Week 3 Story Draft

*Writing In Progress*

Co-Written By: Phoebe Ireland Coleman and Bill Elder

*Mostly described by Bill Elder. Actual animation narrative is being written and will be posted soon. Revisions will be done in dark blue.

CF Med Animation Story
January 30th, 2009

Cystic Fibrosis Medical Animation

Cystic Fibrosis is an autosomal recessive genetic disorder meaning it actually takes two copies of the CF gene to have Cystic Fibrosis. One copy of the CF gene and one normal gene means that the individual is a carrier. One of the explanations given for why CF still exists in the gene pool is that carriers of the gene may have a better chance of surviving a Cholera infection by decreasing the amount of water loss and preventing dehydration.

(see first set of images)

[Animation: Show Chromosome number 7, rotating into the scene, away from the camera. Landing next to the other chromosomes sets and adjacent to the other chromosome number 7. Labeling the first chromosome (on the right) as the chromosome where the DNA information would lie. Label right with “carrier.” If a person has two mutant genes, the person is diagnosed with CF.]

The CF gene codes for the Cystic Fibrosis Transmembrane conductance Regulator or CFTR for short. The CFTR is found on smooth tissue throughout the body, most importantly in the airways and the pancreas. The CFTR is an ion channel that helps move water into the mucus in the lungs making it less viscous and easier to clear from the airways. While there are numerous mutations in the CF gene they all lead to a dysfunctional CFTR that is inable to pump ions across the membrane onto the surface of the lungs. This dysfunctional ion channel (CFTR) leads to mucus that is too thick for the cilia to move out of the lungsand the mucus builds up.

(See second set of images)

In the lungs this thick mucus become a problem when bacteria manages to make it's way inside the mucus. The mucus acts as a sort of "bio-dome" for the bacteria allowing it to colonize the lungs. Once a bacteria (most commonly Psuedomonas, although very rarely and very dangerously B. Cepacia) manages to get inside the mucus the body will send white blood cells (lymphocytes) to kill the bacteria, but the chemicals produced by the white blood cells will be blocked by the thick mucus and will instead destroy the surrounding lung tissue. The bacteria itself also damages the lung as it grows.

The majority of CF research is focused on clearing mucus from the lungs because nearly all patients die from some form of lung infection (or conditions associated with it.) As a result the majority of CF treatment is focused on the lungs. Pulmozyme is a nebulized medication which is actually an enzyme which breaks apart DNA. As it turns out the bacteria leaves strands of DNA in the mucus which make it much thicker. By breaking this DNA up into smaller bits it makes the mucus much less viscous and it can be coughed up by the patient using the Huff Cough Technique: http://www.sierrabiotech.com/bt_copd_huff.html. Many nebulized antibiotics are also used help kill the Psuedomonas such as Tobi (Tobramycin for inhalation), Colistin, Aztreonam and a few more I can't remember. Along with inhaled antibiotics patients are often prescribed Ciprofloxacin which is in pill form and can be a very effective measure for fighting more serious infections.

Aside from antibiotics, many inhalers such as Atrovent, Serevent, Albuterol and Advair are used to help reduce the constriction and inflamation of the airways as a result of infection (Asthma.) Hypertonic Saline has also begun to be nebulized as treatment for CF. It is essentially really salty water and the exact mechanism of how it works is unknown (at least to me!) although it may help stimulate other ion channels to open in the airway. While a patient does a nebulizer treatment they will also commonly use "the vest". The therapy vest sits on the outside of the chest and inflates with air. It then inflates and deflates rapidly causing the lungs to shake and causing the mucus to be thrown off of the lung surface and then expelled. Along with this therapy CF patients should also try and stay active by running as often as they can. It is hypothesized that running may cause other channels in the airway to open up and help clear mucus.

In the pancreas the thick mucus can block the enzymes from leaving the pancreas and can over time begin to destroy the pancreas. This destruction can also destroy the Islets of Langerhans whcih produce insulin and this can lead to Cystic Fibrosis Related Diabetes (CFRD). This is why many CF patients must take digestive enzymes (the ones I take are called Creon) and why CF patients have a hard time maintaining their weight. Many individuals who have a more serious condition must have a feeding tube (called a G-tube) inserted into their stomach.

[Animation: A cross-section of the airway epithelia and the CFTR. I would then show that because of the lack of CFTR function the mucus becomes far more viscous and the cilia are unable to adequately move it out of the airway. Then you could show the colonization of the mucus by Psuedomonas and the resulting immune response which damages the lungs.]

Here's a site with some decent pictures of the CFTR: http://old.schoolscience.co.uk/content/5/biology/mrc/3/page3.html (It is actually far more complicated than that, it turns out it does a lot more than just let chloride through)

[Animation note: that the CFTR also causes problems with the formation of the vas deferens in males leading to infertility. Also the CFTR is present in sweat glands and as a result CF patients have much saltier sweat than normal, which is the most common means of diagnosis for CF.]

For the lungs you could show mucus accumulating over time and gradually turning from clear to yellow to green as a result of infection. You could then show how a mucus plug could block off one of the branches in the airway and how this could dramatically drop lung function due to the loss of volume.

[Animation: show mucus accumulating over time, with gradual color as a result from an infection. Change from clear, yellow, and ending with green.]

[Animation: show mucus plug block off one of the branches in the airway and how this could dramatically drop lung function due to the loss of volume.]

[End Animation: Show credits]

From the Cystic Fibrosis Foundation, Colorado Chapter Website: About Cystic Fibrosis

What You Need to Know

What Is Cystic Fibrosis?

Cystic fibrosis is an inherited chronic disease that affects the lungs and digestive system of about 30,000 children and adults in the United States (70,000 worldwide). A defective gene and its protein product cause the body to produce unusually thick, sticky mucus that:

• clogs the lungs and leads to life-threatening lung infections; and
• obstructs the pancreas and stops natural enzymes from helping the body break down and absorb food.

In the 1950s, few children with cystic fibrosis lived to attend elementary school. Today, advances in research and medical treatments have further enhanced and extended life for children and adults with CF. Many people with the disease can now expect to live into their 30s, 40s and beyond.

Symptoms of Cystic Fibrosis

People with CF can have a variety of symptoms, including:

• very salty-tasting skin;
• persistent coughing, at times with phlegm;
• frequent lung infections;
• wheezing or shortness of breath;
• poor growth/weight gain in spite of a good appetite; and
• frequent greasy, bulky stools or difficulty in bowel movements.

Statistics

• About 1,000 new cases of cystic fibrosis are diagnosed each year.
• More than 70% of patients are diagnosed by age two.
• More than 40% of the CF patient population is age 18 or older.
• The predicted median age of survival for a person with CF is more than 37 years.

The Cystic Fibrosis Foundation

Since 1955, the Cystic Fibrosis Foundation has been the driving force behind the pursuit of a cure. Thanks to the dedication and financial backing of our supporters--patients, families and friends, clinicians, researchers, volunteers, individual donors, corporations and staff, we are making a difference.

• Learn more about Testing for Cystic Fibrosis.
• Explore all aspects of Living with CF at every stage of life.
• See what Treatments are available and what’s in development.

Source: http://www.cff.org/AboutCF/