Cystic fibrosis Classification and external resources
ICD-10	E84.
ICD-9	277
OMIM	219700
DiseasesDB	3347
MedlinePlus	000107
eMedicine	ped/535
MeSH	D003550

Cystic fibrosis (also known as CF, mucoviscoidosis, or mucoviscidosis) is a hereditary disease that affects the exocrine (mucus) glands of the lungs, liver, pancreas, and intestines, causing progressive disability due to multisystem failure. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings E00-E35 - Endocrine diseases (E00-E07 Thyroid gland / Thyroid hormone ( Congenital iodine-deficiency syndrome ( The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books A genetic disorder is a condition caused by abnormalities in Genes or Chromosomes While some diseases such as Cancer, are due to genetic abnormalities acquired

Thick mucus production, as well as a less competent immune system, results in frequent lung infections. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Pneumonia is an inflammatory illness of the Lung. Frequently it is described as lung Parenchyma / alveolar inflammation and abnormal Diminished secretion of pancreatic enzymes is the main cause of poor growth, fatty diarrhea and deficiency in fat-soluble vitamins. Failure to thrive (FTT is a medical term which denotes poor weight gain and physical growth failure over an extended period of time in Infancy. Steatorrhea is the presence of excess fat in Feces. Stools may also float due to excess gas have an oily appearance and be foul smelling Males can be infertile due to the condition congenital bilateral absence of the vas deferens. Female infertility|Male infertility Infertility primarily refers to the biological inability of a Man or a Woman to contribute to conception. Congenital absence of the vas deferens ( CAVD) is a condition in which the two Vas deferens, male reproductive organs fail to form properly Often, symptoms of CF appear in infancy and childhood. Meconium ileus is a typical finding in newborn babies with CF. Meconium is the earliest

Individuals with cystic fibrosis can be diagnosed prior to birth by genetic testing. Genetic testing allows the genetic Diagnosis of vulnerabilities to inherited Diseases, and can also be used to determine a person's Ancestry. Newborn screening tests are increasingly common and effective. The Guthrie test, also known as the Guthrie bacterial inhibition assay, is a medical test performed on newborn infants to detect Phenylketonuria, an The diagnosis of CF may be confirmed if high levels of salt are found during a sweat test, although some false positives may occur. The sweat test measures the Concentration of Chloride and Sodium that is excreted in sweat

There is no cure for CF, and most individuals with cystic fibrosis die young: many in their 20s and 30s from lung failure. 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. Lung transplantation is a surgical procedure in which a patient's diseased Lungs are partially or totally replaced by lungs which come from a donor

Cystic fibrosis is one of the most common life-shortening, childhood-onset inherited diseases. In the United States, 1 in 3,900 children is born with CF^[1]. It is most common among Europeans and Ashkenazi Jews; one in twenty-two people of European descent are carriers of one gene for CF, making it the most common genetic disease in these populations. The European peoples are the various Nations and Ethnic groups of Europe. Ashkenazi Jews, also known as Ashkenazic Jews or Ashkenazim ( Hebrew: אַשְׁכֲּנָזִים, ˌaʃkəˈnazim sing A genetic carrier (or just carrier) is a person or other organism that has inherited a genetic trait or Mutation, but who does not display that Ireland has the highest rate of CF carriers in the world (1 in 19).

CF is caused by a mutation in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR). In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance CFTR ( cystic fibrosis transmembrane conductance regulator ATP-binding cassette (sub-family C member 7) is a Human Gene that provides instructions for The product of this gene is a chloride ion channel important in creating sweat, digestive juices, and mucus. Cystic fibrosis transmembrane conductance regulator ( CFTR) is an ABC transporter -class Protein and Ion channel that transports Chloride Digestion is the breaking down of chemicals in the body into a form that can be absorbed In vertebrates mucus is a slippery secretion produced by and covering Mucous membranes It is a viscous Colloid containing Antiseptic enzymes (such as 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. An autosome is a non-sex Chromosome. It is an ordinarily paired type of chromosome that is the same in both Sexes of a species.

Contents 1 Symptomatic diseases 1.1 Lung and sinus disease 1.2 Gastrointestinal, liver and pancreatic disease 1.3 Endocrine disease and growth 1.4 Infertility 2 Diagnosis and monitoring 2.1 Prenatal diagnosis 2.2 Pathophysiology 2.3 The role of chronic infection in lung disease 2.4 Molecular biology 3 Treatment 3.1 Antibiotics to treat lung disease 3.2 Other methods to treat lung disease 3.3 Treatment of other aspects of CF 3.4 Transplantation and gene therapy 4 Prognosis 5 Epidemiology 5.1 Theories about the prevalence of CF 6 History 7 Public Awareness 8 See also 9 References 10 External links

Symptomatic diseases

Lung and sinus disease

Lung disease results from clogging the airways due to mucus buildup and resulting inflammation. Inflammation and infection cause injury to the lungs and structural changes that lead to a variety of symptoms. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens In the early stages, incessant coughing, copious phlegm production, and decreased ability to exercise are common. Phlegm ( is sticky Fluid secreted by the Mucous membranes of Humans and other Animals. Many of these symptoms occur when bacteria that normally inhabit the thick mucus grow out of control and cause pneumonia. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have In later stages of CF, changes in the architecture of the lung further exacerbate chronic difficulties in breathing.

