Category Archives: Cf

Samir Nasri missed a penalty as Sevilla ended with a 0-0 draw at home against Villarreal in La Liga. The missed the chance to close the gap with leaders Real Madrid C.F. in points table

Samir Nasri missed a second-half penalty as Sevilla squandered the chance to close to within a point of La Liga leaders Real Madrid with a 0-0 draw home to Villarreal on Sunday.

The Frenchmans low spot-kick was well saved by Sergio Asenjo, who then made a spectacular stop from Vicente Iborras late header as La Ligas best defence held out for a point at the Sanchez Pizjuan stadium.

Sevilla trail Madrid by three points, but the European champions have two games in hand.

Real were due to be in action later on Sunday, but their clash at Celta Vigo was postponed after bad weather damaged Celtas Balaidos stadium.

Sevilla dominated throughout, but had to wait until the second half to enjoy their best openings.

The hosts were generously awarded a penalty just three minutes after the break when Vitolo went down in the area under pressure from Mario Gaspar.

Nasri confidently stepped up, but the on-loan Manchester City midfielders strike lacked the power or accuracy to beat Asenjo, who saved low to his left.

Villarreal then had a huge chance of their own to go in front on the counter-attack as Adrian Lopez rounded Sevilla goalkeeper Sergio Rico, but could only fire into the side-netting with the goal gaping.

The visitors were rescued by the offside flag moments later when Wissam Ben Yedder fired into the roof of the net.

And it was Asenjo who proved the Villarreal hero once more seven minutes from time with a remarkable save to his right to prevent Sevilla captain Iborras header from close range flying into the far corner.

We deserved more, said Sevilla coach Jorge Sampaoli.

To miss out on two points is frustrating given the dreams we have.

Villarreal remain in sixth, four points off the top four, as Real Sociedad came from behind at a windswept Anoeta to beat Osasuna 3-2.

- Floodlight failure -

The match in San Sebastian threatened to become the third La Liga game of the weekend called off by extreme weather in the north of Spain as relentless rain fell during the first 45 minutes.

Osasuna were the keener to continue at half-time as Kenan Kodro handed them a 25th minute lead.

However, Osasuna remain without a league win since October as Sociedad roared back with three goals in 15 minutes from Raul Navas, Carlos Vela and Juanmi to move to within a point of Atletico Madrid.

Sergio Leon gave Osasuna hope with a fine solo effort 11 minutes from time and only a stunning save from Geronimo Rulli to turn Jaime Romeros effort onto the bar denied the visitors an unlikely point.

And even a fleeting last minute floodlight failure couldnt save Osasuna from defeat as they remain rooted in the relegation zone in 19th.

Sporting Gijon also failed to ease their relegation fears as a much-changed Alaves won 4-2 at El Molinon.

Alaves had the second leg of their Copa del Rey semi-final with Celta on Wednesday in mind, but goals Ruben Soriano, Cristian Santos, Edgar Mendez and Alexis left Sporting still five points off safety.

kca/dmc

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Real Madrid CF still on top of La Liga as Villarreal hold Sevilla to a draw - Hindustan Times

We have gathered the technical data on CF Industries Holdings, Inc. (CF), and see some interesting trends in the stocks behavior of late. Every professional at some point comes to respect the actual behavior of a stock as the true arbiter of right and wrong with any bet. The chart captures that best.

CF has been trading in a bearish trend, based on the relative levels of its 50-day and 200-day simple moving averages. This suggests that the broad sum of capital flow in the stock has been generally negative over the recent period. In terms of the relative level of interest afforded this stock among active participants in the market, relative volume measures have been weak, indicating apathy for the name by traders, investors, and money managers during the past month of action. This suggests something of the significance of other current technical measures as well.

For market timers, its also important to take measure of the relative level of recent lift or pressure in the stock is it overbought or oversold? For that, we turn to RSI and stochastic measures. The 14-day RSI stands at 59.25%. That shows that the stock, according to a traditional interpretation and usage of the RSI indicator, is not particularly predisposed to a reactive price movement based on this measure If we look at the stochastic measure, the raw data over the stocks last month of action shows a score of 77.03%. Based on a raw data interpretation, the stock is relatively overbought from this perspective.

As professionals know, risk is best understood through a measure of volatility in an investment vehicle. In recent action, CF has made a move of +2.63 over the past month. Over the trailing year, the stock is underperforming the S&P 500 by -4.32%, and its gotten there by action that has been more volatile on a day-to-day basis than most other stocks on the exchange. The stocks recent movement has come on a historical volatility score of 42.28%, which represents the standard deviation of returns of a theoretical long position from a mean price during that period. On a daily basis over the past month, the average true range of the stock, as expressed in percentage terms, is 3.5%. That should give you a pretty good sense of the level of risk implied in a short-term trading approach in the stock with a stop-loss in place.

As it stands at present, the stock might find important action at key Fibonacci levels. Fibonacci levels are used by major Wall Street firm technical desks. The math is drawn from the Fibonacci series that defines growth systems by an interval increase characterized by steps divisible by the golden ratio of 61.8%. In this case, the critical 38.2% level drawn off the 52-weeklow of $20.25 sits at $26.71. CF also has additional support below at the stocks 200-day simple moving average, which sits at $27.57.

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Technicals in Focus for CF Industries Holdings, Inc. (CF) - The USA Commerce

The abbreviation cf. derives from the Latin verb conferre, to bring together (from which confer is the conjugation of the imperative form), while in English it is commonly read as "compare". The abbreviation advises readers to consult other material, usually for the purpose of drawing a contrast. Many usage guides recommend against the common use of cf. to mean "see also."

