{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:03:09Z","timestamp":1791421389136,"version":"4.3.3"},"reference-count":144,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Danish Regions Medical Fund &amp; Danish Council for Independent Research","award":["grant no. 5894\/16 & grant no. 6110-00268B"],"award-info":[{"award-number":["grant no. 5894\/16 & grant no. 6110-00268B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Chronic obstructive pulmonary disease (COPD) and asthma are two of the most common chronic diseases worldwide. Both diseases are heterogenous and complex, and despite their similarities, they differ in terms of pathophysiological and immunological mechanisms. Mounting evidence supports the presence of several phenotypes with various responses to treatment. A systematic and thorough assessment concerning the diagnosis of both asthma and COPD is crucial to the clinical management of the disease. The identification of different biomarkers can facilitate targeted treatment and monitoring. Thanks to the presence of numerous immunological studies, our understanding of asthma phenotypes and mechanisms of disease has increased markedly in the last decade, and several treatments with monoclonal antibodies are available. There are compelling data that link eosinophilia with an increased risk of COPD exacerbations but a greater treatment response and lower all-cause mortality. Eosinophilia can be considered as a treatable trait, and the initiation of inhaled corticosteroid in COPD patients with eosinophilia is supported in many studies. In spite of advances in our understanding of both asthma and COPD in terms pathophysiology, disease mechanisms, biomarkers, and response to treatment, many uncertainties in the management of obstructive airways exist.<\/jats:p>","DOI":"10.3390\/diagnostics11091668","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T21:37:12Z","timestamp":1631569032000},"page":"1668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Treatment Response Biomarkers in Asthma and COPD"],"prefix":"10.3390","volume":"11","author":[{"given":"Howraman","family":"Meteran","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Respiratory Medicine Section, Copenhagen University Hospital\u2014Herlev and Gentofte, 2900 Hellerup, Denmark"},{"name":"Department of Microbiology and Immunology, University of Copenhagen, 1353 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8620-3655","authenticated-orcid":false,"given":"Pradeesh","family":"Sivapalan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Respiratory Medicine Section, Copenhagen University Hospital\u2014Herlev and Gentofte, 2900 Hellerup, Denmark"},{"name":"Department of Internal Medicine, Zealand University Hospital, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4036-0521","authenticated-orcid":false,"given":"Jens-Ulrik","family":"St\u00e6hr Jensen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Respiratory Medicine Section, Copenhagen University Hospital\u2014Herlev and Gentofte, 2900 Hellerup, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, 1353 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1056\/NEJM199010113231505","article-title":"Eosinophilic Inflammation in Asthma","volume":"323","author":"Bousquet","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nri2254","article-title":"Immunology of asthma and chronic obstructive pulmonary disease","volume":"8","author":"Barnes","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.jaci.2006.02.039","article-title":"The role of the mast cell in the pathophysiology of asthma","volume":"117","author":"Bradding","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.immuni.2018.01.007","article-title":"Human T Cell Development, Localization, and Function throughout Life","volume":"48","author":"Kumar","year":"2018","journal-title":"Immunity"},{"key":"ref_5","first-page":"39","article-title":"Eosinophilic airway inflammation in COPD","volume":"1","author":"Saha","year":"2006","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1177\/2040622315609251","article-title":"Eosinophilic airway inflammation: Role in asthma and chronic obstructive pulmonary disease","volume":"7","author":"George","year":"2016","journal-title":"Ther. Adv. Chronic Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1183\/16000617.0064-2017","article-title":"Personalised medicine in asthma: Time for action: Number 1 in the Series \u201cPersonalised medicine in respiratory diseases\u201d Edited by Renaud Louis and Nicolas Roche","volume":"26","author":"Chung","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1164\/rccm.200906-0896OC","article-title":"Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program","volume":"181","author":"Moore","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1183\/13993003.00779-2015","article-title":"Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort","volume":"46","author":"Shaw","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Calv\u00e9n, J., Ax, E., and R\u00e5dinger, M. (2020). The Airway Epithelium\u2014A Central Player in Asthma Pathogenesis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21238907"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1164\/rccm.201612-2427OC","article-title":"Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in Subjects with