Cystic fibrosis (CF) is a progressive and multisystemic disease that can affect any organ that exhibits significant exocrine function.1,2 CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; these CFTR abnormalities can cause a domino effect, leading to complications in several organs.2–4


Effects of CFTR Protein Dysfunction in the Lungs

CFTR protein abnormalities result in a domino effect, which ultimately leads to structural damage in several organs. For example, in the lungs3–6:


charts-protein-dysfunction charts-protein-dysfunction

A similar cascade of effects occurs in other organ systems as well; with the end result being inflammation leading to organ and tissue damage.1,3,4,6–12

For many individuals with CF,  symptoms manifest early in life, with certain signs appearing in utero.3,8–10,13 Additionally, certain organ damage, including: lungs, liver, or pancreas, can occur before symptoms.1,10,14 As individuals with CF age, complications from CF extend beyond lung disease.1,15–17 As a result, patients with CF require complete care from multidisciplinary teams as their complications change over time.1,15–17


Disease Progression in the Lungs

In a patient with CF, lung disease begins early and develops throughout their lifetime.3

Lung Disease Progression3,10,13,14,17,18
0-5 years 6-10 years 11-20 years 20+ years

Early mucinous
plugging and

Advancing bronchiectasis and pulmonary exacerbationsimages-lung-6-to-10
Bronchiectasis with recurrent exacerbations, requiring nutritional support, supplementary oxygen, and noninvasive ventilator supportimages-lung-11-to-20

Bronchiectasis with hemoptysis, pneumothorax;
progressive, respiratory failure; lung transplantimages-lung-20-plus

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 Pancreas

CF can affect both the exocrine and endocrine functions, which can result in pancreatic insufficiency.9,10



Clogged pancreatic ducts prevent digestive enzymes from passing into the intestines, causing the pancreas to breakdown9,10


CFTR protein dysfunction can result in impaired insulin secretion and carbohydrate intolerance, leading to cystic fibrosis-related diabetes mellitus (CFRD)9,10

Pancreatic insufficiency can begin at birth and progresses throughout a patient’s life.3,4
Pancreatic Insufficiency Progression3,9,10,13,19
0-5 years 6-10 years 11-20 years 20+ years

Pancreatic exocrine 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%images-pancreatic-0-to-5

Up to 2% of patients <10 years of age may have CF-related diabetes mellitusimages-pancreatic-6-to-10
Up to 19% of adolescents have CF-related diabetes mellitus images-pancreatic-11-to-20

Up to 40%-50% of adults have CF-related diabetes mellitus images-pancreatic-20-plus

Additional Considerations

Nutritional/caloric deficiency issue (growth impairment)
Ongoing pancreatic tissue degradation, as thickened secretions clog more ducts

Disease Progression in the Liver

CFTR protein dysfunctions can cause altered liver secretions, which can result in changed bile viscosity, causing the blockage of bile ducts.1,10,11 Subsequently, this blockage can result in liver scarring, inflammation, abnormal liver function, and eventually, liver damage.1,11,12

Liver Damage Progression3,10,20
0-5 years 6-10 years 11-20 years 20+ years

Onset of abnormal liver function tests

5% of patients may
develop biliary cirrhosis
by age 15 yearsimages-liver-11-to-20

5%-10% of patients develop portal hypertension and a liver transplant may be required in some patients (typically age >35 years)images-liver-20-plus

Disease Progression in the Gastrointestinal Tract

Gastrointestinal complications and symptoms can occur throughout a patient with CF’s lifetime.3,10,11,13,17,20–22

Gastrointestinal Complications and Symptoms3,10,11,13,17,20–22
0-5 years 6-10 years 11-20 years 20+ years

Up to 21% of newborns with CF have gastrointestinal problems, such as meconium ileus, within the first days of lifeimages-gastrointestional-0-to-5

Constant vigilance regarding malnutritionimages-gastrointestional-6-to-10
Decreased motility may lead to chronic constipationimages-gastrointestional-11-to-20

Distal intestinal obstruction syndrome (DIOS)images-gastrointestional-20-plus

Additional Considerations

Gastrointestinal abnormalities are often evident before birth

  • DIOS may occur in 15% of all patients with CF
  • DIOS in older children and adults presents with clinical overlap to meconium ileus seen in newborns
  • One study found that 65% of adults with DIOS had meconium ileus as newborns

Progression of Bone Disease

Due to increasing evidence, it is suggested that CFTR dysfunction affects bone metabolism.23 The prevalence of bone disease increases in older patient populations.17,24 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.3,24

Bone Disease Progression¹⁷


<18 years

  • 1.1% osteopenia
  • 0.3% osteoporosis

≥18 years

  • 17.9% osteopenia
  • 7.0% osteoporosis

Disease Progression of Reproductive Organs

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


Reproductive Organs Disease Progression²


Male Infertility

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

Female Infertility

  • Women can experience fertility impairment related to thick cervical mucus that fails to undergo the usual mid-cycle thinning


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 with CF, it’s important to keep in mind the complications—beyond lung disease—that will develop and progress as patients age.1,15–17 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.1,13,14,16,17,20,25

ppFEV1, percent predicted forced expiratory volume in 1 second.

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Multi-Organ Disease Progression