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Multi-Organ Disease Progression

On this page:
Lungs, Pancreas, Liver, GI Tract Bones Reproductive Organs

Cystic fibrosis (CF) is a progressive and multisystemic disease.1,2 For many individuals with CF, symptoms manifest early in life, with certain signs appearing in utero.3-7 Additionally, certain organ damage, including lungs, liver, or pancreas, can occur before symptoms, and continue to progress over time.1,5,8-11 These complications vary between patients.11 As a result, patients with CF may require complete care from multidisciplinary teams as their complications change over time.1,9-11

Select the Potential Disease Progression You’d Like to Explore More:

 

View disease progression by organ

  • Lung
  • Pancreas
  • Liver
  • GI Tract
    Lung
    Disease Progression in the Lung5-7,11,13
     
    In a patient with CF, CFTR protein dysfunction causes lung disease that begins early and progresses throughout their lifetime.
    InfancyEarly ChildhoodChildhood, Adolescence, and Early AdulthoodAdulthood and Aging

    Inflammation may occur as early as in utero and into infancy, with the possibility of mucus plugging and bronchiectasis

    Lungs with early stages of inflammation

    Airway inflammation, lung structure and lung function may progress throughout childhood

    Lungs with mucus trapped in small and medium bronchioles

    Lower airway inflammation and worsening airway abnormalities including established bronchiectasis may occur, driven by the inflammation in the lungs

    Lungs with widespread inflammation and mucus trapped in more bronchioles

    Airway destruction and complications, including bacterial infections, bronchiectasis with hemoptysis, and pneumothorax, may occur and may lead to progressive respiratory failure, often requiring lung transplant

    Lungs with increased inflammation and mucus plugging throughout all bronchioles

     

    Additional Considerations

    Potentially irreversible damage as early as 2 years of age; eventually pulmonary insufficiency is responsible for ~80% of CF-related deaths

    • Patients may experience structural lung damage before ppFEV1 declines
     
    Disease Progression in the Lung5-7,11,13
     
    In a patient with CF, CFTR protein dysfunction causes lung disease that begins early and progresses throughout their lifetime.
    Infancy

    Inflammation may occur as early as in utero and into infancy, with the possibility of mucus plugging and bronchiectasis

    Lungs with early stages of inflammation

    Early Childhood

    Airway inflammation, lung structure and lung function may progress throughout childhood

    Lungs with mucus trapped in small and medium bronchioles

    Childhood, Adolescence, and Early Adulthood

    Lower airway inflammation and worsening airway abnormalities including established bronchiectasis may occur, driven by the inflammation in the lungs

    Lungs with widespread inflammation and mucus trapped in more bronchioles

    Adulthood and Aging

    Airway destruction and complications, including bacterial infections, bronchiectasis with hemoptysis, and pneumothorax, may occur and may lead to progressive respiratory failure, often requiring lung transplant

    Lungs with increased inflammation and mucus plugging throughout all bronchioles

    Additional Considerations
     

    Potentially irreversible damage as early as 2 years of age; eventually pulmonary insufficiency is responsible for ~80% of CF-related deaths

    • Patients may experience structural lung damage before ppFEV1 declines
    Pancreas
    Disease Progression in the Pancreas3,5-7,14
     
    CF can affect both the exocrine and endocrine functions of the pancreas. Pancreatic insufficiency may begin at birth.
    InfancyEarly ChildhoodChildhood, Adolescence, and Early AdulthoodAdulthood and Aging

    As early as in utero, acinar cells are obstructed with loss of tissue in infanthood

    Pancreatic insufficiency; up to 71% of patients with CF are pancreatic insufficient at birth

    By 1 year of age, the percent of patients with pancreatic insufficiency rises to approximately 90%

    Pancreas with clustered deficient acinar cells

    Clogged pancreatic ducts prevent digestive enzymes from passing into intestines and causing inflammation and pancreatic tissue breakdown

    Up to 2% of patients <10 years of age may have CF-related diabetes

    Pancreas with inflammation caused by mucus-clogged exocrine ducts

    Inflammation may progress to fibrosis and islet cells are destroyed, resulting in impaired insulin secretion and carbohydrate intolerance

    Up to 19% of adolescents have CF-related diabetes

    Pancreas with increased inflammation and destruction of cells

    Over time, the healthy tissue in the pancreas may be replaced with adipose cells, and only some islet cells and pancreatic ducts may remain

    Up to 40%-50% of adults have CF-related diabetes

    Pancreas with very few functional cells, largely replaced by fat cells

    Additional Considerations

     

    Nutritional or caloric deficiency may lead to growth impairment

    Ongoing pancreatic tissue degradation, as thickened secretions clog more ducts

    Disease Progression in the Pancreas3,5-7,14
     
    CF can affect both the exocrine and endocrine functions of the pancreas. Pancreatic insufficiency may begin at birth.
    Infancy

    As early as in utero, acinar cells are obstructed with loss of tissue in infanthood

    Pancreatic insufficiency; up to 71% of patients with CF are pancreatic insufficient at birth.

