1,139
Views
15
CrossRef citations to date
0
Altmetric
Review

Endo-phenotyping of COPD patients

Pages 27-37 | Received 19 Jun 2020, Accepted 29 Jul 2020, Published online: 10 Aug 2020

References

  • Soriano JB, Lamprecht B, Ramirez AS, et al. Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2007 and 2011 staging systems: a pooled analysis of individual patient data. Lancet Resp Med. 2015;3:443–450.
  • Burgel PR, Paillasseur JL, Roche N. Identification of clinical phenotypes using cluster analyses in COPD patients with multiple comorbidities. Biomed Res Int. 2014;2014:420134.
  • Galban CJ, Han MK, Boes JL, et al. Computed tomography-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression. Nat Med. 2012;18:1711–1715.
  • Koo H, Vasilescu DM, Booth S, et al. Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study. Lancet Resp Med. 2018;6:591–602.
  • Lee JH, Lee YK, Kim EK, et al. Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype. Respir Med. 2010;104:542–549.
  • Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Am J Respir Crit Care Med. 2017;195:557–582.
  • Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J. 2009;33:1165–1185.
  • Vanfleteren LE, Spruit MA, Groenen M, et al. Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187:728–735.
  • Rutten EP, Gopal P, Wouters EF, et al. various mechanistic pathways representing the aging process are altered in COPD. Chest. 2016;149:53–61.
  • Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet. 2009;374:733–743.
  • Sood A, Assad NA, Barnes PJ, et al. ERS/ATS workshop report on respiratory health effects of household air pollution. Eur Respir J. 2018;51:1700698.
  • Salvi SS, Brashier BB, Londhe J, et al. Phenotypic comparison between smoking and non-smoking chronic obstructive pulmonary disease. Respir Res. 2020;21(1):50.
  • Ghosh B, Gaike AH, Pyasi K, et al. Bacterial load and defective monocyte-derived macrophage bacterial phagocytosis in biomass-smoke COPD. Eur Respir J. 2019;53:1702273.
  • Sarkar M, Srinivasa MI, Kumar K. Tuberculosis associated chronic obstructive pulmonary disease. Clin Respir J. 2017;11:285–295.
  • Strnad P, McElvaney NG, Lomas DA. Alpha(1)-antitrypsin deficiency. N Engl J Med. 2020;382:1443–1455.
  • Chapman KR, Chorostowska-Wynimko J, Koczulla AR, et al. Alpha 1 antitrypsin to treat lung disease in alpha 1 antitrypsin deficiency: recent developments and clinical implications. Int J COPD. 2018;13:419–432.
  • Stanley SE, Chen JJ, Podlevsky JD, et al. Telomerase mutations in smokers with severe emphysema. J Clin Invest. 2015;125:563–570.
  • Hoffman TW, van Moorsel CHM, Borie R, et al. Pulmonary phenotypes associated with genetic variation in telomere-related genes. Curr Opin Pulm Med. 2018;24:269–280.
  • Barnes PJ. Inflammatory mechanisms in COPD. J Allergy Clin Immunol. 2016;138(1):16–27.
  • Barnes PJ. Cellular and molecular mechanisms of asthma and COPD. Clin Sci. 2017;131:1541–1558.
  • Barnes PJ. Targeting cytokines to treat asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2018;18:454–466.
  • Agache I. Severe asthma phenotypes and endotypes. Semin Immunol. 2019;46:101301.
  • Barnes PJ. Inflammatory endotypes in COPD. Allergy. 2019;74:1249–1256.
  • Bateman ED, Reddel HK, van Zyl-smit RN, et al. The asthma-COPD overlap syndrome: towards a revised taxonomy of chronic airways diseases? Lancet Resp Med. 2015;3:719–728.
  • Toledo-Pons N, van Boven JFM, Roman-Rodriguez M, et al. ACO: time to move from the description of different phenotypes to the treatable traits. PloS One. 2019;14:e0210915.
  • Papi A, Romagnoli M, Baraldo S, et al. Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;162:1773–1777.
  • Hayden LP, Hardin ME, Qiu W, et al. Asthma is a risk factor for respiratory exacerbations without increased rate of lung function decline: five-year follow-up in adult smokers from the COPDGene Study. Chest. 2018;15:368–377.
