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COPD Phenotyping

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Precision in Pulmonary, Critical Care, and Sleep Medicine

Part of the book series: Respiratory Medicine ((RM))

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Abstract

Phenotypic classification of chronic obstructive pulmonary disease (COPD) has evolved from the classic phenotypes of emphysema, chronic bronchitis, and asthma to numerous phenotypes that reflect the heterogeneity of this complex lung disease. Novel imaging modalities, high-performance platforms for protein, gene, and metabolite assessment, and integrative computational approaches to disease classification have led to the characterization of multiple phenotypes over the past decade. The adoption of these techniques, already widespread in the research realm, in clinical practice will facilitate the classification of individuals with differential responses to therapy and variable disease trajectories in order to deliver precision-based therapy for COPD.

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Abbreviations

AATD:

Alpha-1 antitrypsin deficiency

ACO:

Asthma COPD overlap

COPD:

Chronic obstructive pulmonary disease

CRP:

C reactive protein

CT:

Computerized tomography

DLCO:

Diffusion capacity for carbon monoxide

FEV1:

Forced expiratory volume in 1 second

FFMI:

Fat free mass index

FVC:

Forced vital capacity in 1 second

GERD:

Gastroesophageal reflux disease

GOLD:

Global initiative for obstructive lung disease

HU:

Hounsfield unit

ICS:

Inhaled corticosteroid

IL-5:

Interleukin-5

LABA:

Long-acting beta agonist

LAMA:

Long-acting muscarinic antagonist

mMRC:

Modified Medical Research Council (Dyspnea Score)

PD15:

HU value at the 15th percentile of the HU value histogram of lung voxels

PRISm:

Preserved ratio impaired spirometry

RV:

Residual volume

SPD:

Surfactant protein D

sRAGE:

Soluble advanced glycosylation end products

TLC:

Total lung capacity

References

  1. Abboud RT, Vimalanathan S. Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysema [State of the Art Series. Chronic obstructive pulmonary disease in high- and low-income countries. Edited by G. Marks and M. Chan-Yeung. Number 3 in the series]. International Union Against Tuberculosis and Lung Disease; 2008.

    Google Scholar 

  2. Jha P, Ramasundarahettige C, Landsman V, Rostron B, Thun M, Anderson RN, et al. 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med. 2013;368(4):341–50.

    Article  CAS  PubMed  Google Scholar 

  3. Harris HW, Meneely GR, Renzetti AD, Steele JD Jr, Wyatt JP. Chronic bronchitis, asthma, and pulmonary emphysema. Arch Environ Health. Routledge. 1962;5(4):375–82.

    Article  Google Scholar 

  4. Petty TL. The history of COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(1):3–14.

    PubMed  PubMed Central  Google Scholar 

  5. Calverley PMA, Rennard SI. What have we learned from large drug treatment trials in COPD? Lancet. 2007;370(9589):774–85.

    Article  PubMed  Google Scholar 

  6. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187(4):347–65.

    Article  CAS  PubMed  Google Scholar 

  7. Laurell CB, Eriksson S. The electrophoretic α; 1-globulin pattern of serum in α; 1-antitrypsin deficiency. Scand J Clin Lab Invest. 1963;15(2):132–40.

    Article  CAS  Google Scholar 

  8. Rennard SI. The promise of observational studies (ECLIPSE, SPIROMICS, and COPDGene) in achieving the goal of personalized treatment of chronic obstructive pulmonary disease. Semin Respir Crit Care Med. 2015;36(4):478–90.

    Article  PubMed  Google Scholar 

  9. Svanes C, Sunyer J, Plana E, Dharmage S, Heinrich J, Jarvis D, et al. Early life origins of chronic obstructive pulmonary disease. Thorax. BMJ Publishing Group Ltd. 2010;65(1):14–20.

    CAS  Google Scholar 

  10. De Soyza A, Calverley PMA. Large trials, new knowledge: the changing face of COPD management. Eur Respir J. 2015;45(6):1692–703.

    Article  PubMed  Google Scholar 

  11. Calverley PMA, Rabe KF, Goehring U-M, Kristiansen S, Fabbri LM, Martinez FJ, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009;374(9691):685–94.