Other 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. Hemoptysis or haemoptysis (see American and British spelling differences) is the expectoration ( Coughing up of Blood or of blood-stained Bronchiectasis is a disease that causes localized irreversible dilatation of part of the Bronchial tree. Blood pressure is also the title of a short story by Damon Runyan in Guys and Dolls and Other Stories In Medicine, pulmonary hypertension (PH is an increase in blood pressure in the Pulmonary artery, Pulmonary vein, or pulmonary capillaries together known Heart failure is a Cardiac condition that occurs when a problem with the structure or function of the Heart impairs its ability to supply Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the In Medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing when patients cannot do so on their own ^[2] 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. In Medicine, allergic bronchopulmonary aspergillosis ( ABPA) is a condition characterised by an exaggerated response of the Immune system (a hypersensitivity A fungus (ˈfʌŋgəs is a eukaryotic Organism that is a member of the kingdom Fungi (ˈfʌndʒaɪ Aspergillus fumigatus is a Fungus of the Genus Aspergillus, and is one of the most common Aspergillus species to cause disease in 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. Mycobacterium avium complex (MAC is a group of Genetically -related Bacteria belonging to the genus Mycobacterium. Tuberculosis (abbreviated as TB for tubercle bacillus or T u' b' erculosis Bacillus --> is a common

Mucus in the paranasal sinuses is equally thick and may also cause blockage of the sinus passages, leading to infection. Paranasal sinuses are air-filled spaces communicating with the nasal cavity within the bones of the Skull and face This may cause facial pain, fever, nasal drainage, and headaches. A headache ( cephalalgia in medical terminology is a condition of pain in the Head; sometimes Neck or upper back pain may also be interpreted Individuals with CF may develop overgrowth of the nasal tissue (nasal polyps) due to inflammation from chronic sinus infections. Nasal polyps are polypoidal masses arising mainly from the Mucous membranes of the Nose and Paranasal sinuses They are overgrowths of the These polyps can block the nasal passages and increase breathing difficulties. ^[3][4]

Gastrointestinal, liver and pancreatic disease

Prior to prenatal and newborn screening, cystic fibrosis was often diagnosed when a newborn infant failed to pass faeces (meconium). Newborn screening is the process of testing newborn babies for treatable genetic, endocrinologic, metabolic and hematologic diseases Meconium is the earliest Meconium may completely block the intestines and cause serious illness. In Biology the small Intestine is the part of the Gastrointestinal tract (gut between the Stomach and the Large intestine, and comprises This condition, called meconium ileus, occurs in 10% of newborns with CF. Meconium is the earliest ^[5] 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. The rectum (from the Latin rectum intestinum, meaning straight intestine) is the final straight portion of the Large intestine in some Mammals Rectal prolapse normally describes a medical condition wherein the walls of the Rectum protrude through the Anus and hence become visible outside the body The Valsalva maneuver is performed by forcibly exhaling against a closed airway ^[6]

The thick mucus seen in the lungs has its counterpart in thickened secretions from the pancreas, an organ responsible for providing digestive juices which help break down food. Pancreatic juice is a juice produced by the Pancreas. It contains a variety of Enzymes, including Trypsinogen, Chymotrypsinogen, Elastase 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). In Anatomy of the Digestive system, the duodenum is a hollow jointed tube about 25-30 cm (10-12 in long connecting the Stomach to the Jejunum Pancreatitis is the Inflammation of the Pancreas. See also Acute pancreatitis and Chronic pancreatitis for more details ^[7] The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the faeces, a disorder known as malabsorption. Malabsorption is a state arising from abnormality in Digestion or Absorption of food nutrients across the gastrointestinal(GI tract. Malabsorption leads to malnutrition and poor growth and development because of calorie loss. Malnutrition is a general term for a medical condition caused by an improper or insufficient diet. Individuals with CF also have difficulties absorbing the fat-soluble vitamins A, D, E, and K. Vitamin A refers to a family of similarly shaped molecules the Retinoids. Vitamin D is a group of fat-soluble Prohormones, the two major forms of which are vitamin D2 (or Ergocalciferol) and vitamin D3 (or See also Tocopherol, Tocotrienol Vitamin E is the collective name for a set of 8 related Tocopherols and Tocotrienols which are fat-soluble Vitamin K (K from "Koagulations-Vitamin" in German Danish Swedish and Norwegian denotes a group of Lipophilic, Hydrophobic Vitamins that In addition to the pancreas problems, people with cystic fibrosis experience more heartburn, intestinal blockage by intussusception, and constipation. Gastroesophageal reflux disease ( American English and Canadian English) or Gastro-oesophageal reflux disease ( British English, Hiberno-English An intussusception (a blockage of the intestine is a medical condition in which a part of the small Intestine has invaginated into another section of intestine similar to the Constipation, costiveness, or irregularity, is a condition of the Digestive system in which a person (or animal experiences hard Feces that ^[8] Older individuals with CF may also develop distal intestinal obstruction syndrome when thickened faeces cause intestinal blockage. Distal intestinal obstruction syndrome ( DIOS) involves blockage of the Intestines by thickened stool and occurs in individuals with Cystic fibrosis ^[9]

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. Bile or gall is a bitter yellow or green Alkaline fluid secreted by Hepatocytes from the Liver of most Vertebrates In many species A bile duct is any of a number of long tube-like structures that carry Bile. 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. Cirrhosis is a consequence of chronic Liver Disease characterized by replacement of liver tissue by fibrous Scar tissue as well as regenerative Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby ^[10][11]

Endocrine disease and growth

The pancreas contains the islets of Langerhans, which are responsible for making insulin, a hormone that helps regulate blood glucose. Islets of Langerhans is the area in which the Endocrine (ie hormone-producing cells of the Pancreas are grouped Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Damage of the pancreas can lead to loss of the islet cells, leading to diabetes that is unique to those with the disease. The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called ^[12] 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. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc ^[13] Vitamin D is involved in calcium and phosphorus regulation. Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 Phosphorus, (ˈfɒsfərəs is the Chemical element that has the symbol P and Atomic number 15 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. Osteoporosis is a Disease of Bone that leads to an increased risk of fracture. A bone fracture (sometimes abbreviated # or Fx or Fx) is a medical condition in which a Bone is cracked or broken ^[14] In addition, people with CF often develop clubbing of their fingers and toes due to the effects of chronic illness and low oxygen on their tissues. In Medicine, clubbing, finger clubbing, or digital clubbing is a deformity of the Fingers and fingernails that is associated with a Chronic Hypoxia is a pathological condition in which the body as a whole ( generalized hypoxia) or region of the body ( tissue hypoxia) is deprived of adequate

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.