    By 1 year of age, the percent of patients with pancreatic insufficiency rises to approximately 90%

    Pancreas with clustered deficient acinar cells

    Early Childhood

    Clogged pancreatic ducts prevent digestive enzymes from passing into intestines and causing inflammation and pancreatic tissue breakdown

    Up to 2% of patients <10 years of age may have CF-related diabetes

    Pancreas with inflammation caused by mucus-clogged exocrine ducts

    Childhood, Adolescence, and Early Adulthood

    Inflammation may progress to fibrosis and islet cells are destroyed, resulting in impaired insulin secretion and carbohydrate intolerance

    Up to 19% of adolescents have CF-related diabetes

    Pancreas with increased inflammation and destruction of cells

    Adulthood and Aging

    Over time, the healthy tissue in the pancreas may be replaced with adipose cells, and only some islet cells and pancreatic ducts may remain

    Up to 40%-50% of adults have CF-related diabetes

    Pancreas with very few functional cells, largely replaced by fat cells

    Additional Considerations
     

     

    Nutritional or caloric deficiency may lead to growth impairment

    Ongoing pancreatic tissue degradation, as thickened secretions clog more ducts

    Liver
    Disease Progression in the Liver1,5,7,15-18
     
    CFTR protein dysfunctions can cause altered liver secretions, which can result in changed bile viscosity, and the subsequent blockage of bile ducts.
    InfancyEarly ChildhoodChildhood, Adolescence, and Early AdulthoodAdulthood and Aging

    Potential abnormalities in liver function tests

     

    Decreased bile flow, increased bile precipitation, and changes in bile viscosity may lead to accumulation of toxic bile acids and bile duct blockage

     

    Bile duct blockage may lead to inflammation, fibrosis, and cirrhosis around the bile ducts

    5% of patients may develop biliary cirrhosis by age 15 years

     

    Extensive liver damage may occur due to biliary cirrhosis, hepatic steatosis, or portal hypertension

    5% to 10% of patients develop portal hypertension, and a liver transplant may be required in some patients (typically age >35 years)

    Normal liverLiver with bile ducts showing accumulated bileLiver with inflammation and fibrosis around the bile ductsLiver with widespread inflammation, fibrosis, and fat cell accumulation
     

    Additional Considerations

    Blockage of bile ducts may result in liver scarring, inflammation, abnormal liver function, and eventually, liver damage.

     
    Disease Progression in the Liver1,5,7,15-18
     
    CFTR protein dysfunctions can cause altered liver secretions, which can result in changed bile viscosity, and the subsequent blockage of bile ducts.
    Infancy

    Potential abnormalities in liver function tests

    Normal liver

    Early Childhood

    Decreased bile flow, increased bile precipitation, and changes in bile viscosity may lead to accumulation of toxic bile acids and bile duct blockage

    Liver with bile ducts showing accumulated bile

    Childhood, Adolescence, and Early Adulthood

    Bile duct blockage may lead to inflammation, fibrosis, and cirrhosis around the bile ducts

    5% of patients may develop biliary cirrhosis by age 15 years

    Liver with inflammation and fibrosis around the bile ducts

    Adulthood and Aging

    Extensive liver damage may occur due to biliary cirrhosis, hepatic steatosis, or portal hypertension

    5% to 10% of patients develop portal hypertension, and a liver transplant may be required in some patients (typically age >35 years)

    Liver with widespread inflammation, fibrosis, and fat cell accumulation

    Additional Considerations
     

    Blockage of bile ducts may result in liver scarring, inflammation, abnormal liver function, and eventually, liver damage.

