==Signs and symptoms==

<!-- [[File:Cystic fibrosis manifestations.png|thumb|Signs and symptoms of cystic fibrosis<ref name="isbn0-8089-2325-0">{{cite book | author = Kliegman, Robert; Richard M Kliegman | title = Nelson essentials of pediatrics | publisher = Elsevier Saunders | location = St. Louis, Mo | year = 2006 | isbn = 0-8089-2325-0 }}</ref>]] -->

[[File:Blausen 0286 CysticFibrosis.png|thumb|Health problems associated with cystic fibrosis]]

The main signs and symptoms of cystic fibrosis are salty tasting [[skin]],<ref name="pmid17557942">{{cite journal | author = Quinton PM | title = Cystic fibrosis: lessons from the sweat gland | journal = Physiology (Bethesda) | volume = 22 | issue = 3| pages = 212–25 |date=June 2007 | pmid = 17557942 | doi = 10.1152/physiol.00041.2006 | url = http://nips.physiology.org/cgi/pmidlookup?view=long&pmid=17557942 }}</ref> poor growth and poor weight gain despite normal food intake,<ref name="pmid15339250">{{cite journal | author = Hardin DS | title = GH improves growth and clinical status in children with cystic fibrosis – a review of published studies | journal = Eur. J. Endocrinol. | volume = 151 | issue =Suppl 1 | pages = S81–5 |date=August 2004 | pmid = 15339250 | doi = 10.1530/eje.0.151S081 | url = http://eje-online.org/cgi/pmidlookup?view=long&pmid=15339250 }}</ref> accumulation of thick, sticky mucus,<ref name="pmid19726878">{{cite journal | author = De Lisle RC | title = Pass the bicarb: the importance of HCO3- for mucin release | journal = J. Clin. Invest. | volume = 119 | issue = 9 | pages = 2535–7 |date=September 2009 | pmid = 19726878 | pmc = 2735941| doi = 10.1172/JCI40598 }}</ref> frequent chest infections, and coughing or shortness of breath.<ref name="pmid19393108">{{cite journal | author = O'Malley CA | title = Infection control in cystic fibrosis: cohorting, cross-contamination, and the respiratory therapist | journal = Respir Care | volume = 54 | issue = 5 | pages = 641–57 |date=May 2009 | pmid = 19393108 | doi = 10.4187/aarc0446| url = http://www.rcjournal.com/contents/05.09/05.09.0641.pdf }}</ref> Males can be [[infertility|infertile]] due to [[congenital absence of the vas deferens]].<ref name="pmid19535829">{{cite journal | author = Makker K, Agarwal A, Sharma R | title = Oxidative stress & male infertility | journal = Indian J. Med. Res. | volume = 129 | issue = 4 | pages = 357–67 |date=April 2009 | pmid = 19535829 | url = http://www.icmr.nic.in/ijmr/2009/april/0403.pdf }}</ref> Symptoms often appear in infancy and childhood, such as [[bowel obstruction]] due to [[meconium ileus]] in newborn babies.<ref name="pmid17030173">{{cite journal | author = Blackman SM, Deering-Brose R, McWilliams R, ''et al.'' | title = Relative contribution of genetic and nongenetic modifiers to intestinal obstruction in cystic fibrosis | journal = Gastroenterology | volume = 131 | issue = 4 | pages = 1030–9 |date=October 2006 | pmid = 17030173 | pmc = 1764617 | doi = 10.1053/j.gastro.2006.07.016 | url = http://linkinghub.elsevier.com/retrieve/pii/S0016-5085(06)01659-3 }}</ref> As the children grow, they must exercise to release mucus in the alveoli.<ref name="pmid19393104">{{cite journal | author = Ratjen FA | title = Cystic fibrosis: pathogenesis and future treatment strategies | journal = Respir Care | volume = 54 | issue = 5 | pages = 595–605 |date=May 2009 | pmid = 19393104 | doi = 10.4187/aarc0427| url = http://www.rcjournal.com/contents/05.09/05.09.0595.pdf }}</ref> [[cilium|Ciliated]] [[epithelium|epithelial cells]] in the patient have a mutated protein that leads to abnormally viscous mucus production.<ref name="pmid19726878" /> The poor growth in children typically presents as an inability to gain weight or height at the same rate as their peers and is occasionally not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multifactorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness.<ref name="pmid15339250" />

