In a patient with a single-breath nitrogen washout test, a steep phase III slope (elevated delta N2/L > 2%) indicates which pathophysiology?

• A Reduced diffusing capacity of the alveolar membrane for nitrogen
• B Uneven distribution of ventilation with asynchronous emptying of lung units with different N2 concentrations ✓
• C Increased closing capacity due to small airway collapse during tidal breathing
• D Reduced alveolar surface area from emphysema reducing the plateau of phase III

Explanation

In the single-breath N2 washout test, the subject inhales 100% O2 then slowly exhales. Phase III (alveolar plateau) represents mixed alveolar gas. A steep phase III slope (>2% N2 per litre exhaled) indicates maldistribution of ventilation: poorly ventilated lung units (higher N2 concentration, less O2 dilution) empty later and asynchronously compared to well-ventilated units, creating a rising N2 concentration during exhalation. This is an early, sensitive marker of airway disease (COPD, asthma) before conventional spirometry becomes abnormal. The slope reflects ventilation inequality, not diffusion limitation.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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