1-Year Prospective Study of the Relationship of Serial Exhaled Nitric Oxide Level and Asthma Control

Figures & data

Table 1 Demographic Data of the Subjects (n = 136)

Age	51.51 ± 15.09
Gender (Male)	46 (33.8%)
Body mass index (kg/m^2)	24.95 ± 4.80
Baseline medication use
ICS alone	9 (6.62%)
ICS + LABA	116 (85.3%)
LAMA	41 (30.1%)
Montelukast	59 (43.4%)
Theophylline	14 (10.3%)
Dose of ICS: (n=125)
Low	21 (16.8%)
Medium	50 (40.0%)
High	54 (43.2%)
Eosinophil count (X10^9/L) (n=135)	0.34 ± 0.44
Eosinophil (%) (n=135)	4.69 ± 4.26
IgE (IU/mL)(n=134)	118.5 [41–312]
Skin prick test (n=133)
Positive	83 (62.4%)
Spirometry
Pre-bronchodilator(n=121)
FEV1 (L)	1.98 ± 0.67
FVC (L)	2.80 ± 0.75
FEV1/FVC %	70.68 ± 13.54
FEV1% predicted	80.80 ± 20.71
FVC % predicted	91.81 ± 16.50
Post-bronchodilator(n=133)
FEV1 (L)	2.03 ± 0.66
FVC (L)	2.81 ± 0.77
FEV1/FVC (%)	72.36 ± 12.97
FEV1% predicted	83.41 ± 19.12
FVC % predicted	92.64 ± 16.70
Comorbidities
Rhinitis	97 (71.3%)
Eczema	20 (14.7%)
Sleep apnoea	20 (14.7%)
Heart failure	1 (0.7%)
Hypertension	33 (24.3%)
Diabetes	17 (12.5%)
Ischaemic heart disease	1 (0.7%)
Gastroesophageal reflux	17 (12.5%)
Psychiatric disorder	10 (7.4%)
Number of asthma exacerbations in the past 12 months	0.14 ± 0.91

Note: Data were presented as mean ± SD, median [IQR] or number (%).

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LAMA, long-acting anti-cholinergic agent.

Table 2 FeNO Levels and Asthma Control at Baseline Visit

	n	Mean (SD) ppb	Median [IQR] ppb	p value*
GINA
Controlled	48	36.8 (26.4)	27.5 [19.0–46.5]	0.157
Partly controlled	49	41.3 (34.7)	28.0 [14.0–55.0]
Uncontrolled	39	53.8 (41.4)	34.0 [21.0–84.5]
ACT
20–25	85	39.0 (29.6)	29.0 [17.0–53.0]_	0.302
19–16	31	51.6 (38.5)	35.0 [20.5–85.5]
<16	20	48.7 (45.9)	29.0 [18.0–66.5]
ACQ
≤0.75	79	42.1 (31.4)	32.0 [18.50–58.0]	0.991
0.75–1.5	30	41.2 (33.6)	31.5 [17.0–52.0]
≥1.5	27	49.1 (44.6)	26.0 [17.5–84.5]

Note: P* value by comparisons of the median levels using Kruskal-Wallis Test.

Abbreviations: GINA, Global Initiative of Asthma level of asthma control; ACT, Asthma Control Test; ACQ, Asthma Control Questionnaire.

