The Role of Nasal Nitric Oxide and Anterior Active Rhinomanometry in the Diagnosis of Allergic Rhinitis and Asthma: A Message for Pediatric Clinical Practice

Figures & data

Figure 1 Flow chart of the study recruitment process.

Table 1 Characteristics of the Study Participants, Evaluation of Respiratory NO Metabolites and Rhinomanometric/Spirometric Values Within All Groups, Subset A and B

	Group				Subset A	Subset B
	0	1	2	3	1+3	1+2+3
	N 40	N 64	N 22	N 34	N 98	N 120
Age (years)	8.32 ± 1.64*	8.41 ± 1.69*	8.27 ± 1.81*	8.32 ± 2.04*	8.38 ± 1.81	8.36 ± 1.8*
Male, N (%)	20 (50%)	32 (50%)	13 (59.1%)	19 (55.8%)	51 (61.7%)	64 (76%)
nFeNO	106.5 [35.25] **	879.5 [247.25] **	784 [456.75] **	1063.5 [279.75] **	966 [243. 50] **	899.5 [240.75] **
eFeNO	3 [3] **	11 [3] **	37.5 [11.25]**	42.5 [7] **	12.5 [28] **	14.5 [29.25]**
FEV 1	100.17 ± 11.61**	96.08 ± 8.17 **	86.36 ± 12.5**	78.88 ± 9.18 **	90.11 ± 11.82 **	89.42 ± 11.98**
mNF	94.78 [11] **	61.81 [46.25] **	78.84 [30.5] **	66.18 [49] **	63.33 [51.5] **	66.17 [52] **
nFeNO/ eFeNO	32.5 [37.45] **	81 [39.64] **	19.5 [9.67] **	26 [9.01] **	26 [57.92] **	43 [57.79] **

Notes: Summary table with demographical characteristics of the population under study and nFeNO, eFeNO, FEV1 and mNF. Age is indicated as mean ± SD and the p-value of the one-way ANOVA F-statistic; the factorial variable is represented as numbers of males and frequency of them among each group (%) in line with the descriptive statistics. The total of boys was 84. The numerical variables used in our study shown with median and interquartile range [IQR], except for FEV1 that is represented as mean±sd. The p-values refer to Kruskal–Wallis test for multiple comparison of all the variables, except for FEV1 for which it is reported the ANOVA F-statistic’s p-value since it is normal and homoscedastic. In case of single comparisons, the p-value shown results from the Wilcoxon rank-sum test for all the variables, but FEV1 was studied with T student. The extremely high significant p values (<0.0001) are indicated by **, whereas the non-significant ones (p value > 0.05) are identified with *.

Table 2 Post Hoc Analysis of nFeNO, mNF, eFeNO, and FEV1 between Groups

nFeNO	Controls	AR	Asthma
AR	< 0.0001	–
ASTHMA	< 0.0001	0.22	–
AR+ASTHMA	< 0.0001	< 0.0001	< 0.0001
mNF	Controls	AR	Asthma
AR	< 0.0001	–
ASTHMA	0.0012	0.0120	-
AR+ASTHMA	< 0.0001	0.3623	0.0796
eFeNO	Controls	AR	Asthma
AR	< 0.0001	-	-
ASTHMA	< 0.0001	< 0.0001	-
AR+ASTHMA	< 0.0001	< 0.0001	0.078
FEV1	Controls	AR	Asthma
AR	<0.05	-	-
ASTHMA	<0.0001	< 0.001	-
AR+ASTHMA	< 0.0001	<0.0001	0.0137
RATIO nFeNO/eFeNO	Controls	AR	Asthma
AR	< 0.0001	-	-
ASTHMA	0.005	< 0.0001	-
AR+ASTHMA	< 0.0001	< 0.0001	0.02

Notes: Post hoc analysis for Holm’s or Bonferroni (ratio nFeNO/eFeNO) p-value adjustment after Kruskal–Wallis rank-sum test of nFeNO, mNF, eFeNO, and FEV1 between groups. Non-significant values (p>0.05) are in italic.

Figure 2 Boxplots of the distribution of the variables between groups. Boxplots representing the distribution of the variables nFeNO (A), eFeNO (B), FEV1 (C), mNF (D) and nFeNO/eFeNO (E) among the four groups of the population: white (group 1, ie controls), light yellow (group 2, ie allergic rhinitis), light blue (group 3, ie asthma) and grey (group 3, ie allergic rhinitis and asthma). All the p values were <0.0001 for each variables between groups using Kruskal-Wallis rank-sum test (A–E). See also the post hoc analysis tables for each couple of the comparisons.

Figure 3 ROC curves of nFeNO for subset A. ROC curves of nFeNO as a predictor for allergic rhinitis alone or with asthma (subset A) without the covariate sex (A). Next, two analogue sex-adjusted curves, respectively, for males (B) and females (C). All the graphs report the cut-off values of nFeNO, specificity (Sp) and sensitivity (Se) levels with also the area under curve (AUC) values and its 95% confidence interval (CI). Below each figure, there is the relative summary: AUC, AUC CI 95%, Se and Sp.

Figure 4 ROC curves of nFeNO for group 3. ROC curves of nFeNO as a predictor for asthma and allergic rhinitis (group 3) without the covariate sex (A). Next, two analogue sex-adjusted curves, respectively, for males (B) and females (C). All the graphs report the cut off values of nFeNO, specificity (Sp) and sensitivity (Se) levels with also the area under curve (AUC) values and its 95% confidence interval (CI). Below each figure, there is the relative summary: AUC, AUC CI 95%, Se and Sp.

Figure 5 Scatter plots and Pearson’s correlation among nFeNO, mNF, eFeNO, FEV1 and the ratio nFeNO/eFeNO. The scatter plots with the regression line and Pearson’s correlation coefficient of the linear correlation: positive correlation (r= - 0.51) between nFeNO with eFeNO (A), negative correlation (r=- 0.61) between FEV1 with eFeNO (B), negative correlation (r= - 0.61) between FEV1 and nFeNO (C), negative correlation (r =- 0.39) between nFeNO and mNF (D), positive correlation (r=0.25) between FEV1 and the ratio nFeNO/eFeNO (E), and the negative correlation (r=−0.12) between mNF and the ratio nFeNO/eFeNO (F).

Abbreviation: NS, non-significant.