In rare cases, cystic fibrosis can manifest itself as a coagulation disorder. Vitamin K is normally absorbed from breast milk, formula, and later solid foods. This absorption is impaired in some cystic fibrosis patients. Young children are especially sensitive to [[vitamin K]] malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves and limited ability to absorb Vitamin K from dietary sources after birth. Because factors II, VII, IX, and X (clotting factors) are vitamin 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 there is an underlying disease.<ref>{{cite journal |author=Reaves J, Wallace G |title=Unexplained bruising: weighing the pros and cons of possible causes |journal=Consultant for Pediatricians |volume=9 |pages=201–2 |year=2010 |url=http://www.consultantlive.com/pediatrics/display/article/10162/1583642}}</ref>

===Lungs and sinuses===

[[File:Cystic Fibrosis Respiratory Infections by Age.svg|thumb|Respiratory infections in CF varies 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 | author = Flume PA, Mogayzel Jr PJ, Robinson KA, ''et al.'' | title = Cystic Fibrosis Pulmonary Guidelines: Pulmonary Complications: Hemoptysis and Pneumothorax | journal = Am J Respir Crit Care Med | volume = 182| issue = 3| page = 298|date=March 2010 | pmid = 20299528 | doi = 10.1164/rccm.201002-0157OC}}</ref><ref name=kumar2007>{{cite book |author=Mitchell, Richard Sheppard; Kumar, Vinay; Robbins, Stanley L.; Abbas, Abul K.; Fausto, Nelson |title=Robbins basic pathology |publisher=Saunders/Elsevier |year=2007 |isbn=1-4160-2973-7}}</ref> Inflammation and infection cause injury and structural changes to the lungs, leading to a variety of symptoms. In the early stages, incessant coughing, copious [[phlegm]] production, and decreased ability to exercise are common. Many of these symptoms occur when [[bacteria]] that normally inhabit the thick mucus grow out of control and cause pneumonia.

In later stages, changes in the architecture of the lung, such as pathology in the major airways ([[bronchiectasis]]), further exacerbate difficulties in breathing. Other symptoms include coughing up blood ([[hemoptysis]]), 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/> In addition to typical bacterial infections, people with CF more commonly develop other types of lung disease. Among these is [[allergic bronchopulmonary aspergillosis]], in which the body's response to the common [[fungus]] ''[[Aspergillus fumigatus]]'' causes worsening of breathing problems. Another is infection with ''[[Mycobacterium avium complex|Mycobacterium avium]]'' complex (MAC), a group of bacteria related to [[tuberculosis]], which can cause a lot of lung damage and does not respond to common antibiotics.<ref name="pmid16266669">{{cite journal | author = Girón RM, Domingo D, Buendía B, Antón E, Ruiz-Velasco LM, Ancochea J | title = Nontuberculous mycobacteria in patients with cystic fibrosis | language = Spanish; Castilian | journal = Arch. Bronconeumol. | volume = 41 | issue = 10 | pages = 560–5 |date=October 2005 | pmid = 16266669| url = http://www.elsevier.es/revistas/0300-2896/41/560| doi = 10.1016/S1579-2129(06)60283-8 }}</ref>

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 | author = Franco LP, Camargos PA, Becker HM, Guimarães RE | title = Nasal endoscopic evaluation of children and adolescents with cystic fibrosis | journal = Braz J Otorhinolaryngol | volume = 75 | issue = 6 | pages = 806–13 |date=December 2009 | pmid = 20209279 | doi = 10.1590/S1808-86942009000600006| url = http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1808-86942009000600006&lng=en&nrm=iso&tlng=en }}</ref> Recurrent sinonasal polyps can occur in as many as 10% to 25% of CF patients.<ref name=kumar2007/> These polyps can block the nasal passages and increase breathing difficulties.<ref>{{cite journal |author=Maldonado M, Martínez A, Alobid I, Mullol J |title=The antrochoanal polyp |journal=Rhinology |volume=42 |issue=4 |pages=178–82 |date=December 2004 |pmid=15626248 }}</ref><ref>{{cite journal |author=Ramsey B, Richardson MA |title=Impact of sinusitis in cystic fibrosis |journal=J. Allergy Clin. Immunol. |volume=90 |issue=3 Pt 2 |pages=547–52 |date=September 1992 |pmid=1527348 |doi= 10.1016/0091-6749(92)90183-3|url=}}</ref>

