Cystic Fibrosis

There was a German saying that goes all the way back to the 18th century: “A child whose forehead tastes like salt when kissed will soon die.” This was the general wisdom of the dreaded childhood disease cystic fibrosis (CF). Today, due to an improved medical profession, cystic fibrosis patients are living longer than ever before.

Cystic Fibrosis has existed probably since the beginning of human existence, although it was mostly misdiagnosed as something else. For instance, it would have been diagnosed as whooping cough, chronic bronchitis, or pneumonia. It really wasn't until the 1930's that there was widespread documentation of this disease. (1)

The textbook, "Respiratory Disease: Principles of Patient Care, edited by Robert L. Wilkins & James R. Dexter, 1993, describes a paper written in 1936 by Swiss Pediatrician Dr. Franconi and his colleagues where he describes two children with cystic fibrosis. He actually referred to it as celiac disease, a disease of the pancreas. (2)

Also in the 1930s a pathologist named Dr. Dorothy Hansine Andersen became interested in the disease after performing an autopsy. She was the first to recognize this condition as a disease. She named it cystic fibrosis after the scarring and cyst formation that she observed on the pancreas of these patients. Later, in the 1950's,  she helped discover a test that is still used to diagnose cystic fibrosis. She also theorized the condition was caused by a deficiency in vitamin A. (3)

In the 1940's, thick sputum was observed to be the cause of respiratory infections, and the use of antibiotics was started as a primary treatment. During a heat wave in 1948, Dr. Paul di Sant’Agnese discovered that many of the kids admitted to the hospital were actually CF patients. In 1952, during a second heat wave, he realized these kids secreted salt from their skin while sweaty. From this wisdom he ultimately came up with the sweat test. (4)

By the 1950's, emphasis shifted to early detection of the disease, and presently children are tested right at birth.

The 1950's was also a decade in which high fat diets were first studied as a source of treatment for CF, and in the 1960's and 1970's similar studies were performed to show that high fat diets benefited patients with CF. Likewise, during this time, parents, and CF patients who grew to adulthood, helped to create CF research and organizations such as the Cystic Fibrosis Foundation. (5)

A major breakthrough came in the 1980's when the CF gene was discovered. It was discovered on chromosome 7.

According to the textbook, Respiratory Disease: Principles of Patient Care:

"The gene may be altered (mutated) in at least 20 different ways; several of these mutations cause CF. The most common abnormality of the gene is deletion of three base pairs in the DNA. This three-base pair deletion leads to the loss of one amino acid from the protein coded for by the gene. This mutation is known as delta F. The delta F gene accounts for 70-75% of the genetic abnormalities responsible for CF. The severity of CF is in part related to the genetic form of the disease the patient inherits. 

The CF gene contains the code for a large protein that regulates the flow of ions (salt) through glands that secrete fluids (exocrine glands). As a result, CF patients are unable to regulate the salt composition of their secretions as a normal person would. This malregulation of secretions is responsible tor most if not all of the problems that these patients experience." (6)

Those who have CF have the Cystic fibrosis transmembrane conductance regulator (CFTR), which is a protein that in humans is encoded by the CFTR gene. Diseases caused by mutations in this gene result in a blockage in the movement of salt into and out of cells. This results in cells that line the lungs, pancreas and other organs to produce thick, sticky mucus. 
This mucus obstructs the airways and glands, causing the characteristic signs and symptoms of cystic fibrosis. In addition, thin mucus can be removed by cilia. However, thick mucus cannot be removed by cilia, so it remains in the lungs. Here, bacteria get trapped in it. This is what gives cystic fibosis sputum that hard, crusty appearance.  This also makes these patients prone to getting respiratory infections.

Inexplicably, CF is a disease that effects mainly 1 in 25 whites of European dissent. Carriers of the CF gene have no symptoms, and the only way a child can get CF is if both parents are carriers. Children where both parents are carriers have a 1 in 4 chance of developing CF.

The 1990's saw the use of gene replacement therapies where genes are inhaled through the nose or mouth with the hope that they would replace cells with defective genes, or injecting CF patients with a virus with non CF genes in the hope they reproduce and replace CF genes. This testing is still ongoing to this day with variable results.

The 1990's also saw the approval of a drug called Pulmozyne, the first drug used to specifically treat CF, which decreases the risk of pulmonary infection and improves lung function. It basically acts as scissors and cuts extracellular DNA of mucus to decrease it's viscosity (thickness) of mucus.

CF is a disease that has three main components:

1. Bronchiectasis (abnormal dilation of the air passages of the lungs)
2. Pancreatic exocrine insufficiency
3. Elevated sweat electrolyte concentration

The cause of most morbidity and mortality among these patients is due to pulmonary complications. As these patients age the number of goblet cells (mucous glands) increase and peribronchilar tissue becomes inflamed. Secretions become tenacious (thick) and therefore difficult to expectorate (spit up). This makes these patients especially prone to developing respiratory infections that are treated with antibiotics. In some cases they are even treated prophylactically with antibiotics. (6)

They also suffer from (signs and symptoms of):

