{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:05:52Z","timestamp":1740146752627,"version":"3.37.3"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The U4 Network"},{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","award":["20150609"],"award-info":[{"award-number":["20150609"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bror Hjerpstedts stiftelse"},{"DOI":"10.13039\/501100007051","name":"Uppsala Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009230","name":"Landstinget i Uppsala l\u00e4n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Rationale<\/jats:title>\n<jats:p>Fixed airflow obstruction (FAO) can complicate asthma. Inflammation is a proposed underlying mechanism.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Our aim in this cross-sectional investigation was to evaluate the blood leucocyte pattern and level of exhaled nitric oxide in asthmatics and non-asthmatics with or without FAO.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A total of 11,579 individuals aged \u226520 years from the US National Health and Nutrition Examination Survey were included. They were grouped as: controls without asthma and FAO (n = 9,935), asthmatics without FAO (n = 674), asthmatics with FAO (n = 180) and non-asthmatics with FAO (n = 790). FAO was defined as post-bronchodilator FEV1\/FVC &lt; lower limit of normal. Exhaled nitric oxide \u2265 25ppb, blood eosinophil levels \u2265300 cells\/\u03bcL, and blood neutrophil levels \u22655100 cells\/\u03bcL were defined as elevated. Stratified analyses for smoking and smoking history were performed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Elevated blood eosinophil levels were more common in all groups compared to the controls, with the highest prevalence in the group with asthma and fixed airflow obstruction (p&lt;0.01). In a multiple logistic regression model adjusted for potential confounders including smoking, the asthma groups had significantly higher odds ratios for elevated B-Eos levels compared to the control group (odds ratio 1.4, (confidence interval: 1.1\u20131.7) for the asthma group without fixed airflow obstruction and 2.5 (1.4\u20134.2) for the asthma group with fixed airflow obstruction). The group with fixed airflow obstruction without asthma had higher odds ratio for elevated blood neutrophil levels compared to the controls: 1.4 (1.1\u20131.8). Smoking and a history of smoking were associated to elevated B-Neu levels.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Fixed airflow obstruction in asthma was associated with elevated blood eosinophil levels, whereas fixed airflow obstruction without asthma was associated with elevated blood neutrophil levels.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0243109","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T19:09:52Z","timestamp":1607022592000},"page":"e0243109","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inflammatory patterns in fixed airflow obstruction are dependent on the presence of asthma"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0198-2718","authenticated-orcid":true,"given":"Ida","family":"Mogensen","sequence":"first","affiliation":[]},{"given":"Tiago","family":"Jacinto","sequence":"additional","affiliation":[]},{"given":"Kjell","family":"Alving","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o A.","family":"Fonseca","sequence":"additional","affiliation":[]},{"given":"Christer","family":"Janson","sequence":"additional","affiliation":[]},{"given":"Andrei","family":"Malinovschi","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"issue":"3","key":"pone.0243109.ref001","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/all.13323","article-title":"Airway pathology in severe asthma is related to airflow obstruction but not symptom control","volume":"73","author":"DS Ferreira","year":"2018","journal-title":"Allergy"},{"issue":"5","key":"pone.0243109.ref002","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.jaci.2007.06.031","article-title":"Asthma therapy and airway remodeling","volume":"120","author":"T Mauad","year":"2007","journal-title":"J Allergy Clin Immunol"},{"issue":"9823","key":"pone.0243109.ref003","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/S0140-6736(11)60968-9","article-title":"Chronic obstructive pulmonary disease","volume":"379","author":"M Decramer","year":"2012","journal-title":"Lancet"},{"issue":"5","key":"pone.0243109.ref004","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1164\/ajrccm.164.5.2011026","article-title":"Factors Associated with Persistent Airflow Limitation in Severe Asthma","volume":"164","author":"A ten