Pediatric Respirology and Critical Care Medicine

ORIGINAL ARTICLE
Year
: 2017  |  Volume : 1  |  Issue : 1  |  Page : 17--21

The correlation of exhaled nitric oxide, atopy, and severity of allergic rhinitis in taiwanese children with moderate persistent asthma


Yu-Ting Yu1, Shyh-Dar Shyur2, Szu-Hung Chu1, Yu-Hsuan Kao1, Hou-Ling Lung1, Wei-Te Lei1, Li-Ching Fang1, Chien-Hui Yang1,  
1 Department of Pediatrics, Mackay Memorial Hospital, Taipei; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan, Republic of China
2 Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China

Correspondence Address:
Shyh-Dar Shyur
Department of Pediatrics, Mackay Memorial Hospital, 92, Section 2, Chung.Shan North Road, Taipei 104, Taiwan
Republic of China

Abstract

Background: Allergic rhinitis (AR) is characterized by eosinophilic infiltration and immunoglobulin E (IgE)-mediated reaction after exposure to an allergen. Its severity may be correlated to fractional exhaled nitric oxide (FeNO). This study aimed to evaluate the correlation of FeNO and various parameters with severity of AR in Taiwanese children with moderate persistent asthma. Materials and Methods: The study enrolled 103 children aged 5–18 years with AR and moderate persistent asthma from the Outpatient Department, Mackay Memorial Hospital, Taipei. Based on Total Nasal Symptom Score (TNSS), the patients were divided into high-score group (TNSS ≥5) and low-score group (TNSS <5). Both groups were assessed and compared by FeNO, blood eosinophil percentage, serum total IgE level, specific IgE levels to 8 allergens, and pulmonary function tests. Results: The low-score group showed significantly lower FeNO (18.57 ± 14.47 vs. 26.83 ± 17.84 ppb; P < 0.05), lower blood eosinophil percentage (3.08 ± 3.43 vs. 4.53 ± 3.37%; P < 0.05), lower level of serum total IgE (232.64 ± 438.88 vs. 510.63 ± 732.64 IU/mL; P < 0.05), and lower specific IgE to Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), and dog (1.80 ± 2.35 vs. 3.66 ± 2.23, P < 0.05; 1.78 ± 2.36 vs. 3.56 ± 2.31, P < 0.05; and 0.00 ± 0.00 vs. 0.29 ± 0.81, P < 0.05). There are no significant differences between two groups about forced expiratory volume in 1 s (FEV1) (96.95 ± 13.39 vs. 97.85 ± 14.98% predicted; P = 0.75), FEV1/forced vital capacity percentage (89.00 ± 9.78 vs. 90.20 ± 5.85%; P = 0.47), and forced expiratory flow 25%–75% (55.16 ± 18.48 vs. 56.75 ± 20.15% predicted; P = 0.68). Conclusions: Taiwanese children with moderate persistent asthma with more severe symptoms of AR are significantly associated with higher levels of FeNO, total IgE, specific IgE to Der p, Der f, and dog, and higher blood eosinophil percentage.



How to cite this article:
Yu YT, Shyur SD, Chu SH, Kao YH, Lung HL, Lei WT, Fang LC, Yang CH. The correlation of exhaled nitric oxide, atopy, and severity of allergic rhinitis in taiwanese children with moderate persistent asthma.Pediatr Respirol Crit Care Med 2017;1:17-21


How to cite this URL:
Yu YT, Shyur SD, Chu SH, Kao YH, Lung HL, Lei WT, Fang LC, Yang CH. The correlation of exhaled nitric oxide, atopy, and severity of allergic rhinitis in taiwanese children with moderate persistent asthma. Pediatr Respirol Crit Care Med [serial online] 2017 [cited 2021 May 10 ];1:17-21
Available from: https://www.prccm.org/text.asp?2017/1/1/17/201976


Full Text

 Introduction



The human nasal cavity is an important airflow orifice and the gatekeeper of the human airway. Its functions are heating, humidification of inspired air, filtration of hazardous air pollutants and allergen particles, and protection of the peripheral airway. As such, it becomes the most vulnerable organ for accumulating allergic inflammation and the manifestation of clinical symptoms.

