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 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.


RESULTS
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% predicted, exacerbations occurred in 20 of 31 asthmatics (65%). If 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) </= 76% predicted increased RR by 1.7 (95% CI, 1.0 to 2.7; p = 0.02). Combined baseline FENO >/= 28 ppb and FEV(1) </= 76% of predicted identified 13 stable asthmatics with 85% probability for future exacerbation, whereas 9 asthmatics with FENO < 28 ppb and FEV(1) > 76% of predicted had a 0% probability of exacerbation.


CONCLUSIONS
Combining FENO and FEV(1) percentage of predicted can stratify risk for asthma exacerbation.
Gelb
Arthur F
AF
Lakewood Regional Medical Center, Lakewood, CA 90712, USA. afgelb@msn.com
Flynn Taylor
Colleen
C
Shinar
Chris M
CM
Gutierrez
Carlos
C
Zamel
Noe
N
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D001944:Breath Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D013147:Spirometry; D014109:Total Lung Capacity / Q000502:physiology
D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D009569:Nitric Oxide