A 62-year-old male smoker (40 pack-year history) presents with progressive exertional dyspnea and basal crackles on examination. Spirometry shows FEV1/FVC ratio of 0.65 and FVC of 68% predicted. Body plethysmography reveals TLC of 75% predicted. HRCT chest demonstrates upper-lobe centrilobular emphysema with lower-lobe usual interstitial pneumonia pattern and honeycombing. The clinical-radiological-physiological picture is consistent with the syndrome marked D in the diagram. Which of the following is the MOST SENSITIVE diagnostic parameter for confirming this syndrome?

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