Cystic Fibrosis

What is Cystic Fibrosis?

Cystic fibrosis is genetic disorder characterized by abnormal chloride channels.  This characteristically results in disease affecting multiple organ systems, most notably the lungs and gastrointestinal tract.  Lung disease is usually manifested as obstructive lung disease due to bronchiectasis.  Paints often develop difficulty breathing, cough, and wheezing.  The pancreas is also frequently damaged in cystic fibrosis, which leads to recurrent pancreatitis, abdominal pain, diabetes, and malabsorption of nutrients.

Patients that do not receive treatment typically progress and develop end-stage lung and pancreatic disease that may require organ transplantation.  Due to the importance of this condition, it is critical that patients understand its causes, symptoms, and treatment.  By the end of this article, you will have the answers to these essential questions

What causes Cystic Fibrosis?

Cystic fibrosis occurs due to mutations in a gene called CFTR.  This gene codes for a protein located in chloride channels.  Mutations in this protein lead to abnormal chloride transport, resulting in thick and viscous secretions in various organs – this includes the lungs, pancreas, liver, intestine, and reproductive tract.

Abnormal secretions in the lungs characteristically cause chronic obstruction in the airways, leading to chronic lung infection with various bacteria such as Haemophilus influenzae, Staphylococcus aureus, and Pseudomonas aeruginosa.  Chronic pulmonary injury and inflammation eventually lead to bronchiectasis – pus-filled secretions in dilated airways of the lung.

Pancreatic insufficiency is the most common gastrointestinal manifestation of cystic fibrosis.  Thick pancreatic secretions frequently lead to obstruction of the pancreatic ducts, which impairs release of pancreatic enzymes (exocrine deficiency).  This often results in malabsorption of vitamins, nutrients, and minerals.  The pancreatic islet cells responsible for insulin release may also become damaged, resulting in diabetes.

Other complications of cystic fibrosis may include:

  • Sinusitis
  • Meconium ileus & distal ileal obstruction
  • Rectal prolapse
  • Hepatobiliary disease & liver cirrhosis
  • Male infertility – absence of vas deferens
  • Decreased female fertility

How common is Cystic Fibrosis?

Cystic fibrosis most commonly affects Caucasians, with a prevalence of about 1:3000 persons in Caucasian Americans.  As screening improves and disease recognition increases, the prevalence of disease is anticipated to rise.  Patients with cystic fibrosis typically require referral to a pulmonary medicine specialist.

What are the symptoms and signs of Cystic Fibrosis?

Cystic fibrosis causes protean manifestations, but the most common include lung and gastrointestinal symptoms.

Respiratory symptoms often involve recurrent cough that eventually becomes persistent and productive of mucus.  Patients also typically have wheezing and may complain of shortness of breath.

Pancreatic insufficiency is usually characterized by:

  • Fat malabsorption
  • Diarrhea
  • Impaired growth
  • Vitamin deficiencies – vitamins A, D, E, and K
  • Abdominal pain – due to recurrent pancreatitis

Male patients frequently have infertility due to absence of the vas deferens during development.

How is Cystic Fibrosis diagnosed?

Cystic fibrosis if often identified during newborn screening programs in the United States.  Some cases are missed by newborn screening; therefore, the condition may be present in children or adults with characteristic symptoms.

The diagnosis of cystic fibrosis typically requires symptoms affecting at least one organ system and evidence of abnormal CFTR function.  CFTR function is usually evaluated with a sweat chloride tests or genetic testing.  Patients with cystic fibrosis typically have elevated sweat chloride levels.  Individuals with equivocal sweat chloride levels generally undergo DNA analysis.

Patients with a confirmed diagnosis generally undergo genotyping to evaluate for specific mutations as this can affect treatment – some mutations are approved for use of a medication called Kalydeco (ivacaftor).

If you have pulmonary symptoms, your doctor will likely order a chest x-ray to evaluate your lung anatomy and rule out other conditions that cause difficulty breathing – such as pneumonia or heart failure.  They may also need to obtain a CT scan of the chest to acquire a more detailed lung examination.