    GI Tract
    Disease Progression in the Gastrointestinal Tract3,5,16,19-21
     
    CFTR protein dysfunction causes gastrointestinal complications, and symptoms can occur throughout a patient with CF’s lifetime.
    InfancyEarly ChildhoodChildhood, Adolescence, and Early AdulthoodAdulthood and Aging

    Abnormal secretions result in an acidic environment in the ileum, causing thick mucus and meconium to block the small intestine

    Up to 20% of newborns with CF have gastrointestinal problems, such as meconium ileus, within the first days of life

    Intestines showing stool blockage in the small intestine

    Lack of digestive enzymes in the intestines (caused by exocrine pancreatic insufficiency) leads to risk of malnutrition if diet is not actively managed

    Intestines showing low levels of enzyme secretions in the small intestine

    Decreased motility, prolonged gut transit, and fat malabsorption, among other factors, may lead to chronic constipation

    Distal intestinal obstruction syndrome (DIOS) may occur in 15% of all patients with CF

    DIOS in older children and adults has a similar clinical presentation as meconium ileus in newborns

    One study found that 65% of adults with DIOS had meconium ileus as newborns

    Intestines showing stool blockage in the large intestine as well as low levels of enzyme secretion in the small intestineIntestines showing widespread stool blockage in the large intestine

     
     
    Disease Progression in the Gastrointestinal Tract3,5,16,19-21
     
    CFTR protein dysfunction causes gastrointestinal complications, and symptoms can occur throughout a patient with CF’s lifetime.
    Infancy

    Abnormal secretions result in an acidic environment in the ileum, causing thick mucus and meconium to block the small intestine

    Up to 20% of newborns with CF have gastrointestinal problems, such as meconium ileus, within the first days of life

    Intestines showing stool blockage in the small intestine

    Early Childhood

    Lack of digestive enzymes in the intestines (caused by exocrine pancreatic insufficiency) leads to risk of malnutrition if diet is not actively managed

    Intestines showing low levels of enzyme secretions in the small intestine

    Childhood, Adolescence, and Early Adulthood

    Intestines showing stool blockage in the large intestine as well as low levels of enzyme secretion in the small intestine

    Decreased motility, prolonged gut transit, and fat malabsorption, among other factors, may lead to chronic constipation

    Distal intestinal obstruction syndrome (DIOS) may occur in 15% of all patients with CF

    Adulthood and Aging

    DIOS in older children and adults has a similar clinical presentation as meconium ileus in newborns

    One study found that 65% of adults with DIOS had meconium ileus as newborns

    Intestines showing widespread stool blockage in the large intestine

     

    Progression of Bone Disease

    Due to increasing evidence, it is suggested that CFTR dysfunction affects bone metabolism.22 The prevalence of bone disease increases in older patient populations.11,23 Between ages 20-35, a patient with CF may demonstrate arthropathy and CF-related bone disease; these patients are also at an increased risk of low bone density fractures.7,23

    Bone Disease Progression11

    <18 years

    • 0.9% osteopenia
    • 0.3% osteoporosis

    ≥18 years

    • 18.5% osteopenia
    • 7.8% osteoporosis

    Disease in Reproductive Organs

    CFTR gene mutations may impair normal function of both male and female reproductive tracts. As a result, CF may lead to infertility in both men and women.2

    Reproductive Organ Disease2

    Male Infertility

    • Mutations in the CFTR gene can cause congenital bilateral absence of the vas deferens (CBAVD)
    • 98% of men with CF are infertile with obstructive azoospermia

    Female Infertility

    • Women may experience fertility impairment related to thick cervical mucus

    The Importance of Monitoring Multi-Organ Disease Progression

    As advances in CF knowledge and care are potentially able to prolong the life expectancy of many patients, it’s important to keep in mind the complications—beyond lung disease—that will develop and progress as patients age.1,9-11 Monitoring for these complications can help detect their emergence and progression, which can ensure earlier intervention; this has been associated with better outcomes in patients.1,6,8,10,11,15,24

    GI, gastrointestinal; ppFEV1, percent predicted forced expiratory volume in 1 second.

