to cell membrane but defective
- V - reduced mRNA/reduced protein production; so CFTR exists but not enough (may have milder form - normal sweat tests; just pancreatitis, recurrent resp infections, no liver involvement)
CFTR in Lungs
- Normally regulates other channels on apical membrane
- Mutation –> dec Cl- conductance and inc ENaC activity (normally regulates this) –> not enough airway surface liquid –> dec mucociliary clearance
CFTR in Other Organs
- Less NaCl absorption in sweat ducts –> hypertonic sweat
- Dec bicarb secretion in pancreas (b/c CFTR is a Cl-bicarb channel) –> less alkaline pancreatic secretions –> pancreatic fibrosis and recurrent pancreatitis
- Malabsorption; dec fat and fat-soluble vitamin absorption
- Mucus plug in bowel - bowel obstruction (meconium ileus)
- Liver - hepatobiliary disease
- Infertility in men b/c CFTR needed for development an patency of vas deferens (congenital bilateral absence of vas deferens -CBAVD)
How to dx CF
- Newborn screening for 40+ mutations
- 2 sweat Cl- tests (>60)
- 2 CF gene mutations
- Lack of Cl- on nasal pot diff meas
How to dx Immotile Cilia Syndrome
- Dec saccharin in nasal mucosa
- lack of dynein arms on EM of nasal epithelium (see 9+2 structure w/ inner arms but not outer)
- abnormal radionuclide mucus clearance scan
- abnormal ciliary beat freq seen in in vitro cells
Ivacafator & Lumacaftir/Ivacaftor
- Ivacaftor (CFTR potentiator) restores chloride conductance in G551D mutation; keep channel locked in open position (15%)
- Lumacaftir/Ivacaftor (corrector + potentiator) to correct deltaF508 mutation (most common); stabilizes mutant form to get it to cell surface
