Is just enzyme replacement therapy enough for Fabry disease treatment? Have we missed a trick? / ¿Es suficiente la terapia enzimática para tratar la enfermedad de Fabry? ¿Nos falta algún detalle?

Background and aim: In Fabry disease (FD), primary factors such as glycosphingolipid deposition that initiate kidney damage and secondary factors that advance kidney damage to fibrosis are different. Periostin is a molecule of proven importance in renal inflammation and fibrosis. It was previously shown that periostin plays an essential role in the process leading to renal fibrosis and its expression is increased in many kidney diseases. In the present study, we aimed to reveal the relationship between periostin and Fabry nephropathy. Material-method: This cross-sectional study included 18 FD patients (10 males, 8 females) with enzyme replacement therapy (ERT) indications and 22 healthy control patients of similar age and gender. At the time of diagnosis, plasma alpha-galactosidase A (α-gal-A) and globotriaosylsphingosine (lyso-Gb3), proteinuria, and kidney function tests of all FD patients before ERT were scanned from the hospital system. Periostin was studied from serum samples collected and stored before ERT. Parameters related to serum periostin levels in Fabry disease were investigated. Results: In FD patients, serum periostin was negatively correlated with age of first symptom and GFR; and positively correlated with proteinuria and lyso-Gb3. In regression analysis, we found that serum periostin was the only independent determinant of proteinuria in patients with Fabry disease. The serum periostin levels were significantly lower in patients with low proteinuria, and the serum periostin levels were correlated with proteinuria. Discussion: Periostin may be a valuable marker of Fabry nephropathy and proteinuria. Periostin seems to be one of the molecules that may have an important role in the management of the fibrotic process in Fabry nephropathy. We think that the role of periostin among these mechanisms is worth investigating... (AU)

Antecedente y objetivo: En la enfermedad de Fabry (EF), son diferentes los factores primarios tales como el depósito de glicoesfingolípidos que inicia el daño renal, y los factores secundarios que progresan de daño renal a fibrosis. Periostina es una molécula de importancia probada en la inflamación renal y la fibrosis. Se ha demostrado previamente que periostina juega un papel esencial en el proceso que causa la fibrosis renal, y que su expresión se incrementa en muchas enfermedades renales. En el presente estudio, nuestro objetivo fue revelar la relación entre la periostina y la nefropatía de Fabry. Material y método: Este estudio transversal incluyó 18 pacientes con EF (10 varones y 8 mujeres) con indicación de terapia enzimática (ERT) y 22 controles sanos con edad y sexo similares. En el momento del diagnóstico se escanearon del sistema hospitalario las pruebas de alfa-galactosidasa A (α-gal-A) plasmática y globotriaosilsfingosina (lyso-Gb3), proteinuria y función renal de todos los pacientes con EF antes de la ERT. Se analizó el nivel de periostina en las muestras séricas recogidas y almacenadas antes de realizar la ERT. Se investigaron los parámetros relacionados con los niveles séricos de periostina en la enfermedad de Fabry. Resultados: En los pacientes con EF, el nivel de periostina sérica se correlacionó negativamente con la edad del primer síntoma y la GFR, y positivamente con proteinuria y lyso-Gb3. En el análisis de regresión, encontramos que el nivel de periostina sérico fue el único determinante independiente de proteinuria en los pacientes con EF. Los niveles séricos de periostina fueron significativamente menores en los pacientes con baja proteinuria, correlacionándose los niveles séricos de periostina con proteinuria. Discusión: La periostina puede ser un marcador valioso de nefropatìa de Fabry y proteinuria.... (AU)

Is just enzyme replacement therapy enough for Fabry disease treatment? Have we missed a trick?

BACKGROUND AND AIM: In Fabry disease (FD), primary factors such as glycosphingolipid deposition that initiate kidney damage and secondary factors that advance kidney damage to fibrosis are different. Periostin is a molecule of proven importance in renal inflammation and fibrosis. It was previously shown that periostin plays an essential role in the process leading to renal fibrosis and its expression is increased in many kidney diseases. In the present study, we aimed to reveal the relationship between periostin and Fabry nephropathy. MATERIAL-METHOD: This cross-sectional study included 18 FD patients (10 males, 8 females) with enzyme replacement therapy (ERT) indications and 22 healthy control patients of similar age and gender. At the time of diagnosis, plasma alpha-galactosidase A (α-gal-A) and globotriaosylsphingosine (lyso-Gb3), proteinuria, and kidney function tests of all FD patients before ERT were scanned from the hospital system. Periostin was studied from serum samples collected and stored before ERT. Parameters related to serum periostin levels in Fabry disease were investigated. RESULTS: In FD patients, serum periostin was negatively correlated with age of first symptom and GFR; and positively correlated with proteinuria and lyso-Gb3. In regression analysis, we found that serum periostin was the only independent determinant of proteinuria in patients with Fabry disease. The serum periostin levels were significantly lower in patients with low proteinuria, and the serum periostin levels were correlated with proteinuria. DISCUSSION: Periostin may be a valuable marker of Fabry nephropathy and proteinuria. Periostin seems to be one of the molecules that may have an important role in the management of the fibrotic process in Fabry nephropathy. We think that the role of periostin among these mechanisms is worth investigating. In addition to standard ERTs, periostin-reducing therapies may contribute to better kidney survival in Fabry disease. Progressive fibrosis processes caused by periostin in patients with Fabry disease are still a hidden issue waiting to be clarified. Progressive fibrosis processes caused by periostin in Fabry patients are still a hidden issue waiting to be clarified.

