1. Increased Exhaled Nitric Oxide and Risk of Loss of Control in Children Undergoing Clinical Asthma Remission  
D.V. Chang, J.E. Balinotti, C. Castro Simonelli, C. Kofman, A. Teper
Centro Respiratorio, Hospital de Niños Ricardo Gutiérrez - Buenos Aires/AR
RESULTS
RESULTS
RESULTS
INTRODUCTION
Childhood asthma is a complex disease often characterized by heightened airway reactivity, and airway inflammation. Great efforts have been focused on how to achieve optimal disease control. However, knowledge about how to proceed in children with remission of asthma symptoms after controlled therapy withdrawal is a topic that still remains unclear.
It has been suggested that exhaled nitric oxide (eNO) is a useful noninvasive biomarker that contribute to identify the eosinophilic asthma phenotype, assess poor asthma control, and could predict asthma exacerbations. Cumulatively, this findings suggests that eNO may be a useful tool for longitudinal assessment of asthma control.
The aim of the study was to determine the association between increased eNO values and the subsequent loss of control in children undergoing asthma clinical remission after withdrawal of inhaled steroid medication. Additionally, we thought to determine possible airway inflammation patterns in this particular stage of childhood asthma.
Table 2. Baseline anthropometric, atopy and lung function data.
Figure 3. Increased eNO (eNO ≥ 21.8ppb) and time for LOC.
Figure 2. ROC curve. eNObaseline and LOC N 37
Age (years)
11 (2.7)
Gender (Male)
62%
Height (cm)
141 (14.4)
Weight (Kg.)
41 (12.4)
FVC (% pred.)
101 (12.9)
FEV1 (% pred.)
100 (13.3)
FEV1 Post BD change (%)
3.9(5.4)
FEV1/FVC
87 (6.7)
FEF (% pred.)
95 (30)
Positive Prick Test
76%
eNO baseline †(ppb)
29.1 ( )
21.8ppb
AUC p
95%CI
0.74
0.041
Methods
Sensitivity
68%
Specificity
70%
† Median (Range)
Inclusion criteria:
Children aged 6-18 years old
Asthma diagnosis by physician with history of bronchodilator response (FEV1 post bronchodilator ≥ 12% or 200 ml change at FEV1) and/or positive methacholine provocation test (PC20 <2)
Clinically controlled disease, according to GINA guidelines, for at least six months with a low-dose of ICS (budesonide 200 µg/day or equivalent) and with normal lung function.
Who were to discontinue control therapy according their physician decision.
Exclusion criteria:
Chronic lung disease different than asthma
Heart disease
Upper airway viral infection in last 4 weeks
Table 3. Loss of control (LOC)
Time to LOC (weeks)
Variable
Median (IQR)
p-value
Increased eNO
8 (4-29.5)
p=0.02
Control
28 (16-48) N 25
Severity
1. Asthma exacerbation wo. systemic CT
68%
2. Asthma exacerbation w. systemic CT
16%
3. Airway obstruction at spirometry only
12%
4. ACT < 19 only 4%
Upper airway infection prior to asthma exacerbation
45%
Table 4. Association between eNObaseline , Increased eNObaseline (≥ 21.8 ppb.), and LOC.
Figure 4. Increased eNO and eNO follow up.
Predictor
Loss of clinical control
Univariable model
Multivariable Model‡ OR
95% CI
p- value
95% CI
eNO†
2.96
0.030
7.67
0.013
eNO ≥21.8 ppb
4.96
0.049
9.01
0.041
Table 1. Study design
(Summer)
ENTRY
CT: corticosteroids, ACT: asthma control test
Follow up
Time (weeks) -4 4 8 12 16 20 24 28 32 36 40 44 48
Assessments
Clinical control X
ACT
eNO XB
Spirometry PT
eNObaseline
eNOpre-end
Figure 1. Association between eNO baseline and LOC.
Variable
Increased eNO
Controls
p-value¶
eNObaseline (ppb)†
54 (31.6)
11.5 (5.5)
<0.001‡
eNOpre-end (ppb)†
58 (32.8)
14.4 (10.7)
eNOratio†
1.14 (0.5)
1.23 (0.5)
0.53
Predictor
Outcome OR
95% CI
p-value
eNO baseline†
LOC
2.96
0.030
eNO: Exhaled nitric oxide, ppb: parts per billion; OR: Odds ratio; 95%CI: 95% confidence interval.
† values were log transformed.
‡ The model was adjusted by height, gender, positive prick test and passive smoking exposure.
eNO: exhaled nitric oxide; ppb: parts per billion; eNObaseline: First eNO assessment; eNOpre-end: eNO assessment prior to loss of control and last eNO assessment for subjects without loss of clinical control. eNOratio: eNOPre-end / eNObaseline
† Mean (SD). ‡ eNO values were log transformed.
¶ The model was adjusted by height, gender, positive prick test and passive smoking exposure.
† values were log transformed.
ACT: asthma control test; eNO: exhaled nitric oxide; PT: prick test; XB: baseline measurement
Loss of control (at least one of the following):
ACT questionnaire < 19
Bronchial obstruction in spirometry ( VEF1<80%)
Asthma exacerbation assessed by a physician.
CONCLUSIONS
We found that increased eNO, measured 4 weeks after inhaled steroids withdrawal during clinical remission in childhood asthma, was associated with an increased risk for subsequent LOC.
Those with increased eNO presented an earlier LOC compared to subjects with normal eNO.
Airway inflammation patterns may be identify over time in this particular stage of childhood asthma.
Cumulatively, eNO may be a useful noninvasive tool for predicting LOC and may contribute for clinical follow up decisions during childhood asthma clinical remission.
eNO measurement: eNO was measured on-line with a chemiluminescence analyzer (CLD 88sp, Eco Medics AG, Durnten, Switzerland) at an expiratory flow of 50ml/s.