Cystic Fibrosis: Overview and Practice Questions (2024)

Cystic fibrosis (CF) is a debilitating genetic disorder that profoundly impacts the lives of those affected by it.

This inherited condition disrupts normal mucus production in the body, leading to severe respiratory and digestive complications.

This article breaks down the fundamentals of cystic fibrosis, exploring its causes, symptoms, and available treatment methods.

What is Cystic Fibrosis?

Cystic fibrosis is a genetic disorder that primarily affects the respiratory and digestive systems. It leads to the production of thick, sticky mucus that can clog airways and impair lung function, causing breathing difficulties and increasing the risk of lung infections.

CF also affects the pancreas, leading to digestive problems and malnutrition. It is a lifelong condition with no cure, but treatments aim to manage symptoms and improve quality of life.

Pathophysiology

Cystic fibrosis is characterized by a defect in the CFTR gene, which encodes for a protein that regulates the movement of chloride and sodium ions across epithelial membranes.

This defect impairs the function of the CFTR protein, leading to thick, sticky mucus production in various organs.

In the lungs, this mucus obstructs the airways, causing difficulty in breathing and making the lungs prone to bacterial infections and inflammation. This can lead to chronic respiratory diseases such as bronchiectasis.

In the digestive system, the thick mucus blocks pancreatic ducts, inhibiting the release of digestive enzymes. This results in malabsorption of nutrients and difficulties in digestion, often leading to malnutrition and poor growth.

Additionally, CF can affect the liver, leading to biliary cirrhosis due to blocked bile ducts, and can also impact the reproductive system. Sweat glands are also affected, producing sweat with an abnormally high salt content.

Summary: The pathology of cystic fibrosis involves multiple organ systems, primarily affecting the respiratory and digestive systems, and is characterized by chronic infections, inflammation, and complications related to mucus buildup.

Signs and Symptoms

The signs and symptoms of cystic fibrosis vary, often depending on the severity of the disease.

Key symptoms include:

• Respiratory Symptoms: Persistent cough, often producing thick mucus, frequent lung infections, leading to chronic bronchitis or pneumonia, and wheezing or shortness of breath.
• Digestive Symptoms: Poor weight gain and growth (failure to thrive) in infants and children, steatorrhea (fatty, smelly stools) due to poor absorption of nutrients. and intestinal blockage, particularly in newborns (meconium ileus).
• Salty-tasting Skin: Parents often notice that their child’s skin tastes salty when kissed.
• Additional Symptoms: Nasal polyps and sinusitis, clubbing (enlargement and rounding) of fingers and toes, fatigue, and reduced exercise tolerance.
• Male Reproductive System: Most males with CF are infertile due to obstructed or absent vas deferens.
• Other Complications: Diabetes, liver disease, and bone thinning (i.e., osteoporosis).

Note: Symptoms can vary in intensity, and individuals with CF might experience different sets of symptoms over time. Early diagnosis and management are crucial to improve quality of life and longevity.

Diagnosis

Diagnosing cystic fibrosis involves several tests, often initiated due to the presence of symptoms or a positive newborn screening result.

Key diagnostic tests include:

• Sweat Chloride Test: The most definitive test for CF. It measures the amount of chloride in the sweat. High levels of chloride suggest CF.
• Genetic Testing: Used to identify mutations in the CFTR gene. This is particularly useful for confirming a diagnosis following a positive sweat test or as part of a newborn screening program.
• Newborn Screening: In many places, newborns are screened for CF using a blood test. This test looks for elevated levels of immunoreactive trypsinogen (IRT), an indicator of CF.
• Pulmonary Function Tests: These tests assess lung function and are often used to monitor the disease’s progression rather than for initial diagnosis.
• Chest X-rays or CT Scans: Imaging tests can identify lung infections and other abnormalities associated with CF.
• Stool Tests: These can be used to evaluate fat absorption, which can be impaired in CF due to pancreatic dysfunction.
• Sputum Tests: Analysis of sputum can detect lung infections common in people with CF.

