CYSTIC FIBROSIS

Cystic fibrosis is an inherited disease characterized by the buildup of thick, sticky mucus
that can damage many of the body's organs. The disorder's most common signs and
symptoms include progressive damage to the respiratory system and chronic digestive
system problems. The features of the disorder and their severity varies among affected
individuals.

Mucus is a slippery substance that lubricates and protects the linings of the airways,
digestive system, reproductive system, and other organs and tissues. In people
with cystic fibrosis, the body produces mucus that is abnormally thick and sticky. This
abnormal mucus can clog the airways, leading to severe problems with breathing and
bacterial infections in the lungs. These infections cause chronic coughing, wheezing,
and inflammation. Over time, mucus buildup and infections result in permanent lung
damage, including the formation of scar tissue (fibrosis) and cysts in the lungs.

Most people with cystic fibrosis also have digestive problems. Some affected babies
have meconium ileus, a blockage of the intestine that occurs shortly after birth. Other
digestive problems result from a buildup of thick, sticky mucus in the pancreas. The
pancreas is an organ that produces insulin (a hormone that helps control blood sugar
levels). It also makes enzymes that help digest food. In people with cystic fibrosis,
mucus often damages the pancreas, impairing its ability to produce insulin and
digestive enzymes. Problems with digestion can lead to diarrhea, malnutrition, poor
growth, and weight loss. In adolescence or adulthood, a shortage of insulin can cause a
form of diabetes known as cystic fibrosis-related diabetes mellitus (CFRDM).

Cystic fibrosis used to be considered a fatal disease of childhood. With improved

treatments and better ways to manage the disease, many people with cystic
fibrosis now live well into adulthood. Adults with cystic fibrosis experience health
problems affecting the respiratory, digestive, and reproductive systems. Most men
with cystic fibrosis have congenital bilateral absence of the vas deferens (CBAVD), a
condition in which the tubes that carry sperm (the vas deferens) are blocked by mucus
and do not develop properly. Men with CBAVD are unable to father children (infertile)
unless they undergo fertility treatment. Women with cystic fibrosis may experience
complications in pregnancy
 SYMPTOMS
People with CF can have a variety of symptoms, including:
 Very salty-tasting skin
 Persistent coughing, at times with phlegm
 Frequent lung infections including pneumonia or bronchitis
 Wheezing or shortness of breath
 Poor growth or weight gain in spite of a good appetite
 Frequent greasy, bulky stools or difficulty with bowel
movements
 Male infertility
ACKNOWLEDGEMENTS
I would like to express my special thanks of gratitude to my teacher, Ms
Rachna Misra, as well as our principal Kaamini Bhasin, who gave me
the golden opportunity to do this wonderful project on the topic ‘Any
Disease with a Case Study’ which also helped me in doing a lot of
research on Cystic Fibrosis and I came to know about so many new
things I am really thankful to them.

Secondly I would also like to thank my parents who helped me in

finalizing this project within the limited time frame.
 INDEX
• What is Cystic Fibrosis?
• Symptoms
• Complications
• Types of Cystic Fibrosis
• Burkholderia Cepacia Complex
• Diagnosis
• Treatments
• Case Study
• Bibliography
 TYPES OF CYSTIC
FIBROSIS
Cystic fibrosis is caused by mutations, or errors, in the cystic fibrosis trans membrane
conductance regulator (CFTR) gene which result in either no CFTR protein being made
or a malformed CFTR protein that can’t perform its key function in the cell. Its function
is to create channels on the cell surface to allow the movement of chloride (a
component of salt) in and out of the cell. When the CFTR protein functions properly, the
balance of chloride and fluid at the cell surface remains normal.

If the CFTR protein does not function properly, the balance of chloride and fluids is
disrupted, causing mucus in various organs to become thick and sticky. This leads to
lung infections and eventually, respiratory failure, in the lungs, poor digestion and
problems in the reproductive system.

Every person has two copies of the CFTR gene, one inherited from the mother and one
from the father. For a person to have CF, there has to be a mutation in both copies of
the CFTR gene.