Asthma","volume":"196","author":"Chen","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/nri954","article-title":"The lineage decisions of helper T cells","volume":"2","author":"Murphy","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Singh, V., and Agrewala, J.N. (2006). Regulatory role of pro-Th1 and pro-Th2 cytokines in modulating the activity of Th1 and Th2 cells when B cell and macrophages are used as antigen presenting cells. BMC Immunol., 7.","DOI":"10.1186\/1471-2172-7-17"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.immuni.2009.08.014","article-title":"Innate Cells and T Helper 2 Cell Immunity in Airway Inflammation","volume":"31","author":"Barrett","year":"2009","journal-title":"Immunity"},{"key":"ref_15","unstructured":"Global Initiative for Asthma (2021, January 20). Global Strategy for Asthma Management and Prevention. Available online: https:\/\/ginasthma.org\/wp-content\/uploads\/2021\/05\/GINA-Main-Report-2021-V2-WMS.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1080\/02770903.2017.1296157","article-title":"Novel monoclonal treatments in severe asthma","volume":"54","author":"Meteran","year":"2017","journal-title":"J. Asthma"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.2147\/JAA.S258594","article-title":"Anti-IL5 Therapies for Severe Eosinophilic Asthma: Literature Review and Practical Insights","volume":"13","author":"Menzella","year":"2020","journal-title":"J. Asthma Allergy"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jaip.2019.08.050","article-title":"Dupilumab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Allergic Asthma","volume":"8","author":"Corren","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jaci.2010.03.026","article-title":"Eosinophil protein in airway macrophages: A novel biomarker of eosinophilic inflammation in patients with asthma","volume":"126","author":"Kulkarni","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/j.jaci.2013.09.036","article-title":"Lysis of primed eosinophils in severe asthma","volume":"132","author":"Persson","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1034\/j.1399-3003.2000.15e26.x","article-title":"Airway smooth muscle cells: Contributing to and regulating airway mucosal inflammation?","volume":"15","author":"Chung","year":"2000","journal-title":"Eur. Respir. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1183\/09031936.00201813","article-title":"Importance of concomitant local and systemic eosinophilia in uncontrolled asthma","volume":"44","author":"Schleich","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.anai.2020.04.025","article-title":"Predictive factors of response to inhaled corticosteroids in newly diagnosed asthma: A real-world observational study","volume":"125","author":"Rhyou","year":"2020","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0091-6749(97)70082-4","article-title":"Measuring airway inflammation in asthma: Eosinophils and eosinophilic cationic protein in induced sputum compared with peripheral blood","volume":"99","author":"Pizzichini","year":"1997","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jaci.2013.03.044","article-title":"Biomarker surrogates do not accurately predict sputum eosinophil and neutrophil percentages in asthmatic subjects","volume":"132","author":"Hastie","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1136\/thoraxjnl-2014-205634","article-title":"External validation of blood eosinophils, FENOand serum periostin as surrogates for sputum eosinophils in asthma","volume":"70","author":"Wagener","year":"2015","journal-title":"Thorax"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12931-019-1111-1","article-title":"Do blood eosinophils strictly reflect airway inflammation in COPD? Comparison with asthmatic patients","volume":"20","author":"Pignatti","year":"2019","journal-title":"Respir. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S2213-2600(17)30432-0","article-title":"Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: An analysis of the SPIROMICS cohort","volume":"5","author":"Hastie","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2000838","DOI":"10.1183\/13993003.00838-2020","article-title":"High eosinophil counts predict decline in FEV1: Results from the CanCOLD study","volume":"57","author":"Tan","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S2213-2600(15)00367-7","article-title":"Blood eosinophil count and prospective annual asthma disease burden: A UK cohort study","volume":"3","author":"Price","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.chest.2016.01.026","article-title":"Blood Eosinophils and Outcomes in Severe Hospitalized Exacerbations of COPD","volume":"150","author":"Bafadhel","year":"2016","journal-title":"Chest"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1513\/AnnalsATS.201310-354OC","article-title":"Blood Eosinophil Count Is a Useful Biomarker to Identify Patients with Severe Eosinophilic Asthma","volume":"11","author":"Katz","year":"2014","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S2213-2600(18)30006-7","article-title":"Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: A post-hoc analysis of three randomised trials","volume":"6","author":"Bafadhel","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1016\/S0140-6736(16)31322-8","article-title":"Benralizumab, an anti-interleukin-5 receptor \u03b1 monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): A