Content deleted Content added
Citation bot (talk | contribs) Removed parameters. | Use this bot. Report bugs. | Suggested by Jay8g | Category:CS1 maint: PMC embargo expired | #UCB_Category 2/2 |
|||
Line 1:
{{Short description|Genetic disorder affecting mostly the lungs}}
{{Use dmy dates|date=December 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox medical condition (new)
| name = '''Cystic fibrosis'''
| image = File:Cysticfibrosis01.jpg
| alt =
| field = [[Medical genetics]], [[pulmonology]]
| synonyms = Mucoviscidosis
| symptoms = [[Shortness of breath|Difficulty breathing]], coughing up [[sputum|mucus]], [[failure to thrive|poor growth]], [[Steatorrhea|fatty stool]]<ref name=O2009/>
| complications =
| onset = Symptoms recognizable ~6 months<ref name="Allen-2016">{{cite book | vauthors = Allen JL, Panitch HB, Rubenstein RC |title=Cystic Fibrosis|date=2016|publisher=CRC Press|isbn=9781439801826|page=92|url=https://books.google.com/books?id=xmbMBQAAQBAJ&pg=PA92|language=en|url-status=live|archive-url=https://web.archive.org/web/20170908140759/https://books.google.com/books?id=xmbMBQAAQBAJ&pg=PA92|archive-date=8 September 2017}}</ref>
| duration = Long term<ref name=Mas2013/>
| causes = Genetic ([[autosomal recessive]])<ref name=O2009/>
| risks = Genetic
| diagnosis = [[Sweat test]], [[genetic testing]]<ref name=O2009/>
| differential =
| prevention =
| treatment = [[Physiotherapy]], [[antibiotics]], [[pancreatic enzyme replacement]], [[cystic fibrosis transmembrane conductance regulator]] modulators, [[lung transplantation]]<ref name="pmid34090606">{{cite journal | vauthors = Shteinberg M, Haq IJ, Polineni D, Davies JC | title = Cystic fibrosis | journal = Lancet | volume = 397 | issue = 10290 | pages = 2195–2211 | date = June 2021 | pmid = 34090606 | doi = 10.1016/s0140-6736(20)32542-3 | s2cid = 235327978 }}</ref>
| medication =
| prognosis = Life expectancy between 42 and 50 years (developed world)<ref name=Ong2015/>
| frequency = {{Plainlist|
* 1 out of 3,000 ([[Northern European]])<ref name=O2009/>
* 1 out of 30 in the United States is a carrier{{Citation needed|date=April 2025}}
}}
| deaths = 40 percent of the population is affected
}}
'''Cystic fibrosis''' ('''CF''') is a [[genetic disorder]] inherited in an [[autosomal recessive]] manner that impairs the normal clearance of [[Sputum|mucus]] from the [[lungs]], which facilitates the colonization and infection of the lungs by bacteria, notably ''[[Staphylococcus aureus]]''.<ref name="pmid37211214">{{cite journal | vauthors = Xu X, Zhang X, Zhang G, Abbasi Tadi D | title = Prevalence of antibiotic resistance of Staphylococcus aureus in cystic fibrosis infection: a systematic review and meta-analysis | journal = Journal of Global Antimicrobial Resistance | volume = 36 | issue = | pages = 419–425 | date = March 2024 | pmid = 37211214 | doi = 10.1016/j.jgar.2023.05.006 | doi-access = free }}</ref> CF is a rare<ref name="Sencen">{{Cite web | vauthors = Sencen L |title=Cystic Fibrosis |url=https://rarediseases.org/rare-diseases/cystic-fibrosis/ |access-date=29 July 2022 |website=NORD (National Organization for Rare Disorders) |language=en-US}}</ref><ref name="www.orpha.net">{{Cite web |title=Orphanet: Cystic fibrosis |url=https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=586 |access-date=29 July 2022 |website=www.orpha.net |language=en}}</ref> genetic disorder that affects mostly the lungs, but also the [[pancreas]], [[liver]], [[kidney]]s, and [[intestine]].<ref name=O2009/><ref name=CF2012/> The hallmark feature of CF is the accumulation of thick mucus in different organs. Long-term issues include [[Shortness of breath|difficulty breathing]] and coughing up mucus as a result of frequent [[pneumonia|lung infections]].<ref name=O2009/> Other signs and [[symptom]]s may include [[Sinusitis|sinus infections]], [[failure to thrive|poor growth]], [[Steatorrhea|fatty stool]], [[Nail clubbing|clubbing]] of the fingers and toes, and [[infertility]] in most males.<ref name=O2009/> Different people may have different degrees of symptoms.<ref name=O2009/>
Cystic fibrosis is inherited in an [[autosomal recessive]] manner.<ref name=O2009/> It is caused by the presence of mutations in both copies (alleles) of the [[gene]] encoding the [[cystic fibrosis transmembrane conductance regulator]] (CFTR) protein.<ref name=O2009/> Those with a single working copy are carriers and otherwise mostly healthy.<ref name="Mas2013">{{cite journal | vauthors = Massie J, Delatycki MB | title = Cystic fibrosis carrier screening | journal = Paediatric Respiratory Reviews | volume = 14 | issue = 4 | pages = 270–275 | date = December 2013 | pmid = 23466339 | doi = 10.1016/j.prrv.2012.12.002 }}</ref> CFTR is involved in the production of sweat, [[digestion|digestive]] fluids, and mucus.<ref name="Buckingham-2012">{{cite book|url=https://books.google.com/books?id=1cTZAAAAQBAJ&pg=PA351|title=Molecular Diagnostics: Fundamentals, Methods and Clinical Applications|vauthors=Buckingham L|publisher=F.A. Davis Co.|year=2012|isbn=978-0-8036-2975-2|edition=2nd|___location=Philadelphia|pages=351|archive-url=https://web.archive.org/web/20170908140759/https://books.google.com/books?id=1cTZAAAAQBAJ&pg=PA351|archive-date=8 September 2017|url-status=live}}</ref> When the CFTR is not functional, secretions that are usually thin instead become thick.<ref name="pmid14734689">{{cite journal | vauthors = Yankaskas JR, Marshall BC, Sufian B, Simon RH, Rodman D | title = Cystic fibrosis adult care: consensus conference report | journal = Chest | volume = 125 | issue = 1 Suppl | pages = 1S–39S | date = January 2004 | pmid = 14734689 | doi = 10.1378/chest.125.1_suppl.1S | citeseerx = 10.1.1.562.1904 }}</ref> The condition is diagnosed by a [[sweat test]] and [[genetic testing]].<ref name=O2009/> The sweat test measures sodium concentration, as people with cystic fibrosis have abnormally salty sweat, which can often be tasted by parents kissing their children. Screening of infants at birth takes place in some areas of the world.<ref name=O2009/>
There is no known cure for cystic fibrosis.<ref name=Mas2013/> Lung infections are treated with [[antibiotics]] which may be given intravenously, inhaled, or by mouth.<ref name=O2009/> Sometimes, the antibiotic [[azithromycin]] is used long-term.<ref name=O2009/> Inhaled [[hypertonic saline]] and [[salbutamol]] may also be useful.<ref name=O2009/> [[Lung transplantation]] may be an option if lung function continues to worsen.<ref name=O2009/> [[Pancreatic enzyme replacement]] and [[fat-soluble vitamin]] supplementation are important, especially in the young.<ref name=O2009/> [[Airway clearance technique]]s such as [[chest physiotherapy]] may have some short-term benefit, but long-term effects are unclear.<ref name="pmid37042825">{{cite journal | vauthors = Warnock L, Gates A | title = Airway clearance techniques compared to no airway clearance techniques for cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 4 | pages = CD001401 | date = April 2023 | pmid = 37042825 | pmc = 10091803 | doi = 10.1002/14651858.CD001401.pub4 }}</ref> The average life expectancy is between 42 and 50 years in the [[developed world]],<ref name="Ong2015">{{cite journal | vauthors = Ong T, Ramsey BW | title = Update in Cystic Fibrosis 2014 | journal = American Journal of Respiratory and Critical Care Medicine | volume = 192 | issue = 6 | pages = 669–675 | date = September 2015 | pmid = 26371812 | doi = 10.1164/rccm.201504-0656UP }}</ref><ref name="pmid24115706">{{cite journal | vauthors = Nazareth D, Walshaw M | title = Coming of age in cystic fibrosis - transition from paediatric to adult care | journal = Clinical Medicine | volume = 13 | issue = 5 | pages = 482–486 | date = October 2013 | pmid = 24115706 | pmc = 4953800 | doi = 10.7861/clinmedicine.13-5-482 }}</ref> with a median of 40.7 years,<ref name="pmid28944141">{{cite journal | vauthors = Agrawal A, Agarwal A, Mehta D, Sikachi RR, Du D, Wang J | title = Nationwide trends of hospitalizations for cystic fibrosis in the United States from 2003 to 2013 | journal = Intractable & Rare Diseases Research | volume = 6 | issue = 3 | pages = 191–198 | date = August 2017 | pmid = 28944141 | pmc = 5608929 | doi = 10.5582/irdr.2017.01043 }}</ref> although improving treatments have contributed to a more optimistic recent assessment of the median in the United States as 59 years.<ref>{{Cite web |last=Cystic Fibrosis Foundation |date=September 2021 |title=Patient Registry 2020 Annual Data Report |url=https://www.cff.org/sites/default/files/2021-10/2019-Patient-Registry-Annual-Data-Report.pdf |access-date=26 September 2024 |website=www.cff.org/}}</ref> Lung problems are responsible for death in 70% of people with cystic fibrosis.<ref name=O2009/>
CF is most common among people of [[Northern European]] ancestry, for whom it affects about 1 out of 3,000 newborns,<ref name=O2009/> and among which around 1 out of 25 people is a carrier.<ref name=Mas2013/> It is least common in Africans and Asians, though it does occur in all [[Cystic fibrosis and race|races]].<ref name="O2009">{{cite journal | vauthors = O'Sullivan BP, Freedman SD | title = Cystic fibrosis | journal = Lancet | volume = 373 | issue = 9678 | pages = 1891–1904 | date = May 2009 | pmid = 19403164 | doi = 10.1016/s0140-6736(09)60327-5 | s2cid = 46011502 }}</ref> 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.<ref name="CF2012">{{cite book|url=https://books.google.com/books?id=9x_cBQAAQBAJ&pg=PA3|title=Cystic Fibrosis|publisher=Hodder Arnold|year=2012|isbn=978-1-4441-1369-3|veditors=Hodson M, Geddes D, Bush A|edition=3rd|___location=London|pages=3|archive-url=https://web.archive.org/web/20170908140759/https://books.google.com/books?id=9x_cBQAAQBAJ&pg=PA3|archive-date=8 September 2017|url-status=live}}</ref> The name "cystic fibrosis" refers to the characteristic [[fibrosis]] and [[cyst]]s that form within the [[pancreas]].<ref name=CF2012/><ref name="andersen">{{cite journal|vauthors=Andersen DH|year=1938|title=Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathological study|journal=[[American Journal of Diseases of Children|Am. J. Dis. Child.]]|volume=56|issue=2|pages=344–99|doi=10.1001/archpedi.1938.01980140114013}}</ref>
[[File:En.Wikipedia-VideoWiki-Cystic fibrosis.webm|thumb|thumbtime=1:08|upright=1.4|Video summary ([[Wikipedia:VideoWiki/Cystic fibrosis|script]])]]
==
[[File:Blausen 0286 CysticFibrosis.png|thumb|upright=1.3|Health problems associated with cystic fibrosis]]
Cystic fibrosis typically manifests early in life. Newborns and infants with cystic fibrosis tend to have frequent, large, greasy [[Human feces|stools]] (a result of [[malabsorption]]) and are [[Failure to thrive|underweight for their age]].<ref name = "Egan_2020">{{cite book|vauthors=Egan ME, Schechter MS, Voynow JA |chapter=Cystic Fibrosis |title=Nelson Textbook of Pediatrics |pages=2282–2297 |veditors=Kliegman RM, St Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM |isbn=978-0-323-56890-6 |publisher=Elsevier |date=2020}}</ref>{{rp|Clinical Manifestations}} Of newborns, 15–20% have their [[small intestine]] blocked by [[meconium]], often requiring surgery to correct.<ref name = "Egan_2020" />{{rp|Clinical Manifestations}} Newborns occasionally have [[neonatal jaundice]] due to blockage of the [[bile duct]]s.<ref name = "Egan_2020" />{{rp|Clinical Manifestations}} Children with cystic fibrosis lose excessive salt in their sweat, and parents often notice salt crystallizing on the skin, or a salty taste when they kiss their child.<ref name = "Egan_2020" />{{rp|Clinical Manifestations}}
The primary cause of [[morbidity]] and death in people with cystic fibrosis is progressive lung disease, which eventually leads to [[respiratory failure]].<ref name = "Egan_2020" />{{rp|Respiratory Tract}} This typically begins as a prolonged respiratory infection that continues until treated with [[antibiotic]]s.<ref name = "Egan_2020" />{{rp|Respiratory Tract}} Chronic infection of the respiratory tract is nearly universal in people with cystic fibrosis, with ''[[Pseudomonas aeruginosa]]'', fungi, and [[mycobacteria]] all becoming increasingly common over time.<ref name=Shteinberg2021>{{cite journal | vauthors = Shteinberg M, Haq IJ, Polineni D, Davies JC | title = Cystic fibrosis | journal = Lancet | volume = 397 | issue = 10290 | pages = 2195–2211 | date = June 2021 | pmid = 34090606 | doi = 10.1016/S0140-6736(20)32542-3 | s2cid = 235327978 }}</ref> Inflammation of the upper airway results in frequent [[Rhinorrhea|runny nose]] and [[Nasal congestion|nasal obstruction]]. [[Nasal polyp]]s are common, particularly in children and teenagers.<ref name = "Egan_2020" />{{rp|Respiratory Tract}} As the disease progresses, people tend to have [[shortness of breath]], and a chronic cough that produces [[sputum]].<ref name = "Egan_2020" />{{rp|Biliary Tract}} Breathing problems make it increasingly challenging to exercise, and prolonged illness causes those affected to be underweight for their age.<ref name = "Egan_2020" />{{rp|Biliary Tract}} In late adolescence or adulthood, people begin to develop severe signs of lung disease: wheezing, [[digital clubbing]], [[cyanosis]], [[Hemoptysis|coughing up blood]], [[pulmonary heart disease]], and collapsed lung ([[atelectasis]] or [[pneumothorax]]).<ref name = "Egan_2020" />{{rp|Respiratory Tract}}
In rare cases, cystic fibrosis can manifest itself as a [[Coagulopathy|coagulation disorder]]. [[Vitamin K]] is normally absorbed from [[breast milk]], formula, and later, solid foods. This absorption is impaired in some CF 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 clotting factors II, VII, IX, and X are vitamin K–dependent, 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 an underlying disease is present.<ref name="Reaves-2010">{{cite journal|vauthors=Reaves J, Wallace G|date=2010|title=Unexplained bruising: weighing the pros and cons of possible causes|url=https://www.pediatricsconsultantlive.com/vitamin-d-insufficiency/unexplained-bruising-weighing-pros-and-cons-possible-causes|journal=Consultant for Pediatricians|volume=9|pages=201–2|access-date=22 February 2020|archive-date=22 February 2020|archive-url=https://web.archive.org/web/20200222200803/https://www.pediatricsconsultantlive.com/vitamin-d-insufficiency/unexplained-bruising-weighing-pros-and-cons-possible-causes|url-status=dead}}</ref>
===Lungs and sinuses===
[[File:Cystic Fibrosis Respiratory Infections by Age.svg|thumb|upright=1.3|Respiratory infections in CF vary according to age.<br><br>Green = ''[[Pseudomonas aeruginosa]]''<br>Brown = ''[[Staphylococcus aureus]]''<br>Blue = ''[[Haemophilus influenzae]]''<br>Red = ''[[Burkholderia cepacia]]'' complex]]
Lung disease results from clogging of the airways due to mucus build-up, decreased [[mucociliary clearance]], and resulting [[inflammation]].<ref name="pmid20299528">{{cite journal | vauthors = Flume PA, Mogayzel PJ, Robinson KA, Rosenblatt RL, Quittell L, Marshall BC | title = Cystic fibrosis pulmonary guidelines: pulmonary complications: hemoptysis and pneumothorax | journal = American Journal of Respiratory and Critical Care Medicine | volume = 182 | issue = 3 | pages = 298–306 | date = August 2010 | pmid = 20675678 | doi = 10.1164/rccm.201002-0157OC }}</ref><ref name="kumar2007">{{cite book|title=Robbins Basic Pathology |url=https://books.google.com/books?id=-keXQ6LaXVIC |vauthors=Mitchell RS, Kumar V, Robbins SL, Abbas AK, Fausto N|publisher=Saunders/Elsevier|year=2007|isbn=978-1-4160-2973-1 |page=[https://books.google.com/books?id=-keXQ6LaXVIC&pg=PT1253 1253], [https://books.google.com/books?id=-keXQ6LaXVIC&pg=PT1254 1254] }}</ref> 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 high [[blood pressure]] in the lung ([[pulmonary hypertension]]), [[heart failure]], difficulties getting enough [[oxygen]] to the body ([[Hypoxia (medical)|hypoxia]]), and respiratory failure requiring support with breathing masks, such as [[bilevel positive airway pressure]] machines or [[Mechanical ventilation|ventilators]].<ref name="Rowe" /> ''[[Staphylococcus aureus]]'', ''[[Haemophilus influenzae]]'', and ''[[Pseudomonas aeruginosa]]'' are the three most common organisms causing lung infections in CF patients.<ref name=kumar2007/>{{rp|1254}} In addition, opportunistic infection due to [[Burkholderia cepacia complex|''Burkholderia cepacia'' complex]] can occur, especially through transmission from patient to patient.<ref name="pmid14726455">{{cite journal | vauthors = Saiman L, Siegel J | title = Infection control in cystic fibrosis | journal = Clinical Microbiology Reviews | volume = 17 | issue = 1 | pages = 57–71 | date = January 2004 | pmid = 14726455 | pmc = 321464 | doi = 10.1128/CMR.17.1.57-71.2004 | doi-access = free }}</ref>
In addition to typical bacterial infections, people with CF more commonly develop other types of lung diseases. 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|Mycobacterium avium]]'' complex, a group of bacteria related to [[tuberculosis]], which can cause lung damage and do not respond to common antibiotics.<ref name="pmid16266669">{{cite journal | vauthors = Girón RM, Domingo D, Buendía B, Antón E, Ruiz-Velasco LM, Ancochea J | title = [Nontuberculous mycobacteria in patients with cystic fibrosis] | language = es | journal = Archivos de Bronconeumologia | volume = 41 | issue = 10 | pages = 560–565 | date = October 2005 | pmid = 16266669 | doi = 10.1016/S1579-2129(06)60283-8 }}</ref>
The mucus in the [[paranasal sinus]]es is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and [[headache]]s. Individuals with CF may develop overgrowth of the nasal tissue ([[nasal polyp]]s) due to inflammation from chronic sinus infections.<ref name="pmid20209279">{{cite journal | vauthors = Franco LP, Camargos PA, Becker HM, Guimarães RE | title = Nasal endoscopic evaluation of children and adolescents with cystic fibrosis | journal = Brazilian Journal of Otorhinolaryngology | volume = 75 | issue = 6 | pages = 806–813 | date = 2009 | pmid = 20209279 | pmc = 9446041 | doi = 10.1590/S1808-86942009000600006 | doi-access = free }}</ref> Recurrent sinonasal polyps can occur in 10% to 25% of CF patients.<ref name=kumar2007/>{{rp|1254}} These polyps can block the nasal passages and increase breathing difficulties.<ref name="pmid15626248">{{cite journal | vauthors = Maldonado M, Martínez A, Alobid I, Mullol J | title = The antrochoanal polyp | journal = Rhinology | volume = 42 | issue = 4 | pages = 178–182 | date = December 2004 | pmid = 15626248 }}</ref><ref name="pmid1527348">{{cite journal | vauthors = Ramsey B, Richardson MA | title = Impact of sinusitis in cystic fibrosis | journal = The Journal of Allergy and Clinical Immunology | volume = 90 | issue = 3 Pt 2 | pages = 547–552 | date = September 1992 | pmid = 1527348 | doi = 10.1016/0091-6749(92)90183-3 | doi-access = free }}</ref>
