DOI QR코드

DOI QR Code

Exacerbation Prevention and Management of Bronchiectasis

  • Joon Young Choi (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • 투고 : 2023.01.25
  • 심사 : 2023.05.03
  • 발행 : 2023.07.31

초록

Bronchiectasis, which is characterized by irreversibly damaged and dilated bronchi, causes significant symptoms, poor quality of life, and increased economic burden and mortality rates. Despite its increasing prevalence and clinical significance, bronchiectasis was previously regarded as an orphan disease, and ideal treatment of this disease has been poorly understood. The European Respiratory Society and British Thoracic Society have recently published guidelines to assist physicians in the clinical field. Guidelines and reports suggest comprehensive management that includes both non-pharmacological and pharmacological treatment. Physiotherapy and pulmonary rehabilitation are two of the most important non-pharmacologic therapies in bronchiectasis patients; long-term inhaled antibiotics and macrolide therapy have gained significant evidence in reducing exacerbation risk in frequent exacerbators. In this review, we summarize recent updates on bronchiectasis treatment to prevent exacerbation and manage clinical deterioration.

키워드

참고문헌

  1. Macfarlane L, Kumar K, Scoones T, Jones A, Loebinger MR, Lord R. Diagnosis and management of non-cystic fibrosis bronchiectasis. Clin Med (Lond) 2021;21:e571-7. https://doi.org/10.7861/clinmed.2021-0651
  2. 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. https://doi.org/10.1136/thx.2010.136119
  3. Keistinen T, Saynajakangas O, Tuuponen T, Kivela SL. Bronchiectasis: an orphan disease with a poorly-understood prognosis. Eur Respir J 1997;10:2784-7. https://doi.org/10.1183/09031936.97.10122784
  4. Chalmers JD. Bronchiectasis from 2012 to 2022. Clin Chest Med 2022;43:1-6. https://doi.org/10.1016/j.ccm.2021.12.001
  5. Weycker D, Hansen GL, Seifer FD. Prevalence and incidence of noncystic fibrosis bronchiectasis among US adults in 2013. Chron Respir Dis 2017;14:377-84. https://doi.org/10.1177/1479972317709649
  6. Quint JK, Millett ER, Joshi M, Navaratnam V, Thomas SL, Hurst JR, et al. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study. Eur Respir J 2016;47:186-93. https://doi.org/10.1183/13993003.01033-2015
  7. Monteagudo M, Rodriguez-Blanco T, Barrecheguren M, Simonet P, Miravitlles M. Prevalence and incidence of bronchiectasis in Catalonia, Spain: a population-based study. Respir Med 2016;121:26-31. https://doi.org/10.1016/j.rmed.2016.10.014
  8. Choi H, Lee H, Ra SW, Jang JG, Lee JH, Jhun BW, et al. Developing a diagnostic bundle for bronchiectasis in South Korea: a modified Delphi consensus study. Tuberc Respir Dis (Seoul) 2022;85:56-66. https://doi.org/10.4046/trd.2021.0136
  9. Choi H, Yang B, Nam H, Kyoung DS, Sim YS, Park HY, et al. Population-based prevalence of bronchiectasis and associated comorbidities in South Korea. Eur Respir J 2019;54:1900194.
  10. Diel R, Chalmers JD, Rabe KF, Nienhaus A, Loddenkemper R, Ringshausen FC. Economic burden of bronchiectasis in Germany. Eur Respir J 2019;53:1802033.
  11. Choi H, Yang B, Kim YJ, Sin S, Jo YS, Kim Y, et al. Increased mortality in patients with non cystic fibrosis bronchiectasis with respiratory comorbidities. Sci Rep 2021;11:7126.
  12. Kim Y, Kim K, Rhee CK, Ra SW. Increased hospitalizations and economic burden in COPD with bronchiectasis: a nationwide representative study. Sci Rep 2022;12:3829.
  13. Yang B, Jang HJ, Chung SJ, Yoo SJ, Kim T, Kim SH, et al. Factors associated with bronchiectasis in Korea: a national database study. Ann Transl Med 2020;8:1350.
  14. Sin S, Yun SY, Kim JM, Park CM, Cho J, Choi SM, et al. Mortality risk and causes of death in patients with non-cystic fibrosis bronchiectasis. Respir Res 2019;20:271.
  15. 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. https://doi.org/10.1164/rccm.201309-1575OC
  16. Chalmers JD, Aliberti S, Filonenko A, Shteinberg M, Goeminne PC, Hill AT, et al. Characterization of the "frequent exacerbator phenotype" in bronchiectasis. Am J Respir Crit Care Med 2018;197:1410-20. https://doi.org/10.1164/rccm.201711-2202OC