Brinke","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"issue":"8","key":"pone.0243109.ref005","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1164\/rccm.2201011","article-title":"Determinants of maximally attained level of pulmonary function","volume":"169","author":"X Wang","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"pone.0243109.ref006","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.02536-2017","article-title":"Associations between blood eosinophils and decline in lung function among adults with and without asthma","volume":"51","author":"RJ Hancox","year":"2018","journal-title":"Eur Respir J"},{"issue":"2","key":"pone.0243109.ref007","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01785-2017","article-title":"Predictors of accelerated decline in lung function in adult-onset asthma","volume":"51","author":"H Coumou","year":"2018","journal-title":"Eur Respir J"},{"issue":"11","key":"pone.0243109.ref008","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.rmed.2015.09.009","article-title":"Persistent airflow obstruction in patients with asthma: Characteristics of a distinct clinical phenotype","volume":"109","author":"E Konstantellou","year":"2015","journal-title":"Respir Med"},{"issue":"6","key":"pone.0243109.ref009","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaip.2018.03.004","article-title":"Type 2 Biomarkers and Prediction of Future Exacerbations and Lung Function Decline in Adult Asthma","volume":"6","author":"R Semprini","year":"2018","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"4","key":"pone.0243109.ref010","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1183\/13993003.00336-2016","article-title":"Blood granulocyte patterns as predictors of asthma phenotypes in adults from the EGEA study","volume":"48","author":"R Nadif","year":"2016","journal-title":"Eur Respir J"},{"issue":"5","key":"pone.0243109.ref011","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1164\/ajrccm\/143.5_Pt_1.987","article-title":"Blood eosinophilia and FEV1. Cross-sectional and longitudinal analyses","volume":"143","author":"C Frette","year":"1991","journal-title":"Am Rev Respir Dis"},{"key":"pone.0243109.ref012","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.pmedr.2016.08.009","article-title":"Current cigarette smoking is a reversible cause of elevated white blood cell count: Cross-sectional and longitudinal studies","volume":"4","author":"T Higuchi","year":"2016","journal-title":"Prev Med Rep"},{"issue":"6","key":"pone.0243109.ref013","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":"GW Chalmers","year":"2001","journal-title":"Chest"},{"key":"pone.0243109.ref014","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.rmed.2018.03.036","article-title":"Chronic airway obstruction in a population-based adult asthma cohort: Prevalence, incidence and prognostic factors","volume":"138","author":"H Backman","year":"2018","journal-title":"Respir Med"},{"key":"pone.0243109.ref015","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.rmed.2018.07.011","article-title":"Systemic inflammatory markers in relation to lung function in NHANES. 2007\u20132010","volume":"142","author":"E Nerpin","year":"2018","journal-title":"Respir Med"},{"key":"pone.0243109.ref016","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":"AH Mansur","year":"2018","journal-title":"Respir Med"},{"issue":"2","key":"pone.0243109.ref017","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/cea.13302","article-title":"Fixed airflow obstruction relates to eosinophil activation in asthmatics","volume":"49","author":"I Mogensen","year":"2019","journal-title":"Clin Exp Allergy"},{"key":"pone.0243109.ref018","unstructured":"NHANES. Centers for Disease Control and Prevention (CDC). National Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey Data. Hyattsville, MD: U.S.: Department of Health and Human Services, Centers for Disease Control and Prevention; 2008\u20132012 [2018-10-23]. Available from: https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/continuousnhanes\/overviewquex.aspx?BeginYear=2011; https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/continuousnhanes\/overviewquex.aspx?BeginYear=2009; https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/continuousnhanes\/overviewquex.aspx?BeginYear=2007. (accessed 2018-10-23)"},{"issue":"3","key":"pone.0243109.ref019","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1164\/ajrccm.152.3.7663792","article-title":"Standardization of Spirometry, 1994 Update. American Thoracic Society","volume":"152","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"pone.0243109.ref020","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1164\/ajrccm.159.1.9712108","article-title":"Spirometric