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Yes any chasis fits any upper i have the new f50s but also use the England 2002 upper for these boots
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What kind of pattern of inheritance of cystic fibrosis?
Inheritance - Autosomal recessive, requires mutations on both alleles - A single gene on chromosome 7, which encodes for the cystic fibrosis transmembrane conductance regulator - There are over 1000 different mutations for this gene - The most common is Delta F508, which makes up 67% of all mutations in the Caucasian population - Caucasians most effected
What type of mutation causes cystic fibrosis?
The most common mutation (seen in approx. 70% of cystic fibrosis patients) that causes the disease is known as Delta F508. It affects the functions of a gene found in chromosome 7 called Cystic Fibrosis Transmembrane Regulator (CFTR) by displacing it from its normal location on the chromosome. This prevents it from making a protein (which has the same name as the gene) responsible for ion channels used by Cl ions as well as Na ions. The former facilitates osmosis (diffusion of water). It also is known as an ATP-binding cassette transporter protein, which are able to span the biological membrane to transport a variety of materials, such as products of metabolism.
How does a person inherit cystic fibrosis?
For a baby to be born with Cystic Fibrosis, both parents must be carriers of the faulty CF gene. Where both parents carry the faulty gene, each child has a one in four chance of having CF, a two in four chance of being a carrier and a one in four chance of not having any CF genes.
What is cystic fibrosis cure?
In truth, there is no cure for cystic fibrosis; the disease is most commonly caused by a genetic mutation. The mutation is caused by an incorrect protein made by the "Cystic Fibrosis Transmembrane Conductance Regulator" which is responsible for managing most of the body's sodium-chloride channel. The problem is the protein is not made correctly into a 3-dimensional biological structure (or it's not coded in the right way) and so the body's detection system throws it out. Without this gene, the body is unable to process water and salt correctly. This in turn causes multiple systematic infections and even failures. Due to inability to process water, a CF patient's body cannot make thin and easily removable mucus. This mucus is used by the body to lubricate organs and pick up pathogens (germs and stuff that are capable of attacking the body.) Normally a person's body is able to dispose or throw out the mucus quite easily (i.e. when you get sick, your body amps up fluid and mucus production in order to rid the body of infection, hence the reason for a runny nose or wet cough) but in Cystic Fibrosis the mucus is not hydrated with enough water and salt, so it becomes uncontrollably thick. At first, a person with the most common mutation of CF (Delta-f508) will display malnourishment due to their inability to process enzymes. For those who need simpler explanations, the mucus in the organ "the pancreas" is so thick that most of the body's tools to break down and eat food are trapped. This means the body cannot absorb or use food. This leads to weight loss and death if untreated. Further on in childhood, a CFer (as we call ourselves) starts to cough and succumb to infections in the lungs and elsewhere. The lungs are filled with mucus in order to catch germs in the air we breathe in order to prevent people from getting sick (sometimes you still get sick though) and for other reasons as well. The mucus in CF patients, however, is too thick for the body to get rid of and so the bacteria sit there and grow until they become too much for the body's immune (defense) system to fight. This causes scarring and destruction of the lung tissue, which in turn decreases the body's ability to absorb oxygen and eventually, its ability to breathe. This will likely be the reason for the patient's death when they can no longer tolerate the loss of lung function. Other ailments for CF patients-due to the genetic mutation-are: liver failure from mucus buildup which stops the liver from being able to detoxify food and other things; liver bile can also become too thick and acidic; inadvertently it can cause kidney failure from the antibiotics which are used to treat infections; infertility among males is also at 99%-women on the other hand can have a tough time getting pregnant and at having birth due to thick mucus preventing sperm from entering the female reproduction system and due to the fact the patient will have a tough time supporting not only themselves but also the child within them (another problem to consider is the affects of the medication the mother needs to take to treat her CF on the baby.) Diabetes (CFRD-Cystic Fibrosis Related Diabetes) can also be caused by CF due to possible steroid treatment and the fact that the pancreas can get blocked up with mucus even more and be unable to release insulin to decrease sugar levels. Another problem which is inadvertently caused by CF is increased cholesterol levels in part because doctors told CF patients to go out and eat whatever food they want as much as