Cystic Fibrosis
Alexandra Kejner, M.D.
Bradford A. Woodworth, M.D.
introduction
Cystic fibrosis (pronounced "sis-tick fy-broh-sus" and abbreviated CF) is a disease that affects multiple systems in the body including the lungs, the digestive tract, and the sinuses. CF is what is called an autosomal recessive disease. Typically, people have chromosomes which come in sets of two. If a trait is “recessive”, then the expected or “healthy” trait will be expressed if there is a normal chromosome associated with it. If there are two recessives at one time, then the result is that the disease trait will be expressed. This can be likened to multiplying two negative numbers. When multiplying two negatives, the resultant answer is a positive. Thus, two parents who are “carriers” of the recessive trait, despite NOT expressing the diseased trait themselves, can have a child who has CF. This carrier trait is quite common in Caucasian persons and can be seen in up to 1 in 25 people of European descent (Figure 1).
Pathophysiology
Cystic fibrosis affects many parts of the body. The most notable manifestation is in the lungs and in the pancreas. Patients often suffer from multiple lung infections. The underlying issue is the lack of a crucial protein (the Cystic Fibrosis Transmembrane Conductance Regulator or CFTR) that allows the transport of ions, specifically chloride, between the cells lining the surface of the respiratory system and gastrointestinal tract and the liquid that coats the cells (Figure 2). Under normal conditions, the balance of transport of these ions maintains the hydration of the liquid. One of the components of this liquid is mucus. In people who have CF, chloride ions are not well transported across the cell membranes so the mucus becomes extremely dehydrated and sticks to the surface. What does this mean? If you put soap on your hands to wash off honey versus just trying to wipe your hands off, it makes sense to translate that to the lungs. Inside of the lungs, there are very small fingerlike projections called cilia that move gently to push mucus up and out of the lungs. Pushing very thin and watery mucus is much easier than pushing very thick mucus. Because of this thick and sticky mucus, large pockets start to collect in the lungs and become infected. These pockets of mucus expand and cause scarring inside of the lungs (Figure 3).
Additionally, nearly all patients with this disease will have swelling, thickened mucus, and subsequent infection that develop inside of the sinuses. When swelling becomes severe, large bags of watery inflamed skin may form called polyps (Figure 4). This can create even more problems because now there are both mechanical barriers AND thick mucus. People with CF may develop significant sinus pain and infections. Also, the bacteria that grow inside of their sinuses can infect their lungs and worsen the lung disease that is already present.
treatment
How is the disease treated? Currently, there are therapies that work to treat medically and mechanically the thick mucus by improving hydration through washing the sinuses or lungs. In the sinuses, removing obstructing polyps and opening the sinuses through surgery can facilitate mucus clearance, allow access for mechanical irrigations, and help with symptoms. However, this does not solve the underlying basis of disease and individuals tend to have chronic, lifelong problems.
Currently there is no cure for CF. Families are always encouraged to undergo genetic testing, but parents who are carriers often do not know that they are carriers. Medical therapies like hypertonic saline, intravenous and topical/nebulized antibiotics, and pancreatic enzymes have somewhat alleviated the symptoms of this disease and have helped extend expected life spans of CF patients. Research efforts dedicated to improving the quality of life and life expectancy on individuals with this debilitating disease are ongoing and include attempts to genetically re-engineer the cells to start functioning properly. Most importantly, several exciting therapies that work to restore CFTR function are currently in the drug development pipeline for CF, so there is promise for the future.
Figures
Figure 1 – Autosomal Recessive Inheritance. If one parent is a carrier, then two out of four children will be carriers (note half blue/half black illustration). If BOTH parents are carriers, then one child will be affected, two will be carriers, and one will not have carrier status or the disease.
