Periostin - A biomarker in adults with asthma
Authors:   , Semprini Ruth 
Published: December 2021

<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>