1. Prolonged neonatal jaundice (excess biliruben due to ineffective pancreas)
2. Poor growth (due to lack of pancreatic enzymes that leads to maldigestion and malabsorption.
3. Diabetes (due to pancreatic exocrine insufficiency stools contain large amounts of fat)
4. Diarrhea: Due to pancreatic exocrine insufficiency
5. Malnutrition: Due to pancreatic problems
6. Infertility
7. Airway reactivity (asthma)
8. Emphysema (when they are in the end stages)
9. Pulmonary hemorrhage (again during the end stage)
10. Mucus plugging (due to thick, tenacious secretions)
11. Pneumonia episodes (due to bacteria trapped in thick secretions)
12. Respiratory infections (may lead to destruction of lung tissue and loss of pulmonary function)
13. Pneumothorax (Collapsed lung during advanced stages)
14. Atelectasis (due to being unable to expand alveoli)
15. Pulmonary hypertension (in advanced stages)
16. Jugular vein distension (if pulmonary hypertension in advanced stages)
17. Pedal edema (if CHF presents in end stage)
18. Cor Pulmonale (Caused by right heart working hard to pump blood through lungs. Usually results in left heart failure eventually or CHF)
19. Respiratory failure (accumulation of respiratory complications)
20. Chronic cough
21. Wheezing
22. Clubbing of the digits (due to chronic hypoxia)
23. Dyspnea (shortness of breath or air hunger)
24. Mild fever during exacerbations of bronchiectasis
25. High fever during episodes of pneumonia
26. Recurrent pancreatitis
27. Excessive salt in sweat (salt crystals in shoes and socks, shirts on hot day, etc.)
28. Heat intolerance (due to loss of electrolytes during warm months of year
29. Electrolyte depletion
30. Dehydration
31. Typically thin, young children
32. Sterile (if women get pregnant usually have miscarriages)
33. Barrel chest
34. Frequent sinus infections
35. Polyps (due to sinus infections similar to asthma. These are probalby caused by increased eosinophils)
36. Diffuse coarse crackles upon auscultation
37. Hypoxemia (advanced stages)

Signs of CF exacerbation:

1. Dyspnea
2. Accessory muscle use
3. Productive cough
4. New onset cough
5. Change in character or consistency of sputum
6. Sudden deterioration in pulmonary function
7. Fever
8. Chest x-ray changes
9. Lack of expected weight gain

Usually, CF patients learn to identify their own unique signs and symptoms of of an oncoming flare up. They usually are very compliant with their treatment regimens, especially as they learn this prevents flare ups. They usually require regular doctor visits and occasional hospital admissions for antibiotics. Sometimes they can get antibiotic therapy at home.

The most common pathogens present in the sputum of CF patients are:

1. staphylococcus aureus
2. Haemophilus influenzae
3. Pseudomonas aeronenosa (unique to CF patients, and usually end stage presentation)

Diagnosis is usually made by the following tests:

1. Test for delta F. Usually identifies 70% of abnormal genes and 50% of affected patients
2. Sweat test (this is usually done at birth, and a positive test will result in further testing)

Treatment includes educating the patient and parents and family members about CF, and helping them learn the early warning signs of a CF exacerbation so they may obtain swift treatment.

Basic treatment includes (as per Healthcentral.com):

1. Bronchodilators (to treat airway bronchospasm)
2. Mucolytics to thin secretions (such as mucomyst or pulmozyne)
3. Antibiotics (exact timing uncertain, although usually CF patients are treated as soon as they observe the signs of CF exacerbation (early warning signs) noted above.
4. Bronchoscopy with bronchoalveolar lavage to clear mucus plugs from imtermediate and small airways.
5. Aerobic exercise to tolerance
6. Autogenic drainage (CPT) They will generally require that you do CPT to all the recommended positions. They quite often have their own mechanical percussors.
7. Lung transplant (yet this has complications all its own)
8. Gene replacement therapy (has positive short term effects on lung function. Involves inhaling sprays that deliver normal cells to hopefully replace CF cells in the lungs. Not yet approved for general use).
9. Enzyme replacement therapy (If their pancreatic ducts are blockes they won't secrete enzymes needed to digest food. Replacement enzymes can be taken in tablet or powder they put on their food).
10. Vitamin supplements

Usually CF patients are among your better patients, and tend to be cheerful and happy despite their condition. They know their disease better than you, and will generally let you know of and how to perform basic therapies (may even have their own mechanical percussor)

Generally, they bring in their own internet and video games to connect to the TV, and almost always have their rooms nice and cool. Sitting on the bedside table will be all sorts of candy bars and goodies that they are encouraged to eat regularly as part of their high fat diet. (Update: Today, this would include iphones and laptops).

CF research is ongoing, and all this new wisdom that's been obtained just since the 1930's has greatly improved the lives of the approximately 30,000 Americans with the disease. There was a time when the average lifespan of CF patients was only a few years. Now many are living a lot longer, to the point where the average life expectancy was 37 years in 2005.

References and further reading:

1. About Cystic Fibrosis: A history of cystic fibrosis
2. Respiratory Disease: Principles of Patient Care, edited by Robert L. Wilkins & James R. Dexter (1993)
3. Changing the Face of Medicine, "Dr. Dorothy Hansine Andersen
4. Cystic Fibrosis Foundation: The Paul di Sant' Agnese Society
5. Cystic Fibosis.com: About Cystic Fibrosis
6. Respiratory Disease: Principles of Patient Care (Wilkins & Dexter, 1993,) page 59)