    Article  CAS  PubMed  Google Scholar 

  12. Global strategy for the diagnosis, management and prevention of COPD, global initiative for chronic obstructive lung disease (GOLD). 2018. https://goldcoped.org/. Accessed 17 Nov 2018.

  13. Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev (Online). 2014;(3):CD010115.

    Google Scholar 

  14. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med. 1980;93(3):391–8.

    Google Scholar 

  15. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet. 1981;1(8222):681–6.

    Google Scholar 

  16. Long-Term Oxygen Treatment Trial Research Group, Albert RK, Au DH, Blackford AL, Casaburi R, Cooper JA, et al. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med. 2016;375(17):1617–27.

    Article  CAS  Google Scholar 

  17. Rochester CL, Vogiatzis I, Holland AE, Lareau SC, Marciniuk DD, Puhan MA, et al. An official American Thoracic Society/European Respiratory Society policy statement: enhancing implementation, use, and delivery of pulmonary rehabilitation. Am J Respir Crit Care Med. 2015;192:1373–86.

    Article  PubMed  Google Scholar 

  18. Lacasse Y, Goldstein R, Lasserson TJ, Martin S. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev (Online). 2006;(4):CD003793.

    Google Scholar 

  19. Puhan MA, Gimeno-Santos E, Cates CJ, Troosters T. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev (Online). 2016;(12):CD005305.

    Google Scholar 

  20. Tan WC, Bourbeau J, Hernandez P, Chapman KR, Cowie R, FitzGerald JM, et al. Exacerbation-like respiratory symptoms in individuals without chronic obstructive pulmonary disease: results from a population-based study. Thorax. BMJ Publishing Group Ltd. 2014;69(8):709–17.

    Google Scholar 

  21. Wan ES, Castaldi PJ, Cho MH, Hokanson JE, Regan EA, Make BJ, et al. Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene. Respir Res. 2014;15:89.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Woodruff PG, Barr RG, Bleecker E, Christenson SA, Couper D, Curtis JL, et al. Clinical significance of symptoms in smokers with preserved pulmonary function. N Engl J Med. Massachusetts Medical Society. 2016;374(19):1811–21.

    Article  CAS  Google Scholar 

  23. Tashkin DP, Altose MD, Bleecker ER, Connett JE, Kanner RE, Lee WW, et al. The lung health study: airway responsiveness to inhaled methacholine in smokers with mild to moderate airflow limitation. The Lung Health Study Research Group. Am Rev Respir Dis. 1992;145(2 Pt 1):301–10.

    Article  CAS  PubMed  Google Scholar 

  24. van den Berge M, Vonk JM, Gosman M, Lapperre TS, Snoeck-Stroband JB, Sterk PJ, et al. Clinical and inflammatory determinants of bronchial hyperresponsiveness in COPD. Eur Respir J. 2012;40(5):1098–105.

    Article  PubMed  Google Scholar 

  25. Tashkin DP, Altose MD, Connett JE, Kanner RE, Lee WW, Wise RA. Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. The Lung Health Study Research Group. Am J Respir Crit Care Med. 1996;153(6 Pt 1):1802–11.

    Article  CAS  PubMed  Google Scholar 

  26. Vestbo J, Hansen EF. Airway hyperresponsiveness and COPD mortality. Thorax. 2001;56(Suppl 2):ii11–4.

    PubMed  PubMed Central  Google Scholar 

  27. Postma DS, Rabe KF. The asthma-COPD overlap syndrome. N Engl J Med. 2015;373(13):1241–9.

    Article  CAS  PubMed  Google Scholar 

  28. Barrecheguren M, Esquinas C, Miravitlles M. The asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): opportunities and challenges. Curr Opin Pulm Med. 2015;21(1):74–9.

    Article  CAS  PubMed  Google Scholar 

  29. Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363(12):1128–38.

    Article  CAS  PubMed  Google Scholar 

  30. Pasquale MK, Sun SX, Song F, Hartnett HJ, Stemkowski SA. Impact of exacerbations on health care cost and resource utilization in chronic obstructive pulmonary disease patients with chronic bronchitis from a predominantly Medicare population. COPD. 2012;7:757–64.

    Article  Google Scholar 

  31. Wedzicha JA, Miravitlles M, Hurst JR, Calverley PMA, Albert RK, Anzueto A, et al. Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2017;49(3):1600791.

