1. It’s estimated that about 1 in every 3,600 children are born in Canada with Cystic
Fibrosis. Almost 4,000 of the children, teenagers and adults suffering from Cystic
Fibrosis go to specialized clinics in Canada. Also, approximately 1 in 25 Canadians carry
the abnormal version of the gene responsible for CF.
2. Most children who suffer from CF are diagnosed by the age of 2 in the U.S. Others
sometimes are not diagnosed until the age of 18 due to them having a mild version of
CF.
3. CF greatly affects the Caucasian population (in the US, 1 in every 2,500 births), but also
affects Hispanics (1 in every 13,500 births), African Americans (1 in every 15,100 births) ,
and others.
4. CF is very deadly; it infects and destroys the lungs, slowly suffocating and disabling the
lungs until the person cannot inhale and exhale anymore and they pass away. However
the life expectancy has increased significantly; in the 1950’s, children were lucky if they
made it to elementary school. However, now the average life expectancy ranges from
the mid 30’s to 60’s depending on how severe the disease is. The sooner the disease in
the child is found, the
more their life expectancy
increases, since they have
more time to receive
treatment.
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5. Newborns
● Immediate signs may not appear, but newborn with CF may have blocked intestines which
prevent meconium (sticky greenish material which is the first stool healthy babies pass
after birth).
● Also, babies born with CF may not develop/grow normally, suffer from respiratory
infections, and pass greasy, bulky stools. If this is the case,a doctor can take a blood
sample and do genetic testing to confirm the diagnosis.
Children and Young Adults
● A physical symptom of CF is salty skin. This is due to their skin having higher than normal
amounts of Sodium Chloride (or salt) in their sweat.
● The same bowel activity as seen in newborns and infants can be seen in children.
● Weight loss or inability to gain weight despite seemingly big appetite.
● Growth patterns are slowed.
● Wheezing, and coughing up of thick sputum from the lungs.
● Pneumonia results from repeated lung and sinus infections.
● Clubbing (enlarged or rounded fingertips and toes) occurs in almost every CF patient.
Scientists have not pinpointed exactly the reason for clubbing, but they think this is due to
the abnormal circulation of oxygen especially due to parts that are hard to reach distantwise, such as fingers and toes.
● Nasal Polyps are common in children and older people with CF. They are associated very
commonly with CF. Even if they are surgically removed, they tend to grow again and cause
problems, which impair the patient’s ability to breathe even more.
● Cirrhosis of the liver can also occur in people who suffer from CF and it is fatal. It’s caused
by liver inflammation and/or clogged bile ducts. The gland performs functions such as
secreting bile (a yellow-green fluid which helps digest/break down and absorb fat). The
liver must also filter harmful microorganisms and toxins from blood. If the normal flow of
fluids and bile is prevented, then the bile becomes stuck in the liver to the point where it
cannot function anymore. This can cause a patient to die.
● Asthma can appear in CF patients if the bronchial linings become chronically inflamed.
Sometimes due to the wear and tear of having CF, a lung can collapse and air can leak out
into the chest cavity. If their conditions worsens, it may result in death.
● CF causes infertility in many men due to an internal problem with the vas deferens being
clogged up. In women, fertility can be slightly decreased due to the body producing
thicker cervical mucus than regular women, it may be harder for her to become pregnant.
Sometimes reproductive organs in women do not fully develop, or they may have
irregular period cycles which may lead to infertility. CF symptoms worsen during
pregnancy and diabetes could also appear, so women with CF are urged to discuss
pregnancy with their doctors.
● Pancreatitis- inflammation of the pancreas
6. CF is an autosomal recessive genetic disease. CF is caused by a specific mutated gene called
the "mutated CFTR gene". CF can occur by a) inheriting the defective gene from one or both
parents, or b) acquiring an abnormal gene during the patient's life.
Inherited Mutations
If the gene is inherited from one or both parents, the child’s cells will carry the mutation for
their lifetime. If one parent is a carrier of the gene but is not affected by it and marries the
other parent who is completely healthy, the child has no chance of having the disease. They
may inherit the mutation and be a carrier, or they could be completely healthy and not a carrier
at all. However, if both parents carry the disease, and the child inherits the mutated gene from
both parents, the child will suffer from the disease. If only one of the parents gives the mutated
gene, then the child will become a carrier, but not suffer from the disease.
