Cystic Fibrosis

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Basics

Description

  • Cystic fibrosis (CF) is an autosomal recessive mutation that most prominently affects the pulmonary and pancreatic systems but may involve any organ system.
  • Due to improvements in medical care leading to a dramatic increase in survival, adults living with CF now outnumber children (1).

Epidemiology

Although CF is the most common lethal inherited disease in Caucasians, it is found in every racial group.

Incidence
Number of infants born with CF in relation to the total number of live births in the United States

  • 1 in 3,200 Caucasians
  • 1 in 10,000 Latin Americans
  • 1 in 10,500 Native Americans
  • 1 in 15,000 African Americans
  • 1 in 30,000 Asian Americans

Prevalence
There are >30,000 patients with CF living in the United States and 70,000 worldwide. The median predicted survival for CF patients in the United States was 46.2 years (95% CI, 45.2–47.6).

Etiology and Pathophysiology

  • Primary defect is abnormal function of an epithelial chloride channel protein encoded by the CFTR (CF transmembrane conductance regulator) gene on chromosome band 7q31.2. CFTR is a regulated chloride channel that affects the activity of chloride and sodium channels on the cell surface, with mutations leading to abnormally viscous secretions that alter organ functions.
  • Obstruction, infection, and inflammation negatively affect lung growth, structure, and function, leading to decreased mucociliary clearance, intense neutrophilic response with infection, and eventual degradation of supporting tissues leading to bronchiectasis and eventual failure.

Genetics

  • CF is an autosomal recessive, single-gene disorder. There exist >1,500 mutations in the CFTR gene that can cause varying severity of phenotypic CF. Most common is the deltaF508 mutation, which accounts for 85.3% of cases in the United States, followed by the G542X (4.5%) and G551D (4.3%) mutations.
  • The severity of disease can also be affected by modifier genes (CFTM1 for meconium ileus), GERD, severe respiratory infection, or environmental factors such as smoke exposure.

General Prevention

Preconception counseling

  • American Congress of Obstetricians and Gynecologists recommends preconception or 1st/2nd trimester genetic analysis for all North American couples.
  • Newborn screening has been integral in early diagnosis, with 62.4% of new CF cases in 2019 identified with this method.
  • Patients diagnosed prior to onset of symptoms have better lung function and nutritional outcomes.

Commonly Associated Conditions

  • CF-related diabetes (CFRD)
    • May present as steady decline in weight, lung function, or increased frequency of exacerbation
    • Leading comorbid complication (20.7%)
    • Result of progressive insulin deficiency
    • Early screening and treatment may improve survival.
  • Upper respiratory
    • Rhinosinusitis is seen in up to 100% of patients with CF.
    • Nasal polyps are seen in up to 86% of patients.
  • The GI tract
    • Pancreatic exocrine insufficiency (85–90%)
    • Malabsorption of fat, protein, and fat-soluble vitamins (A, D, E, and K)
    • Hepatobiliary disease (12.6%) including focal biliary cirrhosis and cholelithiasis
    • Meconium ileus at birth (10–15%)
    • Distal intestinal obstruction syndrome (DIOS): (5.3%)
    • GERD (32.7%)
  • Endocrine
    • Bone mineral disease (16.6%)
    • Joint disease (3.0%)
    • Hypogonadism
    • Frequent low testosterone levels in men
    • Menstrual irregularities
  • Reproductive organs
    • Congenital bilateral absence of the vas deferens with obstructive azoospermia in 98% of males
  • Depression (12.8%)

Pregnancy Considerations

  • Pulmonary disease may worsen during pregnancy.
  • CF may cause increased incidence of preterm delivery, IUGR, and cesarean section.
  • Advances in fertility treatments now allow men with CF to father children.

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Basics

Description

  • Cystic fibrosis (CF) is an autosomal recessive mutation that most prominently affects the pulmonary and pancreatic systems but may involve any organ system.
  • Due to improvements in medical care leading to a dramatic increase in survival, adults living with CF now outnumber children (1).

Epidemiology

Although CF is the most common lethal inherited disease in Caucasians, it is found in every racial group.

Incidence
Number of infants born with CF in relation to the total number of live births in the United States

  • 1 in 3,200 Caucasians
  • 1 in 10,000 Latin Americans
  • 1 in 10,500 Native Americans
  • 1 in 15,000 African Americans
  • 1 in 30,000 Asian Americans

Prevalence
There are >30,000 patients with CF living in the United States and 70,000 worldwide. The median predicted survival for CF patients in the United States was 46.2 years (95% CI, 45.2–47.6).

Etiology and Pathophysiology

  • Primary defect is abnormal function of an epithelial chloride channel protein encoded by the CFTR (CF transmembrane conductance regulator) gene on chromosome band 7q31.2. CFTR is a regulated chloride channel that affects the activity of chloride and sodium channels on the cell surface, with mutations leading to abnormally viscous secretions that alter organ functions.
  • Obstruction, infection, and inflammation negatively affect lung growth, structure, and function, leading to decreased mucociliary clearance, intense neutrophilic response with infection, and eventual degradation of supporting tissues leading to bronchiectasis and eventual failure.

Genetics

  • CF is an autosomal recessive, single-gene disorder. There exist >1,500 mutations in the CFTR gene that can cause varying severity of phenotypic CF. Most common is the deltaF508 mutation, which accounts for 85.3% of cases in the United States, followed by the G542X (4.5%) and G551D (4.3%) mutations.
  • The severity of disease can also be affected by modifier genes (CFTM1 for meconium ileus), GERD, severe respiratory infection, or environmental factors such as smoke exposure.

General Prevention

Preconception counseling

  • American Congress of Obstetricians and Gynecologists recommends preconception or 1st/2nd trimester genetic analysis for all North American couples.
  • Newborn screening has been integral in early diagnosis, with 62.4% of new CF cases in 2019 identified with this method.
  • Patients diagnosed prior to onset of symptoms have better lung function and nutritional outcomes.

Commonly Associated Conditions

  • CF-related diabetes (CFRD)
    • May present as steady decline in weight, lung function, or increased frequency of exacerbation
    • Leading comorbid complication (20.7%)
    • Result of progressive insulin deficiency
    • Early screening and treatment may improve survival.
  • Upper respiratory
    • Rhinosinusitis is seen in up to 100% of patients with CF.
    • Nasal polyps are seen in up to 86% of patients.
  • The GI tract
    • Pancreatic exocrine insufficiency (85–90%)
    • Malabsorption of fat, protein, and fat-soluble vitamins (A, D, E, and K)
    • Hepatobiliary disease (12.6%) including focal biliary cirrhosis and cholelithiasis
    • Meconium ileus at birth (10–15%)
    • Distal intestinal obstruction syndrome (DIOS): (5.3%)
    • GERD (32.7%)
  • Endocrine
    • Bone mineral disease (16.6%)
    • Joint disease (3.0%)
    • Hypogonadism
    • Frequent low testosterone levels in men
    • Menstrual irregularities
  • Reproductive organs
    • Congenital bilateral absence of the vas deferens with obstructive azoospermia in 98% of males
  • Depression (12.8%)

Pregnancy Considerations

  • Pulmonary disease may worsen during pregnancy.
  • CF may cause increased incidence of preterm delivery, IUGR, and cesarean section.
  • Advances in fertility treatments now allow men with CF to father children.

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