Non-CF Bronchiectasis, CF, and NTM

Question 1

Etiology of non-CF bronchiectasis

Answer 1

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

Question 2

Tests to find etiology of bronchiectasis in young adults (7 - at least)

Answer 2

1. Aspergillus IgE/IgG
2. Immunoglobulin levels
3. Sweat test, CFTR testing
4. Ciliary testing (nasal NO, genetic, ciliary biopsy)
5. A1AT lvl
6. Autoimmune workup
7. GI for aspiration

Question 3

Definition of “Bronchiectasis Exacerbation”

Answer 3

3/5 or more of below and for at least 48 hrs:
- cough
- sputum production or purulence is worse
- dyspnea
- malaise/fatigue
- hemoptysis

Question 4

Tx for non-CF bronchiectasis with “frequent exacerbations” in those without pseudomonas and what is the benefit

Answer 4

Macrolide antibiotics 3x/week in those without NTM –> decreased exacerbations

Azithro (Wong, Lancet 2012; Altenburg JAMA 2013)

Erythro (Serisier JAMA 2013)

Question 5

Definition of “frequent exacerbation” in bronchiectasis

Answer 5

2 or more exacerbations

Question 6

Inhaled abx for Bronchiectasis

Answer 6

Inhaled tobramycin (Loebinger ERS 2021)
Inhaled Aztreonam (Crichton ERS 2020)
Inhaled colistin (Haworth ERS 2021)

Question 7

Tx for first time seeing pseudomonas and multiple exacerbations a year

Answer 7

inhaled tobramycin to eradicate

Add IV anti-pseudomonal if they are having an exacerbation

Question 8

Risk stratification in NCFB and what does it predict (4)

Answer 8

Bronchiectasis severity index (BSI) and FACED
1. FEV1
2. Dyspnea
3. Pseudomonas colonization
4. Radiographic features

Predicts hospitalizations

Question 9

Anti-inflammatory agents in NCFB

Answer 9

ICS (unless you have NTM)
Short course oral steroids

Macrolide

NO STUDIES: NSAIDs, LRTAs
Statins are being investigated

Question 10

Brensocatib moa and benefit in NCFB

Answer 10

DPP-1 inhibitor: reduces neutrophil activity (IL-8) and neutrophil elastase

Prolong time to first exacerbation

Question 11

Eosinophilic NCFB biologic being studied (approved in severe eos asthma)

Answer 11

Benralizumab

Question 12

Slow growing NTM

Answer 12

MAC
M. Kansasii
M. Xenopi

Question 13

Rapidly growing NTM

Answer 13

M. abscessus
M. Fortuitum
M. Chelonae

Question 14

Phenotype of those with NTM

Answer 14

> 65 yo
Low BMI
Tall
Vit D deficiency
Asymptomatic GERD
Mitral valve prolapse
Thoracic anomalies

Question 15

Criteria to begin treatment for NTM

Answer 15

2 positive sputum cultures for NTM
radiographic evidence of disease
+/- clinical symptoms (weight loss, cough, hemoptysis)

Question 16

Risk factors for progression of NTM disease

Answer 16

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

Question 17

Gene mutation associated with macrolide resistance in M. avium and M. abscessus

Answer 17

23S rRNA gene (or erm gene)

Question 18

Gene mutation associated with amikacin resistance in M. avium

Answer 18

16S rRNA gene

Question 19

Gene mutation associated with rifamycin resistance in M. kansasii

Answer 19

rpo B gene

Question 20

Tx for Nodular disease with M. avium pulmonary disease with symptoms

Answer 20

3x/week azithro, ethambutol, rifampin

Question 21

Tx for cavitary or multilobular NTM disease in symptomatic patient

Answer 21

daily Azithro, Ethambutol, Rifampin
+ IV amikacin
+ surgical resection

Question 22

Most of microbiologic recurrence are ___ reinfection or relapse?

Answer 22

reinfection

Question 23

Regimen that promotes macrolide resistance

Answer 23

Azithromycin and Quinolone

Question 24

When to stop NTM treatment

Answer 24

Consistent negative sputum cultures for 12 mo (takes most patient 3-6 mo to culture convert)

Question 25

Addition of clofazamine is good or bad?

Answer 25

Competitive outcomes compared to AER

Question 26

3 different subspecies of M. abscessus

Answer 26

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

Question 27

Screening tests for CF

Answer 27

Newborn (immunoreactive trypsinogen measurement IRT)
Genetic testing
Sweat chloride testing

Question 28

Interpretation of sweat chloride testing

Answer 28

Intermediate 30-59
Abnormal >60

If normal (<29) but there is strong clinical evidence of CF, then repeat testing

Question 29

CFTR mutation interpretation

Answer 29

CF confirmed if: 2 CF-causing variants

CF possible if 0-1 CF-causing variants present

Question 30

When is Trikafta indicated and what is the benefit

Answer 30

Pt has at least 1 copy of F508del

Improves
1. FEV1
2. Decreases exacerbation
3. Increases weight
4. Improves QOL

Question 31

When is 2-drug therapy indicated in CF (what are they and why choose one over another)

Answer 31

when pt is Homozygous for F508del) - traffics and transports

Question 32

Normal movement of chloride vs. CF

Answer 32

Normal: Chloride goes out of the cell into the lumen, helps with bringing water out and keeping mucus thin

Question 33

MOA of Ivacaftor, benefit

Answer 33

Works on gating and conductance mutations (Gly551Asp/G551D): keeps gate open

1. increase FEV1
2. Fewer exacerbations
3. Weight gain
4. Improved QOL

durable benefit

Question 34

Absolute indication for lung transplant in CF

Answer 34

massive hemoptysis

Likely to recurr

Question 35

Criteria for ABPA diagnosis

Answer 35

Obligatory:
1. IgE against A. fumigatus or aspergillum skin test
2. IgE >500

Other criteria
1. Eos >500
2. Radiographic opacities
3. IgG aspergillus