What Is CF?

Wehe dem Kind, das beim Kuß auf die Stirn salzig schmekt, er ist verhext und muss bald sterbe.
"Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon must die."

I've had several people (OK, just about everyone) ask what Cystic Fibrosis is and how it affects the body.  Interestingly, CF is the most common severe genetic disease in the Caucasian population, and can be found in other forms (although rarely) in other races around the world (except Japan, where it's almost unheard of).

The main reason for illness is pancreatic insufficiency (the pancreas is not supplying enough enzymes to break down food, especially fats and proteins, and therefore not breaking down and absorbing vitamins A, D, E, and K), and the basic defect of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR); this is what makes several organs not function properly.  Although some emphasis is focused on nutrition and enzymes, the focus of the doctors is on the lungs.

With the defect in the CFTR, the lungs slowly fill with thick, sticky mucus.  The mucus is there naturally to catch fuzz and lint that we breathe in.  Under that layer of mucus is water (periciliary liquid), and in the water is a lot of little hairs (cilia) that sway and wave, like seaweed in the ocean, moving the layer of mucus along and out of the body.  In CF patients, the layer of water is decreased, causing the cilia to get gummed up in the mucus and not sway properly to get rid of the mucus.  This causes more cough, which over time can irritate the lung lining causing swelling, and the mucus becomes a breeding ground for infection.  The infection brings on white blood cells, and pretty soon you have a really crowded hallway gummed up with stuff.  If it's not cleared out, it becomes clogged, hardens, scarred and permanently plugged.

Like other illnesses, there are several varieties of the disease--in this case, there are six types (there are actually dozens of mutations, but each of them fall into one of these six categories).  I often think of these in terms of a manufacturing plant, because the cells are, in fact, trying to manufacture chloride ions to deliver from the cell to the outside of the organ, which could be the lungs, the intestines, the liver, the pancreas, or the skin.  So imagine the cell is the manufacturing plant and they're trying to build the chloride.

Type I:  In this plant, you have the Premature Termination Mutations.  Here the workers are trying to build the thing, but they're missing a page (or 10) of the directions.  They have all the parts to put it together and no idea how to do it.  They scrap the project and open the next box, hoping to find a good set of the instructions only to find that it's exactly the same, box after box.  The chloride doesn't make it to the cell surface.  This mutation has a drug being developed, and is now in Phase III study, called Ataluren (or PTC124).

Type II:  This is our battlefield here--the most common of CF mutations, covering more than 85% of patients, is called Delta F508 mutation and has the chloride ions built into long strands and needs to be folded into an accordion-like shape and be sent on to the next phase.  Unfortunately, it doesn't fold properly.  Using our factory model, the materials from step 1 in the manufacturing has been created nicely and this group receives it and has to package up the product for the customer.  Unfortunately, these guys went on a weekend-long bender and it's Monday morning, so they're having a heck of a time folding the thing to fit into the package.  They keep doing it wrong and the Quality Assurance guys pitch them out into the burn barrel.  The drugs being tested now for this is VX-809 and VX-661, called a CFTR corrector.  This is only half of the puzzle that is needed to normalize cell function; the other half is from the already approved VX-770, also called Kalydeco (kal-eye-deh-coh), a Potentiator.

Type III:  This is the Activation/Channel Mutations and requires a Potentiator drug to cause the body to function properly.  This is caused by the chloride channels not opening properly; in our factory model, it's the shipping department being unable to open the overhead doors to get the product out to the trucks.  Some buffoon doesn't realize that the doors are locked or that the spring is broken.  The drug already developed for this is the VX-770 (Kalydeco).  This only serves to help about 4% of the CF population, which amounts to approximately 1200 people in the US, and 2500 people worldwide.  Not very many, but when it's combined with the 85% of patients who have the F508 mutation, it will jump to some 30,000 in the US, and 60,000 worldwide.

Type IV:  Another delivery issue, this one I *think* is where the door will open, but the incorrectly folded chloride ion can't fit through it properly.  I don't know what's going on with QA that they let these mis-folded pieces get by, or if the doors are unusually small, but somehow they still can't get the product on the truck.

Type V:  This is another kind of stop mutation where it looks like the directions are flawed and the factory workers make two pieces and no idea how to join them together.  It's quite rare, so I can't find any information on it, although if you want to wade through heavy medical journals, it's called a "Splice Mutation".  Good luck.

Type VI:  classified as "Turnover mutations", this doesn't have anything written online that I can find.  Must be really rare, but it appears that it's a problem with the bay doors again.  Maybe they forgot to install them at the factory...This is another job for Potentiator Man!

Still an orphan disease by any standard, it will change the lives of thousands of individuals and ease the burden of care for the families of the children and adults who suffer.

What is burden of care?  Let me run down my day.
7 a.m.:  wake up, go into Ben's room with a large syringe full of water to wash out the feeding tube he wears at night.  Tell him to get dressed while I take the pump apart and throw away the feed bag, take the ice pack out and run it down stairs to the freezer.  I run into my bedroom to get dressed.
7:15:  tell Ben to get dressed again and start threatening him.  Emma starts her breathing treatments.
7:20:  Ben finally gets downstairs and I administer the "Red Medicine" (albuterol).  
7:22:  Set up Ben's inhaled 7% saline.  Start nebulizer.  Then I start making his breakfast.
7:30:  Give Ben breakfast and 3 enzymes and tell him to eat quickly.  Emma makes lunches
7:45:  Tell Ben to eat quicker.  Go looking for wallet, keys, phone and my own shoes.
7:50:  Tell Ben to leave breakfast and go get his socks and shoes on.  Make tea for the road.
7:55:  Tell Ben to get his socks and shoes on again, and search for his backpack.
7:58:  Grab backpack, socks, shoes, coat and Ben and throw them all in the car along with the acapella and Flovent inhaler.  He does these on his way to school.
(Sometimes I'm more with it and I monitor him while he gets dressed, so he's downstairs by 7:05 rather than 7:20...even then, there's a lot of dawdling involved.)

At 7 pm, we do all this again:
Albuterol, saline, acapella, another medicine called Pulmozyme, Flovent and another new one, Flonase.

Soon we'll get to add another 20 minute treatment with his vest, which we will be able to combine with the saline and/or acapella treatment.  Still, in all, we spend 90 minutes a day on his treatments.  Every day.  That's a fairly typical regimen--some people spend two to three HOURS a day doing treatments.  That, my friends, is the burden of care.

We're doing a fundraiser next weekend in Fremont called the Troll Stroll.  All proceeds raised will go to the Cystic Fibrosis Foundation to fund research to find a cure, which is how Kalydeco was discovered.  Hopefully we'll be able to find Kaly's sister....I wonder what her name will be?