    Article  Google Scholar 

  32. Niewoehner DE, Rice K, Cote C, Paulson D, Cooper JAD, Korducki L, et al. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med. 2005;143(5):317–26.

    Article  CAS  PubMed  Google Scholar 

  33. Kardos P, Wencker M, Glaab T, Vogelmeier C. Impact of salmeterol/fluticasone propionate versus salmeterol on exacerbations in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175(2):144–9.

    Article  CAS  PubMed  Google Scholar 

  34. Wedzicha JA, Calverley PMA, Seemungal TA, Hagan G, Ansari Z, Stockley RA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177(1):19–26.

    Article  CAS  PubMed  Google Scholar 

  35. Fabbri LM, Calverley PMA, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet. 2009;374(9691):695–703.

    Article  CAS  PubMed  Google Scholar 

  36. Leuppi JD, Schuetz P, Bingisser R, Bodmer M, Briel M, Drescher T, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. American Medical Association. 2013;309(21):2223–31.

    Article  CAS  Google Scholar 

  37. Han MK, Quibrera PM, Carretta EE, Barr RG, Bleecker ER, Bowler RP, et al. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2017;5(8):619–26.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur Respir J. 2006;28(6):1245–57.

    Article  CAS  PubMed  Google Scholar 

  39. Chatila WM, Thomashow BM, Minai OA, Criner GJ, Make BJ. Comorbidities in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5(4):549–55.

    Article  PubMed  PubMed Central  Google Scholar 

  40. MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Part one. Am J Respir Crit Care Med. 1994;150(3):833–52.

    Article  CAS  PubMed  Google Scholar 

  41. Hill K, Geist R, Goldstein RS, Lacasse Y. Anxiety and depression in end-stage COPD. Eur Respir J. 2008;31(3):667–77.

    Article  CAS  PubMed  Google Scholar 

  42. Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J. 2009;33(5):1165–85.

    Article  CAS  PubMed  Google Scholar 

  43. Schols AMWJ. Pulmonary cachexia. Int J Cardiol. 2002;85(1):101–10.

    Article  PubMed  Google Scholar 

  44. Bernard S, LeBlanc P, Whittom F, Carrier G, Jobin J, Belleau R, et al. Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;158(2):629–34.

    Article  CAS  PubMed  Google Scholar 

  45. Allaire J, Maltais F, Doyon JF, Noël M, LeBlanc P, Carrier G, et al. Peripheral muscle endurance and the oxidative profile of the quadriceps in patients with COPD. Thorax. 2004;59(8):673–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gosselink R, Troosters T, Decramer M. Peripheral muscle weakness contributes to exercise limitation in COPD. Am J Respir Crit Care Med. 1996;153(3):976–80.

    Article  CAS  PubMed  Google Scholar 

  47. Gosker HR, Zeegers MP, Wouters EFM, Schols AMWJ. Muscle fibre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis. Thorax. 2007;62(11):944–9.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Marquis K, Debigaré R, Lacasse Y, LeBlanc P, Jobin J, Carrier G, et al. Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002;166(6):809–13.

    Article  PubMed  Google Scholar 

  49. Patel MS, Natanek SA, Stratakos G, Pascual S, Martínez-Llorens J, Disano L, et al. Vastus lateralis fiber shift is an independent predictor of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014;190(3):350–2.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Agusti A, Calverley PMA, Celli B, Coxson HO, Edwards LD, Lomas DA, et al. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Res. 2010;11:122.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Schols AMWJ, Broekhuizen R, Weling-Scheepers CA, Wouters EF. Body composition and mortality in chronic obstructive pulmonary disease. Am J Clin Nutr. 2005;82(1):53–9.

    Article  CAS  PubMed  Google Scholar 

  52. Diaz AA, Zhou L, Young TP, McDonald M-L, Harmouche R, Ross JC, et al. Chest CT measures of muscle and adipose tissue in COPD: gender-based differences in content and in relationships with blood biomarkers. Acad Radiol. 2014;21(10):1255–61.

    Article  PubMed  PubMed Central  Google Scholar 

  53. McDonald M-LN, Diaz AA, Ross JC, San José Estépar R, Zhou L, Regan EA, et al. Quantitative computed tomography measures of pectoralis muscle area and disease severity in chronic obstructive pulmonary disease. A cross-sectional study. Ann Am Thorac Soc. 2014;11(3):326–34.