  17. Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, et al. Inflammatory responses, spirometry, and quality of life in subjects with bronchiectasis exacerbations. Respir Care 2015;60:1180-9. https://doi.org/10.4187/respcare.04004
  18. Hill AT, Sullivan AL, Chalmers JD, De Soyza A, Elborn SJ, Floto AR, et al. British Thoracic Society guideline for bronchiectasis in adults. Thorax 2019;74(Suppl 1):1-69. https://doi.org/10.1136/thoraxjnl-2018-212463
  19. Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J 2017;50:1700629.
  20. Murray MP, Pentland JL, Hill AT. A randomised crossover trial of chest physiotherapy in non-cystic fibrosis bronchiectasis. Eur Respir J 2009;34:1086-92. https://doi.org/10.1183/09031936.00055509
  21. O'Neill B, Bradley JM, McArdle N, MacMahon J. The current physiotherapy management of patients with bronchiectasis: a UK survey. Int J Clin Pract 2002;56:34-5. https://doi.org/10.1111/j.1742-1241.2002.tb11186.x
  22. Thompson CS, Harrison S, Ashley J, Day K, Smith DL. Randomised crossover study of the Flutter device and the active cycle of breathing technique in non-cystic fibrosis bronchiectasis. Thorax 2002;57:446-8. https://doi.org/10.1136/thorax.57.5.446
  23. Patterson JE, Bradley JM, Hewitt O, Bradbury I, Elborn JS. Airway clearance in bronchiectasis: a randomized crossover trial of active cycle of breathing techniques versus acapella. Respiration 2005;72:239-42. https://doi.org/10.1159/000085363
  24. Eaton T, Young P, Zeng I, Kolbe J. A randomized evaluation of the acute efficacy, acceptability and tolerability of flutter and active cycle of breathing with and without postural drainage in non-cystic fibrosis bronchiectasis. Chron Respir Dis 2007;4:23-30. https://doi.org/10.1177/1479972306074481
  25. Lee AL, Williamson HC, Lorensini S, Spencer LM. The effects of oscillating positive expiratory pressure therapy in adults with stable non-cystic fibrosis bronchiectasis: a systematic review. Chron Respir Dis 2015;12:36-46. https://doi.org/10.1177/1479972314562407
  26. Munoz G, de Gracia J, Buxo M, Alvarez A, Vendrell M. Long-term benefits of airway clearance in bronchiectasis: a randomised placebo-controlled trial. Eur Respir J 2018;51:1701926.
  27. Huang HY, Chung FT, Lin CY, Lo CY, Huang YT, Huang YC, et al. Influence of comorbidities and airway clearance on mortality and outcomes of patients with severe bronchiectasis exacerbations in Taiwan. Front Med (Lausanne) 2022;8:812775.
  28. Liu Y, Lu HW, Gu SY, Wang WW, Ge J, Jie ZJ, et al. Bronchoscopic airway clearance therapy for acute exacerbations of bronchiectasis. EBioMedicine 2021;72:103587.
  29. Ora J, Prendi E, Ritondo BL, Pata X, Spada F, Rogliani P. Pulmonary rehabilitation in noncystic fibrosis bronchiectasis. Respiration 2022;101:97-105. https://doi.org/10.1159/000517527
  30. Yang F, Gao L, Wang Q, Deng W, Gao W. Effect of exercise-based pulmonary rehabilitation in patients with bronchiectasis: a meta-analysis. Respir Med Res 2022;81:100910.
  31. Cedeno de Jesus S, Almadana Pacheco V, Valido Morales A, Muniz Rodriguez AM, Ayerbe Garcia R, Arnedillo-Munoz A. Exercise capacity and physical activity in non-cystic fibrosis bronchiectasis after a pulmonary rehabilitation home-based programme: a randomised controlled trial. Int J Environ Res Public Health 2022;19:11039.
  32. Candemir I, Ergun P, Satar S, Karamanli H, Kaymaz D, Demir N. Efficacy of pulmonary rehabilitation for bronchiectasis and related factors: which patients should receive the most treatment? Adv Respir Med 2021;89:15-22. https://doi.org/10.5603/ARM.a2021.0029
  33. Chalmers JD, Crichton ML, Brady G, Finch S, Lonergan M, Fardon TC. Pulmonary rehabilitation after exacerbation of bronchiectasis: a pilot randomized controlled trial. BMC Pulm Med 2019;19:85.
  34. Alcaraz-Serrano V, Gimeno-Santos E, Scioscia G, Gabarrus A, Navarro A, Herrero-Cortina B, et al. Association between physical activity and risk of hospitalisation in bronchiectasis. Eur Respir J 2020;55:1902138.