Note: A combination of these tests, along with the evaluation of clinical symptoms, is typically used to diagnose cystic fibrosis. It’s important to start treatment early to manage symptoms and improve quality of life.

Treatment

Treatment for cystic fibrosis is comprehensive and aims to manage symptoms, reduce complications, and improve quality of life.

Key aspects include:

• Airway Clearance Techniques:  These help loosen and clear mucus from the lungs. Techniques include chest physiotherapy, positive expiratory pressure (PEP) therapy, and exercise.
• Inhaled Medications: Bronchodilators to open the airways, mucolytics to thin mucus, and antibiotics to treat and prevent lung infections.
• Pancreatic Enzyme Supplements: These aid in digestion and nutrient absorption for patients with pancreatic insufficiency.
• High-calorie, High-salt Diet: Essential to address malnutrition and maintain overall health. Dietitians often work with patients to create individualized meal plans.
• CFTR Modulators: These are a class of drugs that target the underlying genetic defect in CF, helping the CFTR protein function more effectively. Their availability and efficacy depend on the specific genetic mutations a person has.
• Regular Exercise: Encouraged to improve lung function and overall well-being.
• Management of Complications: Includes treatment for diabetes, liver disease, and other CF-related conditions.
• Psychosocial Support: Counseling and support groups help patients and families cope with the challenges of living with CF.
• Regular Monitoring: Regular follow-ups with healthcare providers to monitor lung function, nutritional status, and overall health.
• Lung Transplantation: In severe cases, a lung transplant may be considered when lung function significantly declines.

CF treatment is typically managed by a team of healthcare professionals, including doctors, nurses, dietitians, physiotherapists, and social workers, providing comprehensive care tailored to each individual’s needs.

Cystic Fibrosis Practice Questions

1. What is cystic fibrosis characterized by?
Cystic fibrosis is a hereditary disease characterized by lung congestion and infection along with malabsorption of nutrients by the pancreas. It’s a multifaceted disease caused by genetically defective chloride ions in the apical surface of the epithelial lining resulting in impaired chloride flow across membranes through the cystic fibrosis conductance regulator (CFTR) channel.

2. What happens in cystic fibrosis?
Mucus clogs the lungs leading to chronic respiratory infections, and mucus obstructs the ducts of the pancreas preventing digestive enzymes from reaching the intestines.

3. What system is cystic fibrosis a dysfunction of?
Exocrine system

4. What causes thick secretions in cystic fibrosis?
The disruption of the chloride transport causes thick secretions, and sodium is absorbed in the airways, pancreas, and bile ducts.

5. Which ethnicity is most likely to carry the CFTR gene?
Caucasian/white

6. What does the x-ray typically look like in patients with cystic fibrosis?
Translucencies, an enlarged heart, and a flattened diaphragm.

7. How is cystic fibrosis diagnosed?
Sweat chloride test

8. What two infections are common in patients with cystic fibrosis?
Staphylococcus aureus and pseudomonas

9. What common respiratory issues does a patient with cystic fibrosis have?
Atelectasis, bronchial hyperreactivity, asthma, hemoptysis, pneumothorax, pulmonary hypertension, respiratory failure, sleep-related breathing problems, and symptomatic rhinosinusitis.

10. Aside from respiratory issues, what other clinical effects may come from cystic fibrosis?
Anemia, appendicitis, and cystic fibrosis-related diabetes (CFRD) due to the scarring of the pancreas, gallbladder disease, gastroesophageal reflux disease (GERD), malnutrition, growth failure, infertility, pancreatitis, and meconium ileus.

11. How many positive results should one have to be diagnosed with cystic fibrosis?
Two positive results

12. What are the common signs and symptoms of cystic fibrosis?
Salty sweat, residue on skin and/or clothes, abdominal distention and cramping, fatty stools, and malnutrition even with a ravenous appetite. Pulmonary indications include advanced chronic obstructive pulmonary disease (COPD), hypercapnia, and severe hypoxemia when the disease is advanced.

13. How can you manage patients with cystic fibrosis?
Most patients suffering from cystic fibrosis are treated with pulmozyme, sympathomimetics, percussion, and postural drainage. In addition, positive expiratory pressure (PEP), flutter, vest therapy, hypertonic saline and xanthines must also be considered for managing this disease.