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa induced by an immunoglobulin E (IgE)-mediated reaction. It is defined by sensitization to inhaled allergens and symptoms such as rhinorrhea, nasal obstruction, nasal itching, and sneezing during exposure to relevant allergens.[1],[2],[3] Thus, AR has become one of the most common chronic disorders in childhood and adolescence, and its prevalence rate has doubled over the past decades such that the current prevalence rates in countries with the Western lifestyle may be as high as 40%.[1],[4]

Fractional exhaled nitric oxide (FeNO) is a noninvasive biomarker of eosinophilic airway inflammation.[5] It is produced by airway epithelial cells in response to inflammatory cytokines.[6],[7] Evidence based on the previous studies supports the tight relationship between increased FeNO levels and allergic airway inflammation.[7],[8],[9],[10] Recent opinions by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) recognize the role of FeNO in the assessment and management of airway diseases. Recommendations for the standardized procedures of measurement have also been made.[11],[12] Various studies have proven that AR is associated with increased FeNO levels.[8],9,[13],[14],[15],[16],[17]

This study attempted to evaluate the correlation of the severity of AR, FeNO, and various parameters including atopy-related biomarkers in Taiwanese children with moderate persistent asthma. The results may help clarify the role of FeNO and other parameters in assessing the conditions of Taiwanese moderate persistent asthmatic children with AR.

 Materials and Methods



Study design and subjects

This cross-sectional study enrolled 103 children aged 5–18 years old. All of them were first diagnosed with AR and moderate persistent asthma at the Outpatient Department, Mackay Memorial Hospital, Taipei. Besides, the enrolled children were not undergoing any known treatment of asthma and AR including oral drugs and inhaled agents. The diagnosis of AR was done based on a typical history of allergic symptoms and diagnostic tests by the Allergic Rhinitis and its Impact on Asthma guidelines.[18] Diagnosis of moderate persistent asthma was made according to the Global Initiative for Asthma 2008 guidelines.[19] The children's parents provided written informed consent whereas the children provide verbal assent.

After diagnosis had been established, evaluation of symptoms and measurement of parameters were performed before any treatment of asthma and AR including oral drugs and inhaled agents. The following symptoms of AR were evaluated in all children: sneezing, rhinorrhea, nasal itching, and nasal stuffiness. The severity of each symptom was evaluated using the Total Nasal Symptom Score (TNSS),[20],[21] which had a 4-point scale (0, absent; 1, mild; 2, moderate; and 3, severe). Thus, each score ranged from 0 to 3 points, and possible total score ranged from 0 to 12 points. General characteristics, including age, sex, height, body weight, body mass index (BMI), gestational age at birth, and birth weight, were obtained from medical records and questionnaires completed by the patients and their parents. Symptoms of asthma including night cough, shortness of breath in the early morning, dyspnea or wheezing in daytime, and cough in daytime were also evaluated using asthma symptom score.[22] Each asthma symptom score ranged from 1 to 4 points, and possible total score ranged from 0 to 16 points.

Other parameters measured were FeNO, blood eosinophil percentage, blood absolute eosinophil count, serum total IgE level, specific IgE levels to eight allergens (i.e., Dermatophagoides pteronyssinus [Der p], Dermatophagoides farinae [Der f], cat, dog, cockroach, egg white, milk, and fish), and pulmonary function test.

After evaluating the symptoms and measuring the parameters, the children were divided into two groups arbitrarily as per the clinical practice of the authors. The high-score group included 59 children with TNSS ≥5 whereas the low-score group included 44 children with TNSS <5. Both groups were then compared.

