目的·分析哮喘（asthma，AS）合并变应性鼻炎（allergic rhinitis，AR）儿童在AS不同临床分期下不同AR严重程度时的鼻呼出气一氧化氮（fractional concentration of nasally exhaled nitric oxide，FnNO）、口呼出气一氧化氮（fractional concentration of exhaled nitric oxide，FeNO）水平，为指导临床诊治提供依据。方法·纳入2021年4月至11月期间于苏州大学附属儿童医院呼吸科确诊为AS合并AR的儿童，选取同期至儿保科正常体检的健康儿童作为对照组。所有入组儿童均行FeNO、FnNO、外周血嗜酸细胞（eosinophil，EOS）检测，以评估患儿的病情严重程度。对比分析AS合并AR的儿童在AS不同临床分期下不同AR严重程度时的FeNO、FnNO水平及其与肺功能的相关性。结果·哮喘急性发作期儿童中鼻炎持续中重度的比例更高，哮喘临床缓解期儿童中的鼻炎间歇轻度比例更高。哮喘急性发作期的FeNO值高于慢性持续期、临床缓解期（调整后P=0.022、P=0.000），慢性持续期高于临床缓解期（调整后P=0.002）；哮喘急性发作期FnNO值高于临床缓解期（调整后P=0.044）。哮喘慢性持续期中，鼻炎持续轻度组及持续中重度组的FnNO水平高于间歇轻度组（调整后P=0.001、P=0.000）。在临床缓解期中，鼻炎持续轻度组及持续中重度组的FnNO水平高于间歇轻度组（调整后P=0.001、P=0.007）。在鼻炎间歇轻度组中，急性发作期的FnNO高于慢性持续期及临床缓解期（调整后P=0.010、P=0.019）。哮喘急性发作期的部分肺功能指标与FeNO、FnNO水平具有一定负相关性（均P<0.05），而慢性持续期的FEV1/pred 与FeNO水平具有一定负相关性（P=0.010）。结论·AS急性发作期儿童的FeNO、FnNO水平更高，且AR症状积分更高；AS合并AR儿童的FeNO、FnNO水平与肺功能指标呈负相关。
关键词：哮喘
;
变应性鼻炎
;
呼出气一氧化氮
;
儿童
Abstract
Objective ·To determine the levels of nasally exhaled nitric oxide (FnNO) combined with fractional concentration of exhaled nitric oxide (FeNO) in children with asthma (AS) complicated with allergic rhinitis (AR), and analyze the levels of FnNO and FeNO in different clinical stages of AS with different severities of AR, so as to provide basis for guiding clinical diagnosis and treatment. Methods ·Children diagnosed with AR with AS in the Department of Respiratory and Otolaryngology of Children's Hospital of Soochow University from April 2021 to November 2021 were included, and healthy children who visited the Department of Pediatrics for normal physical examination during the same period were enrolled as the control group. FeNO and FnNO were measured in all children to assess the severity of the children's diseases. The levels of FeNO and FnNO in children with AR and AS at different clinical stages of AS and their correlation with pulmonary function were compared and analyzed. Results ·The proportion of persistent moderate-to-severe rhinitis was higher in the acute exacerbation stage of AS, and the proportion of intermittent mild rhinitis was higher in the clinical remission stage of AS. The FeNO level in the acute exacerbation stage were higher than that in the chronic persistent stage and clinical remission stage of AS (adjusted P=0.022, 0.000), and higher in the chronic persistent stage than that in the clinical remission stage of AS (adjusted P=0.002). The FnNO level in the acute exacerbation stage was higher than that in the clinical remission stage of AS (adjusted P=0.044). In the chronic persistent stage of AS, the FnNO levels in the persistent mild group and persistent moderate-to-severe control group were higher than those in the intermittent mild group (adjusted P=0.001, 0.000). In the clinical remission stage of AS, the FnNO levels in the persistent mild group and persistent moderate to severe control group were higher than those in the intermittent mild group (adjusted P=0.001, 0.007). In the intermittent mild group of AR, the FnNO levels in the acute exacerbation stage were higher than those in the chronic persistent stage and clinical remission stage of AS (adjusted P=0.010, 0.019). Part of pulmonary functions in the acute exacerbation stage of AS children were negatively correlated with the FeNO and FnNO levels (all P<0.05), while FEV1/pred in the chronic persistent stage was negatively correlated with FeNO level (P=0.010). Conclusion ·FeNO and FnNO levels increased in the acute exacerbation stage of AS, and symptom scores of AR also increased. FeNO and FnNO levels were negatively correlated with pulmonary function in AS with AR children.