randomised, double-blind, placebo-controlled phase 3 trial","volume":"388","author":"FitzGerald","year":"2016","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S2213-2600(16)30031-5","article-title":"Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: A secondary analysis of the DREAM and MENSA studies","volume":"4","author":"Ortega","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.chest.2016.03.018","article-title":"Phase 3 Study of Reslizumab in Patients With Poorly Controlled Asthma: Effects Across a Broad Range of Eosinophil Counts","volume":"150","author":"Corren","year":"2016","journal-title":"Chest"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Chipps, B.E., Jarjour, N., Calhoun, W.J., Iqbal, A., Haselkorn, T., Yang, M., Brumm, J., Corren, J., Holweg, C.T., and Bafadhel, M. (2021). A Comprehensive Analysis of the Stability of Blood Eosinophil Levels. Ann. Am. Thorac. Soc., Online ahead of print.","DOI":"10.1513\/AnnalsATS.202010-1249OC"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.2147\/COPD.S100338","article-title":"Peripheral blood eosinophils: A surrogate marker for airway eosinophilia in stable COPD","volume":"11","author":"Negewo","year":"2016","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jaci.2004.12.1129","article-title":"Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids","volume":"115","author":"Deykin","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/j.1440-1843.2007.01222.x","article-title":"Predictors for failed dose reduction of inhaled corticosteroids in childhood asthma","volume":"13","author":"Li","year":"2008","journal-title":"Respirology"},{"key":"ref_41","first-page":"CD005603","article-title":"Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults","volume":"8","author":"Petsky","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e018186","DOI":"10.1136\/bmjopen-2017-018186","article-title":"Effectiveness of inhaled corticosteroids in real life on clinical outcomes, sputum cells and systemic inflammation in asthmatics: A retrospective cohort study in a secondary care centre","volume":"7","author":"Demarche","year":"2017","journal-title":"BMJ Open"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2004098","DOI":"10.1183\/13993003.040982020","article-title":"BDP\/formoterol MART asthma exacerbation benefit increases with blood eosinophil level","volume":"58","author":"Brusselle","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"106156","DOI":"10.1016\/j.rmed.2020.106156","article-title":"The effects of oral corticosteroids on lung function, type-2 biomarkers and patient-reported outcomes in stable asthma: A systematic review and meta-analysis","volume":"173","author":"Busby","year":"2020","journal-title":"Respir. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/thoraxjnl-2018-212709","article-title":"Change in type-2 biomarkers and related cytokines with prednisolone in uncontrolled severe oral corticosteroid dependent asthmatics: An interventional open-label study","volume":"74","author":"Busby","year":"2019","journal-title":"Thorax"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S2213-2600(17)30344-2","article-title":"Predictors of enhanced response with benralizumab for patients with severe asthma: Pooled analysis of the SIROCCO and CALIMA studies","volume":"6","author":"FitzGerald","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S2213-2600(15)00042-9","article-title":"Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: Results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials","volume":"3","author":"Castro","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.chest.2016.03.032","article-title":"Reslizumab for Inadequately Controlled Asthma with Elevated Blood Eosinophil Levels: A Randomized Phase 3 Study","volume":"150","author":"Bjermer","year":"2016","journal-title":"Chest"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1136\/thx.2003.014894","article-title":"Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath","volume":"59","author":"Lane","year":"2004","journal-title":"Thorax"},{"key":"ref_50","first-page":"1391","article-title":"NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid-dependent childhood asthma","volume":"13","author":"Mattes","year":"1999","journal-title":"Eur. Respir. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.2147\/COPD.S167600","article-title":"Clinical utility of fractional exhaled nitric oxide and blood eosinophils counts in the diagnosis of asthma-COPD overlap","volume":"13","author":"Takayama","year":"2018","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_52","first-page":"239","article-title":"Comparison of exhaled nitric oxide measurement with conventional tests in steroid-naive asthma patients","volume":"16","author":"Zietkowski","year":"2006","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.jaci.2010.08.028","article-title":"Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide: A random-sample population study","volume":"126","author":"Sverrild","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1164\/rccm.9120-11ST","article-title":"An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications","volume":"184","author":"Dweik","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1465-9921-8-82","article-title":"Factors affecting exhaled nitric oxide measurements: The effect of sex","volume":"8","author":"Taylor","year":"2007","journal-title":"Respir. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4193\/Rhin17.111","article-title":"Exhaled and nasal nitric oxide in chronic rhinosinusitis patients with nasal polyps in primary care","volume":"56","author":"Hakansson","year":"2018","journal-title":"Rhinol. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"731","DOI":"10.2147\/JAA.S289592","article-title":"Annual Fractional Exhaled Nitric Oxide Measurements and Exacerbations in Severe Asthma","volume":"13","author":"Abe","year":"2020","journal-title":"J. Asthma Allergy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1111\/cea.13170","article-title":"Prospective predictors of exacerbation status in severe asthma over a 3-year follow-up","volume":"48","author":"Kimura","year":"2018","journal-title":"Clin. Exp. Allergy"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1136\/thx.54.5.403","article-title":"Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma","volume":"54","author":"Straathof","year":"1999","journal-title":"Thorax"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1183\/09031936.02.01582001","article-title":"Changes of exhaled nitric oxide during steroid treatment of childhood asthma","volume":"19","author":"Griese","year":"2002","journal-title":"Eur. Respir. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S2213-2600(17)30424-1","article-title":"Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility: A randomised controlled trial","volume":"6","author":"Price","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0140-6736(11)60971-9","article-title":"Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: A double-blind, randomised controlled trial","volume":"378","author":"Powell","year":"2011","journal-title":"Lancet"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"00147-02017","DOI":"10.1183\/23120541.00147-2017","article-title":"FeNO-based asthma management results in faster improvement of airway hyperresponsiveness","volume":"4","author":"Bernholm","year":"2018","journal-title":"ERJ Open Res."},{"key":"ref_64","first-page":"CD011440","article-title":"Exhaled nitric oxide levels to guide treatment for adults with asthma","volume":"9","author":"Petsky","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(67)90792-1","article-title":"Raised levels of a new immunoglobulin class (ignd) in asthma","volume":"290","author":"Johansson","year":"1967","journal-title":"Lancet"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1111\/j.1365-2222.2006.02525.x","article-title":"Total serum immunoglobulin E levels in a case\u2013control study in asthmatic\/allergic patients, their family members, and healthy subjects from India","volume":"36","author":"Sharma","year":"2006","journal-title":"Clin. Exp. Allergy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1164\/ajrccm.152.1.7599870","article-title":"Longitudinal evaluation of the association between pulmonary function and total serum IgE","volume":"152","author":"Sherrill","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2147\/COPD.S16383","article-title":"Lower FEV1 in non-COPD, nonasthmatic subjects: Association with smoking, annual decline in FEV1, total IgE levels, and TSLP genotypes","volume":"6","author":"Hizawa","year":"2011","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/0091-6749(78)90134-3","article-title":"The effects of acute corticosteroid therapy for asthma on serum immunoglobulin levels","volume":"62","author":"Posey","year":"1978","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.jaip.2015.01.023","article-title":"Markers of Differential Response to Inhaled Corticosteroid Treatment Among Children with Mild Persistent Asthma","volume":"3","author":"Gerald","year":"2015","journal-title":"J. Allergy Clin. Immunol. Pr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1067\/mai.2001.117880","article-title":"Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma","volume":"108","author":"Busse","year":"2001","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1080\/1744666X.2020.1676731","article-title":"SQ house dust mite sublingual immunotherapy for the treatment of adults with house dust mite-induced allergic rhinitis","volume":"15","author":"Meteran","year":"2019","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"AB16","DOI":"10.1016\/j.jaci.2015.12.050","article-title":"Response to Omalizumab Therapy Based on Level of IgE: A Two Year Observational Study (REALITY Study)","volume":"137","author":"Peters","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1111\/all.13345","article-title":"The clinical response to omalizumab in chronic spontaneous urticaria patients is linked to and predicted by IgE levels and their change","volume":"73","author":"Ertas","year":"2017","journal-title":"Allergy"},{"key":"ref_75","first-page":"266","article-title":"Omalizumab in asthmatics with IgE levels > 700 IU\/mL","volume":"38","author":"Maselli","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1164\/ajrccm.155.6.9196083","article-title":"Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response","volume":"155","author":"Boulet","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1056\/NEJM199912233412603","article-title":"Treatment of allergic asthma with monoclonal anti-IgE antibody. rhuMAb-E25 Study Group","volume":"341","author":"Milgrom","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1016\/j.rmed.2007.01.011","article-title":"Predicting and evaluating response to omalizumab in patients with severe allergic asthma","volume":"101","author":"Bousquet","year":"2007","journal-title":"Respir. