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 Table of Contents  
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


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

Date of Web Publication14-Mar-2017

Correspondence Address:
Shyh-Dar Shyur
Department of Pediatrics, Mackay Memorial Hospital, 92, Section 2, Chung.Shan North Road, Taipei 104, Taiwan
Republic of China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/prcm.prcm_12_16

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  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.

Keywords: Allergic rhinitis, children, fractional exhaled nitric oxide, moderate persistent asthma


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 2017 Aug 23];1:17-21. Available from: http://www.prccm.org/text.asp?2017/1/1/17/201976


  Introduction Top


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 Top


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 Top


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: Basic characteristics of the two groups

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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: Fractional exhaled nitric oxide level and pulmonary function tests between the two groups

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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: Eosinophil percentage and total serum immunoglobulin E levels between the two groups

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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: Serum levels of allergen-specific immunoglobulin E between the two groups

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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 Top


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 Top


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.

 
  References Top

1.
Rotiroti G, Roberts G, Scadding GK. Rhinitis in children: Common clinical presentations and differential diagnoses. Pediatr Allergy Immunol 2015;26:103-10.  Back to cited text no. 1
    
2.
Skiepko R, Zietkowski Z, Tomasiak-Lozowska MM, Tomasiak M, Bodzenta-Lukaszyk A. Bronchial hyperresponsiveness and airway inflammation in patients with seasonal allergic rhinitis. J Investig Allergol Clin Immunol 2011;21:532-9.  Back to cited text no. 2
    
3.
Chawes BL, Bønnelykke K, Kreiner-Møller E, Bisgaard H. Children with allergic and nonallergic rhinitis have a similar risk of asthma. J Allergy Clin Immunol 2010;126:567-73.e1-8.  Back to cited text no. 3
    
4.
de Groot EP, Nijkamp A, Duiverman EJ, Brand PL. Allergic rhinitis is associated with poor asthma control in children with asthma. Thorax 2012;67:582-7.  Back to cited text no. 4
    
5.
Kamekura R, Shigehara K, Miyajima S, Jitsukawa S, Kawata K, Yamashita K, et al. Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma. Clin Immunol 2015;158:204-11.  Back to cited text no. 5
    
6.
Zhao Z, Huang C, Zhang X, Xu F, Kan H, Song W, et al. Fractional exhaled nitric oxide in Chinese children with asthma and allergies – A two-city study. Respir Med 2013;107:161-71.  Back to cited text no. 6
    
7.
Munakata M. Exhaled nitric oxide (FeNO) as a non-invasive marker of airway inflammation. Allergol Int 2012;61:365-72.  Back to cited text no. 7
    
8.
Linhares D, Jacinto T, Pereira AM, Fonseca JA. Effects of atopy and rhinitis on exhaled nitric oxide values – A systematic review. Clin Transl Allergy 2011;1:8.  Back to cited text no. 8
    
9.
Choi BS, Kim KW, Lee YJ, Baek J, Park HB, Kim YH, et al. Exhaled nitric oxide is associated with allergic inflammation in children. J Korean Med Sci 2011;26:1265-9.  Back to cited text no. 9
    
10.
Gupta N, Goel N, Kumar R. Correlation of exhaled nitric oxide, nasal nitric oxide and atopic status: A cross-sectional study in bronchial asthma and allergic rhinitis. Lung India 2014;31:342-7.  Back to cited text no. 10
[PUBMED]  [Full text]  
11.
Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al. An official ATS clinical practice guideline: Interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 2011;184:602-15.  Back to cited text no. 11
    
12.
American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med 2005;171:912-30.  Back to cited text no. 12
    
13.
Malinovschi A, Alving K, Kalm-Stephens P, Janson C, Nordvall L. Increased exhaled nitric oxide predicts new-onset rhinitis and persistent rhinitis in adolescents without allergic symptoms. Clin Exp Allergy 2012;42:433-40.  Back to cited text no. 13
    
14.
Takeno S, Noda N, Hirakawa K. Measurements of nasal fractional exhaled nitric oxide with a hand-held device in patients with allergic rhinitis: Relation to cedar pollen dispersion and laser surgery. Allergol Int 2012;61:93-100.  Back to cited text no. 14
    
15.
Di Cara G, Marcucci F, Palomba A, Milioni M, Pecoraro L, Ciprandi G, et al. Exhaled nitric oxide in children with allergic rhinitis: A potential biomarker of asthma development. Pediatr Allergy Immunol 2015;26:85-7.  Back to cited text no. 15
    