Patients with symptoms of pancreatic or hepatobiliary disease generally receive an abdominal ultrasound or CT scan of the abdomen.

Your doctor will likely order routine blood tests such as a CMP (comprehensive metabolic panel), lipase, and CBC (complete blood cell count).  A CMP evaluates for kidney and liver function, as well as glucose and electrolyte levels.  Lipase is a marker for pancreatic injury.  A complete blood cell count evaluates your red cells, white cells, and platelets.

How is Cystic Fibrosis treated?

Cystic fibrosis is treated with various approaches depending on the organ system affected and the age of the patient.  The following treatments generally apply to individuals age >6.

Chronic lung disease in cystic fibrosis is treated with a variety of therapies.  Patients with certain mutations found on CFTR genotyping may benefit from treatment with one of the following agents:

  • Kalydeco (ivacaftor).
  • Orkambi (lumacaftor-ivacaftor)

Pulmonzyme (dornase alfa) is typically recommended for children with moderate to severe lung disease.

Chronic therapy with hypertonic saline given through a nebulizer may help patients with chronic cough and signs of obstructive lung disease.  Patients with significant sputum production are often treated with physiotherapy to promote mucus clearance. Those with evidence of airway inflammation and chronic cough may also improve with the antibiotic Zithromax (azithromycin).  Short-acting bronchodilators such as ProAir or Ventolin (albuterol) are typically recommended for patients prior to inhalation of hypertonic saline, antibiotic treatment, or chest physiotherapy.

High-dose ibuprofen may help preserve lung function in children and young adolescents.  Patients with advanced lung disease may be candidates for lung transplantation.

Cystic fibrosis patients with pancreatic insufficiency frequently require pancreatic enzyme replacement therapy – these agents contain enzymes such as lipase, amylase, and protease.  These agents are important as they may reduce the risk of malabsorption and nutritional deficiencies.  The most commonly prescribed therapies include:

Cystic Fibrosis Patient Summary:

  • Cystic fibrosis is a genetic disorder characterized by abnormal chloride channels, which characteristically results in multi-organ disease, most notably in the lungs and gastrointestinal tract.
  • Lung disease is usually manifested as obstructive lung disease due to bronchiectasis. Patients often develop difficulty breathing, cough, and wheezing. 
  • Pancreatic disease manifests as recurrent pancreatitis, abdominal pain, diabetes, and malabsorption of nutrients.
  • Cystic fibrosis if often identified during newborn screening programs in the United States. Some cases are missed and present during older age.
  • The diagnosis of cystic fibrosis requires symptoms affecting at least one organ system and evidence of abnormal CFTR function (sweat chloride tests or genetic testing).
  • Patients with certain mutations found on CFTR genotyping may benefit from treatment with Kalydeco (ivacaftor) or Orkambi (lumacaftor-ivacaftor).
  • Pulmozyme (dornase alfa) is typically recommended for children with moderate to severe lung disease.
  • Chronic therapy with hypertonic saline, physiotherapy, and the antibiotic Zithromax (azithromycin) often help improve pulmonary symptoms. Short-acting bronchodilators such as ProAir or Ventolin (albuterol) are recommended prior to these strategies.
  • High-dose ibuprofen may help preserve lung function in children and young adolescents. Advanced lung disease may require lung transplantation.

Pancreatic insufficiency frequently requires pancreatic enzyme replacement therapy (lipase, amylase, and protease).  The most commonly prescribed agents include Pancreaze, Creon, and Zenpep.

References:

  1. De Boeck K, Wilschanski M, Castellani C, et al. Cystic fibrosis: terminology and diagnostic algorithms. Thorax 2006; 61:627.
  2. Farrell PM, Rosenstein BJ, White TB, et al. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr 2008; 153:S4.
  3. Ratjen F, Döring G. Cystic fibrosis. Lancet 2003; 361:681.

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The above information is an educational aid only. It is not intended as medical advice for individual conditions or treatments. Talk to your doctor, nurse or pharmacist before following any medical regimen to see if it is safe and effective for you.