Bronchiectasis and Cystic Fibrosis

Question 1

Bronchiectasis - what is it?

Answer 1

Permanent dilatation of bronchi and bronchioles due to destruction of airway muscles and elastic connective tissue

Question 2

Bronchiectasis can be a first manifestation of CF at any age T or F?

Answer 2

T

Question 3

Pseudomonas aeruginosa why so difficult to clear?

Answer 3

Ability to form biofilms, virulence factors e.g. pili, capsule, toxins, proteases, adhesins, increasing resistance, clonality, microbiome, uses Fe, incites inflammation

Question 4

Organisms implicated in bronchiectasis

Answer 4

Pseudomonas aeruginosa, nontuberculous mycobacteria, Aspergillus, Stenotrophomonas maltophilia, Staph aureus

Question 5

Cystic fibrosis functional classification CFTR protein defects. Majority of patients have which defects?

Answer 5

Class 2 - absent functional CFTR - CFTR trafficking defect, missense aminoacid deletion
Phe408del
Asn1303Lys
Ile507del
Arg560Thr

Question 6

Current CFTR modulators

Answer 6

Ivacaftor (Kalydeco) - CFTR potentiator - opens the channel of the protein
Tezacaftor - CFTR corrector - moves the protein to the cell surgace
Elexacaftor - CFTR corrector - moves the protein to the cell surface
Ivacaftor plus Tezacaftor (Symdeco) for homozygous DF508 mutations
Elexacaftor/Ivacaftor/Tezacaftor (Trikafta) for heterozygous DF508 mutations

Question 7

Cystic Fibrosis - role of macrolides?

Answer 7

Still a mainstay of therapy. Azithromycin as effective as Erythromycin

Question 8

Stages of Pseudomonas colonisation

Answer 8

1. Initial Adhesion - bacteria- surface assoc, EPS biosynthesis
2. Early attachment - Irreversible adherence, bacterial division
3. Young biofilm - microcolony formation, cell-to-cell interaction
4. Mature biofilm - mushroom-shaped structures, increased antibiotic tolerance
5. Dispersal - matrix cavity formation, release of dispersed cells