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 (C-alvNO), may provide better predictors of future asthma exacerbation than exhaled nitric oxide fraction at an expiratory flow rate of 50 mL.s(-1) (F-ENO50). We aimed to determine whether any partitioned nitric oxide parameters were more closely associated than F-ENO50 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, F-ENO50, C-alvNO, bronchial flux of nitric oxide (J(awNO)), transfer factor of nitric oxide (D-awNO) and airway wall concentration of nitric oxide (C-awNO) 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) F-ENO50, J(awNO), C-alvNO, D-awNO and C-awNO 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 C-alvNO (p<0.001), there was no difference between the two groups. C-alvNO >7 ppb predicted asthma exacerbation with specificity 90.9% and positive likelihood ratio (LR) 3.1. Conversely, C-alvNO <4 ppb excluded an exacerbation with sensitivity 71.4% and negative LR 0.48. An increase of C-alvNO 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 C-alvNO improved prediction of subsequent exacerbation, highlighting the importance of distal inflammation in asthma outcomes in children.