Acquired Mutations
Acquired Mutations are triggered by external forces which includes radiation or chemical
exposure, or even unknown pathogens like viruses which bring the disease into the body. it can
acquired if the person’s skin is too exposed to the sun’s radiation, which causes the skin cells to
mutate; this can also lead to several types of skin cancers.
The CFTR gene normally is meant to control the flow of Sodium Chloride/Salt and water in and
out of the body’s cells. If the gene is mutated, this means that the normal flow of salt and water
between cells is disrupted. This results in dehydration of body secretions, which then results in
the production of thick, sticky mucus: a characteristic of CF. This dehydration is also the cause
of extreme loss through sweat, which is another symptom of CF. The CFTR gene is also known
as the “Transmembrane Conductance Regulator”. Dr. Francis S. Collins who is a global expert
and leader of the Human Genome Project claims and proved that there is a specific amino acid
is missing in patients who suffer from CF. He explains that the CFTR mutation causes an
important protein to fold improperly. He gives the example of a paper airplane; the paper must
be folded perfectly, accurately and sharply so that the plane can glide through the air to its
target location. If it is folded inaccurately, it won’t fly straight. The same is with the protein; if it
is not folded perfectly, it does not function well. He hypothesizes that if the protein is refolded,
then the missing amino acid will have a mild effect, but not enough to cause CF. Medicine
which may help “cushion the molecule and help it fold correctly” are in development.
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7. CF is a point mutation: about 70% of mutations discovered in CF patients result from the
deletion of three base pairs in CFTR’s nucleic sequence. The deletion causes the loss of amino
acid ‘Phenylalanine’ which is essential to humans. How and where it happens greatly
determines the effect on CFTR function. Some cause a mild form of the disease, some cause
more severe forms. Other mutations can cause congenital bilateral aplasia in males, which
does not allow the vas deferens in males to develop fully. This causes infertility since the sperm
cannot reach the woman’s egg.
In CF, the gene that mutates is located on chromosome 7.
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8. Sweat Chloride Test
The sweat chloride test measures how much sodium chloride exists in a person’s sweat. This is
a standard test for CF.
Procedure: In this test, a small amount of sweat-producing chemical is put on a person’s arm or
leg. An electrode (which creates a weak electrical current) is attached which then causes the
person to simulate their sweat production. The sample of sweat is collected and sent to a lab
where the levels of salt/sodium chloride are measured. If the levels seem to be abnormally high
when compared with regular samples, additional diagnostic procedures must be conducted to
determine whether the patient has CF.
Immunoreactive Trypsinogen
This test is done on newborns who are suspected of having CF, since only an insufficient sweat
sample can be collected so they cannot have the sweat chloride test done.
Procedure: A few days after birth, blood samples are taken from the baby and inspected for
increased levels of a pancreatic enzyme which is called “immunoreactive trypsinogen” (also
known as IRT). However, increased levels of this enzyme are not a very strong indicator as to
whether the baby has CF, since the baby could have other neonatal functions which would
affect the function of the pancreas. Therefore, additional tests such as gene mutation analysis
can be done which would show a mutation in the CFTR gene, allowing the clear diagnosis of CF.
Chorionic Villus Sampling (CVS)
A small sample of the placenta is obtained and taken to the lab for inspection of a mutation in
the CFTR gene. Karyotyping is done and chromosome number 7 is specifically looked at in the
case of CF.
Amniocentesis
A sample of amniotic fluid which surrounds the baby in the mother’s stomach is obtained and
sent to a lab to test for a mutation in the CFTR gene.
DNA Mutation Analysis
A variety of genetic tests which (in this case of CF) look for the presence of mutations in the
CFTR gene. As technology is getting better, these tests confirm CF diagnosis since they are
becoming very specific and much more accurate.
Procedure: First, DNA cells are obtained from a blood sample or cheek swab (also called a
buccal smear) and purified. Then, a variety of methods are used to detect any diseased genes
and identify (a) mutation(s) within specific DNA sequences.
DNA Microarray
This is a new method of mutation analysis. It is proven to be highly useful for pinpointing
mutations in the CFTR gene.
Procedure: Thousands of molecules or molecular fragments of DNA (called genetic probes of
chips) are organized in a prearranged way to stick to a slide or silicon chip. This allows scientists
to study which particular genes are active, which have a low activity, and which genes are
inactive. Active and inactive genes are sorted in a cell. This is done by gathering the cell’s
messenger RNA (mRNA (-this provides insight into the cell’s map for creating proteins))
molecules. The researcher shifts the cell’s normal function, causing a specific gene to activate.
