Editing Cystic fibrosis (section)

==Diagnosis==
[[File:CFTR gene on chromosome 7.svg|thumb|80px|The location of the ''CFTR'' gene on chromosome 7]]

Diagnosis of CF is initially based on clinical findings indicative of respiratory diseases, various digestive problems, meconium ileus, and more. Definitive diagnosis may involve genetic testing based on family history or chloride concentration testing in sweat, which is relatively high (>60mEq/L) in individuals with CF.

In many localities all newborns are screened for cystic fibrosis within the first few days of life, typically by [[Neonatal heel prick|blood test]] for high levels of [[immunoreactive trypsinogen]].<ref name="Cystic Fibrosis Foundation-3">{{cite web|url=https://www.cff.org/intro-cf/newborn-screening-cf |access-date=25 January 2022 |title=Newborn Screening for CF |publisher=Cystic Fibrosis Foundation}}</ref> Newborns with positive tests or those who are otherwise suspected of having cystic fibrosis based on symptoms or family history, then undergo a [[sweat test]]. An [[iontophoresis|electric current]] is used to drive [[pilocarpine]] into the skin, stimulating sweating. The sweat is collected and analyzed for salt levels. Having unusually high levels of chloride in the sweat suggests [[CFTR]] is dysfunctional; the person is then diagnosed with cystic fibrosis.<ref name = "Egan_2020" />{{rp|Diagnosis and Assessment}}{{efn|group=note|The [[Cystic Fibrosis Foundation]] recommends a diagnosis of cystic fibrosis for anyone suspected of cystic fibrosis (positive newborn screen, symptoms of cystic fibrosis, or a family history of cystic fibrosis) with sweat chloride above 60 [[millimole]]s/liter. Those with less than 30 millimoles/liter sweat chloride are unlikely to develop cystic fibrosis. For people with intermediate sweat chloride between 30 and 59 millimoles/liter, they recommend additional genetic testing.<ref name="pmid28129811">{{cite journal | vauthors = Farrell PM, White TB, Ren CL, Hempstead SE, Accurso F, Derichs N, Howenstine M, McColley SA, Rock M, Rosenfeld M, Sermet-Gaudelus I, Southern KW, Marshall BC, Sosnay PR | title = Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation | journal = The Journal of Pediatrics | volume = 181S | issue =  | pages = S4–S15.e1 | date = February 2017 | pmid = 28129811 | doi = 10.1016/j.jpeds.2016.09.064 | hdl-access = free | s2cid = 206410545 | doi-access = free | hdl = 1805/14356 }}</ref>}} Genetic testing is also available to identify the CFTR mutations typically associated with cystic fibrosis. Many laboratories can test for the 30–96 most common CFTR mutations, which can identify over 90% of people with cystic fibrosis.<ref name = "Egan_2020" />{{rp|Diagnosis and Assessment}}

People with CF have less thiocyanate and [[hypothiocyanite]] in their saliva<ref name="MinarowskiSands2008">{{cite journal | vauthors = Minarowski Ł, Sands D, Minarowska A, Karwowska A, Sulewska A, Gacko M, Chyczewska E | title = Thiocyanate concentration in saliva of cystic fibrosis patients | journal = Folia Histochemica et Cytobiologica | volume = 46 | issue = 2 | pages = 245–246 | date = 2008 | pmid = 18519245 | doi = 10.2478/v10042-008-0037-0 | doi-access = free }}</ref> and mucus (Banfi et al.). In the case of milder forms of CF, [[transepithelial potential difference]] measurements can be helpful. CF can also be diagnosed by the identification of mutations in the CFTR gene.<ref name="pmid9017943">{{cite journal | vauthors = Stern RC | title = The diagnosis of cystic fibrosis | journal = The New England Journal of Medicine | volume = 336 | issue = 7 | pages = 487–491 | date = February 1997 | pmid = 9017943 | doi = 10.1056/NEJM199702133360707 }}</ref>

In many cases, a parent makes the diagnosis because the infant tastes salty.<ref name=kumar2007/> Immunoreactive 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 positive]]s, CF screening in newborns can be controversial.<ref name="pmid18718257">{{cite journal | vauthors = Ross LF | title = Newborn screening for cystic fibrosis: a lesson in public health disparities | journal = The Journal of Pediatrics | volume = 153 | issue = 3 | pages = 308–313 | date = September 2008 | pmid = 18718257 | pmc = 2569148 | doi = 10.1016/j.jpeds.2008.04.061 }}</ref><ref name="pmid12196308">{{cite journal | vauthors = Assael BM, Castellani C, Ocampo MB, Iansa P, Callegaro A, Valsecchi MG | title = Epidemiology and survival analysis of cystic fibrosis in an area of intense neonatal screening over 30 years | journal = American Journal of Epidemiology | volume = 156 | issue = 5 | pages = 397–401 | date = September 2002 | pmid = 12196308 | doi = 10.1093/aje/kwf064 | doi-access = free }}</ref>

