Determination of production of nitric oxide by lower airways of humans - Theory

Exercise and inflammatory lung disorders such as asthma and acute lung injury increase exhaled nitric oxide (NO). This finding is interpreted as a rise in production of NO by the lungs (V̇NO) but fails to take into account the diffusing capacity for NO (DNO) that carries NO into the pulmonary capillary blood. We have derived equations to measure V̇NO from the following rates, which determine NO tension in the lungs (PL) at any moment from 1) production (V̇NO); 2) diffusion, where DNO(PL) = rate of removal by lung capillary blood; and 3) ventilation, where V̇A(PL)/(PB - 47) = the rate of NO removal by alveolar ventilation (V̇A) and PB is barometric pressure. During open-circuit breathing when PL is not in equilibrium, d/dt PL[V(L)/(PB - 47)] (where V(L) is volume of NO in the lower airways) = V̇NO - DNO(PL) - V̇A(PL)/(PB - 47). When PL reaches a steady state so that d/dt = 0 and V̇A is eliminated by rebreathing or breath holding, then PL = V̇NO/DNO. PL can be interpreted as NO production per unit of DNO. This equation predicts that diseases that diminish DNO but do not alter V̇NO will increase expired NO levels. These equations permit precise measurements of V̇NO that can be applied to determining factors controlling NO production by the lungs.