The cell begins to copy specific segments of the gene which results in the mRNA. The researcher
then takes the mRNA, applies fluorescent dye to it, and places it onto a DNA microarray slide.
The mRNA from the cell will begin to bind to its complementary DNA and leave its fluorescent
dye behind. A special scanner is used to measure the fluorescent places on the slide and their
brightness. The very bright places indicate the specific gene is active. Places which are not as
bright indicate the specific gene is slightly active. Places with no colour at all are indicators that
the specific gene is inactive. DNA Microarray tests can be done on infants and general genetic
testing for CF.
Lung X-rays and Function Tests
Lung function or Pulmonary function tests measure the amount of air the lungs can hold, how
fast a person can exhale, and how well the lungs add oxygen to and remove carbon dioxide
from the blood. A chest x-ray has the ability to show scars in the lungs due to repeated
inflammations. These tests are not reliable enough to diagnose a patient with CF, but they can
help with identifying how severe their lung damage is. The tests can be repeated to see if there
are any changes to the lungs.
Sinus X-rays
Sinus x-rays can reveal signs of sinusitis, which is an infection or inflammation of the nasal
cavities. If Sinusitis is found through x-rays, finding the problem is vital. There are many reasons
for Sinusitis such as allergies or the patient’s poorly functioning immune system. Sweat chloride
tests are followed after sinus x-rays, along with other tests which can be used to give a
diagnosis of the patient’s condition.
Sputum Cultures
A sample of a person’s phlegm is examined by a physician, which helps them to see what
microorganisms live there. If a person’s phlegm happens to contain a fungus or bacteria which
is commonly found in patients with CF, it adds to the prediagnosis information. For example,
Aspergillus fumigatus is a fungus commonly found in CF patients, adding to evidence a doctor
needs to give a proper diagnosis. Another example is a bacteria called Pseudomonas aeruginosa
which is found in the lungs of CF patients. Sputum tests have showed a decreasing significance
over the years due to advancements in the diagnostic process over the years, but are still done
and remain important and routine checkups for patients with CF because they allow an insight
into the specific infections in the lungs or airways.
Fecal Fat Test
Fecal fat tests measure the amount of fat in a stool sample to determine patients’ ability to
absorb fat. This would indicate how well the patient’s liver, gallbladder, pancreas and intestines
are working.
Pancreatic Test
A pancreatic test measures the patient’s fecal pancreatic elastase (which is an enzyme) to
assess how well the Pancreas is functioning.
Nasal Passage Potential Differences
The nasal passage test uses electrodes to measure the rate at which salt flows in and out of
nasal cavities. Since people with CF have an abnormal movement of salt across cell walls in the
nasal passages, they tend to show different voltage measurements than people who do not
have CF. This measurement can help a doctor advance in his process of diagnosing a patient.
Genotyping
Genotyping is used to determine the genetic makeup of an individual. It narrows down a
patient’s specific CF mutations, which aids in determining the level of risk for organ dysfunction.
Prenatal tests can be done, as well as testing carriers in families with the known CFTR mutation.
9. Although Cystic Fibrosis does not have a cure, there are many ways CF patients can be
treated. These treatments are aimed at decreasing the amount of mucus in patients’ lungs, as
well as keep them active and healthy with exercise and maintaining a nutritional diet. For
example, bronchodilators are medical devices which were invented to loosen mucus from the
lungs.
● For thinning mucus in the lungs, antibiotics and anti-inflammatory medications exist, which
are high-dose vitamins and replacement enzymes. Additionally, modern physical therapy
along with older lung-clearing techniques are used on CF patients have a high success in
loosening mucus from the lungs. These solutions bring comfort to the patient and improve
their health.
● Nutrition- babies with CF are given oral pancreatic enzymes so that they are able to break
down starches, proteins, and fats which can be found in milk and solid foods. They also
must eat higher calorie foods than other babies since their digestive system is less efficient
than other babies’. Children and adults who have CF must take daily vitamin supplements
A, D, E and K as well as consume vitamin-rich foods such as fruits and vegetables, as well as
protein-rich foods like fish, eggs and meat. Diets for people with CF consist of an intake of
high-fat and high-calorie foods which are not generally considered healthy, such as cheese,
butter, bacon, etc. This is so they can gain weight, but this usually does not work, so they
require special nutritional supplements such as milk shakes, fruit juices, or high-calorie
powders and liquids. Sometimes this does not help either, and if patients suffer from
detrimental weight loss, they are tube fed with high-calorie nutrient-enriched liquids. This
is done through nose tubes or tubes feeding straight into the stomach.