Scientists have found more than 1,700 different mutations in the CFTR gene that can
cause CF. (A mutation can be a very tiny change; a switch of one single letter to
another letter, or a deletion of one or more letters.) Over the years, scientists have
used several different ways of grouping these mutations into different classes. The most
recent classification system groups mutations by the problems that they cause in the
production of the CFTR protein:

• Protein production mutations (Class 1)

• Protein processing mutations (Class 2)

• Gating mutations (Class 3)

• Conduction mutations (Class 4)

• Insufficient protein mutations (Class 5)

Protein Production Mutations

Protein production mutations, which include nonsense and splice mutations, interfere
with the production of the CFTR protein.

All proteins, including CFTR, are made of building blocks called amino acids that are
linked together into a long chain. The protein-building instructions spelled out in the
CFTR gene tell the cell which of the 20 available amino acids to use at each position in
the chain. The letters in the gene also spell out a “stop” signal that lets the cell know
that it has reached the end of the instructions and can stop making the protein.

If the CFTR gene has a nonsense mutation, the protein-building instructions contain an
early stop signal that causes the production of the CFTR protein to stop prematurely.

Splice mutations interfere with the ability of the cell to correctly read the instructions
for making the CFTR protein. In a healthy person, the instructions spelled out in a gene
are interrupted by stretches of DNA letters that do not code for protein. In order to
make the protein, the cell copies the DNA letters into RNA, and then follows the signals
to clip out all of the irrelevant letters. That way, the instructions can be read straight
through from start to finish.

A splice mutation changes the signal that tells the cell where the irrelevant letters in the
instructions begin or end. When the cell tries to read its RNA copy of the instructions, it
no longer can tell where to begin and end reading. As a result, the cell will either leave
in some irrelevant letters, or remove some relevant ones. When the cell tries to follow
the RNA instructions containing the irrelevant letters, or missing relevant ones, it will be
unable to build a correct CFTR protein.

Protein Processing Mutations

The CFTR protein is made up of 1,480 amino acids. When the CFTR protein is made
using all of the correct amino acids, it forms a stable 3-D shape. It has to be the right
shape to transport chloride.

When a mutation causes an amino acid to be deleted or an incorrect amino acid to be

added, the CFTR protein cannot form its correct 3-D shape and function properly. These
mutations are considered to be protein processing mutations.

Gating Mutations

The CFTR protein is shaped like a tunnel, or channel, with a gate. The cell can open the
gate when chloride needs to flow through the channel. Otherwise, the gate stays
closed.

Gating mutations lock the gate in the closed position so that chloride cannot get
through. Some drugs help people with gating mutations by forcing the gate on the
CFTR channel to stay open. This enables chloride to move through the channel and
reduces the symptoms of CF.

Conduction Mutations

Sometimes, a change in one of the amino acids of CFTR means that even though the
protein makes the right 3-D shape, it doesn't function as well as it should. In order for
CFTR to work correctly, chloride has to be able to move quickly and smoothly through
the protein's channel. Some mutations change the shape of the inside of the tunnel so
that chloride cannot move through as easily as it should. This kind of mutation is called
a conduction mutation.

Insufficient Protein Mutations

Insufficient protein mutations result in a reduced amount of normal CFTR protein at the
cell surface. This occurs for several reasons: a limited amount of CFTR protein is
produced; only a small number of protein at the cell surface works correctly; or normal
protein at the cell surface degrades too quickly, leaving small numbers of protein
behind.

In each case, insufficient functional proteins at the cell surface produce only some, or
residual, function of the chloride channel. Insufficient protein can be caused by several
mutations, including missense and splice mutations.

As mentioned above, some splice mutations interfere with the way the cell reads the
DNA instructions for making a protein. This can result in a limited quantity of normal
CFTR protein reaching the cell surface, which results in residual function.

Researchers are developing a new type of modulator called amplifiers, which would
increase the amount of CFTR protein produced in the cell. Amplifiers could be combined
with other modulators, such as ivacaftor and lumacaftor, to fix other problems with the
CFTR protein.
 BIBLIOGRAPHY
 https://www.cff.org/What-is-CF/About-Cystic-Fibrosis/
 https://ghr.nlm.nih.gov/condition/cystic-fibrosis
 https://www.cff.org/What-is-CF/Genetics/Types-of-CFTR-Mutations/
 https://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/symptoms-causes/syc-
20353700
 https://www.nhlbi.nih.gov/health-topics/cystic-fibrosis
 https://www.nhs.uk/conditions/cystic-fibrosis/treatment/
 BURKHOLDERIA
CEPACIA COMPLEX
(B. Cepacia)
Burkholderia bacteria are often resistant to many antibiotics, which makes them difficult
to treat once they infect the lungs. However, some species may be successfully treated
with combinations of antibiotics.