Cardiorespiratory complications are the most common causes of death (about 80%) in patients at most CF centers in the United States.<ref name=kumar2007/>{{rp|1254}}
===Gastrointestinal===
Digestive problems are also prevalent in individuals with CF. Approximately 15%-20% of newborns diagnosed with CF experience intestinal blockage ([[meconium ileus]]), and other digestive issues may arise due to mucus accumulation in the pancreas.<ref name="pmid31353045">{{cite journal | vauthors = Padoan R, Cirilli N, Falchetti D, Cesana BM | title = Risk factors for adverse outcome in infancy in meconium ileus cystic fibrosis infants: A multicentre Italian study | journal = Journal of Cystic Fibrosis | volume = 18 | issue = 6 | pages = 863–868 | date = November 2019 | pmid = 31353045 | doi = 10.1016/j.jcf.2019.07.003 | doi-access = free }}</ref> Consequently, there is impaired insulin production, leading to cystic fibrosis-related diabetes mellitus. Moreover, enzyme transport disruption from the pancreas to the intestines results in digestive problems such as recurrent diarrhea or weight loss.<ref name="pmid16131979">{{cite journal | vauthors = Borowitz D, Durie PR, Clarke LL, Werlin SL, Taylor CJ, Semler J, De Lisle RC, Lewindon P, Lichtman SM, Sinaasappel M, Baker RD, Baker SS, Verkade HJ, Lowe ME, Stallings VA, Janghorbani M, Butler R, Heubi J | title = Gastrointestinal outcomes and confounders in cystic fibrosis | journal = Journal of Pediatric Gastroenterology and Nutrition | volume = 41 | issue = 3 | pages = 273–285 | date = September 2005 | pmid = 16131979 | doi = 10.1097/01.mpg.0000178439.64675.8d | doi-access = free }}</ref>
In cystic fibrosis, there is impaired chloride secretion due to the mutation of CFTR. This disrupts the ionic balance, causes impaired bicarbonate secretion, and alters the pH. The pancreatic enzymes that work in a specific pH range cannot act as the chyme is not neutralized by bicarbonate ions. This causes impairment of the digestion process.<ref name="Silbernagl-2015">{{Cite book | vauthors = Silbernagl S |title=Color Atlas of Physiology , Physiology |publisher=Thieme Publishing Group |year=2015 |isbn=978-3135450070 |edition=7th |publication-date=13 May 2015 |pages=260–61 |language=}}</ref>
The thick mucus seen in the lungs has a counterpart in thickened secretions from the [[pancreas]], an organ responsible for providing [[Pancreatic juice|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]]).<ref name="pmid9725922">{{cite journal | vauthors = Cohn JA, Friedman KJ, Noone PG, Knowles MR, Silverman LM, Jowell PS | title = Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis | journal = The New England Journal of Medicine | volume = 339 | issue = 10 | pages = 653–658 | date = September 1998 | pmid = 9725922 | doi = 10.1056/NEJM199809033391002 | doi-access = free }}</ref> The [[pancreatic duct]]s are totally plugged in more advanced cases, usually seen in older children or adolescents.<ref name=kumar2007/> This causes atrophy of the exocrine glands and progressive fibrosis.<ref name=kumar2007/>
In addition, protrusion of internal [[rectum|rectal]] membranes ([[rectal prolapse]]) is more common, occurring in as many as 10% of children with CF,<ref name="kumar2007" /> and it is caused by increased fecal volume, [[malnutrition]], and [[Valsalva maneuver|increased intra–abdominal pressure]] due to coughing.<ref name="pmid13578072">{{cite journal | vauthors = Kulczycki LL, Shwachman H | title = Studies in cystic fibrosis of the pancreas; occurrence of rectal prolapse | journal = The New England Journal of Medicine | volume = 259 | issue = 9 | pages = 409–412 | date = August 1958 | pmid = 13578072 | doi = 10.1056/NEJM195808282590901 }}</ref>
Individuals with CF also have difficulties absorbing the fat-soluble vitamins [[vitamin A|A]], [[vitamin D|D]], [[vitamin E|E]], and [[vitamin K|K]].<ref name="Assis2016"/>
In addition to the pancreas problems, people with CF experience more [[gastroesophageal reflux disease|heartburn]],<ref name="Assis2016"/> intestinal blockage by [[Intussusception (medical disorder)|intussusception]], and [[constipation]].<ref name="pmid1755649">{{cite journal | vauthors = Malfroot A, Dab I | title = New insights on gastro-oesophageal reflux in cystic fibrosis by longitudinal follow up | journal = Archives of Disease in Childhood | volume = 66 | issue = 11 | pages = 1339–1345 | date = November 1991 | pmid = 1755649 | pmc = 1793275 | doi = 10.1136/adc.66.11.1339 }}</ref> Older individuals with CF may develop [[distal intestinal obstruction syndrome]], which occurs when feces becomes thick with mucus ([[inspissated]]) and can cause bloating, pain, and incomplete or complete bowel obstruction.<ref name="pmid34936085">{{cite journal | vauthors = Carroll W, Green J, Gilchrist FJ | title = Interventions for preventing distal intestinal obstruction syndrome (DIOS) in cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 12 | pages = CD012619 | date = December 2021 | pmid = 34936085 | pmc = 8693853 | doi = 10.1002/14651858.CD012619.pub3 }}</ref><ref name="Assis2016">{{cite journal | vauthors = Assis DN, Freedman SD | title = Gastrointestinal Disorders in Cystic Fibrosis | journal = Clinics in Chest Medicine | volume = 37 | issue = 1 | pages = 109–118 | date = March 2016 | pmid = 26857772 | doi = 10.1016/j.ccm.2015.11.004 | type = Review }}</ref>
[[Exocrine pancreatic insufficiency]] occurs in the majority (85–90%) of patients with CF.<ref name=kumar2007/>{{rp|1253}} It is mainly associated with "severe" CFTR mutations, where both alleles are completely nonfunctional (e.g. [[ΔF508]]/ΔF508).<ref name=kumar2007/>{{rp|1253}} It occurs in 10–15% of patients with one "severe" and one "mild" CFTR mutation where little CFTR activity still occurs, or where two "mild" CFTR mutations exist.<ref name=kumar2007/>{{rp|1253}} In these milder cases, a sufficient pancreatic exocrine function is still present so enzyme supplementation is not required.<ref name=kumar2007/>{{rp|1253}} Usually, no other GI complications occur in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development.<ref name=kumar2007/>{{rp|1254}} 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.<ref name=kumar2007/>
Liver diseases are another common complication in CF patients. The prevalence in studies ranged from 18% at age two to 41% at age 12, with no significant increase thereafter.<ref name="pmid15582124">{{cite journal | vauthors = Lamireau T, Monnereau S, Martin S, Marcotte JE, Winnock M, Alvarez F | title = Epidemiology of liver disease in cystic fibrosis: a longitudinal study | journal = Journal of Hepatology | volume = 41 | issue = 6 | pages = 920–925 | date = December 2004 | pmid = 15582124 | doi = 10.1016/j.jhep.2004.08.006 }}</ref> Another study found that males with CF are more prone to liver diseases compared to females, and those with meconium ileus have an increased risk of liver diseases.<ref name="pmid12447862">{{cite journal | vauthors = Colombo C, Battezzati PM, Crosignani A, Morabito A, Costantini D, Padoan R, Giunta A | title = Liver disease in cystic fibrosis: A prospective study on incidence, risk factors, and outcome | journal = Hepatology | volume = 36 | issue = 6 | pages = 1374–1382 | date = December 2002 | pmid = 12447862 | doi = 10.1002/hep.1840360613 | doi-access = free }}</ref>
Thickened secretions also may cause liver problems in patients with CF. [[Bile]] secreted by the liver to aid in digestion may block the [[bile duct]]s, leading to liver damage. Impaired digestion or absorption of lipids can result in [[steatorrhea]]. 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 [[coagulation|blood clotting]].<ref name="pmid1458306">{{cite journal | vauthors = Williams SG, Westaby D, Tanner MS, Mowat AP | title = Liver and biliary problems in cystic fibrosis | journal = British Medical Bulletin | volume = 48 | issue = 4 | pages = 877–892 | date = October 1992 | pmid = 1458306 | doi = 10.1093/oxfordjournals.bmb.a072583 }}</ref><ref name="liver">{{cite journal | vauthors = Colombo C, Russo MC, Zazzeron L, Romano G | title = Liver disease in cystic fibrosis | journal = Journal of Pediatric Gastroenterology and Nutrition | volume = 43 | issue = Suppl 1 | pages = S49–S55 | date = July 2006 | pmid = 16819402 | doi = 10.1097/01.mpg.0000226390.02355.52 | s2cid = 27836468 | doi-access = free }}</ref> Liver disease is the third-most common cause of death associated with CF.<ref name="kumar2007" />
Around 5–7% of people experience [[biliary cirrhosis|liver damage]] severe enough to cause symptoms: typically [[gallstone]]s causing [[biliary colic]].<ref name = "Egan_2020" />{{rp|Biliary Tract}}
===Endocrine===
The pancreas contains the [[islets of Langerhans]], which are responsible for making [[insulin]], a hormone that helps regulate blood [[glucose]]. Damage to the pancreas can lead to loss of the islet cells, leading to a type of diabetes unique to those with the disease.<ref name="pmid8039595">{{cite journal | vauthors = Moran A, Pyzdrowski KL, Weinreb J, Kahn BB, Smith SA, Adams KS, Seaquist ER | title = Insulin sensitivity in cystic fibrosis | journal = Diabetes | volume = 43 | issue = 8 | pages = 1020–1026 | date = August 1994 | pmid = 8039595 | doi = 10.2337/diabetes.43.8.1020 }}</ref> This [[cystic fibrosis-related diabetes]] shares characteristics of [[Diabetes mellitus type 1|type 1]] and [[Diabetes mellitus type 2|type 2]] diabetes, and is one of the principal nonpulmonary complications of CF.<ref name="Alves"/>
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 [[bone fracture|fracture]]s.<ref name="pmid10525552">{{cite journal | vauthors = Haworth CS, Selby PL, Webb AK, Dodd ME, Musson H, McL Niven R, Economou G, Horrocks AW, Freemont AJ, Mawer EB, Adams JE | title = Low bone mineral density in adults with cystic fibrosis | journal = Thorax | volume = 54 | issue = 11 | pages = 961–967 | date = November 1999 | pmid = 10525552 | pmc = 1745400 | doi = 10.1136/thx.54.11.961 }}</ref>
===Infertility===
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.<ref name="pmid11035677">{{cite journal | vauthors = McCallum TJ, Milunsky JM, Cunningham DL, Harris DH, Maher TA, Oates RD | title = Fertility in men with cystic fibrosis: an update on current surgical practices and outcomes | journal = Chest | volume = 118 | issue = 4 | pages = 1059–1062 | date = October 2000 | pmid = 11035677 | doi = 10.1378/chest.118.4.1059 }}</ref> The main cause of infertility in men with cystic fibrosis is [[congenital absence of the vas deferens]] (which normally connects the [[Testicle|testes]] to the [[ejaculatory duct]]s of the [[Human penis|penis]]), but potentially also by other mechanisms causing [[azoospermia|no sperm]], [[teratospermia|abnormally shaped sperm]], and [[oligoasthenospermia|few sperm with poor motility]].<ref name="pmid22709980">{{cite journal | vauthors = Chen H, Ruan YC, Xu WM, Chen J, Chan HC | title = Regulation of male fertility by CFTR and implications in male infertility | journal = Human Reproduction Update | volume = 18 | issue = 6 | pages = 703–713 | date = 2012 | pmid = 22709980 | doi = 10.1093/humupd/dms027 | doi-access = free }}</ref> Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF.<ref name="pmid7968122">{{cite journal | vauthors = Augarten A, Yahav Y, Kerem BS, Halle D, Laufer J, Szeinberg A, Dor J, Mashiach S, Gazit E, Madgar I | title = Congenital bilateral absence of vas deferens in the absence of cystic fibrosis | journal = Lancet | volume = 344 | issue = 8935 | pages = 1473–1474 | date = November 1994 | pmid = 7968122 | doi = 10.1016/S0140-6736(94)90292-5 | s2cid = 28860665 }}</ref> While females with CF are generally fertile, around 20% of women with CF have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts [[ovulation]] and causes [[amenorrhoea|a lack of menstruation]].<ref name="pmid10893364">{{cite journal | vauthors = Gilljam M, Antoniou M, Shin J, Dupuis A, Corey M, Tullis DE | title = Pregnancy in cystic fibrosis. Fetal and maternal outcome | journal = Chest | volume = 118 | issue = 1 | pages = 85–91 | date = July 2000 | pmid = 10893364 | doi = 10.1378/chest.118.1.85 | s2cid = 32289370 }}</ref>
==Causes==
[[File:autorecessive.svg|thumb|upright=1.3|Cystic fibrosis has an autosomal recessive pattern of inheritance.]]
CF is caused by having no functional copies (alleles) of the [[gene]] [[CFTR (gene)|cystic fibrosis transmembrane conductance regulator]] (''CFTR''). As of 2018, over 1,900 mutations leading to CF have been described, but only 5 of them have a frequency greater than 1% among patients. The most common mutant allele, [[ΔF508]] (also termed F508del), is a deletion ([[delta (letter)#Mathematics and the Sciences|Δ]] signifying deletion) of three nucleotides that results in a loss of the amino-acid residue [[phenylalanine]] (F) at the 508th position of the protein.<ref name="pmid28881097">{{cite journal | vauthors = Guimbellot J, Sharma J, Rowe SM | title = Toward inclusive therapy with CFTR modulators: Progress and challenges | journal = Pediatric Pulmonology | volume = 52 | issue = S48 | pages = S4–S14 | date = November 2017 | pmid = 28881097 | pmc = 6208153 | doi = 10.1002/ppul.23773 }}</ref><ref name="pmid32512483">{{cite journal | vauthors = Sharma J, Keeling KM, Rowe SM | title = Pharmacological approaches for targeting cystic fibrosis nonsense mutations | journal = European Journal of Medicinal Chemistry | volume = 200 | article-number = 112436 | date = August 2020 | pmid = 32512483 | pmc = 7384597 | doi = 10.1016/j.ejmech.2020.112436 }}</ref> This mutant allele is already present in 1 in 20 to 25 people of Northern European ancestry; it accounts for 70% of CF cases worldwide and 90% of cases in the [[United States]]; however, over 700 other mutant alleles, some of which represent new mutations, can produce CF.<ref name="prevalence">[http://www.cftr2.org/mutations_history 'CFTR2 Variant List History']</ref> 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 disorder#Dominant and recessive genetic diseases in humans|autosomal recessive disease]].<ref name="Lancet2016" />
The ''CFTR'' gene, found at the q31.2 [[locus (genetics)|locus]] of [[chromosome 7]], is 230,000 [[base pair]]s long, and encodes a protein that is 1,480 [[amino acid]]s long. More specifically, the ___location is between base pair 117,120,016 and 117,308,718 on the long arm of chromosome 7, region 3, band 1, subband 2, represented as 7q31.2. Structurally, the ''CFTR'' is a type of gene known as an [[ATP-binding cassette transporter genes|ABC gene]]. The product of this gene (the CFTR protein) is a chloride ion channel important in creating sweat, digestive juices, and mucus. This protein possesses two [[ATP hydrolysis|ATP-hydrolyzing]] [[Structural ___domain|domains]], which allows the protein to use energy in the form of [[Adenosine triphosphate|ATP]]. It also contains two domains comprising six [[Alpha helix|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]].<ref name="Rowe" /> The [[C-terminal end|carboxyl terminal]] of the protein is anchored to the [[cytoskeleton]] by a [[PDZ (biology)|PDZ]] ___domain interaction.<ref name="pmid9677412">{{cite journal | vauthors = Short DB, Trotter KW, Reczek D, Kreda SM, Bretscher A, Boucher RC, Stutts MJ, Milgram SL | title = An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton | journal = The Journal of Biological Chemistry | volume = 273 | issue = 31 | pages = 19797–19801 | date = July 1998 | pmid = 9677412 | doi = 10.1074/jbc.273.31.19797 | doi-access = free }}</ref> Most CFTR in lung passages is produced by rare ion-transporting cells that regulate mucus properties.<ref name="pmid30097657">{{cite journal | vauthors = Travaglini KJ, Krasnow MA | title = Profile of an unknown airway cell | journal = Nature | volume = 560 | issue = 7718 | pages = 313–314 | date = August 2018 | pmid = 30097657 | doi = 10.1038/d41586-018-05813-7 | doi-access = free | bibcode = 2018Natur.560..313T }}</ref>
In addition, the evidence is increasing 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. [[Polymorphism (biology)|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.<ref name=kumar2007/>
===Carriers===
Up to one in 25 individuals of Northern European ancestry is considered a [[genetic carrier]].<ref name="Edwards" /> The disease appears only when two of these carriers have children, as each pregnancy between them has a 25% chance of producing a child with the disease. Although only about one of every 3,000 newborns of the affected ancestry has CF, since the CFTR gene's discovery in 1989, over 2,000 variants have been identified, but only about 700 of these have been recognized as responsible for causing CF.<ref name="pmid37699417">{{cite journal | vauthors = Graeber SY, Mall MA | title = The future of cystic fibrosis treatment: from disease mechanisms to novel therapeutic approaches | journal = Lancet | volume = 402 | issue = 10408 | pages = 1185–1198 | date = September 2023 | pmid = 37699417 | doi = 10.1016/s0140-6736(23)01608-2 | s2cid = 261623275 }}</ref> Current tests look for the most common mutations.<ref name="Edwards">{{cite journal | vauthors = Edwards QT, Seibert D, Macri C, Covington C, Tilghman J | title = Assessing ethnicity in preconception counseling: genetics--what nurse practitioners need to know | journal = Journal of the American Academy of Nurse Practitioners | volume = 16 | issue = 11 | pages = 472–480 | date = November 2004 | pmid = 15617360 | doi = 10.1111/j.1745-7599.2004.tb00426.x | s2cid = 7644129 }}</ref>
The mutant alleles screened by the test vary according to a person's ethnic group or by the occurrence of CF already in the family. More than 10 million Americans, including one in 25 white Americans, are carriers of one mutant allele of the CF gene. [[Cystic fibrosis and race|CF is present in other races]], though not as frequently as in white individuals. About one in 46 Hispanic Americans, one in 65 African Americans, and one in 90 Asian Americans carry a mutation of the CF gene.<ref name="Edwards"/>
==Pathophysiology==
[[File:CFTR Protein Panels.svg|thumb|upright=1.3|The CFTR protein is a channel protein that controls the flow of H<sub>2</sub>O and Cl<sup>−</sup> ions in and out of cells inside the lungs. When the CFTR protein is working correctly, ions freely flow in and out of the cells. However, when the CFTR protein is malfunctioning, these ions cannot flow out of the cell due to a blocked channel. This causes cystic fibrosis, characterized by the buildup of thick mucus in the lungs.]]