Table 3 Changes in Asthma Control and FeNO Levels Over Time

Change of Level of Control	n	Mean (SD)	Median [IQR]	P^#	n	Mean (SD)	Median [IQR]	P^#	n	Mean (SD)	Median [IQR]	P^#
	Changes from Baseline to 4 Months				Changes from Baseline to 8 Months				Changes from Baseline to 12 Months
GINA
Worsened	18	3.21 (21.1)ppb	2.0 [−4.0–12.0]ppb	0.021*	12	8.5 (21.8)ppb	1.5 [−4.5–12.0]ppb	0.048*	14	4.9 (10.5)ppb	3.5 [−5.0–12.0]ppb	0.036*
		18.6 (63.6)%	6.6 [−25.0–60.0]%	0.034*		43.1 (84.5)%	13.1[−15.7–83.1]%	0.116		32.7 (71.8)%	14.1 [−20 – 69.2]%	0.112
No change	43	0.7 (24.4)ppb	−1.0 [−10.5–9.0] ppb		39	0.5(19.4)ppb	−1 [−11.5–10.0]ppb		32	2.3 (21.0)ppb	−0.5 [−9.0–10.0]ppb
		18.5 (102.2)%	−8.0 [−34.9–34.6]%			19.9 (79.5)%	−7.1 [−40.4–44.5]%			40.2 (130.1)%	−1.6 [−25 – 41.4]%
Improved	38	−16.8 (28.4)ppb	−7.0 [−32.0–3.0]ppb		36	−17.7 (36.6)ppb	−6.5 [−35.5–6.5]ppb		39	−16.2 (35.7)ppb	−7.0 [−25.5–6.0]ppb
		−17.3 (44.0)%	−27.5[−43.8–11.6]%			−4.6 (64.0)%	−16.1 [−53.8–32.8]%			−2.2 (64.9)%	−13.8 [−42.5–29.0]%
ACT
Worsened	13	−2.6 (22.7)ppb	−3.0 [−5.0–5.0]ppb	0.016*	12	2.0 (24.9) ppb	−3 [−12.5–10.5]ppb	0.149	11	3.8 (21.4)ppb	1.0 [−5.5–17.0]ppb	0.129
		3.1 (63.8)%	−16.7[−33.3–19.8]%	0.007*		13.2 (73.4)%	−9.6 [−39.4–36.9]%	0.165		73.1 (183.7)%	5.9 [−31.0–57.5]%	0.194
No change	61	0.7 (22.43)ppb	0 [−10.0–9.0]ppb		53	−2.2 (24.5)ppb	0.0 [−1.02–11.0]ppb		55	−2.2 (23.3)ppb	−1.0 [−9.0–9.0]ppb
		18.5 (90.2)%	0 [−28.6–37.5]%			22.1 (78.6)%	0.0 [−41.7–50]%			19.1 (78.3)%	−3.5 [−25.0–38.0]%
Improved	25	−22.5 (31.8)ppb	−15.0 [−45.0–3.0]ppb		22	−19.3 (39.1)ppb	−9.5 [−35.0–3.0]ppb		19	−21.6 (41.7)ppb	−12.0 [−36.5–2.0]ppb
		−27.6 (38.2)%	−35.5 [−57.0–6.7]%			−9.1 (65.8)%	−22.7 [−55.8–12.5]%			−10.4 (62.3)%	−18.2 [−61.2–12.4]%
ACQ5
Worsened	14	3.9 (15.3)ppb	2.0 [−4.0–9.0]ppb	0.003*	12	−6.5 (39.0)ppb	−7.5 [−11.0–10.5]ppb	0.004*	17	−1.5 (34.5)ppb	−4.0 [−7.0–12.0]ppb	0.295
		15.1 (57.8)%	−4.00 [−20 – 31.25]%	0.004*		3.3 (77.4)%	−19.9 [−42.4–24.7]	<0.001*		54.8 (167.2)%	−6.3 [−28.6–34.9]%	0.160
No change	61	−1.0 (24.8)ppb	0.0 [−11.0–9.0]ppb		51	2.1 (18.5)ppb	2.0 [−8.5–12.0]ppb		47	−0.2 (14.7)ppb	−1.0 [−10.5–9.5]ppb
		16.0 (91.3)%	0.0 [−33.3–34.6]%			32.9 (76.4)%	20 [−25.4–62.8]%			21.1 (69.1)%	−3.23 [−23.6–47.6]%
Improved	24	−22.9 (29.9)ppb	−14.5 [−40.0–0.5]ppb		24	−22.8 (37.1)ppb	−17.0 [−43.0–1.0]ppb		21	−21.7 (42.1)ppb	−7.0 [−49.0–7.0]ppb
		−29.7 (35.0)%	−36.6 [−52.6–1.9]%			−24.5 (56.4)%	−47.8 [−61.8–3.3]%			−12.8 (61.8)%	−17.1 [−63.4–25.9]%

Notes: Changes in FeNO levels were presented as observed FeNO at certain time points minus baseline level (ppb) and the results were illustrated as absolute change (SD) in ppb and percentage change (SD) in %. ^#Kruskal–Wallis test. *p < 0.05. Changes in levels of control: Improved (improved in at least one level of asthma control, ie, from partly controlled or uncontrolled to control or from partly controlled to controlled), no change (stayed at same level of control), worsened (worsened in at least one level of asthma control, ie, from controlled to partly controlled or uncontrolled, from partly controlled to uncontrolled).

Figure 1 Boxplot of change in FeNO levels at 4, 8 and 12 months compared with baseline (all subjects). (A) Global Initiative of Asthma level of asthma control (GINA), (B) Asthma Control Test (ACT), (C) Asthma Control Questionnaire (ACQ). Changes in FeNO levels were presented as observed FeNO at certain time point minus baseline level (ppb). p value was calculated by Kruskal–Wallis test. * = p < 0.05. The solid line represents the median level, the box represents the IQR and the upper / lower whiskers are from the upper/lower quartile to the highest/lowest actual value within the 75th percentile/25th percentile ± 1.5 × IQR. Changes in levels of control: Improved (improved in at least one level of asthma control, ie, from partly controlled or uncontrolled to control, or from uncontrolled to partly controlled), no change (stayed at same level of control), worsened (worsened in at least one level of asthma control, ie from controlled to partly controlled or uncontrolled, from controlled to partly controlled).

Figure 2 ROC curves for predicting the improvement for asthma control at different time points. (A) Global Initiative of Asthma level of asthma control (GINA), (B) Asthma Control Test (ACT), (C) Asthma Control Questionnaire (ACQ).