Cystic Fibrosis

&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212- Introduction Cystic fibrosis( in addition calledcf.ormucoviscidosis) is anautosomalrecessivebrokertic turnoverthat affects or so critically thelungs, and to a fault thepancreas, acknowledger, andin examine. It is characterized by perverted transport ofchlorideand atomic number 11a baffle anepithelium, leading to thick, pastelike secretions. The namerefers to the characteristicscarring(fibrosis) andcystformation within thepancreas that was root accepted in the 1930s.Difficulty in breathingis the most serious symptom and runs from buy atlung infectionswhich atomic number 18 treated withantibiotics, therapies and several(prenominal) early(a) medications. almost former(a)wisesymptoms, includingsinus infections, pathetic-down growing, and asepsis affect other parts of the body. A breathing interposition for cystic fibrosis, using a mask nebulizer and a ThAIRapy Vest A breathing treatwork for cet for cystic fibrosis, using a mask nebulizer and a ThAIRapy Vest cfis bring ond by a noveltyin the factorfor theproteincystic fibrosis trans-membrane conductance regulator( cfR).This protein is required to regulate the comp ints of exploit,digestivejuices, andmucus. CFTR regulates the movement ofchlorideandsodium ions a soft touch epithelial membranes, oft(prenominal)(prenominal) as the alveolar epithelia located in thelungs. Although most pack without CF hand devil working copies of the CFTR cistron, just wiz is needed to go on cystic fibrosis collectable to the disorders recessive nature. CF dumb installs when neither divisor works ordinarily (as a number of variance) and thusly hasautosomal recessiveinheritance.CF is most everyday amongCaucasians one in 25 stack of European descentcarries oneallelefor CF. The globe Health Organizationstates that In the European Union, 1 in 20003000 new-innate(p)s is entrap to be affected by CF. Individuals with cystic fi brosis butt be diagnosed before birth by patrimonial examen or by a movement testin early childhood. Ultimately,lung transplantationis truly much necessary as CF worsens. &8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212- Signs and symptomsThe hallmark symptoms of cystic fibrosis atomic number 18 zesty tasting skin,poor growth and poor weight gain contempt a convening food intake,accumulation of thick, sticky mucus, frequent developncy infections, and cough outing or shortness of breath. Signs and symptoms lots appear in early childhood and childhood, much(prenominal) asbowel movement obstructionin new-born babies. As the children grow, they must exercise to release the mucus present in the alveoli. ciliatedepithelial cellphoneular telephones presentin the patient baffle a mutated protein that leads to kinkyly viscous mucus production.The poor growth in children typically presents as an in mogul to gain weight or height at the ali ke(p) rate as their peers and is occasionally non diagnosed until investigation is initiated for poor growth. The ca physical exercises of growth failure ar multifactorial and allow chronic lung infection, poor immersion of nutrients by the gastroenteric tract, and increase metabolic demand referable to chronic illness. In r be cases, cystic fibrosis keister manifest itself as a coagulation disorder. A double recessive allele is needed for cystic fibrosis to be app arnt.Young children ar especially sensitive to vitaminmalabsorptive disorders beca utilisation sole(prenominal) a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves. Be courtship factors II, VII, IX, and X (clotting factors) atomic number 18 vitamin Kdependent, low levels of vitamin K domiciliate take in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation military rating whitethorn be warranted to determine whether thith er is an underlying un healthiness. Lungs and sinuses Lung disease results from clogging of the airways due to mucus build-up, decreasedmucociliary head, and resulting firing.Inflammation and infection cause crack and structural changes to the lungs, leading to a variety of symptoms. In the early stages, symmetrical incessant coughing along with copiousphlegmproduction, and decreased ability to exercise be earthy. Many of these symptoms occur whenbacteria that normally live the thick mucus grow out of chair and cause pneumonia. In later stages, changes in the architecture of the lung, such as pathology in the major(ip) airways (bronchiectasis), move on exacerbate heavyies in breathing.Other symptoms include coughing up declivity (hemoptysis), highblood insistencyin the lung (pulmonary hypertension),heart failure, difficulties getting liberaltype O to the body (hypoxia), and respiratory failure requiring support with breathing masks, such asbi-level positive airway pre ssuremachines orventilators. Staphylococcus aureus, Haemophilus influenzae, andgenus Pseudomonas aeruginosa ar the three most harsh organisms causing lung infections in CF patients. In addition to typical bacterial infections, community with CF much plebeianly develop other events of lung disease.Among these isallergic bronchopulmonary aspergillosis, in which the bodys response to the commonfungusgenus Aspergillus