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Cystic Fibrosis

Basics

  • Autosomal recessive mutation primarily affecting lungs and pancreas; multisystem involvement possible
  • Adults with CF now outnumber children due to improved survival

Epidemiology

  • Most common lethal inherited disease in Caucasians; found in all racial groups
  • Incidence:
  • Caucasians: 1 in 3,200
  • Latin Americans: 1 in 10,000
  • Native Americans: 1 in 10,500
  • African Americans: 1 in 15,000
  • Asian Americans: 1 in 30,000
  • Prevalence: >30,000 in US; 70,000 worldwide
  • Median predicted survival in US: ~46.2 years

Etiology & Pathophysiology

  • Mutation in CFTR gene on chromosome 7q31.2 causes defective chloride and sodium channel activity
  • Results in viscous secretions, impaired mucociliary clearance, neutrophilic inflammation, bronchiectasis
  • Most common mutation: deltaF508 (85.3% cases in US)
  • Modifier genes and environmental factors influence severity

General Prevention

  • Preconception genetic counseling recommended
  • Newborn screening essential for early diagnosis and better outcomes

Associated Conditions

  • CF-related diabetes (CFRD) in ~20.7%
  • Rhinosinusitis (up to 100%) and nasal polyps (up to 86%)
  • Pancreatic exocrine insufficiency (85-90%), malabsorption, vitamin deficiencies (A,D,E,K)
  • Hepatobiliary disease (~12.6%)
  • Meconium ileus at birth (10-15%)
  • Distal intestinal obstruction syndrome (5.3%)
  • GERD (32.7%)
  • Bone mineral disease, joint disease, hypogonadism
  • Male infertility due to congenital bilateral absence of vas deferens (98%)

Pregnancy Considerations

  • Pulmonary disease may worsen during pregnancy
  • Increased risk of preterm delivery, IUGR, cesarean section
  • Fertility treatments allow men with CF to father children

Diagnosis

Criteria

  • At least one typical feature (chronic pulmonary disease, sinusitis, GI abnormalities, obstructive azoospermia, sibling with CF, positive newborn screen)
  • Plus at least one confirmatory test:
  • Elevated sweat chloride (>60 mmol/L on two occasions)
  • Two CF-causing CFTR mutations on separate alleles
  • Abnormal nasal potential difference testing

History & Exam

  • Prenatal: hyperechogenic bowel on ultrasound, meconium peritonitis
  • Neonatal: meconium ileus (20%), prolonged jaundice
  • Infancy: failure to thrive, diarrhea, vitamin deficiencies, anasarca
  • Childhood: recurrent infections, bronchiectasis, sinusitis, steatorrhea
  • Adolescence/adulthood: hemoptysis, pancreatitis, portal hypertension, azoospermia
  • Exam: rhonchi, crackles, nasal polyps, hepatosplenomegaly, digital clubbing, growth/puberty delay

Differential Diagnosis

  • Immunodeficiency, asthma, COPD, recurrent pneumonia, primary ciliary dyskinesia
  • Celiac disease, pancreatitis, Shwachman-Diamond syndrome

Diagnostic Tests

  • Newborn screen: immunoreactive trypsinogen (IRT)
  • Sweat test: gold standard (>60 mmol/L diagnostic)
  • CFTR genetic testing (allele-specific PCR >90% mutations detected)
  • Nasal potential difference if unclear
  • Imaging: CXR, chest CT, sinus CT, flexible bronchoscopy with BAL
  • Follow-up: sputum cultures, PFTs, fecal fat/elastase, OGTT (annually after 10 years)

Treatment

General Measures

  • Multidisciplinary care with regular clinic visits and monitoring
  • PFT goals: adults >75% predicted; children >100%
  • Annual screening for ABPA, influenza vaccination, osteoporosis screening
  • Reduce tobacco exposure; COVID-19 vaccination recommended
  • Telehealth with home spirometry acceptable

Medications

  • Target pulmonary infections with pathogen-specific antibiotics (oral, inhaled, IV)
  • Chronic pulmonary therapies: recombinant human DNase, hypertonic saline, high-dose ibuprofen (children)
  • CFTR modulators (Orkambi, Trikafta) improve lung function and symptoms
  • Pancreatic enzyme replacement and fat-soluble vitamin supplementation
  • Avoid chronic inhaled steroids unless asthma or ABPA present

Additional Therapies

  • Chest physiotherapy and aerobic exercise
  • Bisphosphonates for bone disease

Surgery

  • Lung transplant referral for advanced disease (FEV1 <50% with rapid decline or <30%)
  • Liver transplant for advanced liver disease
  • Nasal polypectomy as needed

Admission Considerations

  • Pulmonary exacerbations, bowel obstruction, pancreatitis
  • Contact precautions and private rooms recommended

Ongoing Care

  • Frequent follow-up post-exacerbation (2-4 weeks)
  • Routine quarterly visits with cultures and PFTs
  • Nutritional evaluation annually

Diet

  • High-calorie, high-fat diet with individualized BMI targets
  • Referral to dietitian or supplemental feeding if needed

Patient Education

  • Resources: Cystic Fibrosis Foundation (https://www.cff.org)

Prognosis

  • Median survival ~48.4 years
  • Lung disease progression primarily determines survival

Clinical Pearls

  • Meconium ileus is pathognomonic for CF
  • Sweat chloride testing followed by CFTR genetic testing is diagnostic
  • Consider CF in any child with chronic diarrhea and poor growth
  • Nasal polyps, clubbing, and bronchiectasis warrant CF evaluation
  • Rapid pulmonary decline suggests resistant organisms or complications like CFRD, ABPA, GERD

ICD10: - E84.9 Cystic fibrosis, unspecified - E84.11 Meconium ileus in cystic fibrosis - E84.0 Cystic fibrosis with pulmonary manifestations