16.
Shirai T, Mochizuki E, Asada K, Suda T. Pollen count and exhaled nitric oxide levels in a seasonal allergic rhinitis patient. Respirol Case Rep 2014;2:113-5.  Back to cited text no. 16
    
17.
Manna A, Montella S, Maniscalco M, Maglione M, Santamaria F. Clinical application of nasal nitric oxide measurement in pediatric airway diseases. Pediatr Pulmonol 2015;50:85-99.  Back to cited text no. 17
    
18.
Bousquet J, Schünemann HJ, Samolinski B, Demoly P, Baena-Cagnani CE, Bachert C, et al. Allergic rhinitis and its impact on asthma (ARIA): Achievements in 10 years and future needs. J Allergy Clin Immunol 2012;130:1049-62.  Back to cited text no. 18
    
19.
Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald M, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008;31:143-78.  Back to cited text no. 19
    
20.
Liang PH, Shyur SD, Huang LH, Wen DC, Chiang YC, Lin MT, et al. Risk factors and characteristics of early-onset asthma in Taiwanese children. J Microbiol Immunol Infect 2006;39:414-21.  Back to cited text no. 20
    
21.
Chiang YC, Shyur SD, Chen TL, Huang LH, Wen TC, Lin MT, et al. A randomized controlled trial of cetirizine plus pseudoephedrine versus loratadine plus pseudoephedrine for perennial allergic rhinitis. Asian Pac J Allergy Immunol 2006;24:97-103.  Back to cited text no. 21
    
22.
Cheng CH, Shyur SD, Huang LH, Kao YH, Lei WT, Lo CY, et al. Factors for high-risk asthma in Taiwanese children. Asian Pac J Allergy Immunol 2010;28:250-5.  Back to cited text no. 22
    
23.
Taylor DR, Pijnenburg MW, Smith AD, De Jongste JC. Exhaled nitric oxide measurements: Clinical application and interpretation. Thorax 2006;61:817-27.  Back to cited text no. 23
    
24.
Jat KR. Spirometry in children. Prim Care Respir J 2013;22:221-9.  Back to cited text no. 24
    
25.
Standardization of spirometry, 1994 update. American Thoracic Society. Am J Respir Crit Care Med 1995;152:1107-36.  Back to cited text no. 25
    
26.
Jerzynska J, Majak P, Janas A, Stelmach R, Stelmach W, Smejda K, et al. Predictive value of fractional nitric oxide in asthma diagnosis-subgroup analyses. Nitric Oxide 2014;40:87-91.  Back to cited text no. 26
    
27.
Kim YH, Park HB, Kim MJ, Kim HS, Lee HS, Han YK, et al. Fractional exhaled nitric oxide and impulse oscillometry in children with allergic rhinitis. Allergy Asthma Immunol Res 2014;6:27-32.  Back to cited text no. 27
    
28.
Lee KJ, Cho SH, Lee SH, Tae K, Yoon HJ, Kim SH, et al. Nasal and exhaled nitric oxide in allergic rhinitis. Clin Exp Otorhinolaryngol 2012;5:228-33.  Back to cited text no. 28
    
29.
Droste JH, Kerhof M, de Monchy JG, Schouten JP, Rijcken B. Association of skin test reactivity, specific IgE, total IgE, and eosinophils with nasal symptoms in a community-based population study. The Dutch ECRHS Group. J Allergy Clin Immunol 1996;97:922-32.  Back to cited text no. 29
    
30.
Chen ST, Sun HL, Lu KH, Lue KH, Chou MC. Correlation of immunoglobulin E, eosinophil cationic protein, and eosinophil count with the severity of childhood perennial allergic rhinitis. J Microbiol Immunol Infect 2006;39:212-8.  Back to cited text no. 30
    
31.
Li J, Huang Y, Lin X, Zhao D, Tan G, Wu J, et al. Influence of degree of specific allergic sensitivity on severity of rhinitis and asthma in Chinese allergic patients. Respir Res 2011;12:95.  Back to cited text no. 31
    
32.
Rolinck-Werninghaus C, Keil T, Kopp M, Zielen S, Schauer U, von Berg A, et al. Specific IgE serum concentration is associated with symptom severity in children with seasonal allergic rhinitis. Allergy 2008;63:1339-44.  Back to cited text no. 32
    



 
 
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