CYSTIC

FIBROSIS
 What Is Cystic Fibrosis?

Cystic fibrosis is a serious genetic condition that causes severe damage to the respiratory and
digestive systems. This damage often results from a buildup of thick, sticky mucus in the organs.
The most commonly affected organs include the:

lungs
pancreas
liver
intestines
Cystic fibrosis affects the cells that produce sweat, mucus, and digestive enzymes. Normally,
these secreted fluids are thin and smooth like olive oil. They lubricate various organs and
tissues, preventing them from getting too dry or infected. In people with cystic fibrosis,
however, a faulty gene causes the fluids to become thick and sticky. Instead of acting as a
lubricant, the fluids clog the ducts, tubes, and passageways in the body. This can lead to life-
threatening problems, including infections, respiratory failure, and malnutrition. It’s critical
to get treatment for cystic fibrosis right away. Early diagnosis and treatment are critical for
improving quality of life and lengthening the expected lifespan.
 Race and Ethnicity

Cystic fibrosis is most common among people of Northern European heritage, affecting one of every 3,000
newborns. It is least common in people of African or Asian descent and affects women only slightly more than
men.

In the United States, the rate of CF varies by racial population. It is estimated that the number of Americans who
carry a CFTR mutation is around:

1 in 29 Caucasian-Americans (1 in 3,500 risk)

1 in 46 Hispanic-Americans (1 in 10,000 risk)
1 in 65 African-Americans (1 in 20,000 risk)
1 in 90 Asian-Americans (1 in 100,000 risk)
The actual rate of babies born with CF is around:

1 in 3,500 Caucasian-Americans
1 in 10,000 Hispanic-Americans
1 in 20,000 African-Americans
1 in 100,000 Asian-Americans
The country with the highest rate of babies born with CF is Ireland, in which one of every 1,353 births will be
affected, according to an epidemiological study published in the Biomedical and Biotechnology Research Journal.
 Disease Progression
The only risk factor for getting CF is having two parents who carry abnormal CFTR genes. With that being
said, there are factors that can influence the severity and progression of the disease.
Chief among these is the timing of diagnosis and treatment. Newborn screening is considered vital as it allows
immediate treatment of the disease. By doing so, we can slow or prevent the damage that can occur as early as
the first two months of life.
According to a study published in Current Opinions in Pulmonary Medicine, children who are treated after CF
symptoms appear will usually have significant airflow impairment and signs of respiratory injury by the age of
two. By comparison, children identified and treated at birth will, by the age of two, have lung function
comparable to a one-year-old in the delayed treatment group.
Early treatment, along with advances in drug therapies, means that children diagnosed with CF today may live
well into their 40s and 50s and remain largely unencumbered by the disease.
 Pathophysiology

CF is a multisystem disease and below we will discuss the basic underlying pathophysiology and complications
of the disease:

Respiratory tract

The CTFR gene encodes the CFTR protein – a chloride channel that is present in numerous epithelial tissues.
Chloride is driven against its concentration gradient using ATP.

In the airway, CFTR is present on airway epithelial cells and submucosal glands and when defective results in
disruption to chloride ion movement and also affects sodium reabsorption (by disturbing the function of ENaC)
which reduces the amount of water in secretions. This results in reduced airway surface liquid.

The airway surface liquid is an important component of the mucociliary escalator and also has key
immunological functions. The effects of reduced airway surface liquid serve to impede mucus clearance.

The altered lung environment provides a niche for bacterial growth with the biofilm mode of growth providing
ideal conditions to protect bacteria from the host immune system and the actions of antibiotics. The pro-
inflammatory cascade contributes to tissue damage.
 Pancreas
In the pancreas the pancreatic duct is usually occluded in-utero causing permanent damage to
the exocrine pancreas rendering patients with CF ‘pancreatic insufficient’. Pancreatic
insufficiency is closely related to genotype. Over time, endocrine pancreas is affected with 28%
of those older than 10 years requiring treatment for CF-related diabetes mellitus.1

Gastrointestinal tract
In the gastrointestinal tract, the small intestine secretes viscous mucus which can cause bowel
obstruction in-utero which can cause meconium ileus. In the biliary tree in-utero, CF can cause
cholestasis which can result in neonatal jaundice. Later in life the same pathology can result in
distal intestinal obstruction syndrome (DIOS) and CF-related liver disease (14% of patients).

Reproductive tract
98% of men with CF are infertile due to a congenital absence of the vas deferens. In women
nutrition is likely to be an important predictor of successful pregnancy. It is suggested that the
timing of pregnancy be carefully planned, as pregnancy is often associated with a deterioration in
lung health.