  • Bafadhel M, Peterson S, De Blas MA, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Resp Med. 2018;6:117–126.
  • Adir Y, Hakrush O, Shteinberg M, et al. Circulating eosinophil levels do not predict severe exacerbations in COPD: a retrospective study. ERJ Open Res. 2018;4:00022–2018.
  • Vedel-Krogh S, Nielsen SF, Lange P, et al. Blood eosinophils and exacerbations in chronic obstructive pulmonary disease. the copenhagen general population study. Am J Respir Crit Care Med. 2016;193:965–974.
  • Yun JH, Lamb A, Chase R, et al. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2018;141:2037–2047.e2010.
  • Negewo NA, McDonald VM, Baines KJ, et al. Peripheral blood eosinophils: a surrogate marker for airway eosinophilia in stable COPD. Int J COPD. 2016;11:1495–1504.
  • Turato G, Semenzato U, Bazzan E, et al. Blood eosinophilia neither reflects tissue eosinophils nor worsens clinical outcomes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;197:1216–1219.
  • Kolsum U, Donaldson GC, Singh R, et al. Blood and sputum eosinophils in COPD; relationship with bacterial load. Respir Res. 2017;18(1):88.
  • Eltboli O, Mistry V, Barker B, et al. Relationship between blood and bronchial submucosal eosinophilia and reticular basement membrane thickening in chronic obstructive pulmonary disease. Respirol. 2015;20(4):667–670.
  • Oshagbemi OA, Burden AM, Braeken DCW, et al. Stability of blood eosinophils in patients with chronic obstructive pulmonary disease and in control subjects, and the impact of sex, age, smoking, and baseline counts. Am J Respir Crit Care Med. 2017;195:1402–1404.
  • Landis SH, Suruki R, Hilton E, et al. Stability of blood eosinophil count in patients with COPD in the UK clinical practice research datalink. COPD. 2017;14:382–388.
  • Casanova C, Celli BR, de-Torres JP, et al. Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD. Eur Respir J. 2017;50:5.
  • Landis S, Suruki R, Maskell J, et al. Demographic and Clinical Characteristics of COPD Patients at Different Blood Eosinophil Levels in the UK Clinical Practice Research Datalink. COPD. 2018;15:177–184.
  • Bafadhel M, Saha S, Siva R, et al. Sputum IL-5 concentration is associated with a sputum eosinophilia and attenuated by corticosteroid therapy in COPD. Respiration. 2009;78:256–262.
  • Costa C, Rufino R, Traves SL, et al. CXCR3 and CCR5 chemokines in the induced sputum from patients with COPD. Chest. 2008;133:26–33.
  • Barczyk A, Pierzchala W, Kon OM, et al. Cytokine production by bronchoalveolar lavage T lymphocytes in chronic obstructive pulmonary disease. J Allergy ClinImmunol. 2006;117:1484–1492.
  • De Grove KC, Provoost S, Verhamme FM, et al. Characterization and quantification of innate lymphoid cell subsets in human lung. PloS One. 2016;11:e0145961.
  • Ying S, O’Connor B, Ratoff J, et al. Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease. J Immunol. 2008;181(4):2790–2798.
  • Tworek D, Majewski S, Szewczyk K, et al. The association between airway eosinophilic inflammation and IL-33 in stable non-atopic COPD. Respir Res. 2018;19:108.
  • Kearley J, Silver JS, Sanden C, et al. Cigarette smoke silences innate lymphoid cell function and facilitates an exacerbated type I interleukin-33-dependent response to infection. Immunity. 2015;42:566–579.
  • Mesnil C, Raulier S, Paulissen G, et al. Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J Clin Invest. 2016;126:3279–3295.
  • Weller PF, Spencer LA. Functions of tissue-resident eosinophils. Nat Rev Immunol. 2017;17:746–760.
  • Pavord ID, Chanez P, Criner GJ, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med. 2017;377:1613–1629.
  • Brightling CE, Bleecker ER, Panettieri RA Jr., et al. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Resp Med. 2014;2:891–901.
  • Criner GJ, Celli BR, Brightling CE, et al. Benralizumab for the Prevention of COPD Exacerbations. N Engl J Med. 2019;381:1023–1034.