Infertility

Infertility affects both men and women. Female infertility|Male infertility Infertility primarily refers to the biological inability of a Man or a Woman to contribute to conception. At least 97 percent of men with cystic fibrosis are sterile. ^[15] These men make normal sperm but are missing the tube (vas deferens), which connects the testes to the ejaculatory ducts of the penis. A spermatozoon or spermatozoan ( pl spermatozoa) from the Ancient Greek σπέρμα (seed and ζῷον (living being and more commonly known The vas deferens (plural vasa deferentia also called ductus deferens, ( Latin: "carrying-away vessel" is part of the Male Anatomy The testicle (from Latin testiculus, diminutive of testis, meaning "witness" virility plural testes) is the male The Ejaculatory ducts ( ductus ejaculatorii) are paired structures in male Anatomy, about 2 cm in length The penis (plural penises, penes ^[16] Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF. Congenital absence of the vas deferens ( CAVD) is a condition in which the two Vas deferens, male reproductive organs fail to form properly ^[17] Some women have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts ovulation and causes amenorrhea. Note This article deals primarily with Human ovulation nonhuman Animal ovulation is touched on briefly at the conclusion Amenorrhoea ( BE) amenorrhea ( AmE) or amenorrhœa, is the absence of a Menstrual period in a woman of reproductive age ^[18]

Diagnosis and monitoring

Cystic fibrosis may be diagnosed by many different categories of testing including those such as, newborn screening, sweat testing, or genetic testing. Newborn screening is the process of testing newborn babies for treatable genetic, endocrinologic, metabolic and hematologic diseases The sweat test measures the Concentration of Chloride and Sodium that is excreted in sweat Genetic testing allows the genetic Diagnosis of vulnerabilities to inherited Diseases, and can also be used to determine a person's Ancestry. 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. Measurement of Immunoreactive trypsinogen ( IRT) in blood of newborn babies is an assay in rapidly increasing use as a screening test for Cystic fibrosis. ^[19] However, 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. Pilocarpine is a muscarinic Alkaloid obtained from the leaves of tropical American shrubs from the Genus Pilocarpus. An electrode is an Electrical conductor used to make contact with a nonmetallic part of a circuit (e Electric current is the flow (movement of Electric charge. The SI unit of electric current is the Ampere. 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. Iontophoresis is a non-invasive method of propelling high concentrations of a charged substance normally medication or bioactive agents transdermally by repulsive electromotive force Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 The chloride Ion is formed when the element Chlorine picks up one Electron to form an Anion (negatively-charged ion Cl&minus 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. ^[20]

A multitude of tests is 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. Radiology is the medical specialty directing Medical imaging technologies to diagnose and treat diseases Computed tomography (CT is a Medical imaging method employing Tomography. Examination of the sputum under a microscope is used to identify which bacteria are causing infection so that effective antibiotics can be given. A sputum culture is a test to detect and identify Bacteria or fungi that infect the Lungs or breathing passages. A microscope ( Greek: ( micron) = small + ( skopein) = to look or see is an instrument for viewing objects that are Antibiotic resistance is the ability of a Microorganism to withstand the effects of Antibiotics. Pulmonary function tests measure how well the lungs are functioning, and are used to measure the need for and response to antibiotic therapy. Spirometry (meaning the measuring of breath) is the most common of the Pulmonary Function Tests (PFTs measuring Lung function specifically the measurement Blood tests can identify liver problems, vitamin deficiencies, and the onset of diabetes. A blood test is a laboratory analysis performed on a Blood sample that is usually extracted from a Vein in the arm using a needle, or via Avitaminosis is any Disease caused by chronic or long-term Vitamin deficiency or caused by a defect in metabolic conversion such as tryptophan to niacin DEXA scans can screen for osteoporosis and testing for fecal elastase can help diagnose insufficient digestive enzymes. Dual energy X-ray absorptiometry ( DXA, previously DEXA is a means of measuring Bone mineral density (BMD Screening, in medicine is a strategy used in a Population to detect a Disease in individuals without signs or Symptoms of that disease Fecal elastase refers to the testing of the Concentration of the pancreatic Elastase -1 Enzyme found in fecal matter with an enzyme-linked

Prenatal diagnosis

Couples 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. A fetus (or foetus or fœtus) is a developing Mammal or other Viviparous Vertebrate, after the Embryonic stage and Cystic fibrosis testing is offered to many couples in the US. ^[21] The American College of Obstetricians and Gynecologists (ACOG) recommends testing for couples who have a personal or close family history. The American College of Obstetricians and Gynecologists ( ACOG) is a Professional association of Medical doctors specializing in Obstetrics and Additionally, ACOG recommends that carrier testing be offered to all Caucasian couples and be made available to couples of other ethnic backgrounds. ^[22]