  35. Xu JF, Gao YH, Song YL, Qu JM, Guan WJ. Research advances and clinical management of bronchiectasis: Chinese perspective. ERJ Open Res 2022;8:00017-2022.
  36. Selman A, Merhej H, Nakagiri T, Zinne N, Goecke T, Haverich A, et al. Surgical treatment of non-cystic fibrosis bronchiectasis in Central Europe. J Thorac Dis 2021;13:5843-50. https://doi.org/10.21037/jtd-21-879
  37. O'Donnell AE, Barker AF, Ilowite JS, Fick RB. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. rhDNase Study Group. Chest 1998;113:1329-34. https://doi.org/10.1378/chest.113.5.1329
  38. Bilton D, Daviskas E, Anderson SD, Kolbe J, King G, Stirling RG, et al. Phase 3 randomized study of the efficacy and safety of inhaled dry powder mannitol for the symptomatic treatment of non-cystic fibrosis bronchiectasis. Chest 2013;144:215-25. https://doi.org/10.1378/chest.12-1763
  39. Bilton D, Tino G, Barker AF, Chambers DC, De Soyza A, Dupont LJ, et al. Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial. Thorax 2014;69:1073-9. https://doi.org/10.1136/thoraxjnl-2014-205587
  40. Gao YH, Abo Leyah H, Finch S, Lonergan M, Aliberti S, De Soyza A, et al. Relationship between symptoms, exacerbations, and treatment response in bronchiectasis. Am J Respir Crit Care Med 2020;201:1499-507. https://doi.org/10.1164/rccm.201910-1972OC
  41. Maiz Carro L, Martinez-Garcia MA. Nebulized hypertonic saline in noncystic fibrosis bronchiectasis: a comprehensive review. Ther Adv Respir Dis 2019;13:1753466619866102.
  42. Qi Q, Ailiyaer Y, Liu R, Zhang Y, Li C, Liu M, et al. Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial. Respir Res 2019;20:73.
  43. Luo A, Liu X, Hu Q, Yang M, Jiang H, Liu W. Efficacy of N-acetylcysteine on idiopathic or postinfective non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis protocol. BMJ Open 2022;12:e053625.
  44. Liao Y, Wu Y, Zi K, Shen Y, Wang T, Qin J, et al. The effect of N-acetylcysteine in patients with non-cystic fibrosis bronchiectasis (NINCFB): study protocol for a multicentre, double-blind, randomised, placebo-controlled trial. BMC Pulm Med 2022;22:401.
  45. Flume PA, Chalmers JD, Olivier KN. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet 2018;392:880-90. https://doi.org/10.1016/S0140-6736(18)31767-7
  46. 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.
  47. Chalmers JD, Moffitt KL, Suarez-Cuartin G, Sibila O, Finch S, Furrie E, et al. Neutrophil elastase activity is associated with exacerbations and lung function decline in bronchiectasis. Am J Respir Crit Care Med 2017;195:1384-93. https://doi.org/10.1164/rccm.201605-1027OC
  48. Chalmers JD, Haworth CS, Metersky ML, Loebinger MR, Blasi F, Sibila O, et al. Phase 2 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N Engl J Med 2020;383:2127-37. https://doi.org/10.1056/NEJMoa2021713
  49. Hakansson KE, Fjaellegaard K, Browatzki A, Donmez Sin M, Ulrik CS. Inhaled corticosteroid therapy in bronchiectasis is associated with all-cause mortality: a prospective cohort study. Int J Chron Obstruct Pulmon Dis 2021;16:2119-27. https://doi.org/10.2147/COPD.S311236
  50. Shoemark A, Shteinberg M, De Soyza A, Haworth CS, Richardson H, Gao Y, et al. Characterization of eosinophilic bronchiectasis: a European multicohort study. Am J Respir Crit Care Med 2022;205:894-902. https://doi.org/10.1164/rccm.202108-1889OC
  51. Aliberti S, Sotgiu G, Blasi F, Saderi L, Posadas T, Martinez Garcia MA. Blood eosinophils predict inhaled fluticasone response in bronchiectasis. Eur Respir J 2020;56:2000453.
  52. Martinez-Garcia MA, Posadas T, Sotgiu G, Blasi F, Saderi L, Aliberti S. Role of inhaled corticosteroids in reducing exacerbations in bronchiectasis patients with blood eosinophilia pooled post-hoc analysis of 2 randomized clinical trials. Respir Med 2020;172:106127.
  53. Rademacher J, Konwert S, Fuge J, Dettmer S, Welte T, Ringshausen FC. Anti-IL5 and anti-IL5Rα therapy for clinically significant bronchiectasis with eosinophilic endotype: a case series. Eur Respir J 2020;55:1901333.
  54. Martinez FJ, Calverley PM, Goehring UM, Brose M, Fabbri LM, Rabe KF. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet 2015;385:857-66. https://doi.org/10.1016/S0140-6736(14)62410-7
