Cystic fibrosis - Allied Guru

Table of Contents

Introduction

Cystic fibrosis (CF) is a hereditary, autosomal recessive disorder.
It primarily affects the respiratory, digestive, and sweat gland systems.
The disease is caused by mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene.
CFTR gene is located on chromosome 7.
Defective CFTR protein leads to abnormal chloride and sodium transport across epithelial cells.
This results in the production of thick, sticky mucus.
The thick mucus causes obstruction of airways and ducts, leading to chronic infections and inflammation.
Cystic fibrosis is one of the most common life-limiting genetic disorders in children.
It affects multiple organs including lungs, pancreas, liver, intestines, and reproductive organs.
Early diagnosis and appropriate management have significantly improved survival and quality of life.

Etiology and Genetics

Cystic fibrosis is caused by mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene
The CFTR gene is located on chromosome 7
Inheritance pattern: Autosomal recessive
Both parents must be carriers for the child to be affected

Common Mutation

ΔF508 (Delta F508) mutation is the most common
Leads to misfolding and degradation of CFTR protein

Pathophysiology

The CFTR protein functions as a chloride ion channel in epithelial cells.

Normal Function

Regulates chloride and sodium transport
Maintains hydration of secretions

In Cystic Fibrosis

Defective chloride secretion
Increased sodium and water reabsorption
Dehydrated, thick mucus

Consequences

Airway obstruction
Chronic bacterial infections
Pancreatic duct blockage
Malabsorption

Organ System Involvement

1. Respiratory System

Thick mucus blocks the bronchi and bronchioles
Chronic cough with sputum
Recurrent lung infections (Pseudomonas, Staphylococcus)
Bronchiectasis
Progressive respiratory failure (leading cause of death)

2. Digestive System

Pancreatic duct obstruction
Deficiency of digestive enzymes
Fat malabsorption
Steatorrhea
Failure to thrive in children
Deficiency of fat-soluble vitamins (A, D, E, K)

3. Sweat Glands

Increased chloride and sodium in sweat
Basis of diagnostic sweat test
Risk of dehydration and electrolyte imbalance

4. Reproductive System

Male infertility due to congenital absence of vas deferens
Reduced fertility in females due to thick cervical mucus

Clinical Features

Chronic productive cough
Recurrent chest infections
Failure to thrive
Bulky, greasy stools
Salty taste of skin
Nasal polyps
Digital clubbing (late stage)

Diagnosis

1. Sweat Chloride Test (Gold Standard)

Measures chloride concentration in sweat
Based on defective CFTR-mediated chloride reabsorption
Chloride ≥ 60 mmol/L → diagnostic of cystic fibrosis
30–59 mmol/L → intermediate (requires repeat testing)
< 30 mmol/L → unlikely CF
Performed using pilocarpine iontophoresis

2. Newborn Screening

Initial screening test in many countries
Based on elevated immunoreactive trypsinogen (IRT) in blood
Positive screening requires confirmatory sweat test or genetic testing
Helps in early diagnosis before symptoms appear

3. Genetic Testing

Detects CFTR gene mutations
Useful for:
- Confirming diagnosis
- Identifying carriers
- Prenatal diagnosis
Common mutation detected: ΔF508

4. Pulmonary Function Tests (PFTs)

Assess lung involvement and disease severity
Shows:
- Obstructive pattern
- Reduced FEV₁
Used for monitoring progression, not primary diagnosis

5. Microbiological Examination

Sputum or throat swab culture
Identifies chronic infections like:
- Pseudomonas aeruginosa
- Staphylococcus aureus
Guides antibiotic therapy

6. Imaging Studies

Chest X-ray / HRCT chest
Findings include:
- Hyperinflation
- Bronchiectasis
- Mucus plugging
Helpful in assessing extent of lung damage

7. Pancreatic Function Tests

Low fecal elastase
Evidence of exocrine pancreatic insufficiency
Supports diagnosis in symptomatic patients

Management

Cystic fibrosis has no cure, but early and aggressive management improves survival.

