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Correlation between nasal nitric oxide, nasal airway resistance and atopy in patients of allergic rhinitis Raj Kumar, Nitesh Gupta
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ABSTRACT
Website: www.ijaai.in
DOI: 10.4103/0972-6691.124396 Quick Response Code:
Background: Nasal airway resistance (NAR) is dependent upon the tone of the nasal vasculature, which is regulated by endothelially derived nitric oxide (NO). Aim: The aim of this study was to investigate the relationship between nasal nitric oxide (nNO) levels, NAR and atopy in patients of allergic rhinitis (AR). Materials and Methods: The subjects were assessed for nNO levels by NIOX chemiluminescence analyzer. NAR was measured by 4‑Phase‑Rhinomanometry using RHINOTEST 1000. Atopy was assessed by skin prick testing against 58 common aeroallergens. Statistical Analysis: SPSS, Chicago, IL, USA, statistical package version 14 using independent sample t‑test and Pearson correlation. Results: In the study, 15 diagnosed cases of AR and five healthy volunteers as control were included. In the control group, the mean total NAR was 0.16 ± 0.08 kPa/l/s while in AR group mean total NAR was 0.22 ± 0.1 kPa/ l/s (P = 0.4). In AR group mean left and right NAR were 0.50 ± 0.28 kPa/l/s and 0.52 ± 0.4 kPa/l/s respectively and mean nNO levels of right and left nostrils were 291.2 ± 122.90 ppb and 251 ± 171.16 ppb (P = 0.7). No correlation was found between the left or right unilateral NAR and nNO levels, respectively. Similarly, no significant correlation of unilateral NAR and NO levels were found in the control group. Atopic AR patients had higher NAR (P = 0.001) and nNO (P = 0.06) compared with non‑atopic rhinitis patients. Conclusion: In our study, AR group had higher NAR, but no correlation was found between nNO and NAR in either groups. The atopic AR patients had significantly higher NAR in comparison with non‑atopic patients. Key words: Allergic rhinitis, nasal nitric oxide, rhinomanometry
INTRODUCTION Nasal obstruction is a common condition in patients suffering from allergic rhinitis (AR).[1] The degree to which nasal obstruction causes symptoms is determined by the severity of the obstruction and by the subjective perception
of obstruction to nasal airflow. In general, rhinomanometry provides information about nasal airway flow, resistance and assessment of patency of the nose.[2‑4] Thus, it provides a sensitive and functional measure of nasal patency during normal breathing. Nasal nitric oxide (nNO) originates from the nasal epithelium and paranasal sinuses [5,6] and this
Department of Respiratory Allergy and Applied Immunology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India Address for correspondence: Dr. Raj Kumar, Department of Respiratory Allergy and Applied Immunology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi ‑ 110 007, India. E‑mail:
[email protected]
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Kumar and Gupta: nNO, NAR and atopy in allergic rhinitis
endothelially derived nitric oxide (NO) is an established vasodilator. Nasal airway resistance (NAR) is dependent upon the tone of the nasal vasculature, which in turn is regulated by endothelially derived NO. After an extensive search of databases and to the best of our knowledge no study correlating the marker of nasal inflammation (nNO), NAR and atopy was found in Indian population. Hence, the present study was undertaken to study the correlation.
MATERIALS AND METHODS Study population and design The study was conducted at out‑patient department between August and November 2012. The patients of AR visiting the out‑patient department were included for the study. The study group consisted of total 20 subjects; 15 cases of AR and five healthy volunteers as controls. The age of the patients ranged from 18 to 36 years. The diagnosis of AR was made based on the clinical definition of AR as per Allergic Rhinitis and its impact on asthma guidelines i.e., any patient with symptoms of rhinorrhea, nasal obstruction, nasal itching and sneezing, which are reversible spontaneously or with treatment.[7] The nNO measurements were performed by the nasal aspiration method, using chemiluminescence analyzer (NIOX Aerocrine AB, Solna, Sweden) in accordance with the 2005 American Thoracic Society/European Respiratory Society recommendations for standardized online measurements.[8] Patient exhaled through a tightly fitting nasal mask adapted to the analyzer enabling nNO measurements. The NAR was measured by 4‑Phase‑Rhinomanometry (4PR) using the RHINOTEST 1000, by examining flow and pressure in the upper respiratory airway. This is active anterior rhinomanometry using the 4PR software of Vogt et al.[9,10] Skin prick test (SPT) was performed against 58 aeroallergens, routinely used for allergy testing in our department. Atopy was defined as a positive SPT (wheal diameter of >3 mm as compared to Buffer saline as control) for at least one aeroallergen.[11] A patient with negative SPT to all aeroallergens was labeled as non‑atopic. Statistical analysis All data analysis was performed using SPSS statistical package version 14.0 for windows (SPSS, Chicago, IL, USA) and Prism 6.0. The univariate analyses of factors associated with nNO was done using Pearson correlation. The measurements for nNO were compared between groups using the independent sample t‑test.
