A 36-year-old man has 2 years of exertional dyspnoea with minimal sputum production. He has never smoked. CT chest shows extensive panacinar emphysema involving both lung bases, and liver enzymes are mildly elevated. Which investigation will best establish the underlying diagnosis?

• A Diffusion capacity for carbon monoxide alone
• B Measurement of serum alpha-1 antitrypsin level with Pi phenotype analysis ✓
• C Sweat chloride estimation
• D Echocardiography for pulmonary artery pressures

Explanation

Basal-predominant panacinar emphysema in a young non-smoker, especially with hepatic involvement from intrahepatic accumulation of misfolded protein, strongly suggests homozygous ZZ alpha-1 antitrypsin deficiency. B low serum level with Pi typing confirms the diagnosis and allows family screening. B reduced DLCO merely quantifies the emphysema and does not identify its cause, sweat chloride tests for cystic fibrosis which presents differently, and echocardiography assesses complications rather than aetiology, ruling out all three distractors.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.