they can-which included fast food-expecting that CF patients wouldn't live long enough to suffer from high cholesterol but as new treatments have come out which prolong the life of CFers, people are now suffering from this. Constipation is also prevalent due to the body's lack of support for the sodium chloride channel. The sinuses are also stuffed with mucus and can form polyps with numerous nasal infections. When lung function is bad enough, a lung transplant occurs (if the patient is able to receive a donor that is) and then the problem of the body rejecting the organ can come up. Medicines are needed to stop the body from attacking the new lungs, but then this weakens the immune system and increases the likelihood of getting a new infection that can weaken or kill the patient. Towards the end, CF patients will have to deal with a lot of bad pain. This can be treated with pain medicine (that is if the doctor actually cares whether or not the patient is in pain and will help treat them) but sometimes it won't help much. Throughout their life, a CF patient will feel much pain, from pulled muscles and scratched throats from the coughing, to stomach pain and side effects from powerful antibiotics. Fortunately, the CF Foundation (CFF) has worked vigorously to increase the lifespan and livelihood of us CFers and now the average life expectancy went from 5 years of age to around 30 years of age in the last 60 years. All in all, the reason there is no cure for CF is because medical science is currently unable to correct or infuse a working CFTR protein. Only when this is accomplished can most of the mutations from Cystic Fibrosis be truly "cured." For those of us who were born with CF and have been alive more than a decade, a cure will not cure us, but will stop the progression and destruction of the disease. The problem is that since so much damage has already been done to people who have lived a while with CF, a working protein will not fix the damage just stop it. My Sources: I have CF and have dealt with most of this. For more information, go to www.cff.org.
Can you develop cystic fibrosis or do you have to be born with it at birth?
Cystic Fibrosis (also known as CF, mucovoidosis, or mucoviscidosis) is a hereditary disease affecting the exocrine (mucous) glands of the lungs, liver, pancreas, and intestines, causing progressive disability due to multisystem failure.The main hallmarks of cystic fibrosis are salty tasting skin, appetite but poor growth and poor weight gain, excess mucus production and coughing/shortness of breath. Males can be infertile due to the condition congenital bilateral absence of the vas deferens. Often, symptoms of CF appear in infancy and childhood. Meconium ileus is a typical finding in newborn babies with CF.Cystic fibrosis is one of the most common life-shortening genetic diseases. In the United States, 1 in 4,000 children are born with CF.[1] It is most common among western European populations; one in twenty-two people of Mediterranean descent is a carrier of one gene for CF, making it the most common genetic disease in these populations. In 1997, about 1 in 3,300 caucasian children in the United States was born with cystic fibrosis. In contrast, only 1 in 15,000 African American children suffered from cystic fibrosis, and in Asian Americans the rate was even lower at 1 in 32,000CauseCF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR). The product of this gene is a chloride ion channel important in creating sweat, digestive juices and mucus. Although most people without CF have two working copies (alleles) of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither allele can produce a functional CFTR protein. Therefore, CF is considered an autosomal recessive disease.CureThere is no known cure for cystic fibrosis, and most individuals with cystic fibrosis die young: many in their 20s and 30s from lung failure. The predicted median age of survival for a person with CF is 37 years. However, with the continuous introduction of many new treatments, the life expectancy of a person with CF is increasing to ages as high as 40 or 50. Lung transplantation is often necessary as CF worsens.There are many foundations and trusts dedicated to researching cures and treatments for cystic fibrosis, and assisting people suffering from the disease. A list of cystic fibrosis organizations is available and more information can be found on the disease and living with cystic fibrosis from these organizationsDiagnosis and monitoringCystic fibrosis may be diagnosed by many different categories of testing including those such as, newborn screening, sweat testing, or genetic testing. As of 2006 in the United States, 10 percent of cases are diagnosed shortly after birth as part of newborn screening programs. The newborn screen initially measures for raised blood concentration of immunoreactive trypsinogen.[3] Infants with an abnormal newborn screen need a sweat test in order to confirm the CF diagnosis. Trypsinogen levels can be increased in individuals who have a single mutated copy of the CFTR gene (carriers) or, in rare instances, even in individuals with two normal copies of the CFTR gene. Due to these false positives, CF screening in newborns is somewhat controversial.