Improved Prediction of Asthma Exacerbations by Measuring Distal Airway Inflammation

Introduction: Partitioning parameters measured from exhaled nitric oxide, such as the alveolar concentration of nitric oxide (CalvNO), may provide better predictors of future asthma exacerbation than exhaled nitric oxide fraction at an expiratory flow rate of 50 mL·s−1 (FENO50). We aimed to determine whether any partitioned nitric oxide parameters were more closely associated than FENO50 with subsequent asthma exacerbations.

Methods: 68 asthmatic children (mean±sd age 9.0±2.4 years) were followed prospectively (134 visits) and exacerbations were recorded. Childhood Asthma Control Test (cACT), spirometry, FENO50, CalvNO, bronchial flux of nitric oxide (JawNO), transfer factor of nitric oxide (DawNO) and airway wall concentration of nitric oxide (CawNO) were measured.

Results: No exacerbation was recorded in 99 visits (Group 1) and an exacerbation was recorded in 35 visits (Group 2). The median (range) FENO50, JawNO, CalvNO, DawNO and CawNO of Group 1 versus Group 2: 12.7 (4–209) versus 13.5 (3.8–149.9) ppb, 715 (10–12 799) versus 438 (40–7457) pL·s−1, 3.4 (0.2–10.8) versus 5.2 (1.7–23.6) ppb, 38.3 (0.2–113.3) versus 38 (1.3–144.5) pL·s−1·ppb−1 and 26.8 (4.1–2163) versus 29.9 (5.5–3054) ppb, respectively. Other than for CalvNO (p<0.001), there was no difference between the two groups. CalvNO >7 ppb predicted asthma exacerbation with specificity 90.9% and positive likelihood ratio (LR) 3.1. Conversely, CalvNO <4 ppb excluded an exacerbation with sensitivity 71.4% and negative LR 0.48. An increase of CalvNO by 0.5 ppb between visits could also predict an exacerbation with sensitivity 92%, specificity 92%, positive LR 11.8 and negative LR 0.08.

Conclusions: Assessment of CalvNO improved prediction of subsequent exacerbation, highlighting the importance of distal inflammation in asthma outcomes in children.