● Antibiotics help fight off the bacterial infections CF patients may encounter; they are
effective in treating low-grade lung infections most CF patients endure. Although they treat
the bacterial infections and decrease their frequency of outbreaks, they cannot destroy
these bacteria completely. The bacteria that has been left behind will again continue
multiplying and cause another infection. This is treated again, but this unfortunate cycle is
repeated. Using antibiotics repeatedly also has a downside since the bacteria eventually
becomes antibiotic-resistant, and so the antibiotics have no use anymore. Inhalation of
aerosolized medications is a very useful treatment since the mist which is inhaled contains
a drug that reaches airway targets very quickly. Inhalation therapy includes tobramycin
solution (TOBI, an antibiotic) and/or dornase alpha (Pulmozyme, a recombinant drug).
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These drugs are extremely effective, but they are also very expensive. More drugs are being
developed, but so far only these two inhalation drugs seem to be working.
Steroids lessen lung inflammation. They can be taken orally or inhalated. (Examples such as
Flovent or fluticasone propionate and Pulmicort or budesonide)
Mucolytic drugs increase sputum volume and thin mucus. They make it easier for patients
to rid their lungs and airways of mucus. (Examples such as guaifenesin, DNase and Nacetylcysteine)
Hypertonic saline chemically pulls additional water into the airways, making the airways
more slippery (it almost acts like a lubricant) so that patients can cough up the mucus more
easily.
Bronchodilators relax bronchial muscles, which allow the airways to expand and making
breathing much easier. (Examples such as albuterol and Combivent or ipratropium
bromide)
High Frequency Chest Wall Oscillation (HFCWO) or vest airway clearance system is an
inflatable vest attached to a machine which vibrates on the patient. The machine helps the
mucus become unattached to the insides so it is easier to get out. Needs more testing
before it is released into the market.
A Frequencer uses mechanical pressure and sound waves which cause vibration and allow
mucus unattach from small airways into larger airways so it is easier to get out. Needs more
testing before it is released into the market.
Ibuprofen, a drug which is used for anti-inflammation is able to slow the rate of
deterioration to the patients’ lungs (only works for some patients).
Human DNase (dornase alpha) is meant for loosening mucus in the lungs. It may also
reduce hospital time for patients, allowing them to go home earlier. (Example such as
Pulmozyme)
Sometimes, lung transplants in adults have shown to prolong their lives, but lung
transplants are a last resort when treating end-stage lung disease since it is very risky and
not guaranteed to work. In children, lung transplants are sometimes successful, but often
the child’s body is not strong enough to survive the very powerful anti-rejection
medications they are given and they end up rejecting the foreign lung tissue since their
body is not able to recognize it as their own and treats it like a threat. However, recently
there has been an increase in the survival rate of children undergoing lung transplants; the
solution is simply to increase the amount of immunosuppression treatment. However,
immunosuppression agents can lead to the development of osteoporosis, obesity, growth
or loss of (body) hair, and a dramatic growth of the gums (also known as gingival
overgrowth) which can lead to mouth infections and teeth displacements. New therapies
are always in development which will one day allow children not to have the need for antirejection drugs following a major surgery (such as the lung transplant).
● Active Cycle of Breathing Techniques (ACBT) is used to control breath, provide chest
expansion exercises, and force expiratory technique or huffing.
● Postural Drainage and Percussion (PD&P) or Chest Physiotherapy- a patient is put in
different positions to drain mucus from different parts in the lungs.
● Autogenic Drainage (AD) uses someone’s airflow to (while they breathe out) move mucus
from the small to larger airways where it can be cleared. This is done by adjusting the level
of breathing.
10. Although there are currently no cures for CF, research is focusing on advanced technologies.
Gene therapy, nanotechnology, pharmacogenomics and the use of rDNA are current studies
which may help with CF therapy.
