00:01
So I’m going to talk about
a little bit about
cystic fibrosis which is a very specific cause
of bronchiectasis. Now this is a severe inherited
genetic disorder. It is the commonest fatal
genetic disease in the Western world.
00:14
It's present in 1 in 2000 to 3000 births. And what
it causes is a progressive bronchiectasis
with airways obstruction. Patients are universally
colonized of Pseudomonas, they frequently
have additional clinical problems, which I’ll
describe in a short while, and most patients
will end up dying over the cystic fibrosis
when they are 40s or 50s. The cystic fibrosis,
the genetics of this is an autosomal recessive
disease, and it’s due to mutations of the
cystic fibrosis transmembrane conductance
regulator gene (CFTR), the CFTR gene. The
CFTR is an ABC transporter protein that's
present in the membrane of airway epithelium
and exports chloride into the mucous. And
when it’s not working, the mucous becomes much
thicker and does not flow and that allows
bacterial infection to occur within the lungs
and bronchiole wall damage to occur and bronchiectasis
to develop. There are a very large number
of mutations, which have been identified as
CFTR the cause of cystic fibrosis, but in
fact, 60 to 70% of patients will have a problem
with the deletion of the amino acid 508 of
the CFTR gene. Now, the complications of cystic
fibrosis. We’ve already mentioned the lungs.
01:32
Most patients will develop bronchiectasis,
most patients will develop respiratory failure
due to airways obstruction. In addition, they
can get lobar collapse due to thick sputum
plugs in the bronchi, they get pneumothorax,
major hemoptysis, can have super infections,
allergic broncopulmonary aspergillosis, non-tuberculosis
mycobacteria infections. But because of this
problem with the CFTR affects all the body,
there are other organs that get affected as
well. And the most important of these are
the pancreas, where obstruction of the pancreatic
ducks eventually leads to pancreatic damage
and the patient will have malabsorbtion due
to lack of release of the pancreatic enzymes
into the gut, and many patients will develop
significant diabetes or at least glucose intolerance.
In addition, the men will be infertile because
of the lack of production of sperm. And the upper
airways are frequently affected in patients
with cystic fibrosis. There are occasionally
other complications that occur. Biliary obstruction
and liver cirrhosis occur in a minority of
patients. Gallstones are not that common,
and small bowel obstruction is one of the
relatively common serious complications of
cystic fibrosis. How to make the
diagnosis? It’s the sweat
test that will indicate whether somebody has
cystic fibrosis. It has a raised chloride
concentration. There are other methods of testing,
nasal potential differences for example,
and eventually we actually do genetic testing
on patients suspected of cystic fibrosis.
03:04
In fact, in the UK and other Western World
countries cystic fibrosis is screened for at
birth nowadays. Treatment is similar to
that of bronchiectasis
but more intense. Daily physiotherapy, Frequent
antibiotic for exacerbations. Those often
need to be intravenous because the patient
is colonized with Pseudomonas.
03:23
Prophylactic antibiotics to stop those exacerbations and
therefore to slow down the progression of
respiratory failure. Nebulized hypertonic saline.
Nebulized DNA. These are non-antibiotic
mechanisms that try to reduce the phlegm production
and keep the patient free of exacerbations.
03:39
Bronchodilators of the airways obstruction.
But in addition they need other treatment.
03:43
They need pancreatic enzyme replacement therapy,
Insulin for the diabetics, Dietary support.
03:51
And really the only life-saving treatment
that can be used is lung transplantation.
03:55
So that is the treatment that will cure the
patient in the minority that manage to get
to that point. So I've just listed here for
interest the standard therapy for somebody
who has cystic fibrosis, an adult with significant
disease. And as you can see, it's a very considerable
treatment load. The patient needs to take
daily antibiotics azithromycin, they'll have
daily nebulized tobramycin, nebulized salbutamol,
nebulized DNAs. Each of those takes a few
minutes to take, so that's a considerable portion
of the day is taken up by doing nebulized
therapy. Perhaps they have to do physiotherapy twice
a day, again, that takes a lot of their day
up. They will require Creon capsules to help
with the digestion of their food due to their
pancreatic insufficiency, they may require
insulin injections and overnight PEG feeding
is very common in patients to try and supplement
their feed and keep their BMI above a 19 or
20. So this is a very considerable treatment
load that's required for these patients and
despite this, almost all these patients will
die by their 40 or 50 years of age.
05:04
Allergic bronchopulmonary aspergillosis, now
this is a disease that has been mentioned
in several different talks. It's an allergic
response to inhaled aspergillus spores and
it's a complication of asthma, cystic fibrosis
and is a cause of bronchiectasis. What's actually
happened is that you inhale the aspergillus
spores which are ubiquitous in the atmosphere,
so you cannot avoid them, and because the body
has developed an allergy to those aspergillus
spores, you get inflammation in response to
the inhaled aspergillus spores. And that results
in poorly controlled asthma, progressive airways
destruction, upper lobe and central bronchiectasis
and frequent lobar collapse in potentially
bronchoceles as shown in this x-ray where
sputum plugs are clogging off the bronchi
and causing fluid retention or collapse of
the lobe distorter. How do you make the
diagnosis of ABPA? Well
you need to think about it in somebody who
has asthma, that has become poorly controlled
or has been associated with a fall in their
FEV1. It's also routinely tested for in patients
with bronchiectasis. The diagnosis is made
mainly by blood test, a high total IgE and
aspergillus specific antibodies IgE or IgG,
which show that there is a reaction in that
person to aspergillus specific antigens, and
skin tests does the same, also demonstrates
that there is an aspergillus specific allergy.
Treatment is pretty much the same as it is
for asthma and for bronchiectasis, with inhalers,
antibacterials for excessive exacerbations,
but they often need a high dose of inhaled
steroids and frequently they need oral prednisolone,
and occasionally we use antifungals as
they are beneficial in patients, especially
those that need high doses of oral prednisolone
to control their disease.