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Role of Spirometry and Exhaled Nitric Oxide To Predict Exacerbations in Treated Asthmatics^*

^* From Lakewood Regional Medical Center (Drs. Gelb and Shinar, and Ms. Flynn Taylor); Lakewood, CA; and School of Medicine (Drs. Gutierrez and Zamel), University of Toronto, Toronto, ON, Canada.

Correspondence to: Arthur F. Gelb, MD, FCCP, 3650 E. South St, Suite 308, Lakewood, CA 90712; e-mail: afgelb{at}msn.com

Abstract

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 µg of fluticasone/50 µg 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 µg 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 FEV₁ was 76% predicted, exacerbations occurred in 20 of 31 asthmatics (65%). If baseline FEV₁ was > 76% of predicted, exacerbations occurred only in 2 of 13 asthmatics (15%) [p = 0.003, ²]. Using a receiver operating characteristic (ROC) curve for first exacerbation, the area under the curve was 0.67 with cutoff FEV₁ 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, 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, FEV₁ 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 FEV₁ > 76% of predicted had a 0% probability of exacerbation.

Conclusion: Combining FENO and FEV₁ percentage of predicted can stratify risk for asthma exacerbation.

Key Words: asthma exacerbations • exhaled nitric oxide • spirometry

This article has been cited by other articles:

				K. G. Lim and C. Mottram The Use of Fraction of Exhaled Nitric Oxide in Pulmonary Practice Chest, May 1, 2008; 133(5): 1232 - 1242. [Abstract] [Full Text] [PDF]