Respiratory Management

Chest physiotherapy
Mucolytics (e.g., DNase)
Bronchodilators
Antibiotics for infections

Nutritional Management

Pancreatic enzyme replacement therapy
High-calorie, high-protein diet
Supplementation of fat-soluble vitamins

CFTR Modulator Therapy

Target specific CFTR mutations
Improves CFTR function
Example: correctors and potentiators

Complications

Chronic respiratory failure
Cor pulmonale
Diabetes mellitus (CFRD)
Liver disease
Osteoporosis

Prognosis

Prognosis has significantly improved with early diagnosis
Median survival now exceeds 40–50 years in many countries
Quality of life depends on early treatment and compliance

Prevention and Genetic Counseling

Carrier screening for at-risk couples
Prenatal diagnosis
Genetic counseling is essential

MCQs

1. Cystic fibrosis is inherited as:

A. Autosomal dominant
B. X-linked recessive
C. Autosomal recessive
D. Mitochondrial

2. The gene defective in cystic fibrosis is:

A. BRCA1
B. CFTR
C. HBB
D. p53

3. CFTR gene is located on which chromosome?

A. Chromosome 5
B. Chromosome 6
C. Chromosome 7
D. Chromosome 11

4. CFTR protein primarily functions as a:

A. Sodium channel
B. Potassium channel
C. Chloride channel
D. Calcium pump

5. Most common mutation in cystic fibrosis is:

A. G551D
B. R117H
C. ΔF508
D. N1303K

6. Pathophysiology of CF mainly results in:

A. Increased water secretion
B. Thick, dehydrated mucus
C. Excess mucus clearance
D. Alkaline secretions

7. The organ system most commonly affected in CF is:

A. Nervous system
B. Cardiovascular system
C. Respiratory system
D. Endocrine system

8. Major cause of morbidity and mortality in CF patients is:

A. Liver failure
B. Renal failure
C. Respiratory failure
D. Cardiac arrhythmia

9. Thick mucus in CF leads to:

A. Improved gas exchange
B. Airway obstruction
C. Increased ciliary movement
D. Reduced infections

10. Common organism causing lung infection in CF is:

A. Mycobacterium tuberculosis
B. Pseudomonas aeruginosa
C. Streptococcus pyogenes
D. Klebsiella pneumoniae

11. Pancreatic involvement in CF causes:

A. Hypersecretion of insulin
B. Exocrine pancreatic insufficiency
C. Acute pancreatitis
D. Pancreatic carcinoma

12. Fat malabsorption in CF leads to deficiency of:

A. Water-soluble vitamins
B. Vitamin B complex
C. Fat-soluble vitamins
D. Vitamin C

13. Steatorrhea in CF occurs due to deficiency of:

A. Bile salts
B. Digestive enzymes
C. Gastric acid
D. Intestinal hormones

14. Sweat chloride test is based on abnormal:

A. Sodium secretion
B. Potassium secretion
C. Chloride reabsorption
D. Calcium absorption

15. Diagnostic sweat chloride value for CF is:

A. < 30 mmol/L
B. 30–40 mmol/L
C. > 60 mmol/L
D. > 100 mmol/L only

16. Gold standard diagnostic test for CF is:

A. Chest X-ray
B. Genetic testing
C. Sweat chloride test
D. Pulmonary function test

17. Newborn screening for CF commonly measures:

A. Serum amylase
B. Immunoreactive trypsinogen (IRT)
C. Sweat sodium
D. Serum lipase

18. CFTR dysfunction causes increased reabsorption of:

A. Chloride
B. Potassium
C. Sodium and water
D. Calcium

19. Lung pathology in CF commonly shows:

A. Emphysema
B. Bronchiectasis
C. Pleural effusion
D. Pneumothorax only

20. Male infertility in CF is due to:

A. Testicular atrophy
B. Low testosterone
C. Absence of vas deferens
D. Erectile dysfunction

21. Female infertility in CF is mainly due to:

A. Ovarian failure
B. Thick cervical mucus
C. Hormonal imbalance
D. Endometrial damage

22. CF-related diabetes occurs due to:

