CYSTIC FIBROSIS

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CYSTIC FIBROSIS

• Olav-Trond Storrøsten, M.D.
• National center for cystic fibrosis
• Ullevaal University Hospital

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CYSTIC FIBROSIS

• Autosomal recessive hereditary disease
• Occurs in one of 3-5000 humans in Scandinavian
  countries
• 271 patients in Norway, more than 60 beeing
  older than 18 years of age
• One in 35 beeing carriers of the CF gene

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GENETICS
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Proposed Structure for Cystic Fibrosis
Transmembrane Conductance Regulator (CFTR)
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Structure and function of CFTR
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Salt Transport by Sweat-Gland Duct
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Pilocarpin-iontophoresis
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Sweat test

• Chloride more than 60 mmol/l
• lt 3 mo 30 mmol/l highly suggestive
• Sodium and chloride within 15 mmol/l
• Sodium/chloride rato lt 1.0
• Chloride gt 160 mmol/l physiologically impossible

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Gene Replacement Therapy
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Ion Channel Modulators
CFTR
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Under the Microscope CF Lung Disease
Normal Airway
CF Airway
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Incidence of Major Airway Pathogens by Patient Age
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One-year period prevalence
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CF Epithelia Fail to Kill Bacteria Because of
altered NaCl in Arway Surface Fluid
Normal
CF
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Shematic model of pathogenetic sequence
hypothesized to link volume homeostasis to
chronic airway disease in CF patients.
Progress in Respiratory Research. Vol 34 Cystic
Fibrosis in the 21st Century
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ASL depletion and reduced mucus clearence in CF
Progress in Respiratory Research. Vol 34 Cystic
Fibrosis in the 21st Century
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Mucus plugging
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Chronic Inflammation in CF
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Epithelial-Cell Cytokines and Inflammation in CF
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Cystic Fibrosis Lung Disease
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Treatment

• Antibiotics
• Inhalation
• Systemic
• I.v.

• Anti inflammatory
• Steroids
• Systemic
• Inhalation
• Macrolides
• Ibuprofen
• BIIL 284 BS (LTB4 antagonist)

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Treatment

• Mucolytics
• N-acetylcystein
• Dornase alfa
• Hypertonic saline
• Mannitol

• Chest physiotherapy
• Gentle
• Efficient
• Motivating
• Self-supporting

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Routine Output Monitoring FEV1 and FVC
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Poor HRCT / PFT Correlation

• 10-year-old boy HRCT score 33 FEV1 127 pred.

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HRCT Scoring System

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CLUBBING
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Nutritional abnormalities
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Nutritional abnormalities
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Rectalprolapse
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Meconiumileus
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Normal liver, gall stone
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Severe biliary cirrhosis with portal hypertension
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