Role of spirometry and exhaled nitric oxide to predict exacerbations in treated asthmatics

To evaluate the complementary roles of exhaled nitric oxide (NO) and spirometry to predict asthma exacerbations requiring one or more tapering courses of systemic corticosteroids.

We prospectively studied 44 nonsmoking asthmatics (24 women) aged 51 +/- 21 years (mean +/- SD) who were clinically stable for 6 weeks and receiving 250 mug of fluticasone/50 mug of salmeterol or equivalent for 3 years. Total exhaled NO (FENO), small airway/alveolar NO (CANO), large airway NO flux (J'awNO), and spirometry were measured.

Baseline FEV(1) was 2.1 +/- 0.7 L, 70 +/- 20% of predicted after 180 mug of albuterol. Twenty-two of 44 asthmatics had one or more exacerbations over 18 months, 16 of 22 asthmatics had two exacerbations, and 6 of 22 asthmatics were hospitalized, including 1 asthmatic with near-fatal asthma. When baseline FEV(1) was 76% of predicted, exacerbations occurred only in 2 of 13 asthmatics (15%) [p = 0.003, chi(2)]. Using a receiver operating characteristic (ROC) curve for first exacerbation, the area under the curve was 0.67 with cutoff FEV(1) of 76% of predicted (sensitivity, 0.91; specificity, 0.50; positive predictive value, 0.65; negative predictive value, 0.85; positive likelihood ratio [LR(+)], 1.8; negative likelihood ratio [LR(-)], 0.18). When baseline FENO was >/= 28 parts per billion (ppb), exacerbations occurred in 13 of 17 asthmatics (76%); if baseline FENO was < 28 ppb, exacerbations occurred in only 9 of 27 asthmatics (33%) [p = 0.005, chi(2)]. Using the ROC curve for first exacerbation, the area under the curve was 0.71 with FENO cutoff point of 28 ppb (sensitivity, 0.59; specificity, 0.82; positive predictive value, 0.77; negative predictive value, 0.87; LR(+), 3.3; LR(-), 0.5). Independent of baseline FEV(1), FENO >/= 28 ppb increased the relative risk (RR) for exacerbation by 3.4 (95% confidence interval [CI], 1.3 to 9.1; Mantel-Haenszel, p = 0.007). An abnormal increase in CANO increased RR by 3.0 (95% CI, 0.9 to 9.9; p = 0.04), and abnormal J'awNO increased RR by 2.4 (95% CI, 1.0 to 5.6; p = 0.04). Independent of baseline FENO, FEV(1) /= 28 ppb and FEV(1) 76% of predicted had a 0% probability of exacerbation.

Combining FENO and FEV(1) percentage of predicted can stratify risk for asthma exacerbation.