What is the most appropriate study to determine the diagnosis in a 9-month-old infant with wheezing, labored breathing, productive cough, failure to gain weight, and greasy stools, with a history of meconium ileus at birth?

Sweat Chloride Test is the Most Appropriate Diagnostic Study for This Infant

The sweat chloride test is the most appropriate diagnostic study for this 9-month-old infant with wheezing, labored breathing, productive cough, failure to gain weight, greasy stools, and history of meconium ileus at birth.

Clinical Presentation Analysis

The infant presents with a constellation of symptoms highly suggestive of cystic fibrosis (CF):

• Respiratory symptoms: wheezing, labored breathing, productive cough for 4 weeks
• Gastrointestinal symptoms: greasy stools (steatorrhea)
• Growth failure: eating well but not gaining weight
• History of meconium ileus at birth - a critical finding present in 90% of CF cases 1

Diagnostic Approach

Why Sweat Chloride Test is the Best Choice:

• The sweat chloride test is the gold standard initial test for diagnosing CF 2
• It's performed via pilocarpine iontophoresis to collect and analyze sweat chloride concentration
• Diagnostic values:
  • ≥60 mmol/L: diagnostic of CF
  • 30-59 mmol/L: intermediate, requires further evaluation
  • <30 mmol/L: makes CF unlikely 2

Interpretation of Results:

• The test can be accurately performed on infants as young as 2-3 weeks of age 2
• For this 9-month-old, the test is well within the appropriate age range
• Bilateral testing is recommended to increase the likelihood of adequate specimen collection 2

Why Other Tests Are Less Appropriate:

1. Alpha-1 Antitrypsin Test:

   • While alpha-1 antitrypsin deficiency can cause respiratory symptoms, it doesn't typically present with meconium ileus or steatorrhea

2. Arterial Blood Gas Analysis:

   • Would only provide information about current respiratory status, not the underlying diagnosis
   • Not specific for CF diagnosis

3. Chest X-ray:

   • May show hyperinflation or bronchial wall thickening in CF
   • However, it's not diagnostic and would be considered a secondary test after establishing diagnosis

4. CT Scan of Thorax:

   • Excessive radiation for initial diagnosis
   • More appropriate for evaluating complications or progression of established disease

Clinical Reasoning

The history of meconium ileus at birth is particularly significant, as it occurs in approximately 15-20% of CF patients and is highly specific for CF 3. When combined with the ongoing respiratory symptoms, failure to thrive despite good appetite, and steatorrhea, the clinical picture strongly points to CF as the most likely diagnosis.

Important Considerations

• If sweat chloride results are intermediate or if clinical suspicion remains high despite normal results, repeat testing or CFTR genetic analysis may be necessary 2
• Rarely, patients with CF may have normal sweat chloride values, particularly those with certain CFTR mutations like delta F508/3849 + 10 kb C→T 4
• Early diagnosis is critical as it allows for prompt initiation of therapy, which can significantly impact morbidity, mortality, and quality of life 3

Follow-up Testing

After confirming the diagnosis with sweat chloride testing, additional evaluations may include:

• CFTR genetic analysis to identify specific mutations
• Pancreatic function tests
• Respiratory cultures to identify pathogens
• Nutritional assessment

Early diagnosis and treatment of CF are essential to prevent complications, improve growth, and preserve lung function, which directly impacts long-term morbidity, mortality, and quality of life outcomes.