    Article  PubMed  PubMed Central  Google Scholar 

  54. McDonald M-LN, Diaz AA, Rutten E, Lutz SM, Harmouche R, San José Estépar R, et al. Chest computed tomography-derived low fat-free mass index and mortality in COPD. Eur Respir J. 2017;50(6):1701134.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Vogiatzis I, Simoes DCM, Stratakos G, Kourepini E, Terzis G, Manta P, et al. Effect of pulmonary rehabilitation on muscle remodelling in cachectic patients with COPD. Eur Respir J. 2010;36(2):301–10.

    Article  CAS  PubMed  Google Scholar 

  56. Jones SE, Maddocks M, Kon SSC, Canavan JL, Nolan CM, Clark AL, et al. Sarcopenia in COPD: prevalence, clinical correlates and response to pulmonary rehabilitation. Thorax. 2015;70(3):213–8.

    Article  PubMed  Google Scholar 

  57. Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov. 2015;14(1):58–74.

    Article  CAS  PubMed  Google Scholar 

  58. Martinez FJ, Donohue JF, Rennard SI. The future of chronic obstructive pulmonary disease treatment--difficulties of and barriers to drug development. Lancet. 2011;378(9795):1027–37.

    Article  CAS  PubMed  Google Scholar 

  59. Agusti A, Sobradillo P, Celli B. Addressing the complexity of chronic obstructive pulmonary disease: from phenotypes and biomarkers to scale-free networks, systems biology, and P4 medicine. Am J Respir Crit Care Med. 2011;183(9):1129–37.

    Article  PubMed  Google Scholar 

  60. Müller NL, Staples CA, Miller RR, Abboud RT. “Density mask.” An objective method to quantitate emphysema using computed tomography. Chest. 1988;94(4):782–7.

    Article  PubMed  Google Scholar 

  61. Gevenois PA, de Maertelaer V, De Vuyst P, Zanen J, Yernault JC. Comparison of computed density and macroscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med. 1995;152(2):653–7.

    Article  CAS  PubMed  Google Scholar 

  62. Gevenois PA, De Vuyst P, de Maertelaer V, Zanen J, Jacobovitz D, Cosio MG, et al. Comparison of computed density and microscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med. 1996;154(1):187–92.

    Article  CAS  PubMed  Google Scholar 

  63. Kinsella M, Müller NL, Abboud RT, Morrison NJ, DyBuncio A. Quantitation of emphysema by computed tomography using a “density mask” program and correlation with pulmonary function tests. Chest. 1990;97(2):315–21.

    Article  CAS  PubMed  Google Scholar 

  64. Nakano Y, Sakai H, Muro S, Hirai T, Oku Y, Nishimura K, et al. Comparison of low attenuation areas on computed tomographic scans between inner and outer segments of the lung in patients with chronic obstructive pulmonary disease: incidence and contribution to lung function. Thorax. 1999;54(5):384–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Chapman KR, Burdon JGW, Piitulainen E, Sandhaus RA, Seersholm N, Stocks JM, et al. Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(9991):360–8.

    Article  CAS  PubMed  Google Scholar 

  66. McNamara AE, Müller NL, Okazawa M, Arntorp J, Wiggs BR, Paré PD. Airway narrowing in excised canine lungs measured by high-resolution computed tomography. J Appl Physiol. 1992;73(1):307–16.

    Article  CAS  PubMed  Google Scholar 

  67. Amirav I, Kramer SS, Grunstein MM, Hoffman EA. Assessment of methacholine-induced airway constriction by ultrafast high-resolution computed tomography. J Appl Physiol. 1993;75(5):2239–50.

    Article  CAS  PubMed  Google Scholar 

  68. Okazawa M, Müller N, McNamara AE, Child S, Verburgt L, Paré PD. Human airway narrowing measured using high resolution computed tomography. Am J Respir Crit Care Med. 1996;154(5):1557–62.

    Article  CAS  PubMed  Google Scholar 

  69. McNitt-Gray MF, Goldin JG, Johnson TD, Tashkin DP, Aberle DR. Development and testing of image-processing methods for the quantitative assessment of airway hyperresponsiveness from high-resolution CT images. J Comput Assist Tomogr. 1997;21(6):939–47.

