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Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Monocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled <jats:italic>Haemophilus influenzae<\/jats:italic> or <jats:italic>Streptococcus pneumoniae<\/jats:italic> for 4\u00a0h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Phagocytosis of <jats:italic>H. influenza<\/jats:italic>e was negatively correlated with exacerbation frequency (r\u2009=\u20090.440, p\u2009&lt;\u20090.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9\u2009\u00d7\u200910<jats:sup>3<\/jats:sup> RFU vs. 2.5\u2009\u00d7\u200910<jats:sup>3<\/jats:sup> RFU, p\u2009&lt;\u20090.01). There was no correlation for <jats:italic>S. pneumoniae<\/jats:italic>. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2\u00a0weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p\u2009&lt;\u20090.001) and TNF\u03b1 (p\u2009&lt;\u20090.01) compared to stable state.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Impaired COPD macrophage phagocytosis of <jats:italic>H. influenza<\/jats:italic>e, but not <jats:italic>S. pneumoniae<\/jats:italic> is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-021-01718-8","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T18:37:27Z","timestamp":1618943847000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD"],"prefix":"10.1186","volume":"22","author":[{"name":"COPDMAP consortium","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. B. R.","family":"Belchamber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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KBRB\u2014Reports grants from Alpha-1 foundation outside the submitted work. PF\u2014The author declares that they have no competing interests. KKC\u2014The author declares that they have no competing interests. GD\u2014Reports grants from Aztra Zeneca and personal fees from Astra-Zeneca, American Thoracic Society and FWO Flanders outside the submitted work. JW\u2014Reports grants from GSK, Novartis, Boehringer Ingelheim, Astra Zeneca and Chiesi outside the submitted work. PJB\u2014Reports grants and personal fees from Astra Zeneca, Boehringer Ingelheim, and personal fees from Novartis, Pieris and Epi-Endo outside the submitted work. LED\u2014Reports grant from Astra-Zeneca and Boehringer Ingelheim outside the submitted work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"113"}}