A 34-year-old man, current smoker of 10 pack-years, has 3 years of progressive exertional dyspnea. HRCT shows severe bibasal panlobular emphysema out of proportion to his smoking history. Liver biopsy elsewhere showed cirrhosis, and his brother died of liver disease at 38 years. Which investigation will confirm the underlying diagnosis?

• A Sweat chloride estimation
• B Bronchoalveolar lavage fluid analysis for CD4 to CD8 ratio
• C Serum anti-neutrophil cytoplasmic antibody titres
• D Serum alpha-1 antitrypsin level with PI phenotype genotyping ✓

Explanation

Early onset basal panlobular emphysema with hepatic cirrhosis and a suggestive family history points to homozygous PiZZ alpha-1 antitrypsin deficiency. Diagnosis rests on a low serum AAT concentration followed by PI phenotyping or genotyping, since levels alone can be misleadingly normalised by inflammation, pregnancy or oestrogens. BAL lymphocyte ratios assess sarcoidosis and hypersensitivity pneumonitis, ANCA tests vasculitis, and sweat chloride tests cystic fibrosis.

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.