The ''CFTR'' gene regulates the transport of salts and water through cell membranes, providing instructions for creating a pathway that allows the passage of chloride ions.<ref name="pmid9922379">{{cite journal | vauthors = Schwiebert EM, Benos DJ, Egan ME, Stutts MJ, Guggino WB | title = CFTR is a conductance regulator as well as a chloride channel | journal = Physiological Reviews | volume = 79 | issue = 1 Suppl | pages = S145–S166 | date = January 1999 | pmid = 9922379 | doi = 10.1152/physrev.1999.79.1.S145 }}</ref> A mutation in the CFTR gene can impair the normal function of chloride channels, leading to abnormal transport of chloride ions and water, resulting in the formation of thick and abnormal mucus.<ref name="pmid16157656">{{cite journal | vauthors = Linsdell P | title = Mechanism of chloride permeation in the cystic fibrosis transmembrane conductance regulator chloride channel | journal = Experimental Physiology | volume = 91 | issue = 1 | pages = 123–129 | date = January 2006 | pmid = 16157656 | doi = 10.1113/expphysiol.2005.031757 | s2cid = 37254079 }}</ref>
In the pancreatic duct, chloride transport occurs through the voltage-gated chloride channels influenced by CFTR (Cystic Fibrosis transmembrane conductance regulator). These channels are localised in the apical membrane of epithelial cells in the pancreatic duct.<ref name="Pal-2023">{{Cite book | vauthors = Pal GK |title=Comprehensive Textbook of Medical Physiology , Medical |publisher=Jaypee Brothers Medical Publishers |year=2023 |isbn=9789356962897 |edition=3rd |___location= Daryaganj, New Delhi, India |publication-date=July 2023 |pages=643–44 |language=}}</ref>
Several mutations in the ''CFTR'' gene can occur, 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. [[ΔF508|ΔF508-CFTR]] gene mutation, which occurs in >90% of patients in the U.S., creates a protein that does not [[Protein folding|fold]] normally and is not appropriately transported to the cell membrane, resulting in its degradation.<ref name="pmid24970227">{{cite journal | vauthors = Wang XR, Li C | title = Decoding F508del misfolding in cystic fibrosis | journal = Biomolecules | volume = 4 | issue = 2 | pages = 498–509 | date = May 2014 | pmid = 24970227 | pmc = 4101494 | doi = 10.3390/biom4020498 | doi-access = free }}</ref>
Other mutations result in proteins that are too short (truncated) because [[Translation (genetics)|production]] is ended prematurely. Other mutations produce proteins that do not use energy (in the form of ATP) normally, do not allow chloride, iodide, and thiocyanate to cross the membrane appropriately,<ref name="pmid16934416">{{cite journal | vauthors = Childers M, Eckel G, Himmel A, Caldwell J | title = A new model of cystic fibrosis pathology: lack of transport of glutathione and its thiocyanate conjugates | journal = Medical Hypotheses | volume = 68 | issue = 1 | pages = 101–112 | date = 2007 | pmid = 16934416 | doi = 10.1016/j.mehy.2006.06.020 }}</ref> and degrade faster than normal. Mutations may also lead to fewer copies of the CFTR protein being produced.<ref name="Rowe" />
The protein created by this gene is anchored to the [[cell membrane|outer membrane]] of cells in the [[sweat gland]]s, lungs, pancreas, and all other remaining exocrine glands in the body.
The protein spans this membrane and acts as a [[Ion channel|channel]] connecting the inner part of the cell ([[cytoplasm]]) to the [[extracellular fluid|surrounding fluid]]. This channel is primarily responsible for controlling the movement of halide anions 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<ref name="pmid19918082">{{cite journal | vauthors = Xu Y, Szép S, Lu Z | title = The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 48 | pages = 20515–20519 | date = December 2009 | pmid = 19918082 | pmc = 2777967 | doi = 10.1073/pnas.0911412106 | doi-access = free | bibcode = 2009PNAS..10620515X }}</ref> released from sweat glands are trapped inside the ducts and pumped to the skin.{{citation needed|date=August 2025}}
Additionally, [[hypothiocyanite]] (OSCN<sup>−</sup>) cannot be produced by the immune defense system.<ref name="pmid17082494">{{cite journal | vauthors = Moskwa P, Lorentzen D, Excoffon KJ, Zabner J, McCray PB, Nauseef WM, Dupuy C, Bánfi B | title = A novel host defense system of airways is defective in cystic fibrosis | journal = American Journal of Respiratory and Critical Care Medicine | volume = 175 | issue = 2 | pages = 174–183 | date = January 2007 | pmid = 17082494 | pmc = 2720149 | doi = 10.1164/rccm.200607-1029OC }}</ref><ref name="pmid17204267">{{cite journal | vauthors = Conner GE, Wijkstrom-Frei C, Randell SH, Fernandez VE, Salathe M | title = The lactoperoxidase system links anion transport to host defense in cystic fibrosis | journal = FEBS Letters | volume = 581 | issue = 2 | pages = 271–278 | date = January 2007 | pmid = 17204267 | pmc = 1851694 | doi = 10.1016/j.febslet.2006.12.025 | bibcode = 2007FEBSL.581..271C }}</ref> Because chloride is [[Electric charge|negatively charged]], this modifies the electrical potential inside and outside the cell that normally causes [[cation]]s 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.<ref name="Rowe">{{cite journal | vauthors = Rowe SM, Miller S, Sorscher EJ | title = Cystic fibrosis | journal = The New England Journal of Medicine | volume = 352 | issue = 19 | pages = 1992–2001 | date = May 2005 | pmid = 15888700 | doi = 10.1056/NEJMra043184 }}</ref>
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 feces, etc. Several theories have been posited on how the defects in the protein and cellular function cause the clinical effects. The current theory suggests that defective ion transport leads to dehydration in the airway epithelia, thickening mucus.<ref name="pmid26719229">{{cite journal | vauthors = Haq IJ, Gray MA, Garnett JP, Ward C, Brodlie M | title = Airway surface liquid homeostasis in cystic fibrosis: pathophysiology and therapeutic targets | journal = Thorax | volume = 71 | issue = 3 | pages = 284–287 | date = March 2016 | pmid = 26719229 | doi = 10.1136/thoraxjnl-2015-207588 | doi-access = free }}</ref> 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 such as CFTR. CFTR allows chloride ions to be drawn from the cell and into the ASL, but it also regulates another channel called ENac, which 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 flows freely from the ASL and into the cell.<ref>{{Cite journal |last1=Chambers |first1=Lucy A. |last2=Rollins |first2=Brett M. |last3=Tarran |first3=Robert |date=2007-12-15 |title=Liquid movement across the surface epithelium of large airways |journal=Respiratory Physiology & Neurobiology |series=Liquids in the Lung |volume=159 |issue=3 |pages=256–270 |doi=10.1016/j.resp.2007.06.005 |issn=1569-9048 |pmc=2696130 |pmid=17692578}}</ref>
As water follows sodium, the depth of ASL will be depleted and the cilia will be left in the mucous layer.<ref name="pmid12475759">{{cite journal | vauthors = Verkman AS, Song Y, Thiagarajah JR | title = Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease | journal = American Journal of Physiology. Cell Physiology | volume = 284 | issue = 1 | pages = C2-15 | date = January 2003 | pmid = 12475759 | doi = 10.1152/ajpcell.00417.2002 | s2cid = 11790119 }}</ref> As cilia cannot effectively move in a thick, viscous environment, mucociliary clearance is deficient and a buildup of mucus occurs, clogging small airways.<ref name="Marieb-2014">{{cite book|title=Human Anatomy and Physiology|vauthors=Marieb EN, Hoehn K, Hutchinson M|publisher=Pearson Education|year=2014|isbn=978-0805361179|pages=906|chapter=22: The Respiratory System}}</ref> 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.{{citation needed|date=August 2025}}
The presence of the same CFTR proteins causes mucous plugging and obstruction pathologies in other organs. In the pancreas, obstruction of the pancreatic duct inhibits secretion of bicarbonate and pancreatic enzymes into the duodenum. The pH of [[chyme]] entering the small intestine is not effectively neutralized, degrading what pancreatic enzymes do reach the intestines. Fat in the chyme goes unprocessed, and poor absorption of fat-soluble vitamins results. Obstruction of the [[biliary tract]] results in gallstones for up to 15% of CF patients. Increased pressure in the [[Portal vein|hepatic portal vein]] can lead to [[splenomegaly]]. Increased fluid absorption in the intestinal tract leads to constipation and, in infants, meconium ileus. In sweat glands, the flow of chloride through CFTR channels is reversed compared to other affected organs. In CF, chloride cannot be absorbed back into the body through sweat gland tissues, causing a buildup of chloride in sweat, salty skin, fluid loss, and in severe cases, [[Hyponatremia|hyponatremic]] dehydration.<ref>{{Citation |last1=Sankari |first1=Abdulghani |title=Cystic Fibrosis |date=2024-12-11 |work=StatPearls [Internet] |url=http://www.ncbi.nlm.nih.gov/books/NBK493206/ |access-date=2025-07-30 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29630258 |last2=Sharma |first2=Sandeep}}</ref>
===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 [[biofilm]]s that are difficult for immune cells and antibiotics to penetrate. Viscous secretions and persistent respiratory infections repeatedly damage the lungs by gradually remodeling the airways, which makes infection even more difficult to eradicate.<ref name="Saiman">{{cite journal | vauthors = Saiman L | title = Microbiology of early CF lung disease | journal = Paediatric Respiratory Reviews | volume = 5 | issue = Suppl A | pages = S367–S369 | year = 2004 | pmid = 14980298 | doi = 10.1016/S1526-0542(04)90065-6 }}</ref> The natural history of CF lung infections and airway remodeling is poorly understood, largely due to the immense spatial and temporal heterogeneity both within and between the microbiomes of CF patients.<ref name="Khanolkar">{{cite journal | vauthors = Khanolkar RA, Clark ST, Wang PW, Hwang DM, Yau YC, Waters VJ, Guttman DS | title = Ecological Succession of Polymicrobial Communities in the Cystic Fibrosis Airways | journal = mSystems | volume = 5 | issue = 6 | article-number = e00809-20 | date = December 2020 | pmid = 33262240 | pmc = 7716390 | doi = 10.1128/mSystems.00809-20 }}</ref>
Over time, the types of bacteria and their characteristics change in individuals with CF. In the initial stage, common bacteria such as ''S. aureus'' and ''H. influenzae'' colonize and infect the lungs.<ref name=kumar2007/> Eventually, ''[[Pseudomonas aeruginosa]]'' (and sometimes ''[[Burkholderia cepacia complex|Burkholderia cepacia]]'') dominates. By 18 years of age, 80% of patients with classic CF harbor ''P. aeruginosa'', and 3.5% harbor ''B. cepacia''.<ref name=kumar2007/> Once within the lungs, these bacteria adapt to the environment and develop [[antibiotic resistance|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 who do not have CF.<ref name="Saiman" /> Scientific evidence suggests the [[interleukin 17]] pathway plays a key role in resistance and modulation of the inflammatory response during ''P. aeruginosa'' infection in CF.<ref name="Lorè">{{cite journal | vauthors = Lorè NI, Cigana C, Riva C, De Fino I, Nonis A, Spagnuolo L, Sipione B, Cariani L, Girelli D, Rossi G, Basso V, Colombo C, Mondino A, Bragonzi A | title = IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa | journal = Scientific Reports | volume = 6 | article-number = 25937 | date = May 2016 | pmid = 27189736 | pmc = 4870500 | doi = 10.1038/srep25937 | bibcode = 2016NatSR...625937L }}</ref> In particular, interleukin 17-mediated immunity plays a double-edged activity during chronic airways infection; on one side, it contributes to the control of ''P. aeruginosa'' burden, while on the other, it propagates exacerbated pulmonary neutrophilia and tissue remodeling.<ref name="Lorè" />
Infection can spread by passing between different individuals with CF.<ref name="pmid1907611">{{cite journal | doi=10.1128/jcm.29.6.1265-1267.1991 | title=Nosocomial acquisition of Pseudomonas aeruginosa by cystic fibrosis patients | date=1991 | last1=Tümmler | first1=B. | last2=Koopmann | first2=U. | last3=Grothues | first3=D. | last4=Weissbrodt | first4=H. | last5=Steinkamp | first5=G. | last6=von Der Hardt | first6=H. | journal=Journal of Clinical Microbiology | volume=29 | issue=6 | pages=1265–1267 | pmid=1907611 | pmc=271975 }}</ref> In the past, people with CF often participated in summer "CF camps" and other recreational gatherings.<ref name="pmid7684813">{{cite journal | title = Pseudomonas cepacia at summer camps for persons with cystic fibrosis | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 42 | issue = 23 | pages = 456–459 | date = June 1993 | pmid = 7684813 | author-link = Centers for Disease Control and Prevention | author1 = Centers for Disease Control and Prevention (CDC) }}</ref><ref name="pmid7513755">{{cite journal | vauthors = Pegues DA, Carson LA, Tablan OC, FitzSimmons SC, Roman SB, Miller JM, Jarvis WR | title = Acquisition of Pseudomonas cepacia at summer camps for patients with cystic fibrosis. Summer Camp Study Group | journal = The Journal of Pediatrics | volume = 124 | issue = 5 Pt 1 | pages = 694–702 | date = May 1994 | pmid = 7513755 | doi = 10.1016/S0022-3476(05)81357-5 | url = https://zenodo.org/record/1259645 }}</ref> Hospitals grouped patients with CF into common areas and routine equipment (such as [[nebulizer]]s)<ref name="pmid8744509">{{cite journal | vauthors = Pankhurst CL, Philpott-Howard J | title = The environmental risk factors associated with medical and dental equipment in the transmission of Burkholderia (Pseudomonas) cepacia in cystic fibrosis patients | journal = The Journal of Hospital Infection | volume = 32 | issue = 4 | pages = 249–255 | date = April 1996 | pmid = 8744509 | doi = 10.1016/S0195-6701(96)90035-3 }}</ref> was not sterilized between individual patients.<ref name="pmid12775867">{{cite journal | vauthors = Jones AM, Govan JR, Doherty CJ, Dodd ME, Isalska BJ, Stanbridge TN, Webb AK | title = Identification of airborne dissemination of epidemic multiresistant strains of Pseudomonas aeruginosa at a CF centre during a cross infection outbreak | journal = Thorax | volume = 58 | issue = 6 | pages = 525–527 | date = June 2003 | pmid = 12775867 | pmc = 1746694 | doi = 10.1136/thorax.58.6.525 }}</ref> This led to the 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.<ref name="pmid7643943">{{cite journal | vauthors = Høiby N | title = Isolation and treatment of cystic fibrosis patients with lung infections caused by Pseudomonas (Burkholderia) cepacia and multiresistant Pseudomonas aeruginosa | journal = The Netherlands Journal of Medicine | volume = 46 | issue = 6 | pages = 280–287 | date = June 1995 | pmid = 7643943 | doi = 10.1016/0300-2977(95)00020-N }}</ref>
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 such as ''Penicillium emersonii'' and ''[[Acrophialophora fusispora]]'' are encountered in patients almost exclusively in the context of CF.<ref name="Pihet">{{cite journal | vauthors = Pihet M, Carrere J, Cimon B, Chabasse D, Delhaes L, Symoens F, Bouchara JP | title = Occurrence and relevance of filamentous fungi in respiratory secretions of patients with cystic fibrosis--a review | journal = Medical Mycology | volume = 47 | issue = 4 | pages = 387–397 | date = June 2009 | pmid = 19107638 | doi = 10.1080/13693780802609604 | hdl-access = free | doi-access = free | hdl = 20.500.12210/37415 }}</ref> Defective mucociliary clearance characterizing CF is associated with local immunological disorders. In addition, prolonged therapy with antibiotics and 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 bronchopulmonary aspergillosis'' ''– the most common fungal disease in the context of CF, involving a Th2-driven immune response to ''Aspergillus'' species.<ref name="Pihet" /><ref name="pmid18668399">{{cite journal | vauthors = Rapaka RR, Kolls JK | title = Pathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis: current understanding and future directions | journal = Medical Mycology | volume = 47 | issue = Suppl 1 | pages = S331–S337 | date = 2009 | pmid = 18668399 | doi = 10.1080/13693780802266777 | doi-access = free }}</ref>
==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.{{citation needed|date=August 2025}}
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 | pmc = 1800541 }}</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>
==Management==
Treatment for CF is diverse, tailored to different symptoms, and includes various devices, inhalation medications to alleviate respiratory difficulties, oral enzyme supplements to address exocrine pancreatic insufficiency, and, in some cases, surgical interventions for conditions such as meconium ileus.<ref name="Chest-2022">{{Cite journal |date=2022 |title=Treatment preference among people with cystic fibrosis: the importance of reducing treatment burden. |journal=Chest |volume=162|issue=6 }}</ref> While treatment alleviates symptoms and prevents potential complications, there is currently no cure for the disease.{{citation needed|date=August 2025}}