14. What other treatments are available for cystic fibrosis?
Lung transplant, gene replacement, vitamins, food supplements, and oxygen therapy.

15. What is the prognosis for cystic fibrosis?
The disease has no cure but can be managed. The life expectancy of a person suffering from this condition is 37.5 years.

16. What deficiencies does cystic fibrosis involve?
Nutritional deficiencies

17. What is the typical arterial blood gas (ABG) for a patient with cystic fibrosis?
Mixed respiratory acidosis and metabolic alkalosis

18. What kind of disease is cystic fibrosis?
It is an inherited obstructive disease.

19. Where can you find the defective gene for cystic fibrosis?
Chromosome 7

20. What pathological findings are associated with cystic fibrosis?
Hyperinflation, thick tenacious mucus, and airway obstructions that lead to atelectasis.

21. What is a common sign of a person with cystic fibrosis?
They present as malnourished with excessive secretions and may also suffer from meconium ileus (i.e., bowel obstruction).

22. What symptom of cystic fibrosis is common in men?
Male infertility

23. What are the chances that a child will be a carrier of the cystic fibrosis gene if both the mother and father are carriers?
There is a 50% chance that the child will be a carrier.

24. What may be seen on the fingers and toes of patients with cystic fibrosis?
Digital clubbing

25. What is the cause of digital clubbing?
Clubbing is mainly caused by chronically low levels of oxygen.

26. What is the median age of survival for people with cystic fibrosis?
37 years

27. What test must be elevated to diagnose cystic fibrosis?
An elevated sweat chloride test is performed to diagnose cystic fibrosis.

28. What are the four commonly used therapies in the management of cystic fibrosis?
Oral enzymes and vitamins, antibiotics, postural drainage, and expectorants.

29. A cystic fibrosis patient appears malnourished even on what kind of diet?
A high-calorie diet.

30. Lung infections like pseudomonas aeruginosa are most often treated with what antibiotic?
Tobramycin (TOBI)

31. A cystic fibrosis patient in generally good condition may be a candidate for what surgical procedure?
Lung transplant

32. What percussion note if often heard in patients with cystic fibrosis?
Hyperresonant percussion note

33. What are the typical breath sounds of a patient with cystic fibrosis?
Crackles (i.e., rales)

34. What is a common non-respiratory clinical manifestation of cystic fibrosis?
Sinusitis

35. What supplementary vitamins do cystic fibrosis patients need?
A, E, D, and K

36. Cystic fibrosis patients can have chest percussion done manually, or they can use what?
The theravest.

37. What medications are used to treat cystic fibrosis?
Short-acting beta-agonists, hypertonic saline, pulmozyme, and tobramycin (TOBI).

38. What contributes to bone disease among individuals with cystic fibrosis?
Malabsorption of vitamins D and K, failure to thrive, delayed puberty, physical inactivity, and the use of corticosteroids.

39. What protein is responsible for cystic fibrosis?
Cystic fibrosis transmembrane conductance regulator protein.

40. What are the four reasons associated with poor appetite among children with cystic fibrosis?
Depression, anxiety, fatigue and anorexia.

41. How are enzyme tablets administered to infants and young children?
They  can be mixed with soft acidic food.

42. What is the probability that child will have cystic fibrosis if both parents carry the cystic fibrosis gene?
One in four children will inherit the disease.

43. What is the average life expectancy for people with cystic fibrosis?
The average life expectancy for people with cystic fibrosis is 45 years.

44. Eighty-five percent of patients with cystic fibrosis has what condition?
Pancreatic insufficiency

45. What are the two linked clinical manifestations of cystic fibrosis?
Meconium Ileus and distal intestinal obstructive syndrome.

46. What lung and upper respiratory tract diseases are associated with cystic fibrosis?
Persistent bacterial infection, inflammation, airway destruction, bronchiectasis, mucus plugged airways, goblet cell hyperplasia, and disrupted cilia function.

