309.2 🩺 國考版

309.2.1 高頻考點

309.2.1.1 Inheritance + Mutations

  • Autosomal recessive
  • CFTR gene (chr 7)
  • F508del: ~ 70% of alleles in Caucasian populations
  • 6 functional classes (I-VI)
  • Class I-III severe; IV-VI milder

309.2.1.2 Multi-Organ Manifestations

  • Lung: bronchiectasis, infection, respiratory failure
  • Pancreas: exocrine insufficiency (85-90%), CFRD (40-50% adult)
  • GI: meconium ileus (newborn), DIOS (older)
  • Liver: cirrhosis (10%)
  • Sinus / nasal polyps
  • Reproductive: CBAVD (male infertility 98%)

309.2.1.3 Diagnosis

  • Sweat chloride ≥ 60 mmol/L = positive
  • 30-59 = borderline
  • < 30 = negative
  • Plus clinical features OR genetic testing

309.2.1.4 Lung Pathogens (Age-Stratified)

  • Pediatric: S. aureus + H. influenzae
  • Adolescent: Pseudomonas
  • Adult: Pseudomonas + B. cepacia complex + NTM (MAC, M. abscessus)

309.2.1.5 CFTR Modulators (Revolutionary)

  • Ivacaftor (Kalydeco, 2012): G551D class III
  • Lumacaftor + ivacaftor (Orkambi, 2015): F508del homozygous
  • Tezacaftor + ivacaftor (Symdeko, 2018): improved version
  • ETI = elexacaftor + tezacaftor + ivacaftor (Trikafta/Kaftrio, 2019): F508del-containing genotypes; ~ 90% of CF patients eligible

309.2.1.6 CFTR Modulator Effects

  • Improved lung function (FEV1 ↑ 10-15%)
  • Reduced exacerbations (~ 60%)
  • Weight gain
  • QOL improvement
  • Reversed reproductive consequences (some)

309.2.1.7 Treatment Pillars

  • CFTR modulator
  • Airway clearance (chest PT, OPEP, HFCWO, hypertonic saline, dornase alfa)
  • Antibiotics (acute + chronic suppressive inhaled)
  • Pancreatic enzyme replacement
  • Nutrition support
  • CFRD management

309.2.1.8 B. cepacia Complex

  • Worst prognosis CF pathogen
  • Antibiotic resistant
  • May exclude from lung transplant
  • ↑ Mortality

309.2.2 易混淆比范

Feature CF Non-CF Bronchiectasis
Genetics CFTR mutation Variable (post-infectious, immune, etc.)
Sweat Cl ≥ 60 Normal
Pancreas Exocrine + endocrine insufficiency Variable
Reproductive CBAVD (male) Variable
Sinus Chronic + polyps Variable
Pathogens Pseudomonas, B. cepacia, NTM H. influenzae, Pseudomonas (less)

309.2.3 Special Topics

309.2.3.1 Pancreatic Sufficient vs Insufficient

  • Pancreatic insufficient (PI): 85-90%; classical
  • Pancreatic sufficient (PS): 10-15%; later onset, milder
  • Determines PERT need

309.2.3.2 CFRD vs Type 1 vs Type 2 DM

  • Combined insulin deficiency (β-cell destruction) + insulin resistance
  • HbA1c misleading (faster RBC turnover)
  • CGM essential
  • Insulin only treatment (oral agents less effective)
  • Microvascular complications (retinopathy, nephropathy)

309.2.3.3 CF in Adults (Different Pathogens)

  • Late-onset diagnosis (atypical CF, milder mutations)
  • Bronchiectasis predominant
  • Pancreatic sufficient often
  • Adult CF center

309.2.3.4 B. cepacia “Cepacia Syndrome”

  • Acute deterioration
  • Sepsis-like
  • High mortality
  • Multidrug resistance