{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:48:22Z","timestamp":1791103702564,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1998,10,1]],"date-time":"1998-10-01T00:00:00Z","timestamp":907200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We examined the feasibility of using induced sputum to evaluate the airway inflammatory response to natural acute respiratory virus infections. We recruited eight asthmatics and nine healthy subjects on Day 4 of a cold. Viral infection was confirmed in six of the asthmatics (influenza A or B) and six of the healthy subjects (influenza A, rhinovirus, adenovirus, respiratory syncytial virus, and coronavirus). In the subjects with confirmed virus infection, five of the asthmatics had an objective exacerbation of asthma during the cold. Their sputum on Day 4 showed a high median total cell count of 19.7 \u00d7 106 cells\/ml with a modest neutrophilia (58.5%) and high levels of interleukin-8 (IL-8) (16,000 pg\/ml), eosinophilic cationic protein (ECP) (1,880 \u03bc g\/L) and very high levels of fibrinogen (250 mg\/L). In contrast, the proportion (1.3%) and absolute number of eosinophils was low. IL-2 levels were within the normal range, whereas IL-5 and interferon gamma were under the limit of detection of the assays. In the healthy subjects with a confirmed virus infection the sputum findings were qualitatively similar but significantly less prominent. Sputum IL-8 on Day 4 was strongly correlated with neutrophils (rs = 0.8, p &amp;lt; 0.001). This correlation was also significant when each group was analyzed separately. On Day 21 there was a fall in the absolute number of neutrophils and in ECP and fibrinogen levels in both groups. Similar results were found in the two asthmatic and three healthy subjects with a cold of comparable severity but in whom viral infection was not confirmed. We conclude that induced sputum examination can be used to study the effects of natural colds and influenza on the airways of the lungs. The results also suggest that natural colds, on Day 4, cause neutrophilic lower airway inflammation that is greater in asthmatics than in healthy subjects. The greater inflammatory response in asthmatics may be due to the changes associated with trivial eosinophilia or to the different viruses involved.<\/jats:p>","DOI":"10.1164\/ajrccm.158.4.9712082","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:47:41Z","timestamp":1365083261000},"page":"1178-1184","source":"Crossref","is-referenced-by-count":161,"title":["Asthma and Natural Colds: Inflammatory Indices in Induced Sputum: A Feasibility Study"],"prefix":"10.1093","volume":"158","author":[{"given":"MARCIA M. M.","family":"PIZZICHINI","sequence":"first","affiliation":[{"name":"Asthma Research Group, Departments of Medicine and Paediatrics, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada; and Department of University Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EMILIO","family":"PIZZICHINI","sequence":"additional","affiliation":[{"name":"Asthma Research Group, Departments of Medicine and Paediatrics, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada; and Department of University Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANN","family":"EFTHIMIADIS","sequence":"additional","affiliation":[{"name":"Asthma Research Group, Departments of Medicine and Paediatrics, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada; and Department of University Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANOOP J.","family":"CHAUHAN","sequence":"additional","affiliation":[{"name":"Asthma Research Group, Departments of Medicine and Paediatrics, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada; and Department of University Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SEBASTIAN L.","family":"JOHNSTON","sequence":"additional","affiliation":[{"name":"Asthma Research Group, Departments of Medicine and Paediatrics, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada; and Department of University Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PAT","family":"HUSSACK","sequence":"additional","affiliation":[{"name":"Asthma Research Group, Departments of Medicine and Paediatrics, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada; and Department of University Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JIM","family":"MAHONY","sequence":"additional","affiliation":[{"name":"Asthma Research Group, Departments of Medicine and Paediatrics, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada; and Department of University Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JERRY","family":"DOLOVICH","sequence":"additional","affiliation":[{"name":"Asthma Research Group, Departments of Medicine and Paediatrics, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada; and Department of University Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FREDERICK E.","family":"HARGREAVE","sequence":"additional","affiliation":[{"name":"Asthma Research Group, Departments of Medicine and Paediatrics, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada; and Department of University Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1998,10,1]]},"reference":[{"key":"2026032709041921200_B1","first-page":"1225","article-title":"Community study role of viral infections in exacerbations of asthma of asthma in 9-11 year old children.","volume":"310","author":"Johnston","year":"1995","journal-title":"B.M.J."