47. What is the most common amino acid that is deleted from the channel protein in cystic fibrosis?
Phenylalanine changes the structure of the CFTR (cystic fibrosis transmembrane conductance regulator) protein (channel) in a way that it can no longer transport chloride.

48. What cellular mechanism takes place within the sweat glands of cystic fibrosis patients?
There is an inhibited chloride reabsorption that results in inhibited sodium reabsorption, which makes sweat saltier than normal.

49. How would you explain the “low-volume” model as a result of cystic fibrosis?
In the “low-volume” model, the chloride channel is involved in chloride outflow into the mucus that somewhat traps the sodium and water, retaining its fluidity. Normally, a significant amount of chloride remains in the mucus, causing sodium and water to remain in the mucus. In a cystic fibrosis patient, there are not enough chloride that outflows into the mucus. This results in less negative charge that is capable of keeping the sodium and water in the mucus, thus, causing the mucus to thicken and lose its fluidity.

50. What two organs are affected by the thickened mucus in cystic fibrosis patients?
Lungs and pancreas

51. What happens in the lungs as a result of thickened mucus?
Bronchiectasis is a result of thickened mucus that stays in the bronchioles and physically pushes them open, distending them and causing them to widen. The result is permanent and eventually leads to fibrosis of these bronchioles.

52. How does mucous affect cilia?
It flattens the cilia

53. How is cystic fibrosis manifested in the lungs?
Cystic fibrosis is manifested in lungs as acute exacerbations that include cough, dyspnea, decreased exercise tolerance, fatigue, and increased sputum production. This leads to accelerated permanent loss of lung function.

54. How are sinuses affected by cystic fibrosis?
It may cause nasal and sinus polyps.

55. How is cystic fibrosis diagnosed?
If a newborn screening is positive, a cystic fibrosis genetic panel is done followed by a sweat chloride test and complete CFTR sequencing.

56. What mucolytic agents are given for cystic fibrosis?
Dornase alfa and hypertonic saline

57. What is the brand name for dornase alfa?
Pulmozyme

58. How does Pulmozyme work?
It breaks down extracellular DNA, decreased mucus viscosity, and increases the expectoration of mucus.

59. Which antibiotics are used to treat cystic fibrosis?
Tobramycin (TOBI), aztreonam (Cayston) and colistemethate (Colistin).

60. How is tobramycin taken?
300 mg BID

61. What is the dose for tobramycin?
10 mg/kg IV every 24 hours

62. When are tobramycin levels checked?
Two and ten hours after infusion.

63. What tests are given for cystic fibrosis?
Sweat chloride test, pulmonary function testing (PFT), arterial blood gas (ABG), and chest x-ray.

64. What results of the sweat chloride test indicate cystic fibrosis?
Increased concentrations of NaCl (sodium chloride) and K (potassium) in the sweat.

65. What are the typical results of pulmonary function testing in patients with cystic fibrosis?
Airflow obstruction

66. What can be observed in the chest x-ray of a person suffering from cystic fibrosis?
Hyperinflation and increased pulmonary markings.

67. What do the ABG results show in patients with severe cystic fibrosis?
Hypoxemia and hypercapnia

68. What methods are generally used to manage cystic fibrosis?
Chest physiotherapy for secretion drainage, pancreatic enzyme replacement, administration of salbutamol and ipratropium bromide, inhalation of hypertonic saline or DNAse, and antibiotics for infectious exacerbations.

69. What is the gold standard treatment for cystic fibrosis?
Lung transplant

70. How do you get a diagnosis of cystic fibrosis?
Sweat chloride test, CFTR gene analysis, nasal electrical potential difference, and newborn screening

Final Thoughts

Cystic fibrosis is a complex genetic disorder with widespread effects, primarily impacting the respiratory and digestive systems.

Although there is no cure, advancements in diagnostic techniques and comprehensive treatment strategies have significantly improved the quality of life and life expectancy for those affected.

Ultimately, a multidisciplinary approach, combining medical, nutritional, and psychosocial support, is key to effectively managing cystic fibrosis and enhancing the lives of those living with this challenging condition.