Respiratory genetics

Question 1

what is cystic fibrosis in general terms

Answer 1

chronic monogenetic disease with multi-organ involvement

Question 2

what is the prevelance of CF in the UK

Answer 2

> 10,000

Question 3

What are the features of CF

Answer 3

abnormal ion transport, impaired muscocilliary clearance, recurrent and chronic infections, impaired digestion, fertility problems, liver disease, diabetes

Question 4

what causes CF

Answer 4

defect in long arm of chromosome 7 coding for CF transmembrane regulator (CFTR) protein (transport protein)

Question 5

what are the challenges in treating CF

Answer 5

treatment adherence/ high treatment burder
expensive treatment
allergies/ intolerance
different infectious organisms and theur resistace to drugs

Question 6

what is the inheritance pattern of CF

Answer 6

autosomal recessive

Question 7

what is the penetrance of CF

Answer 7

variable

Question 8

what is the inheritance pattern of alpha-1-antitryptase deficiency

Answer 8

autosomal recessive

Question 9

what is alpha-1-antitryptase deficiency in general terms

Answer 9

inherited monogenetic condition resulting in early onset emphysema and bronchiectasis

Question 10

what is bronchiectasis

Answer 10

long term condition where airways become abnormally widened leading to built up of excess mucus that can increase vulnerability to infections

Question 11

why does alpha-1-antitryptase deficiency lead to early onset emphysema and bronchiectasis

Answer 11

unopposed action of neutrophil elastase in lungs

Question 12

what is the mutation in alpha-1-antitryptase deficiency

Answer 12

serum antiprotease; bSERPINEA1 on chromosome 14

• M phenotype is normal
• S and Z phenotype = major disease association

Question 13

describe the characteristics of the aging lung

Answer 13

delayed response to hypercapnia/ hypoxia

Question 14

what is the effect of aging lung

Answer 14

increased vulnerability to respiratory failure

Question 15

what happens to FEV and FVC in aging lung

Answer 15

decrease; normal spirometry may indicate obstructive; may mask/ mimic respiratory symptoms and disease

Question 16

why does the aging lung have delayed response to hypercapnia/ hypoxia

Answer 16

impaired gas exchange and reduced immune function

Question 17

why does the aging lung have impaired gas exchange

Answer 17

• costal cartilages stiff so harder to breath
• respiratory muscles decrease in mass so less effective
• denervation of muscle fibres means less contraction so inspiration worse
• loss of elastic recoil in lungs as elastin fibres degenerate/ rupture
• increased V/ Q mismatch
• decrease in alveolar SA and lung capillary/ blood flow
• decreased O2 saturation of Hb

Question 18

why does the aging lung have reduced immune function

Answer 18

glandular epithelial cells decrease so less protective mucus made
decreased sputum clearance
less effective mucoscilliary system