fumigatuscauses worsening of breathing problems. A nonher is infection with Mycobacterium avium interlinking (MAC), a group of bacteria related totuberculosis, which can cause a lot of lung disparage and does not respond to common antibiotics. Mucus in theparanasal sinusesis equally thick and whitethorn similarly cause law of closure of the sinus passages, leading to infection. This whitethorn cause facial pain, fever, nasal drainage, andheadaches.Individuals with CF may develop overgrowth of the nasal tissue (nasal polyps) due to inflammation from chronic sinu s infections. Recurrent sinonasal polyps can occur in as many as 10% to 25% of CF patients. These polyps can cube the nasal passages and increase breathing difficulties. Cardiorespiratory complications are the most common cause of death (80%) in patients at most CF centers in the unify States. Gastrointestinal Prior to prenatal and new-sprung(a) essaying, cystic fibrosis was often diagnosed when a new-sprung(a) infant failed to pass feces (meconium).Meconium may completely auction block theintestinesand cause serious illness. This condition, calledmeconium ileus, occurs in 510%of newborns with CF. In addition, protrusion of internalrectalmembranes (rectal prolapse) is more common, occurring in as many as 10% of children with CF, and it is caused by increased faecal volume, mal support, andpressure due to coughing. The thick mucus seen in the lungs has a love seat in inspissate secretions from thepancreas, an organ responsible for providing digestivethat helper appal down food.These secretions block theexocrinemovement of the digestive enzymes into theduodenum and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis). Thepancreatic ductsare totally plugged in more advanced cases, usually seen in older children or adolescents. This causes atrophy of the exocrine glands and progressive tense fibrosis. The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the feces, a disorder cognise as malabsorption. Malabsorption leads tomalnutritionand poor growth and evelopment because of calorie loss. Resultant hypoproteinemiamay be severe enough to cause generalized edema. Individuals with CF in like manner have difficulties absorbing the fat-soluble vitaminsA,D,E, andK. In addition to the pancreas problems, pile with cystic fibrosis have moreheartburn, intestinal blockage byintussusception, and constipation. Older individuals with CF may developdistal intestinal obst ruction syndromewhen pachydermatous feces cause intestinal blockage. Exocrine pancreatic insufficiency occurs in the majority (85% to 90%) of patients with CF.It is principal(prenominal)ly associated with severe CFTR renewings, where twain alleles are completely non run foral (e. g. ?F508/? F508). 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. In these milder cases, there is still sufficient pancreatic exocrine function so that enzyme supplementation is not required. on that point are usually no other GI complications in pancreas-sufficient pheno character references, and in general, such individuals usually have excellent growth and development.Despite this, idiopathicchronic pancreatitiscan occur in a subset of pancreas-sufficient individuals with CF, and is associated with recurrent abdominal pain and austere complications. Thickened secretions too may cause liver problems in patients with CF. Bilesecreted by the liver to aid in digestion may block thebile ducts, leading to liver damage. everywhere time, this can lead to scarring and nodularity (cirrhosis). The liver fails to rid the blood of toxins and does not make pregnantproteins, such as those responsible forblood clotting. Liver disease is the third most common cause of death associated with cystic fibrosis.Endocrine Clubbing in the fingers of a soul with cystic fibrosis Clubbing in the fingers of a person with cystic fibrosis Thepancreas acquits theislets of Langerhans, which are responsible for making insulin, a hormone that helps regulate bloodglucose. detriment of the pancreas can lead to loss of the isletcells, leading to a type of diabetes that is unique to those with the disease. This cystic fibrosis-related diabetes(CFRD) shares characteristics that can be found intype 1andtype 2diabetics, and is one of the principal non-pulmonary complications of CF.Vitamin D is involved incalciumandphosphateregulation. Poor uptake of vitamin D from the diet because of malabsorption can lead to the bone diseaseosteoporosisin which weakened bones are more susceptible tofractures. In addition, people with CF often develop clubbingof their fingers and toes due to the effects of chronic illness andlow oxygenin their tissues. In fertility rate Infertilityaffects both men and women. At least 97% of men with cystic fibrosis are infertile, but not infertile and can have children with assisted reproductive techniques.The main cause of infertility in men with cystic fibrosis is congenital absence seizure of the vas deferens(which normally connects thetestesto theejaculatory ductsof thepenis), but electromotive forcely also by other mechanisms such as causingazoo spermatozoan cell cellia,teratospermiaandoligoas pastospermia. Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF. Some women have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disruptsovulationand causesamenorrhea. &8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212 Cause CF is caused by amutationin thegenecystic fibrosis trans-membrane conductance regulator(CFTR). The most common mutation,? F508, is a deletion (? signifying deletion) of three nucleotidesthat results in a loss of the amino acidphenylalanine(F) at the 508th position on the protein. This mutation accounts for two-thirds (6670%) of CF cases worldwide and 90% of cases in theUnited States however, there are over 1500 other mutations that can produce CF.Although most people have two working copies (alleles) of the CFTR gene, only one is needed to endure cystic fibrosis. CF develops when neither allele can produce a functional CFTR protein. Thus, CF is con locatingred anautosomal recessive disease. TheCFTR gene, found at the q31. 2 venueofchromo some 7, is 230,000base pairslong, and creates a protein that is 1,480amino acidslong. More particularizedally the muddle is between base pair 117,120,016 to 117,308,718 on the long arm of chromosome 7, constituent 3, band 1 and sub-band 2, represented as 7q31. . Structurally, CFTR is a type of gene cognize as anABC gene. The product of this gene (the CFTR) is a chloride ion communicate important in creating sweat,digestivejuices andmucus. This protein possesses twoATP-hydrolyzingdomains, which drop by the waysides the protein to useenergyin the form ofATP. It also contains two domains comprising 6alpha helicesapiece, which allow the protein to cross the cell membrane. A regulatorybinding siteon the protein allows energizing byphosphorylation, mainly bycAMP-dependent protein kinase.Thecarboxyl terminalof the protein is anchored to thecytoskeletonby aPDZdomain interaction. In addition, there is increasing evidence that patrimonial modifiers in any case CFTR modulate the frequenc y and severity of the disease. unitary example ismannan-binding lectin, which is involved ininnate immunityby facilitatingphagocytosisof microorganisms. Polymorphisms in one or both mannan-binding lectin alleles that result in lower circulating levels of the protein are associated with a threefold high essay of end-stage lung disease, as well as an increased load of chronic bacterial infections. &8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212 Pathophysiology Molecular structure of the CFTR protein Molecular structure of the CFTR protein There are several mutations in theCFTRgene, and different mutations cause different fractures 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 notfoldnormally and is degraded by the cell.Other mutations result in proteins that are too short ( cut) becauseproductionis ended untimelyly. Other mutations produce proteins that do not use energy normally, do not allowchloride iodideandthiocyanateto cross the membrane appropriately,or are degraded at a faster rate than normal. Mutations may also lead to less copies of the CFTR protein being produced. The protein created by this gene is anchored to theouter membrane ofcellsin thesweat glands, lungs, pancreas, and all other remaining exocrine glands in the body.The protein spans this membrane and acts as a stemmaconnecting the inner part of the cell (cytoplasm) to thesurrounding peregrine. 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 into the cytoplasm. When the CFTR protein does not work, chloride and thiocyanateare pin down inside the cells in the airway and outside in the skin. Thenhypothio cyanite, OSCN, cannot be produced by immune defense form.Because chloride isnegatively charged, this creates a difference in the galvanisingal potential inside and outside the cell causingcationsto cross into the cell. Sodium is the most common cation in the extracellular space and the cabal of sodium and chloride creates the saltiness, which is incapacitated in high amounts in the sweat of individuals with CF. This lost salt forms the basis for the sweat test. 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. One theory is that the lack of halogen and pseudohalogen (mainly, chloride, iodide and thiocyanate) exiting by means of the CFTR prote in leads to the accumulation of more viscous, nutrient-rich mucus in the lungs that allows bacteria to hide from the bodysimmune system.Another theory is 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 is that abnormal chloride movementoutof the cell leads to dehydration of mucus, pancreatic secretions, biliary secretions, etc. Chronic infections 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 remode ling the airways, which makes infection even more difficult to eradicate. Over time, both the types of bacteria and their individual characteristics change in individuals with CF. In the initial stage, common bacteria such asStaphylococcus aureusandHemophilus influenzaecolonize and infect the lungs.Eventually,Pseudomonas aeruginosa(and sometimesBurkholderia cepacia) dominates. By 18 years of age, 80% of patients with classic cystic fibrosis obligatePseudomonas aeruginosa, and another 3. 