Bronchial and alveolar components of exhaled nitric oxide and their relationship.

Considerable confusion exists about the clinical use of exhaled nitric oxide measurement in general, and its bronchial and alveolar contributions in particular, for instance in response to treatment. An additional effect needs to be factored in when considering the degree of alveolar nitric oxide abnormality and its response to therapeutic interventions that may or may not be targeted to the lung periphery. Indeed, the alveolar nitric oxide value computed from exhaled nitric oxide measurement at multiple flows with the so-called slope-intercept method [1, 2] can overestimate the true nitric oxide produced by inflammation in the alveolar air spaces. Such overestimation arises when the bronchial nitric oxide back-diffuses into the alveolar air space and thus contaminates the alveolar nitric oxide measurement with nitric oxide that originates from the more proximal airways. Two correction formulas have been published independently [3, 4] proposing to estimate true alveolar nitric oxide by subtracting from the measured alveolar nitric oxide a bronchial nitric oxidedependent portion corresponding to back-diffusion. However, it has also been shown that airway constriction of peripheral conductive airways may at least partly impair back-diffusion [5]. Thus, in the case of peripheral lung disease, the application of correction formulas that assume unimpaired back-diffusion can erroneously lead to overcorrection and, ultimately, to negative alveolar nitric oxide values. The problem with the real lung is that it is difficult to judge whether and to what extent back-diffusion is impaired, although independent measures of small airway constriction could be envisioned in an attempt to determine this. In the meantime, we advocate here a more pragmatic approach.