Serum Periostin Concentrations Research Articles

The role of periostin as an inflammatory marker in bronchial asthma in children

Introduction. The extracellular matrix protein periostin, expressed in a number of body tissues, is considered as a marker of type 2 T cell inflammation and of asthma control.Objective. To study the relationship the serum periostin concentration in blood serum depending on the severity of asthma and indicators of respiratory function in children.Materials and methods. The cross-sectional (simultaneous) study included 80 children aged 6 to 17 years (average age 12±3.2), who were divided into 2 groups: 1st — children with asthma (n=40); 2nd — comparison group (n=40). The concentration of periostin in the blood serum was determined by the ELISA method. The spirographic study was performed on a computer spirometer Spirolab 1, MIR (Italy).Results. The Me of periostin in group 1 was within the normal range (730.2 ng/ml), but statistically significantly exceeded the indicator of group 2 (539.7 ng/ml, p<0.05) and did not depend on the age, duration and severity of asthma, anthropometric parameters of the examined. The level of periostin in the blood serum significantly correlated with the frequency of exacerbations of the disease during the year (r=0.74, p=0.000), with the status of asthma control (r=0.32, p=0.04). A moderate correlation was found between the level of periostin and FEV1 (r=−0.34; p=0.03).Conclusions. In children with asthma, the median periostin in the blood serum increased in proportion to the severity of asthma, disease control and the frequency of exacerbation of the disease.

Periostin Predicts All-Cause Mortality in Male but Not Female End-Stage Renal Disease Patients on Hemodialysis.

Periostin is a matricellular protein. Elevated serum concentrations of periostin have been reported in patients with various cardiovascular diseases, including heart failure. Patients with end-stage renal disease have a substantially increased risk for cardiovascular diseases. However, there is a lack of clinical studies to clarify the prognostic significance of systemic periostin on all-cause mortality in patients with end-stage renal disease on hemodialysis. 313 stable end-stage renal disease patients were recruited and followed for 5 years concerning all-cause mortality. At baseline, we collected blood samples and clinical data. Serum periostin concentrations were measured using a certified ELISA. The optimal cut-off value for serum periostin regarding all-cause mortality, calculated through receiver operating characteristic analysis, was 777.5 pmol/L. Kaplan-Meier survival analysis using this cut-off value demonstrated that higher periostin concentrations are linked to higher all-cause mortality (log-rank test: p = 0.002). Subgroup analysis revealed that serum periostin concentrations only affected all-cause mortality in male but not in female patients (p = 0.002 in male patients and p = 0.474 in female patients). Multivariate Cox regression analyses, adjusted for confounding factors, likewise showed that elevated serum periostin concentrations were positively associated with all-cause mortality in male (p = 0.028) but not in female patients on hemodialysis (p = 0.313). Baseline serum periostin is an independent risk factor for all-cause mortality in male patients with chronic renal disease on hemodialysis.

Periostin as a marker of eosinophilic inflammation in patients with asthma and chronic obstructive pulmonary disease

BACKGROUND: Asthma and chronic obstructive pulmonary disease are common chronic respiratory diseases. Given their heterogeneity, the study of periostin is a relevant area for establishing the endotypes of airway inflammation and determining further therapy tactics. AIM: To evaluate periostin levels and determine its significance as a marker of eosinophilic inflammation in patients with asthma and chronic obstructive pulmonary disease. MATERIALS AND METHODS: The study included 59 patients with asthma and 33 patients with chronic obstructive pulmonary disease. The control group consisted of 37 apparently healthy people, comparable in age and sex, without allergic and bronchial obstructive diseases in anamnesis. The anamnesis data, the number of peripheral blood eosinophils and induced sputum, indices of external respiratory function were evaluated. Levels of specific immunoglobulin E to allergens, periostin level were determined in blood serum by immunoenzyme method. The obtained data were processed using STATISTICA 13 and SPSS Statistic 27 software systems. RESULTS: The maximum serum periostin concentration 22.5 (17–38) ng/ml was recorded in the patients with asthma, which was significantly higher than in the chronic obstructive pulmonary disease group [16 (12–21) ng/ml; p = 0.006] and control group [20.1 (14.6–24.8) ng/ml; p = 0.044]. The level of periostin in induced sputum in the patients with asthma was significantly higher than in the chronic obstructive pulmonary disease group — 0.05 (0.03–0.6) ng/ml vs 0.03 (0.02–0.04) ng/ml (p = 0.008). The study revealed the correlation between serum periostin level and eosinophil level (r = 0.406; p 0.05) and with forced expiratory volume in the first second after bronchodilator test (r = 0.366; p 0.05) as well as with forced expiratory volume in the first second divided by forced vital capacity after bronchodilator test (r = 0.572; p 0.05). CONCLUSIONS: Periostin is a promising marker of eosinophilic inflammation in patients with asthma, which can be considered as an indicator of fixed bronchial obstruction and a molecule linking T2-inflammation and airway remodelling. In a group of chronic obstructive pulmonary disease patients, the use of periostin for diagnostic and prognostic purposes requires further investigation and larger studies.