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.jaci.2011.11.029","article-title":"Reduction of total IgE by targeted coengagement of IgE B-cell receptor and Fc\u03b3RIIb with Fc-engineered antibody","volume":"129","author":"Chu","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/j.1365-2125.2011.03962.x","article-title":"Omalizumab decreases IgE production in patients with allergic (IgE-mediated) asthma; PKPD analysis of a biomarker, total IgE","volume":"72","author":"Lowe","year":"2011","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jaci.2005.04.003","article-title":"Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity","volume":"116","author":"Reisinger","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/S0955-0674(02)00361-7","article-title":"Matricellular proteins: Extracellular modulators of cell function","volume":"14","author":"Bornstein","year":"2002","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1111\/all.13814","article-title":"Periostin: An emerging biomarker for allergic diseases","volume":"74","author":"Izuhara","year":"2019","journal-title":"Allergy"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1080\/02770903.2018.1455855","article-title":"Serum periostin levels serve as a biomarker for both eosinophilic airway inflammation and fixed airflow limitation in well-controlled asthmatics","volume":"56","author":"Takahashi","year":"2018","journal-title":"J. Asthma"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/resp.12687","article-title":"Effect of treatment with inhaled corticosteroid on serum periostin levels in asthma","volume":"21","author":"Hoshino","year":"2015","journal-title":"Respirology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.rmed.2018.08.005","article-title":"Disconnect of type 2 biomarkers in severe asthma; dominated by FeNO as a predictor of exacerbations and periostin as predictor of reduced lung function","volume":"143","author":"Mansur","year":"2018","journal-title":"Respir. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1056\/NEJMoa1106469","article-title":"Lebrikizumab Treatment in Adults with Asthma","volume":"365","author":"Corren","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S2213-2600(15)00197-6","article-title":"Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: A randomised, double-blind, placebo-controlled, phase 2b trial","volume":"3","author":"Brightling","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1164\/rccm.201109-1640OC","article-title":"A Large Subgroup of Mild-to-Moderate Asthma Is Persistently Noneosinophilic","volume":"185","author":"McGrath","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1136\/thx.2006.073429","article-title":"Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma","volume":"62","author":"Berry","year":"2007","journal-title":"Thorax"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/all.13985","article-title":"Mechanisms and therapeutic strategies for non-T2 asthma","volume":"75","author":"Sze","year":"2020","journal-title":"Allergy"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1901846","DOI":"10.1183\/13993003.01846-2019","article-title":"Neutrophilic asthma: Welcome back!","volume":"54","author":"Gibson","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1164\/ajrccm.161.2.9903097","article-title":"Induced Sputum Cell Counts in Healthy Adults","volume":"161","author":"Belda","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/MCP.0000000000000120","article-title":"Therapeutic implications of \u2018neutrophilic asthma\u2019","volume":"21","author":"Nair","year":"2015","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/resp.12079","article-title":"Relationship between airway neutrophilia and ageing in asthmatics and non-asthmatics","volume":"18","author":"Brooks","year":"2013","journal-title":"Respirology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1136\/thoraxjnl-2020-215986","article-title":"Neutrophils in asthma: The good, the bad and the bacteria","volume":"76","author":"Crisford","year":"2021","journal-title":"Thorax"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1378\/chest.120.6.1917","article-title":"Smoking and Airway Inflammation in Patients With Mild Asthma","volume":"120","author":"Chalmers","year":"2001","journal-title":"Chest"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1111\/j.1398-9995.2012.02855.x","article-title":"Obesity in asthma: More neutrophilic inflammation as a possible explanation for a reduced treatment response","volume":"67","author":"Telenga","year":"2012","journal-title":"Allergy"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1136\/thx.54.12.1061","article-title":"Effect of inhaled ozone on exhaled nitric oxide, pulmonary function, and induced sputum in normal and asthmatic subjects","volume":"54","author":"Nightingale","year":"1999","journal-title":"Thorax"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1016\/S0140-6736(14)60617-6","article-title":"Outdoor air pollution and asthma","volume":"383","author":"Guarnieri","year":"2014","journal-title":"Lancet"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1183\/09031936.00170110","article-title":"Different