},{"key":"2026032709041921200_B2","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1164\/ajrccm.154.3.8810601","article-title":"The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis.","volume":"154","author":"Johnston","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709041921200_B3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0091-6749(97)70216-1","article-title":"Viruses in asthma.","volume":"100","author":"Busse","year":"1997","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026032709041921200_B4","first-page":"879","article-title":"Lower airway inflammation during rhinovirus colds in normal and in asthmatic subjects.","volume":"151","author":"Fraenkel","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709041921200_B5","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1164\/ajrccm.156.2.9610079","article-title":"Experimental rhinovirus 16 infection: effects on cell differentials and soluble markers in sputum of asthmatic subjects.","volume":"156","author":"Gr\u00fcnberg","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709041921200_B6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/infdis\/150.2.195","article-title":"A model for obtaining predictable natural transmission of rhinovirus in human volunteers.","volume":"150","author":"Meschievitz","year":"1984","journal-title":"J. Infect. Dis."},{"key":"2026032709041921200_B7","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1172\/JCI117581","article-title":"A common cold virus, rhinovirus 16, potentiates airway inflammation after segmental antigen bronchoprovocation in allergic subjects.","volume":"94","author":"Calhoun","year":"1994","journal-title":"J. Clin. Invest."},{"key":"2026032709041921200_B8","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1164\/ajrccm\/136.5.1285","article-title":"Standardization of spirometry: 1987 update.","volume":"136","author":"American Thoracic Society","year":"1987","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709041921200_B9","first-page":"659","article-title":"Reference spirometric values using techniques and equipment that meets ATS recommendation.","volume":"123","author":"Crapo","year":"1981","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709041921200_B10"},{"key":"2026032709041921200_B11"},{"key":"2026032709041921200_B12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1136\/thx.47.1.25","article-title":"Use of induced sputum cell counts to investigate airway inflammation in asthma.","volume":"47","author":"Pin","year":"1992","journal-title":"Thorax"},{"key":"2026032709041921200_B13","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1164\/ajrccm.155.5.9154849","article-title":"Sputum in severe exacerbations of asthma: kinetics of inflammatory indices after prednisone treatment.","volume":"155","author":"Pizzichini","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709041921200_B14"},{"key":"2026032709041921200_B15"},{"key":"2026032709041921200_B16","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/infdis\/157.1.133","article-title":"Kinins are generated during experimental rhinovirus cold.","volume":"1","author":"Naclerio","year":"1988","journal-title":"J. Infect. Dis."},{"key":"2026032709041921200_B17","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1164\/ajrccm.155.4.9105080","article-title":"Role of nasal interleukin-8 in neutrophil recruitment and activation in children with virus induced asthma.","volume":"155","author":"Teran","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709041921200_B18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1136\/thx.49.2.121","article-title":"Microvascular exudative hyperresponsiveness in human coronavirus-induced cold.","volume":"49","author":"Greiff","year":"1994","journal-title":"Thorax"},{"key":"2026032709041921200_B19","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1111\/j.1365-2222.1996.tb00593.x","article-title":"Bronchial inflammation and the common cold: a comparison of atopic and non-atopic individuals.","volume":"26","author":"Trigg","year":"1996","journal-title":"Clin. Exp. Allergy"},{"key":"2026032709041921200_B20","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1172\/JCI114265","article-title":"Neutrophil activating peptide-1\/interleukin-8, a novel cytokine that stimulates neutrophils.","volume":"84","author":"Bagglioni","year":"1989","journal-title":"J. Clin. Invest."