Such abbreviations appear most frequently in scholarly contexts, such as in academic articles in humanities, physics, chemistry, geology, open nomenclature biology, theology, philology,[1] or in economic[2][3] or legal writing.[4]

The abbreviation cf. is used in essays,[5]theses,[6]technical books,[7]law review articles,[8]legal opinions,[9] and scientific nomenclature.[10]

This abbreviation's general purpose is to compare the immediately preceding statement with another statement in the same work or, more commonly, a statement in another work.[6] For example, it might appear in legal writing like this:

While cars are required by law to stop at all stop signs (Vehicle Code section 1234 ["Cars must stop at stop signs"]), pedestrians are not (cf. Vehicle Code section 4321 ["Pedestrians need not stop at stop signs"]).

However, while the cf. abbreviation has widespread use as a shorthand for "see", particularly in citations, The Chicago Manual of Style recommends against its use in this sense and prefers instead that cf. be used only to mean "compare" or "see, by way of comparison".[11]

In biological naming conventions, cf. is used in a few ways; commonly it is placed between the generic name and the specific name to describe a specimen that is difficult to identify because of practical difficulties, such as the specimen being poorly preserved. For example, Barbus cf. holotaenia implies that the specimen is believed to be Barbus holotaenia but the actual identification cannot be certain.

The use of cf. in biological nomenclature expresses a possible identity, or at least a significant resemblance, such as between a newly observed specimen and a known species or taxon.[10] Such a usage might suggest a specimen's membership of the same genus or possibly of a shared higher taxon, such as in "Diptera: Tabanidae, cf. Tabanus" where the author is confident of the order Diptera and family Tabanidae, but can offer the genus Tabanus only as a suggestion, and has no information favouring a particular species.[12]

The abbreviation only has a single period placed at the end ("cf.", not "c.f.") because cf. is a shortening of the single word, "confer", not a shortening of two words (cf. "q.v." for "quod vide").

Use of italics for abbreviations of foreign words and phrases has become less common in modern usage, especially for such common abbreviations as cf., e.g., etc., i.e., q.v., and viz.

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Cf. - Wikipedia

Addtoportfolio

$22.32 USD

22.32

6,610,397

Updated Aug 12, 2016 02:40 PM ET

Volume: 6,610,397

Open: $22.22

Prior Close: $22.26

5-Strong Sell 5

Value: C | Growth: F | Momentum: F | VGM: F

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CF Industries Holdings, Inc. is the holding company for the operations of CF Industries, Inc. CF Industries, Inc. is a major producer and distributor of nitrogen and phosphate fertilizer products. CF Industries operates world-scale nitrogen fertilizer plants in Louisiana and Alberta, Canada; conducts phosphate mining and manufacturing operations in Central Florida; and distributes fertilizer products through a system of terminals, warehouses, and associated transportation equipment located primarily in the midwestern United States.

Full Company Report for CF

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Cf Indus Hldgs - CF - Stock Price Today - Zacks

