Which laboratory tests should be ordered for a patient with recurrent respiratory infections, chronic cough, possible allergic triggers, and a family history suggestive of cystic fibrosis?

Laboratory Testing for Recurrent Respiratory Infections with Family History of Cystic Fibrosis

Given the family history suggestive of cystic fibrosis combined with recurrent respiratory infections and chronic cough, you should order a sweat chloride test as the primary diagnostic test, followed by CFTR genetic testing if the sweat test is positive or intermediate. 1, 2

Essential Initial Laboratory Tests

Cystic Fibrosis Screening (Priority Testing)

• Quantitative sweat chloride test using pilocarpine iontophoresis with collection on gauze, filter paper, or Macroduct coil 1, 3, 4
  • Values ≥60 mmol/L confirm CF diagnosis 3, 4
  • Values 30-59 mmol/L are intermediate and require extended CFTR gene analysis 3
  • Values <30 mmol/L make CF unlikely but don't completely exclude it 3
• CFTR genetic testing should follow if sweat chloride is elevated or intermediate, particularly in children with nasal polyps or Pseudomonas colonization 1, 2

Immunodeficiency Evaluation

• Complete blood count to assess for lymphopenia or other hematologic abnormalities 2
• Serum immunoglobulin levels (IgG, IgA, IgM) to screen for antibody deficiency syndromes, which occur in 7% of bronchiectasis patients 2
• Baseline specific antibody levels against Streptococcus pneumoniae capsular polysaccharides to investigate specific antibody deficiency 2
  • If low, immunize with 23-valent polysaccharide pneumococcal vaccine
  • Remeasure specific antibody levels 4-8 weeks post-vaccination 2
• HIV-1 serology if clinical features suggest increased retroviral infection risk 2, 1

Allergic/Inflammatory Assessment

• Serum total IgE to screen for allergic bronchopulmonary aspergillosis (ABPA) 2
• Aspergillus-specific IgE or skin prick testing if total IgE >500 IU/mL 2
• Nasal cytology to evaluate for allergic rhinitis, eosinophilic nonallergic rhinitis, or neutrophilic rhinitis 1

Microbiological Studies

• Sputum cultures for routine bacterial pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and Burkholderia cepacia complex 2, 5
• Mycobacterial culture (acid-fast bacilli smear and culture) from sputum if patient can expectorate 2, 6
  • Use induced sputum if spontaneous expectoration not possible 6
  • Incubate cultures for minimum 6 weeks 6

Additional Testing for Primary Ciliary Dyskinesia

Test for PCD if the patient has supporting clinical features including neonatal respiratory distress, symptoms from childhood, recurrent otitis media, rhinosinusitis, or if nasal polyps are present 3, 2

Key indicators requiring PCD evaluation: 3

• Situs inversus with respiratory symptoms
• Daily lifelong wet cough
• Sibling with PCD
• Unexplained bronchiectasis
• Serous otitis media with lower/upper airway symptoms

Common Pitfalls to Avoid

Do not rely on oropharyngeal swabs for CF screening or mycobacterial detection—they lack sensitivity and do not provide sufficient material 6

Do not dismiss borderline sweat chloride results (30-59 mmol/L)—these require extended CFTR genetic analysis and potentially CFTR functional testing like nasal potential difference measurement 3, 4

Do not assume immunodeficiency is ruled out by normal immunoglobulin levels—functional antibody testing with pneumococcal vaccine challenge is essential to detect specific antibody deficiency 2

Be aware that transient sweat chloride elevation can occur in hypogammaglobulinemia without CF, making combined testing essential 7

Testing Sequence Algorithm

1. First-line: Sweat chloride test + serum immunoglobulins (IgG, IgA, IgM) + total IgE + sputum culture 1, 2

2. If sweat chloride ≥30 mmol/L: Proceed with CFTR genetic testing 3

3. If immunoglobulins abnormal: Pneumococcal antibody levels before and after vaccination 2

4. If total IgE >500 IU/mL: Aspergillus-specific testing 2

5. If clinical features suggest PCD: Refer for specialized ciliary testing including electron microscopy and genetic analysis 3, 2