A novel pathophysiologic link between upper and lower airways in patients with chronic rhinosinusitis: Association of sputum periostin levels with upper airway inflammation and olfactory function

Yoshihiro Kanemitsu,Satoshi Fukuda,Hirono Nishiyama,Ryota Kurokawa,Kensuke Fukumitsu,Norihisa Takeda,Yutaka Ito,Akio Niimi,Yoshihisa Nakamura,Tetsuya Oguri,Kenji Izuhara,Motohiko Suzuki,Ken Maeno,Hirotsugu Ohkubo,Junya Ono,Masaki Awata ,Yuichi Ozawa ,Jennifer Maries Yap ,Masashi Takemura ,Tomohiko Asano

doi:10.1016/j.waojou.2019.100094

Yoshihiro Kanemitsu, Satoshi Fukuda + Show 18 more

Open Access

https://doi.org/10.1016/j.waojou.2019.100094

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Abstract

BackgroundChronic rhinosinusitis (CRS) and asthma are collectively called unified airway diseases. Periostin has been implicated in the pathophysiologic link of these conditions but only by serum measurements. We sought to investigate sputum levels of periostin and their association with upper airway inflammation and olfactory function in CRS patients. MethodsWe prospectively recruited 56 CRS patients who underwent endoscopic sinus surgery (20 with and 36 without comorbid asthma), and 28 healthy controls between October 2015 and December 2017. Lower and upper airway indices such as sputum periostin levels and eosinophil and neutrophil counts, exhaled fractional nitric oxide (FeNO) levels, and olfactory function were evaluated in the three groups. Radiological severity of CT images and tissue eosinophilia of surgical specimens were also assessed in the CRS patients. ResultsSputum periostin levels were highest, and olfactory function was most impaired, in the CRS patients with comorbid asthma, followed by those without asthma and controls in this order. CRS with asthma group showed higher sputum eosinophils and FeNO levels than the other two groups, while CRS patients without asthma showed significantly higher neutrophils in sputum than the other two groups. When confined to CRS patients, olfactory dysfunction was correlated with sputum eosinophil counts. Eosinophil counts of nasal polyps showed a significant positive correlation with sputum periostin and FeNO levels. Radiological severity of CRS was correlated with sputum eosinophil counts and FeNO levels. ConclusionsPeriostin levels and inflammatory cells such as eosinophils and neutrophils in the lower airways are increased in patients with CRS, suggesting the presence of mutual interactions between upper and lower airways even if asthma does not coexist. Olfactory dysfunction and eosinophilic nasal polyps may be potential indicators of Th2-driven inflammation in the lower airways. Trial registrationThis study was registered on the UMIN Clinical Trials Registry (Registry ID UMIN000018672).

Highlights

There are close interactions between chronic rhinosinusitis (CRS) and asthma because upper and lower airways are continuous from nasal cavity to the lung parenchyma and functionally linked; they are often collectively called “unified airway diseases”
When confined to Chronic rhinosinusitis (CRS) patients, olfactory dysfunction was correlated with sputum eosinophil counts
Periostin levels and inflammatory cells such as eosinophils and neutrophils in the lower airways are increased in patients with CRS, suggesting the presence of mutual interactions between upper and lower airways even if asthma does not coexist

Summary

Introduction

There are close interactions between chronic rhinosinusitis (CRS) and asthma because upper and lower airways are continuous from nasal cavity to the lung parenchyma and functionally linked; they are often collectively called “unified airway diseases”. Acute allergen exposure conducted out of hay fever seasons into nasal cavity could facilitate the infiltration of eosinophils in nasal and bronchial mucosa in patients with seasonal allergic rhinitis but without asthma.[5] Rhinitis patients, irrespective of the presence or absence of asthma, showed marked infiltration of eosinophils in nasal and bronchial tissues when compared to subjects without rhinitis.[6] marked eosinophilia in nasal mucosa was present in patients with asthma even if they did not have concomitant rhinitis.[7] In patients with severe asthma, Th2-driven biomarkers such as blood and sputum eosinophils and fractional exhaled nitric oxide (FeNO) were associated with radiological severity of concomitant CRS. Chronic rhinosinusitis (CRS) and asthma are collectively called unified airway diseases. We sought to investigate sputum levels of periostin and their association with upper airway inflammation and olfactory function in CRS patients

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