Basic infection prevention and control practices reduce the risk of getting or
spreading B. cepacia. These bacteria pose very little medical risks to healthy people.
However, some people who have a serious illness such as cancer or acquired
immunodeficiency syndrome (AIDS) may be at risk of an infection from these bacteria.

B. Cepacia and CF
How B. cepacia complex species affect people with CF varies. Researchers do not yet
know why some people with CF are more likely to get B. cepacia than others.

In many people with CF, infection with B. cepacia may not worsen lung disease. In up
to one-third of people infected with B. cepacia, the rate of lung function decline appears
to be only slightly faster. However, for a smaller number of people, B. cepacia can
cause a rapid decline in lung function and health. This can lead to more severe lung
disease and maybe death. Among the different species of B. cepacia complex, some
may be more harmful than others (for example, B. cenocepacia and B. dolosa). The
Cystic Fibrosis Foundation is working with researchers to learn more about the B.
cepacia complex and help identify new treatments.

How it Spreads
It is not always known how people with CF become infected with B. cepacia complex.
Research has shown that people with CF can get B. cepacia from others who are
infected with these bacteria. The germs spread either by direct contact, such as kissing,
or indirectly from touching objects with the germs, such as doorknobs. This is known as
cross-infection and can happen in social settings like events, gatherings or meetings.
In some cases, shared infection was not found in the lungs of a person with CF until two
years after being exposed to someone else who was infected with the germ.

For many people with CF, infection with B. cepacia complex cannot be traced back to
exposure to another infected person. In these cases, infection may have occurred by
exposure to Burkholderia in the natural environment.

Diagnosing B. Cepacia
When a doctor or nurse gets a throat or sputum culture from a person with CF, the
laboratory tests the culture in a specific way to help find any B. cepacia complex
species. Ask your CF care center about the results of your last throat or sputum culture.
Keep in mind that medical evidence shows that everyone living with CF could have
germs that might spread to others with CF. Plus, sputum cultures may not find all
germs that could spread among people with CF.

Research on B. Cepacia
The CF Foundation is supporting research on B. cepacia complex to find new ways to
prevent or get rid of lung infections caused by these bacteria in people with CF. Some
researchers are studying whole new classes of antibiotics to fight B. cepacia complex
bacteria.

In addition, basic scientific research is underway to describe the differences between

the B. cepacia complex species. The CF Foundation supports the B. cepacia Research
Laboratory and Repository at the University of Michigan, Ann Arbor. The laboratory is a
resource to the CF medical community to help researchers identify B. cepacia complex
species, investigate their spread and store samples for future research studies.

The laboratory also enables scientists to learn more about how B. cepacia causes
infection and to help find new treatments for people with CF. Care centers can send
sputum cultures to the lab to confirm and identify the specific species of B.
cepacia complex.
 DIAGNOSIS
To diagnose cystic fibrosis, your doctor may recommend some of the following tests
and procedures:

 Genetic testing to detect mutated CFTR genes. This test can confirm a positive
cystic fibrosis screening test and sweat test. If genetic testing is done as part of
newborn or other screening, it may not be repeated during the newborn stage. Genetic
testing is described in more detail in Screening and Prevention.
 Prenatal diagnostic tests to diagnose cystic fibrosis in an unborn baby, using
mutated CFTR genes. This is done with procedures that take either a sample of
amniotic fluid, the liquid in the sac surrounding your unborn baby, or tissue from
the placenta. Cells from these samples are checked for gene mutations. Infants with
positive prenatal testing for cystic fibrosis will be further tested after birth to confirm
the diagnosis of cystic fibrosis.
 Sweat test for high sweat chloride to see if you have high levels of chloride in your
sweat. The sweat test is the standard test for diagnosing cystic fibrosis. It may be used
if you have symptoms that may indicate cystic fibrosis, or to confirm a positive
diagnosis from a screening of your newborn baby. A normal sweat chloride test alone
does not mean you do not have cystic fibrosis. Lower levels of chloride may indicate the
need for further testing to diagnose or rule out cystic fibrosis.

