{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:26:47Z","timestamp":1790180807958,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T00:00:00Z","timestamp":1550448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570023"],"award-info":[{"award-number":["81570023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670023"],"award-info":[{"award-number":["81670023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870027"],"award-info":[{"award-number":["81870027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004602","name":"Program for New Century Excellent Talents in University","doi-asserted-by":"publisher","award":["NCET\u201012\u20100380"],"award-info":[{"award-number":["NCET\u201012\u20100380"]}],"id":[{"id":"10.13039\/501100004602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2019,6]]},"abstract":"Summary<\/jats:title>Background<\/jats:title>Depressive symptoms worsen asthma outcomes; however, the mechanism remains largely unexplored.<\/jats:p><\/jats:sec>Objective<\/jats:title>This study aimed to determine whether depressive symptom\u2010associated immune inflammation correlates with impaired bronchodilator response (BDR<\/jats:styled-content>) and airway inflammatory phenotypes.<\/jats:p><\/jats:sec>Methods<\/jats:title>Eligible adults with asthma (n\u00a0=\u00a0198) underwent clinical assessment, sputum induction and blood sampling. Depressive symptoms were defined by scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS<\/jats:styled-content>\u2010D). Pre\u2010 and post\u2010bronchodilator spirometry was performed for BDR<\/jats:styled-content>. Airway inflammatory phenotypes were defined by sputum cell counts. CRP<\/jats:styled-content>, IL<\/jats:styled-content>\u20101\u03b2, IL<\/jats:styled-content>\u20105, IL<\/jats:styled-content>\u20106, IL<\/jats:styled-content>\u20108, TNF<\/jats:styled-content>\u2010\u03b1, IFN<\/jats:styled-content>\u2010\u03b3, CCL<\/jats:styled-content>17 and CCL<\/jats:styled-content>22 in serum and sputum were detected.<\/jats:p><\/jats:sec>Results<\/jats:title>Compared with the non\u2010depressive group (n\u00a0=\u00a0174), the depressive group (n\u00a0=\u00a024) exhibited impaired BDR<\/jats:styled-content> (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.032) and increased sputum neutrophils (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.023), which correlated with the HADS<\/jats:styled-content>\u2010D scores (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.027 and P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.029). Levels of IL<\/jats:styled-content>\u20101\u03b2, TNF<\/jats:styled-content>\u2010\u03b1 and IFN<\/jats:styled-content>\u2010\u03b3 in the serum and those of IL<\/jats:styled-content>\u20101\u03b2 and IFN<\/jats:styled-content>\u2010\u03b3 in the sputum were elevated in the depressive group compared to those in the non\u2010depressive group (all P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.05). Multiple regression models indicated that TNF<\/jats:styled-content>\u2010\u03b1 in the sputum and IL<\/jats:styled-content>\u20101\u03b2, IL<\/jats:styled-content>\u20106 and IFN<\/jats:styled-content>\u2010\u03b3 in both the serum and sputum were inversely associated with BDR<\/jats:styled-content>; TNF<\/jats:styled-content>\u2010\u03b1 in the sputum and IL<\/jats:styled-content>\u20101\u03b2 in both the serum and sputum were positively correlated with sputum neutrophils. Mediation analyses revealed that IL<\/jats:styled-content>\u20101\u03b2 and TNF<\/jats:styled-content>\u2010\u03b1 in the sputum and IL<\/jats:styled-content>\u20101\u03b2 in both the serum and sputum mediate the correlations of the HADS<\/jats:styled-content>\u2010D scores with BDR<\/jats:styled-content> and sputum neutrophils, respectively.<\/jats:p><\/jats:sec>Conclusions and Clinical Relevance<\/jats:title>Asthma patients with depressive symptoms present worse asthma control, which is most likely explained by impaired BDR<\/jats:styled-content> and neutrophilic airway inflammation. IL<\/jats:styled-content>\u20101\u03b2 and TNF<\/jats:styled-content>\u2010\u03b1, which are two key pro\u2010inflammatory cytokines that mediate the correlation of depressive symptoms with impaired BDR<\/jats:styled-content> and neutrophilic airway inflammation, may serve as targeted biomarkers in the neuropsychological phenotype of asthma; however, this result needs to be further validated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13346","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T21:29:19Z","timestamp":1548365359000},"page":"770-780","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Depressive symptom\u2010associated IL<\/scp>\u20101\u03b2 and TNF<\/scp>\u2010\u03b1 release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma"],"prefix":"10.1111","volume":"49","author":[{"given":"Li","family":"Zhang","sequence":"first","affiliation":[{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine State Key Laboratory of Biotherapy Collaborative Innovation Center for Biotherapy West China Hospital Sichuan University Chengdu China"},{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine State Key Laboratory of Biotherapy Collaborative Innovation Center for Biotherapy West China Hospital Sichuan University Chengdu China"},{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine West China Hospital Sichuan University Chengdu China"},{"name":"Department of Respiratory and Critical Care Medicine Clinical Research Center for Respiratory Disease West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine Xinqiao Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine State Key Laboratory of Biotherapy Collaborative Innovation Center for Biotherapy West China Hospital Sichuan University Chengdu China"},{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Wang","sequence":"additional","affiliation":[{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine State Key Laboratory of Biotherapy Collaborative Innovation Center for Biotherapy West China Hospital Sichuan University Chengdu China"},{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine State Key Laboratory of Biotherapy Collaborative Innovation Center for Biotherapy West China Hospital Sichuan University Chengdu China"},{"name":"West China School of Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine State Key Laboratory of Biotherapy Collaborative Innovation Center for Biotherapy West China Hospital Sichuan University Chengdu China"},{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De Ying","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Evidence\u2010based Medicine and Clinical Epidemiology West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu Gui","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Psychiatry The Mental Health Center West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Lin","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Clinical Research Center for Respiratory Disease