A. Autoimmune destruction
B. Insulin resistance only
C. Pancreatic damage
D. Excess insulin

23. Which vitamin deficiency is common in CF?

A. Vitamin C
B. Vitamin A
C. Vitamin B12
D. Vitamin B1

24. Chest physiotherapy in CF helps in:

A. Reducing inflammation
B. Improving nutrition
C. Clearing mucus
D. Treating infection

25. Dornase alfa acts by:

A. Breaking DNA in mucus
B. Killing bacteria
C. Dilating bronchi
D. Reducing inflammation

26. CFTR modulators are used to:

A. Cure CF completely
B. Treat infections only
C. Improve CFTR protein function
D. Replace pancreatic enzymes

27. CFTR modulators are mutation-specific because:

A. All mutations behave similarly
B. CFTR protein defects vary
C. They act on bacteria
D. They suppress immunity

28. High sweat chloride in CF results in:

A. Hypotension
B. Electrolyte imbalance
C. Metabolic alkalosis
D. Hyperglycemia

29. Clubbing of fingers in CF indicates:

A. Early disease
B. Acute infection
C. Chronic hypoxia
D. Cardiac failure

30. CF is most common in which population?

A. African
B. Asian
C. Caucasian
D. Native American

31. Mode of inheritance requires parents to be:

A. Both affected
B. One affected
C. Both carriers
D. One carrier only

32. Fecal elastase test assesses:

A. Liver function
B. Intestinal absorption
C. Pancreatic exocrine function
D. Renal function

33. Major cause of failure to thrive in CF children is:

A. Poor appetite
B. Chronic fever
C. Malabsorption
D. Anemia

34. Chronic infection in CF lungs leads to:

A. Reduced inflammation
B. Fibrosis and bronchiectasis
C. Alveolar collapse only
D. Pleural thickening

35. Which electrolyte is increased in CF sweat?

A. Calcium
B. Magnesium
C. Chloride
D. Bicarbonate

36. Prenatal diagnosis of CF is done by:

A. Ultrasound
B. Sweat test
C. Genetic testing
D. Chest X-ray

37. CF patients are advised high-calorie diet because of:

A. Increased appetite
B. Increased metabolic demand
C. Reduced physical activity
D. Hormonal imbalance

38. Which enzyme replacement is used in CF?

A. Lactase
B. Pepsin
C. Pancreatic enzymes
D. Amylase only

39. CF primarily affects epithelial cells of:

A. Blood vessels
B. Muscle
C. Exocrine glands
D. Neurons

40. Primary defect in CF is in transport of:

A. Proteins
B. Lipids
C. Electrolytes
D. Glucose

41. CF lung disease is characterized by:

A. Dry cough
B. Productive cough
C. No cough
D. Hemoptysis only

42. Chronic hypoxia in CF may cause:

A. Polycythemia
B. Leukopenia
C. Thrombocytopenia
D. Anemia

43. CFTR protein belongs to which family?

A. G-protein receptors
B. Ion channels
C. ABC transporter family
D. Nuclear receptors

44. Which test helps monitor lung disease progression?

A. Sweat test
B. Genetic test
C. Pulmonary function test
D. Stool examination

45. Main aim of CF management is to:

A. Cure disease
B. Prevent complications
C. Improve quality of life
D. Both B and C

46. CF patients commonly have stools that are:

A. Hard and dry
B. Watery
C. Bulky and greasy
D. Bloody

47. Liver involvement in CF may lead to:

A. Cirrhosis
B. Hepatitis A
C. Fatty liver only
D. Liver cancer

48. Early diagnosis of CF improves:

A. Cure rate
B. Survival and quality of life
C. Genetic mutation
D. Sweat chloride levels

49. CF is a life-limiting disease mainly because of:

A. Pancreatic failure
B. Renal failure
C. Progressive lung disease
D. Liver failure

50. Genetic counseling in CF is important for:

A. Treating disease
B. Carrier detection
C. Preventing inheritance
D. All of the above

Answer Key