[citation needed] Most states and countries do not screen for CF routinely at birth. Therefore, most individuals are diagnosed after symptoms prompt an evaluation for cystic fibrosis. The most commonly used form of testing is the sweat test. Sweat-testing involves application of a medication that stimulates sweating (pilocarpine) to one electrode of an apparatus and running electric current to a separate electrode on the skin. This process, called iontophoresis, causes sweating; the sweat is then collected on filter paper or in a capillary tube and analyzed for abnormal amounts of sodium and chloride. People with CF have increased amounts of sodium and chloride in their sweat. CF can also be diagnosed by identification of mutations in the CFTR gene.[4]A multitude of tests are used to identify complications of CF and to monitor disease progression. X-rays and CAT scans are used to examine the lungs for signs of damage or infection. Examination of the sputum under a microscope is used to identify which bacteria are causing infection so that effective antibiotics can be given. Pulmonary function tests measure how well the lungs are functioning, and are used to measure the need for and response to antibiotic therapy. Blood tests can identify liver abnormalities, vitamin deficiencies, and the onset of diabetes. DEXA scans can screen for osteoporosis and testing for fecal elastase can help diagnose insufficient digestive enzymes.[edit] Prenatal diagnosisCouples who are pregnant or who are planning a pregnancy can themselves be tested for CFTR gene mutations to determine the likelihood that their child will be born with cystic fibrosis. Testing is typically performed first on one or both parents and, if the risk of CF is found to be high, testing on the fetus can then be performed. Cystic fibrosis testing is offered to many couples in the US.[5] The American College of Obstetricians and Gynecologists (ACOG) recommends testing for couples who have a personal or close family history. Additionally, ACOG recommends that carrier testing be offered to all Caucasian couples and be made available to couples of other ethnic backgrounds.[6]Because development of CF in the fetus requires each parent to pass on a mutated copy of the CFTR gene and because CF testing is expensive, testing is often performed on just one parent initially. If that parent is found to be a carrier of a CFTR gene mutation, the other parent is then tested to calculate the risk that their children will have CF. CF can result from more than a thousand different mutations and, as of 2006, it is not possible to test for each one. Testing analyzes the blood for the most common mutations such as ΔF508 - most commercially available tests look for 32 or fewer different mutations. If a family has a known uncommon mutation, specific screening for that mutation can be performed. Because not all known mutations are found on current tests, a negative screen does not guarantee that a child will not have CF.[7] In addition, because the mutations tested are necessarily those most common in the highest risk groups, testing in lower risk ethnicities is less successful because the mutations commonly seen in these groups are less common in the general population. These couples may therefore consider testing through labs that offer CF screens with a high number of mutations tested.Couples who are at high risk for having a child with CF will often opt to perform further testing before or during pregnancy. In vitro fertilization with preimplantation genetic diagnosis offers the possibility to examine the embryo prior to its placement into the uterus. The test, performed 3 days after fertilization, looks for the presence of abnormal CF genes. If two mutated CFTR genes are identified, the embryo is not used for embryo transfer and an embryo with at least one normal gene is implanted.During pregnancy, testing can be performed on the placenta (chorionic villus sampling) or the fluid around the fetus (amniocentesis). However, chorionic villus sampling has a risk of fetal death of 1 in 100 and amniocentesis of 1 in 200,[8] although a recent study has indicated this may actually be much lower, perhaps 1 in 1,600,[1] so the benefits must be determined to outweigh these risks prior to going forward with testing. Alternatively, some couples choose to undergo third party reproduction with egg or sperm donors.[edit] PathophysiologyCystic fibrosis occurs when there is a mutation in the CFTR gene. The protein created by this gene is anchored to the outer membrane of cells in the sweat glands, lungs, pancreas, and other affected organs. The protein spans this membrane and acts as a channel connecting the inner part of the cell (cytoplasm) to the surrounding fluid. This channel is primarily responsible for controlling the movement of chloride from inside to outside of the cell; however, in the sweat ducts it facilitates the movement of chloride from the sweat into the cytoplasm. When the CFTR protein does not work, chloride is trapped inside the cells in the airway and outside in the skin. Because chloride is negatively charged, positively charged ions cross into the cell because they are affected by the electrical attraction of the chloride ions. Sodium is the most common ion in the extracellular space and the combination of sodium and chloride creates the salt, which is lost in high amounts in the sweat of individuals with CF. This lost salt forms the basis for the sweat test.