Asthma is characterized by an inflammation of both the proximal and the distal lung airways. Exhaled nitric oxide (NO) is considered a noninvasive marker of lung airway and alveolar inflamma-tion. Increased NO output ((Qno) in asthma has been extensively documented. Cellular inflammation located in the very small airways and alveoli could contribute to this increased QNO output. Along this line, increased numbers of total eosinophils, activated eosinophils, and lymphocytes have been found in the distal asthmatic lung. Furthermore, there is compelling evidence linking proinflammatory cytokine expression, eosinophil recruitment, and NO synthase expression or reactive nitrogen species in distal airspaces as evaluated by BAL. Consequently, we hypothesized that an increased QNO output could occur from distal airways and/or alveoli of asthmatic subjects.
The flow dependency of exhaled NO fraction
(FEno) has been extensively reported. Convincing mathematical models have related this experimental observation to a dual origin of NO, which is produced both by the proximal airway compartment and by the expansible compartment comprising the alveolar space and very small airways. More recently, Tornberg and colleagues demonstrated that oral cavity contributes significantly to exhaled NO; consequently, the nonexpansible compartment would better be named proximal or conducting airways (orotracheal plus bronchial parts). The ability of multiple-flow analysis to differentiate increase in FEno due to either distal (alveolitis or hepatopul-monary syndrome) or to bronchial (asthma) origin has been verified.
We previously demonstrated, as others, that the increased QNO observed in asthma is due to an increased maximal proximal airway (Qno (Qbr,maxNo), the alveolar NO concentration (FAno) being normal. However, these studies were not designed to assess whether FAno could be elevated owing to the presence of symptoms or bronchial obstruction. Consequently, our objectives were to evaluate the respective contributions of Qbr,maxNO and FAno to FEno in asthmatic children using multiple-flow analysis of (Qno, and to evaluate whether recent symptoms and/or airway obstruction in these children were related to significant increases in Qbr,maxNO or FAno. To ensure the validity of FAno calculation, two approaches of its determination were used using multiple-flow analysis, both of them based on the two-compartment model of the NO exchange dynamic.
Materials and Methods
Patients
Informed consent for the participation to the study was obtained from the parents in every case. Asthma was defined as a history of recurrent wheezing episodes,