Measurements of fractional exhaled nitric oxide

The FeNO was measured in all participants using a handheld, portable Nitric Oxide Analyzer (NIOX MINO, Aerocrine AB, Solna, Sweden) before pulmonary function testing by spirometry. All FeNO measurements followed the ATS/ERS recommendations.[12] Only measurement results from correctly performed procedures and under the correct conditions would be presented. The participants were asked to inhale to total lung capacity and then exhale through the NIOX MINO at a mouth flow rate of 50 mL/s over 10 s, assisted by visual and auditory cues.[23] The measurement range of NIOX MINO was 5–300 ppb.

Measurement of blood eosinophils, serum total immunoglobulin E, and specific immunoglobulin E

Laboratory examination included blood eosinophil percentage, absolute eosinophil count, serum total IgE, and specific IgE to Der p, Der f, cat, dog, cockroach, egg white, milk, and fish. Serum total IgE concentration was determined by the IMMULITE chemiluminescent immunoassay system (Diagnostic Products Corporation, Los Angeles, CA, USA). The normal range of total IgE was <100 IU/ml. The Pharmacia CAP system (Modal Auto-CAP V1 Pharmacia, Uppsala, Sweden) was used to quantify specific IgE antibody concentration in the serum. The degree of hypersensitivity was classified according to the concentrations of specific IgE: Class 0 (<0.35 kuA/L), Class 1 (0.35–0.7 kuA/L), Class 2 (0.7–3.5 kuA/L), Class 3 (3.5–17.5 kuA/L), Class 4 (17.5–50 kuA/L), Class 5 (50–100 kuA/L), and Class 6 (>100 kuA/L).

Pulmonary function tests

Pulmonary function testing included assessments of the forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow (FEF) in 1 sec/FVC ratio (FEV1/FVC), and FEF rate over the middle 50% of the FVC (FEF 25%–75%). All pulmonary function tests were performed using an automated spirometer (Model 2130; SensorMedics, Yorba Linda, CA, USA). A well-trained, experienced technologist performed all of the procedures to ensure that the quality of tests fulfilled the ATS standards.[24],[25]

Statistical analysis

Data from the total group of children were divided into the high-score group (children with TNSS ≥5) and low-score group (TNSS <5). Group data were expressed as means ± standard deviation (SD). Analysis was performed using SPSS 19 for Windows (SPSS Inc., Chicago, Illinois, USA). Variables of clinical parameters between the two groups were compared using Student's t-test and Mann–Whitney U-test, as needed. Variables of basic characteristics were compared using Mann–Whitney U-test and Chi-squared analysis, as appropriate. The FeNO and serum total IgE values were log transformed before analysis to achieve a near normal distribution. For presentation, log-transformed means and SDs were reconverted to their original scale. Statistical significance was set at P < 0.05.

 Results



Basic characteristics of patients

The low-score group (n = 44) had a mean age of 9.48 ± 2.77 years whereas the high-score group (n = 59) had a mean age of 9.74 ± 3.24 years. The ratio of boys to girls was 1.24:1.

In terms of basic characteristics, there were no statistically significant differences between the two groups with regard to sex (61.4% vs. 50.8% male; P = 0.29), age (9.48 ± 2.77 vs. 9.74 ± 3.24 years; P = 0.87), height (138.53 ± 17.38 vs. 137.60 ± 16.67 cm; P = 0.78), weight (36.20 ± 15.53 vs. 35.18 ± 14.39 kg; P = 0.95), BMI (18.88 ± 8.23 vs. 18.27 ± 3.11 kg/m 2; P = 0.53), birth gestational age (39.05 ± 1.37 vs. 38.84 ± 1.73 week; P = 0.75), birth body weight (3219 ± 458.49 vs. 3117 ± 413.55 g; P = 0.26), and asthma symptom score (4.16 ± 1.60 vs. 4.71 ± 1.89 g; P = 0.31) [Table 1].{Table 1}

Relationship between the two groups in terms of fractional exhaled nitric oxide

In terms of FeNO, the low-score group had significantly lower FeNO levels than the high-score group (18.57 ± 14.47 vs. 26.83 ± 17.84 ppb; P < 0.01) [Table 2].{Table 2}