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. ^[23] 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. In vitro fertilisation ( IVF) is a process by which In Medicine and (clinical Genetics preimplantation genetic diagnosis (PGD (or also known as Embryo Screening) refers to procedures that are performed An embryo (from Greek:, plural, lit "that which grows" from en- "in" + bryein "to swell be full" is a multicellular The test, performed 3 days after fertilization, looks for the presence of abnormal CF genes. For soil improvement see Fertilization (soil. 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. Embryo transfer refers to a step in the process of in vitro fertilization (IVF whereby one or several Embryos are placed into the Uterus

During pregnancy, testing can be performed on the placenta (chorionic villus sampling) or the fluid around the fetus (amniocentesis). The placenta is an Ephemeral organ present in placental Vertebrates, such as Eutherial Mammals and Sharks during Gestation Chorionic villus sampling (CVS is a form of Prenatal diagnosis to determine chromosomal or Genetic disorders in the Fetus. Amniocentesis (also referred to as amniotic fluid test or AFT) is a medical procedure used in Prenatal diagnosis of genetic abnormalities and fetal However, chorionic villus sampling has a risk of fetal death of 1 in 100 and amniocentesis of 1 in 200,^[24] so the benefits must be determined to outweigh these risks prior to going forward with testing. Chorionic villus sampling (CVS is a form of Prenatal diagnosis to determine chromosomal or Genetic disorders in the Fetus. Alternatively, some couples choose to undergo third party reproduction with egg or sperm donors. Third party reproduction refers to a process where another person provides sperm or eggs or where another woman provides her Uterus so that a woman can Egg donation is the process by which a woman provides one or several eggs ( Ova, oocytes for purposes of assisted reproduction or biomedical research Sperm donation is the name of the practice by which a Man, known as a sperm donor, provides his Semen with the intention that it be used to produce a baby

Pathophysiology

Cystic 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 cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called The skin contains two different groups of sweat glands: Apocrine sweat glands and Merocrine sweat glands. In Biology, an organ ( Latin: organum, "instrument tool" from Greek όργανον - organon "organ instrument The protein spans this membrane and acts as a channel connecting the inner part of the cell (cytoplasm) to the surrounding fluid. Ion channels are pore-forming Proteins that help establish and control the small Voltage Gradient across the Plasma membrane of all living The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. Extracellular fluid (ECF usually denotes all body fluid outside of cells In the airway 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 also cannot cross into the cell because they are affected by the electrical attraction of the chloride ions. Electric charge is a fundamental conserved property of some Subatomic particles which determines their Electromagnetic interaction. An ion is an Atom or Molecule which has lost or gained one or more Valence electrons giving it a positive or negative electrical charge Electrostatics is the branch of Science that deals with the Phenomena arising from what seems to be stationary Electric charges Since Classical 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. For sodium chloride in the diet see Salt. Sodium chloride, also known as common salt, table salt, or Halite, is a This lost salt forms the basis for the sweat test. ^[2]

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. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor 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. ^[2]

The role of chronic infection in lung disease

The 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. A biofilm is a structured community of Microorganisms encapsulated within a self-developed polymeric matrix and adherent to a living or inert surface 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. Bronchiectasis is a disease that causes localized irreversible dilatation of part of the Bronchial tree. ^[25]

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. Staphylococcus aureus (ˌstæfɨləˈkɒkəs ˈɔriəs literally "Golden Cluster Seed" and also known as golden staph) is the most common cause of Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, is a non-motile Gram-negative Coccobacillus Eventually, however, Pseudomonas aeruginosa (and sometimes Burkholderia cepacia) dominates. Pseudomonas aeruginosa is a Gram-negative, aerobic, rod-shaped Bacterium with unipolar motility. Burkholderia cepacia complex (BCC, or simply Burkholderia cepacia is a group of Catalase -producing non- Lactose - fermenting Once within the lungs, these bacteria adapt to the environment and develop resistance to commonly used antibiotics. Antibiotic resistance is the ability of a Microorganism to withstand the effects of Antibiotics. Pseudomonas can develop special characteristics that allow the formation of large colonies, known as "mucoid" Pseudomonas and rarely seen in people that do not have CF. ^[25]

One way in which infection has spread is by passage between different individuals with CF. ^[26] In the past, people with CF often participated in summer "CF Camps" and other recreational gatherings. ^[27][28] Hospitals grouped patients with CF into common areas and routine equipment (such as nebulizers)^[29] was not sterilized between individual patients. In Medicine, a nebulizer is a device used to administer medication to people in the form of a mist inhaled into the lungs ^[30] 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. ^[31] Often, patients with particularly damaging bacteria will attend clinics on different days and in different buildings than those without these infections.

Molecular biology

The CFTR gene is found at the q31. CFTR ( cystic fibrosis transmembrane conductance regulator ATP-binding cassette (sub-family C member 7) is a Human Gene that provides instructions for 2 locus of chromosome 7, is 230 000 base pairs long, and creates a protein that is 1,480 amino acids long. In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 7 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome In Molecular biology, two Nucleotides on opposite complementary DNA or RNA strands that are connected via Hydrogen bonds are called In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this 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. ΔF508 is a specific Mutation within the Human genome. The mutation is a deletion of three Base pairs at position 508 in the Nucleotide sequence Phe redirects here For the BitTorrent feature see PHE. For the constellation see Phoenix (constellation. This mutation accounts for seventy percent of CF worldwide and 90 percent of cases in the United States. The United States of America —commonly referred to as the There are over 1,400 other mutations that can produce CF, however. In Caucasian populations, the frequency of mutations is as follows:^[32]

Mutation	Frequency worldwide
ΔF508	66. The Caucasian race, sometimes the Caucasoid race, is a term of Racial classification, coined around 1800 by Johann Friedrich Blumenbach for the " 0%
G542X	2. 4%
G551D	1. 6%
N1303K	1. 3%
W1282X	1. 2%