Bradford A. Woodworth, M.D.
introduction
Cystic fibrosis (pronounced "sis-tick fy-broh-sus" and abbreviated CF) is a disease that affects multiple systems in the body including the lungs, the digestive tract, and the sinuses. CF is what is called an autosomal recessive disease. Typically, people have chromosomes which come in sets of two. If a trait is “recessive”, then the expected or “healthy” trait will be expressed if there is a normal chromosome associated with it. If there are two recessives at one time, then the result is that the disease trait will be expressed. This can be likened to multiplying two negative numbers. When multiplying two negatives, the resultant answer is a positive. Thus, two parents who are “carriers” of the recessive trait, despite NOT expressing the diseased trait themselves, can have a child who has CF. This carrier trait is quite common in Caucasian persons and can be seen in up to 1 in 25 people of European descent (Figure 1).
Pathophysiology
Cystic fibrosis affects many parts of the body. The most notable manifestation is in the lungs and in the pancreas. Patients often suffer from multiple lung infections. The underlying issue is the lack of a crucial protein (the Cystic Fibrosis Transmembrane Conductance Regulator or CFTR) that allows the transport of ions, specifically chloride, between the cells lining the surface of the respiratory system and gastrointestinal tract and the liquid that coats the cells (Figure 2). Under normal conditions, the balance of transport of these ions maintains the hydration of the liquid. One of the components of this liquid is mucus. In people who have CF, chloride ions are not well transported across the cell membranes so the mucus becomes extremely dehydrated and sticks to the surface. What does this mean? If you put soap on your hands to wash off honey versus just trying to wipe your hands off, it makes sense to translate that to the lungs. Inside of the lungs, there are very small fingerlike projections called cilia that move gently to push mucus up and out of the lungs. Pushing very thin and watery mucus is much easier than pushing very thick mucus. Because of this thick and sticky mucus, large pockets start to collect in the lungs and become infected. These pockets of mucus expand and cause scarring inside of the lungs (Figure 3).
Additionally, nearly all patients with this disease will have swelling, thickened mucus, and subsequent infection that develop inside of the sinuses. When swelling becomes severe, large bags of watery inflamed skin may form called polyps (Figure 4). This can create even more problems because now there are both mechanical barriers AND thick mucus. People with CF may develop significant sinus pain and infections. Also, the bacteria that grow inside of their sinuses can infect their lungs and worsen the lung disease that is already present.
treatment
How is the disease treated? Currently, there are therapies that work to treat medically and mechanically the thick mucus by improving hydration through washing the sinuses or lungs. In the sinuses, removing obstructing polyps and opening the sinuses through surgery can facilitate mucus clearance, allow access for mechanical irrigations, and help with symptoms. However, this does not solve the underlying basis of disease and individuals tend to have chronic, lifelong problems.
Currently there is no cure for CF. Families are always encouraged to undergo genetic testing, but parents who are carriers often do not know that they are carriers. Medical therapies like hypertonic saline, intravenous and topical/nebulized antibiotics, and pancreatic enzymes have somewhat alleviated the symptoms of this disease and have helped extend expected life spans of CF patients. Research efforts dedicated to improving the quality of life and life expectancy on individuals with this debilitating disease are ongoing and include attempts to genetically re-engineer the cells to start functioning properly. Most importantly, several exciting therapies that work to restore CFTR function are currently in the drug development pipeline for CF, so there is promise for the future.
Figures
Figure 1 – Autosomal Recessive Inheritance. If one parent is a carrier, then two out of four children will be carriers (note half blue/half black illustration). If BOTH parents are carriers, then one child will be affected, two will be carriers, and one will not have carrier status or the disease.
Figure 2 – A diagram representing the most prevalent theory of the biologic basis of airway disease in cystic fibrosis. Although overly simplified, transport of sodium and chloride across the cell membrane works to maintain the hydration of the airway surface liquid. Loss of CFTR chloride channel function results in increased sodium absorption with passive water absorption. The net result is dehydration of mucus and poor mucociliary clearance.
Figure 3 – Artistic rendering of normal (left of image) and cystic fibrosis (right of image) lungs. Red arrows point to dilated distal airways.
Figure 4 – Nasal polyps (big arrow) obstructing the sinuses of a cystic fibrosis patient. Note the green, sticky mucus indicative of cystic fibrosis sinusitis (small arrow).
Revised 9/2011
©American Rhinologic Society