Clinical patterns in asthma based on proximal and distal airway nitric oxide categories

<p>Abstract</p> <p>Background</p> <p>The exhaled nitric oxide (eNO) signal is a marker of inflammation, and can be partitioned into proximal [J'aw_NO(nl/s), maximum airway flux] and distal contributions [CA_NO(ppb), distal airway/alveolar NO concentration]. We hypothesized that J'aw_NOand CA_NOare selectively elevated in asthmatics, permitting identification of four inflammatory categories with distinct clinical features.</p> <p>Methods</p> <p>In 200 consecutive children with asthma, and 21 non-asthmatic, non-atopic controls, we measured baseline spirometry, bronchodilator response, asthma control and morbidity, atopic status, use of inhaled corticosteroids, and eNO at multiple flows (50, 100, and 200 ml/s) in a cross-sectional study design. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J'aw_NOand CA_NO.</p> <p>Results</p> <p>J'aw_NOwas not correlated with CA_NO, and thus asthmatic subjects were grouped into four eNO categories based on upper limit thresholds of non-asthmatics for J'aw_NO(≥ 1.5 nl/s) and CA_NO(≥ 2.3 ppb): Type I (normal J'aw_NOand CA_NO), Type II (elevated J'aw_NOand normal CA_NO), Type III (elevated J'aw_NOand CA_NO) and Type IV (normal J'aw_NOand elevated CA_NO). The rate of inhaled corticosteroid use (lowest in Type III) and atopy (highest in Type II) varied significantly amongst the categories influencing J'aw_NO, but was not related to CA_NO, asthma control or morbidity. All categories demonstrated normal to near-normal baseline spirometry; however, only eNO categories with increased CA_NO(III and IV) had significantly worse asthma control and morbidity when compared to categories I and II.</p> <p>Conclusions</p> <p>J'aw_NOand CA_NOreveal inflammatory categories in children with asthma that have distinct clinical features including sensitivity to inhaled corticosteroids and atopy. Only categories with increase CA_NOwere related to poor asthma control and morbidity independent of baseline spirometry, bronchodilator response, atopic status, or use of inhaled corticosteroids.</p