genetic determinants of lung function Flashcards
5 common respiratory conditions influenced by genetics
- cystic fibrosis
- alpha-1 antitrypsin deficiency
- asthma
- COPD
- lung cancer
how many phases are there in the normal lung function trajectory from birth to death
3
- growth phase (from birth to early adulthood)
- a plateau phase (that lasts for a few years)
- a decline phase resulting from physiological lung ageing
examples of factors that cause low lung function growth trajectory
- genetics
- preterm birth
- early life environmental exposures
- LRTI
- childhood persistent asthma
how many people in UK affected by cystic fibrosis
more than 10,000
what type of genetic disease is cystic fibrosis
autosomal recessive
it is the most common lethal autosomal recessive genetic disorder in caucasians
what causes cystic fibrosis
defect in long arm of chromosome 7 coding for the CFTR protein
how many mutations of CFTR are there
more than 1600
what is the most common mutation causing CF
F508del
what does normal CFTR protein do
moves chloride ions outside of the cell
this controls movement of water in tissues
this moderates production of mucus
what happens when CFTR protein is mutant
does not move chloride ions, causing sticky mucus to build up on the outside of the cell
leads to dysregulated epithelial fluid transport
cycle of lung disease
- microbial attack
- defect in host defence
- respiratory tract infection
- bronchial inflammation
- progressive lung disease
respiratory symptoms of CF
- persistent cough and productive thick mucus
- wheezing and shortness of breath
- frequent chest infections
- sinusitis, nasal polyps
digestive symptoms of CF
- bowel disturbance
- weight loss
- obstruction
- constipation
reproductive problems with CF
- 95% men and 20% women are infertile
- osteoporosis
- arthirtis
issues with antibiotics
- allergies
- renal impairment
- resistance
- access problems
what are the methods for CF prevention
- segregation
- surveillance - frequent review every 3 months
- airway clearance
- nutrition
- psychosocial support
- drugs
which types of drugs are used in CF prevention management
antibiotic nebs - suppression of chronic infections
salbutamol nebs - bronchodilation
steroids, azithromycin - anti inflammatory
insulin - diabetes
influenza, pneumococcal - vaccinations
what is personalised medicine
individual tailored or targeted medicine
how is personalised medicine used in CF
targeted treatments based on infectious organisms and resistance patterns
genotype directed therapies
challenges when treating CF
- adherence to treatment
- high treatment burden
- high cost of certain treatments
- allergies/ intolerances to treatment
- different infectious organisms and their resistance to drugs
what is alpha 1 antitrypsin deficiency (AATD)
autosomal recessive genetic disorder
a condition that raises your risk for lung and other diseases
