Elsevier

Auris Nasus Larynx

Volume 46, Issue 4, August 2019, Pages 507-512
Auris Nasus Larynx

Nasal nitric oxide in the inferior turbinate surface decreases with intranasal steroids in allergic rhinitis: A prospective study

https://doi.org/10.1016/j.anl.2018.11.005Get rights and content

Abstract

Objective

It remains controversial whether nasal nitric oxide (NO) serves as a reliable parameter to evaluate treatment efficacy in patients with allergic rhinitis (AR). The measurement of local nasal NO levels has been shown to be a sensitive marker for the diagnosis of symptomatic AR patients. Here we assessed the applicability of nasal NO to evaluations of the efficacy of intranasal steroids (INS) in a prospective design.

Methods

We enrolled 25 patients with perennial AR and 10 age-matched healthy participants. The AR patients received fluticasone furoate (FF) once daily for 2 months. Fractional exhaled NO and nasal NO measurements were carried out using an electrochemical analyzer at pretreatment and at 2 weeks and 2 months after treatment. Nasal NO levels were directly measured at two different areas of the nasal cavity: the surface of the inferior turbinate (IT area) and the front of the middle meatus (MM area). Subjective nasal symptoms were also recorded at each visit.

Results

The mean total nasal symptom score in the AR patients decreased significantly after FF treatment (p < 0.0001). The mean nasal NO levels in the IT area in the AR patients were significantly higher at pretreatment than those of the healthy participants (109 vs. 62.5 ppb, respectively; p < 0.001). After FF administration, the nasal NO levels in the IT area of the AR group showed a significant reduction at both 2 weeks and 2 months (79.1 and 71.9 ppb, respectively; p < 0.05 and p < 0.01). There was no significant difference in nasal NO levels in the MM area between the controls and the AR group at any visit timepoint. When the ratio of the MM area to the IT area (MM/IT ratio) was plotted for each subject, the untreated AR patients showed a marked decrease in the ratio, whereas after the FF treatment, the AR patients' mean MM/IT ratios showed a significant increase. No significant difference compared to the control group existed at 2 months.

Conclusion

Nasal NO measurement around the inferior turbinate is an objective measure to evaluate allergic conditions and is useful to monitor therapeutic effects of INS.

Introduction

Patients with allergic rhinitis (AR) show augmented activity of the nitric oxide (NO) metabolism in the inferior turbinate mucosa, similar to that seen in bronchial asthma [1], [2], [3], [4]. In this sense, nasal NO can be used as an objective marker for AR, similar to the situation in lower airways where fractional exhaled NO (FeNO) has been used for asthma diagnoses, screening tests, and assessments of steroid treatment efficacy [5], [6]. However, the issue of whether nasal NO serves as a reliable index of the clinical efficacy of various therapeutic modalities in AR patients has been controversial. The conflicting results are likely due to the functional complexity of NO as well as to variations in the anatomical structure of the nasal cavity and paranasal sinuses [3], [7].

We reported that increased nasal NO levels near the surface of the inferior turbinate can be a sensitive marker for the diagnosis of AR, with the significance being more prominent than FeNO levels [8]. In the present study, we examined the applicability of nasal NO as an objective outcome parameter for clinical intervention trials. For this purpose, we assessed the effect of intranasal steroids (INS) on nasal NO in a group of perennial AR patients in a prospective design.

Treatment with INS is widely recognized to be the first-line anti-inflammatory treatment for AR in current guidelines [9], [10]. We also examined the consecutive reproducibility of the nasal NO measurement in normal healthy participants without AR. Our investigation revealed that the untreated AR patients showed higher nasal NO levels in a specific area around the inferior turbinate [8], and these levels showed a significant reduction after INS treatment corresponding to the improvement of subjective symptoms.

Section snippets

Study design

This was a prospective normal subjects-controlled between-group study conducted at the Department of Otorhinolaryngology—Head and Neck Surgery, Hiroshima University Hospital, Hiroshima, Japan between May 2015 and March 2017. The subjects were 25 patients with perennial AR without bronchial asthma and 10 age-matched healthy participants without nasal symptoms. The exclusion criteria of asthma were based on the absence of a clinical history of episodic symptoms with airflow limitation. The

Nasal symptoms and FeNO levels

The demographics, clinical background and changes of nasal symptoms and FeNO levels of the study population are summarized in Table 1. There was no significant difference between the AR and control groups in the baseline data of age or gender distribution. All subjects were able to complete the study protocol including the three different maneuvers of NO level measurements. None of the subjects had adverse events of any relevance to the study. FeNO levels were measured in the healthy

Discussion

Allergic rhinitis has been associated with increased nasal NO levels by an enhanced expression of inducible nitric oxide synthase (iNOS) in the nasal turbinate mucosa [2], [3]. However, it has not yet been determined whether nasal NO serves as a valid objective marker for therapeutic efficacy. In the present study, we examined to what extent NO concentrations inside the nose contribute to the pathologies caused by allergic inflammation, and we tried to assess the applicability of nasal NO as a

Ethical statement

The study protocol was approved by the Institutional Review Board of Hiroshima University (no. 496), and registered in the UMIN Clinical Trials Registry System (ID. 000016536).

Acknowledgments

We thank Ms. Ai Kashima for the technical assistance.

This study was supported in part by a Japan Society for the Promotion of Science KAKENHI grant (no. 16K11213) and a Practical Research Project grant (no. 28080401) for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development.

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