CF Compact Flash (solid state memory technology) CF Cold Fusion (Allaire web application development product) CF Canadian Forces CF Center Field (Baseball) CF Copy(ies) Furnished CF Configuration File CF Carbon Fiber CF Cash Flow CF Congo CF Compact Framework (Microsoft) CF Christian Fellowship CF Cardiff University (Wales) CF Cardiff (postal code for Cardiff, Wales) CF Capital Federal CF Calf CF Community Forestry CF Central African Republic (country code, top level domain) CF Christian Forums CF Collaborative Filtering CF Confer (Latin: Compare) CF Compact Fluorescent (lamp/bulb) CF Conceptual Framework CF Complement Fixation (assay method for determination of infection in blood or serum) CF Center Front (tailoring) CF Constituio Federal (Brazil; Federal Constitution) CF Continuous Flow CF Conservation Foundation CF Continued Fractions CF Calgary Flames (NHL hockey team of Calgary, Alberta, Canada) CF Conservative Future CF Climate and Forecast CF Cerebrospinal Fluid CF Carry Flag CF Chinese Food CF Capacity Factor CF Coal Fired CF Californium CF Coldfire CF Centrifugal Force CF Carry Forward CF Codice Fiscale (Italian: fiscal code) CF Cardiac Failure CF Cease-Fire CF Cienfuegos (postcode, Cuba) CF Cold Front (meteorology) CF Call Forwarding CF Carrier Frequency CF Combining Form (linguistics) CF Cadillac Fairview CF Canadian French (language) CF Common Functions CF Change Form CF Causal Factor CF Chronic Future (band) CF Captain Falcon (Nintendo) CF Cold Feet (movie) CF Center Frequency CF Childfree CF Consolidated Freightways (trucking company) CF Charcoal Filter CF Celtic Frost (band) CF Career Field CF Center Fire (Ammunition) CF Customer Focus CF Coopration Franaise (French) CF Commercial Film CF Computing Facility CF Common Formats (United States Patient Safety and Quality Improvement Act of 2005) CF Center Forward (soccer position) CF Change Filter CF Climbing Fiber (neuroscience) CF Calibration Factor CF Central Facility CF Charlie-Foxtrot (slang for Cluster Flock; polite form) CF Communication Function CF Canadian Fighter CF Consulting Forester CF Coalition Force CF Central Files CF Change Frequency CF Compound Fracture CF Confidence Factor CF Caucasian Female CF Coated Front (paper) CF Compression Factor CF Complementary Function CF Cahiers Francais CF Communications Flight CF Center Funded CF Charter One Financial (NYSE Symbol) CF Centrally Funded CF Collection Function CF Citrovorum Factor CF Conseco Fieldhouse (Indiana) CF Cloud Fraction CF Completion Form CF Cowboys Fringants (band) CF Co-facilitator CF Cathode Follower CF Contra Fidem (Latin: Against My Will) CF Christmas Factor CF Commonwealth Funding CF Cold Finish CF Cervical Fracture (neck) CF Carbolfuchsin CF Charleston Forge CF Commodities Finance CF Concept Formulation CF Chicago Force CF Chart Field CF Concept Feasibility CF Compress-and-Forward (networking) CF Confinement Factor CF Continental Freight (trucking company) CF Counts Fingers (used with the 20/ scale after c. 20/400; ophthalmology) CF Construction Forces CF Clearance Facility CF Coupling Fault CF Center of Flotation CF Compliance Finding CF Computation Facility CF Consulting Fellow CF Conservation Farmers (Nepal) CF Comit de Facilitation CF Cumulus Fractus CF Cape Fear Railways, Inc. CF Calf-Fed Cf Frictional Resistance Coefficient CF Constructed Fare (airlines) CF Confrontation Field (ophthalmology) CF Clinical Facilitator CF Contingency Flag CF Content Freeze CF Coin First Payphone CF Chikara Fansubs CF Creative Fluff (website) CF Construction Flagman (NYC Transit Authority) CF Condensate and Feed CF Cab to Frame CF Cable, Fuzing or Firing CF Clarissima Foemina (Latin: Most Famous Lady, epigraphy) CF Cluster Foulup (polite form; military slang) CF Compartmented Facility CF Imagery and Geospatial Community Management Office (NIMA) CF Controlled Flaw CF Air Post Registration (Scott Catalogue prefix; philately) CF Campus Focus, Student Organization (University of Akron) CF Cassville Ferry (Wisconsin) CF Civilingenjors Forbundet CF Countermeasure Factor CF Controlled Iteration First Pass CF Conversion Facility CF Conversion Factor CF Convertible Freighter CF Cooling Fan CF Contractor-Furnished CF Contributing Factor CF Control Flow CF Control Freak CF Control Functions CF Core Fighter (Gundam) CF Core Foundation (Apple Computer) CF Corkscrew Follies (Rollercoaster Tycoon game) CF Corn Flakes CF Corn Flour CF Corporate Finance CF Corporate Fraud CF Correctional Facility CF Correlation Factor CF Cost and Freight CF Count Forward CF Counter Force CF Counterfire CF Crazy Frog (advertisement) CF Crest-Factor (distribution in multiplexed transmission signals) CF Critically Factor CF Crossfire CF Cubic Foot CF Cumulative Frequency (statistics) CF Continuous Form CF Court Filing CF Covering Force CF County Fair CF Coupling Facility (IBM mainframes) CF Hundred Feet CF Customer Fulfilment CF Customer Furnished CF Cutoff Frequency CF Cyberfair CF Cystic Fibrosis CF Cystic Fibrosis Foundation CF Drift Error Confidence Factor (US DoD) CF Flying Deck Cruiser (US Navy) CF French Canadian CF Civic Force (Japan) CF Chaplain to the Forces CF Causeway Ferry (US DoD) CF Carrier Free CF Capita Financial (various companies) CF Compact Flash

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CF - Definition by AcronymFinder

The abbreviation cf. derives from the Latin verb conferre, to bring together (from which confer is the conjugation of the imperative form), while in English it is commonly read as "compare". The abbreviation advises readers to consult other material, usually for the purpose of drawing a contrast. Many usage guides recommend against the common use of cf. to mean "see also".

Such abbreviations appear most frequently in scholarly contexts, such as in academic articles in humanities, physics, chemistry, geology, open nomenclature biology, theology, philology,[1] or in economic[2][3] or legal writing.[4]

The abbreviation cf. is used in essays,[5] theses,[6] technical books,[7] law review articles,[8] legal opinions,[9] and scientific nomenclature.[10] Its purpose is to compare the immediately preceding statement with another statement in the same work or more commonly, a statement in another work.[6] The following legal fabrication provides an example:

While cars are required by law to stop at all stop signs (Vehicle Code section 1234 ["Cars must stop at stop signs"]), pedestrians are not (cf. Vehicle Code section 4321 ["Pedestrians need not stop at stop signs"]).

While the cf. abbreviation has widespread use as a shorthand for "see", particularly in citations, The Chicago Manual of Style recommends against its use in this sense and prefers instead that cf. be used only to mean "compare" or "see, by way of comparison".[11]

In biological naming conventions, cf. is variously used; commonly it is placed between the generic name and the specific name to describe a specimen whose designation is uncertain because of practical difficulties such as poor preservation of the specimen. For example: Barbus cf. holotaenia implies that the specimen is believed to be Barbus holotaenia but the actual identification cannot be certain. The use of cf. in biological nomenclature expresses a possible identity, or at least a significant resemblance, such as between a newly observed specimen and a known species or taxon.[10] Such a usage might suggest a specimen's membership of the same genus or possibly of a shared higher taxon, such as in "Diptera: Tabanidae, cf. Tabanus" where the author is confident of the order Diptera and family Tabanidae, but can offer the genus Tabanus only as a suggestion, and has no information favouring a particular species.[12]

Formatted properly, the abbreviation ends in a single period ("cf.", not "c.f.") because it represents a shortening of "confer" as a single word, not a shortening of two words (cf. "q.v.").