},{"key":"2026032709041921200_B21","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/S0091-6749(96)80195-3","article-title":"Expression of IL-6, IL-8, and RANTES of human bronchial epithelial cells, NCL-H292, induced by influenza virus A.","volume":"98","author":"Matsukura","year":"1996","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026032709041921200_B22","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1093\/infdis\/174.2.262","article-title":"Induction of interleukin (IL)-8 gene expression by respiratory syncytial virus involves activation of nuclear factor (NF)-kappa B and NF-IL-6.","volume":"174","author":"Mastronarde","year":"1996","journal-title":"J. Infect. Dis."},{"key":"2026032709041921200_B23","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1172\/JCI118067","article-title":"Infection of a human respiratory epithelial cell line with rhinovirus: induction of cytokine release and modulation of susceptibility to infection by cytokine exposure.","volume":"96","author":"Subauste","year":"1995","journal-title":"J. Clin. Invest."},{"key":"2026032709041921200_B24","first-page":"609","article-title":"Effects of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin-8 in nasal lavage in asthmatic subjects in vivo.","volume":"156","author":"Gr\u00fcnberg","year":"1995","journal-title":"Clin. Exp. Allergy"},{"key":"2026032709041921200_B25","doi-asserted-by":"crossref","first-page":"932","DOI":"10.4049\/jimmunol.149.3.932","article-title":"A kinetic study of immune mediators in the lungs of mice infected with influenza A virus.","volume":"149","author":"Hennet","year":"1992","journal-title":"J. Immunol."},{"key":"2026032709041921200_B26","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/infdis\/162.3.591","article-title":"Peripheral blood mononuclear cell interleukin-2 and interferon-gamma production, cytotoxicity, and antigen-stimulated blastogenesis during experimental rhinovirus infection.","volume":"162","author":"Hsia","year":"1990","journal-title":"J. Infect. Dis."},{"key":"2026032709041921200_B27","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1086\/514101","article-title":"Characterization of the T cell response to human rhinovirus in children: implications for understanding the immunopathology of the common cold.","volume":"176","author":"Wimalasundera","year":"1997","journal-title":"J. Infect. Dis."},{"key":"2026032709041921200_B28","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1164\/ajrccm.155.2.9032177","article-title":"Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma and normal subjects.","volume":"155","author":"Keatings","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709041921200_B29","first-page":"183s","article-title":"Sputum eosinophil and neutrophil proteins in smokers with severe airflow limitation.","volume":"10","author":"Pizzichini","year":"1997","journal-title":"Eur. Respir. J."},{"key":"2026032709041921200_B30","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/jlb.63.6.715","article-title":"Localization of eosinophils-derived neurotoxin and eosinophil cationic protein in neutrophilic leukocytes.","volume":"63","author":"Sur","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"2026032709041921200_B31","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1164\/ajrccm.157.6.9707163","article-title":"Virus-induced airway hyperresponsiveness and asthma.","volume":"157","author":"Folkerts","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709041921200_B32","doi-asserted-by":"crossref","first-page":"642","DOI":"10.3109\/00016489309135878","article-title":"Mucosal exudation of fibrinogen in coronavirus-induced common colds.","volume":"113","author":"Ackerlund","year":"1993","journal-title":"Acta. Otolaringol. (Stockh.)"},{"key":"2026032709041921200_B33"},{"key":"2026032709041921200_B34","first-page":"858","article-title":"Effect of inhaled corticosteroid on episodes of wheezing associated with viral infection in school age children: randomized double blind placebo controlled trial.","volume":"315","author":"Doull","year":"1997","journal-title":"B.M.J."}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/158\/4\/1178\/67435533\/ajrccm_158_4_1178.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/158\/4\/1178\/67435533\/ajrccm_158_4_1178.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:05:38Z","timestamp":1774616738000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/158\/4\/1178\/8530238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,10,1]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[1998,10,1]]},"published-print":{"date-parts":[[1998,10,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.158.4.9712082","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1998,10]]},"published":{"date-parts":[[1998,10,1]]}}}