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. Protein folding is the physical process by which a Polypeptide folds into its characteristic and functional three-dimensional structure. Several mutations, which are common in the Ashkenazi Jewish population, result in proteins that are too short because production is ended prematurely. Translation is the first stage of Protein biosynthesis (part of the overall process of Gene expression) 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. ^[2]

Structurally, CFTR is a type of gene known as an ABC gene. ATP-binding cassette transporters ( ABC-transporter) are members of a superfamily that is one of the largest and most ancient families with representatives in all extant ^[2] Its protein possesses two ATP-hydrolyzing domains which allows the protein to use energy in the form of ATP. ATP hydrolysis is the reaction by which chemical energy that has been stored and transported in the high-energy phosphoanhydridic bonds in ATP (Adenosine triphosphate A protein domain is a part of protein sequence and structure that can evolve, function and exist independently of the rest of the protein chain In Physics and other Sciences energy (from the Greek grc ἐνέργεια - Energeia, "activity operation" from grc ἐνεργός Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy It also contains two domains comprising 6 alpha helices apiece, which allow the protein to cross the cell membrane. A common motif in the Secondary structure of Proteins the alpha helix (α-helix is a right-handed coiled conformation resembling a spring, in which A regulatory binding site on the protein allows activation by phosphorylation, mainly by cAMP-dependent protein kinase. In Biochemistry, a binding site is a region on a Protein, DNA, or RNA to which specific other Molecules and Ions &mdash Phosphorylation is the addition of a Phosphate (PO4 group to a Protein molecule or a small molecule In Cell biology, protein kinase A, refers to a family of Enzymes whose activity is dependent on the level of Cyclic AMP (cAMP in the cell ^[2] The carboxyl terminal of the protein is anchored to the cytoskeleton by a PDZ domain interaction. The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal end, or cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm. The PDZ domain is a common Structural domain of 80-90 amino-acids found in the signaling Proteins of Bacteria, Yeast, Plants ^[33]

Treatment

The cornerstones of management are proactive treatment of airway infection, and encouragement of good nutrition and an active lifestyle. The ThAIRapy Vest is a device and system for clearing excess mucus from lung airways ( Bronchi and Bronchioles. 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), the reproductive organs (including Assisted Reproductive Technology (ART)) and psychological support. lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance A sex organ, or primary sexual characteristic, as narrowly defined is any of the anatomical parts of the body which are involved in sexual reproduction and constitute Assisted reproductive technology ( ART) is a general term referring to methods used to achieve Pregnancy by artificial or partially artificial means ^[34] In addition, therapies such as transplantation and gene therapy aim to cure some of the effects of cystic fibrosis. Gene therapy is the insertion of Genes into an individual's cells and tissues to treat a Disease, and Hereditary diseases in which a

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. Quality of life is the degree of well-being felt by an individual or group of people Intravenous, inhaled, and oral antibiotics are used to treat chronic and acute infections. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. Inhalation (also known as respiration) is the movement of air from the external environment through the air ways and into the Alveoli. Mechanical devices and inhalation medications are used to alter and clear the thickened mucus.

Antibiotics to treat lung disease

Antibiotics are given whenever pneumonia is suspected or there has been a decline in lung function. In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa Antibiotics are often chosen based on information about prior infections. 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. Vancomycin ( INN) (ˌvæŋkoʊˈmaɪsɪn is a Glycopeptide Antibiotic used in the Prophylaxis and treatment of infections caused by Tobramycin sulfate is an Aminoglycoside Antibiotic used to treat various types of Bacterial infections particularly Gram-negative infections Meropenem is an ultra-broad spectrum injectable Antibiotic used to treat a wide variety of infections including Meningitis and Pneumonia. Piperacillin is an extended spectrum beta-lactam Antibiotic of the Ureidopenicillin class This prolonged therapy often necessitates hospitalization and insertion of a more permanent IV such as a PICC line or Port-a-Cath. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. A peripherally inserted central catheter ( PICC or PIC line) is a form of Intravenous access that can be used for a prolonged period of time e In Medicine, a port (or portacath) is a small medical appliance that is installed beneath the skin 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. Colistin (polymyxin E is a Polymyxin Antibiotic produced by certain strains of Bacillus polymyxa var ^[35][36] Oral antibiotics such as ciprofloxacin or azithromycin are sometimes given to help prevent infection or to control ongoing infection. Azithromycin is an Azalide, a subclass of Macrolide Antibiotics. ^[37] 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 or kidney problems with long-term use. Ototoxicity is damage of the Ear ( oto) specifically the Cochlea or auditory nerve and sometimes the Vestibulum, by a Toxin Renal failure or kidney In order to prevent these side-effects, the amount of antibiotics in the blood are routinely measured and adjusted accordingly. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences

Other methods to treat lung disease

Several mechanical techniques are used to dislodge sputum and encourage its expectoration. In the hospital setting, physical therapy is utilized; a therapist pounds an individual's chest with his or her hands several times a day. Devices that recreate this percussive therapy include the ThAIRapy Vest and the intrapulmonary percussive ventilator (IPV). The ThAIRapy Vest is a device and system for clearing excess mucus from lung airways ( Bronchi and Bronchioles. Intrapulmonary percussive ventilator s ( IPV) are machines which deliver short bursts of air through a mouthpiece to help individuals with Lung disease clear Sputum 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 ( BCV) is a method of Ventilation which requires the patient to wear an upper body shell or Cuirass, so named after the body-armour Biphasic Cuirass Ventilation is also shown to provide a bridge to transplantation. Biphasic Cuirass Ventilation ( BCV) is a method of Ventilation which requires the patient to wear an upper body shell or Cuirass, so named after the body-armour These are portable and adapted for home use. ^[38] Aerobic exercise is of great benefit to people with cystic fibrosis. Aerobic exercise refers to Exercise that involves or improves oxygen consumption by the body 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. Dornase alfa (proprietary name Pulmozyme from Genentech) is a highly purified solution of recombinant human Deoxyribonuclease I (rhDNase an Enzyme Tonicity is a measure of blood capacity or effective osmolality in cell Biology. In Medicine, saline (also saline solution) is a general term referring to a sterile solution of Sodium chloride (table Salt) in water ^[39] Dornase is a recombinant human deoxyribonuclease, which breaks down DNA in the sputum, thus decreasing its viscosity. Recombinant DNA is a form of synthetic DNA that is engineered through the combination or insertion of one or more DNA strands thereby combining DNA sequences A deoxyribonuclease ( DNase, for short is any Enzyme that catalyzes the hydrolytic cleavage of phosphodiester linkages in the DNA Sputum is matter that is Expectorated from the respiratory tract such as Mucus or Phlegm, mixed with Saliva, which can then be spat Viscosity is a measure of the resistance of a Fluid which is being deformed by either Shear stress or Extensional stress. ^[40] N-Acetylcysteine may also decrease sputum viscosity, but research and experience have shown its benefits to be minimal. Acetylcysteine ( rINN; ˌæsɛtəlˈsɪstiːn əˌsɛtəl- also known as N -acetylcysteine or N -acetyl-L-cysteine (abbreviated Albuterol and ipratropium bromide are inhaled to increase the size of the small airways by relaxing the surrounding muscles. Salbutamol ( INN) or albuterol ( USAN) is a short-acting β2-adrenergic receptor agonist used for the relief of Bronchospasm Ipratropium (as ipratropium Bromide, trade name Atrovent) is an Anticholinergic drug

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. ^[41] During severe illness, people with CF may need to have a tube placed in their throats and their breathing supported by a ventilator. In Medicine, intubation refers to the placement of a tube into an external or internal orifice of the body

Treatment of other aspects of CF

Newborns with meconium ileus typically require surgery, whereas adults with distal intestinal obstruction syndrome typically do not. In fields of Anatomy, anatomical terms of location are descriptive terms to help identify relative positions or directions within a species 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. Vitamin A refers to a family of similarly shaped molecules the Retinoids. Vitamin D is a group of fat-soluble Prohormones, the two major forms of which are vitamin D2 (or Ergocalciferol) and vitamin D3 (or See also Tocopherol, Tocotrienol Vitamin E is the collective name for a set of 8 related Tocopherols and Tocotrienols which are fat-soluble Vitamin K (K from "Koagulations-Vitamin" in German Danish Swedish and Norwegian denotes a group of Lipophilic, Hydrophobic Vitamins that 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 and unsaturated fats/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. Saturated fat is Fat that consists of Triglycerides containing only saturated Fatty acids Explanation Fat that occurs An unsaturated fat is a Fat or Fatty acid in which there are one or more Double bonds in the fatty acid chain Trans fat is the common name for a type of Unsaturated fat with trans - isomer Fatty acid (s So far, no large-scale research involving the incidence of atherosclerosis and coronary heart disease in adults with cystic fibrosis has been conducted. Atherosclerosis is a Disease affecting arterial Blood vessels It is a chronic inflammatory response in the walls of arteries in large part due to the accumulation Coronary disease (or coronary heart disease) refers to the failure of Coronary circulation to supply adequate circulation to Cardiac muscle and surrounding 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. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance An insulin pump is a medical device used for the administration of Insulin in the treatment of Diabetes mellitus, also known as continuous subcutaneous ^[42] Development of osteoporosis can be prevented by increased intake of vitamin D and calcium, and can be treated by bisphosphonates. Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 In Pharmacology, bisphosphonates (also called diphosphonates) are a class of drugs that inhibit Osteoclast action and the resorption of bone ^[43] Poor growth may be avoided by insertion of a feeding tube for increasing calories through supplemental feeds or by administration of injected growth hormone. A feeding tube is a medical device used to provide nutrition to patients who cannot obtain nutrition by swallowing This article is about the unit of energy For its use in Nutrition and Food labelling regulations, see the article on Food energy. Growth hormone ( GH) is a Peptide hormone that stimulates growth and cell reproduction in humans and other animals ^[44]

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. Fluticasone is a potent synthetic Corticosteroid often prescribed as treatment for Asthma and Allergic rhinitis. ^[45] Female infertility may be overcome by assisted reproduction technology, particularly embryo transfer techniques. In vitro fertilisation ( IVF) is a process by which Embryo transfer refers to a step in the process of in vitro fertilization (IVF whereby one or several Embryos are placed into the Uterus Male infertility may be overcome with intracytoplasmic sperm injection. Intracytoplasmic sperm injection ( ICSI, pronounced "eeksee" is an ''in vitro'' fertilization procedure in which a single sperm is injected directly ^[46] Third party reproduction is also a possibility for women with CF. Embryo transfer refers to a step in the process of in vitro fertilization (IVF whereby one or several Embryos are placed into the Uterus

Transplantation and gene therapy

Lung transplantation often becomes necessary for individuals with cystic fibrosis as lung function and exercise tolerance declines. Lung transplantation is a surgical procedure in which a patient's diseased Lungs are partially or totally replaced by lungs which come from a donor Exercise intolerance is a condition where the Patient is unable to do Physical exercise at the level or for the duration that would be expected of someone in 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. ^[47] Lung transplantation is considered when lung function approaches a point where it threatens survival or requires assistance from mechanical devices. ^[48]

