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

Objective: 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. Methods: We prospectively studied 44 nonsmoking asthmatics (24 women) aged 51 +/- 21 years (mean +/- SD) who were clinically stable for 6 weeks and receiving 250 mu g of fluticasone/50 mu g 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. Results: Baseline FEV1 was 2.1 +/- 0.7 L, 70 +/- 20% of predicted after 180 mu g of albuterol. Twenty-two of 44 asthmatics had one or more exacerbations over IS 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, was <= 76% predicted, exacerbations occurred in 20 of 31 asthmatics (65%). If baseline FEV, 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, of 76% of predicted (sensitivity, 0.91; specificity, 0.50; positive predictive value, 0.65; negative predictive value, 0.85; positive likelihood ratio [LB(+)], 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 FEV1, 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, <= 76% predicted increased RR by 1.7 (95% CI, 1.0 to 2.7; p = 0.02). Combined baseline FENO >= 28 ppb and FEV1 <= 76% of predicted identified 13 stable asthmatics with 85% probability for future exacerbation, whereas 9 asthmatics with FENO < 28 ppb and FEV, > 76% of predicted had a 0% probability of exacerbation. Conclusion: Combining FENO and FEV1 percentage of predicted can stratify risk for asthma exacerbation.