5% harbor Burkholderia cepacia. Once within the lungs, these bacteria adapt to the environment and develop opponentto commonly used antibiotics. Pseudomonascan develop special characteristics that allow the formation of large colonies, known as mucoidPseudomonas, which are exaltedly seen in people that do not have CF. One way infection spreads is by passing between different individuals with CF.In the past, people with CF often participated in summer CF Camps and other recreational gatherings. Ho spitals grouped patients with CF into common areas and routine equipment (such asnebulizers)was not sterilized between individual patients. 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 promote to wear gowns and gloves when examining patients with CF to limit the spread of virulent bacterial strains.CF patients may also have their airways chronically colonized by threadlike fungus kingdom (such asAspergillus fumigatus,Scedosporium apiospermum,Aspergillus terreus) and/or yeasts (such asCandida albicans) other threadlike kingdom Fungi less commonly isolated include Aspergillus flavusandAspergillus nidulans(occur transiently in CF respiratory secretions), andExophiala dermatitidisand Scedosporium prolificans(chronic airway-colonizers) some filamentous fungi likePenicillium emersoniiandAcrophialophora fusisporaare encountered in patients almost exclusively in the linguistic context of CF.Defective mucociliary clearance characterizing CF is associated with local immunological disorders. In addition, the prolonged therapy with antibiotics and the use of corticosteroid discourses 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 ost common fungal disease in the context of CF, involving a Th2-driven immune response to Aspergillus. &8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212- diagnosing and monitoring CFTR gene on chromosome 7 CFTR gene on chromosome 7 Cystic fibrosis may be diagnosed by many different methods includingnewborn screening,sweat testing, and genetic testin g. As of 2006 in the United States, 10 portion of cases are diagnosed shortly after birth as part of newborn screening programs.The newborn screen initially measures for raised blood constriction of immunoreactive trypsinogen. Infants with an abnormal newborn screen need a sweat test to confirm the CF diagnosis. In many cases, a leaven makes the diagnosis because the infant tastes salty. Trypsinogenlevels can be increased in individuals who have a single mutated copy of theCFTRgene ( immune carriers) or, in rare instances, in individuals with two normal copies of theCFTRgene. Due to thesefalse positives, CF screening in newborns can be controversial.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) 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 stim ulates sweating (pilocarpine). To deliver the medication through the skin, iontophoresisis used to, whereby oneelectrodeis placed onto the applied medication and an electric currentis 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 ofsodiumandchloride. People with CF have increased amounts of sodium and chloride in their sweat. In contrast, people with CF have less thiocyanate andhypothiocyanitein their saliva and mucus. CF can also be diagnosed by identification of mutations in the CFTR gene. People with CF may be listed in adisease registrythat allows researchers and doctors to track health results and identify candidates forclinical trials. PrenatalCouples who are pregnant or planning a pregnancy can have themselves well-tried for the CFTR gene mutations to determine the risk that their child will be born with cystic fibrosis. Testing is typically performed inaugural on one or both adverts and, if the risk of CF is high, testing on thefetusis performed. TheAmerican 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.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 bet 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 assertable 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 mut ation, 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. During pregnancy, testing can be performed on theplacenta(chorionic villus sampling) or the fluid around the fetus (amniocentesis). However,chorionic villus samplinghas a risk of fetal death of 1 in 100 and amniocentesis of 1 in 200a new culture has indicated this may be much lower, round 1 in 1,600.Economically, for carrier couples of cystic fibrosis, when comparing pre-implantation genetic diagnosis (PGD) with natural conception (NC) followed by prenatal testing and stillbirth of affected pregnancies, PGD provides net economic benefits up to a maternal age of somewhat 40 years, after which NC, prenatal testing and abortion has higher economic benefit. &8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212- Management While there are no cures for cystic fibrosis th ere are several treatment methods. The steering of cystic fibrosis has amend 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 manner less encumbered by their condition. The cornerstones of management are proactive treatment ofairway infection, and encouragement of good nutrition and an active lifestyle. Management of cystic fibrosis continues throughout a patients life, and is leaseed at maximizing organ function, and therefore quality of life.At best, current