[9]How this malfunction of cells in cystic fibrosis causes the clinical manifestations of CF is not well understood. One theory suggests that the lack of chloride exodus through the CFTR protein leads to the accumulation of more viscous, nutrient-rich mucus in the lungs that allows bacteria to hide from the body's immune system. Another theory proposes that the CFTR protein failure leads to a paradoxical increase in sodium and chloride uptake, which, by leading to increased water reabsorption, creates dehydrated and thick mucus. Yet another theory focuses on abnormal chloride movement out of the cell, which also leads to dehydration of mucus, pancreatic secretions, biliary secretions, etc. These theories all support the observation that the majority of the damage in CF is due to blockage of the narrow passages of affected organs with thickened secretions. These blockages lead to remodeling and infection in the lung, damage by accumulated digestive enzymes in the pancreas, blockage of the intestines by thick faeces, etc.[9][edit] The role of chronic infection in lung diseaseThe lungs of individuals with cystic fibrosis are colonized and infected by bacteria from an early age. These bacteria, which often spread amongst individuals with CF, thrive in the altered mucus, which collects in the small airways of the lungs. This mucus encourages the development of bacterial microenvironments (biofilms) that are difficult for immune cells (and antibiotics) to penetrate. The lungs respond to repeated damage by thick secretions and chronic infections by gradually remodeling the lower airways (bronchiectasis), making infection even more difficult to eradicate.[10]Over time, both the types of bacteria and their individual characteristics change in individuals with CF. In the initial stage, common bacteria such as Staphylococcus aureus and Hemophilus influenzae colonize and infect the lungs. Eventually, however, Pseudomonas aeruginosa (and sometimes Burkholderia cepacia) dominates. Once within the lungs, these bacteria adapt to the environment and develop resistance to commonly used antibiotics. Pseudomonas can develop special characteristics that allow the formation of large colonies, known as "mucoid" Pseudomonas, which are rarely seen in people that do not have CF.[10]One way in which infection has spread is by passage between different individuals with CF.[11] In the past, people with CF often participated in summer "CF Camps" and other recreational gatherings.[12][13] Hospitals grouped patients with CF into common areas and routine equipment (such as nebulizers)[14] was not sterilized between individual patients.[15] This led to transmission of more dangerous strains of bacteria among groups of patients. As a result, individuals with CF are routinely isolated from one another in the healthcare setting and healthcare providers are encouraged to wear gowns and gloves when examining patients with CF in order to limit the spread of virulent bacterial strains.[16] Often, patients with particularly damaging bacteria will attend clinics on different days and in different buildings than those without these infections.[edit] Molecular biologyCFTR protein - Molecular structure of the CFTR proteinThe CFTR gene is found at the q31.2 locus of chromosome 7, is 230,000 base pairs long, and creates a protein that is 1,480 amino acids long. The most common mutation, ΔF508, is a deletion (Δ) of three nucleotides that results in a loss of the amino acid phenylalanine (F) at the 508th (508) position on the protein. This mutation accounts for two-thirds of CF cases worldwide and 90 percent of cases in the United States; however, there are over 1,400 other mutations that can produce CF.[17] In Caucasian populations, the frequency of mutations is as follows:[18]Mutation FrequencyworldwideΔF508 66.0% G542X 2.4% G551D 1.6% N1303K 1.3% W1282X 1.2% All others 27.5%There are several mechanisms by which these mutations cause problems with the CFTR protein. ΔF508, for instance, creates a protein that does not fold normally and is degraded by the cell. Several mutations, which are common in the Ashkenazi Jewish population, result in proteins that are too short because production is ended prematurely. Less common mutations produce proteins that do not use energy normally, do not allow chloride to cross the membrane appropriately, or are degraded at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced.[9]The location of the CFTR gene on chromosome 7Structurally, CFTR is a type of gene known as an ABC gene.[9] Its protein possesses two ATP-hydrolyzing domains which allows the protein to use energy in the form of ATP. It also contains two domains comprising 6 alpha helices apiece, which allow the protein to cross the cell membrane. A regulatory binding site on the protein allows activation by phosphorylation, mainly by cAMP-dependent protein kinase.