The management of CF has improved significantly over the past 70 years. While infants born with it 70 years ago would have been unlikely to live beyond their first year, infants today are likely to live well into adulthood. Advances in the treatment of cystic fibrosis have meant that people with cystic fibrosis can live a fuller life less encumbered by their condition. The cornerstones of management are the proactive treatment of [[respiratory tract infection|airway infection]], encouragement of good nutrition, and an active lifestyle. [[Pulmonary rehabilitation]] as a management of CF continues throughout a person's life, and is aimed at maximizing organ function, and therefore the quality of life.<ref name="Kalamara_2021">{{cite journal | vauthors = Kalamara EI, Ballas ET, Pitsiou G, Petrova G | title = Pulmonary rehabilitation for cystic fibrosis: A narrative review of current literature | journal = Monaldi Archives for Chest Disease = Archivio Monaldi per le Malattie del Torace | volume = 91 | issue = 2 | pages = | date = March 2021 | pmid = 33792230 | doi = 10.4081/monaldi.2021.1501 | doi-access = free }}</ref> Occupational therapists use energy conservation techniques in the rehabilitation process for patients with cystic fibrosis.<ref name="Italian Congress">{{cite journal | vauthors = | title = Abstracts from the 25th Italian Congress of Cystic Fibrosis and the 15th National Congress of Cystic Fibrosis Italian Society: Assago, Milan. 10 - 12 October 2019 | journal = Italian Journal of Pediatrics | volume = 46 | issue = Suppl 1 | pages = 32 | date = April 2020 | pmid = 32234058 | pmc = 7110616 | doi = 10.1186/s13052-020-0790-z | doi-access = free }}</ref> Examples of energy conservation techniques are ergonomic principles, pursed lip breathing, and diaphragmatic breathing.<ref name="pmid32272478">{{cite journal | vauthors = Wingårdh AS, Göransson C, Larsson S, Slinde F, Vanfleteren LE | title = Effectiveness of Energy Conservation Techniques in Patients with COPD | language = english | journal = Respiration; International Review of Thoracic Diseases | volume = 99 | issue = 5 | pages = 409–416 | date = 2020 | pmid = 32272478 | pmc = 7265758 | doi = 10.1159/000506816 }}</ref> People with CF tend to have fatigue and dyspnoea due to chronic pulmonary infections, so reducing the amount of energy spent during activities can help people feel better and gain more independence.<ref name="Italian Congress" /> At best, current treatments delay the decline in organ function.{{Citation needed|date=July 2023}} 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]]), and psychological support.<ref name="Davies">{{cite journal | vauthors = Davies JC, Alton EW, Bush A | title = Cystic fibrosis | journal = BMJ | volume = 335 | issue = 7632 | pages = 1255–1259 | date = December 2007 | pmid = 18079549 | pmc = 2137053 | doi = 10.1136/bmj.39391.713229.AD }}</ref>
The most consistent aspect of therapy in CF is limiting and treating the lung damage caused by thick mucus and infection, with the goal of maintaining [[quality of life]]. [[Intravenous therapy|Intravenous]], [[inhalation|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. [[Oxygen therapy]] at home is recommended in those with significantly low oxygen levels.<ref name="pmid30707039">{{cite journal | vauthors = Hayes D, Wilson KC, Krivchenia K, Hawkins SM, Balfour-Lynn IM, Gozal D, Panitch HB, Splaingard ML, Rhein LM, Kurland G, Abman SH, Hoffman TM, Carroll CL, Cataletto ME, Tumin D, Oren E, Martin RJ, Baker J, Porta GR, Kaley D, Gettys A, Deterding RR | title = Home Oxygen Therapy for Children. An Official American Thoracic Society Clinical Practice Guideline | journal = American Journal of Respiratory and Critical Care Medicine | volume = 199 | issue = 3 | pages = e5–e23 | date = February 2019 | pmid = 30707039 | pmc = 6802853 | doi = 10.1164/rccm.201812-2276ST }}</ref> Many people with CF use [[probiotics]], which are thought to be able to correct intestinal dysbiosis and inflammation, but the clinical trial evidence regarding the effectiveness of probiotics for reducing pulmonary exacerbations in people with CF is uncertain.<ref name="pmid31962375">{{cite journal | vauthors = Coffey MJ, Garg M, Homaira N, Jaffe A, Ooi CY | title = Probiotics for people with cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD012949 | date = January 2020 | pmid = 31962375 | pmc = 6984633 | doi = 10.1002/14651858.CD012949.pub2 }}</ref>
=== Antibiotics ===
Many people with CF are on one or more antibiotics at all times, even when healthy, to [[Preventive healthcare|prophylactically]] suppress infection. The choice of antibiotics for cystic fibrosis depends on the specific bacteria that are causing the infection, as well as the patient's age, weight, and other medical conditions.{{Citation needed|date=July 2023}} Antibiotics are necessary whenever pneumonia is suspected or a noticeable decline in lung function is seen, and are usually chosen based on the results of a sputum analysis and the person's past response.{{Citation needed|date=July 2023}} This prolonged therapy often necessitates hospitalization and insertion of a more permanent [[Heparin lock|IV]] such as a [[peripherally inserted central catheter]] 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.<ref name="pmid11568993">{{cite journal | vauthors = Pai VB, Nahata MC | title = Efficacy and safety of aerosolized tobramycin in cystic fibrosis | journal = Pediatric Pulmonology | volume = 32 | issue = 4 | pages = 314–327 | date = October 2001 | pmid = 11568993 | doi = 10.1002/ppul.1125 | s2cid = 30108514 }}</ref><ref name="pmid15463883">{{cite journal | vauthors = Westerman EM, Le Brun PP, Touw DJ, Frijlink HW, Heijerman HG | title = Effect of nebulized colistin sulphate and colistin sulphomethate on lung function in patients with cystic fibrosis: a pilot study | journal = Journal of Cystic Fibrosis | volume = 3 | issue = 1 | pages = 23–28 | date = March 2004 | pmid = 15463883 | doi = 10.1016/j.jcf.2003.12.005 | doi-access = free }}</ref><ref name="pmid18658109">{{cite journal | vauthors = McCoy KS, Quittner AL, Oermann CM, Gibson RL, Retsch-Bogart GZ, Montgomery AB | title = Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis | journal = American Journal of Respiratory and Critical Care Medicine | volume = 178 | issue = 9 | pages = 921–928 | date = November 2008 | pmid = 18658109 | pmc = 2577727 | doi = 10.1164/rccm.200712-1804OC }}</ref> Inhaled antibiotic therapy helps lung function by fighting infection, but also has significant drawbacks such as development of antibiotic resistance, tinnitus, and changes in the voice.<ref name="pmid21412868">{{cite journal | vauthors = Ryan G, Singh M, Dwan K | title = Inhaled antibiotics for long-term therapy in cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD001021 | date = March 2011 | pmid = 21412868 | doi = 10.1002/14651858.CD001021.pub2 }}</ref> Inhaled [[levofloxacin]] may be used to treat ''[[Pseudomonas aeruginosa]]'' in people with cystic fibrosis who are infected.<ref name="European Medicines Agency">{{cite web|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002789/human_med_001846.jsp&mid=WC0b01ac058001d124|title=Quinsair (levofloxacin)|website=European Medicines Agency|url-status=live|archive-url=https://web.archive.org/web/20161226220044/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002789%2Fhuman_med_001846.jsp&mid=WC0b01ac058001d124|archive-date=26 December 2016|access-date=26 December 2016}}</ref>
Antibiotics by mouth such as ciprofloxacin or [[azithromycin]] are given to help prevent infection or to control ongoing infection.<ref name="pmid15752679">{{cite journal | vauthors = Hansen CR, Pressler T, Koch C, Høiby N | title = Long-term azitromycin treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection; an observational cohort study | journal = Journal of Cystic Fibrosis | volume = 4 | issue = 1 | pages = 35–40 | date = March 2005 | pmid = 15752679 | doi = 10.1016/j.jcf.2004.09.001 | doi-access = free }}</ref> The [[aminoglycoside]] antibiotics (e.g. tobramycin) used can cause [[Ototoxicity|hearing loss]], damage to the [[Vestibular system|balance system]] in the [[inner ear]] or kidney failure with long-term use.<ref name="pmid12623858">{{cite journal | vauthors = Tan KH, Mulheran M, Knox AJ, Smyth AR | title = Aminoglycoside prescribing and surveillance in cystic fibrosis | journal = American Journal of Respiratory and Critical Care Medicine | volume = 167 | issue = 6 | pages = 819–823 | date = March 2003 | pmid = 12623858 | doi = 10.1164/rccm.200109-012CC }}</ref> To prevent these [[Adverse drug reaction|side-effect]]s, the amount of antibiotics in the blood is routinely measured and adjusted accordingly.<ref name="Fact Sheet-2020">{{Cite web |title=Antibiotic resistance |url=https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance |access-date=24 June 2022 |publisher=World Health Organization |date=31 July 2020 |work=Fact Sheet}}</ref>
Currently, no reliable clinical trial evidence shows the effectiveness of antibiotics for pulmonary exacerbations in people with cystic fibrosis and ''Burkholderia cepacia'' complex<ref name="pmid32239690">{{cite journal | vauthors = Lord R, Jones AM, Horsley A | title = Antibiotic treatment for Burkholderia cepacia complex in people with cystic fibrosis experiencing a pulmonary exacerbation | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 4 | pages = CD009529 | date = April 2020 | pmid = 32239690 | pmc = 7117566 | doi = 10.1002/14651858.CD009529.pub4 }}</ref> or for the use of antibiotics to treat [[nontuberculous mycobacteria]] in people with CF.<ref name="pmid32521055">{{cite journal | vauthors = Waters V, Ratjen F | title = Antibiotic treatment for nontuberculous mycobacteria lung infection in people with cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | pages = CD010004 | date = June 2020 | pmid = 32521055 | pmc = 7389742 | doi = 10.1002/14651858.CD010004.pub5 }}</ref>
==== ''Pseudomonas aeruginosa'' ====
The early management of ''Pseudomonas aeruginosa'' infection is usually suggested using nebulised antibiotics with or without oral antibiotics to remove the bacteria from the person's airways for some time.<ref name="pmid37268599">{{cite journal | vauthors = Langton Hewer SC, Smith S, Rowbotham NJ, Yule A, Smyth AR | title = Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 6 | pages = CD004197 | date = June 2023 | pmid = 37268599 | pmc = 10237531 | doi = 10.1002/14651858.CD004197.pub6 }}</ref> When choosing antibiotics to treat lung infections caused by ''Pseudomonas aeruginosa'' in people with cystic fibrosis, it is still unclear whether the choice of antibiotics should be based on the results of testing antibiotics separately (one at a time) or in combination with each other.<ref name="pmid32412092">{{cite journal | vauthors = Smith S, Ratjen F, Remmington T, Waters V | title = Combination antimicrobial susceptibility testing for acute exacerbations in chronic infection of Pseudomonas aeruginosa in cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 5 | issue = 5 | pages = CD006961 | date = May 2020 | pmid = 32412092 | pmc = 7387858 | doi = 10.1002/14651858.CD006961.pub5 }}</ref> It is also unclear if these treatment approaches for the ''Pseudomonas aeruginosa'' infection improve the person's quality of life or lifespan.<ref name="pmid37268599" /> The negative side effects of antibiotics for this infection are also poorly studied.<ref name="pmid37268599" /> Intravenous antibiotic therapy to treat ''Pseudomonas aeruginosa'' infections is not any better than antibiotics taken orally.<ref name="pmid37268599" />
==== Methicillin-resistant ''Staphylococcus aureus'' ====
[[Methicillin-resistant Staphylococcus aureus|Methicillin-resistant ''Staphylococcus aureus'']] (MRSA) infections can be dangerous for people with cystic fibrosis and can worsen lung damage leading to more rapid decline. Early antibiotic treatment is standard; however, further research is needed to determine longer-term effects and benefits (3–6 months after the treatment or longer) and survival rates associated with different treatment options.<ref name="pmid36511181">{{cite journal | vauthors = Lo DK, Muhlebach MS, Smyth AR | title = Interventions for the eradication of meticillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 12 | issue = 12 | pages = CD009650 | date = December 2022 | pmid = 36511181 | pmc = 9745639 | doi = 10.1002/14651858.CD009650.pub5 | collaboration = Cochrane Cystic Fibrosis and Genetic Disorders Group }}</ref>
==== Antibiotic adjuvant therapy ====
Factors related to antibiotic use, the chronicity of the disease, and the emergence of resistant bacteria demand more exploration for different strategies such as antibiotic [[adjuvant]] therapy.<ref name="pmid32671834">{{cite journal | vauthors = Hurley MN, Smith S, Forrester DL, Smyth AR | title = Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 7 | issue = 7 | pages = CD008037 | date = July 2020 | pmid = 32671834 | pmc = 8407502 | doi = 10.1002/14651858.CD008037.pub4 }}</ref> Antibiotic adjuvant therapy refers to therapeutic approaches that aim to improve the action of antibiotics such a pharmaceutical agents or supplements that impact the virulence of the bacterium or that change the susceptibility of the organism to the antibiotic so that the antibiotics are more effective.<ref name="pmid32671834" /> There is no strong evidence to recommend specific antibiotic adjuvant therapies such as [[Β-Carotene|β-carotene]], [[nitric oxide]], [[zinc supplements]], or KB001-A.<ref name="pmid32671834" />
=== Other medication ===
{{See also|Cystic fibrosis transmembrane conductance regulator#Drug target}}
Aerosolized medications that help loosen secretions include [[dornase alfa]] and [[Hypertonicity|hypertonic]] [[Saline (medicine)|saline]].<ref name="pmid16642591">{{cite journal | vauthors = Kuver R, Lee SP | title = Hypertonic saline for cystic fibrosis | journal = The New England Journal of Medicine | volume = 354 | issue = 17 | pages = 1848–51; author reply 1848–51 | date = April 2006 | pmid = 16642591 | doi = 10.1056/NEJMc060351 | s2cid = 26244542 }}</ref> Dornase is a [[Recombinant DNA|recombinant]] human [[deoxyribonuclease]], which breaks down DNA in the sputum, thus decreasing its viscosity.<ref name="pmid5694947">{{cite journal | vauthors = Lieberman J | title = Dornase aerosol effect on sputum viscosity in cases of cystic fibrosis | journal = JAMA | volume = 205 | issue = 5 | pages = 312–313 | date = July 1968 | pmid = 5694947 | doi = 10.1001/jama.205.5.312 }}</ref> Dornase alpha improves lung function and probably decreases the risk of exacerbations but there is insufficient evidence to know if it is more or less effective than other similar medications.<ref name="pmid33735508" /> Dornase alpha may improve lung function; however, there is no strong evidence that it is better than other hyperosmolar therapies.<ref name="pmid33735508">{{cite journal | vauthors = Yang C, Montgomery M | title = Dornase alfa for cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 3 | pages = CD001127 | date = March 2021 | pmid = 33735508 | pmc = 8094421 | doi = 10.1002/14651858.CD001127.pub5 | collaboration = Cochrane Cystic Fibrosis and Genetic Disorders Group }}</ref>
[[Denufosol]], an investigational drug, opens an alternative chloride channel, helping to liquefy mucus.<ref name="pmid18276176">{{cite journal | vauthors = Kellerman D, Rossi Mospan A, Engels J, Schaberg A, Gorden J, Smiley L | title = Denufosol: a review of studies with inhaled P2Y(2) agonists that led to Phase 3 | journal = Pulmonary Pharmacology & Therapeutics | volume = 21 | issue = 4 | pages = 600–607 | date = August 2008 | pmid = 18276176 | doi = 10.1016/j.pupt.2007.12.003 }}</ref> Whether [[inhaled corticosteroids]] are useful is unclear, but stopping inhaled corticosteroid therapy is safe.<ref name="Inhaled corticosteroids for cystic">{{cite journal | vauthors = Balfour-Lynn IM, Welch K, Smith S | title = Inhaled corticosteroids for cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 7 | issue = 7 | pages = CD001915 | date = July 2019 | pmid = 31271656 | pmc = 6609325 | doi = 10.1002/14651858.CD001915.pub6 }}</ref> There is weak evidence that corticosteroid treatment may cause harm by interfering with growth.<ref name="Inhaled corticosteroids for cystic"/> [[Pneumococcal vaccination]] has not been studied {{as of|2014|lc=y}}.<ref name="pmid25093421">{{cite journal | vauthors = Burgess L, Southern KW | title = Pneumococcal vaccines for cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD008865 | date = August 2014 | pmid = 25093421 | doi = 10.1002/14651858.CD008865.pub3 | veditors = Burgess L }}</ref> {{as of|2014}}, there is no clear evidence from randomized controlled trials that the [[influenza vaccine]] is beneficial for people with cystic fibrosis.<ref name="pmid24604671">{{cite journal | vauthors = Dharmaraj P, Smyth RL | title = Vaccines for preventing influenza in people with cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 3 | pages = CD001753 | date = March 2014 | pmid = 24604671 | pmc = 7066935 | doi = 10.1002/14651858.CD001753.pub3 }}</ref>
[[Ivacaftor]] is a medication taken by mouth for the treatment of CF due to several specific mutations responsive to ivacaftor-induced CFTR protein enhancement.<ref name=Whit2014/><ref name="pmid25148205">{{cite journal | vauthors = Wainwright CE | title = Ivacaftor for patients with cystic fibrosis | journal = Expert Review of Respiratory Medicine | volume = 8 | issue = 5 | pages = 533–538 | date = October 2014 | pmid = 25148205 | doi = 10.1586/17476348.2014.951333 | s2cid = 39537446 }}</ref> It improves lung function by about 10%; however, {{as of|2014|lc=y}} it is expensive.<ref name="Whit2014">{{cite journal | vauthors = Whiting P, Al M, Burgers L, Westwood M, Ryder S, Hoogendoorn M, Armstrong N, Allen A, Severens H, Kleijnen J | title = Ivacaftor for the treatment of patients with cystic fibrosis and the G551D mutation: a systematic review and cost-effectiveness analysis | journal = Health Technology Assessment | volume = 18 | issue = 18 | pages = 1–106 | date = March 2014 | pmid = 24656117 | pmc = 4780965 | doi = 10.3310/hta18180 }}</ref> The first year it was on the market, the list price was over $300,000 per year in the United States.<ref name=Whit2014/> In July 2015, the U.S. Food and Drug Administration approved [[lumacaftor/ivacaftor]].<ref name="FDA-2015">{{Cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453565.htm|title=Press Announcements - FDA approves new treatment for cystic fibrosis |website=FDA |date=2 July 2015 |language=en|access-date=16 January 2017|url-status=dead |archive-url=https://web.archive.org/web/20170118091335/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453565.htm|archive-date=18 January 2017}}</ref> In 2018, the FDA approved the combination [[ivacaftor/tezacaftor]]; the manufacturer announced a list price of $292,000 per year.<ref name="The Boston Globe-2018">{{cite web|url=https://www.bostonglobe.com/business/2018/02/12/fda-approves-another-vertex-drug-for-treatment-cystic-fibrosis/uU5Jfnirrwv57kH1aj2W5N/story.html|title=FDA approves another Vertex drug for treatment of cystic fibrosis |date=12 February 2018 |website=[[The Boston Globe]] |url-access=subscription |url-status=live |archive-url=https://archive.today/20231226081346/https://www.bostonglobe.com/business/2018/02/12/fda-approves-another-vertex-drug-for-treatment-cystic-fibrosis/uU5Jfnirrwv57kH1aj2W5N/story.html |archive-date= 26 December 2023 }}</ref> [[Tezacaftor]] helps move the CFTR protein to the correct position on the cell surface, and is designed to treat people with the [[F508del]] mutation.<ref name="Cystic Fibrosis News Today">{{cite web|url=https://cysticfibrosisnewstoday.com/tezacaftor-vx-661-for-cystic-fibrosis|title=Tezacaftor (VX-661) for Cystic Fibrosis |website=Cystic Fibrosis News Today|access-date=23 December 2018|archive-url=https://web.archive.org/web/20180929042325/https://cysticfibrosisnewstoday.com/tezacaftor-vx-661-for-cystic-fibrosis|archive-date=29 September 2018|url-status=dead}}</ref>