Use of italics for abbreviations of foreign words and phrases has become less common in modern usage, especially for such common abbreviations as cf., e.g., etc., i.e., q.v., and viz.

See the rest here:

cf. - Wikipedia, the free encyclopedia

Cystic fibrosis (CF) is a genetic disorder that affects mostly the lungs but also the pancreas, liver, kidneys, and intestine.[1][2] Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in males, among others. Different people may have different degrees of symptoms.[1]

CF is inherited in an autosomal recessive manner. It is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein.[1] Those with a single working copy are carriers and otherwise mostly normal.[3] CFTR is involved in production of sweat, digestive fluids, and mucus.[4] When CFTR is not functional, secretions which are usually thin instead become thick.[5] The condition is diagnosed by a sweat test and genetic testing.[1] Screening of infants at birth takes place in some areas of the world.[1]

There is no cure for cystic fibrosis.[3] Lung infections are treated with antibiotics which may be given intravenously, inhaled, or by mouth. Sometimes the antibiotic azithromycin is used long term. Inhaled hypertonic saline and salbutamol may also be useful. Lung transplantation may be an option if lung function continues to worsen. Pancreatic enzyme replacement and fat-soluble vitamin supplementation are important, especially in the young. While not well supported by evidence, many people use airway clearance techniques such as chest physiotherapy.[1] The average life expectancy is between 42 and 50 years in the developed world.[6][7] Lung problems are responsible for death in 80% of people with cystic fibrosis.[1]

CF is most common among people of Northern European ancestry and affects about one out of every 3,000 newborns.[1] About one in 25 people are carriers.[3] It is least common in Africans and Asians.[1] It was first recognized as a specific disease by Dorothy Andersen in 1938, with descriptions that fit the condition occurring at least as far back as 1595.[2] The name cystic fibrosis refers to the characteristic fibrosis and cysts that form within the pancreas.[2][8]

The main signs and symptoms of cystic fibrosis are salty-tasting skin,[9] poor growth, and poor weight gain despite normal food intake,[10] accumulation of thick, sticky mucus,[11] frequent chest infections, and coughing or shortness of breath.[12] Males can be infertile due to congenital absence of the vas deferens.[13] Symptoms often appear in infancy and childhood, such as bowel obstruction due to meconium ileus in newborn babies.[14] As the children grow, they exercise to release mucus in the alveoli.[15]Ciliated epithelial cells in the person have a mutated protein that leads to abnormally viscous mucus production.[11] The poor growth in children typically presents as an inability to gain weight or height at the same rate as their peers and is occasionally not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multifactorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness.[10]

In rare cases, cystic fibrosis can manifest itself as a coagulation disorder. Vitamin K is normally absorbed from breast milk, formula, and later, solid foods. This absorption is impaired in some cystic fibrosis patients. Young children are especially sensitive to vitamin K malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves and limited ability to absorb vitamin K from dietary sources after birth. Because factors II, VII, IX, and X (clotting factors) are vitamin Kdependent, low levels of vitamin K can result in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whether there is an underlying disease.[16]

Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation.[17][18] Inflammation and infection cause injury and structural changes to the lungs, leading 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, changes in the architecture of the lung, such as pathology in the major airways (bronchiectasis), further exacerbate difficulties in breathing. Other signs include coughing up blood (hemoptysis), 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.[19]Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa are the three most common organisms causing lung infections in CF patients.[18] 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 a lot of lung damage and does not respond to common antibiotics.[20]

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.[21] Recurrent sinonasal polyps can occur in as many as 10% to 25% of CF patients.[18] These polyps can block the nasal passages and increase breathing difficulties.[22][23]

Cardiorespiratory complications are the most common cause of death (~80%) in patients at most CF centers in the United States.[18]

Prior 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 510%[18][24] of newborns with CF. In addition, protrusion of internal rectal membranes (rectal prolapse) is more common, occurring in as many as 10% of children with CF,[18] and it is caused by increased fecal volume, malnutrition, and increased intraabdominal pressure due to coughing.[25]

The thick mucus seen in the lungs has a counterpart in thickened secretions from the pancreas, an organ responsible for providing digestive juices that help break down food. These secretions block the exocrine movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis).[26] The pancreatic ducts are totally plugged in more advanced cases, usually seen in older children or adolescents.[18] This causes atrophy of the exocrine glands and progressive fibrosis.[18]

The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the feces, a disorder known as malabsorption. Malabsorption leads to malnutrition and poor growth and development because of calorie loss. Resultant hypoproteinemia may be severe enough to cause generalized edema.[18] 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.[27] Older individuals with CF may develop distal intestinal obstruction syndrome when thickened feces cause intestinal blockage.[28]

Exocrine pancreatic insufficiency occurs in the majority (85% to 90%) of patients with CF.[18] It is mainly associated with "severe" CFTR mutations, where both alleles are completely nonfunctional (e.g. F508/F508).[18] It occurs in 10% to 15% of patients with one "severe" and one "mild" CFTR mutation where there still is a little CFTR activity, or where there are two "mild" CFTR mutations.[18] In these milder cases, there is still sufficient pancreatic exocrine function so that enzyme supplementation is not required.[18] There are usually no other GI complications in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development.[18] Despite this, idiopathic chronic pancreatitis can occur in a subset of pancreas-sufficient individuals with CF, and is associated with recurrent abdominal pain and life-threatening complications.[18]

