lecture 7

Question 1

What are the main features of cystic fibrosis?

Answer 1

• common inherited disorder (in particular for people of northern european backgrounds)
• variable severity - severe forms have poor prognosis - no cure at present
• improvements in treatment have resulted in increased life spans
• death usually due to respiratory failure/cardiac complications

Question 2

What system is affected?

Answer 2

multiple systems affected, including:

• respiratory
• digestive
• reproductive

Question 3

What is the common feature of those with CF?

Answer 3

all affected by production of excessively thick/viscous, dehydrated, secretions of mucus

This is the intimate problem that gives rise to all the features that we see. It traps bacteria in parts of the body - particularly the lungs

Question 4

What causes the thick mucus?

Answer 4

Caused by a failure of salt (specifically chloride ions) and subsequently water transport by epithelial cells lining ducts

Question 5

What are the respiratory clinical features of CF?

Answer 5

• frequent coughing
• chronic infections
• lung damage

Question 6

What are these respiratory clinical features due to?

Answer 6

• obstruction of the bronchioles by mucus
• colonisation by bacteria, especially antibiotic resistant strains
• damage (fibrosis) caused by inflammatory responses

Question 7

What are the digestive clinical features of CF?

Answer 7

• failure to thrive
• chronic malabsorption - poor digestion, mostly of fats but also some proteins
• intestinal obstruction in newborns (‘meconium ileus’; 15% of neonates with CF)
• ‘Pancreatic insufficiency’ (85% of patients)
• Chronic pancreatitis (&diabetesm 40% of adults), liver disease (>=5%)

Question 8

What are the digestive clinical features of CF due to?

Answer 8

• blockage of various intestinal and pancreatic ducts by mucus
• poor digestion of fats (mainly) and proteins

Question 9

What are the clinical reproductive features of CF?

Answer 9

• infertility in males

- sub-fertility in females

Question 10

What are the clinical reproductive features of CF due to?

Answer 10

• blockage of vas deferens in males, leading to fibrosis or usually atrophy: congenital bilateral absence of the vas deferens (CBAVD)
• cervical mucus in females acting as barrier to passage of sperm
• females may be anovulatory

Question 11

What is Sean’s family history of diagnosis?

Answer 11

• sean is a compound heterozygote

- had an older sister who was diagnosed with CF after he was

Question 12

How was Steven diagnosed with CF?

Answer 12

• didn’t put on any weight despite eating lots but as time progressed he was falling behind in terms of weight and height
• diagnosed at age 2 - took almost 6 months because at the time little was known
• at 2 had the Sweat Test
• diagnosis was pretty bad at that time - told he would be lucky to make it to the age of 10

Question 13

When was newborn screening for CF introduced?

Answer 13

• after 1989

Question 14

What is Steven’s family history?

Answer 14

• two elder sisters who are carriers but do not have CF
• elder sister has three children, none of whom have CF
• parents come from switzerland
• auntie of mother had 8 children, 6 of whom died before the age of 3 but not known why - suspected CF
• often common that there is no family history (or no known family history) because it is an autosomal recessive condition

Question 15

What was the impact of his diagnosis on Steven’s family?

Answer 15

• parents very optimistic people
• immediately they tried to find out what the one/several thing/s they could do for him to ensure that his life lasted as long as it possibly could
• the only thing they really did know was that it was the buildup of mucus overtime that would kill him
• made sense to them to make him as active and as physical as possible: from a young age was involved in many sports
• not a directive from the hospital back then at the time sport was not actively encouraged
• faced with this kind of prognosis it is very easy to become insular and negative: his parents were the opposite

Question 16

What treatments did Steven have to undergo as he grew up?

Answer 16

• The experience of patients is very different
• Steven lived a very normal life up to the age of 18
• Only thing he had to do was take pancrease tablets to help digest food
• Lung mucus was not so much of an issue until 18 - didn’t undergo any physiotherapy until that age purely because of sport and activity
• most people have to undergo a lot of physiotherapy for mucus drainage

Question 17

What treatments did Sean have to undergo as he grew up?

Answer 17

• several hours a day of intensive physiotherapy to drain the mucus that involves ‘beating’ the mucus out of him
• lots of different types of inhalation therapies to try and dissolve the mucus /make it more watery/less of a site for organisms and bacteria to grow
• very intensive therapy
• pancreatic insufficient and required a lot of enzyme treatment

Question 18

What sort of diet do people with CF have? How has this changed over time?

Answer 18

• one of the things about CF is that you excrete a lot of sweat
• you can’t digest fats very well
• if you take the enzymes that allow fat digestion then you are recommended to have a high fat/high salt diet
• i.e. Maccas (no joke)
• this was not actively encouraged in the past

From 72-78 steven had a very strict diet.
All fried food was to be cooked in a special oil, weren’t encouraged to eat additional fats or supplement salt intake (this was basically flipped on its head overnight) –> each as much crap as you can was the directive

Some individuals with CF might need to take 40-60 tablets per day

Question 19

What is something important to understand about genetic mutations?

Answer 19

• people with the same genetic mutations can have quite different phenotypes
• CF does not have just one phenotype nor one genetic mutation associated (though usually in the same gene)
• whilst we do have genotype to phenotype correlation there is a broad spectrum for individuals who have CF

Question 20

How can having CF affect an individual’s relationship with others?

Answer 20

• even if the individual is totally in acceptance of their lot in life, CF can be very confronting for a lot of people
• they cannot expect others to deal with it in the same way
• Individuals with CF at the age of 20 don’t know what their future is in regards to having children/life expectancy etc and that can be hard for non-affected peers/prospective relationships to deal with
• the same can be true for people who know they are carriers of the disease

sometimes both people in the partnership have and the disease has other impacts

Question 21

What was Steven’s experience with having a lung transplant?

Answer 21

• difficult for patients: you have to go into transplant fully committed.
• cannot force anyone to do it
• hard to process the idea that you will die without the operation
• 2002 listed at Prince Alfred’s hospital - takes a few weeks to run through a series of tests to make sure there are no other major issues going on
• 30 days later got a phone call to say that they’d found a donor (much sooner than normal)
• extremely quick process
• important to go in optimistically
• saw the lungs
• 8 hour long surgery
• left lung first to allow the right to keep functioning.
• lung was black and shrunken –> difference between old and new extraordinary
• bizarre feeling: hard to breathe with new lungs because they have so much more capacity than you are used to –> sucking in too much oxygen, couldn’t control the rate of breath
• 10 days after: on lots of pain drugs, having delusions, struggling to breathe
• walking after 2 days, got out after 10
• had the same set of lungs 8 years later

Question 22

At what point do physicians recommend having a lung transplant?

Answer 22

• when lung function reaches 30%

Question 23

what was Steven’s experience with having a family?

Answer 23

• CF: absence of the vas - makes it hard to have children
• IVF treatment
• difficult experience with little success in the first few years
• wasn’t producing good quality sperm
• successful with embryos produced post transplant
• originally predicted that the child had CF however did not
• grandmother suspected not as stool was not oily/runny, and didn’t have club fingernails

Question 24

How is it that someone can test negative for carrying CF but still have a child with CF?

Answer 24

• there are over 1600 mutations in CF and we test for the most common: approx 19
• therefore possible (though rarely ) to have a child with CF when someone tests negative for CF

Question 25

What are the financial burdens related to having cystic fibrosis?

Answer 25

• $80 a week (without a healthcare card, which reduces the costs considerably)
• adults with severe CF have big financial problems because they can’t work - only able to get disability support pension which is minimal