In 2019, the [[combination drug]] [[elexacaftor/ivacaftor/tezacaftor]], marketed as Trikafta and described as modulator therapy,<ref name="Cystic Fibrosis Foundation"/> was approved for CF patients over the age of 12 in the United States,<ref name=Drugs2019>{{cite web |title=Trikafta (elexacaftor, ivacaftor and tezacaftor) FDA Approval History |url=https://www.drugs.com/history/trikafta.html |website=Drugs.com |language=en}}</ref><ref name="Office of the Commissioner-2020a">{{Cite web | author = Office of the Commissioner |date=24 March 2020 |title=FDA approves new breakthrough therapy for cystic fibrosis |url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-breakthrough-therapy-cystic-fibrosis |archive-url=https://web.archive.org/web/20191023030845/https://www.fda.gov/news-events/press-announcements/fda-approves-new-breakthrough-therapy-cystic-fibrosis |url-status=dead |archive-date=23 October 2019 |access-date=28 April 2022 |website=FDA |language=en}}</ref> extended to age 6 in 2021.<ref name="www.cff.org-2021">{{Cite web |title=FDA Accepts Vertex Application for Expansion of Trikafta to Include Children ages 6-11 {{!}} Cystic Fibrosis Foundation |url=https://www.cff.org/news/2021-01/fda-accepts-vertex-application-expansion-trikafta-include-children-ages-6-11 |access-date=28 April 2022 |website=www.cff.org |date=26 January 2021 |language=en}}</ref> In Europe this drug was approved in 2020 and marketed as Kaftrio.<ref name="NHSEngland">{{cite web |title=NHS England » Landmark NHS deal to open up access to life-changing cystic fibrosis drug |url=https://www.england.nhs.uk/2020/08/landmark-nhs-deal-to-open-up-access-to-life-changing-cystic-fibrosis-drug/ |website=www.england.nhs.uk |date=21 August 2020 |access-date=8 August 2021}}</ref> It is used in those who have a f508del mutation, found in about 90% of patients with cystic fibrosis.<ref name=Drugs2019/><ref name="Office of the Commissioner-2020">{{Cite web | author = Office of the Commissioner |date=24 March 2020|title=FDA approves new breakthrough therapy for cystic fibrosis|url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-breakthrough-therapy-cystic-fibrosis|archive-url=https://web.archive.org/web/20191023030845/https://www.fda.gov/news-events/press-announcements/fda-approves-new-breakthrough-therapy-cystic-fibrosis|url-status=dead|archive-date=23 October 2019|access-date=12 August 2020|website=FDA|language=en}}</ref> According to the [[Cystic Fibrosis Foundation]], "this medicine represents the single greatest therapeutic advancement in the history of CF, offering a treatment for the underlying cause of the disease that could eventually bring modulator therapy to 90 percent of people with CF."<ref name="Cystic Fibrosis Foundation">{{Cite press release| ___location = Bethesda, Md. | publisher = Cystic Fibrosis Foundation |title=Statement on FDA approval of Trikafta, the first triple-combination therapy for the most common CF mutation|url=https://www.cff.org/About-Us/Media-Center/Press-Releases/Cystic-Fibrosis-Foundation-statement-on-FDA-approval-of-TRIKAFTA-the-first-triple-combination-therapy-for-the-most-common-CF-mutation/|access-date=12 August 2020| date = 21 October 2019 |language=en}}</ref> In a clinical trial, participants who were administered the combination drug experienced a subsequent 63% decrease in pulmonary exacerbations and a 41.8 mmol/L decrease in sweat chloride concentration.<ref name="Elexacaftor-Tezacaftor-Ivacaftor fo">{{cite journal | vauthors = Middleton PG, Mall MA, Dřevínek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R | title = Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele | journal = The New England Journal of Medicine | volume = 381 | issue = 19 | pages = 1809–1819 | date = November 2019 | pmid = 31697873 | pmc = 7282384 | doi = 10.1056/NEJMoa1908639 }}</ref> By mitigating a repertoire of symptoms associated with cystic fibrosis, the combination drug significantly improved quality-of-life metrics among patients with the disease as well.<ref name="Elexacaftor-Tezacaftor-Ivacaftor fo"/><ref name="Cystic Fibrosis Foundation"/> The combination drug is also known to interact with CYP3A inducers,<ref name="pmid9131486">{{cite journal | vauthors = Wilkinson GR | title = Cytochrome P4503A (CYP3A) metabolism: prediction of in vivo activity in humans | journal = Journal of Pharmacokinetics and Biopharmaceutics | volume = 24 | issue = 5 | pages = 475–490 | date = October 1996 | pmid = 9131486 | doi = 10.1007/BF02353475 | s2cid = 30289771 }}</ref> such as carbamazepine used in the treatment of bipolar disorder, causing elexacaftor/ivacaftor/tezacaftor to circulate in the body at decreased concentrations. As such, concurrent use is not recommended.<ref name="pmid32265602">{{cite journal | vauthors = Ridley K, Condren M | title = Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy | journal = The Journal of Pediatric Pharmacology and Therapeutics | volume = 25 | issue = 3 | pages = 192–197 | date = 1 April 2020 | pmid = 32265602 | pmc = 7134581 | doi = 10.5863/1551-6776-25.3.192 }}</ref> The list price in the US is going to be $311,000 per year;<ref name="Reuters-2019">{{cite web |title=Vertex prices cystic fibrosis combo treatment at $311,000-per-year |url=https://www.reuters.com/article/us-vertex-pharms-fda/vertex-prices-cystic-fibrosis-combo-treatment-at-311000-per-year-idUSKBN1X024U |website=Reuters |access-date=23 October 2019 |language=en |date=21 October 2019}}</ref> however, insurance may cover much of the cost of the drug.<ref name="Good News Network-2019">{{Cite web |date=3 November 2019|title=FDA Approves the First New Cystic Fibrosis Treatment in Decades|url=https://www.goodnewsnetwork.org/fda-approves-the-first-new-cystic-fibrosis-treatment-in-decades/|access-date=12 August 2020|website=Good News Network|language=en-US}}</ref>
[[Ursodeoxycholic acid]], a [[Bile acid|bile salt]], has been used; however, a 2021 study aimed at evaluating whether the incidence of severe liver disease differed between CF centers routinely prescribing or not prescribing UDCA found no reduction in portal hypertension.<ref>{{cite journal |display-authors=5| last1=Colombo | first1=Carla | last2=Alicandro | first2=Gianfranco | last3=Oliver | first3=Mark | last4=Lewindon | first4=Peter J | last5=Ramm | first5=Grant A | last6=Ooi | first6=Chee Y. | last7=Alghisi | first7=Federico | last8=Kashirskaya | first8=Nataliya | last9=Kondratyeva | first9=Elena | last10=Corti | first10=Fabiola | last11=Padoan | first11=Rita | last12=Asherova | first12=Irina | last13=Evans | first13=Helen | last14=de Monestrol | first14=Isabelle | last15=Strandvik | first15=Birgitta | last16=Lindblad | first16=Anders | title=Ursodeoxycholic acid and liver disease associated with cystic fibrosis: A multicenter cohort study | journal=Journal of Cystic Fibrosis | volume=21 | issue=2 | date=2022 | doi=10.1016/j.jcf.2021.03.014 | pages=220–226| pmid=33814323 | doi-access=free }}</ref>
The combination [[vanzacaftor/tezacaftor/deutivacaftor]] (Alyftrek) was approved for medical use in the United States in December 2024.<ref>{{cite press release | title=Vertex Announces US FDA Approval of Alyftrek, a Once-Daily Next-in-Class CFTR Modulator for the Treatment of Cystic Fibrosis | publisher=Vertex | via=Business Wire | date=20 December 2024 | url=https://www.businesswire.com/news/home/20241220133127/en/ | access-date=24 December 2024}}</ref>
=== Nutrient supplementation ===
It is uncertain whether [[vitamin A]] or [[beta-carotene]] supplementation has any effect on eye and skin problems caused by vitamin A deficiency.<ref name="pmid30091146">{{cite journal | vauthors = de Vries JJ, Chang AB, Bonifant CM, Shevill E, Marchant JM | title = Vitamin A and beta (β)-carotene supplementation for cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD006751 | date = August 2018 | pmid = 30091146 | pmc = 6513379 | doi = 10.1002/14651858.CD006751.pub5 }}</ref>
There is no strong evidence that people with cystic fibrosis can prevent [[osteoporosis]] by increasing their intake of [[vitamin D]].<ref name="pmid24823922">{{cite journal | vauthors = Ferguson JH, Chang AB | title = Vitamin D supplementation for cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD007298 | date = May 2014 | pmid = 24823922 | doi = 10.1002/14651858.CD007298.pub4 | pmc = 11254375 }}</ref>
For people with [[vitamin E]] deficiency and cystic fibrosis, there is evidence that vitamin E supplementation may improve vitamin E levels, although it is still uncertain what effect supplementation has on vitamin E-specific deficiency disorders or on lung function.<ref name="pmid32892350">{{cite journal | vauthors = Okebukola PO, Kansra S, Barrett J | title = Vitamin E supplementation in people with cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 9 | pages = CD009422 | date = September 2020 | pmid = 32892350 | pmc = 8406985 | doi = 10.1002/14651858.CD009422.pub4 }}</ref>
Robust evidence regarding the effects of [[vitamin K]] supplementation in people with cystic fibrosis is lacking as of 2020.<ref name="pmid32497260">{{cite journal | vauthors = Jagannath VA, Thaker V, Chang AB, Price AI | title = Vitamin K supplementation for cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | pages = CD008482 | date = June 2020 | pmid = 32497260 | pmc = 7272115 | doi = 10.1002/14651858.CD008482.pub6 | publisher = John Wiley & Sons, Ltd }}</ref>
Various studies have examined the effects of omega-3 fatty acid supplementation for people with cystic fibrosis but the evidence is uncertain whether it has any benefits or adverse effects.<ref name="pmid32275788">{{cite journal | vauthors = Watson H, Stackhouse C | title = Omega-3 fatty acid supplementation for cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 4 | issue = 4 | pages = CD002201 | date = April 2020 | pmid = 32275788 | pmc = 7147930 | doi = 10.1002/14651858.CD002201.pub6 }}</ref>
=== Procedures ===
Several mechanical techniques are used to dislodge sputum and encourage its expectoration. One technique good for short-term airway clearance is [[Pulmonary hygiene#Conventional Chest physiotherapy|chest physiotherapy]] where a respiratory therapist percusses an individual's chest by hand several times a day, to loosen up secretions. This "percussive effect" can be administered also through specific devices that use [[chest wall oscillation]] or [[intrapulmonary percussive ventilator]]. Other 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.<ref name="pmid37042825"/>
Another technique is positive expiratory pressure physiotherapy which consists of providing back pressure to the airways during expiration. This effect is provided by devices that consist of a mask or a mouthpiece in which resistance is applied only during the expiration phase.<ref name="pmid31774149">{{cite journal | vauthors = McIlwaine M, Button B, Nevitt SJ | title = Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 11 | date = November 2019 | pmid = 31774149 | pmc = 6953327 | doi = 10.1002/14651858.CD003147.pub5 }}</ref> Operating principles of this technique seem to be the increase of gas pressure behind mucus through [[collateral ventilation]] along with a temporary increase in functional residual capacity preventing the early collapse of small airways during exhalation.<ref name="pmid392747">{{cite journal | vauthors = Andersen JB, Qvist J, Kann T | title = Recruiting collapsed lung through collateral channels with positive end-expiratory pressure | journal = Scandinavian Journal of Respiratory Diseases | volume = 60 | issue = 5 | pages = 260–266 | date = October 1979 | pmid = 392747 }}</ref><ref name="pmid3899222">{{cite journal | vauthors = Groth S, Stafanger G, Dirksen H, Andersen JB, Falk M, Kelstrup M | title = Positive expiratory pressure (PEP-mask) physiotherapy improves ventilation and reduces volume of trapped gas in cystic fibrosis | journal = Bulletin Européen de Physiopathologie Respiratoire | volume = 21 | issue = 4 | pages = 339–343 | date = July 1985 | pmid = 3899222 }}</ref>
As lung disease worsens, mechanical breathing support may become necessary. Individuals with CF may need to wear special masks at night to help push air into their lungs. These machines, known as [[bilevel positive airway pressure]] (BiPAP) ventilators, help prevent low blood oxygen levels during sleep. Non-invasive ventilators may be used during physical therapy to improve sputum clearance.<ref name="Moran2017">{{cite journal | vauthors = Moran F, Bradley JM, Piper AJ | title = Non-invasive ventilation for cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 2 | pages = CD002769 | date = February 2017 | pmid = 28218802 | pmc = 6464053 | doi = 10.1002/14651858.CD002769.pub5 }}</ref> It is not known if this type of therapy has an impact on pulmonary exacerbations or disease progression.<ref name="Moran2017" /> It is unknown what role non-invasive ventilation therapy has in improving exercise capacity in people with cystic fibrosis.<ref name="Moran2017" /> However, the authors noted that "non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with cystic fibrosis who have difficulty expectorating sputum".<ref name="pmid28218802">{{cite journal | vauthors = Moran F, Bradley JM, Piper AJ | title = Non-invasive ventilation for cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 2 | pages = CD002769 | date = February 2017 | pmid = 28218802 | pmc = 6464053 | doi = 10.1002/14651858.CD002769.pub5 }}</ref> During severe illness, a tube may be placed in the throat (a procedure known as a [[tracheostomy]]) to enable breathing supported by a ventilator.<ref name="NHS-2018">{{cite web | title = Tracheostomy Why it's used | date = 3 October 2018 | publisher = NHS | url = https://www.nhs.uk/conditions/tracheostomy/why-its-done/ | access-date = 10 May 2020}}</ref><ref name="Molnar-2023">{{cite web| vauthors = Molnar H |title=Types of Tracheostomy Tubes |date=11 April 2023 |url= http://www.hopkinsmedicine.org/tracheostomy/about/types.html |language=en }}</ref>
For children, preliminary studies show [[massage therapy]] may help people and their families' quality of life.<ref name="pmid16229132">{{cite journal | vauthors = Huth MM, Zink KA, Van Horn NR | title = The effects of massage therapy in improving outcomes for youth with cystic fibrosis: an evidence review | journal = Pediatric Nursing | volume = 31 | issue = 4 | pages = 328–332 | year = 2005 | pmid = 16229132 }}</ref>
Some lung infections require surgical removal of the infected part of the lung. If this is necessary many times, lung function is severely reduced.<ref name="Leinwand-2019">{{cite web | vauthors = Leinwand MJ | veditors = Windle ML, Odim J | date = 28 December 2019 | work = Medscape | title = Surgical Treatment of Infections of the Lung, Pleura, and Mediastinum | url = http://emedicine.medscape.com/article/906209-overview#a2 | archive-url = https://web.archive.org/web/20161005230647/http://emedicine.medscape.com/article/906209-overview | archive-date=5 October 2016 }}</ref> The most effective treatment options for people with CF who have spontaneous or recurrent [[Pneumothorax|pneumothoraces]] is not clear.<ref name="Amin2012">{{cite journal | vauthors = Amin R, Noone PG, Ratjen F | title = Chemical pleurodesis versus surgical intervention for persistent and recurrent pneumothoraces in cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 12 | issue = 12 | pages = CD007481 | date = December 2012 | pmid = 23235645 | pmc = 7208277 | doi = 10.1002/14651858.CD007481.pub3 }}</ref>
=== Transplantation ===
[[Lung transplantation]] may become necessary for individuals with CF as lung function and [[Exercise intolerance|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 to alleviate liver disease and/or diabetes.<ref name="pmid16298663">{{cite journal | vauthors = Fridell JA, Vianna R, Kwo PY, Howenstine M, Sannuti A, Molleston JP, Pescovitz MD, Tector AJ | title = Simultaneous liver and pancreas transplantation in patients with cystic fibrosis | journal = Transplantation Proceedings | volume = 37 | issue = 8 | pages = 3567–3569 | date = October 2005 | pmid = 16298663 | doi = 10.1016/j.transproceed.2005.09.091 }}</ref> Lung transplantation is considered when lung function declines to the point where assistance from mechanical devices is required or survival is threatened.<ref name="pmid16387803">{{cite journal | vauthors = Belkin RA, Henig NR, Singer LG, Chaparro C, Rubenstein RC, Xie SX, Yee JY, Kotloff RM, Lipson DA, Bunin GR | title = Risk factors for death of patients with cystic fibrosis awaiting lung transplantation | journal = American Journal of Respiratory and Critical Care Medicine | volume = 173 | issue = 6 | pages = 659–666 | date = March 2006 | pmid = 16387803 | pmc = 2662949 | doi = 10.1164/rccm.200410-1369OC }}</ref> According to [[Merck Manual of Diagnosis and Therapy|''Merck Manual'']], "bilateral lung transplantation for severe lung disease is becoming more routine and more successful with experience and improved techniques. Among adults with CF, median survival posttransplant is about 9 years."<ref name="Cystic Fibrosis - Pediatrics">{{Cite web|title=Cystic Fibrosis - Pediatrics|url=https://www.merckmanuals.com/professional/pediatrics/cystic-fibrosis-cf/cystic-fibrosis|access-date=12 August 2020|website=Merck Manuals Professional Edition|language=en-US}}</ref>
=== Other aspects ===
[[File:Icsi.JPG|thumb|upright=1.3|Intracytoplasmic sperm injection can be used to provide fertility for men with cystic fibrosis.]]