    References: 1. Kobelska-Dubiel N, Klincewicz B, Cichy W. Liver disease in cystic fibrosis. Prz Gastroenterol. 2014;9(3):136-141. doi:10.5114/pg.2014.43574 2. Ahmad A, Ahmed A, Patrizio P. Cystic fibrosis and fertility. Curr Opin Obstet Gynecol. 2013;25(3):167-172. doi:10.1097/GCO.0b013e32835f1745 3. Gibson-Corely KN, Meyerholz DK, Engelhardt JF. Pancreatic pathophysiology in cystic fibrosis. J Pathol. 2016;238(2):311-320. doi:10.1002/path.4634 4. Zielenski J. Genotype and phenotype in cystic fibrosis. Respiration. 2000;67(2):117‐133. doi:10.1159/000029497 5. O’Sullivan BP, Freedman SD. Cystic fibrosis. Lancet. 2009;373(9678):1891-1904. doi:10.1016/S0140-6736(09)60327-5 6. VanDevanter DR, Kahle JS, O’Sullivan AK, Sikirica S, Hodgkins PS. Cystic fibrosis in young children: a review of disease manifestation, progression, and response to early treatment. J Cyst Fibros. 2016;15(2):147-157. doi:10.1016/j.jcf.2015.09.008 7. Elborn JS. Cystic fibrosis. Lancet. 2016;388(10059):2519-2531. doi:10.1016/S0140-6736(16)00576-6 8. Ellemunter H, Fuchs SI, Unsinn KM, et al. Sensitivity of lung clearance index and chest computed tomography in early CF lung disease. Respir Med. 2010;104(12):1834-1842. doi:10.1016/j.rmed.2010.06.010 9. Naehrig S, Chao CM, Naehrlich L. Cystic fibrosis: diagnosis and treatment. Dtsch Arztebl Int. 2017;114(33-34):564-574. doi:10.3238/arztebl.2017.0564 10. Ronan NJ, Elborn JS, Plant BJ. Current and emerging comorbidities in cystic fibrosis. Presse Med. 2017;46(6):e125-e138. doi:10.1016/j.lpm.2017.05.011 11. Cystic Fibrosis Foundation. 2022 patient registry annual data report. Accessed April 1, 2024. https://www.cff.org/media/31216/download 12. de Jong PA, Ottink MD, Robben SG, et al. Pulmonary disease assessment in cystic fibrosis: comparison of CT scoring systems and value of bronchial and arterial dimension measurements. Radiology. 2004;231(2):434-439. doi:10.1148/radiol.2312021393 13. Khan MA, Sabz Ali Z, Sweezey N, Grasemann H, Palaniyar N. Progression of cystic fibrosis lung disease from childhood to adulthood: Neutrophils, neutrophil extracellular trap (NET) formation, and NET degradation. Genes. 2019;10:83. doi:10.3390/genes10030183 14. Rana M, Munns CF, Selvadurai H, Donaghue KC, Craig ME. Cystic fibrosis-related diabetes in children—gaps in the evidence? Nat Rev Endocrinol. 2010;6(7):371-378. doi:10.1038/nrendo.2010.85 15. Gelfond D, Borowitz D. Gastrointestinal complications of cystic fibrosis. Clin Gastroenterol Hepatol. 2013;11(4):333-342. doi:10.1016/j.cgh.2012.11.006 16. Averill S, Lubner MG, Menias CO, et al. Multisystem imaging findings of cystic fibrosis in adults: recognizing typical and atypical patterns of disease. AJR Am J Roentgenol. 2017;209(1):3-18. doi:10.2214/AJR.16.17462 17. Cañas T, Maciá A, Muñoz-Codoceo RA, et al. Hepatic and splenic acoustic radiation force impulse shear wave velocity elastography in children with liver disease associated with cystic fibrosis. Biomed Res Int. 2015;2015:517369. doi:10.1155/2015/517369 18. Sakiani S, Kleiner DE, Heller T, Koh C. Hepatic manifestations of cystic fibrosis. Clin Liver Dis. 2019;23(2):263-277. doi:10.1016/j.cld.2018.12.008 19. Lavie M, Manovitz T, Vilozni D, et al. Long-term follow-up of distal intestinal obstruction syndrome in cystic fibrosis. World J Gastroenterol. 2015;21(1):318-325. doi:10.3748/wjg.v21.i1.318 20. Abraham JM, Taylor CJ. Cystic fibrosis & disorders of the large intestine: DIOS, constipation, and colorectal cancer. J Cyst Fibros. 2017;16(suppl 2):S40-S49. doi:10.1016/j.jcf.2017.06.013 21. Sathe MN, Freeman AJ. Gastrointestinal, pancreatic, and hepatobiliary manifestations of cystic fibrosis. Pediatr Clin North Am. 2016;63(4):679-698. doi:10.1016/j.pcl.2016.04.008 22. Marquette M, Haworth CS. Bone health and disease in cystic fibrosis. Paediatr Respir Rev. 2016;20(suppl):2-5. doi:10.1016/j.prrv.2016.06.003 23. Jacquot J, Delion M, Gangloff S, Braux J, Velard F. Bone disease in cystic fibrosis: new pathogenic insights opening novel therapies. Osteoporos Int. 2016;27(4):1401-1412. doi:10.1007/s00198-015-3343-3 24. Chedevergne F, Sermet-Gaudelus I. Prevention of osteoporosis in cystic fibrosis. Curr Opin Pulm Med. 2019;25(6):660-665. doi:10.1097/MCP.0000000000000624