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Mahmood Yaseen Hachim,1 Noha Mousaad Elemam,1 Rakhee K Ramakrishnan,1 Ibrahim Yaseen Hachim,1 Laila Salameh,1 Bassam Mahboub,1 Saba Al Heialy,2,3 Rabih Halwani,1 Rifat Hamoudi,1 Qutayba Hamid1,2 1Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 2Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada; 3College of Medicine, Mohammed Bin Rashid University, Dubai, United Arab EmiratesCorrespondence: Rifat HamoudiCollege of Medicine, University of Sharjah, PO Box 27272, Sharjah, United Arab EmiratesEmail rhamoudi@sharjah.ac.aeIntroduction: The proper use of serum periostin (POSTN) as a biomarker for asthma is hindered by inconsistent performance in different clinical settings.Objective: To explore patient’s factors that may affect POSTN expression locally and systematically and its utility as a biomarker for asthma development.Materials and Methods: Here we used bioinformatics analysis of publicly available transcriptomics data to confirm that POSTN is an asthma specific gene involved in core signaling pathways enriched in the bronchial epithelium during asthma. We then explored a large number of datasets to identify possible confounders that may affect the POSTN gene expression and consequently, its interpretation as a reliable biomarker for asthma. Plasma and saliva levels of POSTN were determined in locally recruited asthmatic patients (mild, moderate and severe) compared to healthy controls to confirm the bioinformatics findings.Results: Our bioinformatics results confirmed that POSTN was consistently upregulated in the bronchial epithelium in asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) bronchial epithelium. In asthma, its mRNA expression was affected by gender, sample anatomical site and type, steroid therapy, and smoking. In our cohort, plasma POSTN was upregulated in severe and non-severe asthmatic patients. Saliva POSTN was significantly higher in non-severe asthmatic patients compared to healthy and severe asthmatic patients (specifically those who are not on Xolair (omalizumab)). Patients’ BMI, inhaled steroid use and Xolair treatment affected POSTN plasma levels.Conclusion: Up to our knowledge, this is the first study examining the level of POSTN in the saliva of asthmatic patients. Both plasma and saliva POSTN levels can aid in early diagnosis of asthma. Saliva POSTN level was more sensitive than plasma POSTN in differentiating between severe and non-severe asthmatics. Patients’ characteristics like BMI, the use of inhaled steroids, or Xolair treatment should be carefully reviewed before any meaningful interpretation of POSTN level in clinical practice.Keywords: periostin, biomarkers, transcriptomics

Mahmood Yaseen Hachim,1 Ibrahim Yaseen Hachim,2 Noha M Elemam,1 Rifat A Hamoudi1–31Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; 2Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; 3Division of Surgery and Interventional Science, University College London, London, UKCorrespondence: Mahmood Yaseen HachimSharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab EmiratesTel +971 50 945 2674Email U16101425@sharjah.ac.aeRifat A HamoudiDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesTel +971 56 715 4756Email rhamoudi@sharjah.ac.aeBackground: With the increasing incidence of asthma, more attention is focused on the diverse and complex nutritional and environmental triggers of asthma exacerbations. Currently, there are no established risk assessment tools to evaluate asthma triggering potentials of most of the nutritional and environmental triggers encountered by asthmatic patients.Purpose:The objective of this study is to devise a reliable workflow, capable of estimating the toxicogenomic effect of such factors on key player genes in asthma pathogenesis.Methods: Gene expression extracted from publicly available datasets of asthmatic bronchial epithelium were subjected to a comprehensive analysis of differential gene expression to identify significant genes involved in asthma development and progression. The identified genes were subjected to Gene Set Enrichment Analysis using a total of 31,826 gene sets related to chemical, toxins, and drugs to identify common agents that share similar asthma-related targets genes and signaling pathways.Results: Our analysis identified 225 differentially expressed genes between severe asthmatic and healthy bronchial epithelium. Gene Set Enrichment Analysis of the identified genes showed that they are involved in response to toxic substances and organic cyclic compounds and are targeted by 41 specific diets, plants products, and plants related toxins (eg adenine, arachidonic acid, baicalein, caffeic acid, corilagin, curcumin, ellagic acid, luteolin, microcystin-RR, phytoestrogens, protoporphyrin IX, purpurogallin, rottlerin, and salazinic acid). Moreover, the identified chemicals share interesting inflammation-related pathways like NF-κB.Conclusion: Our analysis was able to explain and predict the toxicity in terms of stimulating the differentially expressed genes between severe asthmatic and healthy epithelium. Such an approach can pave the way to generate a cost-effective and reliable source for asthma-specific toxigenic reports thus allowing the asthmatic patients, physicians, and medical researchers to be aware of the potential triggering factors with fatal consequences.Keywords: toxicogenomic, transcriptomic, GSEA, chemical-induced asthma