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 are unclear, as are the risks and long-term effectiveness of this treatment.<ref name="pmid32761612">{{cite journal | vauthors = Somaraju UR, Solis-Moya A | title = Pancreatic enzyme replacement therapy for people with cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD008227 | date = August 2020 | pmid = 32761612 | pmc = 8094413 | doi = 10.1002/14651858.CD008227.pub4 }}</ref>
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 because the vast majority of people with cystic fibrosis do not live long enough to develop clinically significant atherosclerosis or coronary heart disease.<ref name="pmid27751792">{{cite journal | vauthors = Skolnik K, Levy RD, Wilcox PG, Quon BS | title = Coronary artery disease in cystic fibrosis: An emerging concern? | journal = Journal of Cystic Fibrosis | volume = 15 | issue = 6 | pages = e70–e71 | date = November 2016 | pmid = 27751792 | doi = 10.1016/j.jcf.2016.09.010 | doi-access = free }}</ref>
[[Diabetes mellitus|Diabetes]] is the most common nonpulmonary complication of CF. It mixes features of type 1 and type 2 diabetes and is recognized as a distinct entity, [[cystic fibrosis-related diabetes]].<ref name="Alves">{{cite journal | vauthors = ((Alves Cd)), Aguiar RA, Alves AC, Santana MA | title = Diabetes mellitus in patients with cystic fibrosis | journal = Jornal Brasileiro de Pneumologia | volume = 33 | issue = 2 | pages = 213–221 | date = 2007 | pmid = 17724542 | doi = 10.1590/S1806-37132007000200017 | doi-access = free }}</ref><ref name="pmid19651382">{{cite journal | vauthors = Zirbes J, Milla CE | title = Cystic fibrosis related diabetes | journal = Paediatric Respiratory Reviews | volume = 10 | issue = 3 | pages = 118–23; quiz 123 | date = September 2009 | pmid = 19651382 | doi = 10.1016/j.prrv.2009.04.004 }}</ref> While oral [[antidiabetic drug]]s are sometimes used, the recommended treatment is the use of [[insulin]] injections or an [[insulin pump]],<ref name="pmid33075159">{{cite journal | vauthors = Onady GM, Stolfi A | title = Drug treatments for managing cystic fibrosis-related diabetes | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 10 | pages = CD004730 | date = October 2020 | pmid = 33075159 | pmc = 8094754 | doi = 10.1002/14651858.CD004730.pub5 }}</ref> and, unlike in type 1 and 2 diabetes, dietary restrictions are not recommended.<ref name=Alves/> While ''[[Stenotrophomonas maltophilia]]'' is relatively common in people with cystic fibrosis, the evidence about the effectiveness of antibiotics for ''S. maltophilia'' is uncertain.<ref name="pmid32189337">{{cite journal | vauthors = Amin R, Jahnke N, Waters V | title = Antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 3 | issue = 3 | pages = CD009249 | date = March 2020 | pmid = 32189337 | pmc = 7080526 | doi = 10.1002/14651858.CD009249.pub5 }}</ref>
[[Bisphosphonate]]s taken by mouth or [[Intravenous therapy|intravenously]] can be used to improve bone mineral density in people with cystic fibrosis, but there is no proof that this reduces fractures or increases survival rates.<ref name="Conwell2013">{{cite journal | vauthors = Jeffery TC, Chang AB, Conwell LS | title = Bisphosphonates for osteoporosis in people with cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD002010 | date = January 2023 | pmid = 36625789 | pmc = 9831115 | doi = 10.1002/14651858.CD002010.pub5 }}</ref> When taking bisphosphates intravenously, [[adverse drug reaction|adverse effects]] such as pain and flu-like symptoms can be an issue.<ref name=Conwell2013 /> The adverse effects of bisphosphates taken by mouth on the gastrointestinal tract are unknown.<ref name=Conwell2013 />
Poor growth may be avoided by insertion of a [[feeding tube]] for increasing food energy through supplemental feeds or by administration of injected [[growth hormone]].<ref name="pmid15756212">{{cite journal | vauthors = Hardin DS, Rice J, Ahn C, Ferkol T, Howenstine M, Spears S, Prestidge C, Seilheimer DK, Shepherd R | title = Growth hormone treatment enhances nutrition and growth in children with cystic fibrosis receiving enteral nutrition | journal = The Journal of Pediatrics | volume = 146 | issue = 3 | pages = 324–328 | date = March 2005 | pmid = 15756212 | doi = 10.1016/j.jpeds.2004.10.037 }}</ref>
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 propionate]] are used to decrease nasal inflammation.<ref name="pmid9065342">{{cite journal | vauthors = Marks SC, Kissner DG | title = Management of sinusitis in adult cystic fibrosis | journal = American Journal of Rhinology | volume = 11 | issue = 1 | pages = 11–14 | year = 1997 | pmid = 9065342 | doi = 10.2500/105065897781446810 | s2cid = 5606258 }}</ref>
Female infertility may be overcome by [[in vitro fertilisation|assisted reproduction]] technology, particularly [[embryo transfer]] techniques. Male infertility caused by the absence of the vas deferens may be overcome with [[testicular sperm extraction]], collecting sperm cells directly from the testicles. If the collected sample contains too few sperm cells to likely have spontaneous fertilization, [[intracytoplasmic sperm injection]] can be performed.<ref name="pmid10655317">{{cite journal | vauthors = Phillipson GT, Petrucco OM, Matthews CD | title = Congenital bilateral absence of the vas deferens, cystic fibrosis mutation analysis and intracytoplasmic sperm injection | journal = Human Reproduction | volume = 15 | issue = 2 | pages = 431–435 | date = February 2000 | pmid = 10655317 | doi = 10.1093/humrep/15.2.431 | doi-access = free }}</ref> [[Embryo transfer#Third party reproduction|Third party reproduction]] is also a possibility for women with CF. Whether taking [[antioxidant]]s affects outcomes is unclear.<ref name="pmid25102015">{{cite journal | vauthors = Ciofu O, Lykkesfeldt J | title = Antioxidant supplementation for lung disease in cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD007020 | date = August 2014 | pmid = 25102015 | pmc = 6777741 | doi = 10.1002/14651858.CD007020.pub3 }}</ref>
Physical exercise is usually part of outpatient care for people with cystic fibrosis.<ref name="pmid35943025">{{cite journal | vauthors = Radtke T, Smith S, Nevitt SJ, Hebestreit H, Kriemler S | title = Physical activity and exercise training in cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 8 | pages = CD002768 | date = August 2022 | pmid = 35943025 | pmc = 9361297 | doi = 10.1002/14651858.CD002768.pub5 }}</ref> Aerobic exercise seems to be beneficial for aerobic exercise capacity, lung function, and health-related quality of life; however, the quality of the evidence was poor.<ref name="pmid35943025" />
Due to the use of aminoglycoside antibiotics, ototoxicity is common. Symptoms may include "tinnitus, hearing loss, hyperacusis, aural fullness, dizziness, and vertigo".<ref name="pmid29471610">{{cite journal | vauthors = Ganesan P, Schmiedge J, Manchaiah V, Swapna S, Dhandayutham S, Kothandaraman PP | title = Ototoxicity: A Challenge in Diagnosis and Treatment | journal = Journal of Audiology & Otology | volume = 22 | issue = 2 | pages = 59–68 | date = April 2018 | pmid = 29471610 | pmc = 5894487 | doi = 10.7874/jao.2017.00360 | doi-access = free }}</ref>
=== Gastrointestinal ===
Problems with the gastrointestinal system including constipation and obstruction of the gastrointestinal tract including distal intestinal obstruction syndrome are frequent complications for people with cystic fibrosis.<ref name="pmid34936085" /> Treatment of gastrointestinal problems is required in order to prevent a complete obstruction, reduce other CF symptoms, and improve the quality of life.<ref name="pmid34936085" /> While stool softeners, laxatives, and prokinetics (GI-focused treatments) are often suggested, there is no clear consensus from experts as to which approach is the best and comes with the least risks.<ref name="pmid34936085" /> Mucolytics or systemic treatments aimed at dysfunctional CFTR are also sometimes suggested to improve symptoms.<ref name=":0" /> The evidence supporting these recommendations is very weak and more research is needed to understand how to prevent and treat GI problems in people with CF.<ref name=":0">{{Cite journal |last1=Carroll |first1=Will |last2=Green |first2=Jessica |last3=Gilchrist |first3=Francis J. |date=22 December 2021 |title=Interventions for preventing distal intestinal obstruction syndrome (DIOS) in cystic fibrosis |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue=12 |pages=CD012619 |doi=10.1002/14651858.CD012619.pub3 |issn=1469-493X |pmc=8693853 |pmid=34936085}}</ref> In addition, there is a risk of gastrointestinal malignancy, especially in the transplanted patient, and screening procedures may be considered at an earlier age.<ref>{{Cite journal |last1=Vyas |first1=Aditya Pradeep |last2=Ananthaneni |first2=Anil |last3=Abdehou |first3=Sam |last4=Pandit |first4=Sudha |date=2023-08-29 |title=Esophageal squamous cell carcinoma at the site of tracheo-esophageal fistula repair in a patient with cystic fibrosis |journal=BMJ Case Reports |volume=16 |issue=8 |pages=e253542 |doi=10.1136/bcr-2022-253542 |issn=1757-790X |pmc=10465901 |pmid=37643818}}</ref>
==Prognosis==
The prognosis for cystic fibrosis has improved due to earlier diagnosis through screening and better treatment and access to health care. In 1959, the median age of survival of children with CF in the United States was six months.<ref name="Davis2006">{{cite journal | vauthors = Davis PB | title = Cystic fibrosis since 1938 | journal = American Journal of Respiratory and Critical Care Medicine | volume = 173 | issue = 5 | pages = 475–482 | date = March 2006 | pmid = 16126935 | doi = 10.1164/rccm.200505-840OE | s2cid = 1770759 }}</ref>
In 2010, survival is estimated to be 37 years for women and 40 for men.<ref name=Mac2014>{{cite journal | vauthors = MacKenzie T, Gifford AH, Sabadosa KA, Quinton HB, Knapp EA, Goss CH, Marshall BC | title = Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: survival analysis of the Cystic Fibrosis Foundation patient registry | journal = Annals of Internal Medicine | volume = 161 | issue = 4 | pages = 233–241 | date = August 2014 | pmid = 25133359 | pmc = 4687404 | doi = 10.7326/m13-0636 }}</ref> In Canada, median survival increased from 24 years in 1982 to 47.7 in 2007.<ref name="Canadian Cystic Fibrosis Foundation-2007">{{cite web|year=2007 |title=Canadian Cystic Fibrosis Patient Data Registry Report |url=http://www.cysticfibrosis.ca/assets/files/pdf/CPDR_ReportE.pdf |publisher=[[Canadian Cystic Fibrosis Foundation]] |access-date=14 March 2010 |url-status=dead |archive-url=https://web.archive.org/web/20100715043013/http://www.cysticfibrosis.ca/assets/files/pdf/CPDR_ReportE.pdf |archive-date=15 July 2010 }}</ref> In the United States those born with CF in 2016 have a predicted life expectancy of 47.7 when cared for in specialty clinics.<ref name="Annual Data Report 2016 Cystic Fibrosis Foundation Patient Registry">{{cite web |title=Annual Data Report 2016 Cystic Fibrosis Foundation Patient Registry |url=https://www.cff.org/Research/Researcher-Resources/Patient-Registry/2016-Patient-Registry-Annual-Data-Report.pdf |access-date=19 June 2018 |page=4 |archive-date=19 June 2018 |archive-url=https://web.archive.org/web/20180619190052/https://www.cff.org/Research/Researcher-Resources/Patient-Registry/2016-Patient-Registry-Annual-Data-Report.pdf |url-status=dead }}</ref> Due to the recent development of new treatments, such as CFTR modulators, life expectancy has increased rapidly during recent years. In 2020 the median predicted life expectancy was around 59 years, although there are uncertainties in the estimates due to the low number of annual deaths for persons with cystic fibrosis.<ref>{{Cite web |last=Cystic Fibrosis Foundation |date=September 2021 |title=Patient Registry 2020 Annual Data Report |url=https://www.cff.org/sites/default/files/2021-10/2019-Patient-Registry-Annual-Data-Report.pdf |access-date=26 September 2024 |website=www.cff.org/}}</ref>
In the US, of those with CF 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, 9% were unemployed, 56% were single, and 39% were married or living with a partner.<ref name="Cystic Fibrosis Foundation-2009">{{cite web|year=2009 |title=Cystic Fibrosis Patient Registry Annual Data Report 2009 |url=http://www.cff.org/UploadedFiles/research/ClinicalResearch/Patient-Registry-Report-2009.pdf |publisher=[[Cystic Fibrosis Foundation]] |url-status=dead |archive-url=https://web.archive.org/web/20120105093022/http://www.cff.org/UploadedFiles/research/ClinicalResearch/Patient-Registry-Report-2009.pdf |archive-date=5 January 2012 }}</ref>
===Quality of life===
Chronic illnesses can be difficult to manage. CF is a chronic illness that affects the "digestive and respiratory tracts resulting in generalized malnutrition and chronic respiratory infections."<ref name="pmid10722612">{{cite journal | vauthors = Yu H, Nasr SZ, Deretic V | title = Innate lung defenses and compromised Pseudomonas aeruginosa clearance in the malnourished mouse model of respiratory infections in cystic fibrosis | journal = Infection and Immunity | volume = 68 | issue = 4 | pages = 2142–2147 | date = April 2000 | pmid = 10722612 | pmc = 97396 | doi = 10.1128/IAI.68.4.2142-2147.2000 }}</ref> The thick secretions clog the airways in the lungs, which often cause inflammation and severe lung infections.<ref name=Ratjen03>{{cite journal | vauthors = Ratjen F, Döring G | title = Cystic fibrosis | journal = Lancet | volume = 361 | issue = 9358 | pages = 681–689 | date = February 2003 | pmid = 12606185 | doi = 10.1016/S0140-6736(03)12567-6 | s2cid = 24879334 }}</ref><ref name="pmid9457113">{{cite journal | vauthors = Rosenstein BJ, Zeitlin PL | title = Cystic fibrosis | journal = Lancet | volume = 351 | issue = 9098 | pages = 277–282 | date = January 1998 | pmid = 9457113 | doi = 10.1016/S0140-6736(97)09174-5 | s2cid = 44627706 | doi-access = free }}</ref> If it is compromised, it affects the quality of life of someone with CF and their ability to complete [[activities of daily living]] (ADLs).<ref>{{Cite journal |last1=Arikan |first1=Hulya |last2=Yatar |first2=İlker |last3=Calik-Kutukcu |first3=Ebru |last4=Aribas |first4=Zeynep |last5=Saglam |first5=Melda |last6=Vardar-Yagli |first6=Naciye |last7=Savci |first7=Sema |last8=Inal-Ince |first8=Deniz |last9=Ozcelik |first9=Ugur |last10=Kiper |first10=Nural |display-authors=3 |date=2015-10-01 |title=A comparison of respiratory and peripheral muscle strength, functional exercise capacity, activities of daily living and physical fitness in patients with cystic fibrosis and healthy subjects |url=https://www.sciencedirect.com/science/article/pii/S0891422215001055 |journal=Research in Developmental Disabilities |volume=45-46 |pages=147–156 |doi=10.1016/j.ridd.2015.07.020 |pmid=26241869 |issn=0891-4222|url-access=subscription }}</ref>
According to Schmitz and Goldbeck (2006), CF 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".<ref name="pmid16457728">{{cite journal | vauthors = Schmitz TG, Goldbeck L | title = The effect of inpatient rehabilitation programmes on quality of life in patients with cystic fibrosis: a multi-center study | journal = Health and Quality of Life Outcomes | volume = 4 | article-number = 8 | date = February 2006 | pmid = 16457728 | pmc = 1373610 | doi = 10.1186/1477-7525-4-8 | doi-access = free }}</ref> However, Havermans and colleagues (2006) have established that young outpatients with CF who have participated in the Cystic Fibrosis Questionnaire-Revised "rated some quality of life domains higher than did their parents".<ref name="pmid18991968">{{cite journal | vauthors = Hegarty M, Macdonald J, Watter P, Wilson C | title = Quality of life in young people with cystic fibrosis: effects of hospitalization, age and gender, and differences in parent/child perceptions | journal = Child | volume = 35 | issue = 4 | pages = 462–468 | date = July 2009 | pmid = 18991968 | doi = 10.1111/j.1365-2214.2008.00900.x }}<br />{{cite journal | vauthors = Havermans T, Vreys M, Proesmans M, De Boeck C | title = Assessment of agreement between parents and children on health-related quality of life in children with cystic fibrosis | journal = Child | volume = 32 | issue = 1 | pages = 1–7 | date = January 2006 | pmid = 16398786 | doi = 10.1111/j.1365-2214.2006.00564.x }}</ref> Consequently, outpatients with CF have a more positive outlook for themselves. As [[Merck Manual of Diagnosis and Therapy|Merck Manual]] notes, "with appropriate support, most patients can make an age-appropriate adjustment at home and school. Despite myriad problems, the educational, occupational, and marital successes of patients are impressive."<ref name="Cystic Fibrosis - Pediatrics"/>