The effect of vitamin D provision on biomarkers of inflammation in bronchial asthma in children

Introduction. Asthma is a widespread disease in childhood and has a persistent tendency to increase. Therefore, the search for factors influencing this process, as well as biomarkers reflecting the degree of asthma control, is an urgent problem. Objective. To study the relationship of vitamin D levels with the serum periostin and TGF-β1 concentration in children with asthma. Materials and methods. The cross-sectional (one-stage) study included 80 children aged 6 to 17 years (average age — 12 ± 3.2 g). The subjects were divided into 2 groups: children with asthma — group 1 (n = 40); group 2 — the control group (n = 40). In all children, the assessment of the concentration of 25(OH)D, periostin and TGF-β1 in the blood serum was studied. Results. Median (Me) 25(OH) in patients with asthma was statistically significantly lower than in children of the comparison group (16.7 ng/ml, versus 25.7 ng/ml, p = 0.017), and did not depend on the severity of the disease, corresponded to a deficiency condition in both mild (16.2 ng/ml) and with an average severity of asthma (16.8 ng/ml) (p = 0.041). Me of periostin in 1st group was within the normal range (730.2 ng/ml), but statistically significantly exceeded the indicator of 2nd group (539.7 ng/ml, p < 0.05) and did not depend on the age and duration of asthma. High rates of periostin were observed in children with moderate severity of asthma with a disease experience of 4–6 years (617.2 ng/ml). Me of TGF-β1 in both groups corresponded to normal values (309.0 and 369.6 pg/ml, respectively, p > 0.05) and did not depend on the age and duration of asthma. Conclusions. VD deficiency is registered in children with asthma 2 times more often than in healthy children in Ryazan region. The serum concentration of periostin increased in proportion to the severity of asthma. Vitamin D deficiency can be one of the risk factors for the development of asthma and lead to an imbalance in the periostin and TGF-β system.

Association of serum periostin levels with asthma control status and severity in children

Objectives Periostin is a promising indicator in the pathogenesis of T-helper type-2 allergic reactions. This study aimed to identify the relationship between serum periostin levels and asthma control in children. Procedure In this study, 90 children were recruited and grouped as follows: 30 children in a control group (group I), and another group comprising 60 children with physician-diagnosed asthma (group II). The control status and severity of asthma in patients were assessed in accordance with the recent Global Initiative for Asthma guidelines. Serum periostin concentrations were examined in all enrolled patients using an enzyme-linked immunosorbent assay kit. Results The median (interquartile range) periostin levels of asthmatic children were substantially higher than those of healthy children [23 (13.1, 48) vs. 15 (10.5, 24); P = 0.015]. Based on a simple logistic regression analysis, serum periostin concentrations strongly correlated with asthma (odds ratio = 1.037; confidence interval = 1.008–1.066; P = 0.012). In a receiver operator characteristic curve analysis, the area under the curve for serum periostin was 0.984, with 100% sensitivity and 95.35% specificity in detecting uncontrolled asthma. Conclusion Serum periostin levels were shown to be a helpful biomarker for assessing childhood asthma control in children.

Serum Periostin as a Potential Biomarker in Pediatric Patients with Primary Hypertension.

