Phenotyping in bronchiectasis: Are we moving toward a personalized medicine? Phenotyping in bronchiectasis

Paola Faverio; Stefano Carlo Zucchetti; Edoardo Simonetta; Francesco Amati; Andrea Gramegna; Giovanni Sotgiu; Francesco Blasi; Anthony De Soyza; Stefano Aliberti

Authors

Paola Faverio Department of Cardio-Thoracic-Vascular, University of Milan Bicocca, Respiratory Unit, ASST Monza, San Gerardo Hospital, Monza, Italy
Stefano Carlo Zucchetti Department of Cardio-Thoracic-Vascular, University of Milan Bicocca, Respiratory Unit, ASST Monza, San Gerardo Hospital, Monza, Italy
Edoardo Simonetta Department of Cardio-Thoracic-Vascular, University of Milan Bicocca, Respiratory Unit, ASST Monza, San Gerardo Hospital, Monza, Italy
Francesco Amati Department of Pathophysiology and Transplantation, University of Milan, Cardio-Thoracic Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
Andrea Gramegna Department of Pathophysiology and Transplantation, University of Milan, Cardio-Thoracic Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
Giovanni Sotgiu Department of Biomedical Sciences, Clinical Epidemiology and Medical Statistics Unit, University of Sassari, Sassari, Italy
Francesco Blasi Department of Pathophysiology and Transplantation, University of Milan, Cardio-Thoracic Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
Anthony De Soyza Institute of Cellular Medicine, Newcastle University, and UK Bronchiectasis Service, Freeman Hospital, Newcastle Upon Tyne, UK
Stefano Aliberti Department of Pathophysiology and Transplantation, University of Milan, Cardio-Thoracic Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy

Keywords:

Bronchiectasis, etiology, severity, inhaled antibiotics, phenotyping

Abstract

Bronchiectasis (BE) is a heterogeneous disease. Similarly, to other chronic airway diseases, such as asthma and chronic obstructive pulmonary disease, management of BE patients requires a specific and personalized treatment that depends on many clinical, functional, and microbiological variables. Therefore, developing phenotyping methods that can help clinical and therapeutic choices is of paramount importance. Various methodological approaches have been used to personalize patients' management. In this review, we explore the main tools identified so far to classify and phenotype BE patients, including the approaches based on BE etiologies, disease severity, cluster analysis, and endotyping. We also discuss the strengths and limitations of every approach and highlight the similarities and differences between these studies. Finally, we review the therapeutic implications and clinical management connected with each approach.

References

Chalmers JD, Aliberti S, Blasi F. Management of bronchiectasis in adults. Eur Respir J 2015;45:1446-62.

Ringshausen FC, de Roux A, Diel R, Hohmann D, Welte T, Rademacher J. Bronchiectasis in Germany: A population-based estimation of disease prevalence. Eur Respir J 2015;46:1805-7.

Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis Non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax 2010;65 Suppl 1:i1-58.

Aliberti S, Lonni S, Dore S, McDonnell MJ, Goeminne PC, Dimakou K, et al. Clinical phenotypes in adult patients with bronchiectasis. Eur Respir J 2016;47:1113-22.

Guan WJ, Jiang M, Gao YH, Li HM, Xu G, Zheng JP, et al. Unsupervised learning technique identifies bronchiectasis phenotypes with distinct clinical characteristics. Int J Tuberc Lung Dis 2016;20:402-10.

Martínez-García MÁ, Vendrell M, Girón R, Máiz-Carro L, de la Rosa Carrillo D, de Gracia J, et al. The multiple faces of non-cystic fibrosis bronchiectasis. A cluster analysis approach. Ann Am Thorac Soc 2016;13:1468-75.

Buscot M, Pottier H, Marquette CH, Leroy S. Phenotyping adults with non-cystic fibrosis bronchiectasis: A 10-year cohort study in a French regional university hospital center. Respiration 2016;92:1-8.

Anwar GA, McDonnell MJ, Worthy SA, Bourke SC, Afolabi G, Lordan J, et al. Phenotyping adults with non-cystic fibrosis bronchiectasis: A prospective observational cohort study. Respir Med 2013;107:1001-7.

King PT, Holdsworth SR, Farmer M, Freezer N, Villanueva E, Holmes PW. Phenotypes of adult bronchiectasis: Onset of productive cough in childhood and adulthood. COPD 2009;6:130-6.

Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, et al. Chronic obstructive pulmonary disease phenotypes: The future of COPD. Am J Respir Crit Care Med 2010;182:598-604.

Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008;178:218-24.

Gao YH, Guan WJ, Liu SX, Wang L, Cui JJ, Chen RC, et al. Aetiology of bronchiectasis in adults: A systematic literature review. Respirology 2016;21:1376-83.

Aliberti S, Hill AT, Mantero M, Battaglia S, Centanni S, Lo Cicero S, et al. Quality standards for the management of bronchiectasis in Italy: A national audit. Eur Respir J 2016;48:244-8.

Hurst JR, Elborn JS, De Soyza A; BRONCH-UK Consortium. COPD-bronchiectasis overlap syndrome. Eur Respir J 2015;45:310-3.

Chang AB, Bell SC, Torzillo PJ, King PT, Maguire GP, Byrnes CA, et al. Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand Thoracic Society of Australia and New Zealand guidelines. Med J Aust 2015;202:130.

Lonni S, Chalmers JD, Goeminne PC, McDonnell MJ, Dimakou K, et al. Etiology of non-cystic fibrosis bronchiectasis in adults and its correlation to disease severity. Ann Am Thorac Soc 2015;12:1764-70.