Furthermore, there are many ways to enhance the quality of life in CF patients. Exercise is promoted to increase lung function. Integrating an exercise regimen into the CF patient's daily routine can significantly improve quality of life.<ref name="pmid9637933">{{cite journal | vauthors = Moorcroft AJ, Dodd ME, Webb AK | title = Exercise limitations and training for patients with cystic fibrosis | journal = Disability and Rehabilitation | volume = 20 | issue = 6–7 | pages = 247–253 | year = 1998 | pmid = 9637933 | doi = 10.3109/09638289809166735 }}</ref> No definitive cure for CF is known, but diverse medications are used, such as mucolytics, bronchodilators, steroids, and antibiotics, that have the purpose of loosening mucus, expanding airways, decreasing inflammation, and fighting lung infections, respectively.<ref name="Cystic Fibrosis Canada-2011">{{cite web|title=Medications |date=2011 |publisher=Cystic Fibrosis Canada |url=http://www.cysticfibrosis.ca/en/treatment/Medications.php |id=No. 10684-5100 RR0001 |url-status=dead |archive-url=https://web.archive.org/web/20110904003635/http://www.cysticfibrosis.ca/en/treatment/Medications.php |archive-date=4 September 2011 }}</ref>
==Epidemiology==
{| class="wikitable floatright"
|-
! Mutation
! Frequency<br />worldwide<ref name="table">{{cite journal | vauthors = Araújo FG, Novaes FC, Santos NP, Martins VC, Souza SM, Santos SE, Ribeiro-dos-Santos AK | title = Prevalence of deltaF508, G551D, G542X, and R553X mutations among cystic fibrosis patients in the North of Brazil | journal = Brazilian Journal of Medical and Biological Research = Revista Brasileira de Pesquisas Medicas e Biologicas | volume = 38 | issue = 1 | pages = 11–15 | date = January 2005 | pmid = 15665983 | doi = 10.1590/S0100-879X2005000100003 | doi-access = free }}</ref>
|
| ΔF508
| 66–70%<ref name=kumar2007/>
|-
| 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 of European heritage.<ref name="Tobias-2011">{{cite book | vauthors = Tobias E |title=Essential Medical Genetics |year=2011 |publisher=John Wiley & Sons |isbn=978-1-118-29370-6 |page=312 |url=https://books.google.com/books?id=77Dvq_OoMnYC&pg=PT312 |url-status=live |archive-url=https://web.archive.org/web/20160417210736/https://books.google.com/books?id=77Dvq_OoMnYC&pg=PT312 |archive-date=17 April 2016 }}</ref> In the United States, about 30,000 individuals have CF; most are diagnosed by six months of age. In Canada, about 4,000 people have CF.<ref name="cysticfibrosis.ca">{{cite web|title=The Canadian Facts & Figures on Cystic Fibrosis |url=http://www.cysticfibrosis.ca/en/aboutCysticFibrosis/CfStatistics.php |url-status=dead |archive-url=https://web.archive.org/web/20130616202515/http://www.cysticfibrosis.ca/en/aboutCysticFibrosis/CfStatistics.php |work=cysticfibrosis.ca |archive-date=16 June 2013 }}</ref> Around 1 in 25 people of European descent, and one in 30 of white Americans,<ref name="Cystic Fibrosis Foundation-2007">{{cite web |title=Genetic Carrier Testing |date=2007 |publisher=Cystic Fibrosis Foundation |url=http://www.cff.org/aboutcf/testing/geneticcarriertest/ |url-status=dead |archive-url=https://web.archive.org/web/20100323191234/http://www.cff.org/aboutcf/testing/geneticcarriertest/ |archive-date=23 March 2010 }}</ref> is a carrier of a CF mutation. Although CF is less common in these groups, roughly one in 46 [[Hispanic]]s, one in 65 [[Africa#Demographics|Africans]], and one in 90 [[Asian people|Asians]] carry at least one abnormal ''CFTR'' gene.<ref name="pmid9580754">{{cite journal | vauthors = Rosenstein BJ, Cutting GR | title = The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel | journal = The Journal of Pediatrics | volume = 132 | issue = 4 | pages = 589–595 | date = April 1998 | pmid = 9580754 | doi = 10.1016/S0022-3476(98)70344-0 }}</ref><ref name="pmid9506637">{{cite journal | vauthors = Hamosh A, FitzSimmons SC, Macek M, Knowles MR, Rosenstein BJ, Cutting GR | title = Comparison of the clinical manifestations of cystic fibrosis in black and white patients | journal = The Journal of Pediatrics | volume = 132 | issue = 2 | pages = 255–259 | date = February 1998 | pmid = 9506637 | doi = 10.1016/S0022-3476(98)70441-X | doi-access = free }}</ref> Ireland has the world's highest prevalence of CF, at one in 1353;<ref name="pmid17955689">{{cite journal | vauthors = Farrell P, Joffe S, Foley L, Canny GJ, Mayne P, Rosenberg M | title = Diagnosis of cystic fibrosis in the Republic of Ireland: epidemiology and costs | journal = Irish Medical Journal | volume = 100 | issue = 8 | pages = 557–560 | date = September 2007 | pmid = 17955689 | url = http://www.imj.ie//ViewArticleDetails.aspx?ArticleID=2497 | url-status = dead | archive-url = https://web.archive.org/web/20131203001750/http://www.imj.ie//ViewArticleDetails.aspx?ArticleID=2497 | archive-date = 3 December 2013 }}</ref> Japan's prevalence of CF is among the lowest in the world, at one in 350,000.<ref>{{cite journal | vauthors = Yamashiro Y, Shimizu T, Oguchi S, Shioya T, Nagata S, Ohtsuka Y | title = The estimated incidence of cystic fibrosis in Japan | journal = J Pediatr Gastroenterol Nutr | volume = 24 | issue = 5 | pages = 544–547 | date = May 1997 | doi = 10.1097/00005176-199705000-00010 | pmid = 9161949 }}</ref>
Although technically a rare disease, CF 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 carries a CF mutation.<ref name="pmid11813900">{{cite journal | vauthors = Hytönen M, Patjas M, Vento SI, Kauppi P, Malmberg H, Ylikoski J, Kere J | title = Cystic fibrosis gene mutations deltaF508 and 394delTT in patients with chronic sinusitis in Finland | journal = Acta Oto-Laryngologica | volume = 121 | issue = 8 | pages = 945–947 | date = December 2001 | pmid = 11813900 | doi = 10.1080/000164801317166835 }}</ref> The [[World Health Organization]] states, "In the European Union, one in 2000–3000 newborns is found to be affected by CF".<ref name="WHO {{pipe}} Genes and human disease">{{cite web |url=https://www.who.int/genomics/public/geneticdiseases/en/index2.html |title=WHO {{pipe}} Genes and human disease |publisher=Who.int |date=7 December 2010 |access-date=23 January 2013 |url-status=live |archive-url=https://web.archive.org/web/20121020153249/http://www.who.int/genomics/public/geneticdiseases/en/index2.html |archive-date=20 October 2012 }}</ref> In the United States, one in 3,500 children is born with CF.<ref name="Russell-2011">{{cite book| vauthors = Russell P |title=Biology: the dynamic science.|year=2011|publisher=Brooks/Cole, Cengage Learning|___location=Belmont, CA|isbn=978-0-538-49372-7|page=304|url=https://books.google.com/books?id=UxkOTD5LNCwC&pg=PT304|edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20160417205330/https://books.google.com/books?id=UxkOTD5LNCwC&pg=PT304|archive-date=17 April 2016}}</ref> In 1997, about one in 3,300 white children in the United States was born with CF. In contrast, only one in 15,000 African American children have it, and in Asian Americans, the rate was even lower at one in 32,000.<ref name="Consensus Development Conference Statement-1997">{{cite web |title=Genetic testing for cystic fibrosis Genetic Testing for Cystic Fibrosis |date= 14–16 April 1997 |work=Consensus Development Conference Statement |publisher=National Institutes of Health |url=http://consensus.nih.gov/1997/1997GeneticTestCysticFibrosis106html.htm |url-status=dead |archive-url=https://web.archive.org/web/20090327075356/http://consensus.nih.gov/1997/1997GeneticTestCysticFibrosis106html.htm |archive-date=27 March 2009 }}</ref>
Cystic fibrosis is diagnosed equally in males and females. For reasons that remain unclear, data have shown that males tend to have a longer life expectancy than females,<ref name="pmid9143209">{{cite journal | vauthors = Rosenfeld M, Davis R, FitzSimmons S, Pepe M, Ramsey B | title = Gender gap in cystic fibrosis mortality | journal = American Journal of Epidemiology | volume = 145 | issue = 9 | pages = 794–803 | date = May 1997 | pmid = 9143209 | doi = 10.1093/oxfordjournals.aje.a009172 | doi-access = free }}</ref><ref name="pmid19033671">{{cite journal | vauthors = Coakley RD, Sun H, Clunes LA, Rasmussen JE, Stackhouse JR, Okada SF, Fricks I, Young SL, Tarran R | title = 17beta-Estradiol inhibits Ca2+-dependent homeostasis of airway surface liquid volume in human cystic fibrosis airway epithelia | journal = The Journal of Clinical Investigation | volume = 118 | issue = 12 | pages = 4025–4035 | date = December 2008 | pmid = 19033671 | pmc = 2582929 | doi = 10.1172/JCI33893 }}</ref> though recent studies suggest this gender gap may no longer exist, perhaps due to improvements in health care facilities.<ref name="pmid16236961">{{cite journal | vauthors = Verma N, Bush A, Buchdahl R | title = Is there still a gender gap in cystic fibrosis? | journal = Chest | volume = 128 | issue = 4 | pages = 2824–2834 | date = October 2005 | pmid = 16236961 | doi = 10.1378/chest.128.4.2824 | doi-access = free }}</ref><ref name="pmid19542209">{{cite journal | vauthors = Moran A, Dunitz J, Nathan B, Saeed A, Holme B, Thomas W | title = Cystic fibrosis-related diabetes: current trends in prevalence, incidence, and mortality | journal = Diabetes Care | volume = 32 | issue = 9 | pages = 1626–1631 | date = September 2009 | pmid = 19542209 | pmc = 2732133 | doi = 10.2337/dc09-0586 }}</ref> A recent study from Ireland identified a link between the female hormone estrogen and worse outcomes in CF.<ref name="The Irish Times-2010">{{cite news | url=http://www.irishtimes.com/newspaper/health/2010/0810/1224276467970.html | newspaper=The Irish Times | title=CF worse for women 'due to effect of estrogen' | date=8 August 2010 | url-status=live | archive-url=https://web.archive.org/web/20100811021301/http://www.irishtimes.com/newspaper/health/2010/0810/1224276467970.html | archive-date=11 August 2010 }}</ref>
The distribution of CF alleles varies among populations. The frequency of ΔF508 carriers has been estimated at one in 200 in northern Sweden, one in 143 in Lithuanians, and one in 38 in Denmark. No ΔF508 carriers were found among 171 Finns and 151 [[Saami people]].<ref name="pmid8039801">{{cite journal | vauthors = Wennberg C, Kucinskas V | title = Low frequency of the delta F508 mutation in Finno-Ugrian and Baltic populations | journal = Human Heredity | volume = 44 | issue = 3 | pages = 169–171 | year = 1994 | pmid = 8039801 | doi = 10.1159/000154210 }}</ref> ΔF508 does occur in Finland, but it is a minority allele there. CF is known to occur in only 20 families (pedigrees) in Finland.<ref name="pmid2210753">{{cite journal | vauthors = Kere J, Savilahti E, Norio R, Estivill X, de la Chapelle A | title = Cystic fibrosis mutation delta F508 in Finland: other mutations predominate | journal = Human Genetics | volume = 85 | issue = 4 | pages = 413–415 | date = September 1990 | pmid = 2210753 | doi = 10.1007/BF02428286 | s2cid = 38364780 }}</ref>
===Evolution===
The ΔF508 mutation is estimated to have occurred up to 52,000 years ago.<ref name="pmid11556136">{{cite journal | vauthors = Wiuf C | title = Do delta F508 heterozygotes have a selective advantage? | journal = Genetical Research | volume = 78 | issue = 1 | pages = 41–47 | date = August 2001 | pmid = 11556136 | doi = 10.1017/S0016672301005195 | citeseerx = 10.1.1.174.7283 }}</ref> Numerous hypotheses have been advanced as to why such a lethal allele 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, an [[evolutionary trade-off]] known as [[heterozygote advantage]]. Resistance to the following have all been proposed as possible sources of heterozygote advantage:
* [[Cholera]]: With the discovery that [[cholera toxin]] requires normal host CFTR proteins to function properly, it was hypothesized that carriers of mutant ''CFTR'' alleles benefited from resistance to cholera and other causes of diarrhea.<ref name="pmid7524148">{{cite journal | vauthors = Gabriel SE, Brigman KN, Koller BH, Boucher RC, Stutts MJ | title = Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model | journal = Science | volume = 266 | issue = 5182 | pages = 107–109 | date = October 1994 | pmid = 7524148 | doi = 10.1126/science.7524148 | bibcode = 1994Sci...266..107G }}</ref><ref name="pmid20110149">{{cite journal | vauthors = Alfonso-Sánchez MA, Pérez-Miranda AM, García-Obregón S, Peña JA | title = An evolutionary approach to the high frequency of the Delta F508 CFTR mutation in European populations | journal = Medical Hypotheses | volume = 74 | issue = 6 | pages = 989–992 | date = June 2010 | pmid = 20110149 | doi = 10.1016/j.mehy.2009.12.018 }}</ref> Further studies have not confirmed this hypothesis.<ref name="pmid7714835">{{cite journal | vauthors = Cuthbert AW, Halstead J, Ratcliff R, Colledge WH, Evans MJ | title = The genetic advantage hypothesis in cystic fibrosis heterozygotes: a murine study | journal = The Journal of Physiology | volume = 482 | issue = Pt 2 | pages = 449–454 | date = January 1995 | pmid = 7714835 | pmc = 1157742 | doi = 10.1113/jphysiol.1995.sp020531 }}</ref><ref name="pmid11055897">{{cite journal | vauthors = Högenauer C, Santa Ana CA, Porter JL, Millard M, Gelfand A, Rosenblatt RL, Prestidge CB, Fordtran JS | title = Active intestinal chloride secretion in human carriers of cystic fibrosis mutations: an evaluation of the hypothesis that heterozygotes have subnormal active intestinal chloride secretion | journal = American Journal of Human Genetics | volume = 67 | issue = 6 | pages = 1422–1427 | date = December 2000 | pmid = 11055897 | pmc = 1287919 | doi = 10.1086/316911 }}</ref>
* [[Typhoid fever|Typhoid]]: Normal CFTR proteins are also essential for the entry of [[Salmonella Typhi|''Salmonella'' Typhi]] into cells,<ref name="pmid9590693">{{cite journal | vauthors = Pier GB, Grout M, Zaidi T, Meluleni G, Mueschenborn SS, Banting G, Ratcliff R, Evans MJ, Colledge WH | title = Salmonella typhi uses CFTR to enter intestinal epithelial cells | journal = Nature | volume = 393 | issue = 6680 | pages = 79–82 | date = May 1998 | pmid = 9590693 | doi = 10.1038/30006 | s2cid = 5894247 | bibcode = 1998Natur.393...79P }}</ref> suggesting that carriers of mutant ''CFTR'' genes might be resistant to [[typhoid fever]]. No ''in vivo'' study has yet confirmed this. In both cases, the low level of cystic fibrosis outside of Europe, in places where both cholera and typhoid fever are [[endemic (epidemiology)|endemic]], is not immediately explicable.
* [[Diarrhea]]: The prevalence of CF in Europe might be connected with the development of cattle domestication. In this hypothesis, carriers of a single mutant ''CFTR'' allele had some protection from diarrhea caused by [[lactose intolerance]], before the mutations that created lactose tolerance appeared.<ref name="pmid17180122">{{cite journal | vauthors = Modiano G, Ciminelli BM, Pignatti PF | title = Cystic fibrosis and lactase persistence: a possible correlation | journal = European Journal of Human Genetics | volume = 15 | issue = 3 | pages = 255–259 | date = March 2007 | pmid = 17180122 | doi = 10.1038/sj.ejhg.5201749 | hdl-access = free | s2cid = 4650571 | hdl = 2108/29185 }}</ref>
* [[Tuberculosis]]: Another possible explanation is that carriers of the mutant allele could have some resistance to tuberculosis.<ref name="pmid17015291">{{cite journal | vauthors = Poolman EM, Galvani AP | title = Evaluating candidate agents of selective pressure for cystic fibrosis | journal = Journal of the Royal Society, Interface | volume = 4 | issue = 12 | pages = 91–98 | date = February 2007 | pmid = 17015291 | pmc = 2358959 | doi = 10.1098/rsif.2006.0154 }}</ref><ref name="Williams-2006">{{cite journal |doi=10.1016/j.cub.2006.09.009 |title=Footprint fears for new TB threat |year=2006 | vauthors = Williams N |s2cid=2346727 |journal=Current Biology |volume=16 |issue=19 |pages=R821–R822|doi-access=free |bibcode=2006CBio...16.R821W }}</ref> This hypothesis is based on the thesis that ''CFTR'' mutant allele carriers have insufficient action in one of their enzymes – arylsulphatase – which is necessary for ''Mycobacterium tuberculosis'' virulence. As ''M. tuberculosis'' would use its host's sources to affect the individual, and due to the lack of enzyme it could not present its virulence, being a carrier of ''CFTR ''mutant allele could provide resistance against tuberculosis.<ref name="pmid12796199">{{cite journal | vauthors = Tobacman JK | title = Does deficiency of arylsulfatase B have a role in cystic fibrosis? | journal = Chest | volume = 123 | issue = 6 | pages = 2130–2139 | date = June 2003 | pmid = 12796199 | doi = 10.1378/chest.123.6.2130 }}</ref>
==History==
{{See also|List of people diagnosed with cystic fibrosis}}
[[File:Dorothy Hansine Andersen.jpg|thumb|upright|[[Dorothy Hansine Andersen]] first described cystic fibrosis in 1938.]]