treatments delay the pooh-pooh 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 thelungs,gastrointestinal tract(including pancreatic enzyme supplements), thereproductive organs(including (ART) and psychological support. The most consistent aspect of therapy in cystic fibrosis is limiting and treating the lung damage caused by thick mucus and infection. Intravenous,inhaled, and viva 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 for the patient. One of the most important battles that CF patients nervus is decision the time to comply with prescribed treatments while balancing a normal life. In addition, therapies such astransplantationandgene therapyaim to cure some of the effects of cystic fibrosis. Gene therapy aims to introduce normal CFTR to airway. Theoretically this butt against should be simple as the airway is good accessible and there is only a single gene defect to correct.There are two CFTR gene introduc tion mechanisms involved, the first use of a viral vector (adenovirus, adeno-associated virus or retro virus) and secondly the use ofliposome. However there are some problems associated with these methods involving efficiency (liposomes insufficient protein) and slant (virus provokes an immune response). Antibiotics Many CF patients are on one or moreantibioticsat all times, even when healthy, toprophylacticallysuppress infection. Antibiotics are short 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 putum analysis and the patients past response. This prolonged therapy often necessitates hospitalization and insertion of a more permanentIVsuch as aperipherally inserted central catheter(PICC line) orPort-a-Cath. Inhaled therapy with antibiotics such as tobramycin,colistin, andaztreonamis often give for months at a time to reform lung function by hindering the growth of colonized bac teria. Oral antibiotics such as ciprofloxacin orazithromycinare given to help prevent infection or to control ongoing infection. Theaminoglycosideantibiotics (e. g. obramycin) with long-term use can causeseveral side effects such as hearing loss, damaging thebalance systempresent in theinner earand producing many chronic kidney problems. To prevent theseside-effects, the amount of antibiotics in the blood are routinely measured and set accordingly. Other treatments for lung disease Several mechanical techniques are used to unfreeze sputum and encourage its expectoration. In the hospital setting, chest physiotherapy (CPT) is employ a respiratory therapist percusses an individuals chest with his or her hands several times a day, to ride up secretions.Devices that recreate this percussive therapy include theThAIRapy Vestand theintrapulmonary percussive ventilator(IPV). Newer methods such asBiphasic Cuirass Ventilation, and associated clearance mode available in such devices, integr ate a cough avail stagecoach, as well as a vibration phase for dislodging secretions. These are portable and adapted for home use. Aerosolized medications that help loosen secretions includedornase alfaandhypertonicsaline. Dornase is arecombinanthuman deoxyribonuclease, which breaks down DNA in thesputum, thus decreasing itsviscosity.Denufosolis an investigational drug that opens an alternative chloride channel, helping to liquefy mucus. 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 asbi-level 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. During severe illness, atubemay be placed in the throat (a map known as atracheostomy) to enable breathing supported by aventilator.For children living with CF, preliminary s tudies show pediatric massage therapy may improve patients and their families quality of life, though more rigorous studies must be done. Transplantation Lung transplantationoften becomes necessary for individuals with cystic fibrosis as lung function ceases andexercise tolerancedeclines. 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 excuse liver disease and/or diabetes. Lung transplantation is considered when lung function declines to the point where assistance from mechanical devices is required or patient natural selection is threatened. Other aspects Intracytoplasmic sperm injection can be used to provide fertility for men with cystic. .fibrosis Intracytoplasmic sperm injection can be used to provide fertility for men with cystic. .fibrosis New-borns with intestinal obstruction typically require functioning, whereas adults withdistal intestinal obstruction syndrome typically do not.Treatment of pancreatic insufficiency by surrogate of missing digestive enzymes allows the duodenum to properly absorb nutrients and vitamins that would otherwise be lost in the faeces. So far, no large-scale research involving the incidence of coronary artery diseaseandcoronary heart diseasein 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.Diabetesis the most common non-pulmonary complication of CF. It mixes features oftype 1andtype 2diabetes, and is recognized as a apparent entity,cystic fibrosis-related diabetes (CFRD). While oralanti-diabetic drugsare sometimes used, the only recommended treatment is the use ofinsulininjections or aninsulin pump,and u nlike in type 1 and 2 diabetes, dietary restrictions are not recommended. Development ofosteoporosiscan be prevented by increased intake of vitamin D andcalcium, and can be treated bybisphosphonates, althoughadverse effectscan be an issue.Poor growth may be avoided by insertion of afeeding tubefor increasingcaloriesthrough supplemental feeds or by administration of injectedgrowth hormone. 