Increased Serum Periostin Levels and Eosinophils in Nasal Polyps Are Associated with the Preventive Effect of Endoscopic Sinus Surgery for Asthma Exacerbations in Chronic Rhinosinusitis Patients.

BACKGROUND: Eosinophilic nasal polyps (NPs) are associated with the presence of asthma in chronic rhinosinusitis (CRS) patients. Serum periostin has been considered a relevant biomarker for unified airway diseases. OBJECTIVE: To determine the utility of biomarkers including serum periostin that reflects reduction of exacerbations of comorbid asthma in CRS patients. METHODS: We prospectively recruited 56 CRS patients who were subjected to undergo endoscopic sinus surgery (ESS) (20 with asthma) between October 2015 and December 2017 and followed them for 1 year after ESS. Blood eosinophil count, serum periostin, and fractional nitric oxide (FeNO) were measured at enrollment. How these type 2-driven biomarkers reflect comorbid asthma was determined using receiver operating characteristic (ROC) analysis. The frequency of asthma exacerbations during 1 year was counted both before and after ESS. Associations between preoperative biomarkers including eosinophils in NPs and asthma exacerbations were evaluated. RESULTS: Blood eosinophil count, FeNO, and serum periostin levels were significantly higher in CRS patients with asthma than in those without (p < 0.01 for all) and discriminated comorbid asthma among CRS patients (p < 0.05; AUC > 0.80 for all). The increased preoperative serum periostin correlated with lower absolute number of postoperative exacerbations (ρ = -0.49, p = 0.03) and its relative reduction after ESS (ρ = 0.53, p = 0.03) in asthmatic patients. Increased eosinophils in NPs were also associated with reduced asthma exacerbations. CONCLUSION: Preoperative increased serum periostin and eosinophils in NPs are associated with the preventive effect of ESS for asthma exacerbations in CRS patients comorbid with asthma.

Role of serum periostin in severe obstructive sleep apnea with albuminuria: an observational study.

BACKGROUND: Periostin 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. METHODS: Among 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. RESULTS: In 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. CONCLUSIONS: Elevated serum periostin in patients with OSA despite being overweight/obese may be an indicator of severe OSA with comorbidities, particularly albuminuria.

Role of serum periostin in the management of asthma and its comorbidities.

Type-2 airway inflammation is a major characteristic of asthma. Assessing its degree of severity is, therefore, essential in asthma management. Periostin, a matricellular protein belonging to the fasciclin family, is a key molecule linking type-2 airway inflammation and airway remodeling. Fortunately, periostin can be detected in the blood and used to provide sustaining airway information on type-2 inflammation and remodeling. Serum periostin is elevated in the eosinophilic/type 2 subtype of severe asthma, and its levels remain relatively stable and reflect genetic backgrounds. This suggests that serum periostin may serve as a marker of geno-endophenotype with type-2 airway inflammation and thus could be a predictive marker of the long-term prognosis of asthma under treatment. As expected, serum periostin is particularly elevated in comorbidities associated with the eosinophilic/type 2 subtype of severe asthma, including eosinophilic chronic rhinosinusitis, aspirin-exacerbated respiratory diseases, allergic bronchopulmonary aspergillosis, and eosinophilic granulomatosis with polyangiitis. Conversely, serum periostin levels are relatively lower in the overweight/obese. Serum periostin measurements may help to significantly improve the management of patients with severe asthma.

Roles of Periostin in Asthma.

Periostin is a matricellular protein that is deeply involved in type-2/eosinophilic airway inflammation and remodeling in asthma. While its expression in airway epithelial cells is correlated with the thickness of airway basement membrane, more importantly, periostin can be detected stably in blood with little variability, reflecting airway type-2 inflammation and remodeling. As for a result, serum periostin can serve as a valuable marker to identify patients with type-2 severe asthma who are insensitive to inhaled corticosteroids, and consequently have the excess decline of pulmonary function with asthma exacerbations. Serum periostin may significantly help to improve management of patients with severe asthma.