Experimental studies suggest that periostin is involved in tissue repair and remodeling. The study aimed to evaluate serum periostin concentration as potential biomarker in pediatric patients with primary hypertension (PH). We measured serum periostin, blood pressure, arterial damage, biochemical, and clinical data in 50 children with PH and 20 age-matched healthy controls. In univariate analysis, children with PH had significantly lower serum periostin compared to healthy peers (35.42 ± 10.43 vs. 42.16 ± 12.82 [ng/mL], p = 0.038). In the entire group of 70 children serum periostin concentration correlated negatively with peripheral, central, and ambulatory blood pressure, as well as with aortic pulse wave velocity (aPWV). In multivariate analysis, periostin level significantly correlated with age (β = −0.614, [95% confidence interval (CI), −0.831–−0.398]), uric acid (β = 0.328, [95%CI, 0.124–0.533]), body mass index (BMI) Z-score (β = −0.293, [95%CI, −0.492–−0.095]), high-density lipoprotein (HDL)-cholesterol (β = 0.235, [95%CI, 0.054–0.416]), and triglycerides (β = −0.198, [95%CI, −0.394–−0.002]). Neither the presence of hypertension nor blood pressure and aPWV influenced periostin level. To conclude, the role of serum periostin as a biomarker of elevated blood pressure and arterial damage in pediatric patients with primary hypertension is yet to be unmasked. Age, body mass index, uric acid, and lipid concentrations are key factors influencing periostin level in pediatric patients.

Periostin and Thymic Stromal Lymphopoietin-Potential Crosstalk in Obstructive Airway Diseases.

Periostin and thymic stromal lymphopoietin (TSLP) are newly described markers of obstructive airway diseases and the mechanism by which both markers participate in immune response remains poorly understood. The aim of our study was to determine periostin and TSLP concentration in serum and induced sputum (IS) in patients with atopic asthma, chronic obstructive pulmonary disease (COPD), and controls, as well as to evaluate the potential link between periostin, TSLP, and Th2 immune response. Serum and IS levels of periostin, TSLP, IL-4, and IL-13 were determined in 12 atopic asthmatics, 16 COPD sufferers, and 10 controls. We noticed a significantly higher IS periostin and TSLP concentration at protein and mRNA level in asthmatics compared to the two other groups; additionally, periostin and TSLP were correlated positively with IS eosinophil count. A strong positive correlation between IS periostin and TSLP protein levels (r = 0.96) as well as mRNA expression level (r = 0.95) was found in patients with asthma. The results of our study show that periostin and TSLP are associated with eosinophilic airway inflammation and seem to be important drivers of atopic asthma but not COPD pathobiology. Very strong correlations between local periostin, TSLP, eosinophils, and IL-4 in asthma point to the link between periostin–TSLP and Th2 response.

Periostin concentration in exhaled breath condensate in children with mild asthma

Objective Periostin is considered to be a marker of eosinophilic inflammation in patients with asthma. However, there are no literature data on exhaled breath condensate (EBC) periostin level in pediatric patients with asthma. The aim of this study was to analyze EBC periostin concentration in children with mild asthma and to evaluate the potential usefulness of EBC periostin level as a biomarker for the disease. Methods EBC and serum periostin concentrations were measured by enzyme-linked immunosorbent assay in 23 children with asthma and 23 healthy controls. Results EBC periostin concentration was 250- to 780-fold lower than that found in serum. No significant differences between serum nor EBC periostin concentration in asthmatics and the control group were showed. The comparison between children with Th2 and non-Th2 type of asthma did not show significant differences in periostin concentration, both in serum and EBC. Serum periostin concentration inversely correlated with BMI and age not only in asthma patients but also in controls. Conclusions In children with mild asthma, periostin may be measured not only in serum but also in EBC. The low periostin level in patients with mild asthma and lack of difference between asthmatic subjects and controls indicate that EBC periostin may not be useful as an asthma biomarker in this group.

Effect of inhaled corticosteroids on serum periostin levels in adult patients with mild-moderate asthma.