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 patients sense of smell. Sinus surgery is often used to alleviate nasal obstruction and to limit further infections. Nasal steroids such asfluticasoneare used to decrease nasal inflammation.Female infertility may be overcome byassisted trainingtechnology (ART) with the help of embryo transfertechniques. Male infertility caused by absence of thevas deferensmay be overcome withtestic ular sperm extraction(TEST), collecting sperm cells directly from the testicles. If the collected sample contains too few sperm cells to likely have a spontaneousfertilization,intracytoplasmic sperm injectioncan be performed. Third party reproductionis also a possibility for women with CF. &8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212- PrognosisThe 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. In 2008, survival averaged 37. 4 years. In Canada, median survival increased from 24 years in 1982 to 47. 7 in 2007. Of those with cystic fibrosis who are more than 18 years old as of 2009 92% had graduated fromhigh 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.In Ru ssiathe overall median age of patients is 25, which is caused by the absence or high cost of medication and the fact that lung transplantation is not performed. Quality of life 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. The thick secretions clog the airways in the lungs, which often cause inflammation and severe lung infections. Therefore, mucus makes it challenging to breathe.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. Havermans and colleagues (2006) have shown that young outpatients with CF that have participated in the CFQ-R (Cystic Fibrosis Questionnaire-Revised) rated some QOL domains higher t han did their parents. Consequently, outpatients with CF have a more positive scout for themselves.Furthermore, there are many ways to improve the QOL in CF patients. Exercise is promoted to increase lung function. The fact of integrating an exercise regimen into the CF patients daily routine can significantly improve the quality of life. 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 easiness mucus, expanding airways, decreasing inflammation and fighting lung infections. &8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212-Epidemiology Mutation Frequency worldwide ?F508 66%70% G542X 2. 4% G551D 1. 6% N1303K 1. 3% W1282X 1. 2% All others 27. 5% Cystic fibrosis is the most common life-limiting autosomal recessive disease among people ofCaucasian heritage. In the United States, approximately 30,000 individuals have CF most are diagnosed by six months of age. InCanada, there are approximately 3,500 people with CF. Approximately 1 in 25 people of European descent, and one in 30 of Caucasian Americans, is a carrier of a cystic fibrosis mutation.Although CF is less common in these groups, approximately 1 in 46Hispanics, 1 in 65Africansand 1 in 90 Asianscarry at least one abnormal CFTR gene. Ireland has the worlds highest incidence of cystic fibrosis, at 11353. Although technically arare 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 isFinland, where only one in 80 people carry a CF mutation. In the United States, 1 in 4,000 children are born with CF. In 1997, almost 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. Cystic fibrosis is diagnosed in males and females equally. For reasons that remain unclear, data has shown that males tend to have a longerlife expectancythan females,however recent studies propose this gender gap may no longer exist perchance due to improvements in health care facilities,while a recent study from Ireland identified a link between the female hormone, estrogen and worse outcomes in CF.The distribution of CF alleles varies among populations. The frequency of ? F508 carriers has been estimated at 1200 in northern Sweden, 1143 in Lithuanians, and 138 in Denmark. No ? F508 carriers were found among 171Finnsand 151Saami people. ?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. Hypotheses about prevalence The? F508mutation is estimated to be up to 52,000 years old. 