Cardiorespiratory complications are the most common cause of death (~80%) in patients at most CF centers in the United States.<ref name=kumar2007/>

===Gastrointestinal===

Prior to prenatal and [[newborn screening]], cystic fibrosis was often diagnosed when a newborn infant failed to pass feces ([[meconium]]). Meconium may completely block the [[small intestine|intestines]] and cause serious illness. This condition, called [[meconium ileus]], occurs in 5–10%<ref name=kumar2007/><ref>{{cite journal |author=Eggermont E, De Boeck K |title=Small-intestinal abnormalities in cystic fibrosis patients |journal=Eur. J. Pediatr. |volume=150 |issue=12 |pages=824–8 |date=October 1991 |pmid=1743211 |doi= 10.1007/BF01954999 }}</ref> of newborns with CF. 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>{{cite journal |doi=10.1056/NEJM195808282590901 |author=Kulczycki LL, Shwachman H |title=Studies in cystic fibrosis of the pancreas; occurrence of rectal prolapse |journal=N. Engl. J. Med. |volume=259 |issue=9 |pages=409–12 |date=August 1958 |pmid=13578072 }}</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>{{cite journal |author=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=N. Engl. J. Med. |volume=339 |issue=10 |pages=653–8 |date=September 1998 |pmid=9725922 |doi= 10.1056/NEJM199809033391002|url=}}</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/>

The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the feces, a disorder known as [[malabsorption]]. Malabsorption leads to [[malnutrition]] and poor growth and development because of calorie loss. Resultant [[hypoproteinemia]] may be severe enough to cause generalized edema.<ref name=kumar2007/> Individuals with CF also have difficulties absorbing the fat-soluble vitamins [[vitamin A|A]], [[vitamin D|D]], [[vitamin E|E]], and [[vitamin K|K]].

In addition to the pancreas problems, people with cystic fibrosis experience more [[gastroesophageal reflux disease|heartburn]], intestinal blockage by [[Intussusception (medical disorder)|intussusception]], and [[constipation]].<ref>{{cite journal |author=Malfroot A, Dab I |title=New insights on gastro-esophageal reflux in cystic fibrosis by longitudinal follow up |journal=Arch. Dis. Child. |volume=66 |issue=11 |pages=1339–45 |date=November 1991 |pmid=1755649 |pmc=1793275 |doi= 10.1136/adc.66.11.1339|url=}}</ref> Older individuals with CF may develop [[distal intestinal obstruction syndrome]] when thickened feces cause intestinal blockage.<ref>{{cite journal |author=Khoshoo V, Udall JN |title=Meconium ileus equivalent in children and adults |journal=Am. J. Gastroenterol. |volume=89 |issue=2 |pages=153–7 |date=February 1994 |pmid=8304294 }}</ref>

Exocrine pancreatic insufficiency occurs in the majority (85% to 90%) of patients with CF.<ref name=kumar2007/> It is mainly associated with "severe" CFTR mutations, where both alleles are completely nonfunctional (e.g. ΔF508/ΔF508).<ref name=kumar2007/> It occurs in 10% to 15% of patients with one "severe" and one "mild" CFTR mutation where there still is a little CFTR activity, or where there are two "mild" CFTR mutations.<ref name=kumar2007/> In these milder cases, there is still sufficient pancreatic exocrine function so that enzyme supplementation is not required.<ref name=kumar2007/> There are usually no other GI complications in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development.<ref name=kumar2007/> 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/>

