Abstract

In 1915, Krogh 1 first measured the diffusion of carbon monoxide to demonstrate that oxygen passively diffused from the alveolus to pulmonary capillary blood. The history review by Hughes and Bates 2 discusses this excellently. Subsequently, in 1957, Roughton and Forster 3 demonstrated that CO diffusion measured by the diffusing capacity of the lung for CO ( D L,CO) reflected both alveolar capillary membrane diffusion and reaction with pulmonary capillary blood. The overall resistance is: 1/ D L,CO = 1/ D m +1/Θ V c (1) where D m is the membrane diffusing capacity, Θ the specific transfer conductance of the blood (measured by CO reaction with red cells using a rapid reaction apparatus) and V c the pulmonary capillary blood volume 3. In healthy young volunteers, D L,CO is 30 mL·min−1 torr−1, D m is 57 mL·min−1 torr−1 and V c is 80 mL. To acknowledge that the overall process involved more than just diffusion, J. Cotes coined the term transfer factor of the lung for CO ( T L,CO). In 1982, T. Higenbottam and I were studying lung uptake and toxicity of NO in cigarette smokers; A. Chamberlain (our then research assistant) suggested that we measure this as transfer factor of the lung for NO ( T L,NO). Quite independently, ∼10 yrs earlier, the late D. Bargeton and H. Guenard had speculated that if another gas could be found that reacted with haemoglobin, by inhaling it simultaneously with CO, the equation of Roughton and Forster 3 could be solved for D m and V c in a single breath rather than by measuring T L,CO at two or more oxygen concentrations and cardiac outputs. NO reacts, in effect, instantly with haemoglobin. The resulting single-breath studies from our respective two groups 4, 5 generated much interest, including an editorial …

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