Table 3.
Summary of studies investigating the association between FeNO and loss of asthma control in adults
| Loss of control | Association of FeNO | ||
|---|---|---|---|
| Tsurikisawa et al 2012 [51] | Prospective 2-year study | 90 patients with moderate or severe asthma on ICS and without clinical symptoms for ≥6 months. Mean (SD) age: 49.1 (14.6) years in exacerbation-free group (n = 50), 50.9 (15.9) years in exacerbation group (n = 40). Mean (SD) FeNO: 25.6 (12.0) ppb in exacerbation-free group, 43.4 (27.3) ppb in exacerbation group. |
Multivariate logistic regression showed a rank order of predictors of successful ICS reduction while retaining asthma control (exacerbations): acetylcholine PC20 (p < 0.01); length of time with no clinical symptoms before ICS reduction (p < 0.01); FeNO (p = 0.028); and FEV1 (% predicted) (p = 0.03). |
| Jones et al 2001 [52] | Prospective 6-week study | 78 patients with mild to moderate asthma on ICS for ≥6 months. Mean age 42.9 (range 18–74) years. Mean FeNO 9.38 (95% CI, 2.72; 32.35) ppb. |
By regression analysis, single measurements and different FeNO cut-off values (>10 ppb, >15 ppb, or an increase of >60% above baseline) had positive predictive values ranging from 80 to 90% for predicting loss of control. |
| Matsunaga et al 2012 [53] | Prospective observational 12-week study | 250 patients with stable asthma on ICS with/without LABA and/or other therapies. Mean (SD) age 46.6 (14.7) years. Mean (SD) FeNO 34.6 (22.0) ppb. |
Multivariate logistic regression analysis showed that a FeNO level >39.5 ppb gave 67% sensitivity and 76% specificity for identifying the patients with poorly controlled asthma. |
| Michils et al 2008 [54] | Prospective longitudinal 3-month study | 341 patients with mild, moderate or severe asthma, ICS naïve, or on ICS with/without LABA and/or other therapies. Mean (SD) age 41 (16) years. Geometric mean (range) FeNO 32.9 (13.8–78.1) ppb. |
In the whole population, FeNO >45 ppb was not associated with well-controlled asthma (negative predictive value 88%), p < 0.001. The use of FeNO for predicting asthma control was less effective as ICS dose increased. |
| Ozier et al 2011 [55] | Prospective 6-month study | 90 patients with severe or non-severe asthma, 72% on ICS, 50% on LABA and 6.7% on OCS. Mean (SD) age: 38.5 (2.1) years in controlled group (n = 62), 44.8 (3.2) years in uncontrolled group (n = 28). Mean baseline FeNO not stated. |
A correlation analysis was used to determine that a low baseline FeNO <31 ppb was a good predictor of not losing good asthma control (negative predictive value ≥95%), but high FeNO >31 ppb was only a modest predictor of loss of asthma control (positive predictive value 67%). |
| Yamashita et al 2016 [56] | Retrospective 1-year study | 71 patients with mild asthma newly diagnosed and not on ICS. 37 patients continued clinic visits for 1 year. Mean (SD) age 50.9 (15.6) years. Mean (SD) FeNO 42.2 (31.9) ppb. |
In a multivariate logistic regression, FeNO levels at the first visit were identified as a possible predictor of asthma control (OR 0.9459 (95% CI, 0.9024; 0.9915); p = 0.021). |
| Tsilogianni et al 2016 [57] | Ongoing cohort 6-month study | 170 patients with mild to moderate (72%) or severe (28%) asthma on ICS and/or LABA, LTRA, OCS or omalizumab. Median (range) age 53 (42–62) years. Median (range) FeNO 22 (16–35) ppb. |
FeNO levels differed significantly between patients with well-controlled asthma and those with uncontrolled asthma, median (IQR) 21 (14–28) vs. 45 (19–67), p < 0.001. Receiver operating characteristic analysis for the whole study population showed that FeNO <43 ppb was only a modest predictor of well-controlled asthma (negative predictive value 50%). |
| No effect of FeNO | |||
| Kilic et al [58] | Cross-sectional outpatient study | 81 women (41 obese) with mild (84%), moderate (12%) or severe (4%) stable asthma on ≥1 asthma therapy for ≥6 months. Mean (SD) age: 53.9 (10.2) in obese group, 47.3 (15.7) in nonobese group. Median (range) FeNO: 21.0 (11.0–52.0) in obese group, 22.5 (6.0–297.0) in nonobese group. |
By regression analysis, high BMI was found to be the only significant factor that contributed to poor asthma control, with no effect of FeNO (p = 0.799 in the obese group, p = 0.194 in the nonobese group). |
BMI, body mass index; CI, confidence interval; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; IQR, interquartile range; LABA, long-acting beta agonist; LTRA, leukotriene receptor antagonists; n, number of patients; PC20, provocative dose causing a 20% fall in FEV1; OR, odds ratio; ppb, parts per billion; SD, standard deviation.