Cystic fibrosis: diagnosis and treatment
Andrew
Colin, MD, clinical director of Pulmonary Medicine
How has diagnosis of CF changed in recent years?
The disease can now be diagnosed at birth as part of the standard
heel stick screening that looks for other congenital and metabolic
diseases. This means there is no longer a delay of weeks, months
or even years until children are diagnosed. This can have an impact
on growth because you can start to control the malabsorption caused
by the disease. We don’t know how much of a long-term impact this
will have, but emerging studies suggest that early intervention
makes a difference.
What should clinicians know about this disease?
Since the diagnosis is now being established very early, clinicians
may be the first ones to get screening results, so they should
act on them right away. A sweat test should be done immediately;
it’s cheap, readily available and universally diagnostic with
very few exceptions. After diagnosis, a child will need to come
back three or four times a year for throat cultures, infant PFTs,
evaluation of nutritional state, social worker visits, etc. There
is often a shift in the focus of care to Children’s
CF Center, but the staff here works hard to involve each child’s
pediatrician. Referring clinicians should make sure that optimal
growth and weight gain are occurring and alert us if they aren’t.
It turns out that early intervention, as offered by our expert
nutritionists, can have a significant, long-term impact not only
on nutrition, but also on lung health and longevity. Clinicians
should also be very responsive to airway diseases. The usual viral
infection that can be glossed over in a normal child should be
treated quite aggressively (often with antibiotics) in those with
CF, particularly in the young. Finally, if there is a new diagnosis
in the family, it’s important that the rest of the child’s siblings
are screened. We have made the diagnosis of an older brother or
sister based on the presentation of a newborn or young child more
than once.
CF FACTS
- The genetic mutation that causes CF was
discovered in 1989. This led to the development of genetic tests that help determine whether couples are carriers.
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About 30,000 children and adults in the U.S. have CF. While all racial groups are affected, the disease is most common in Caucasians.
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Infants, children and adults with CF have a higher salt concentration in their sweat than unaffected individuals.
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The median life expectancy for CF patients in the U.S. shifts up roughly one year per year; it currently stands at about age 32.
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There are about 450 cystic fibrosis patients at Children’s Hospital Boston.
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How did the discovery of the gene that causes CF
change how it’s diagnosed?
It made it easier because we can test for it at birth, but also
significantly more complicated because we used to think there
was only one gene mutation, but now we know there are at least
a thousand mutations. Any combination can be expressed as a different
disease. To make things more complex, it turns out that the same
mutations can result in huge variations of disease. For example,
in some siblings with the same mutation, one is very sick and
the other is not.
When should clinical intervention of lung disease
associated with CF begin?
Over the last few years evidence has started to emerge that lung
disease may start earlier than previously thought, and it may
be present before it is clinically manifest. This is based on
large studies involving routine bronchoscopies in clinically healthy
infants to evaluate the state of inflammation. Inflammation may
start before infection, and it is likely that early inflammation
is where we should start to intervene.
How early should you start Pulmonary Functions Tests?
Until recently, 6 was the age at which these studies could reliably
be obtained, but infant PFT systems have been developed over the
last three decades that allow us to obtain PFTs in children from
infancy to 2 years at a quality similar to adults. It is much
more time consuming than the adult test because it requires the
child to be sedated, but it could be obtained twice a year as
surveillance. If a child is sick it can help determine whether
an intervention is appropriate. Unfortunately there is a period
between the ages of 2 and 6 when we can’t do PFTs because infant
techniques cannot be applied and children cannot cooperate on
the adult system. Like others, we are trying to develop technologies
for toddlers, and we may be able to bring the age down to age
4, but ages 2 to 4 are going to remain a problem.
Which treatments offer the most promise?
In terms of medications, we have been using DNase (Pulmozyme),
which liquifies the sputum and keeps it from getting thick and
blocking the lungs. We’re finding that it may also reduce inflammation
in lung, which it’s not expected to do, but it may be a nice additional
effect. Nebulized antibiotics have been the other major intervention
introduced in the last decade. There is a boom in novel approaches
that are being investigated, and 10 years from now we’ll have
many more medications in our armamentarium against CF.
One intervention that I think will be the ultimate treatment
is gene therapy, where a gene is replaced in the lung, which then
turns cells from non-functional to functional. It has already
been tried, but the problem is finding the vehicle to deliver
the corrected gene into the cell and nucleus. Viruses have been
used, but the lung has an immune response. I think 10 years from
now the technical hurdles may be overcome and we will be able
to do this.
How has the thinking changed on pseudomonas?
In the past we thought that if a patient got infected with pseudomonas,
it couldn’t be cleared. But it turns out that if it is detected
early, its transition to chronicity can be prevented. Throat cultures
three or four times a year help with early detection, and if the
results are not clear, then perform a bronchoscopy. If the patient
is infected with pseudomonas, immediate, aggressive treatment
with antibiotics should begin. In Europe this has decreased the
prevalence of pseudomonas substantially. In our total population,
the prevalence of the organism is greater than 60 percent, but
they have driven theirs down to as low as 40 percent.
Is it possible to have CF without lung disease?
Yes. We’ve always known that it is a multi-system disease, and
there is an almost endless variety in the types of presentation.
A striking example is congenital absence of the vas deferens.
Most adult males with CF are sterile because of obstruction of
the tubes connecting the testicles to the urethra, a condition
known as obstructive azoospermia. The prevalence of CF genes is
much higher among patients with this condition than in the normal
population, so males with CF can present with sterility being
the only feature of their disease. Right now I’m following a group
of men with obstructive azoospermia who we tested at age 30 and
who had no lung disease. Ten years later we’re bringing them back
to see if they have lost lung functions compared to normal adults.
We don’t know what lung disease, if any, there will be over time
in these patients.
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| Dr. Colin demonstrates an infant pulmonary function test system that can help clinicians obtain PFTs in patients up to 2 years old. |
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