A 33-year-old male smoker (10 pack-years) has progressive exertional dyspnoea. Spirometry shows severe airflow obstruction with reduced DLCO. HRCT shows extensive bullae with striking basal predominance. Liver function tests show mildly raised transaminases. Which single test best confirms the underlying diagnosis?

• A Serum protein electrophoresis for M band
• B Bronchoalveolar lavage fluid analysis
• C Diffusion capacity measured after bronchodilator therapy
• D Serum alpha-1 antitrypsin level with Pi phenotype typing ✓

Explanation

Early-onset basal panacinar emphysema in a young smoker, especially with hepatic involvement, points to alpha-1 antitrypsin deficiency (PiZZ genotype). Diagnosis is confirmed by measuring the serum D1AT level followed by phenotyping or genotyping; levels below about 11 micromolar (roughly 50 to 60 mg/dL by nephelometry) support deficiency. HRCT distribution suggests but cannot confirm the diagnosis, BAL adds nothing specific, and SPEP is irrelevant since D1AT deficiency involves the alpha-1 globulin fraction, not an M band.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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