Reference Values from a Sample of the General U.S. Population","volume":"159","author":"JL Hankinson","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"pone.0243109.ref021","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1378\/chest.09-0919","article-title":"Performance of american thoracic society-recommended spirometry reference values in a multiethnic sample of adults: The multi-ethnic study of atherosclerosis (mesa) lung study","volume":"137","author":"JL Hankinson","year":"2010","journal-title":"Chest"},{"key":"pone.0243109.ref022","unstructured":"National Health and Nutrition Examination Survey https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/ResponseRates.aspx2015 [Available from: http:\/\/www.cdc.gov\/nchs\/nhanes\/about_nhanes.htm. (accessed 2019-10-22)."},{"issue":"8","key":"pone.0243109.ref023","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1111\/cea.13137","article-title":"Simultaneously elevated FeNO and blood eosinophils relate to asthma morbidity in asthmatics from NHANES 2007\u201312","volume":"48","author":"I Mogensen","year":"2018","journal-title":"Clin Exp Allergy"},{"issue":"2","key":"pone.0243109.ref024","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1093\/aje\/kwn301","article-title":"Optimal serum cotinine levels for distinguishing cigarette smokers and nonsmokers within different racial\/ethnic groups in the United States between 1999 and 2004","volume":"169","author":"NL Benowitz","year":"2009","journal-title":"Am J Epidemiol"},{"issue":"5","key":"pone.0243109.ref025","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":"RA Dweik","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"pone.0243109.ref026","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1136\/jcp.27.1.55","article-title":"Normal laboratory values for differential white cell counts established by manual and automated cytochemical methods (Hemalog D-TM)","volume":"27","author":"A Simmons","year":"1974","journal-title":"J Clin Pathol"},{"issue":"1","key":"pone.0243109.ref027","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.anai.2014.04.011","article-title":"High blood eosinophil count is associated with more frequent asthma attacks in asthma patients","volume":"113","author":"TN Tran","year":"2014","journal-title":"Ann Allergy Asthma Immunol"},{"key":"pone.0243109.ref028","unstructured":"NHANES. National Health and Nutrition Examination Survey: Analytic Guidelines, 2011\u20132012 2012 [Available from: https:\/\/wwwn.cdc.gov\/nchs\/data\/nhanes\/2011-2012\/analytic_guidelines_11_12.pdf (accessed 20191022)."},{"issue":"4","key":"pone.0243109.ref029","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaci.2013.06.007","article-title":"Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects","volume":"132","author":"A Malinovschi","year":"2013","journal-title":"J Allergy Clin Immunol"},{"issue":"11","key":"pone.0243109.ref030","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1046\/j.1365-2222.2003.01730.x","article-title":"Effects of asthma on cell components in peripheral blood among smokers and non-smokers","volume":"33","author":"J Sunyer","year":"2003","journal-title":"Clin Exp Allergy"},{"key":"pone.0243109.ref031","article-title":"Both exhaled nitric oxide and blood eosinophil count were associated with mild allergic asthma only in non-smokers","author":"J Giovannelli","year":"2015","journal-title":"Clin Exp Allergy"},{"issue":"3","key":"pone.0243109.ref032","doi-asserted-by":"crossref","first-page":"036005","DOI":"10.1088\/1752-7155\/9\/3\/036005","article-title":"Evolution of exhaled nitric oxide levels throughout development and aging of healthy humans","volume":"9","author":"T Jacinto","year":"2015","journal-title":"J Breath Res"},{"issue":"3","key":"pone.0243109.ref033","doi-asserted-by":"crossref","first-page":"036006","DOI":"10.1088\/1752-7163\/aa746b","article-title":"Differential effect of cigarette smoke exposure on exhaled nitric oxide and blood eosinophils in healthy and asthmatic individuals","volume":"11","author":"T Jacinto","year":"2017","journal-title":"J Breath Res"},{"issue":"2","key":"pone.0243109.ref034","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3109\/15412555.2013.836166","article-title":"Respiratory viral detection and small airway inflammation in lung tissue of patients with stable, mild COPD","volume":"11","author":"S Utokaparch","year":"2014","journal-title":"Copd"},{"issue":"2","key":"pone.0243109.ref035","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1164\/ajrccm.152.2.7543345","article-title":"Acute and chronic effects