inflammatory phenotypes in adults and children with acute asthma","volume":"38","author":"Wang","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.jaci.2018.12.985","article-title":"Lower Airway Microbiota Associates with Inflammatory Phenotype in Severe Preschool Wheeze","volume":"143","author":"Robinson","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jaci.2017.03.044","article-title":"Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology","volume":"141","author":"Taylor","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1164\/rccm.200510-1589OC","article-title":"Effects of Smoking Cessation on Lung Function and Airway Inflammation in Smokers with Asthma","volume":"174","author":"Chaudhuri","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1183\/09031936.00053413","article-title":"Effects of weight loss on asthma control in obese patients with severe asthma","volume":"43","author":"Reis","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2147\/JAA.S153097","article-title":"Non-eosinophilic asthma: Current perspectives","volume":"11","author":"Quirce","year":"2018","journal-title":"J. Asthma Allergy"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1089\/omi.2012.0104","article-title":"Systemic Inflammation Is Associated with Differential Gene Expression and Airway Neutrophilia in Asthma","volume":"17","author":"Fu","year":"2013","journal-title":"OMICS"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0140-6736(17)31281-3","article-title":"Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): A randomised, double-blind, placebo-controlled trial","volume":"390","author":"Gibson","year":"2017","journal-title":"Lancet"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1111\/all.14768","article-title":"Sputum TNF markers are increased in neutrophilic and severe asthma and are reduced by azithromycin treatment","volume":"76","author":"Niessen","year":"2021","journal-title":"Allergy"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1164\/rccm.201509-1869OC","article-title":"Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease. The Copenhagen General Population Study","volume":"193","author":"Nielsen","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.chest.2016.10.003","article-title":"Eosinophils in COPD Exacerbations Are Associated With Increased Readmissions","volume":"151","author":"Couillard","year":"2017","journal-title":"Chest"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.jaip.2017.10.004","article-title":"Relationship of Blood Eosinophil Count to Exacerbations in Chronic Obstructive Pulmonary Disease","volume":"6","author":"Zeiger","year":"2018","journal-title":"J. Allergy Clin. Immunol. Pr."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1016\/j.jaci.2018.04.010","article-title":"Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease","volume":"141","author":"Yun","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.2147\/COPD.S90330","article-title":"The utility of inflammatory markers to predict readmissions and mortality in COPD cases with or without eosinophilia","volume":"10","author":"Duman","year":"2015","journal-title":"Int. J. Chron. Obs. Pulmon. Dis."},{"key":"ref_115","first-page":"CD001288","article-title":"Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease","volume":"9","author":"Walters","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"j1415","DOI":"10.1136\/bmj.j1415","article-title":"Short term use of oral corticosteroids and related harms among adults in the United States: Population based cohort study","volume":"357","author":"Waljee","year":"2017","journal-title":"BMJ"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1164\/rccm.201108-1553OC","article-title":"Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: A randomized placebo-controlled trial","volume":"186","author":"Bafadhel","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S2213-2600(19)30176-6","article-title":"Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation.(CORTICO-COP): A multicentre, randomised, controlled, open-label, non-inferiority trial","volume":"7","author":"Sivapalan","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1164\/rccm.201701-0218PP","article-title":"Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary","volume":"195","author":"Vogelmeier","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_120","first-page":"CD010115","article-title":"Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease","volume":"2014","author":"Kew","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1183\/09031936.06.00043005","article-title":"Low-dose inhaled and nasal corticosteroid use and the risk of cataracts","volume":"27","author":"Ernst","year":"2006","journal-title":"Eur. Respir. J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1136\/bjo.87.10.1247","article-title":"A population based case-control study of cataract and inhaled corticosteroids","volume":"87","author":"Smeeth","year":"2003","journal-title":"Br. J. Ophthalmol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1056\/NEJMoa1713901","article-title":"Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD","volume":"378","author":"Lipson","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1164\/rccm.201612-2525LE","article-title":"Eosinophilia, Frequent Exacerbations, and Steroid Response in Chronic