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 scarring and nodularity (cirrhosis). The liver fails to rid the blood of toxins and does not make important proteins, such as those responsible for blood clotting.[29][30] Liver disease is the third most common cause of death associated with CF.[18]

The 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 a type of diabetes that is unique to those with the disease.[31] This cystic fibrosis-related diabetes (CFRD) shares characteristics that can be found in type 1 and type 2 diabetics, and is one of the principal nonpulmonary complications of CF.[32]Vitamin D is involved in calcium and phosphate regulation. Poor uptake of vitamin D from the diet because of malabsorption can lead to the bone disease osteoporosis in which weakened bones are more susceptible to fractures.[33] 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.[34][35]

Infertility affects both men and women. At least 97% of men with cystic fibrosis are infertile, but not sterile and can have children with assisted reproductive techniques.[36] The main cause of infertility in men with cystic fibrosis is congenital absence of the vas deferens (which normally connects the testes to the ejaculatory ducts of the penis), but potentially also by other mechanisms such as causing no sperm, teratospermia, and few sperm with poor motility.[37] Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF.[38] Approximately 20% of women with CF have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts ovulation and causes a lack of menstruation.[39]

CF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, F508, is a deletion ( signifying deletion) of three nucleotides[40] that results in a loss of the amino acid phenylalanine (F) at the 508th position on the protein. This mutation accounts for two-thirds (6670%[18]) of CF cases worldwide and 90% of cases in the United States; however, there are over 1500 other mutations that can produce CF.[41] Although most people 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. Thus, CF is considered an autosomal recessive disease.

The CFTR gene, 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. More specifically the location is between base pair 117,120,016 to 117,308,718 on the long arm of chromosome 7, region 3, band 1, sub-band 2, represented as 7q31.2. Structurally, CFTR is a type of gene known as an ABC gene. The product of this gene (the CFTR) is a chloride ion channel important in creating sweat, digestive juices and mucus. This 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.[19] The carboxyl terminal of the protein is anchored to the cytoskeleton by a PDZ domain interaction.[42]

In addition, there is increasing evidence that genetic modifiers besides CFTR modulate the frequency and severity of the disease. One example is mannan-binding lectin, which is involved in innate immunity by facilitating phagocytosis of microorganisms. Polymorphisms in one or both mannan-binding lectin alleles that result in lower circulating levels of the protein are associated with a threefold higher risk of end-stage lung disease, as well as an increased burden of chronic bacterial infections.[18]

There are several mutations in the CFTR gene, and different mutations cause different defects in the CFTR protein, sometimes causing a milder or more severe disease. These protein defects are also targets for drugs which can sometimes restore their function. F508-CFTR, which occurs in >90% of patients in the U.S., creates a protein that does not fold normally and is not appropriately transported to the cell membrane, resulting in its degradation. Other mutations result in proteins that are too short (truncated) because production is ended prematurely. Other mutations produce proteins that: do not use energy normally, do not allow chloride, iodide, and thiocyanate to cross the membrane appropriately,[43] degrade at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced.[19]

The protein created by this gene is anchored to the outer membrane of cells in the sweat glands, lungs, pancreas, and all other remaining exocrine glands in the body. 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 halogens from inside to outside of the cell; however, in the sweat ducts it facilitates the movement of chloride from the sweat duct into the cytoplasm. When the CFTR protein does not resorb ions in sweat ducts, chloride and thiocyanate[44] released from sweat glands are trapped inside the ducts and pumped to the skin. Additionally hypothiocyanite, OSCN, cannot be produced by the immune defense system.[45][46] Because chloride is negatively charged, this modifies the electrical potential inside and outside the cell that normally causes cations to cross into the cell. Sodium is the most common cation in the extracellular space. The excess chloride within sweat ducts prevents sodium resorption by epithelial sodium channels 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.[19]

Most 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. There are several theories on how the defects in the protein and cellular function cause the clinical effects. The most current theory suggests that defective ion transport leads to dehydration in the airway epithelia, thickening mucus. In airway epithelial cells, the cilia exist in between the cell's apical surface and mucus in a layer known as Airway Surface Liquid (ASL). The flow of ions from the cell and into this layer is determined by ion channels like CFTR. CFTR not only allows Chloride ions to be drawn from the cell and into the ASL, but it also regulates another channel called ENac. ENac allows sodium ions to leave the ASL and enter the respiratory epithelium. CFTR normally inhibits this channel, but if the CFTR is defective, then sodium will flow freely from the ASL and into the cell. As water follows sodium, the depth of ASL will be depleted and the cilia will be left in the mucous layer.[47] As cilia cannot effectively move in a thick viscous environment, there is deficient mucociliary clearance and a buildup of mucous, clogging small airways.[48] The accumulation of more viscous, nutrient-rich mucus in the lungs allows bacteria to hide from the body's immune system, causing repeated respiratory infections. The presence of the same CFTR proteins in pancreatic duct and skin cells are what cause symptoms in these systems.