  • Criner GJ, Celli BR, Singh D, et al. Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies. Lancet Resp Med. 2020;8:158–170.
  • Agusti A, Fabbri LM, Singh D, et al. Inhaled corticosteroids in COPD: friend or foe? Eur Respir J. 2018;52:1801219.
  • Siva R, Green RH, Brightling CE, et al. Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J. 2007;29:906–913.
  • Pascoe S, Locantore N, Dransfield MT. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir Med. 2015;3:435–442.
  • Pavord ID, Lettis S, Locantore N, et al. Blood eosinophils and inhaled corticosteroid/long-acting beta-2 agonist efficacy in COPD. Thorax. 2016;71:118–125.
  • Barnes NC, Sharma R, Lettis S, et al. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur Respir J. 2016;47:1374–1382.
  • Siddiqui SH, Guasconi A, Vestbo J, et al. Blood eosinophils: a biomarker of response to extrafine beclomethasone/formoterol in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015;192:523–525.
  • Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;378:1671–1680.
  • Roche N, Chapman KR, Vogelmeier CF, et al. Blood eosinophils and response to maintenance chronic obstructive pulmonary disease treatment. data from the FLAME Trial. Am J Respir Crit Care Med. 2017;195:1189–1197.
  • Watz H, Tetzlaff K, Wouters EF, et al. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial. Lancet Respir Med. 2016;4:390–398.
  • Calverley PMA, Tetzlaff K, Vogelmeier C, et al. Eosinophilia, frequent exacerbations, and steroid response in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;196:1219–1221.
  • Chapman KR, Hurst JR, Frent SM, et al. 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. Am J Respir Crit Care Med. 2018;198:329–339.
  • Singh D, Agusti A, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019. Eur Respir J. 2019;53:1900164.
  • Calverley PMA, Magnussen H, Miravitlles M, et al. Triple therapy in COPD: what we know and what we don’t. Copd. 2017;14:648–662.
  • Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018;391:1076–1084.
  • Ferguson GT, Rabe KF, Martinez FJ, et al. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial. Lancet Resp Med. 2018;6:747–758.
  • Pavord ID, Lettis S, Anzueto A, et al. Blood eosinophil count and pneumonia risk in patients with chronic obstructive pulmonary disease: a patient-level meta-analysis. Lancet Resp Med. 2016;4:731–741.
  • Contoli M, Pauletti A, Rossi MR, et al. Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD. Eur Respir J. 2017;50:1700451.
  • Millares L, Pascual S, Montón C, et al. Relationship between the respiratory microbiome and the severity of airflow limitation, history of exacerbations and circulating eosinophils in COPD patients. BMC Pulm Med. 2019;19:112.
  • GOLD. Global Initiative for Chronic Obstructive Lung Disease (GOLD): global strategy for the diagnosis, management and prevention of COPD. GOLD. 2020. Available from: www.goldcopd.com
  • Keatings VM, Barnes PJ. Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma and normal subjects. Am J Respir Crit Care Med. 1997;155:449–453.
  • Pascoe SJ, Papi A, Midwinter D, et al. Circulating neutrophils levels are a predictor of pneumonia risk in chronic obstructive pulmonary disease. Respir Res. 2019;20:195.
  • Singh R, Mackay AJ, Patel A, et al. Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease. Respir Res. 2014;15:114.
  • Traves SL, Culpitt S, Russell REK, et al. Elevated levels of the chemokines GRO and MCP-1 in sputum samples from COPD patients. Thorax. 2002;57:590–595.
  • Donnelly LE, Barnes PJ. Defective phagocytosis in airways disease. Chest. 2012;141:1055–1062.
  • Patel IS, Seemungal TA, Wilks M, et al. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax. 2002;57:759–764.
  • Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689–698.
  • Uzun S, Djamin RS, Kluytmans JA, et al. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Resp Med. 2014;2:361–368.
  • Han MK, Tayob N, Murray S, et al. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med. 2014;189:1503–1508.
  • Jalalvand F, Riesbeck K. Update on non-typeable Haemophilus influenzae-mediated disease and vaccine development. Expert Rev Vaccines. 2018;17:503–512.
