Cystic Fibrosis – Diagnosis, Symptoms, and Treatment

What is Cystic Fibrosis?

Cystic fibrosis is a genetic disorder characterized by abnormal chloride channels, these channels are critical in maintaining the mucosal layers that coat the cells within many organs. Defective channels result in a thicker and stickier mucus that builds up and blocks passages within the body. This abnormal mucus affect many organ systems, most notably the lungs and gastrointestinal tract. 

The abnormal mucus in the lungs blocks the small air passages and is almost impossible to remove with coughing. This leads to a form of chronic obstructive pulmonary disease which presents with difficulty breathing, coughing, 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.

What Causes Cystic Fibrosis?

Cystic fibrosis occurs due to mutations in a gene called CFTR.  This gene codes for a protein in the chloride channels that are located in nearly every cell in the body.  Mutations in this protein lead to abnormal chloride transport resulting in thick and viscous secretions in various organs – this includes the lungs, pancreas, liver, intestines, 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.  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 common complications of cystic fibrosis 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 is a genetic disease that is passed down through families. It is a recessive disease which means that both parents must carry the gene in order for the disease to be present. This means that a parent with cystic fibrosis will not necessarily have a child with cystic fibrosis if their partner does not carry the gene. 

Cystic fibrosis is most common in caucasians, in the United States about 1 in 3,000 people are living with cystic fibrosis. There are some forms that are mild and go undetected until late in life. As screening improves and disease recognition increases, lifespan of people living with cystic fibrosis will rise, and the prevalence of disease is anticipated to rise. 

Signs and Symptoms

Cystic fibrosis has a variety of symptoms that occur from birth until late in life. In very young children gastrointestinal symptoms are more common, while adults generally present with more severe lung disease.

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.

Gastrointestinal symptoms vary based on age. In young children intestinal obstructions from mucus is common. This can result in abdominal pain, lack of stool production, abdominal distinction, and poor feeding. As patients age signs of Pancreatic insufficiency develop, the most common symptoms being:

• Fat malabsorption

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

Diagnosis

Cystic fibrosis if often identified during newborn screening programs in the United States.  Some cases are missed by newborn screening; therefore, the symptoms of cystic fibrosis may appear in older children and adults.

The diagnosis of cystic fibrosis typically requires symptoms affecting at least one organ system and evidence of abnormal CFTR function.  CFTR function is evaluated by either a sweat chloride test or genetic testing.  Patients with cystic fibrosis typically have elevated sweat chloride levels due to abnormalities in the chloride channels, this does not lead to symptoms but is extremely useful for diagnosis. This test is not perfect and in some cases DNA analysis is used instead. 

Patients with a confirmed diagnosis of cystic fibrosis generally undergo genotyping to assess which specific gene mutation is leading to their illness – some mutations are approved for use of a medication called Kalydeco (ivacaftor). Which is more effective than traditional treatments but only works in a small number of cases.

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 if an abnormality is detected on x-ray.

Patients with symptoms of pancreatic, liver, or biliary tract 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.

Cystic Fibrosis Medication and Treatment

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. This medication helps to loosen the abnormal mucus in the lungs, relieving obstructions and preventing severe infections.

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 to assist with opening the airways and improving the effectiveness of these therapies.

High-dose ibuprofen may help preserve lung function in children and young adolescents.  Patients with advanced lung disease may be candidates for lung transplantation. This is considered a last resort as the lifelong imunnosupressive medications that are required can lead to other illnesses and complications. 

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:

• Pancreaze (pancrelipase)
• Creon (pancrelipase)
• Zenpep (pancrelipase)

References:

1. De Boeck K, Wilschanski M, Castellani C, et al. Cystic fibrosis: terminology and diagnostic algorithms. Thorax 2006; 61:627. - https://www.ncbi.nlm.nih.gov/pubmed/16384879
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. - https://www.ncbi.nlm.nih.gov/pubmed/18639722
3. Ratjen F, Döring G. Cystic fibrosis. Lancet 2003; 361:681. -https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(03)12567-6.pdf