The lungs of individuals with cystic fibrosis are colonized and infected by bacteria from an early age. These bacteria, which often spread among individuals with CF, thrive in the altered mucus, which collects in the small airways of the lungs. This mucus leads to the formation of bacterial microenvironments known as biofilms that are difficult for immune cells and antibiotics to penetrate. Viscous secretions and persistent respiratory infections repeatedly damage the lung by gradually remodeling the airways, which makes infection even more difficult to eradicate.[49]

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 Haemophilus influenzae colonize and infect the lungs.[18] Eventually, Pseudomonas aeruginosa (and sometimes Burkholderia cepacia) dominates. By 18 years of age, 80% of patients with classic CF harbor P. aeruginosa, and 3.5% harbor B. cepacia.[18] 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.[49]

One way infection spreads is by passing between different individuals with CF.[50] In the past, people with CF often participated in summer "CF Camps" and other recreational gatherings.[51][52] Hospitals grouped patients with CF into common areas and routine equipment (such as nebulizers)[53] was not sterilized between individual patients.[54] This led to transmission of more dangerous strains of bacteria among groups of patients. As a result, individuals with CF are now routinely isolated from one another in the healthcare setting, and healthcare providers are encouraged to wear gowns and gloves when examining patients with CF to limit the spread of virulent bacterial strains.[55]

CF patients may also have their airways chronically colonized by filamentous fungi (such as Aspergillus fumigatus, Scedosporium apiospermum, Aspergillus terreus) and/or yeasts (such as Candida albicans); other filamentous fungi less commonly isolated include Aspergillus flavus and Aspergillus nidulans (occur transiently in CF respiratory secretions) and Exophiala dermatitidis and Scedosporium prolificans (chronic airway-colonizers); some filamentous fungi like Penicillium emersonii and Acrophialophora fusispora are encountered in patients almost exclusively in the context of CF.[56] Defective mucociliary clearance characterizing CF is associated with local immunological disorders. In addition, the prolonged therapy with antibiotics and the use of corticosteroid treatments may also facilitate fungal growth. Although the clinical relevance of the fungal airway colonization is still a matter of debate, filamentous fungi may contribute to the local inflammatory response and therefore to the progressive deterioration of the lung function, as often happens with allergic broncho-pulmonary aspergillosis (ABPA) the most common fungal disease in the context of CF, involving a Th2-driven immune response to Aspergillus.[56][57]

Cystic fibrosis may be diagnosed by many different methods including newborn screening, sweat testing, and genetic testing.[58] 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.[59] Infants with an abnormal newborn screen need a sweat test to confirm the CF diagnosis. In many cases, a parent makes the diagnosis because the infant tastes salty.[18]Trypsinogen levels can be increased in individuals who have a single mutated copy of the CFTR gene (carriers) or, in rare instances, in individuals with two normal copies of the CFTR gene. Due to these false positives, CF screening in newborns can be controversial.[60][61] Most states and countries do not screen for CF routinely at birth. Therefore, most individuals are diagnosed after symptoms (e.g. sinopulmonary disease and GI manifestations[18]) 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 deliver the medication through the skin, iontophoresis is used to, whereby one electrode is placed onto the applied medication and an electric current is passed to a separate electrode on the skin. The resultant 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. In contrast, people with CF have less thiocyanate and hypothiocyanite in their saliva[62] and mucus (Banfi et al.). CF can also be diagnosed by identification of mutations in the CFTR gene.[63]

People with CF may be listed in a disease registry that allows researchers and doctors to track health results and identify candidates for clinical trials.[64]

Couples who are pregnant or planning a pregnancy can have themselves tested for the CFTR gene mutations to determine the risk 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 high, testing on the fetus is performed. The American College of Obstetricians and Gynecologists (ACOG) recommends testing for couples who have a personal or close family history of CF, and they recommend that carrier testing be offered to all Caucasian couples and be made available to couples of other ethnic backgrounds.[65]

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 initially on one parent. If testing shows that parent is a CFTR gene mutation carrier, the other parent is 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 F508most 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.[66]

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;[67] a recent study has indicated this may be much lower, approximately 1 in 1,600.[68]

Economically, for carrier couples of cystic fibrosis, when comparing preimplantation genetic diagnosis (PGD) with natural conception (NC) followed by prenatal testing and abortion of affected pregnancies, PGD provides net economic benefits up to a maternal age of approximately 40 years, after which NC, prenatal testing and abortion has higher economic benefit.[69]

While there are no cures for cystic fibrosis, there are several treatment methods. The management of cystic fibrosis has improved significantly over the past 70 years. While infants born with cystic fibrosis 70 years ago would have been unlikely to live beyond their first year, infants today are likely to live well into adulthood. Recent advances in the treatment of cystic fibrosis have meant that an individual with cystic fibrosis can live a fuller life less encumbered by their condition. The cornerstones of management are proactive treatment of airway infection, and encouragement of good nutrition and an active lifestyle. Pulmonary rehabilitation as a management of cystic fibrosis continues throughout a person's life, and is aimed at maximizing organ function, and therefore quality of life. At best, current treatments delay the decline in organ function. Because of the wide variation in disease symptoms, treatment typically occurs at specialist multidisciplinary centers, and is tailored to the individual. Targets for therapy are the lungs, gastrointestinal tract (including pancreatic enzyme supplements), the reproductive organs (including assisted reproductive technology (ART)) and psychological support.[59]

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.