Sweat chloride test results for diagnosing cystic fibrosis. The table shows how
much chloride in a person’s sweat sample must be present in order to determine
whether the diagnosis for cystic fibrosis is positive, unclear, or unlikely. A chloride level
of 60 millimoles per liter (mmol/L) or greater indicates cystic fibrosis. A chloride level of
30 to 59 mmol/L indicates a diagnosis of cystic fibrosis is unclear, and that further
testing is needed. A chloride level of less than 30 mmol/L indicates a diagnosis of cystic
fibrosis is unlikely.

How is a sweat chloride test performed?

The sweat test detects a higher amount of chloride—a component of salt that is made
of sodium and chloride—in the sweat of people who have cystic fibrosis. In order to
make sweat for this test, a colorless, odorless chemical and a little electrical stimulation
are applied to a small area of an arm or leg. The sweat is collected and sent to a
hospital lab for testing.
 COMPLICATIONS
Respiratory system complications

 Damaged airways (bronchiectasis). Cystic fibrosis is one of the leading causes of

bronchiectasis, a condition that damages the airways. This makes it harder to move air in
and out of the lungs and clear mucus from the airways (bronchial tubes).

 Chronic infections. Thick mucus in the lungs and sinuses provides an ideal breeding
ground for bacteria and fungi. People with cystic fibrosis may often have sinus infections,
bronchitis or pneumonia.

 Growths in the nose (nasal polyps). Because the lining inside the nose is inflamed and
swollen, it can develop soft, fleshy growths (polyps).

 Coughing up blood (hemoptysis). Over time, cystic fibrosis can cause thinning of the
airway walls. As a result, teenagers and adults with cystic fibrosis may cough up blood.

 Pneumothorax. This condition, in which air collects in the space that separates the lungs
from the chest wall, also is more common in older people with cystic fibrosis.
Pneumothorax can cause chest pain and breathlessness.

 Respiratory failure. Over time, cystic fibrosis can damage lung tissue so badly that it no
longer works. Lung function usually worsens gradually, and it eventually can become life-
threatening.

 Acute exacerbations. People with cystic fibrosis may experience worsening of their
respiratory symptoms, such as coughing and shortness of breath, for several days to
weeks. This is called an acute exacerbation and requires treatment in the hospital.

Digestive system complications

 Nutritional deficiencies. Thick mucus can block the tubes that carry digestive enzymes
from your pancreas to your intestines. Without these enzymes, your body can't absorb
protein, fats or fat-soluble vitamins.

 Diabetes. The pancreas produces insulin, which your body needs to use sugar. Cystic
fibrosis increases the risk of diabetes. Around 30 percent of people with cystic fibrosis
develop diabetes by age 30.
  Blocked bile duct. The tube that carries bile from your liver and gallbladder to your small
intestine may become blocked and inflamed, leading to liver problems and sometimes
gallstones.

 Intestinal obstruction. Intestinal obstruction can happen to people with cystic fibrosis at
all ages. Children and adults with cystic fibrosis are more likely than are infants to develop
intussusception, a condition in which a section of the intestines folds in on itself like an
accordion.

 Distal intestinal obstruction syndrome (DIOS). DIOS is partial or complete obstruction

where the small intestine meets the large intestine.

Reproductive system complications

Almost all men with cystic fibrosis are infertile because the tube that connects the testes
and prostate gland (vas deferens) is either blocked with mucus or missing entirely.
Certain fertility treatments and surgical procedures sometimes make it possible for men
with cystic fibrosis to become biological fathers.

Although women with cystic fibrosis may be less fertile than other women, it's possible
for them to conceive and to have successful pregnancies. Still, pregnancy can worsen
the signs and symptoms of cystic fibrosis, so be sure to discuss the possible risks with
your doctor.

Other complications

 Thinning of the bones (osteoporosis). People with cystic fibrosis are at higher risk of
developing a dangerous thinning of bones.

