{"doi":"10.1111/resp.14491","title":"Sputum periostin is a biomarker of type 2 inflammation but not airway dysfunction in asthma","abstract":"Accurate phenotypic and endotypic characterization of asthma is critical to inform treatment decisions, particularly for patients with eosinophilic or type-2 (T2) high asthma who are more responsive to inhaled corticosteroids and are candidates for biologic therapies targeting T2 inflammation.1 Current biomarkers of T2 inflammation, including blood and sputum eosinophilia, and fractional exhaled nitric oxide (FENO), have limitations. Thus there is an unmet need for additional, more accurate biomarkers and to understand the relationship between such biomarkers and airway immunopathology.1 Periostin, a matrix protein secreted by epithelial and stromal cells and a biomarker of T2 inflammation in clinical research, can be measured in sputum and has been associated with the T2-high endotype and persistent airflow obstruction in patients with severe asthma.2 The relationship of sputum periostin to airway dysfunction in the form of airway hyperresponsiveness (AHR) and airway inflammation was examined in individuals with mild-to-moderate asthma who were not using controller therapies. In this cross-sectional assessment, individuals with and without asthma were recruited based on rigorous diagnostic testing, with further characterization of participants for endogenous AHR in the form of exercise-induced bronchoconstriction (EIB).3, 4 Briefly, individuals underwent methacholine challenge testing, dry air exercise challenge, induced sputum collection and research bronchoscopy. Periostin levels in induced sputum supernatant were measured at a 1:2 dilution using a sandwich ELISA assay (Genentech, Inc., South San Francisco, CA; lower limit of quantitation [LLOQ]: 37 pg/mL).5 We assessed induced sputum cell differentials and expression of selected genes (IL4, IL5, IL13, ARG2, INFG, TPSAB1, CMA1, and CPA3) by qPCR. Individuals were categorized for T2 inflammation using the sputum Type-2 Gene Mean (T2GM), with T2-high asthma defined by a T2GM ≥2 standard deviations above that of healthy controls within the study population.3, 4, 6 Endobronchial biopsies were assessed by immunohistochemistry and quantified by design-based stereology, to precisely quantify the numerical density of mast cells and eosinophils per reference volume within different compartments of the airway wall.3, 4 Nonparametric statistics were used. Correlations between continuous variables were assessed using Spearman's rho (r). Forty-three study participants had sputum periostin measured, and all but two had periostin levels above the LLOQ including 10 healthy controls (median age [IQR], 24.5 [23–34.3]; % females, 80%) and 33 individuals with asthma (median [IQR] for age, 23 [21–28.5]; FEV1% predicted, 92 [83–95] and FEV1/FVC ratio, 0.77 [0.71–0.84]; % females, 72.7%). There was no difference in sputum periostin concentration between healthy controls and subjects with asthma (median [IQR], 0.30 [0.09–0.69] vs. 0.18 [0.06–0.45]; p = 0.51) and there was no significant association between sputum periostin levels and baseline lung function or the severity of AHR to methacholine (Table 1). There was also no association between sputum periostin concentration and baseline lung function amongst individuals with asthma (Table 1). Amongst individuals with asthma, 20 (60.6%) had a positive exercise challenge test (EIB+). Sputum periostin concentration was similar between EIB− and EIB+ asthmatics (median [IQR], 0.14 [0.06 to 0.23] vs. 0.20 [0.12 to 0.74]; p = 0.16) and did not correlate with the severity of endogenous AHR (Table 1). Airway T2 gene expression was available from 31 individuals, with 14/31 classified as T2-high according to their T2GM. Our prior analysis of this cohort found that the T2GM and individual T2 cytokines correlate with the severity of AHR.3, 4 Here, sputum periostin was non-significantly higher amongst T2-high individuals, across the full study population (median [IQR], 0.36 [0.18–0.68] vs. 0.19 [0.06–0.59], p = 0.14) and after restricting analysis to individuals","journal":"Respirology","year":2023,"id":363657,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":368503,"name":"Ryan C. Murphy","orcid":"0000-0003-0094-0003","position":1,"is_corresponding":false},{"id":384464,"name":"Ying Lai","orcid":null,"position":2,"is_corresponding":false},{"id":237282,"name":"Charles W. Frevert","orcid":"0000-0002-1037-3244","position":3,"is_corresponding":false},{"id":239696,"name":"Jason S. Debley","orcid":"0000-0001-6438-9535","position":4,"is_corresponding":false},{"id":239697,"name":"Steven F. Ziegler","orcid":"0000-0003-0657-5529","position":5,"is_corresponding":false},{"id":1118083,"name":"Kit Wong","orcid":"0000-0002-9929-500X","position":6,"is_corresponding":false},{"id":272078,"name":"Guiquan Jia","orcid":"0000-0002-0890-5037","position":7,"is_corresponding":false},{"id":369921,"name":"Cécile Holweg","orcid":"0000-0002-8983-6669","position":8,"is_corresponding":false},{"id":257942,"name":"Michael C. Peters","orcid":"0000-0003-1854-4447","position":9,"is_corresponding":false},{"id":368504,"name":"Teal S. Hallstrand","orcid":"0000-0002-5059-6872","position":10,"is_corresponding":false},{"id":696643,"name":"Taha Al‐Shaikhly","orcid":"0000-0002-1251-8937","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-19T01:14:32.510714Z","pmid":"36914406","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}