LI Pengyun, DAI Yinfang, LU Yanhong, YU Xingmei, XU Lina, DI Wujianfeng, HAO Chuangli. Clinical study of exhaled nitric oxide in children with asthma and allergic rhinitis. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2023, 43(6): 673-679 doi:10.3969/j.issn.1674-8115.2023.06.003
哮喘（asthma，AS）和变应性鼻炎（allergic rhinitis，AR）均系辅助型T细胞2（T helper2 cell，Th2）介导的气道炎症。上、下气道目前被认为是一个整体，需同时评估。多达19％~38%的AR患者伴有AS，30％~80%的AS患者患有AR［1-2］。有学者［3］提出，AS症状恶化可能与AR症状控制不佳有关，AR可增加2~7倍AS发生的可能，上气道的持续炎症可增加下气道的高反应性，进而导致AS症状的加重。过敏原对鼻黏膜的刺激会导致鼻塞、黏膜水肿、鼻甲肥大，从而降低鼻腔的呼吸和过滤功能，导致支气管炎症和下呼吸道阻塞。研究［3］表明，主动治疗AR可减轻AS症状、支气管高反应性，并减少AS药物治疗的需要。目前国内相关研究甚少，本研究拟分析不同AS临床分期下不同AR严重程度时的鼻呼出气一氧化氮（fractional concentration of nasally exhaled nitric oxide，FnNO）、口呼出气一氧化氮（fractional concentration of exhaled nitric oxide，FeNO）水平及其与肺功能的相关性，以期为指导临床诊治提供依据。
Tab 2 Comparison of EOS， FeNO and FnNO among children in different stages of asthma
Item
Acute exacerbation
stage (n=33)
Chronic persistent
stage (n=32)
Clinical remission
stage (n=34)
H/F
P value
EOS proportion/%
3.97±2.80
5.42±2.69
3.55 (2.13, 5.88)
5.437
0.066
EOS count/(×109·L-1)
3.40 (1.95, 5.45)
0.42±0.20
0.29 (0.19, 0.48)
1.916
0.384
FeNO/ppb
45.00 (31.50, 56.00)①②
27.00 (13.25, 45.75)③
12.50 (9.00, 17.25)
38.861
0.000
FnNO/ppb
664.03±244.13④
573.22±261.69
516.29±224.41
3.128
0.048
Note: FeNO/FnNO is expressed in ppb (parts per billion; 1 ppb=1×10-9), which is equivalent to nanoliters per liter. ①Adjusted P=0.022, compared with the chronic persistent stage; ②adjusted P=0.000, ③adjusted P=0.002, ④adjusted P=0.044, compared with the clinical remission stage.
Tab 3 Comparisons of FnNO in different severities of rhinitis among different stages of asthma
Item
Different severities of rhinitis
F value
P value
Intermittent mild (n=45)
Persistent mild (n=32)
Persistent moderate-to-severe (n=22)
Different stages of asthma
Acute exacerbation stage (n=33)
596.70±211.16
614.27±243.68
765.75±255.02
1.725
0.195
Chronic persistent stage (n=32)
373.86±190.12①
678.77±171.15②
857.00±222.23③
15.709
0.000
Clinical remission stage (n=34)
405.05±140.56④
693.38±287.44⑤
700.20±46.19⑥
10.730
0.000
F value
5.510
0.347
0.643
P value
0.008
0.710
0.537
Note: FnNO is expressed in ppb (parts per billion; 1 ppb=1×10-9), which is equivalent to nanoliters per liter. ①Adjusted P=0.010, compared with the acute exacerbation stage; ②adjusted P=0.001, ③adjusted P=0.000, compared with the intermittent mild group; ④adjusted P=0.019, compared with the acute exacerbation stage; ⑤adjusted P=0.001, ⑥adjusted P=0.007, compared with the intermittent mild group.
如表4所示，哮喘急性发作期的第1秒用力呼气容积占预计值百分比（forced expiratory volume in 1 s of the predicted，FEV1/pred）、用力肺活量占预计值百分比（forced vital capacity of the predicted，FVC/pred）、呼气峰流速占预计值百分比（peak expiratory flow of the predicted，PEF/pred）、用力呼气中期流速占预计值百分比（average expiratory flow rate at 25% to 75% of lung capacity of the predicted，MMEF75/25/pred）与FeNO水平具有一定负相关性（r值分别为-0.393、-0.477、-0.367和-0.358，P值分别为0.024、0.005、0.036和0.041），慢性持续期的FEV1/pred与FeNO水平具有一定负相关性（r=-0.451，P=0.010）。
Tab 4
表4
表4哮喘不同分期儿童的肺功能指标与FeNO的相关性分析
Tab 4 Correlation analysis between lung function indicators and FeNO in children with different stages of asthma
Item
Acute exacerbation stage
Chronic persistent stage
Clinical remission stage
r value
P value
r value
P value
r value
P value
FEV1/pred/%
-0.393
0.024
-0.451
0.010
-0.321
0.064
FVC/pred/%
-0.477
0.005
-0.279
0.122
-0.184
0.298
FEV1/FVC/pred/%
-0.015
0.936
-0.308
0.086
-0.324
0.061
PEF/pred/%
-0.367
0.036
-0.050
0.786
0.065
0.714
MEF75/pred/%
-0.154
0.392
-0.197
0.279
-0.304
0.081
MEF50/pred/%
-0.323
0.066
-0.329
0.066
-0.261
0.135
MEF25/pred/%
-0.243
0.174
-0.320
0.074
-0.095
0.592
MMEF75/25/pred/%
-0.358
0.041
-0.266
0.141
-0.248
0.158
Note: MEF75—maximal expiratory flow without exhaling 75% FVC; MEF50—maximal expiratory flow without exhaling 50% FVC; MEF25—maximal expiratory flow without exhaling 25% FVC.
The study was designed by LI Pengyun, DAI Yinfang and YU Xingmei. The data collection and analysis were conducted by LI Pengyun and XU Lina. The manuscript was drafted and revised by LI Pengyun, LU Yanhong, DI Wujianfeng and HAO Chuangli. All the authors have read the last version of paper and consented for submission.
利益冲突声明
所有作者声明不存在利益冲突。
COMPETING INTERESTS
All authors disclose no relevant conflict of interests.
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