Many people with CF are on one or more antibiotics at all times, even when healthy, to prophylactically suppress infection. Antibiotics are absolutely necessary whenever pneumonia is suspected or there has been a noticeable decline in lung function, and are usually chosen based on the results of a sputum analysis and the person's past response. This prolonged therapy often necessitates hospitalization and insertion of a more permanent IV such as a peripherally inserted central catheter (PICC line) or Port-a-Cath. Inhaled therapy with antibiotics such as tobramycin, colistin, and aztreonam is often given for months at a time to improve lung function by impeding the growth of colonized bacteria.[70][71][72] Inhaled antibiotic therapy helps lung function by fighting infection, but also has significant drawbacks like development of antibiotic resistance, tinnitus and changes in the voice.[73] Oral antibiotics such as ciprofloxacin or azithromycin are given to help prevent infection or to control ongoing infection.[74] The aminoglycoside antibiotics (e.g. tobramycin) used can cause hearing loss, damage to the balance system in the inner ear or kidney problems with long-term use.[75] To prevent these side-effects, the amount of antibiotics in the blood is routinely measured and adjusted accordingly.

Several 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 and the intrapulmonary percussive ventilator (IPV). Newer methods such as Biphasic Cuirass Ventilation, and associated clearance mode available in such devices, integrate a cough assistance phase, as well as a vibration phase for dislodging secretions. These are portable and adapted for home use.[76]

Ivacaftor is an oral medication for the treatment of cystic fibrosis due to a number of specific mutations.[77][78] It improves lung function by about 10%; however, as of 2014 is expensive.[77]

Aerosolized medications that help loosen secretions include dornase alfa and hypertonic saline.[79] Dornase is a recombinant human deoxyribonuclease, which breaks down DNA in the sputum, thus decreasing its viscosity.[80]Denufosol is an investigational drug that opens an alternative chloride channel, helping to liquefy mucus.[81] It is unclear if inhaled corticosteroids are useful.[82]

As lung disease worsens, mechanical breathing support 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.[83] During severe illness, a tube may be placed in the throat (a procedure known as a tracheostomy) to enable breathing supported by a ventilator.

For children, preliminary studies show massage therapy may help people and their families quality of life.[84] It is unclear what effect pneumococcal vaccination has as it has not been studied as of 2014.[85]

Lung transplantation often becomes necessary for individuals with cystic fibrosis as lung function and exercise tolerance decline. Although single lung transplantation is possible in other diseases, individuals with CF must have both lungs replaced because the remaining lung might 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.[86] Lung transplantation is considered when lung function declines to the point where assistance from mechanical devices is required or someone's survival is threatened.[87]

Newborns with intestinal obstruction 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 feces. However, the best dosage and form of pancreatic enzyme replacement is unclear, as are the risks and long-term effectiveness of this treatment.[88]

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.

Diabetes is the most common non-pulmonary complication of CF. It mixes features of type 1 and type 2 diabetes, and is recognized as a distinct entity, cystic fibrosis-related diabetes (CFRD).[32][89] While oral anti-diabetic drugs are sometimes used, the only recommended treatment is the use of insulin injections or an insulin pump,[90] and, unlike in type 1 and 2 diabetes, dietary restrictions are not recommended.[32]

Development of osteoporosis can be prevented by increased intake of vitamin D and calcium, and can be treated by bisphosphonates, although adverse effects can be an issue.[91] Poor growth may be avoided by insertion of a feeding tube for increasing calories through supplemental feeds or by administration of injected growth hormone.[92]

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, and over time reduce the person's sense of smell. 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.[93]

Female infertility may be overcome by assisted reproduction technology, particularly embryo transfer techniques. Male infertility caused by absence of the vas deferens may be overcome with testicular sperm extraction (TESE), collecting sperm cells directly from the testicles. If the collected sample contains too few sperm cells to likely have a spontaneous fertilization, intracytoplasmic sperm injection can be performed.[94]Third party reproduction is also a possibility for women with CF. It is unclear if taking antioxidants affects outcomes.[95]

The prognosis for cystic fibrosis has improved due to earlier diagnosis through screening, better treatment and access to health care. In 1959, the median age of survival of children with cystic fibrosis in the United States was six months.[96] In 2010, survival is estimated to be 37 years for women and 40 for men.[97] In Canada, median survival increased from 24 years in 1982 to 47.7 in 2007.[98]

Of those with cystic fibrosis who are more than 18 years old as of 2009, 92% had graduated from high school, 67% had at least some college education, 15% were disabled and 9% were unemployed, 56% were single and 39% were married or living with a partner.[99]

Chronic illnesses can be very difficult to manage. Cystic fibrosis (CF) is a chronic illness that affects the "digestive and respiratory tracts resulting in generalized malnutrition and chronic respiratory infections".[100] The thick secretions clog the airways in the lungs, which often cause inflammation and severe lung infections.[101][102] If it is compromised, it affects the quality of life of someone with CF and their ability to complete such tasks as everyday chores. It is important for CF patients to understand the detrimental relationship that chronic illnesses place on the quality of life. According to Schmitz and Goldbeck (2006), the fact that cystic fibrosis significantly increases emotional stress on both the individual and the family, "and the necessary time-consuming daily treatment routine may have further negative effects on quality of life (QOL)".[103] However, Havermans and colleagues (2006) have shown that young outpatients with CF who have participated in the CFQ-R (Cystic Fibrosis Questionnaire-Revised) "rated some QOL domains higher than did their parents".[104] Consequently, outpatients with CF have a more positive outlook for themselves. Furthermore, there are many ways to improve the QOL in CF patients. Exercise is promoted to increase lung function. Integrating an exercise regimen into the CF patients daily routine can significantly improve the quality of life.[105] There is no definitive cure for cystic fibrosis. However, there are diverse medications used, such as mucolytics, bronchodilators, steroids, and antibiotics, that have the purpose of loosening mucus, expanding airways, decreasing inflammation, and fighting lung infections.[106]