RESULTS The study included 15 diagnosed cases of AR and five healthy volunteers as controls. The age ranged from 18 to
36 years, mean being 21.26 years. There were 11 atopic and four non‑atopic patients in AR group; the control group had only non‑atopic subjects. In AR group mean total NAR was 0.22 ± 0.1 kPa/l/s and in the control group the mean total NAR was 0.16 ± 0.08 kPa/l/s. The AR group had higher NAR in comparison with control group, the difference was not statistically significant (P = 0.24). In AR group, mean left and right NAR were 0.50 ± 0.28 kPa/l/s and 0.52 ± 0.4 kPa/l/s respectively (P = 0.9) and mean nNO levels from the left and right nostrils were 251 ± 171.16 ppb and 291.2 ± 122.90 ppb (P = 0.7). The difference between the levels of NAR and nNO from either nostril were not significant. In patients of AR on evaluation of the left or right unilateral NAR and nNO levels respectively, no correlation was found between these measurements from either nose (right nose r = 0.378, P = 0.16; left nose r = −0.46, P = 0.869). Similarly, the mean nNO levels and NAR did not show any significant correlation [Figure 1] in AR group. Furthermore, there was no significant correlation between total NAR and the left nNO levels (r = −0.002, P = 0.9) or total NAR and right nNO levels (r = 0.101, P = 0.7) in AR patients. Atopic AR patients had significantly higher NAR as compared to non‑atopic patients (0.24 ± 0.05 vs. 0.17 ± 0.02; P = 0.001) [Figure 2], also the nNO levels in atopic rhinitis were higher as compared with non‑atopic rhinitis (292.13 ± 154.1 vs. 213.25 ± 42.3, P = 0.06) [Figure 3]. In the control group, no correlation was found between the right or left unilateral NAR and NO levels respectively (right r = −0.562, P = 0.178; left r = −0.423, P = 0.478). Similarly, no correlation was found between mean nNO levels and NAR in the control group [Figure 4].
DISCUSSION Nasal obstruction is a dominant symptom associated with all types of rhinitis; [12] it is an indirect marker of nasal inflammation, subjecting to the condition that there are no significant permanent nasal anatomical abnormalities which contribute to reduced nasal airflow. The disease processes or drugs cause dilation of nasal blood vessels, thus leading to swelling of the nasal venous sinuses, will be associated with nasal obstruction. In subjects with no signs or symptoms of nasal disease, the NAR has been observed to be ranging between 0.15 and 0.39 Pa/cm3/s.[13] However, to distinguish between skeletal stenosis and mucosal swelling, it is imperative to have reference values for NAR for the technique that is being used. However, generally usable validated normal data for NAR is still lacking and that is a major problem. In a study by Ferguson[14] on 123 healthy volunteers, no relationship was found to exist between nNO concentration and total NAR. Similarly, the study did not found any
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Kumar and Gupta: nNO, NAR and atopy in allergic rhinitis
Figure 1: Correlation between mean nasal nitric oxide and nasal airway resistance in allergic rhinitis
Figure 3: The nasal airway resistance in atopic and non‑atopic allergic rhinitis
correlation between the left or right unilateral NAR and left or right nNO concentration, respectively. In our study results, no correlation was found between nNO and NAR in both AR patients and healthy volunteers. However a study by Imada et al.[15] on healthy volunteers proposed that nNO may be involved in the control of NAR. In a cross‑sectional study of 200 subjects, 112 suffering from nasal disease and 88 normal subjects by Suzina et al.,[16] the mean total NAR was significantly higher in patients with nasal disease (0.33 Pa/cm3/s) as compared with normal subjects (0.24 Pa/cm3/s). However, there was no significant difference in total NAR between patients with symptoms of nasal obstruction and those without the symptoms (P = 0.42). Our study also showed higher NAR in AR group as compared with the healthy group, though not statistically significant. The nNO levels in AR and control group were 274.40 ± 132.23 ppb and 130.20 ± 100.12 ppb respectively. 136
Figure 2: The nasal nitric oxide levels in atopic and non‑atopic allergic rhinitis
Figure 4: Correlation between mean nasal nitric oxide and nasal airway resistance in control group
The AR group had significantly higher nNO levels (P = 0.03). In a study by Kharitonov et al.,[17] the mean nNO levels in AR were significantly (P