[9] The carboxyl terminal of the protein is anchored to the cytoskeleton by a PDZ domain interaction.[19][edit] Symptomatic diseases[edit] Lung and sinus diseaseLung disease results from clogging the airways due to mucosa buildup and resulting inflammation. Inflammation and infection cause injury to the lungs and structural changes that lead to a variety of symptoms. In the early stages, incessant coughing, copious phlegm production, and decreased ability to exercise are common. Many of these symptoms occur when bacteria that normally inhabit the thick mucus grow out of control and cause pneumonia. In later stages of CF, changes in the architecture of the lung further exacerbate chronic difficulties in breathing.Aspergillus fumigatus - A common fungus which can lead to worsening lung disease in people with CFOther symptoms include coughing up blood (hemoptysis), changes in the major airways in the lungs (bronchiectasis), high blood pressure in the lung (pulmonary hypertension), heart failure, difficulties getting enough oxygen to the body (hypoxia), and respiratory failure requiring support with breathing masks such as bilevel positive airway pressure machines or ventilators.[9] In addition to typical bacterial infections, people with CF more commonly develop other types of lung disease. Among these is allergic bronchopulmonary aspergillosis, in which the body's response to the common fungus Aspergillus fumigatus causes worsening of breathing problems. Another is infection with Mycobacterium avium complex (MAC), a group of bacteria related to tuberculosis, which can cause further lung damage and does not respond to common antibiotics.Mucus in the paranasal sinuses is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and headaches. Individuals with CF may develop overgrowth of the nasal tissue (nasal polyps) due to inflammation from chronic sinus infections. These polyps can block the nasal passages and increase breathing difficulties.[20][21][edit] Gastrointestinal, liver and pancreatic diseasePrior to prenatal and newborn screening, cystic fibrosis was often diagnosed when a newborn infant failed to pass feces (meconium). Meconium may completely block the intestines and cause serious illness. This condition, called meconium ileus, occurs in 10% of newborns with CF.[22] In addition, protrusion of internal rectal membranes (rectal prolapse) is more common in CF because of increased fecal volume, malnutrition, and increased intra-abdominal pressure due to coughing.[23]The thick mucus seen in the lungs has a counterpart in thickened secretions from the pancreas, an organ responsible for providing digestive juices which help break down food. These secretions block the movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis).[24] The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the faeces, a disorder known as malabsorption. Malabsorption leads to malnutrition and poor growth and development because of calorie loss. Individuals with CF also have difficulties absorbing the fat-soluble vitamins A, D, E, and K. In addition to the pancreas problems, people with cystic fibrosis experience more heartburn, intestinal blockage by intussusception, and constipation.[25] Older individuals with CF may also develop distal intestinal obstruction syndrome when thickened feces cause intestinal blockage.[26]Thickened secretions also may cause liver problems in patients with CF. Bile secreted by the liver to aid in digestion may block the bile ducts, leading to liver damage. Over time, this can lead to cirrhosis, in which the liver fails to rid the blood of toxins and does not make important proteins such as those responsible for blood clotting.[27][28][edit] Endocrine disease and growthExample of clubbing as seen with some CF patientsThe pancreas contains the islets of Langerhans, which are responsible for making insulin, a hormone that helps regulate blood glucose. Damage of the pancreas can lead to loss of the islet cells, leading to diabetes that is unique to those with the disease.[29] Cystic Fibrosis Related Diabetes (CFRD), as it is known as, shares characteristics that can be found in Type 1 and Type 2 diabetics and is one of the principal non-pulmonary complications of CF.[30] Vitamin D is involved in calcium and phosphorus regulation. Poor uptake of vitamin D from the diet because of malabsorption leads to the bone disease osteoporosis in which weakened bones are more susceptible to fractures.[31] In addition, people with CF often develop clubbing of their fingers and toes due to the effects of chronic illness and low oxygen in their tissues.Poor growth is a hallmark of CF. Children with CF typically do not gain weight or height at the same rate as their peers, and occasionally are not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multi-factorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness.[edit] InfertilityInfertility affects both men and women. At least 97 percent of men with cystic fibrosis are infertile but are not sterile and can have children with assisted reproductive techniques.[32] These men make normal sperm but are missing the tube (vas deferens), which connects the testes to the ejaculatory ducts of the penis.[33] Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF.[34] Some women have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts ovulation and causes amenorrhea.[35][edit] TreatmentA typical breathing treatment for cystic fibrosis, using a mask nebuliser and the ThAIRapy VestThe cornerstones of management are proactive treatment of airway infection, and encouragement of good nutrition and an active lifestyle. The treatment for cystic fibrosis continues throughout a patient's life, and is aimed at maximizing organ function, and therefore quality of life. At best, current treatments delay the decline in organ function. Treatment typically occurs at specialist multidisciplinary centres, and is tailored to the individual, because of the wide variation in disease symptoms. Targets for therapy are the lungs, gastrointestinal tract (including insulin treatment and pancreatic enzyme supplements), the reproductive organs (including Assisted Reproductive Technology (ART)) and psychological support.[3] In addition, therapies such as transplantation and gene therapy aim to cure some of the effects of cystic fibrosis.The most consistent aspect of therapy in cystic fibrosis is limiting and treating the lung damage caused by thick mucus and infection with the goal of maintaining quality of life. Intravenous, inhaled, and oral antibiotics are used to treat chronic and acute infections. Mechanical devices and inhalation medications are used to alter and clear the thickened mucus. These therapies, while effective, can be extremely time consuming to the patient. One of the most important battles that CF patients face is finding the time to comply with all the prescribed treatments while balancing a normal life.[edit] PrognosisIn most cases, CF causes an early death. Average life expectancy is around 36.8 years according to the Cystic Fibrosis Foundation, although improvements in treatments mean a baby born today could expect to live longer.[36][edit] Antibiotics to treat lung diseaseMany CF patients are on one or more antibiotics at all times, even when they are considered healthy, to suppress the infection as much as possible. Antibiotics are absolutely necessary whenever pneumonia is suspected or there has been a noticeable decline in lung function. Antibiotics are usually chosen based on the results of a sputum analysis and the patient's past response. Many bacteria common in cystic fibrosis are resistant to multiple antibiotics and require weeks of treatment with intravenous antibiotics such as vancomycin, tobramycin, meropenem, ciprofloxacin, and piperacillin. This prolonged therapy often necessitates hospitalization and insertion of a more permanent IV such as a PICC line or Port-a-Cath. Inhaled therapy with antibiotics such as tobramycin and colistin is often given for months at a time in order to improve lung function by impeding the growth of colonized bacteria.[37][38] Inhaled therapy with the antibiotic aztreonam is also being developed and clinical trials have shown great promise.[39] Oral antibiotics such as ciprofloxacin or azithromycin are given to help prevent infection or to control ongoing infection.[40] Some individuals spend years between hospitalizations for antibiotics, whereas others require several antibiotic treatments each year.Several common antibiotics such as tobramycin and vancomycin can cause hearing loss, damage to the balance system in the inner ear or kidney problems with long-term use. In order to prevent these side-effects, the amount of antibiotics in the blood are routinely measured and adjusted accordingly.[edit] Other methods to treat lung diseaseSeveral mechanical techniques are used to dislodge sputum and encourage its expectoration. In the hospital setting, chest physiotherapy (CPT) is utilized; a respiratory therapist percusses an individual's chest with his or her hands several times a day, to loosen up secretions. Devices that recreate this percussive therapy include the ThAIRapy Vest (pioneered under Dr. Warren J Warwick at the University of Minnesota) and the intrapulmonary percussive ventilator (IPV). Newer methods such as Biphasic Cuirass Ventilation, and associated clearance mode available in such devices, now integrate a cough assistance phase, as well as a vibration phase for dislodging secretions. Biphasic Cuirass Ventilation is also shown to provide a bridge to transplantation.[citation needed] These are portable and adapted for home use.[41] Physiotherapy is essential to help manage an individuals chest on a long term basis, and can also teach techniques for the older child and teenager to manage themselves at home. Aerobic exercise is of great benefit to people with cystic fibrosis. Not only does exercise increase sputum clearance but it also improves cardiovascular and overall health.Aerosolized medications that help loosen secretions include dornase alfa and hypertonic saline.[42] Dornase is a recombinant human deoxyribonuclease, which breaks down DNA in the sputum, thus decreasing its viscosity.