Background: Periostin is an extracellular matrix protein, and its expression is upregulated in airway epithelial cells in patients with bronchial asthma. Periostin may be a key molecule linked to type 2 T-helper cell inflammation. Inhaled corticosteroids (ICS) may suppress periostin-induced asthmatic inflammation. This study estimated the serum periostin levels in patients with asthma and evaluated the effect of ICS on the levels of periostin, peak expiratory flow rate (PEFR), and quality of life (QOL). Methods: The study design was prospective, open label, and observational. Forty adults with mild-to-moderate bronchial asthma started on ICS and matched healthy controls were enrolled. The patients were evaluated for their serum periostin, PEFR, and QOL by using asthma QOL questionnaire scores at baseline and after 4 weeks. Results: The mean ± standard deviation (SD) serum periostin concentration in patients with asthma was 90.36 ± 19.81 ng/mL, which was significantly higher (p < 0.01) compared with healthy controls (31.88 ± 8.71 ng/mL). ICS treatment for 4 weeks reduced the mean ± SD serum periostin levels to 58.78 ± 14.53 ng/mL. The mean ± SD PEFR increased significantly, from 225.25 ± 60.79 L/min to 292.5 ± 59.18 L/min (p < 0.01), after 4 weeks. Similarly, the mean ± SD when using asthma QOL questionnaire scores significantly increased, from 40.7 ± 7.84 at baseline to 59.33 ± 11.0 on day 28 after ICS therapy (p < 0.01). Conclusion: The serum periostin level, a marker of allergic inflammation and remodeling, increased in bronchial asthma and was reduced with ICS therapy. ICS improved QOL scores and PEFR in patients with asthma.

Role of periostin in Iraqi asthmatic patients

Background: Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. The understanding of the pathogenesis of the disease is essential to improve the plan of management. Objective: The objective of this study is to identify the role of periostin as inflammatory biomarker of asthma. Materials and Methods: A total of 200 participants were enrolled in the study, of which there are 100 controls and 100 asthmatic patients. Blood samples were obtained from the participants for periostin investigations by enzyme-linked immunosorbent assay assay. Results: Serum periostin concentrations were significantly (P < 0.001) higher in asthmatic patients (mean ± standard deviation [SD]; 68.152±9.792) compared to control group (mean ± SD; 46.488 ± 4.237). Periostin correlated negatively with forced expiratory volume (FEV) 1% and FEV1/forced vital capacity (FVC) in asthmatic patients. Conclusions: Serum periostin is increased in Iraqi asthmatic patients compared to controls and periostin correlated negatively with FEV1% and FEV1/FVC in asthmatic patients. Asthma is the most significant variable relates to high periostin serum concentration.

Characterization of tenascin-C as a novel biomarker for asthma: utility of tenascin-C in combination with periostin or immunoglobulin E

BackgroundExtracellular matrix proteins tenascin-C (TNC) and periostin, which were identified as T-helper cell type 2 cytokine-induced genes in human bronchial epithelial cells, accumulate in the airway basement membrane of asthmatic patients. Although serum periostin has been accepted as a type 2 biomarker, serum TNC has not been evaluated as a systemic biomarker in asthma. Therefore, the objective of this study was to evaluate whether serum TNC can serve as a novel biomarker for asthma.MethodsWe evaluated 126 adult patients with mild to severe asthma. Serum TNC, periostin, and total IgE concentrations were quantified using enzyme-linked immunosorbent assays.ResultsSerum TNC levels were significantly higher in patients with severe asthma and high serum total IgE levels. Patients with both high serum TNC (> 37.16 ng/mL) and high serum periostin (> 95 ng/mL) levels (n = 20) or patients with both high serum TNC and high serum total IgE (> 100 IU/mL) levels (n = 36) presented higher disease severity and more severe airflow limitation than patients in other subpopulations.ConclusionsTo our knowledge, this is the first study to show that serum TNC levels in asthmatic patients are associated with clinical features of asthma and that the combination of serum TNC and periostin levels or combination of serum TNC and total IgE levels were more useful for asthma than each single marker, suggesting that serum TNC can serve as a novel biomarker for asthma.

Asthma diagnosis using integrated analysis of eosinophil microRNAs.

Asthma is a syndrome characterized by airway inflammation and obstruction. Due to its heterogeneity, the difficulties in asthma diagnosis and treatment make the discovery of new biomarkers a focus of research. So, we determined the differential miRNA expression of eosinophils between healthy and asthmatic patients and to establish a differentially expressed miRNA profile detectable in sera for use as biomarker. MicroRNAs from peripheral eosinophils from healthy and asthmatic subjects were isolated and analyzed by next-generation sequencing and confirmed by quantitative PCR in 29 asthmatics and 10 healthy individuals. The levels of serum miRNAs were performed by quantitative PCR in 138 asthmatics and 39 healthy subjects. Regression analysis and Random Forest models were performed. We found a set of miRNAs whose expression differs between eosinophils from asthmatics and healthy subjects. These miRNAs can classify asthmatics into two clusters that differed in the number of eosinophils and periostin concentration in serum. Some of these miRNAs were also confirmed in sera, as miR-185-5p which discriminates asthmatics from healthy subjects. Together with other two miRNAs, miR-185-5p allowed us to create a logistic regression model to discriminate better both conditions and a Random Forest model that can even sort the asthmatics into intermittent, mild persistent, moderate persistent, and severe persistent asthma. Our data show that miRNAs profile in eosinophils can be used as asthma diagnosis biomarker in serum and that this profile is able to rank asthma severity.

