Periostin - A biomarker in adults with asthma

<p>Asthma is a common, heterogeneous condition where current treatment options are limited to a ‘one size fits all’ approach. Biological therapies targeting specific components of the Type 2 inflammatory pathway are emerging as potential alternatives for those who are inadequately controlled on current treatment options. Biomarkers, such as serum periostin, can be used in clinical settings to identify potential responders to these treatments. The aim of this research was to investigate the epidemiology of periostin and its ability to predict important clinical outcomes in asthma. Six studies were conducted: two cohort studies observing the change to periostin after bone and dental injury in non-asthmatic adults; a cohort study investigating reference ranges of periostin in Chinese adults with and without asthma; two longitudinal studies measuring the change in periostin in asthmatic adults with stable and unstable disease; and a longitudinal cohort study investigating the association between periostin and risk of exacerbation. There was a biphasic response of serum periostin after bone injury. This was particularly marked after joint replacement surgery where periostin fell within 48 hours by a ratio of geometric means 0.80 (95% CI 0.75 to 0.86) before rising to a maximum level at eight weeks with a ratio of geometric means 1.89 (95% CI 1.77 to 2.02). There was no significant change to periostin after simple or surgical tooth extractions with a maximal ratio of geometric means of 1.02 (95% CI 0.95 to 1.10). Serum periostin was higher in Chinese non-asthmatic adults versus Caucasian non- asthmatic adults, mean periostin 57 ng/ml and 49.7 ng/ml respectively, difference (95% CI) 8.2 (5.8 to 10.6) ng/ml. Serum periostin remained stable in adults with well- controlled asthma with an intra-class coefficient for variation of 0.93. In unstable asthma, there was a decrease in serum periostin one week after the start of a severe exacerbation and treatment with systemic corticosteroids, with a ratio of geometric means 0.86 (95% CI 0.82 to 0.92) before stabilising four weeks later. Finally, adults with mild to moderate asthma with low baseline levels of periostin were more likely to have a severe asthma exacerbation with a hazard ratio (95% CI) 0.62 (0.35 to 1.09) per 0.693 ng/ml increase of log periostin. In conclusion, serum periostin showed significant biphasic variation in response to bone injury, the magnitude and duration of which was proportional to bone size. Whilst this pattern was not replicated in adults undergoing dental surgery, it suggests that serum periostin can be affected by non-asthma related conditions. Periostin demonstrated higher mean values in Chinese adults than in Caucasian adults, indicating ethnicity-specific reference ranges may be required if it were to become a clinical biomarker. Intra-participant variability of serum periostin was low in a homogenous group of well controlled, moderate to severe asthmatic adults, but there was wide variability between individuals in this group suggesting that factors other than asthma are likely to affect serum periostin levels. Serum periostin was suppressed during and after treatment for a severe exacerbation for up to four weeks. This is likely due to the exacerbation and/or its treatment, suggesting the interpretation of periostin as a biomarker for response to biological therapies should not occur within four weeks of a severe exacerbation. The reported positive association between periostin and risk of severe exacerbation in populations with severe eosinophilic asthma does not extend to a general population of mild to moderate asthmatics, in which an inverse associated was observed. Serum periostin may be useful in predicting treatment responsiveness of patients to monoclonal antibody therapy directed against IL-4Rα, IL-13 and IgE. However, it may be difficult to use as a biomarker clinically, as numerous non-asthma related factors, such as bone injury and ethnicity, have been shown to significantly affect serum levels, making interpretation difficult.</p>

Periostin - A biomarker in adults with asthma

<p>Asthma is a common, heterogeneous condition where current treatment options are limited to a ‘one size fits all’ approach. Biological therapies targeting specific components of the Type 2 inflammatory pathway are emerging as potential alternatives for those who are inadequately controlled on current treatment options. Biomarkers, such as serum periostin, can be used in clinical settings to identify potential responders to these treatments. The aim of this research was to investigate the epidemiology of periostin and its ability to predict important clinical outcomes in asthma. Six studies were conducted: two cohort studies observing the change to periostin after bone and dental injury in non-asthmatic adults; a cohort study investigating reference ranges of periostin in Chinese adults with and without asthma; two longitudinal studies measuring the change in periostin in asthmatic adults with stable and unstable disease; and a longitudinal cohort study investigating the association between periostin and risk of exacerbation. There was a biphasic response of serum periostin after bone injury. This was particularly marked after joint replacement surgery where periostin fell within 48 hours by a ratio of geometric means 0.80 (95% CI 0.75 to 0.86) before rising to a maximum level at eight weeks with a ratio of geometric means 1.89 (95% CI 1.77 to 2.02). There was no significant change to periostin after simple or surgical tooth extractions with a maximal ratio of geometric means of 1.02 (95% CI 0.95 to 1.10). Serum periostin was higher in Chinese non-asthmatic adults versus Caucasian non- asthmatic adults, mean periostin 57 ng/ml and 49.7 ng/ml respectively, difference (95% CI) 8.2 (5.8 to 10.6) ng/ml. Serum periostin remained stable in adults with well- controlled asthma with an intra-class coefficient for variation of 0.93. In unstable asthma, there was a decrease in serum periostin one week after the start of a severe exacerbation and treatment with systemic corticosteroids, with a ratio of geometric means 0.86 (95% CI 0.82 to 0.92) before stabilising four weeks later. Finally, adults with mild to moderate asthma with low baseline levels of periostin were more likely to have a severe asthma exacerbation with a hazard ratio (95% CI) 0.62 (0.35 to 1.09) per 0.693 ng/ml increase of log periostin. In conclusion, serum periostin showed significant biphasic variation in response to bone injury, the magnitude and duration of which was proportional to bone size. Whilst this pattern was not replicated in adults undergoing dental surgery, it suggests that serum periostin can be affected by non-asthma related conditions. Periostin demonstrated higher mean values in Chinese adults than in Caucasian adults, indicating ethnicity-specific reference ranges may be required if it were to become a clinical biomarker. Intra-participant variability of serum periostin was low in a homogenous group of well controlled, moderate to severe asthmatic adults, but there was wide variability between individuals in this group suggesting that factors other than asthma are likely to affect serum periostin levels. Serum periostin was suppressed during and after treatment for a severe exacerbation for up to four weeks. This is likely due to the exacerbation and/or its treatment, suggesting the interpretation of periostin as a biomarker for response to biological therapies should not occur within four weeks of a severe exacerbation. The reported positive association between periostin and risk of severe exacerbation in populations with severe eosinophilic asthma does not extend to a general population of mild to moderate asthmatics, in which an inverse associated was observed. Serum periostin may be useful in predicting treatment responsiveness of patients to monoclonal antibody therapy directed against IL-4Rα, IL-13 and IgE. However, it may be difficult to use as a biomarker clinically, as numerous non-asthma related factors, such as bone injury and ethnicity, have been shown to significantly affect serum levels, making interpretation difficult.</p>

Effect of atorvastatin on serum periostin and blood eosinophils in asthma – a placebo-controlled randomized clinical trial

Objective To investigate the effect of atorvastatin on serum periostin level and blood eosinophil count in patients with asthma. Methods Patients diagnosed with asthma were enrolled and randomised into an intervention or placebo group, to receive 40 mg atorvastatin or similar placebo, daily, for 8 weeks. Spirometry was performed at baseline, and at the end of weeks 4 and 8; patients also provided blood samples and completed an asthma control test (ACT) at baseline and at the end of week 8. Primary study outcomes were blood eosinophil count and serum periostin levels. Results Eighty patients completed the study (40 per group). Mean ACT scores were similar between the intervention and placebo groups at baseline (17.95 ± 3.75 versus 17.98 ± 3.77, respectively), and improved in the intervention group (19.88 ± 3.28), but remained unchanged in the placebo group (18.6 ± 3.26) during the treatment period. No statistically significant differences in spirometric changes, blood eosinophil count or serum periostin levels were observed between the groups during the treatment period. Conclusion Spirometric parameters and inflammatory markers did not change significantly in response to atorvastatin treatment, and did not differ between the placebo and intervention groups.

Serum Periostin Predicts Wheezing Exacerbation: A Prospective Study in Preschool Children with Recurrent Wheezing

<b><i>Introduction:</i></b> Wheezing is a common problem in preschool children. Currently, there are no reliable biomarkers that can predict subsequent wheezing in preschool children. This study aimed to compare serum periostin levels between preschool children with and without recurrent wheezing and investigate its utility for predicting acute wheezing exacerbation. <b><i>Methods:</i></b> Children aged 2–5 years with recurrent wheezing and healthy control children were enrolled. They were evaluated for serum periostin level at enrollment and subsequently followed for wheezing episodes in a 1-year prospective study. <b><i>Results:</i></b> A total of 122 children were enrolled. Children in the recurrent wheezing group (<i>n</i> = 80) had a greater median serum periostin level (1,122.32 pg/mL [&#x3c;10–6,978.93]) than that of the healthy control group (<i>n</i> = 40) (&#x3c;10 pg/mL [&#x3c;10–2,116.69]), <i>p</i> value = 0.006. After 1-year follow-up, subjects who experienced subsequent wheezing exacerbation episodes had a greater median of periostin level (5,321 pg/mL) compared with those with no exacerbation (&#x3c;10 pg/mL), <i>p</i> value = 0.014. ROC curve analysis revealed that the level of serum periostin &#x3e;1,200 pg/mL, corresponding to 78.9% sensitivity and 64.6% specificity, with an AUC of 0.701, <i>p</i> value = 0.009, could be a predictor for acute wheezing exacerbation within 1 year. Besides, subjects with serum periostin &#x3e;1,200 pg/mL had greater odds of subsequent wheezing episodes compared with those with lower levels of serum periostin (adjusted odds ratio 10.0, 95% confidence interval: 2.3–43.5). <b><i>Conclusions:</i></b> Preschool children with recurrent wheezing have a greater serum periostin level than healthy control. Serum periostin may be a valuable biomarker for predicting acute wheezing exacerbations in the following year.