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iatroX Rounds #38

Friday, 31 July 2026·Respiratorymoderate

The clues

  1. 1

    A 42-year-old male smoker presents with a six-month history of worsening shortness of breath on exertion and a chronic cough.

  2. 2

    He notes that his exercise tolerance has declined much faster than his peers who also smoke, and he has no history of childhood asthma or atopy.

  3. 3

    His father died in his late 40s from an unspecified chronic lung condition despite having never smoked.

  4. 4

    On examination, he has a hyperexpanded chest with reduced breath sounds; he also has mild jaundice with a bilirubin of 38 µmol/L and spider naevi on his chest.

  5. 5

    Chest X-ray shows hyperinflated lung fields with significant flattening of the diaphragms, with the lucency and bullous changes most prominent at the lung bases.

  6. 6

    Liver histology reveals characteristic PAS-positive, diastase-resistant globules within the hepatocytes, and genetic analysis confirms a homozygous PiZZ genotype.

the diagnosis
Alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency is an autosomal codominant genetic disorder where the lack of a specific protease inhibitor leads to uninhibited neutrophil elastase activity. This results in tissue destruction, typically manifesting as early-onset panacinar emphysema and chronic liver disease, including cirrhosis and hepatocellular carcinoma.

  • Early-onset emphysema, often occurring in the fourth or fifth decade, especially in smokers
  • Panacinar emphysema that characteristically affects the lung bases rather than the apices
  • Associated liver involvement ranging from neonatal cholestasis to adult-onset cirrhosis
  • Low serum levels of the protein and presence of the PiZZ genotype
pearl. In contrast to smoking-related emphysema which is typically centriacinar and apical, the emphysema in this condition is panacinar and predominantly basal.

more Respiratory rounds

A 34 year old woman presents to her GP with a three month history of a persistent dry cough and feeling increasingly tired.#14

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