of cigarette smoking on exhaled nitric oxide","volume":"152","author":"SA Kharitonov","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"issue":"5","key":"pone.0243109.ref036","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1378\/chest.130.5.1319","article-title":"HEight, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample*","volume":"130","author":"A-C Olin","year":"2006","journal-title":"Chest"},{"issue":"8","key":"pone.0243109.ref037","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":"ED Telenga","year":"2012","journal-title":"Allergy"},{"issue":"6","key":"pone.0243109.ref038","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1164\/rccm.201208-1470OC","article-title":"Elevated sputum interleukin-5 and submucosal eosinophilia in obese individuals with severe asthma","volume":"188","author":"D Desai","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"pone.0243109.ref039","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1183\/09031936.00139810","article-title":"Airway inflammation is augmented by obesity and fatty acids in asthma","volume":"38","author":"HA Scott","year":"2011","journal-title":"Eur Respir J"},{"issue":"1","key":"pone.0243109.ref040","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1152\/japplphysiol.00694.2009","article-title":"Physiology of obesity and effects on lung function","volume":"108","author":"CM Salome","year":"2010","journal-title":"J Appl Physiol (1985"},{"issue":"1","key":"pone.0243109.ref041","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1152\/japplphysiol.00482.2019","article-title":"Obesity alters the topographical distribution of ventilation and the regional response to bronchoconstriction","volume":"128","author":"S Rutting","year":"2020","journal-title":"J Appl Physiol (1985)"},{"issue":"11","key":"pone.0243109.ref042","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1111\/resp.13312","article-title":"Predictive value of eosinophils and neutrophils on clinical effects of ICS in COPD","volume":"23","author":"FJ Hartjes","year":"2018","journal-title":"Respirology"},{"issue":"12","key":"pone.0243109.ref043","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1016\/j.rmed.2014.10.007","article-title":"Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR)","volume":"108","author":"F Schleich","year":"2014","journal-title":"Respir Med"},{"issue":"2","key":"pone.0243109.ref044","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1183\/09031936.98.12020380","article-title":"Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease","volume":"12","author":"A Pesci","year":"1998","journal-title":"Eur Respir J"},{"issue":"1","key":"pone.0243109.ref045","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1183\/09031936.00.15110900","article-title":"Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD","volume":"15","author":"SR Rutgers","year":"2000","journal-title":"Eur Respir J"},{"issue":"7","key":"pone.0243109.ref046","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/cea.13143","article-title":"Remodelling and inflammation in preschoolers with severe recurrent wheeze and asthma outcome at school age","volume":"48","author":"G Lezmi","year":"2018","journal-title":"Clin Exp Allergy"},{"issue":"2","key":"pone.0243109.ref047","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1513\/AnnalsATS.201703-276OC","article-title":"Blood Leukocyte Concentrations, FEV1 Decline, and Airflow Limitation. A 15-Year Longitudinal Study of World Trade Center-exposed Firefighters","volume":"15","author":"R Zeig-Owens","year":"2018","journal-title":"Ann Am Thorac Soc"},{"issue":"6","key":"pone.0243109.ref048","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1136\/thx.43.6.462","article-title":"Peripheral leucocyte count and longitudinal decline in lung function","volume":"43","author":"M Chan-Yeung","year":"1988","journal-title":"Thorax"},{"issue":"4","key":"pone.0243109.ref049","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1378\/chest.14-2535","article-title":"Determinants of underdiagnosis of COPD in national and international surveys","volume":"148","author":"B Lamprecht","year":"2015","journal-title":"Chest"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0243109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T19:10:23Z","timestamp":1607022623000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0243109"}},"subtitle":[],"editor":[{"given":"Stelios","family":"Loukides","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2020,12,3]]},"references-count":49,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0243109","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2020,12,3]]}}}