[43] N-Acetylcysteine may also decrease sputum viscosity, but research and experience have shown its benefits to be minimal. Albuterol and ipratropium bromide are inhaled to increase the size of the small airways by relaxing the surrounding muscles.As lung disease worsens, breathing support from machines may become necessary. Individuals with CF may need to wear special masks at night that help push air into their lungs. These machines, known as bilevel positive airway pressure (BiPAP) ventilators, help prevent low blood oxygen levels during sleep. BiPAP may also be used during physical therapy to improve sputum clearance.[44] During severe illness, people with CF may need to have a tube placed in their throats (a procedure known as a tracheostomy) and their breathing supported by a ventilator.[edit] Treatment of other aspects of CFIntracytoplasmic sperm injection is used to provide fertility for men with cystic fibrosis.Newborns with meconium ileus typically require surgery, whereas adults with distal intestinal obstruction syndrome typically do not. Treatment of pancreatic insufficiency by replacement of missing digestive enzymes allows the duodenum to properly absorb nutrients and vitamins that would otherwise be lost in the faeces. Even so, most individuals with CF take additional amounts of vitamins A, D, E, and K and eat high-calorie meals. It should be noted, however, that nutritional advice given to patients is, at best, mixed: Often, literature encourages the eating of high-fat foods without differentiating between saturated, unsaturated fat, and trans-fats; this lack of clear information runs counter to health advice given to the general population, and creates the risk of further serious health problems for people with cystic fibrosis as they grow older. So far, no large-scale research involving the incidence of atherosclerosis and coronary heart disease in adults with cystic fibrosis has been conducted. This is likely due to the fact that the vast majority of people with cystic fibrosis do not live long enough to develop clinically significant atherosclerosis or coronary heart disease.The diabetes common to many CF patients is typically treated with insulin injections or an insulin pump.[45] Development of osteoporosis can be prevented by increased intake of vitamin D and calcium, and can be treated by bisphosphonates.[46] Poor growth may be avoided by insertion of a feeding tube for increasing calories through supplemental feeds or by administration of injected growth hormone.[47]Sinus infections are treated by prolonged courses of antibiotics. The development of nasal polyps or other chronic changes within the nasal passages may severely limit airflow through the nose. Sinus surgery is often used to alleviate nasal obstruction and to limit further infections. Nasal steroids such as fluticasone are used to decrease nasal inflammation.[48] Female infertility may be overcome by assisted reproduction technology, particularly embryo transfer techniques. Male infertility may be overcome with intracytoplasmic sperm injection.[49] Third party reproduction is also a possibility for women with CF.[edit] Transplantation and gene therapyLung transplantation often becomes necessary for individuals with cystic fibrosis as lung function and exercise tolerance declines. Although single lung transplantation is possible in other diseases, individuals with CF must have both lungs replaced because the remaining lung would contain bacteria that could infect the transplanted lung. A pancreatic or liver transplant may be performed at the same time in order to alleviate liver disease and/or diabetes.[50] Lung transplantation is considered when lung function approaches a point where it threatens survival or requires assistance from mechanical devices.[51] This point is typically when lung function declines to approximately 20 to 30 percent, however there is a small time frame when transplantation is feasible as the patient must be healthy enough to endure the procedure.Gene therapy holds promise as a potential avenue to cure cystic fibrosis. Gene therapy attempts to place a normal copy of the CFTR gene into affected cells. Studies have shown that to prevent the lung manifestations of cystic fibrosis, only 5-10% the normal amount of CFTR gene expression is needed.[52] Multiple approaches have been tested for gene transfer, such as liposomes and viral vectors in animal models and clinical trials. However, at this time gene therapy is still a relatively inefficient treatment option.[53] Ideally, transferring the normal CFTR gene into the affected epithelium cells would result in the production of functional CFTR in all target cells, without adverse reactions or an inflammation response. But if too few cells take up the vector and express the gene, the treatment has little effect. Additionally, problems have been noted in cDNA recombination, such that the gene introduced by the treatment is rendered unusable. [54][edit] EpidemiologyCystic fibrosis is the most common life-limiting autosomal recessive disease among people of European heritage.[55] In the United States, approximately 30,000 individuals have CF; most are diagnosed by six months of age. Canada has approximately 3,000 citizens with CF. Approximately 1 in 25 people of European descent is a carrier of a cystic fibrosis mutation. Although CF is less common in these groups, approximately 1 in 46 Hispanics, 1 in 65 Africans and 1 in 90 Asians carry at least one abnormal CFTR gene.