    Article  CAS  PubMed  Google Scholar 

  70. Martinez CH, Chen Y-H, Westgate PM, Liu LX, Murray S, Curtis JL, et al. Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease. Thorax. 2012;67(5):399–406.

    Article  PubMed  Google Scholar 

  71. Boueiz A, Chang Y, Cho MH, Washko GR, San José Estépar R, Bowler RP, et al. Lobar emphysema distribution is associated with 5-year radiological disease progression. Chest. 2018;153(1):65–76.

    Article  PubMed  Google Scholar 

  72. Sciurba FC, Ernst A, Herth FJF, Strange C, Criner GJ, Marquette CH, et al. A randomized study of endobronchial valves for advanced emphysema. N Engl J Med. 2010;363(13):1233–44.

    Article  CAS  PubMed  Google Scholar 

  73. Criner GJ, Sue R, Wright S, Dransfield M, Rivas-Perez H, Wiese T, et al. A multicenter randomized controlled trial of Zephyr endobronchial valve treatment in heterogeneous emphysema (LIBERATE). Am J Respir Crit Care Med. 2018 ed. 2018;198(9):1151–64.

    Article  Google Scholar 

  74. Hogg JC, McDonough JE, Suzuki M. Small airway obstruction in COPD: new insights based on micro-CT imaging and MRI imaging. Chest. 2013;143(5):1436–43.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Galbán CJ, Han MK, Boes JL, Chughtai KA, Meyer CR, Johnson TD, et al. Computed tomography-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression. Nat Med. 2012;18(11):1711–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Bhatt SP, Soler X, Wang X, Murray S, Anzueto AR, Beaty TH, et al. Association between functional small airway disease and FEV1 decline in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2016;194(2):178–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Mannino DM, Tal-Singer R, Lomas DA, Vestbo J, Graham Barr R, Tetzlaff K, et al. Plasma fibrinogen as a biomarker for mortality and hospitalized exacerbations in people with COPD. Chronic Obstr Pulm Dis. 2015;2(1):23–34.

    PubMed  PubMed Central  Google Scholar 

  78. Keene JD, Jacobson S, Kechris K, Kinney GL, Foreman MG, Doerschuk CM, et al. Biomarkers predictive of exacerbations in the SPIROMICS and COPDGene cohorts. Am J Respir Crit Care Med. 3rd ed. American Thoracic Society. 2017;195(4):473–81.

    Article  Google Scholar 

  79. Celli BR, Locantore N, Yates J, Tal-Singer R, Miller BE, Bakke P, et al. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185(10):1065–72.

    Article  CAS  PubMed  Google Scholar 

  80. Cheng DT, Kim DK, Cockayne DA, Belousov A, Bitter H, Cho MH, et al. Systemic soluble receptor for advanced glycation endproducts is a biomarker of emphysema and associated with AGER genetic variants in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188(8):948–57.

    Article  CAS  PubMed  Google Scholar 

  81. Coxson HO, Dirksen A, Edwards LD, Yates JC, Agusti A, Bakke P, et al. The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study. Lancet Respir Med. 2013;1(2):129–36.

    Article  PubMed  Google Scholar 

  82. Zemans RL, Jacobson S, Keene J, Kechris K, Miller BE, Tal-Singer R, et al. Multiple biomarkers predict disease severity, progression and mortality in COPD. Respir Res. 2017;18(1):117.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Lipson DA, Barnhart F, Brealey N, Brooks J, Criner GJ, Day NC, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;378(18):1671–80.

    Article  CAS  PubMed  Google Scholar 

  84. Bafadhel M, Peterson S, De Blas MA, Calverley PM, Rennard SI, Richter K, 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 Respir Med. 2018;6(2):117–26.

    Article  CAS  PubMed  Google Scholar 

  85. Siddiqui SH, Guasconi A, Vestbo J, Jones P, Agusti A, Paggiaro P, 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(4):523–5.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G, 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(10125):1076–84.

    Article  CAS  PubMed  Google Scholar 

  87. Watz H, Tetzlaff K, Wouters EFM, Kirsten A, Magnussen H, Rodriguez-Roisin R, 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(5):390–8.

