Cystic Fibrosis

1. Sweat testing

Since electrolyte abnormalities in sweat were first reported, the sweat test has become the most useful diagnostic method for cystic fibrosis. However, false positives or false negatives may occur depending on the method of sweat collection, electrolyte concentration measurement, and result interpretation. Pilocarpine iontophoresis (The standard method): A chloride concentration of ≥60 mmol/L is considered positive. 

• ≤30 mmol/L: Negative, and if there are no clear clinical symptoms, further diagnostic evaluation is generally not required. 
• 30–60 mmol/L: A repeat test is necessary. If the repeated test also shows intermediate values, testing for CFTR gene mutations is recommended. 

2. Genetic study - CFTR gene mutations

Identifying two CFTR gene mutations in cystic fibrosis has low sensitivity but high specificity, making it diagnostically useful as a supplement to the sweat test. 

* The diagnostic criteria include: 

• Typical clinical features (respiratory, gastrointestinal, or urogenital symptoms), or a sibling with cystic fibrosis, or a positive result from newborn screening, and 
• Evidence of CFTR dysfunction: Elevated sweat chloride concentrations on two separate occasions, identification of two CF-causing CFTR mutations, or abnormal nasal potential difference

To assess the current status of cystic fibrosis, evaluations such as pancreatic function tests, pulmonary function tests, chest imaging, and bacterial cultures are necessary. Organ-specific assessments are performed based on clinical symptoms:

A. Pancreatic function tests

• Include measurement of fecal elastase-1 activity, fat absorption tests, trypsin or chymotrypsin activity, and serum immunoreactive trypsinogen levels.

B. Pulmonary function tests

• Typically show an obstructive pattern, but as the disease progresses and fibrosis develops, a restrictive pattern may appear.

C. Chest radiography or CT

• May reveal findings such as bronchiectasis, atelectasis, and hyperinflation.

D. Bacteria Cultures

• Respiratory secretions commonly yield pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cepacia.

Once diagnosed, it is important to promptly initiate necessary evaluations and treatment. 

Fundamental therapeutic approaches under development include:

•  In vivo gene therapy to insert a normal gene,
•  Agents that aid CFTR protein expression, such as gentamicin, phenylbutyrate, CPX (8-cyclopentyl-1,3-dipropylxanthine), and genistein,
•  Agents that promote chloride secretion, such as uridine triphosphate (UTP),
•  Agents that inhibit sodium absorption, such as amiloride.

Among approved treatments, ivacaftor has been developed to improve CFTR protein function and is approved for patients with the CFTR-G551D mutation.

For respiratory management

• Airway clearance techniques and infection control are most important.  2) Inhaled or bronchoscopically administered recombinant human DNase. 3) Lung or heart-lung transplantation

For pancreatic insufficiency

• Microspheric pancreatic enzyme preparations are administered along with supplementation of fat-soluble vitamins A, D, E, and K.