Increased concentration of serum periostin is associated with poor outcome of patients with aneurysmal subarachnoid hemorrhage.

To explore the role of serum periostin in patients with aneurysmal subarachnoid hemorrhage (aSAH). We conducted a retrospective study and 124 aSAH patients treated in Shenzhen People's hospital during March 1st 2015 to December 30th 2016 were included. Baseline information, neurological status and clinical outcome were recorded. Blood samples on admission were collected and enzyme linked immunosorbent assay (ELISA) kits were used to detect the serum level of periostin. Spearman's Correlation Analysis was used to analyze the correlation between periostin and clinical severity. Receiver operating characteristic (ROC) curve was performed to investigate variables' prognostic value in patients with aSAH. The average age of patients included was 57.23years old. Preliminary analysis revealed that serum periostin was significantly correlated with clinical severity. Patients with poor outcome at 12months had higher level of periostin than patients with good outcome. Multivariate logistic regression analysis showed elevated level of periostin was significantly associated with poor outcome and the AUC was 0.85 for periostin in predicting poor outcome of patient with aSAH. Elevated serum periostin concentrations are significantly associated with clinical severity and poor outcome of aSAH patients, which indicate serum periostin can be used as a prognostic biomarker in patients with aSAH.

Increased serum periostin concentrations are associated with the presence of diabetic retinopathy in patients with type 2 diabetes mellitus.

To determine the association between serum periostin and the presence of diabetic retinopathy (DR). Serum periostin was detected in 114 healthy subjects, 122 patients with type 2 diabetes mellitus (T2DM) and 159 patients with DR and compared among groups. Clinical data and other laboratory measurements such as glycated hemoglobin (HbA1c), lipid profiles, serum creatinine (Cr) and high-sensitivity CRP (hsCRP) were also collected and compared among groups. For subgroup analysis, patients with DR were divided into a non-proliferated diabetic retinopathy (NPDR) group and a proliferated diabetic retinopathy (PDR) group. Multivariate analysis was performed using logistic regression models. The serum periostin level was significantly higher in patients with diabetic retinopathy compared with healthy subjects and patients with T2DM (both P<0.001, respectively). Also, the periostin level was significantly higher in the PDR group compared to the NPDR group (P=0.044). Multivariate logistic regression revealed that serum periostin was independently associated with the presence of DR in patients with T2DM (P<0.001). The receiver operating characteristic (ROC) curves for DR development using serum periostin showed that the area under the receiver operating characteristic curves (AUC) was 0.838 (P<0.001). The current study demonstrated that serum periostin is significantly associated with the presence of DR in patients with T2DM and is an independent risk factor of DR.

Serum Periostin Is Negatively Correlated With Exposure to Formaldehyde and Volatile Organic Compounds in Children.

Epidemiological studies have shown that exposure to tobacco smoke causing irritation and inflammation in the airways tends to reduce serum periostin concentrations in adults. We now investigate prospective cross-sectional study on 135 Korean students aged 7 years in the first grade who were participating in the Seongnam Atopy Project for Children's Happiness 2016 (SAP2016) cohort. To the best of our knowledge, this is the first study to show significant inverse correlations between serum periostin concentration and exposure to xylene and formaldehyde in children. Our findings suggested the need for caution in using the serum periostin level as a marker for allergic diseases, since exposure to volatile organic compounds and formaldehyde may confound the interpretation of these results.