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. Over time, this can lead to scarring and nodularity ([[cirrhosis]]). The liver fails to rid the blood of toxins and does not make important [[protein]]s, such as those responsible for [[coagulation|blood clotting]].<ref>{{cite journal |author=Williams SG, Westaby D, Tanner MS, Mowat AP |title=Liver and biliary problems in cystic fibrosis |journal=Br. Med. Bull. |volume=48 |issue=4 |pages=877–92 |date=October 1992 |pmid=1458306 |doi= |url=}}</ref><ref name="liver">{{cite journal |author=Colombo C, Russo MC, Zazzeron L, Romano G |title=Liver disease in cystic fibrosis |journal=J. Pediatr. Gastroenterol. Nutr. |volume=43 |issue=Suppl 1 |pages=S49–55 |date=July 2006 |pmid=16819402 |doi=10.1097/01.mpg.0000226390.02355.52 |url=}}</ref> Liver disease is the third most common cause of death associated with CF.<ref name=kumar2007/>

===Endocrine===

The [[pancreas]] contains the [[islets of Langerhans]], which are responsible for making insulin, a hormone that helps regulate blood [[glucose]]. Damage of the pancreas can lead to loss of the islet [[Cell (biology)|cell]]s, leading to a type of diabetes that is unique to those with the disease.<ref>{{cite journal |author=Moran A, Pyzdrowski KL, Weinreb J, ''et al.'' |title=Insulin sensitivity in cystic fibrosis |journal=Diabetes |volume=43 |issue=8 |pages=1020–6 |date=August 1994 |pmid=8039595 |doi= 10.2337/diabetes.43.8.1020 }}</ref> This [[cystic fibrosis-related diabetes]] (CFRD) shares characteristics that can be found in [[Diabetes mellitus type 1|type 1]] and [[Diabetes mellitus type 2|type 2]] diabetics, and is one of the principal nonpulmonary complications of CF.<ref>{{cite journal |author=Alves Cde A, Aguiar RA, Alves AC, Santana MA |title=Diabetes mellitus in patients with cystic fibrosis |journal=J Bras Pneumol |volume=33 |issue=2 |pages=213–21 |date=April 2007 |pmid=17724542 |doi=10.1590/S1806-37132007000200017}}</ref> 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>{{cite journal |author=Haworth CS, Selby PL, Webb AK, ''et al.'' |title=Low bone mineral density in adults with cystic fibrosis |journal=Thorax |volume=54 |issue=11 |pages=961–7 |date=November 1999 |pmid=10525552 |pmc=1745400 |doi=10.1136/thx.54.11.961 }}</ref> In addition, people with CF often develop [[Nail clubbing|clubbing]] of their fingers and toes due to the effects of chronic illness and [[Hypoxia (medical)|low oxygen]] in their tissues.<ref name="pmid12806875">{{cite journal | author = Vandemergel X, Decaux G | title = [Review on hypertrophic osteoarthropathy and digital clubbing] | language = French | journal = [[Revue Médicale de Bruxelles]] | volume = 24 | issue = 2 | pages = 88–94 |date=April 2003 | pmid = 12806875 }}</ref><ref name="pmid3488032">{{cite journal | author = Pitts-Tucker TJ, Miller MG, Littlewood JM | title = Finger clubbing in cystic fibrosis | journal = Arch. Dis. Child. | volume = 61 | issue = 6 | pages = 576–9 |date=June 1986 | pmid = 3488032 | pmc = 1777828 | doi = 10.1136/adc.61.6.576| url = }}</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>{{cite journal |author=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=1059–62 |date=October 2000 |pmid=11035677 |doi= 10.1378/chest.118.4.1059|url=}}</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 [[penis]]), but potentially also by other mechanisms such as causing [[azoospermia]], [[teratospermia]], and [[oligoasthenospermia]].<ref>{{cite doi|10.1093/humupd/dms027}}</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>{{cite journal |author=Augarten A, Yahav Y, Kerem BS, ''et al.'' |title=Congenital bilateral absence of vas deferens in the absence of cystic fibrosis |journal=Lancet |volume=344 |issue=8935 |pages=1473–4 |date=November 1994 |pmid=7968122 |doi= 10.1016/S0140-6736(94)90292-5|url=}}</ref> Some women have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts [[ovulation]] and causes [[amenorrhea]].<ref>{{cite journal |author=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|url=}}</ref>