Gene therapy holds promise as a potential avenue to cure cystic fibrosis. Gene therapy is the insertion of Genes into an individual's cells and tissues to treat a Disease, and Hereditary diseases in which a 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. Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such ^[49] Many approaches have been theorized and several clinical trials have been initiated but, as of 2006, many hurdles still exist before gene therapy can be successful. ^[50]

Prognosis

In most cases, CF causes an early death. Average life expectancy is around 36. 8 years, although improvements in treatments mean a baby born today could expect to live longer. ^[51]

Epidemiology

Cystic fibrosis is the most common life-limiting autosomal recessive disease among people of European heritage. 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. Country to "Dominion of Canada" or "Canadian Federation" or anything else please read the Talk Page Approximately 1 in 25 people of European descent and 1 in 22 people of Ashkenazi Jewish descent is a carrier of a cystic fibrosis mutation. Ashkenazi Jews, also known as Ashkenazic Jews or Ashkenazim ( Hebrew: אַשְׁכֲּנָזִים, ˌaʃkəˈnazim sing 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. Hispanic (hispano hispánico hispânico Hispānus adjective from ''Hispānia'', the Roman name for the Iberian Peninsula) is a term that historically Asian or Asiatic is a Demonym for people from Asia. However the use of the term varies by country and person often referring to people from a particular ^[52][53][54]

Cystic fibrosis is diagnosed in males and females equally. For unclear reasons, males tend to have a longer life expectancy than females. Life expectancy is the average number of years of life remaining at a given age ^[55] 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. The Cystic Fibrosis Foundation ( CFF) is a Non-profit organization in the United States established to provide the means to cure and control Cystic ^[51]

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. High school is the name used in some parts of the world (in particular Scotland, North America and Australia) to describe an institution 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.

Theories about the prevalence of CF

The ΔF508 mutation is estimated to be up to 52,000 years old. ΔF508 is a specific Mutation within the Human genome. The mutation is a deletion of three Base pairs at position 508 in the Nucleotide sequence ^[56] 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. Sickle-cell disease or sickle-cell anaemia (or anemia) is a Blood disorder characterized by Red blood cells that assume an abnormal rigid A heterozygote advantage ( heterozygous advantage) describes the case in which the heterozygote genotype has a higher relative fitness than either the 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. A heterozygote advantage ( heterozygous advantage) describes the case in which the heterozygote genotype has a higher relative fitness than either the Cholera, sometimes known as Asiatic cholera or epidemic cholera, is an infectious Gastroenteritis caused by the Bacterium A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low ^[57] Further studies have not confirmed this hypothesis. ^[58][59]
• Typhoid: Normal CFTR proteins are also essential for the entry of Salmonella typhi into cells,^[60] suggesting that carriers of mutant CFTR genes might be resistant to typhoid fever. Salmonella enterica is a rod shaped Flagellated Gram-negative Bacterium, and a member of the Genus Salmonella Typhoid fever, also known as enteric fever, bilious fever, Yellow Jack or commonly just typhoid, is an illness caused by the Bacterium 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. In Epidemiology, an Infection is said to be endemic (from Greek en- in or within + demos people in a Population when
• Diarrhoea: 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. Lactose intolerance is the inability to metabolize Lactose, a sugar found in Milk and other Dairy products because the required enzyme ^[61]
• Tuberculosis: Poolman and Galvani from Yale University have added another possible explanation - that carriers of the gene have some resistance to TB. ^[62][63]

History

The name cystic fibrosis refers to the characteristic 'fibrosis' (tissue scarring) of the biliary tract ("cystic" being a generic term for all that is related to the biliary vesicle and/or the bladder), first recognized in the 1930s. ^[64] Formerly known as cystic fibrosis of the pancreas, this entity has increasingly been labeled simply cystic fibrosis. The pancreas is a Gland organ in the digestive and Endocrine system of Vertebrates. ^[65] Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects of CF were identified much earlier. Indeed, literature from Germany and Switzerland in the 1700s warned "Wehe dem Kind, das beim Kuß auf die Stirn salzig schmekt, es ist verhext und muss bald sterben," which translates to "Woe is the child kissed on the brow who tastes salty, for he is cursed and soon must die," recognizing the association between the salt loss in CF and illness. Carl von Rokitansky described a case of fetal death with meconium peritonitis, complication of meconium ileus associated with cystic fibrosis. Baron Carl von Rokitansky ( German: Carl Freiherr von Rokitansky, Czech: Karel Rokytanský) ( February 19, 1804 &ndash Meconium peritonitis refers to rupture of the bowel prior to birth resulting in fetal stool ( Meconium) escaping into the surrounding space ( Peritoneum Meconium ileus was first described in 1905 by Karl Landsteiner. Karl Landsteiner ( June 14 1868 &ndash June 26 1943) was an Austrian Biologist and Physician. ^[66] In 1936, Guido Fanconi published a paper describing a connection between celiac disease, cystic fibrosis of the pancreas, and bronchiectasis. Guido Fanconi ( 1 January[[ 892]] &ndash 10 October 1979) was a Swiss Pediatrician. Bronchiectasis is a disease that causes localized irreversible dilatation of part of the Bronchial tree. ^[67]

In 1938, Dorothy Hansine Andersen published an article titled "Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathological study" in the American Journal of Diseases of Children. Dorothy Hansine Andersen ( May 15, 1901 - 1963 was the American who was "the first person to identify Cystic fibrosis and the first American In her paper, she described the characteristic cystic fibrosis of the pancreas correlated it with the lung and intestinal disease prominent in CF. ^[64] 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; the sweat test was developed and improved over the next decade. ^[68]