Biomarkers for differentiation of patients with asthma and chronic obstructive pulmonary disease

ABSTRACTObjective: Asthma and chronic obstructive pulmonary disease (COPD) are airflow limitation diseases with similar clinical manifestations but different pathophysiologic mechanisms. To implement the appropriate treatment, it is important to distinguish between asthma and COPD which sometimes might result difficult in clinical practice. We evaluated biomarkers to distinguish between asthma and COPD. Methods: Blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels were analyzed. Serum periostin, interleukin-25 (IL-25), and immunoglobulin E (IgE) concentrations were compared between patients with asthma (n = 60), including atopic-asthma (n = 30) and non-atopic asthma (n = 30), and patients with COPD (n = 30). Results: Significantly higher peripheral blood eosinophil counts (p < 0.001), FeNO levels (p < 0.001), and total serum IgE (P = 0.003) concentrations, but not serum periostin (p = 0.584) or serum IL-25 (p = 0.085) concentrations, were detected in patients with asthma compared to patients with COPD. Serum periostin and IgE concentrations were increased in patients with atopic-asthma compared with those with non-atopic asthma and COPD (p < 0.05). The FeNO levels were significantly correlated with the peripheral blood eosinophil counts (r = 0.430, p = 0.001) and serum IL-25 concentrations (r = 0.338, p = 0.009) in patients with asthma. The serum periostin concentrations were also correlated with the serum IgE concentrations (r = 0.375, p = 0.003)and FeNO levels (r = 0.291, p = 0.024) in patients with asthma. Asthma patients were effectively differentiated from COPD patients based on the FeNO levels (p < 0.001) and peripheral blood eosinophil counts (p < 0.001). Conclusions: FeNO levels and peripheral blood eosinophil counts were useful biomarkers for distinguishing between patients with asthma and COPD. Serum periostin and IgE concentrations could be biomarkers for atopic asthma.

Association between serum periostin concentrations and outcome after acute spontaneous intracerebral hemorrhage

BackgroundHigher serum periostin concentrations are associated with mortality after head trauma. We further determined the relationship between periostin concentrations, severity, and clinical outcome in patients with intracerebral hemorrhage (ICH). MethodsWe prospectively included 128 controls and 128 consecutive patients with acute ICH within the first 24h after onset. At admission, we measured serum periostin concentrations. ResultsSerum periostin concentrations were significantly higher in the patients than in the controls. Serum periostin concentrations were positively related to National Institutes of Health Stroke Scale (NIHSS) score (r=0.526) and hematoma volume (r=0.586). An unfavorable outcome (defined as modified Rankin scale >2) was observed in 65 (50.8%) patients. Serum periostin [odds ratio (OR), 1.008; 95% confidence interval (CI), 1.002–1.013], NIHSS score (OR, 1.462; 95% CI, 1.209–1.767), hematoma volume (OR, 1.134; 95% CI, 1.047–1.227) and age (OR, 1.060; 95% CI, 1.015–1.108) emerged as independent predictors for 6-month unfavorable outcome. In terms of ROC AUC, serum periostin concentrations had significantly higher predictive value compared with age and showed similar predictive value compared with NIHSS score and hematoma volume. ConclusionsHigh concentrations of serum periostin in acute ICH patients are associated with increasing severity and a poor functional prognosis.

Serum periostin concentrations and outcomes after severe traumatic brain injury

BackgroundPeriostin, a neurite outgrowth-promoting factor, is increasingly expressed in rat brain tissues after cerebral ischemia or subarachnoid hemorrhage. However, periostin concentrations are undetermined in peripheral blood from patients with traumatic brain injury (TBI). MethodsIn this prospective, observational study, serum periostin concentrations were measured in 130 controls and 130 severe TBI patients. We investigated its association with trauma severity reflected by Glasgow Coma Scale (GCS) score and prognosis (i.e., 30-day mortality and 30-day overall survival). ResultsAs compared with the controls, serum periostin concentrations were significantly increased in the patients [(median, 246.5ng/ml; interquartile range, 164.5–328.6ng/ml) vs. (median, 61.8ng/ml; interquartile range, 37.9–77.9ng/ml), P<0.001]. Periostin concentrations independently correlated with GCS scores (t=−6.199, P<0.001). Serum periostin concentrations higher than 308.2ng/ml predicted 30-day mortality with a sensitivity of 72.4% and a specificity of 78.2% [area under curve, 815; 95% confidence interval (CI), 0.737–0.878]. Periostin concentrations higher than 246.5ng/ml were independently related to 30-day mortality and 30-day overall survival with odds ratio value of 3.829 (95% CI, 1.104–13.281) and hazard ratio value of 5.667 (95% CI, 1.953–16.443) respectively. ConclusionsIncreased serum periostin concentrations clearly reflect trauma severity and mortality following TBI.