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 assickle-cell anemia have been found to protect carriers from other diseases, a concept known asheterozygote advantage. Resistances to the succeeding(a) have all been proposed as possible sources of heterozygote advantage * Cholera With the finding and discovery thatcholera toxinrequires normal host CFTR proteins to function properly, it was hypothesized that carriers of pas seul CFTR genes benefited from resistor to cholera and other causes of diarrhea. Further studies have not confirmed this hypothesis. typhoid fever Normal CFTR proteins are also required essentially for the entry ofSalmonella typhiinto cells,suggesting that carriers of the mutant CFTR genes might be resistant totyphoid fever. Noin vivostudy has yet confirmed this. In both cases, the low level of cystic fibrosis outside of Europe, in places where both cholera and typhoid fever areendemic, is not immediately explicable. * Diarrhea It has also been hypoth esized that the prevalence of CF in Europe might be connected with the development of cattle domestication. In this hypothesis, carriers of a ingle mutant CFTR chromosome had some protection from diarrhea caused by lactose intolerance, prior to the appearance of the mutations that created lactose tolerance. * Tuberculosis Another explanation is that carriers of the gene could have some resistance to TB. &8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212- History It is supposed that CF appeared about 3,000 BC because of migration of peoples, gene mutations, and new conditions in nourishment. Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects of CF were identified much earlier.Indeed, booksfrom Germany and Switzerland in the 18th century warnedWehe dem Kind, das beim Ku? auf die Stirn salzig schmekt, er ist verhext und pile bald sterbeor Woe to the child who tastes salty from a kiss on the brow, for he is cur sed and soon must die, recognizing the association between the salt loss in CF and illness. Dorothy Hansine Andersen Dorothy Hansine Andersen In the 19th century,Carl von Rokitansky draw and quarterd a case of fetal death withmeconium peritonitis, a complication of meconium ileus associated with cystic fibrosis.Meconium ileus was first described in 1905 byKarl Landsteiner. In 1936,Guido Fanconi make a paper describing a connecting link betweenceliac disease, cystic fibrosis of the pancreas, and bronchiectasis. In 1938Dorothy Hansine Andersenpublished an article, Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease a Clinical and Pathological Study, in theAmerican 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.She also first hypothesized that CF was a recessive disease and first used pancreatic enzyme replacement to treat affected c hildren. In 1952 capital of Minnesota di Sant Agnese discovered abnormalities insweatelectrolytes asweat testwas genuine and improved over the next decade. The first linkage between CF and another marker (Paroxonase) was found in 1985, indicating that only one locus exists for CFHans Eiberg. In 1988 the first mutation for CF,? F508was discovered byFrancis Collins,Lap-Chee Tsuiand illusion R. Riordanon 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 genetic sciencetechniques had been unable to accurately pinpoint the mutated gene. Using protein markers,gene-linkagestudies were able to map the mutation to chromosome 7. Chromosome-walking and-jumpingtechniques were then used to identify andsequencethe gene. In 1989 Lap-Chee Tsui led a team of researchers at the Hospital for Sick ChildreninTorontothat discovered the gene responsible for CF.Cystic fibrosis represents the f irst genetic disorder elucidated strictly by the process ofreverse genetics. &8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212&8212- Research Gene therapy Gene therapyhas been explored as a potential cure for cystic fibrosis. Ideally, gene therapy places a normal copy of theCFTR 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 CFTRgene let outionis needed. 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. The main reason is that very few cells take up the vector and deport the gene, so the treatment has little effect. Add itionally, problems have been noted in cDNA recombination, such that the gene introduced by the treatment is rendered unusable.With the help of theCystic Fibrosis Trust, which has a league of highly professional gene therapists, both somatic and Adeno-associated viral vector have made advances. TheAdenoviridae, or more commonly known as the cold virus, is genetically altered, allowing the CFTR gene to enter lung cells. Small molecules A number ofsmall moleculesthat aim at compensating various mutations of the CFTR gene are under development. One approach is to develop drugs that get the ribosome to overcome thestop codonand synthesize a full-length CFTR protein.About 10% of CF results from a premature stop codon in the DNA, leading to early termination of protein synthesis and truncated proteins. These drugs target hokum mutationssuch as G542X, which consists of the amino acidgenus Glycinein position 542 being replaced by a stop codon. Aminoglycoside antibiotics intercede with DNA synthesis and error-correction. In some cases, they can cause the cell to overcome the stop codon, insert a random amino acid, and express a full-length protein.The aminoglycosidegentamicinhas been used to treat lung cells from CF patients in the laboratory to induce the cells to grow full-length proteins. Another drug targeting nonsense mutations isataluren, which is undergoing Phase III clinical trials as of October 2011. BIBLIOGRAPHY 1. BIOLOGY TEXTBOOK FOR carve up XII (NCERT) 2. TRUEMANS BIOLOGY FOR CLASS XII 3. SCIENCE newsperson (September, 2007) 4. THE NEWYORK TIMES (December 22, 2009) 5. www. google. co. in/cysticfibrosis 6. en. wikipedia. org/wiki/Cystic_fibrosis 7. www. ncbi. nlm. nih. gov 8. www. cff. org/ 9. www. cysticfibrosis. com/ 10. www. cftrust. org. uk/