By 2010 every US state had instituted newborn screening programs<ref name="pmid30259702">{{cite journal | vauthors = Hoch H, Sontag MK, Scarbro S, Juarez-Colunga E, McLean C, Kempe A, Sagel SD | title = Clinical outcomes in U.S. infants with cystic fibrosis from 2001 to 2012 | journal = Pediatric Pulmonology | volume = 53 | issue = 11 | pages = 1492–1497 | date = November 2018 | pmid = 30259702 | doi = 10.1002/ppul.24165 | s2cid = 52845580 }}</ref> and {{as of|2016|lc=y}} 21 European countries had programs in at least some regions.<ref name = "Barben">{{cite journal | vauthors = Barben J, Castellani C, Dankert-Roelse J, Gartner S, Kashirskaya N, Linnane B, Mayell S, Munck A, Sands D, Sommerburg O, Pybus S, Winters V, Southern KW | title = The expansion and performance of national newborn screening programmes for cystic fibrosis in Europe | journal = Journal of Cystic Fibrosis | volume = 16 | issue = 2 | pages = 207–213 | date = March 2017 | pmid = 28043799 | doi = 10.1016/j.jcf.2016.12.012 | doi-access = free }}</ref>

===Prenatal===
Women who are [[pregnant]] or couples planning a pregnancy can have themselves tested for the ''CFTR'' gene mutations to determine the risk that their child will be born with CF. 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]] recommends all people thinking of becoming pregnant be tested to see if they are a carrier.<ref name="American College of Obstetricians and Gynecologists-2017">{{cite web|url=https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/03/carrier-screening-in-the-age-of-genomic-medicine |number=690 |title=Carrier Screening in the Age of Genomic Medicine|date=2017|website=American College of Obstetricians and Gynecologists|url-status=live|archive-url=https://web.archive.org/web/20170225052721/http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Genetics/Carrier-Screening-in-the-Age-of-Genomic-Medicine|archive-date=25 February 2017|access-date=22 February 2020}}</ref>

Because the 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 the 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.<ref name="Lancet2016">{{cite journal | vauthors = Elborn JS | title = Cystic fibrosis | journal = Lancet | volume = 388 | issue = 10059 | pages = 2519–2531 | date = November 2016 | pmid = 27140670 | doi = 10.1016/S0140-6736(16)00576-6 | s2cid = 20948144 }}</ref> {{as of|2016}}, typically only the most common mutations are tested for, such as ΔF508.<ref name=Lancet2016/> Most commercially available tests look for 32 or fewer different mutations. If a family has a known uncommon mutation, specific screening for that mutation can be performed. Because not all known mutations are found on current tests, a negative screen does not guarantee that a child will not have CF.<ref name="pmid2014829">{{cite journal | vauthors = Elias S, Annas GJ, Simpson JL | title = Carrier screening for cystic fibrosis: implications for obstetric and gynecologic practice | journal = American Journal of Obstetrics and Gynecology | volume = 164 | issue = 4 | pages = 1077–1083 | date = April 1991 | pmid = 2014829 | doi = 10.1016/0002-9378(91)90589-j }}</ref>

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 one in 100 and amniocentesis of one in 200;<ref name="pmid2423826">{{cite journal | vauthors = Tabor A, Philip J, Madsen M, Bang J, Obel EB, Nørgaard-Pedersen B | title = Randomised controlled trial of genetic amniocentesis in 4606 low-risk women | journal = Lancet | volume = 1 | issue = 8493 | pages = 1287–1293 | date = June 1986 | pmid = 2423826 | doi = 10.1016/S0140-6736(86)91218-3 | s2cid = 31237495 }}</ref> a recent study has indicated this may be much lower, about one in 1,600.<ref name="pmid17077226">{{cite journal | vauthors = Eddleman KA, Malone FD, Sullivan L, Dukes K, Berkowitz RL, Kharbutli Y, Porter TF, Luthy DA, Comstock CH, Saade GR, Klugman S, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, D'Alton ME | title = Pregnancy loss rates after midtrimester amniocentesis | journal = Obstetrics and Gynecology | volume = 108 | issue = 5 | pages = 1067–1072 | date = November 2006 | pmid = 17077226 | doi = 10.1097/01.AOG.0000240135.13594.07 | s2cid = 19081825 }}</ref>

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 around 40 years, after which NC, prenatal testing, and abortion have a higher economic benefit.<ref name="pmid19439290">{{cite journal | vauthors = Davis LB, Champion SJ, Fair SO, Baker VL, Garber AM | title = A cost-benefit analysis of preimplantation genetic diagnosis for carrier couples of cystic fibrosis | journal = Fertility and Sterility | volume = 93 | issue = 6 | pages = 1793–1804 | date = April 2010 | pmid = 19439290 | doi = 10.1016/j.fertnstert.2008.12.053 | doi-access = free }}</ref>