Non-CF Bronchiectasis, CF, and NTM Flashcards
Etiology of non-CF bronchiectasis
ABPA (central syndromes)
Sarcoid
CTD (central)
Primary ciliary dyskinesia
Post-transplant
HIV
Chronic aspiration
Post radiation
Mechanical obstruction
NTM/MAC (RML or Lingula)
Post-infectious
Chronic aspiration
Tests to find etiology of bronchiectasis in young adults (7 - at least)
- Aspergillus IgE/IgG
- Immunoglobulin levels
- Sweat test, CFTR testing
- Ciliary testing (nasal NO, genetic, ciliary biopsy)
- A1AT lvl
- Autoimmune workup
- GI for aspiration
Definition of “Bronchiectasis Exacerbation”
3/5 or more of below and for at least 48 hrs:
- cough
- sputum production or purulence is worse
- dyspnea
- malaise/fatigue
- hemoptysis
Tx for non-CF bronchiectasis with “frequent exacerbations” in those without pseudomonas and what is the benefit
Macrolide antibiotics 3x/week in those without NTM –> decreased exacerbations
Azithro (Wong, Lancet 2012; Altenburg JAMA 2013)
Erythro (Serisier JAMA 2013)
Definition of “frequent exacerbation” in bronchiectasis
2 or more exacerbations
Inhaled abx for Bronchiectasis
Inhaled tobramycin (Loebinger ERS 2021)
Inhaled Aztreonam (Crichton ERS 2020)
Inhaled colistin (Haworth ERS 2021)
Tx for first time seeing pseudomonas and multiple exacerbations a year
inhaled tobramycin to eradicate
Add IV anti-pseudomonal if they are having an exacerbation
Risk stratification in NCFB and what does it predict (4)
Bronchiectasis severity index (BSI) and FACED
1. FEV1
2. Dyspnea
3. Pseudomonas colonization
4. Radiographic features
Predicts hospitalizations
Anti-inflammatory agents in NCFB
ICS (unless you have NTM)
Short course oral steroids
Macrolide
NO STUDIES: NSAIDs, LRTAs
Statins are being investigated
Brensocatib moa and benefit in NCFB
DPP-1 inhibitor: reduces neutrophil activity (IL-8) and neutrophil elastase
Prolong time to first exacerbation
Eosinophilic NCFB biologic being studied (approved in severe eos asthma)
Benralizumab
Slow growing NTM
MAC
M. Kansasii
M. Xenopi
Rapidly growing NTM
M. abscessus
M. Fortuitum
M. Chelonae
Phenotype of those with NTM
> 65 yo
Low BMI
Tall
Vit D deficiency
Asymptomatic GERD
Mitral valve prolapse
Thoracic anomalies
Criteria to begin treatment for NTM
2 positive sputum cultures for NTM
radiographic evidence of disease
+/- clinical symptoms (weight loss, cough, hemoptysis)
Risk factors for progression of NTM disease
Male gender
Older age
Presence of comorbidities
Low BMI
Immunosuppression
Elevated inflammatory markers (ESR, CRP)
Anemia
Hypoalbuminemia
Fibrocavitary disease
Extent of disease
Bacterial load
Species
Gene mutation associated with macrolide resistance in M. avium and M. abscessus
23S rRNA gene (or erm gene)
Gene mutation associated with amikacin resistance in M. avium
16S rRNA gene
Gene mutation associated with rifamycin resistance in M. kansasii
rpo B gene
Tx for Nodular disease with M. avium pulmonary disease with symptoms
3x/week azithro, ethambutol, rifampin
Tx for cavitary or multilobular NTM disease in symptomatic patient
daily Azithro, Ethambutol, Rifampin
+ IV amikacin
+ surgical resection
Most of microbiologic recurrence are ___ reinfection or relapse?
reinfection
Regimen that promotes macrolide resistance
Azithromycin and Quinolone
When to stop NTM treatment
Consistent negative sputum cultures for 12 mo (takes most patient 3-6 mo to culture convert)
Addition of clofazamine is good or bad?
Competitive outcomes compared to AER
3 different subspecies of M. abscessus
BAM
1. bolletii
2. abscessus
3. massilense - no erm gene (macrolide sensitive)
May have erm gene active (macrolide resistance) - still add macrolide for anti-inflammatory
Screening tests for CF
Newborn (immunoreactive trypsinogen measurement IRT)
Genetic testing
Sweat chloride testing
Interpretation of sweat chloride testing
Intermediate 30-59
Abnormal >60
If normal (<29) but there is strong clinical evidence of CF, then repeat testing
CFTR mutation interpretation
CF confirmed if: 2 CF-causing variants
CF possible if 0-1 CF-causing variants present
When is Trikafta indicated and what is the benefit
Pt has at least 1 copy of F508del
Improves
1. FEV1
2. Decreases exacerbation
3. Increases weight
4. Improves QOL
When is 2-drug therapy indicated in CF (what are they and why choose one over another)
when pt is Homozygous for F508del) - traffics and transports
Normal movement of chloride vs. CF
Normal: Chloride goes out of the cell into the lumen, helps with bringing water out and keeping mucus thin
MOA of Ivacaftor, benefit
Works on gating and conductance mutations (Gly551Asp/G551D): keeps gate open
- increase FEV1
- Fewer exacerbations
- Weight gain
- Improved QOL
durable benefit
Absolute indication for lung transplant in CF
massive hemoptysis
Likely to recurr
Criteria for ABPA diagnosis
Obligatory:
1. IgE against A. fumigatus or aspergillum skin test
2. IgE >500
Other criteria
1. Eos >500
2. Radiographic opacities
3. IgG aspergillus