Obstructive Pulmonary Disease","volume":"196","author":"Calverley","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1900164","DOI":"10.1183\/13993003.00164-2019","article-title":"Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: The GOLD science committee report 2019","volume":"53","author":"Singh","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1136\/thoraxjnl-2015-207021","article-title":"Blood eosinophils and inhaled corticosteroid\/long-acting \u03b2-2 agonist efficacy in COPD","volume":"71","author":"Pavord","year":"2016","journal-title":"Thorax"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.2147\/COPD.S179425","article-title":"Blood eosinophils: A biomarker of COPD exacerbation reduction with inhaled corticosteroids","volume":"13","author":"Siddiqui","year":"2018","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1164\/rccm.201803-0405OC","article-title":"Long-Term Triple Therapy De-escalation to Indacaterol\/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial","volume":"198","author":"Chapman","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1056\/NEJMoa1407154","article-title":"Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD","volume":"371","author":"Magnussen","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/S2213-2600(16)00100-4","article-title":"Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: A post-hoc analysis of the WISDOM trial","volume":"4","author":"Watz","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_131","unstructured":"(2021, January 20). Eosinophil-guided Reduction of Inhaled Corticosteroids (COPERNICOS), Available online: https:\/\/.ClinicalTrials.gov\/show\/NCT04481555."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1056\/NEJMoa1708208","article-title":"Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease","volume":"377","author":"Pavord","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S2213-2600(14)70187-0","article-title":"Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: A randomised, double-blind, placebo-controlled, phase 2a study","volume":"2","author":"Brightling","year":"2014","journal-title":"Lancet Respir. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/0140-6736(93)90277-N","article-title":"High serum procalcitonin concentrations in patients with sepsis and infection","volume":"341","author":"Assicot","year":"1993","journal-title":"Lancet"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.ccm.2008.07.001","article-title":"Biomarkers: Diagnosis and Risk Assessment in Sepsis","volume":"29","author":"Ventetuolo","year":"2008","journal-title":"Clin. Chest Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.2147\/IDR.S173867","article-title":"Antibiotic resistance: A rundown of a global crisis","volume":"11","author":"Aslam","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"100","DOI":"10.5455\/msm.2012.24.100-105","article-title":"Asthma and Chronic Obstructive Pulmonary Disease (Copd) and #8211; Differences and Similarities","volume":"24","author":"Cukic","year":"2012","journal-title":"Mater. Socio Medica"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1001\/jamainternmed.2016.5651","article-title":"Estimating National Trends in Inpatient Antibiotic Use Among US Hospitals From 2006 to 2012","volume":"176","author":"Baggs","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Tang, J., Long, W., Yan, L., Zhang, Y., Xie, J., Lu, G., and Yang, C. (2013). Procalcitonin guided antibiotic therapy of acute exacerbations of asthma: A randomized controlled trial. BMC Infect. Dis., 13.","DOI":"10.1186\/1471-2334-13-596"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1186\/s13054-014-0471-7","article-title":"Procalcitonin guidance for reduction of antibiotic use in patients hospitalized with severe acute exacerbations of asthma: A randomized controlled study with 12-month follow-up","volume":"18","author":"Long","year":"2014","journal-title":"Crit. Care"},{"key":"ref_141","first-page":"57","article-title":"Evaluation of Systemic Corticosteroids in Patients With an Acute Exacerbation of COPD and a Diagnosis of Pneumonia","volume":"5","author":"Scholl","year":"2018","journal-title":"Chronic Obstr. Pulm. Dis. J. COPD Found."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jaci.2016.05.011","article-title":"Inflammatory mechanisms in patients with chronic obstructive pulmonary disease","volume":"138","author":"Barnes","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S1473-3099(17)30592-3","article-title":"Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: A patient level meta-analysis","volume":"18","author":"Schuetz","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_144","first-page":"CD007498","article-title":"Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections","volume":"10","author":"Schuetz","year":"2017","journal-title":"Cochrane Database Syst. Rev."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/9\/1668\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:01:31Z","timestamp":1760166091000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/9\/1668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,13]]},"references-count":144,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["diagnostics11091668"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11091668","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,13]]}}}