CF is supposed to have appeared about 3,000 BC because of the migration of people, gene mutations, and new conditions in nourishment.<ref name= Bosch/> 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 {{Lang|de|"Wehe dem Kind, das beim Kuß auf die Stirn salzig schmeckt, es ist verhext und muss bald sterben"}} ("Woe to the child who tastes salty from a kiss on the forehead, for he is bewitched and soon must die"), recognizing the association between the salt loss in CF and illness.<ref name= "Bosch">{{cite journal | vauthors = Busch R | title = On the history of cystic fibrosis | journal = Acta Universitatis Carolinae. Medica | volume = 36 | issue = 1–4 | pages = 13–15 | year = 1990 | pmid = 2130674 }}</ref>
In the 19th century, [[Carl von Rokitansky]] described a case of fetal death with [[meconium peritonitis]], a complication of meconium ileus associated with CF. Meconium ileus was first described in 1905 by [[Karl Landsteiner]].<ref name="Bosch" /> In 1936, [[Guido Fanconi]] described a connection between [[celiac disease]], cystic fibrosis of the pancreas, and [[bronchiectasis]].<ref name="Fanconi-1936">{{cite journal | vauthors = Fanconi G, Uehlinger E, Knauer C | year = 1936 | title = Das coeliakiesyndrom bei angeborener zysticher pankreasfibromatose und bronchiektasien | journal = Wien. Med. Wochenschr. | volume = 86 | pages = 753–756 }}</ref>
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.<ref name="andersen" /> She also first hypothesized that CF was a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952, [[Paul di Sant'Agnese]] discovered abnormalities in sweat electrolytes; a sweat test was developed and improved over the next decade.<ref name="pmid13111855">{{cite journal | vauthors = Di Sant'Agnese PA, Darling RC, Perera GA, Shea E | title = Abnormal electrolyte composition of sweat in cystic fibrosis of the pancreas; clinical significance and relationship to the disease | journal = Pediatrics | volume = 12 | issue = 5 | pages = 549–563 | date = November 1953 | pmid = 13111855 | doi = 10.1542/peds.12.5.549 | s2cid = 42514224 }}</ref>
The first linkage between CF and another marker ([[paraoxonase]]) was found in 1985 by [[Hans Eiberg]], indicating that only one locus exists for CF.<ref name="pmid2998653">{{cite journal | vauthors = Eiberg H, Mohr J, Schmiegelow K, Nielsen LS, Williamson R | title = Linkage relationships of paraoxonase (PON) with other markers: indication of PON-cystic fibrosis synteny | journal = Clinical Genetics | volume = 28 | issue = 4 | pages = 265–271 | date = October 1985 | pmid = 2998653 | doi = 10.1111/j.1399-0004.1985.tb00400.x | s2cid = 41143417 }}</ref> In 1988, the first mutation for CF, [[Delta-F508|ΔF508]], was discovered by [[Francis Collins (geneticist)|Francis Collins]], [[Lap-Chee Tsui]], and [[John R. Riordan]] on the seventh chromosome.<ref name="pmid2475911">{{cite journal | vauthors = Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL | title = Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA | journal = Science | volume = 245 | issue = 4922 | pages = 1066–1073 | date = September 1989 | pmid = 2475911 | doi = 10.1126/science.2475911 | s2cid = 84566748 | bibcode = 1989Sci...245.1066R }}</ref> Subsequent research has found over 1,000 different mutations that cause CF.<ref name="pmid28031875">{{cite journal | vauthors = Fraser-Pitt D, O'Neil D | title = Cystic fibrosis - a multiorgan protein misfolding disease | journal = Future Science OA | volume = 1 | issue = 2 | article-number = FSO57 | date = September 2015 | pmid = 28031875 | pmc = 5137970 | doi = 10.4155/fso.15.57 }}</ref>
Because mutations in the ''CFTR'' gene are typically small, [[classical genetics]] techniques have been unable to accurately pinpoint the mutated gene.<ref name="Rommens">{{cite journal | vauthors = Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N | title = Identification of the cystic fibrosis gene: chromosome walking and jumping | journal = Science | volume = 245 | issue = 4922 | pages = 1059–1065 | date = September 1989 | pmid = 2772657 | doi = 10.1126/science.2772657 | bibcode = 1989Sci...245.1059R }}</ref> Using protein markers, [[gene linkage|gene-linkage]] studies were able to map the mutation to chromosome 7. [[Chromosome walking]] and [[chromosome jumping]] techniques were then used to identify and [[DNA sequencing|sequence]] the gene.<ref name="Rommens"/> In 1989, Lap-Chee Tsui led a team of researchers at the [[The Hospital for Sick Children, Toronto|Hospital for Sick Children]] in [[Toronto]] that discovered the gene responsible for CF.<ref name="Bonetta-2002">{{Cite journal | vauthors = Bonetta L |date= September 2002 |title=Lap-Chee Tsui |journal=Nature Medicine |language=en |volume=8 |issue=9 |pages=910 |doi=10.1038/nm0902-910 |s2cid=5124983 |issn=1546-170X|doi-access=free }}</ref> CF represents a classic example of how a human genetic disorder was elucidated strictly by the process of [[forward genetics]].<ref name="Rommens"/><ref name="Blakeslee-1989">{{Cite news | vauthors = Blakeslee S |date=12 September 1989 |title=Scientists Develop New Techniques To Track Down Defects in Genes |language=en-US |work=The New York Times |url=https://www.nytimes.com/1989/09/12/science/scientists-develop-new-techniques-to-track-down-defects-in-genes.html |access-date=27 April 2023 |issn=0362-4331}}</ref>
==Research==
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.<ref name="Freudenheim-2009">{{cite news| vauthors = Freudenheim M |url=https://www.nytimes.com/2009/12/22/health/22cyst.html|title=Tool in Cystic Fibrosis Fight: A Registry|date=22 December 2009|newspaper=[[The New York Times]]|access-date=21 December 2009|url-status=live|archive-url=https://web.archive.org/web/20130524095423/http://www.nytimes.com/2009/12/22/health/22cyst.html|archive-date=24 May 2013|pages=D1}}</ref>
===Gene therapy===
[[Gene therapy]] has been explored as a potential cure for CF. Results from clinical trials have shown limited success {{as of|2016|lc=y}}, and using gene therapy as routine therapy is not suggested.<ref name="pmid27314455">{{cite journal | vauthors = Lee TW, Southern KW, Perry LA, Penny-Dimri JC, Aslam AA | title = Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 6 | pages = CD005599 | date = June 2016 | pmid = 27314455 | pmc = 8682957 | doi = 10.1002/14651858.CD005599.pub5 | veditors = Southern KW }}</ref> A small study published in 2015 found a small benefit.<ref name="pmid26149841">{{cite journal | vauthors = Alton EW, Armstrong DK, Ashby D, Bayfield KJ, Bilton D, Bloomfield EV, Boyd AC, Brand J, Buchan R, Calcedo R, Carvelli P, Chan M, Cheng SH, Collie DD, Cunningham S, Davidson HE, Davies G, Davies JC, Davies LA, Dewar MH, Doherty A, Donovan J, Dwyer NS, Elgmati HI, Featherstone RF, Gavino J, Gea-Sorli S, Geddes DM, Gibson JS, Gill DR, Greening AP, Griesenbach U, Hansell DM, Harman K, Higgins TE, Hodges SL, Hyde SC, Hyndman L, Innes JA, Jacob J, Jones N, Keogh BF, Limberis MP, Lloyd-Evans P, Maclean AW, Manvell MC, McCormick D, McGovern M, McLachlan G, Meng C, Montero MA, Milligan H, Moyce LJ, Murray GD, Nicholson AG, Osadolor T, Parra-Leiton J, Porteous DJ, Pringle IA, Punch EK, Pytel KM, Quittner AL, Rivellini G, Saunders CJ, Scheule RK, Sheard S, Simmonds NJ, Smith K, Smith SN, Soussi N, Soussi S, Spearing EJ, Stevenson BJ, Sumner-Jones SG, Turkkila M, Ureta RP, Waller MD, Wasowicz MY, Wilson JM, Wolstenholme-Hogg P | title = Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial | journal = The Lancet. Respiratory Medicine | volume = 3 | issue = 9 | pages = 684–691 | date = September 2015 | pmid = 26149841 | pmc = 4673100 | doi = 10.1016/S2213-2600(15)00245-3 }}</ref>
===Bacteriophage therapy===
Bacteriophage therapy ([[phage therapy]]) is being studied for multidrug-resistant bacteria in people with CF.<ref name="pmid26213462">{{cite journal | vauthors = Hraiech S, Brégeon F, Rolain JM | title = Bacteriophage-based therapy in cystic fibrosis-associated Pseudomonas aeruginosa infections: rationale and current status | journal = Drug Design, Development and Therapy | volume = 9 | pages = 3653–3663 | date = 2015 | pmid = 26213462 | pmc = 4509528 | doi = 10.2147/DDDT.S53123 | doi-access = free }}</ref><ref name="pmid28720345">{{cite journal | vauthors = Trend S, Fonceca AM, Ditcham WG, Kicic A, Cf A | title = The potential of phage therapy in cystic fibrosis: Essential human-bacterial-phage interactions and delivery considerations for use in Pseudomonas aeruginosa-infected airways | journal = Journal of Cystic Fibrosis | volume = 16 | issue = 6 | pages = 663–670 | date = November 2017 | pmid = 28720345 | doi = 10.1016/j.jcf.2017.06.012 | doi-access = free }}</ref> Bacteriophage therapy is a treatment method that uses viruses, known as [[bacteriophage]]s, to target and destroy harmful bacteria in the body. Unlike antibiotics, which can kill a wide range of bacteria and potentially disrupt the body's normal flora, phage therapy is highly specific, targeting only the harmful bacteria while leaving the beneficial ones unharmed. As such, bacteriophage therapy is a promising alternative for treating infections caused by multidrug-resistant bacteria, such as Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa in CF patients, which are often protected by biofilms and thus resistant to conventional antibiotics.<ref name="a">{{cite journal | vauthors = Petrovic Fabijan A, Iredell J, Danis-Wlodarczyk K, Kebriaei R, Abedon ST | title = Translating phage therapy into the clinic: Recent accomplishments but continuing challenges | journal = PLOS Biology | volume = 21 | issue = 5 | pages = e3002119 | date = May 2023 | pmid = 37220114 | doi = 10.1371/journal.pbio.3002119 | doi-access = free | pmc = 10204993 }}</ref><ref name="b">{{cite journal | vauthors = Ashworth EA, Wright RC, Shears RK, Wong JK, Hassan A, Hall JP, Kadioglu A, Fothergill JL | title = Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo | journal = Nature Communications | volume = 15 | issue = 1 | article-number = 1547 | date = February 2024 | pmid = 38378698 | doi = 10.1038/s41467-024-45785-z | pmc = 10879199 | bibcode = 2024NatCo..15.1547A }}</ref><ref name="c">{{cite journal | vauthors = Liu K, Wang C, Zhou X, Guo X, Yang Y, Liu W, Zhao R, Song H | title = Bacteriophage therapy for drug-resistant <i>Staphylococcus aureus</i> infections | journal = Frontiers in Cellular and Infection Microbiology | volume = 14 | article-number = 1336821 | date = 31 January 2024 | pmid = 38357445 | doi = 10.3389/fcimb.2024.1336821 | doi-access = free | pmc = 10864608 }}</ref>
Bacteriophage therapy uses viruses as antimicrobial agents to overcome the antibiotic resistance in bacteria with biofilms<ref name="pmid17566713">{{cite journal | vauthors = Hanlon GW | title = Bacteriophages: an appraisal of their role in the treatment of bacterial infections | journal = International Journal of Antimicrobial Agents | volume = 30 | issue = 2 | pages = 118–128 | date = August 2007 | pmid = 17566713 | doi = 10.1016/j.ijantimicag.2007.04.006 }}</ref> Phage therapy is used to treat the [[Pseudomonas aeruginosa]] infection in the lungs, which is frequently seen in cystic fibrosis patients, as these bacteria produce biofilms which give them multi-drug resistance.<ref name="pmid31130925">{{cite journal | vauthors = Ciofu O, Tolker-Nielsen T | title = Tolerance and Resistance of <i>Pseudomonas aeruginosa</i> Biofilms to Antimicrobial Agents-How <i>P. aeruginosa</i> Can Escape Antibiotics | journal = Frontiers in Microbiology | volume = 10 | article-number = 913 | date = 2019 | pmid = 31130925 | pmc = 6509751 | doi = 10.3389/fmicb.2019.00913 | doi-access = free }}</ref>
===Gene modulators===
Several small molecules that aim at compensating various mutations of the ''CFTR'' gene are under development. CFTR [[Gene modulation|modulator therapies]] has been used instead of other types of genetic therapies. These therapies focus on the expression of a genetic mutation instead of the mutated gene itself. Modulators are split into two classes: potentiators and correctors. Potentiators act on the CFTR ion channels that are embedded in the cell membrane, and these drugs help open up the channel to allow transmembrane flow. Correctors are meant to assist in the transportation of nascent proteins, proteins that are formed by ribosomes before it is morphed into a specific shape, to the cell surface to be implemented into the cell membrane.<ref name=Ram2019>{{cite journal | vauthors = Ramsey BW, Downey GP, Goss CH | title = Update in Cystic Fibrosis 2018 | journal = American Journal of Respiratory and Critical Care Medicine | volume = 199 | issue = 10 | pages = 1188–1194 | date = May 2019 | pmid = 30917288 | pmc = 6519861 | doi = 10.1164/rccm.201902-0310UP | id = {{ProQuest|2230820891}} }}</ref>
Most target the transcription stage of genetic expression. One approach has been to try and develop medication that get the ribosome to overcome the [[stop codon]] and produce 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 [[nonsense mutation]]s 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 the expression of a full-length protein. Future research for these modulators is focused on the cellular targets that can be affected by a change in a gene's expression. Otherwise, genetic therapy will be used as a treatment when modulator therapies do not work given that 10% of people with cystic fibrosis are not affected by these drugs.<ref name="pmid20818846">{{cite journal | vauthors = Dietz HC | title = New therapeutic approaches to mendelian disorders | journal = The New England Journal of Medicine | volume = 363 | issue = 9 | pages = 852–863 | date = August 2010 | pmid = 20818846 | doi = 10.1056/NEJMra0907180 | s2cid = 5809127 | doi-access = free }} Free full text</ref>
[[Elexacaftor/ivacaftor/tezacaftor]] was approved in the United States in 2019 for cystic fibrosis.<ref name=FDA2019Tx>{{Cite web|url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-breakthrough-therapy-cystic-fibrosis|archive-url=https://web.archive.org/web/20191023030845/https://www.fda.gov/news-events/press-announcements/fda-approves-new-breakthrough-therapy-cystic-fibrosis|url-status=dead|archive-date=23 October 2019|title=FDA approves new breakthrough therapy for cystic fibrosis | author = Office of the Commissioner |date=24 October 2019|website=FDA|language=en|access-date=13 November 2019}}</ref> This combination of previously developed medicines can treat up to 90% of people with cystic fibrosis.<ref name=Ram2019/><ref name=FDA2019Tx/> This medication restores some effectiveness of the CFTR protein so that it can work as an ion channel on the cell's surface.<ref name="Cystic Fibrosis Foundation-2">{{Cite web|url=https://www.cff.org/Life-With-CF/Treatments-and-Therapies/Medications/CFTR-Modulator-Therapies/|title=CFTR Modulator Therapies | ___location = Bethesda, Md. | publisher = Cystic Fibrosis Foundation |language=en|access-date=13 November 2019}}</ref>
===Ecological therapy===
It has previously been shown that inter-species interactions are an important contributor to the pathology of CF lung infections. Examples include the production of antibiotic degrading enzymes such as β-lactamases and the production of metabolic by-products such as short-chain fatty acids (SCFAs) by anaerobic species, which can enhance the pathogenicity of traditional pathogens such as ''Pseudomonas aeruginosa''.<ref name="pmid26774156">{{cite journal | vauthors = Sherrard LJ, McGrath SJ, McIlreavey L, Hatch J, Wolfgang MC, Muhlebach MS, Gilpin DF, Elborn JS, Tunney MM | title = Production of extended-spectrum β-lactamases and the potential indirect pathogenic role of Prevotella isolates from the cystic fibrosis respiratory microbiota | journal = International Journal of Antimicrobial Agents | volume = 47 | issue = 2 | pages = 140–145 | date = February 2016 | pmid = 26774156 | pmc = 4746055 | doi = 10.1016/j.ijantimicag.2015.12.004 }}</ref> Due to this, it has been suggested that the direct alteration of CF microbial community composition and metabolic function would provide an alternative to traditional antibiotic therapies.<ref name="Khanolkar"/>
=== Antisense therapy ===
[[Antisense therapy]] is being researched to treat a subset of mutations that have limited or no response to CFTR modulators.<ref name="pmid36697233">{{cite journal | vauthors = Kim YJ, Krainer AR | title = Antisense Oligonucleotide Therapeutics for Cystic Fibrosis: Recent Developments and Perspectives | journal = Molecules and Cells | volume = 46 | issue = 1 | pages = 10–20 | date = January 2023 | pmid = 36697233 | pmc = 9880599 | doi = 10.14348/molcells.2023.2172 }}</ref> Such mutations fall into two classes: splicing (e.g., c.3718-2477C>T) and nonsense (e.g., G542X, W1282X), both of which result in very low expression of CFTR protein, although the protein itself is usually unaffected. This is contrary to the more common mutations such as ΔF508 which have normal CFTR expression but in a non-functional form. Modulators serve only to correct these aberrant proteins and are of little to no benefit in the case of insufficient expression. Antisense oligonucleotides (ASOs) can solve this problem through the promotion of mRNA degradation or by changing pre-mRNA splicing, nonsense-mediated mRNA decay, or translation, thus increasing CFTR expression.{{citation needed|date=August 2025}}
==Society and culture==
* ''Salt in My Soul: An Unfinished Life'', a posthumous memoir by [[Mallory Smith]], a Californian with CF
* ''[[Sick: The Life and Death of Bob Flanagan, Supermasochist]]'', a 1997 documentary film
* ''[[65 Redroses|65_RedRoses]]''<!--Yes, it is really an underscore in the title-->, a 2009 documentary film
* ''[[Breathing for a Living]]'', a memoir by [[Laura Rothenberg]]
* ''Every Breath I Take: Surviving and Thriving with Cystic Fibrosis'', book by [[Claire Wineland]]
* ''[[Five Feet Apart]]'', a 2019 romantic drama film starring [[Cole Sprouse]] and [[Haley Lu Richardson]]
* ''Orla Tinsley: Warrior'', a 2018 documentary film about CF campaigner [[Orla Tinsley]]
* The [[performance art]] of [[Martin O'Brien (artist)|Martin O'Brien]]
* ''[[Hi Nanna]]'', 2023 Telugu-language film about a girl with CF
* ''Sickboy'', a podcast hosted by [[Jeremie Saunders]] about cystic fibrosis and other chronic illnesses<ref>Hillary Gillis, [https://www.vice.com/en/article/meet-sickboy-the-halifax-podcast-normalizing-death-through-dark-laughs/ "Meet Sickboy: The Halifax Podcast Normalizing Death Through Dark Laughs"]. ''[[Vice (magazine)|Vice]]'', 26 July 2017.</ref>
== Explanatory notes ==
{{Reflist|group=note}}
== References ==
{{Reflist}}
== External links ==
{{Commons category}}
* [https://www.genecards.org/cgi-bin/cardsearch.pl?search=cystic+fibrosis&search_type=kwd&mini=yes&speed=fast#results Search GeneCards for genes involved in cystic fibrosis]
* [http://www.
* {{cite web | url = https://medlineplus.gov/cysticfibrosis.html | publisher = U.S. National Library of Medicine | work = MedlinePlus | title = Cystic Fibrosis }}
{{Medical condition classification and resources
| DiseasesDB = 3347
| ICD10 = {{ICD10|E|84||e|70}}
| ICD9 = {{ICD9|277.0}}
| ICDO =
| OMIM = 219700
| MedlinePlus = 000107
| eMedicineSubj = article
| eMedicineTopic = 1001602
| MeshID = D003550
| GeneReviewsID = NBK1250
| GeneReviewsName = CFTR-Related Disorders
| Orphanet = 586
}}
{{Respiratory pathology}}
{{Channelopathy}}
{{ABC transporter disorders}}
{{Authority control}}
[[Category:Cystic fibrosis| ]]
[[Category:Autosomal recessive disorders]]
[[Category:Channelopathies]]
[[Category:Lung disorders]]
[[Category:Pancreas disorders]]
[[
[[Category:Respiratory diseases]]
[[Category:Steatorrhea-related diseases]]
| |||