Cystic fibrosis is the most common life-limiting autosomal recessive disease among people of European heritage.[108] In the United States, approximately 30,000 individuals have CF; most are diagnosed by six months of age. In Canada, there are approximately 4,000 people with CF.[109] Approximately 1 in 25 people of European descent, and one in 30 of Caucasian Americans,[110] 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.[111][112] Ireland has the world's highest prevalence of cystic fibrosis, at 1:1353.[113]

Although technically a rare disease, cystic fibrosis is ranked as one of the most widespread life-shortening genetic diseases. It is most common among nations in the Western world. An exception is Finland, where only one in 80 people carry a CF mutation.[114] The World Health Organization states that "In the European Union, 1 in 20003000 newborns is found to be affected by CF".[115] In the United States, 1 in 3,500 children are born with CF.[116] 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 32,000.[117]

Cystic fibrosis is diagnosed in males and females equally. For reasons that remain unclear, data has shown that males tend to have a longer life expectancy than females,[118][119] however recent studies suggest this gender gap may no longer exist perhaps due to improvements in health care facilities,[120][121] while a recent study from Ireland identified a link between the female hormone estrogen and worse outcomes in CF.[122]

The distribution of CF alleles varies among populations. The frequency of F508 carriers has been estimated at 1:200 in northern Sweden, 1:143 in Lithuanians, and 1:38 in Denmark. No F508 carriers were found among 171 Finns and 151 Saami people.[123] F508 does occur in Finland, but it is a minority allele there. Cystic fibrosis is known to occur in only 20 families (pedigrees) in Finland.[124]

The F508 mutation is estimated to be up to 52,000 years old.[125] 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:

It is supposed that CF appeared about 3,000 BC because of migration of peoples, gene mutations, and new conditions in nourishment.[134] 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 18th century warned "Wehe dem Kind, das beim Ku auf die Stirn salzig schmekt, er ist verhext und muss bald sterbe" or "Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon must die," recognizing the association between the salt loss in CF and illness.[134]

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.[134] In 1936, Guido Fanconi published a paper describing a connection between celiac disease, cystic fibrosis of the pancreas, and bronchiectasis.[135]

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 was the first to describe the characteristic cystic fibrosis of the pancreas and to correlate it with the lung and intestinal disease prominent in CF.[8] She also first hypothesized that CF was a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952 Paul di SantAgnese discovered abnormalities in sweat electrolytes; a sweat test was developed and improved over the next decade.[136]

The first linkage between CF and another marker (Paroxonase) was found in 1985 by Hans Eiberg, indicating that only one locus exists for CF. In 1988 the first mutation for CF, F508 was discovered by Francis Collins, Lap-Chee Tsui and John R. Riordan on the seventh chromosome. Subsequent research has found over 1,000 different mutations that cause CF.

Because mutations in the CFTR gene are typically small, classical genetics techniques had been unable to accurately pinpoint the mutated gene.[137] 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.[138] In 1989 Lap-Chee Tsui led a team of researchers at the Hospital for Sick Children in Toronto that discovered the gene responsible for CF. Cystic fibrosis represents a classic example of how a human genetic disorder was elucidated strictly by the process of forward genetics.

Gene therapy has been explored as a potential cure for cystic fibrosis. Results from trials have shown limited success as of 2013.[139] A small study published in 2015 found a small benefit.[140]

The focus of much cystic fibrosis gene therapy research is aimed at trying to place a normal copy of the CFTR gene into affected cells. 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. Studies have shown that to prevent the lung manifestations of cystic fibrosis, only 510% the normal amount of CFTR gene expression is needed.[141] Multiple approaches have been tested for gene transfer, such as liposomes and viral vectors in animal models and clinical trials. However, both methods were found to be relatively inefficient treatment options.[142] The main reason is that very few cells take up the vector and express the gene, so the treatment has little effect. Additionally, problems have been noted in cDNA recombination, such that the gene introduced by the treatment is rendered unusable.[143] There has been a functional repair in culture of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients.[144]

A number of small molecules that aim at compensating various mutations of the CFTR gene are under development. One approach is to develop drugs that get the ribosome to overcome the stop codon and synthesize a full-length CFTR protein. About 10% of CF result from a premature stop codon in the DNA, leading to early termination of protein synthesis and truncated proteins. These drugs target nonsense mutations such as G542X, which consists of the amino acid glycine in position 542 being replaced by a stop codon. Aminoglycoside antibiotics interfere with protein synthesis and error-correction. In some cases, they can cause the cell to overcome a premature stop codon by inserting a random amino acid, thereby allowing expression of a full-length protein.[145] The aminoglycoside gentamicin has been used to treat lung cells from CF patients in the laboratory to induce the cells to grow full-length proteins.[146] Another drug targeting nonsense mutations is ataluren, which is undergoing Phase III clinical trials as of October 2011[update].[147]

It is unclear as of 2014 if ursodeoxycholic acid is useful for those with cystic fibrosis-related liver disease.[148]

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In the late 1990s, the CF Foundation established key programs to help speed development of CF therapies, including a national network of centers designed to conduct clinical trials and share data, and a therapeutics development program to support and govern research collaborations with biotech and pharmaceutical companies.

By pursuing these bold strategies and others, the CF Foundation has built a robust pipeline of potential new therapies that fight the disease from every angle. And, nearly every CF drug available today was made possible because of Foundation support -- including therapies to treat the underlying cause of the disease.

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