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  Disease summary:

  
  
  
  
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    Cystic fibrosis (CF) is the most common genetically inherited autosomal recessive disease in Caucasians that leads to multisystem organ dysfunction with the majority of morbidity and mortality related to respiratory and gastrointestinal (GI) systems.

    
    
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    CF arises secondary to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on the long arm of chromosome 7; CFTR is translated into a multidomain chloride ion channel belonging to ATP-binding cassette (ABC) transporter superfamily.

    
    
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    Greater than 1800 CFTR mutations are known and may be classified by their functional defect; each mutation leads to varying impact on salt and water balance.

    
    
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    The pathogenesis of CF involving the lungs includes a vicious cycle of infection, inflammation, and bronchiectasis.

    
    
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    The clinical course of CF is typically chronic or progressive punctuated by acute exacerbations and eventual respiratory failure. As patient survival improves, other organ system complications are increasingly identified and require therapy.

  
  
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  Hereditary basis:

  
  
  
  
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    Autosomal recessive pattern with variable clinical phenotype affected by the specific CFTR mutation, modifier genes, and environment

  
  
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  Differential diagnosis:

  
  
  
  
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    Bronchiectasis from other causes: primary ciliary dyskinesia, tuberculosis, chronic aspiration

    
    
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    Primary immune deficiency, for example common variable immune deficiency

    
    
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    Other causes of elevated sweat chloride levels: malnutrition, hypothyroidism, adrenal insufficiency

Diagnostic Criteria

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  Clinical presentation (one or more typical clinical findings)

  
  
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  Sweat chloride concentration greater than or equal to 60 mol/L (40-59 mmol/L considered indeterminate, <40 mmol/L considered negative)

  
  
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  CFTR mutation analysis indicating two known CF disease-causing mutations in trans configuration (Table 114-1). Mutation analysis may include the attempted identification of polymorphisms, deletions, and duplications

  
  
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  Newborn screening: Evidence of elevated immune-reactive trypsinogen (IRT) and/or identification of one or more disease-causing CFTR mutation triggers sweat chloride testing and more extensive CFTR mutation analysis

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  Other considerations:

  
  
  
  
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    CF-related metabolic syndrome (CRMS) is a new term proposed for patients who are asymptomatic but have either nondiagnostic sweat chloride or CFTR mutation analysis concerning for, but not diagnostic of cystic fibrosis.

    
    
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    CFTR-related disorder (CRD) is a term proposed for CRMS patients who are symptomatic in some way.

Clinical Characteristics

Progressive pulmonary disease due to chronic infection, airway inflammation, and bronchiectasis is associated with the greatest morbidity and mortality in patients with CF. However, CF is a multisystem disorder (Table 114-2), a result of CFTR expression in most organs of the body, with varying clinical presentation that requires a multidisciplinary approach to treatment.

Chronic infection with pathogens such as methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA/MRSA), Haemophilus influenzae, Pseudomonas aeruginosa (mucoid and non-mucoid), Burkholderia cepacia complex species, Achromobacter, Stenotrophomonas, and others, complicate sinus and airway infections. Chronic cough and sputum production reflect the persistent infection with such organisms, as well as inflammation that leads to airway obstruction, progression of lung disease, and respiratory failure. The vicious cycle of infection and inflammation leads to radiographic abnormalities such as bronchiectasis, infectious opacities, and hyperinflation. CF patients are also at increased risk for pneumothoraces and hemoptysis. Hemoptysis can range from scant in amount to massive and life threatening. These manifestations eventually lead to chronic respiratory failure and premature death for those not undergoing lung transplantation.