Gene Therapy
Ever since the discovery of the mutated CFTR gene (in 1989), researchers have
been trying to find a way to get the good or correct copy of the CFTR gene into the
lungs and airways to replace the defective genes. Tests done on animals showed a promising
path to finding a successful gene therapy treatment, but when these tests were done on
humans and primates, the results were discouraging. Researchers tried to use the virus
method; a method in which they used a virus such as the common cold, as a vector to carry a
normal CFTR gene into the lungs to replace faulty CFTR genes. However, they found that the
good CFTR gene randomly inserted itself into the patient’s DNA, proving an unsuccessful result.
Gene therapy using lung cells is undergoing experimentation.
Pharmacogenomics
This field combines pharmacology and the study of genetics to study how an individual’s
distinctive genome will affect his or her response to drug therapy. The hopes of the field is to
one day be able to tailor custom drugs to each person’s distinct genetic makeup.
Nanotechnology
Nanotechnology is a new field where scientists are aiming to build tiny microscopic devices.
Nanomedicine is what allowed scientists to be able to catalog all cells, cell parts and the
molecules within those parts. Today, very precise and high-powered microscopes as well as
other visualization tools are used to study and categorize cellular parts and subparts. The goal
of modernday nanomedicine research is to “completely and reliably quantify and catalog each
cell and cell part, down to their molecular and atomic levels” (book reference). They also
eventually hope to:
● Cure disease at the molecular level
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Build synthetic biological components such as tiny implantable pumps
for drug delivery, and
Create tiny sensors which will scan the body to ind infectious agents
Recombinant DNA (rDNA)
This is also known as gene splicing or genetic engineering, the rDNA process results in making a
new gene. rDNA is a controversial topic: some worry it may be dangerous. CF patients have
been benefiting greatly from the recombinant drug Pulmozyme, which is supposed to improve
lung function and thin mucus which clogs airways. rDNA is still currently under development.
Stem Cell Research
Researchers are hopeful and determined in finding a way to use stem cells to treat the mutated
CFTR gene, but it will take several years before it can safely deliver DNA to cells.
Ongoing Cystic Fibrosis Therapy Research
Many experimental treatments are always in development for CF are working on solving the
most prominent symptoms of CF. For example, researchers are trying to find ways to correct
the damaged sodium chloride function which is caused by the mutated CFTR protein. If this
issue is fixed, this would allow the channel controlling the sodium chloride to finally work well,
eliminating the dehydration which causes thick mucus buildup in airways and the lungs and salt
loss through sweat in patients.
Living with Cystic Fibrosis
Patients who are diagnosed with Cystic Fibrosis can sometimes have more complicated lives
than people who do not suffer from it. They must be careful with what they eat so they are able
to at least maintain their weight if not gain some. They need to take pancreatic replacement
enzymes with food to ensure that food is digested properly and nutrients are absorbed. Vitamins
A, D, E and K , as well as mineral supplements are needed to grow and maintain healthy bone
structure. Germs must be avoided and extra care is needed so that they the function of their
lungs re not degraded even more. Flu shots allow CF patients immunity to the most common
strains of influenza virus during flu season. Smoking or second hand smoking would cause lung
damage and decreased health. Clean air is needed for CF patients; this is provided by a
nebulizer which has a medication in it to clear the lungs. Physical activity is essential to Cf
patients to promote the exchange of air in and out of lungs and to keep them open.
For patients with CF, it is essential to keep a positive attitude since it is easy for pessimistic
thoughts to enter the mind. Maintaining an active life style is essential, and although lung
function decreases as the years go by, CF patients are encouraged to spend as much time
outdoors and active even though it may get difficult at times. Doctor's appointments may take
time away from daily life, school, and work, but they are essential to maintain a healthy lifestyle
for CF patients. Support groups are offered to individuals and families battling Cystic Fibrosis.
Germs and viruses are detrimental to CF patients' lung function, so travel is not safe at times.
Weight must always be monitored to ensure the patient is getting a good nutritional intake.
Relationships can be difficult for people with CF, since knowing a loved one will be dying before
them, as well as the possibility of not being able to have their own biological children can be
difficult to accept for some. However, new methods and surgical procedures have found ways to
reverse infertility in some men with CF, and with women there is decreased fertility but they can
still get pregnant. Also, life expectancy of people with CF has increased significantly since 1938,
when the life expectancy was 6 months. Now people with CF are expected to live to the age of
mid-30's ranging to their 60's depending on the severity of the disease.