    Article  PubMed  Google Scholar 

  88. Calverley PMA, Tetzlaff K, Vogelmeier C, Fabbri LM, Magnussen H, Wouters EFM, et al. Eosinophilia, frequent exacerbations, and steroid response in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;196(9):1219–21.

    Article  CAS  PubMed  Google Scholar 

  89. Chapman KR, Hurst JR, Frent S-M, Larbig M, Fogel R, Guerin T, 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(3):329–39.

    Article  CAS  PubMed  Google Scholar 

  90. Pavord ID, Chanez P, Criner GJ, Kerstjens HAM, Korn S, Lugogo N, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med. 2017;377(17):1613–29.

    Article  CAS  PubMed  Google Scholar 

  91. Sedgewick AJ, Buschur K, Shi I, Ramsey JD, Raghu VK, Manatakis DV, et al. Mixed graphical models for integrative causal analysis with application to chronic lung disease diagnosis and prognosis. Wren J, editor. Bioinformatics. 2018;183:1129.

    Google Scholar 

  92. Rennard SI, Locantore N, Delafont B, Tal-Singer R, Silverman EK, Vestbo J, et al. Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis. Ann Am Thorac Soc. 2015;12(3):303–12.

    Article  PubMed  Google Scholar 

  93. Chang Y, Glass K, Liu Y-Y, Silverman EK, Crapo JD, Tal-Singer R, et al. COPD subtypes identified by network-based clustering of blood gene expression. Genomics. 2016;107(2–3):51–8.

    Article  CAS  PubMed  Google Scholar 

  94. Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011;184(6):662–71.

    Article  PubMed  Google Scholar 

  95. Le Rouzic O, Roche N, Cortot AB, Tillie-Leblond I, Masure F, Perez T, et al. Defining the “frequent exacerbator” phenotype in COPD: a hypothesis-free approach. Chest. 2018;153(5):1106–15.

    Article  PubMed  Google Scholar 

  96. Aboussouan LS, Stoller JK. Detection of alpha-1 antitrypsin deficiency: a review. Respir Med. 2009;103(3):335–41.

    Article  PubMed  Google Scholar 

  97. Gildea TR, Shermock KM, Singer ME, Stoller JK. Cost-effectiveness analysis of augmentation therapy for severe alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003;167(10):1387–92.

    Article  PubMed  Google Scholar 

  98. Bals R, Koczulla R, Kotke V, Andress J, Blackert K, Vogelmeier C. Identification of individuals with alpha-1-antitrypsin deficiency by a targeted screening program. Respir Med. 2007;101(8):1708–14.

    Article  PubMed  Google Scholar 

  99. Molloy K, Hersh CP, Morris VB, Carroll TP, O'Connor CA, Lasky-Su JA, et al. Clarification of the risk of chronic obstructive pulmonary disease in α1-antitrypsin deficiency PiMZ heterozygotes. Am J Respir Crit Care Med. 2014;189(4):419–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. McElvaney NG, Burdon J, Holmes M, Glanville A, Wark PAB, Thompson PJ, et al. Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med. 2017;5(1):51–60.

    Article  CAS  PubMed  Google Scholar 

  101. Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003;348(21):2059–73.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Beaumont Hospital, Dublin, Ireland

    Emmet O’Brien & Frank C. Sciurba

  2. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Frank C. Sciurba & Jessica Bon

Authors
  1. Emmet O’Brien
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  2. Frank C. Sciurba
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  3. Jessica Bon
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Correspondence to Jessica Bon .

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Editors and Affiliations

  1. Assistant Professor Pulmonary, Critical Care and Sleep Medicine Section, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA

    Jose L. Gomez

  2. Assistant Professor of Informatics, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA

    Blanca E. Himes

  3. Boehringer-Ingelheim Endowed, Professor of Internal Medicine, Chief of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA

    Naftali Kaminski

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O’Brien, E., Sciurba, F.C., Bon, J. (2020). COPD Phenotyping. In: Gomez, J., Himes, B., Kaminski, N. (eds) Precision in Pulmonary, Critical Care, and Sleep Medicine. Respiratory Medicine. Humana, Cham. https://doi.org/10.1007/978-3-030-31507-8_15

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  • DOI: https://doi.org/10.1007/978-3-030-31507-8_15

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  • Publisher Name: Humana, Cham

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