In 1988, the first mutation for CF, ΔF508, was discovered by Francis Collins, Lap-Chee Tsui and John R. ΔF508 is a specific Mutation within the Human genome. The mutation is a deletion of three Base pairs at position 508 in the Nucleotide sequence Francis S Collins (born April 14, 1950) MD, PhD, is an American Physician - Geneticist, noted for his landmark Lap-Chee Tsui, OC, OOnt ( born December 21, 1950) is a Hong Kong Geneticist and is currently the Vice-Chancellor Riordan on the seventh chromosome. Research has subsequently found over 1000 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. The Hospital for Sick Children, also known as SickKids, is a world-renowned Children's hospital in Toronto, Ontario, Canada. Toronto (təˈrɒntoʊ colloquially pronounced or) is the largest city in Canada and is the provincial capital of Ontario Cystic fibrosis represents the first genetic disorder elucidated strictly by the process of reverse genetics. Reverse genetics is an approach to discovering the function of a Gene that proceeds in the opposite direction of so called forward genetic screens of Classical Because mutations in the CFTR gene are typically small, classical genetics techniques were not able to accurately pinpoint the mutated gene. Classical genetics consists of the techniques and methodologies of Genetics that predate the advent of Molecular biology. ^[69] Using protein markers, gene linkage studies were able to map the mutation to chromosome 7. Genetic linkage occurs when particular genetic loci or Alleles for genes are inherited jointly Chromosome walking and jumping techniques were then used to identify and sequence the gene. Primer walking is a Sequencing method of choice for sequencing DNA fragments between 1 Chromosome jumping is a technique of Molecular biology that is used as a tool in the physical mapping of Genomes It is related to several other tools used The term DNA sequencing encompasses biochemical methods for determining the order of the Nucleotide bases Adenine, Guanine, Cytosine ^[70]

Public Awareness

Some children with cystic fibrosis in the United States call their disease 65 Roses because the words are easier to pronounce. This trademarked phrase has been popularized by the Cystic Fibrosis Foundation. The Cystic Fibrosis Foundation ( CFF) is a Non-profit organization in the United States established to provide the means to cure and control Cystic The phrase came into being when it was used by a young boy who had overheard his mother, a volunteer for the Foundation, speaking of his illness. He later informed her that he knew she was working to help with "sixty-five roses"^[71] The term has since been used as a symbol by organizations and families of cystic fibrosis victims.

The fight against cystic fibrosis has been a news story in France, where on April 30, 2007, the rising pop singer Grégory Lemarchal died from the illness at the age of 23. This article is about the country For a topic outline on this subject see List of basic France topics. Events 313 - Roman emperor Licinius unifies the entire Eastern Roman Empire under his rule Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Grégory Jean-Paul Lemarchal ( May 13, 1983 – April 30, 2007) was a French Singer and winner of the fourth series Grégory won the fourth round of Star Academy (equivalent of Pop Idol) in 2004 with a voting score of 80% at the grand final - a percentage unmatched in the history of the show. Star Academy is a highly successful television show format produced by Endemol, that has been broadcast in over 50 countries On May 4, a special television programme was broadcast on TF1 to commemorate his life, and its 10. Events 1256 - The Augustinian monastic order is constituted at the Lecceto Monastery when Pope Alexander IV for the motorway in Tenerife Spain see TF1 Motorway, for the WWI aircraft Sopwith Camel#(Trench Fighter T 5 million viewers were asked to donate money to help progress research into finding a cure. More than 7. 5 million euros have been raised. ^[72] Following his death, his family started Association Grégory Lemarchal, an advocacy organization supporting people with cystic fibrosis. Grégory Jean-Paul Lemarchal ( May 13, 1983 – April 30, 2007) was a French Singer and winner of the fourth series

Former Real World San Diego Castmate Frankie Abernathy died of cystic fibrosis June 9, 2007. Frankie Jo Abernathy ( December 21, 1981 – June 9, 2007) was a castmate on MTV's The Real World San Diego. Events 53 - Roman Emperor Nero marries Claudia Octavia 62 - Claudia Octavia commits Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century.

In January 2008, a documentary called "A Boy Called Alex" was screened on Channel Four about Alexander Stobbs, a gifted music scholar at Eton College. Channel 4 is a public-service Television and Radio broadcaster in the United Kingdom centred around a television channel of the same name which began Eton College, or just Eton, is a world-famous British Independent school for boys founded in 1440 by King Henry VI. It showed his inspirational determination to conduct Bach's magnificat, despite interruptions due to life-threatening illness. WikipediaWikiProject Composers#Lead section.2 This article is written in British English including maximised use of "-ise" The Magnificat in D major BWV 243 is one of the major vocal works of Johann Sebastian Bach. The documentary has received excellent reviews and rais

Orla Tinsley, a CF sufferer, has written many articles about CF, and the plight it causes, in the Irish Times, and is a frequent campaigner for CF patient rights.

The main character of the play 'John Lennon and Me' by Cherie Bennet has CF and resides at a pediatric hospital.

See also

• List of cystic fibrosis organizations
• List of people diagnosed with cystic fibrosis
• Dor Yeshorim

References

External links

• Cystic fibrosis at the Open Directory Project
• Cystic Fibrosis Worldwide
• Cystic Fibrosis Foundation
• Cystic fibrosis pictures (Univ Geneva, Switzerland)
• cf at NIH/UW GeneTests
• Rare Diseases Clinical Research Network
• Search GeneCards for genes envolved in Cystic Fibrosis

The Open Directory Project ( ODP) also known as dmoz (from directory "NIH" redirects here For other meanings of NIH see NIH (disambiguation. See Washington (disambiguation for other uses The University of Washington, founded in 1861, is a public research University

© 2009 citizendia.org; parts available under the terms of GNU Free Documentation License, from http://en.wikipedia.org
Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic