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Here, we present a multiomics\u2010based time\u2010series assessment of nasal polyp biopsies from three patients with CRS, assessing natural variability over time and local response to systemic corticosteroid therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Polyp tissue biopsies were collected at three time points over two consecutive weeks. Patients were prescribed prednisone (30\u2009mg daily) for 1 week between Collections 2 and 3. Polyp transcriptome, proteome, and microbiota were assessed via RNAseq, SWATH mass spectrometry, and 16S ribosomal RNA and ITS2 amplicon sequencing. Baseline interpatient variability, natural intrapatient variability over time, and local response to systemic corticosteroids, were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, the highly abundant transcripts and proteins were associated with pathways involved in inflammation, FAS, cadherin, integrin, Wnt, apoptosis, and cytoskeletal signaling, as well as coagulation and B\u2010 and T\u2010cell activation. Transcripts and proteins that naturally varied over time included those involved with inflammation\u2010 and epithelial\u2013mesenchymal transition\u2010related pathways, and a number of common candidate target biomarkers of CRS. Ten transcripts responded significantly to corticosteroid therapy, including downregulation of <jats:italic>TNF, CCL20<\/jats:italic>, and <jats:italic>GSDMA<\/jats:italic>, and upregulation of <jats:italic>OVGP1<\/jats:italic>, and <jats:italic>PCDHGB1<\/jats:italic>. Members of the bacterial genus <jats:italic>Streptococcus<\/jats:italic> positively correlated with immunoglobulin proteins IGKC and IGHG1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Understanding natural dynamics of CRS\u2010associated tissues is essential to provide baseline context for all studies on putative biomarkers, mechanisms, and subtypes of CRS. These data further our understanding of the natural dynamics within nasal polypoid tissue, as well as local changes in response to systemic corticosteroid therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.349","type":"journal-article","created":{"date-parts":[[2020,11,21]],"date-time":"2020-11-21T16:40:52Z","timestamp":1605976852000},"page":"90-107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Multiomic analysis identifies natural intrapatient temporal variability and changes in response to systemic corticosteroid therapy in chronic rhinosinusitis"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9323-0830","authenticated-orcid":false,"given":"Michael","family":"Hoggard","sequence":"first","affiliation":[{"name":"School of Biological Sciences The University of Auckland  Auckland New 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