Relationship between the two groups by eosinophil parameters or total immunoglobulin E levels

Comparing blood eosinophil percentage and serum total IgE levels, the low-score group had lower eosinophil percentage (3.08 ± 3.43 vs. 4.53 ± 3.37%; P < 0.01) and absolute eosinophil count (229.97 ± 244.42 vs. 352.08 ± 243.47/μL; P < 0.01) [Table 3]. The low-score group also had lower serum total IgE levels (232.64 ± 438.88 vs. 510.63 ± 732.64 IU/mL; P < 0.01).{Table 3}

Relationship between the two groups in terms of serum allergen-specific immunoglobulin E

The low-score group had significantly lower serum levels of specific IgE to Der p (1.80 ± 2.35 vs. 3.66 ± 2.23; P < 0.01), Der f (1.78 ± 2.36 vs. 3.56 ± 2.31; P < 0.01), and dog (0.00 ± 0.00 vs. 0.29 ± 0.81; P = 0.01) [Table 4]. There were no significant differences between the two groups in terms of serum levels of specific IgE to other agents such as cat, cockroach, egg white, milk, and fish.{Table 4}

Relationship between the two groups by pulmonary function tests

There were no significant differences between the low-score and high-score groups in terms of FEV1 (96.95 ± 13.39 vs. 97.85 ± 14.98% predicted; P = 0.75), FEV1/FVC (89.00 ± 9.78 vs. 90.20 ± 5.85%; P = 0.47), and FEF 25%–75% (55.16 ± 18.48 vs. 56.75 ± 20.15% predicted; P = 0.68) [Table 2].

 Discussion



This cross-sectional study integrated data from a detailed medical history with a variety of physiologic and laboratory examinations in two groups of Taiwanese moderate persistent asthmatic children with AR of varying severities. The integrated approach suggests substantial differences between patients with high scores and those with low scores.

Various studies had described that higher FeNO levels were observed in patients with AR,[8],[26],[27] while AR was associated with increased FeNO levels mainly by the increased expression of inducible nitric oxide synthase.[11] Moreover, some reports also suggested a correlation of symptoms of AR and nasal FeNO or oral FeNO levels.[14],[28] In the present study, oral FeNO level could reflect the degree of allergic inflammatory conditions in Taiwanese moderate persistent asthmatic children with AR of varying severities. The similar positive correlation between symptoms of AR and oral FeNO levels could be found in the study by Lee et al.,[28] which suggested that FeNO reflected an increase in the severity of lower airway inflammation according to increased upper airway inflammation.

Children with more severe symptoms of AR in this study had significantly higher blood eosinophil count. In previous reports, the relationship of blood eosinophil percentage and symptoms of AR was seldom investigated. However, the findings here were consistent with the reports by Droste et al. and Chen et al.[29],[30] A previous study also suggested that simple tests such as blood eosinophil count may provide useful information for diagnosing and predicting the severity of AR.

Higher levels of serum total IgE and specific IgE of Der p, Der f, and dog showed significant association with more severe symptoms of AR. The results were consistent with those of a previous study that showed a significant association between symptom severity of AR and total IgE level.[30] About symptoms of AR and specific IgE levels, previous investigators found a positive association between specific IgE levels and clinical symptoms.[29],[31],[32] In the present study, results of pulmonary function tests showed no significant difference between the two groups of Taiwanese moderate persistent asthmatic children with different severities of AR. In previous studies which described correlation of AR symptoms and FeNO, workup of pulmonary function tests was not mentioned.[14],[28] In our study groups, FeNO reflects higher severity of AR symptoms better then pulmonary function tests.

 Conclusions



Higher eosinophil count, total IgE, specific IgE to Der p, Der f, and dog, and FeNO level are correlated to higher TNSS score in Taiwanese moderate persistent asthmatic children with AR.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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