West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine State Key Laboratory of Biotherapy Collaborative Innovation Center for Biotherapy West China Hospital Sichuan University Chengdu China"},{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Gerard","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Sleep Medicine John Hunter Hospital Hunter Medical Research Institute Priority Research Centre for Healthy Lungs University of Newcastle Newcastle New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5048-6606","authenticated-orcid":false,"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine State Key Laboratory of Biotherapy Collaborative Innovation Center for Biotherapy West China Hospital Sichuan University Chengdu China"},{"name":"Pneumology Group Department of Integrated Traditional Chinese and Western Medicine West China Hospital Sichuan University Chengdu China"},{"name":"Department of Respiratory and Critical Care Medicine Clinical Research Center for Respiratory Disease West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,18]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Global Initiative for Asthma.Global Strategy for Asthma Management and Prevention Updated2018.http:\/\/www.ginasthma.org. Accessed April 10 2018."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2016.04.68"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2015.11.020"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02295-2016"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01359-2015"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01930-2015"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13370"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsb1503104"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4113"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2015.5"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2014.1332"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.57"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2016.37.3928"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1164\/ajrccm.165.8.2109065","article-title":"School examinations enhance airway inflammation to antigen challenge","volume":"165","author":"Liu LY","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200307-979OC"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.118"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1988.01800270053006"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2015.10.004"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201501-0037OC"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1752-699X.2009.00162.x"},{"key":"e_1_2_8_22_1","first-page":"A1319","article-title":"Relationships between depression and bronchodilator response and airway or systemic inflammation in asthma (abstract)","volume":"195","author":"Zhang L","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2017.04.74"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1249\/00005768-198205000-00012"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2016.09.430"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3999(01)00296-3"},{"key":"e_1_2_8_27_1","first-page":"17","article-title":"Application and assessment of hospital anxiety and depression scale in general hospital","volume":"2","author":"Ye WF","year":"1993","journal-title":"Chin J Behavioral Med Sci"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00034805"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01098-2015"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00105013"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2015.12.018"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2015.36.3897"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(90)90005-M"},{"key":"e_1_2_8_34_1","first-page":"123","volume-title":"Using Multivariate Statistics","author":"Tabachnick BG","year":"2006"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1037\/0022-3514.51.6.1173"},{"key":"e_1_2_8_36_1","first-page":"151","article-title":"Direct and indirect effects in linear structural equation\u00a0models","volume":"15","author":"Me S","year":"1987","journal-title":"Sociol Method Res"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3109\/02770903.2011.631238"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-2413"},{"issue":"759","key":"e_1_2_8_39_1","first-page":"e1","article-title":"Progression of irreversible airflow limitation in asthma: correlation with severe exacerbations","volume":"3","author":"Matsunaga K","year":"2015","journal-title":"J Allergy Clin Immunol Pract"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2010.09.007"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200707-1134OC"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.07-1047"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13003"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.07.017"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.1997.tb00720.x"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001039"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2010.06.014"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881117711708"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.09.033"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2015-0012OC"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203017"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2017.07.016"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201402-0314OC"},{"issue":"1075","key":"e_1_2_8_54_1","first-page":"e6","article-title":"Rhinovirus infection causes steroid resistance in airway epithelium through nuclear factor kappaB and c\u2010Jun N\u2010terminal kinase activation","volume":"132","author":"Papi A","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0364OC"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12810"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0129OC"},{"key":"e_1_2_8_58_1","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association","year":"1994"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3153"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60874-X"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)30048-0"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1983.tb09716.x"}],"container-title":["Clinical & Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcea.13346","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.13346","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cea.13346","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.13346","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T14:08:59Z","timestamp":1694354939000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.13346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,18]]},"references-count":61,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1111\/cea.13346"],"URL":"https:\/\/doi.org\/10.1111\/cea.13346","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,18]]},"assertion":[{"value":"2018-04-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}