Serum periostin does not reflect type 2-driven inflammation in COPD.

Although Th2 driven inflammation is present in COPD, it is not clearly elucidated which COPD patients are affected. Since periostin is associated with Th2 driven inflammation and inhaled corticosteroid (ICS)-response in asthma, it could function as a biomarker in COPD. The aim of this study was to analyze if serum periostin is elevated in COPD compared to healthy controls, if it is affected by smoking status, if it is linked to inflammatory cell counts in blood, sputum and endobronchial biopsies, and if periostin can predict ICS-response in COPD patients.Serum periostin levels were measured using Elecsys Periostin immunoassay. Correlations between periostin and inflammatory cell count in blood, sputum and endobronchial biopsies were analyzed. Additionally, the correlation between serum periostin levels and treatment responsiveness after 6 and 30 months was assessed using i.e. ΔFEV1% predicted, ΔCCQ score and ΔRV/TLC ratio. Forty-five COPD smokers, 25 COPD past-smokers, 22 healthy smokers and 23 healthy never-smokers were included. Linear regression analysis of serum periostin showed positive correlations age (B = 0.02, 95%CI 0.01-0.03) and FEV1% predicted (B = 0.01, 95%CI 0.01-0.02) in healthy smokers, but not in COPD patients In conclusion, COPD -smokers and -past-smokers have significantly higher periostin levels compared to healthy smokers, yet periostin is not suitable as a biomarker for Th2-driven inflammation or ICS-responsiveness in COPD.

Diagnostic significance of serum periostin in eosinophilic chronic sinusitis with nasal polyps.

OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease. Eosinophilic CRSwNP (ENP) exhibits a strong tendency for recurrence after surgery. Given that the treatment strategy of ENP differs from that of non-eosinophilic CRSwNP (nENP), clinical diagnostic criteria that distinguish ENP from nENP are needed. METHODS: In total, 94 CRSwNP patients were enrolled in the cohort. Factors associated with ENP were determined with regression analysis, and optimal cutoff points of the predictors were determined by a receiver operating characteristic curve. RESULTS: Serum periostin levels, blood eosinophils and basophils counts significantly differed between ENP and nENP. A combination of the cut-off values for the three predictors, including absolute blood eosinophil and basophil counts, yielded a sensitivity of 79.2% and 70.8%, and a specificity of 84.8% and 73.9%, respectively. Serum periostin levels yielded a sensitivity of 72.9% and a specificity of 60.9% for the diagnosis of ENP. The predicted probability of periostin in combination with blood eosinophils and basophils counts (AUC, 0.872) exhibited moderate accuracy. In addition, patients with ENP displayed an increased prevalence of smoking. CONCLUSIONS: Periostin in combination with blood eosinophils and basophils counts has the potential to better refine current CRSwNP phenotypes.

Utility of serum periostin in combination with exhaled nitric oxide in the management of asthma.

Type-2/eosinophilic inflammation plays a pivotal role in asthma. The identification of severe type-2/eosinophilic asthma is important for improving the management of patients with asthma. Therefore, efforts to develop non-invasive biomarkers for type-2/eosinophilic airway inflammation have been made during this decade. Currently, fraction of exhaled nitric oxide (FeNO) and serum periostin levels are considered markers of type-2/eosinophilic inflammation in asthma. However, a single-marker approach has limited the ability to diagnose severe type-2/eosinophilic asthma accurately and predict disease outcomes precisely. The present article reviews the utility of FeNO and serum periostin levels in a single-marker approach and in a multiple-marker approach in identifying patients with severe type-2/eosinophilic asthma. Furthermore, based on a sub-analysis of the Kinki Hokuriku Airway disease Conference (KiHAC), geno-endo-phenotypes of patients were stratified into four groups according to the FeNO and serum periostin levels.

Clinical and biological markers of asthma control.

Asthma has substantial impact on the patient, their family and health systems, and its control has gained increasing attention. Perception of asthma control has varied widely among patients as well as healthcare providers. Several clinical markers have been developed to define and standardize the measurement of asthma control. They are based primarily on patients' symptoms and have been popular in clinical practice and in clinical studies. With the advances in basic research on the pathology of asthma, several biological markers have evolved that have the advantages of being objective, quantitative and more reflective of the underlying pathology, which makes them a better guide for selecting optimal therapy. In addition to the cost and expertise required, biological makers are influenced by multiple factors that limit their application in clinical practice. Ongoing research is expected to define the role of individual biological markers, the optimal method of their application, and their appropriate interpretation.