Chalmers JD, Goeminne P, Aliberti S, McDonnell MJ, Lonni S, Davidson J, et al. The bronchiectasis severity index. An international derivation and validation study. Am J Respir Crit Care Med 2014;189:576-85.

Martínez-García MÁ, de Gracia J, Vendrell Relat M, Girón RM, Máiz Carro L, de la Rosa Carrillo D, et al. Multidimensional approach to non-cystic fibrosis bronchiectasis: The FACED score. Eur Respir J 2014;43:1357-67.

Li J, Jiao R, Wen LF, Du XB, Gao Y, Li XY, et al. The derivation and validation of a scoring system for identifying patients with bronchiectasis at risk of exacerbations. Zhonghua Jie He He Hu Xi Za Zhi 2016;39:598-602.

Minov J, Karadzinska-Bislimovska J, Vasilevska K, Stoleski S, Mijakoski D. Assessment of the non-cystic fibrosis bronchiectasis severity: The FACED Score vs. the bronchiectasis severity index. Open Respir Med J 2015;9:46-51.

Ellis HC, Cowman S, Fernandes M, Wilson R, Loebinger MR. Predicting mortality in bronchiectasis using bronchiectasis severity index and FACED scores: A 19-year cohort study. Eur Respir J 2016;47:482-9.

McDonnell MJ, Aliberti S, Goeminne PC, Dimakou K, Zucchetti SC, Davidson J, et al. Multidimensional severity assessment in bronchiectasis: An analysis of seven European cohorts. Thorax 2016. pii: Thorax jnl-2016-208481.

Hartigan JA. Clustering. Annu Rev Biophys Bioeng 1973;2:81-101.

Kiley J, Smith R, Noel P. Asthma phenotypes. Curr Opin Pulm Med 2007;13:19-23.

Green RH, Brightling CE, Bradding P. The reclassification of asthma based on subphenotypes. Curr Opin Allergy Clin Immunol 2007;7:43-50.

Stokes JR, Casale TB. Characterization of asthma endotypes: Implications for therapy. Ann Allergy Asthma Immunol 2016;117:121-5.

Izuhara K, Ohta S, Ono J. Using periostin as a biomarker in the treatment of asthma. Allergy Asthma Immunol Res 2016;8:491-8.

Dente FL, Bilotta M, Bartoli ML, Bacci E, Cianchetti S, Latorre M, et al. Neutrophilic bronchial inflammation correlates with clinical and functional findings in patients with noncystic fibrosis bronchiectasis. Mediators Inflamm 2015;2015:642503.

Fuschillo S, De Felice A, Balzano G. Mucosal inflammation in idiopathic bronchiectasis: Cellular and molecular mechanisms. Eur Respir J 2008;31:396-406.

Perlikos F, Hillas G, Loukides S. Phenotyping and endotyping asthma based on biomarkers. Curr Top Med Chem 2016;16:1582-6.

Wells TJ, Whitters D, Sevastsyanovich YR, Heath JN, Pravin J, Goodall M, et al. Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing. J Exp Med 2014;211:1893-904.

McDonnell MJ, Jary HR, Perry A, MacFarlane JG, Hester KL, Small T, et al. Non cystic fibrosis bronchiectasis: A longitudinal retrospective observational cohort study of Pseudomonas persistence and resistance. Respir Med 2015;109:716-26.

Nadig TR, Flume PA. Aerosolized antibiotics for patients with bronchiectasis. Am J Respir Crit Care Med 2016;193:808-10.

Serisier DJ, Martin ML, McGuckin MA, Lourie R, Chen AC, Brain B, et al. Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: The BLESS randomized controlled trial. JAMA 2013;309:1260-7.

Wong C, Jayaram L, Karalus N, Eaton T, Tong C, Hockey H, et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): A randomised, double-blind, placebo-controlled trial. Lancet 2012;380:660-7.

Altenburg J, de Graaff CS, Stienstra Y, Sloos JH, van Haren EH, Koppers RJ, et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: The BAT randomized controlled trial. JAMA 2013;309:1251-9.

Quon BS, Goss CH, Ramsey BW. Inhaled antibiotics for lower airway infections. Ann Am Thorac Soc 2014;11:425-34.

Tay GT, Reid DW, Bell SC. Inhaled antibiotics in cystic fibrosis (CF) and non-CF bronchiectasis. Semin Respir Crit Care Med 2015;36:267-86.

Chalmers JD, Loebinger M, Aliberti S. Challenges in the development of new therapies for bronchiectasis. Expert Opin Pharmacother 2015;16:833-50.

Finch S, McDonnell MJ, Abo-Leyah H, Aliberti S, Chalmers JD. A comprehensive analysis of the impact of pseudomonas aeruginosa colonization on prognosis in adult bronchiectasis. Ann Am Thorac Soc 2015;12:1602-11.

Brodt AM, Stovold E, Zhang L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: A systematic review. Eur Respir J 2014;44:382-93.

Aliberti S, Masefield S, Polverino E, De Soyza A, Loebinger MR, Menendez R, et al. Research priorities in bronchiectasis: A consensus statement from the EMBARC clinical research collaboration. Eur Respir J 2016;48:632-47.

Chalmers JD, Aliberti S, Polverino E, Vendrell M, Crichton M, Loebinger M, et al. The EMBARC European bronchiectasis registry: Protocol for an international observational study. ERJ Open Res 2016;2. pii: 00081-2015.

Phenotyping in bronchiectasis: Are we moving toward a personalized medicine?