A 31-year-old male smoker presents with slowly progressive dyspnea. Spirometry shows severe airflow obstruction with reduced DLCO. High-resolution CT shows diffuse panacinar emphysema with striking lower-zone predominance. Liver function tests reveal mild transaminase elevation. Which investigation will best confirm the underlying diagnosis?

• A Bronchoalveolar lavage fluid analysis
• B Serum alpha-1 antitrypsin level and phenotype testing ✓
• C Serum angiotensin-converting enzyme level
• D Transbronchial lung biopsy

Explanation

Early-onset basal-predominant panacinar emphysema, especially in a young smoker with concurrent liver disease, is classic for alpha-1 antitrypsin deficiency (usually the homozygous PiZZ phenotype). Diagnosis is confirmed by a low serum alpha-1 antitrypsin level followed by phenotype genotyping. Augmentation therapy is considered when levels fall below the protective threshold of about 11 micromolar (approximately 50 mg/dL). BAL, ACE levels, and biopsy do not establish this genetic diagnosis.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.