Cystic fibrosis (CF) is a disease of exocrine gland function that involves multiple organ systems but chiefly results in chronic respiratory infections, pancreatic enzyme insufficiency, and associated complications in untreated patients. Pulmonary involvement (see the image below) occurs in 90% of patients surviving the neonatal period. End-stage lung disease is the principal cause of death.

Signs and symptoms

Median age at diagnosis is 6-8 months; however, age at diagnosis varies widely. Clinical manifestations vary with the patient’s age at presentation.

Gastrointestinal (GI) symptoms may include the following:

• Meconium ileus
• Abdominal distention
• Intestinal obstruction
• Increased frequency of stools
• Failure to thrive (despite adequate appetite)
• Flatulence or foul-smelling flatus, steatorrhea
• Recurrent abdominal pain
• Jaundice
• GI bleeding

Respiratory symptoms may include the following:

• Cough
• Recurrent wheezing
• Recurrent pneumonia
• Atypical asthma
• Dyspnea on exertion
• Chest pain

Genitourinary symptoms may include the following:

• Undescended testicles or hydrocele
• Delayed secondary sexual development
• Amenorrhea

Physical signs depend on the degree of involvement of various organs and the progression of disease, as follows:

• Nose – Rhinitis, nasal polyps
• Pulmonary system – Tachypnea, respiratory distress with retractions, wheeze or crackles, cough (dry or productive of mucoid or purulent sputum), increased anteroposterior chest diameter, clubbing, cyanosis, hyperresonant chest on percussion
• GI tract – Abdominal distention, hepatosplenomegaly, rectal prolapse, dry skin, cheilosis

Diagnosis

Requirements for a CF diagnosis include either positive genetic testing or positive sweat chloride test findings and 1 of the following:

• Typical chronic obstructive pulmonary disease (COPD)
• Documented exocrine pancreatic insufficiency
• Positive family history (usually an affected sibling)

Parameters for the sweat chloride test are as follows:

• The reference value is less than 40 mmol/L
• A value higher than 60 mmol/L of chloride is consistent with CF
• A value of 40-60 mmol/L is considered borderline, and the test must be repeated
• In babies aged 3 months or younger, a value of 30-60 mEq/L is considered borderline and requires retesting ^[1]

Imaging studies that may be helpful include the following:

• Radiography (chest, sinus, abdomen)
• CT of the chest (not yet advised as a routine modality in CF)
• Ultrasonography
• Contrast barium enema

Additional tests that may be warranted are as follows:

• Genotyping
• Nasal potential difference measurement
• Pulmonary function testing
• Bronchoalveolar lavage
• Sputum microbiology
• Immunoreactive trypsinogen

Management

The primary goals of CF treatment include the following:

• Maintaining lung function as near to normal as possible by controlling respiratory infection and clearing airways of mucus
• Administering nutritional therapy (ie, enzyme supplements, multivitamin and mineral supplements) to maintain adequate growth
• Managing complications

Mild acute pulmonary exacerbations of CF can be treated successfully at home with the following measures:

• Increasing the frequency of airway clearance
• Inhaled bronchodilator treatment
• Chest physical therapy and postural drainage
• Increasing the dose of the mucolytic agent dornase alfa
• Use of oral antibiotics (eg, fluoroquinolones)

Medications used to treat CF may include the following:

• Pancreatic enzyme supplements
• Multivitamins (including fat-soluble vitamins)
• Mucolytics
• Nebulized, inhaled, oral, or intravenous antibiotics
• Bronchodilators
• Anti-inflammatory agents
• Agents to treat associated conditions or complications (eg, insulin, bisphosphonates)
• Agents devised to reverse abnormalities in chloride transport (eg, ivacaftor ^[2] )
• Inhaled hypertonic saline

Surgical therapy may be required for the treatment of the following respiratory complications:

• Respiratory – Pneumothorax, massive recurrent or persistent hemoptysis, nasal polyps, persistent and chronic sinusitis
• GI – Meconium ileus, intussusception, gastrostomy tube placement for supplemental feeding, rectal prolapse