Development of a new ARCHITECT automated periostin immunoassay

BackgroundPeriostin is being investigated as a potential biomarker for T-helper-2 (Th2)-driven asthma or eosinophilic inflammation and may help to identify patients more likely to benefit from interleukin-13-targeted treatments. We report the development and analytic performance of the investigational use only ARCHITECT Periostin Immunoassay, a new automated assay developed to detect serum periostin concentrations. MethodsWe assessed assay performance in terms of precision, sensitivity, linearity, interference from classical immunoassay interferents and representatives of common asthma medications, specimen handling, and isoform reactivity. The assay was also used to assess the biological variability of serum periostin concentrations in samples from healthy volunteers and from subjects with uncontrolled asthma (the intended use population). ResultsThe percentage CVs for 5-day total precision, assessed using two instruments, was <6% across 2 controls and one serum-based panel. Limit of quantitation was 4ng/mL (dilution adjusted concentration), suiting the needs for this application. Dilution analysis yielded linear results and no endogenous sample or drug interferences were observed. All known periostin isoforms expressed in the mature human lung were detected by the assay. ConclusionOur studies provide support that the ARCHITECT Periostin Immunoassay is a reliable and robust test for measuring serum periostin concentrations.

Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials

In phase 2 trials, lebrikizumab, an anti-interleukin-13 monoclonal antibody, reduced exacerbation rates and improved FEV1 in patients with uncontrolled asthma, particularly in those with high concentrations of type 2 biomarkers (eg, periostin or blood eosinophils). We undertook replicate phase 3 studies to assess the efficacy and safety of lebrikizumab in patients with uncontrolled asthma despite inhaled corticosteroids and at least one second controller medication. Adult patients with uncontrolled asthma, pre-bronchodilator FEV1 40-80% predicted, and stable background therapy were randomly assigned (1:1:1) with an interactive voice-web-based response system to receive lebrikizumab 37·5 mg or 125 mg, or placebo subcutaneously, once every 4 weeks. Randomisation was stratified by screening serum periostin concentration, history of asthma exacerbations within the last 12 months, baseline asthma medications, and country. The primary efficacy endpoint was the rate of asthma exacerbations over 52 weeks in biomarker-high patients (periostin ≥50 ng/mL or blood eosinophils ≥300 cells per μL), analysed with a Poisson regression model corrected for overdispersion with Pearson χ2 that included terms for treatment group, number of asthma exacerbations within the 12 months before study entry, baseline asthma medications, geographic region, screening periostin concentration, and blood eosinophil counts as covariates. Both trials are registered at ClinicalTrials.gov, LAVOLTA I, number NCT01867125, and LAVOLTA II, number NCT01868061. 1081 patients were treated in LAVOLTA I and 1067 patients in LAVOLTA II. Over 52 weeks, lebrikizumab reduced exacerbation rates in biomarker-high patients in the 37·5 mg dose group (rate ratio [RR] 0·49 [95% CI 0·34-0·69], p<0·0001) and in the 125 mg dose group (RR 0·70 [0·51-0·95], p=0·0232) versus placebo in LAVOLTA I. Exacerbation rates were also reduced in biomarker-high patients in both dose groups versus placebo in LAVOLTA II (37·5 mg: RR 0·74 [95% CI 0·54-1·01], p=0·0609; 125 mg: RR 0·74 [0·54-1·02], p=0·0626). Pooling both studies, the proportion of patients who experienced treatment-emergent adverse events (79% [1125 of 1432 patients] for both lebrikizumab doses vs 80% [576 of 716 patients] for placebo), serious adverse events (8% [115 patients] for both lebrikizumab doses vs 9% [65 patients] for placebo), and adverse events leading to study drug discontinuation (3% [49 patients] for both lebrikizumab doses vs 4% [31 patients] for placebo) were similar between lebrikizumab and placebo. The following serious adverse events were reported in the placebo-controlled period: one event of aplastic anaemia and five serious adverse events related to raised concentrations of eosinophils in patients treated with lebrikizumab and one event of eosinophilic pneumonia in the placebo group. Lebrikizumab did not consistently show significant reduction in asthma exacerbations in biomarker-high patients. However, it blocked interleukin-13 as evidenced by the effect on interleukin-13-related pharmacodynamic biomarkers, and clinically relevant changes could not be ruled out. F Hoffmann-La Roche.