 Electrolyte imbalances and dehydration. Because people with cystic fibrosis have
saltier sweat, the balance of minerals in their blood may be upset. Signs and symptoms
include increased heart rate, fatigue, weakness and low blood pressure.
 CASE STUDY
A male child was born in 1980. He did not gain weight normally and had frequent,
loose, foul-smelling bowel movements. At four months of age, he developed a
cough that produced phlegm. A sweat test showed elevated chloride levels, which
are diagnostic of cystic fibrosis. He was referred to a CF center and was treated with
pancreatic enzymes, chest physiotherapy (to clear excessive secretions in the
chest), and antibiotics. He was in fairly good health for a number of years, although
he struggled to gain weight and had several hospital stays for breathing problems.
At age 10, he became infected with the bacterium Pseudomonas aeruginosa. His
pulmonary function worsened, and he required hospital stays lasting up to two
weeks once or twice a year. At age 14, he began taking a new drug, dornase alfa,
and showed improvement. Three years later, he began taking nebulized
tobramycin, and showed further improvement. When he turned 18, he transitioned
to an adult CF program. He continued to have frequent pulmonary exacerbations
requiring repeated courses of intravenous antibiotics. He developed complications
from the antibiotics, including kidney damage and hearing loss. At age 24, he
received a lung transplant. He now maintains normal lung function but takes
several medications to prevent infection and lung rejection. He works part time and
takes classes at a community college.

This case is representative of an early presentation of an infant with cystic fibrosis

with malabsorption and failure to thrive symptoms. Going forward, most patients
will be diagnosed by newborn screening, which is now mandatory in all states. He
developed bronchiectasis at an early age and became infected with the bacterium
Pseudomonas aeruginosa, the most important infection for CF patients. He had
severe pulmonary disease as marked by frequent pulmonary exacerbations, rapid
loss of lung function, and need for a lung transplant.
 TREATMENTS
There's no cure for cystic fibrosis, but a range of treatments can help control the
symptoms, prevent or reduce complications, and make the condition easier to live with.

Regular appointments to monitor the condition are needed and a care plan will be set
up based on the person's needs.

People with cystic fibrosis are treated by a team of healthcare professionals. Sometimes
the condition will require treatment in hospital.

Medicines for lung problems

People with cystic fibrosis may need to take different medicines to treat and prevent
lung problems. These may be swallowed, inhaled or injected.

Medicines for lung problems include:

• antibiotics to prevent and treat chest infections

• medicines to make the mucus in the lungs thinner and easier to cough up – for
example, dornase alfa, hypertonic saline and mannitol dry powder

• medicine to help reduce the levels of mucus in the body – for example, ivacaftor
taken on its own (Kalydeco) or in combination with lumacaftor (Orkambi, but this is
only available on compassionate grounds if people fulfil several criteria set by the
manufacturer)

• bronchodilators to widen the airways and make breathing easier

• steroid medicine to treat small growths inside the nose (nasal polyps)

It's also important that people with cystic fibrosis are up-to-date with all routine
vaccinations and have the flu jab each year once they're old enough.

Exercise

Any kind of physical activity, like running, swimming or football, can help clear mucus
from the lungs and improve physical strength and overall health. A physiotherapist can
advise on the right exercises and activities for each individual.

Airway clearance techniques

A physiotherapist can also teach techniques to help keep the lungs and airways clear.

These include:

• the active cycle of breathing techniques (ACBT) – a cycle of deep breathing,

huffing, coughing and relaxed breathing to move mucus
• autogenic drainage – a series of gentle controlled breathing techniques that clear
mucus from the lungs

• airway clearance devices – handheld devices that use breathing techniques,

vibration and air pressure to help remove mucus from the airways (for example, a
positive expiratory pressure, or PEP, device)

Dietary and nutritional advice

Eating well is important for people with cystic fibrosis because the mucus can make it
difficult to digest food and absorb nutrients. The pancreas often doesn't work properly,
making it even harder to digest food. A dietitian will advise on how to take in extra
calories and nutrients to avoid malnutrition. They may recommend a high-calorie diet,
vitamin and mineral supplements, and taking digestive enzyme capsules with food to
help with digestion.

Lung transplants

In severe cases of cystic fibrosis, when the lungs stop working properly and all medical
treatments have failed to help, a lung transplant may be recommended. A lung
transplant is a serious operation that carries risks, but it can greatly improve the length
and quality of life for people with severe cystic fibrosis.
 CERTIFICATE
This is to certify that this Biology Project on the topic of Cystic
Fibrosis has been successfully covered by Aviva Tuteja of class
XII-A under the guidance of Ms. Rachna Misra Ma’am in
particular fulfillment of the curriculum Central Board of
Education (CBSE) leading to the award of annual examination
of the year 2019-2020

_______________ _______________
Teacher In-Charge External Examiner