[56][57]Cystic fibrosis is diagnosed in males and females equally. For unclear reasons, males tend to have a longer life expectancy than females.[58] Life expectancy for people with CF depends largely upon access to health care. In 1959, the median age of survival of children with cystic fibrosis was six months. In the United States, the life expectancy for infants born in 2006 with CF is 36.8 years, based upon data compiled by the Cystic Fibrosis Foundation.[36]The Cystic Fibrosis Foundation also compiles lifestyle information about American adults with CF. In 2004, the foundation reported that 91% had graduated high school and 54% had at least some college education. Employment data revealed 12.6% of adults were disabled and 9.9% were unemployed. Marital information showed that 59% of adults were single and 36% were married or living with a partner. In 2004, 191 American women with CF were pregnant.[edit] Theories about the prevalence of CFThe ΔF508 mutation is estimated to be up to 52,000 years old.[59] Numerous hypotheses have been advanced as to why such a lethal mutation has persisted and spread in the human population. Other common autosomal recessive diseases such as sickle-cell anemia have been found to protect carriers from other diseases, a concept known as heterozygote advantage. Resistance to the following have all been proposed as possible sources of heterozygote advantage:Cholera: With the discovery that cholera toxin requires normal host CFTR proteins to function properly, it was hypothesized that carriers of mutant CFTR genes benefited from resistance to cholera and other causes of diarrhea.[60] Further studies have not confirmed this hypothesis.[61][62]Typhoid: Normal CFTR proteins are also essential for the entry of Salmonella typhi into cells,[63] suggesting that carriers of mutant CFTR genes might be resistant to typhoid fever. No in vivo study has yet confirmed this. In both cases, the low level of cystic fibrosis outside of Europe, in places where both cholera and typhoid fever are endemic, is not immediately explicable.Diarrhea: It has also been hypothesized that the prevalence of CF in Europe might be connected with the development of cattle domestication. In this hypothesis, carriers of a single mutant CFTR chromosome had some protection from diarrhoea caused by lactose intolerance, prior to the appearance of the mutations that created lactose tolerance.[64]Tuberculosis: Poolman and Galvani from Yale University have added another possible explanation - that carriers of the gene have some resistance to TB.[65][66][edit] HistoryNational Library of Medicine photo of Dorothy Hansine Andersen. Andersen first described cystic fibrosis of the pancreas.[edit] EtymologyThe name cystic fibrosis comes from the characteristic histologic (microscopic) appearance of the pancreas in the disease, with cysts (fluid filled cavities) and fibrosis prominently seen.[67] Formerly known as "cystic fibrosis of the pancreas," this entity has increasingly been labeled simply "cystic fibrosis."[68]Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects were identified much earlier. Indeed, literature from Germany and Switzerland in the 18th century warned, "Wehe dem Kind, das beim Kuß auf die Stirn salzig schmekt, es ist verhext und muss bald sterben" - "Woe is the child who tastes salty when kissed on the forehead, for it is cursed and soon must die," recognizing the association between the salt loss in CF and illness.In the 19th century, Carl von Rokitansky described a case of fetal death with meconium peritonitis, a complication of meconium ileus associated with cystic fibrosis. Meconium ileus was first described in 1905 by Karl Landsteiner.[69] In 1936, Guido Fanconi published a paper describing a connection between celiac disease, cystic fibrosis of the pancreas, and bronchiectasis.[70]In 1938 Dorothy Hansine Andersen published an article, "Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: a Clinical and Pathological Study," in the American Journal of Diseases of Children. She described the characteristic cystic fibrosis of the pancreas and correlated it with the lung and intestinal disease prominent in CF.[67] She also first hypothesized that CF is a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952 Paul di Sant' Agnese discovered abnormalities in sweat electrolytes; a sweat test was developed and improved over the next decade.[71]In 1988 the first mutation for CF, ΔF508 on the seventh chromosome, was discovered by Francis Collins, Lap-Chee Tsui and John R. Riordan. Research has subsequently found over 1,000 different mutations that cause CF. Lap-Chee Tsui led a team of researchers at the Hospital for Sick Children in Toronto that discovered the gene responsible for CF in 1989. Cystic fibrosis represents the first genetic disorder elucidated strictly by the process of reverse genetics.Because mutations in the CFTR gene are typically small, classical genetics techniques had been unable to accurately pinpoint the mutated gene.[72] Using protein markers, gene-linkage studies were able to map the mutation to chromosome 7. Chromosome-walking and -jumping techniques were then used to identify and sequence the gene.[73]