  • Barnes PJ, Baker J, Donnelly LE. Cellular senescence as a mechanism and target in chronic lung diseases. Am J Respir Crit Care Med. 2019;200:556–564.
  • To M, Takagi D, Akashi K, et al. Sputum PAI-1 elevation by oxidative stress-dependent NF-kappaB activation in chronic obstructive pulmonary disease. Chest. 2013;144:515–521.
  • Nakamaru Y, Vuppusetty C, Wada H, et al. A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9. Faseb J. 2009;23:2810–2819.
  • Yanagisawa S, Papaioannou AI, Papaporfyriou A, et al. Decreased serum sirtuin-1 in chronic obstructive pulmonary disease. Chest. 2017;152:343–352.
  • Rajendrasozhan S, Yang SR, Kinnula VL, et al. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:861–870.
  • Gao W, Yuan C, Zhang J, et al. Klotho expression is reduced in COPD airway epithelial cells: effects on inflammation and oxidant injury. Clin Sci. 2015;129:1011–1023.
  • Culpitt SV, Nightingale JA, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1635–1639.
  • Barnes PJ. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy ClinImmunol. 2013;131:636–645.
  • Rennard SI, Dale DC, Donohue JF, et al. CXCR2 antagonist MK-7123- a phase 2 proof-of-concept trial for chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015;191:1001–1011.
  • Barnes PJ. New anti-inflammatory treatments for chronic obstructive pulmonary disease. Nat Rev Drug Discov. 2013;12:543–559.
  • Gross NJ, Barnes PJ. New therapies for asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;195:159–166.
  • Garnock-Jones KP. Roflumilast: a review in COPD. Drugs. 2015;75:1645–1656.
  • Rennard SI, Calverley PM, Goehring UM, et al. Reduction of exacerbations by the PDE4 inhibitor roflumilast–the importance of defining different subsets of patients with COPD. Respir Res. 2011;12(18):18.
  • Woodruff PG, Barr RG, Bleecker E, et al. Clinical significance of symptoms in smokers with preserved pulmonary function. N Engl J Med. 2016;374:1811–1821.
  • Kesimer M, Ford AA, Ceppe A, et al. airway mucin concentration as a marker of chronic bronchitis. N Engl J Med. 2017;377:911–922.
  • Nadel JA, Burgel PR. The role of epidermal growth factor in mucus production. Curr Opin Pharmacol. 2001;1:254–258.
  • Vestbo J, Lange P. Can GOLD Stage 0 provide information of prognostic value in chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 2015;75(3):329–332.
  • Han MK, Quibrera PM, Carretta EE, et al. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2017;5:619–626.
  • Wedzicha JA, Singh R, Mackay AJ. Acute COPD exacerbations. Clin Chest Med. 2014;35:157–163.
  • Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363:1128–1138.
  • Bewley MA, Preston JA, Mohasin M, et al. Impaired mitochondrial microbicidal responses in chronic obstructive pulmonary disease macrophages. Am J Respir Crit Care Med. 2017;196:845–855.
  • Papi A, Bellettato CM, Braccioni F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J RespirCrit Care Med. 2006;173:1114–1121.
  • Aaron SD, Angel JB, Lunau M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;163:349–355.
  • Crooks SW, Bayley DL, Hill SL, et al. Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis: the role of leukotriene B4. Eur Respir J. 2000;15:274–280.
  • Biernacki WA, Kharitonov SA, Barnes PJ. Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD. Thorax. 2003;58:294–298.
  • Mallia P, Footitt J, Sotero R, et al. Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186:1117–1124.
  • Bafadhel M, McKenna S, Terry S, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011;184:662–671.
  • Aksoy E, Karakurt Z, Gungor S, et al. Neutrophil to lymphocyte ratio is a better indicator of COPD exacerbation severity in neutrophilic endotypes than eosinophilic endotypes. Int J COPD. 2018;13:2721–2730.
  • Bafadhel M, McKenna S, Terry S, et al. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2012;186:48–55.
  • Bafadhel M, Greening NJ, Harvey-Dunstan TC, et al. Blood eosinophils and outcomes in severe hospitalised exacerbations of COPD. Chest. 2016;150:320–328.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.