Abstract

BackgroundPeriostin is a matricellular protein and is a useful marker in respiratory diseases. However, the roles of periostin in patients with obstructive sleep apnea (OSA) remain unclear. Several in vitro studies have suggested that mechanical stress, hypoxia, impaired metabolism, and kidney injury, which often accompany OSA, may upregulate the expression of periostin. Meanwhile, serum periostin level has been negatively associated with body mass index (BMI) in the general population. In this study, we hypothesized that a high level of serum periostin despite being overweight/obese may discriminate severe OSA or OSA with comorbidities from mild OSA with obesity alone. We aimed to clarify the roles of periostin in patients with OSA to assist in elucidating the heterogeneity of OSA with comorbidities.MethodsAmong patients diagnosed as OSA, we examined the associations between serum periostin levels and clinical indices, including the severity of OSA, BMI, and comorbidities, using a multifaceted approach. The serum periostin levels and clinical indices were assessed after 3 months of continuous positive airway pressure (CPAP) treatment.ResultsIn 96 patients with OSA, serum periostin level was negatively correlated with BMI, albeit marginally, and tended to be higher in severe OSA than in others when adjusted for BMI. Cluster analysis identified four clusters, including two severe OSA clusters, one of which was characterized by high serum periostin levels and the presence of comorbidities, including albuminuria. In a comparative analysis of severe OSA cases (n = 53), the level of serum-free fatty acids and the frequency of albuminuria were higher in patients with high serum periostin level of ≥87 ng/mL, which was the highest quintile among all participants, than in those with low serum periostin levels (< 87 ng/mL, n = 41). In patients with severe OSA and high serum periostin levels, the levels of serum periostin and urinary albumin significantly decreased after 3 months of CPAP treatment.ConclusionsElevated serum periostin in patients with OSA despite being overweight/obese may be an indicator of severe OSA with comorbidities, particularly albuminuria.

Highlights

  • Periostin is a matricellular protein and is a useful marker in respiratory diseases

  • These findings suggested that the serum periostin levels in patients with obstructive sleep apnea (OSA) may reflect a combination of its downregulation by obesity and upregulation by hypoxic stimulation or metabolic comorbidities

  • The mean serum periostin level was 67.3 ± 22.8 ng/mL, which was equivalent to the average of the general population in Japan [15]

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Summary

Introduction

Periostin is a matricellular protein and is a useful marker in respiratory diseases. the roles of periostin in patients with obstructive sleep apnea (OSA) remain unclear. Several in vitro studies have suggested that mechanical stress, hypoxia, impaired metabolism, and kidney injury, which often accompany OSA, may upregulate the expression of periostin. Serum periostin level has been negatively associated with body mass index (BMI) in the general population. Several recent studies on asthma and the general population have revealed that serum periostin was negatively associated with body mass index (BMI) [12,13,14,15,16] and serum leptin [15]. In addition to Th2 inflammation, periostin has been shown by in vitro studies to be upregulated under several stimulations, including mechanical stress [17] and hypoxic stimulation [18], which are major features of OSA [19]. Other studies reported that the expression of periostin was upregulated in fatty liver tissues [23] and in the renal tissues of a kidney injury mouse model [24]

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