  55. Juthong S, Panyarath P. Efficacy of roflumilast in bronchiectasis patients with frequent exacerbations: a double-blinded, randomized, placebo-controlled pilot clinical trial. Tuberc Respir Dis (Seoul) 2022;85:67-73. https://doi.org/10.4046/trd.2021.0051
  56. Sobala R, De Soyza A. Bronchiectasis and chronic obstructive pulmonary disease overlap syndrome. Clin Chest Med 2022;43:61-70. https://doi.org/10.1016/j.ccm.2021.11.005
  57. Kim SH, Kim C, Jeong I, Lee SJ, Kim TH, Lee CY, et al. Chronic obstructive pulmonary disease is associated with decreased quality of life in bronchiectasis patients: findings from the KMBARC Registry. Front Med (Lausanne) 2021;8:722124.
  58. Jeong HJ, Lee H, Carriere KC, Kim JH, Han JH, Shin B, et al. Effects of long-term bronchodilators in bronchiectasis patients with airflow limitation based on bronchodilator response at baseline. Int J Chron Obstruct Pulmon Dis 2016;11:2757-64. https://doi.org/10.2147/COPD.S115581
  59. Lee SY, Lee JS, Lee SW, Oh YM. Effects of treatment with long-acting muscarinic antagonists (LAMA) and long-acting beta-agonists (LABA) on lung function improvement in patients with bronchiectasis: an observational study. J Thorac Dis 2021;13:169-77. https://doi.org/10.21037/jtd-20-1282
  60. Jayaram L, Vandal AC, Chang CL, Lewis C, Tong C, Tuffery C, et al. Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial. Eur Respir J 2022;59:2102184.
  61. Chalmers JD, Chotirmall SH. Bronchiectasis: new therapies and new perspectives. Lancet Respir Med 2018;6:715-26. https://doi.org/10.1016/S2213-2600(18)30053-5
  62. 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.
  63. Martinez-Garcia MA, Oscullo G, Posadas T, Zaldivar E, Villa C, Dobarganes Y, et al. Pseudomonas aeruginosa and lung function decline in patients with bronchiectasis. Clin Microbiol Infect 2021;27:428-34. https://doi.org/10.1016/j.cmi.2020.04.007
  64. Kwok WC, Ho JC, Tam TC, Ip MS, Lam DC. Risk factors for Pseudomonas aeruginosa colonization in non-cystic fibrosis bronchiectasis and clinical implications. Respir Res 2021;22:132.
  65. Murray MP, Govan JR, Doherty CJ, Simpson AJ, Wilkinson TS, Chalmers JD, et al. A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med 2011;183:491-9. https://doi.org/10.1164/rccm.201005-0756OC
  66. Serisier DJ, Bilton D, De Soyza A, Thompson PJ, Kolbe J, Greville HW, et al. Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial. Thorax 2013;68:812-7. https://doi.org/10.1136/thoraxjnl-2013-203207
  67. Haworth CS, Foweraker JE, Wilkinson P, Kenyon RF, Bilton D. Inhaled colistin in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. Am J Respir Crit Care Med 2014;189:975-82. https://doi.org/10.1164/rccm.201312-2208OC
  68. Aksamit T, De Soyza A, Bandel TJ, Criollo M, Elborn JS, Operschall E, et al. RESPIRE 2: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis. Eur Respir J 2018;51:1702053.
  69. De Soyza A, Aksamit T, Bandel TJ, Criollo M, Elborn JS, Operschall E, et al. RESPIRE 1: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis. Eur Respir J 2018;51:1702052.
  70. Haworth CS, Bilton D, Chalmers JD, Davis AM, Froehlich J, Gonda I, et al. Inhaled liposomal ciprofloxacin in patients with non-cystic fibrosis bronchiectasis and chronic lung infection with Pseudomonas aeruginosa (ORBIT-3 and ORBIT-4): two phase 3, randomised controlled trials. Lancet Respir Med 2019;7:213-26. https://doi.org/10.1016/S2213-2600(18)30427-2
  71. Crichton ML, Lonergan M, Barker AF, Sibila O, Goeminne P, Shoemark A, et al. Inhaled aztreonam improves symptoms of cough and sputum production in patients with bronchiectasis: a post hoc analysis of the AIR-BX studies. Eur Respir J 2020;56:2000608.
  72. Sangiovanni S, Morales EI, Fernandez-Trujillo L. Inhaled tobramycin for chronic infection with pseudomonas aeruginosa in non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis. Respir Med 2021;176:106283.
  73. Laska IF, Crichton ML, Shoemark A, Chalmers JD. The efficacy and safety of inhaled antibiotics for the treatment of bronchiectasis in adults: a systematic review and meta-analysis. Lancet Respir Med 2019;7:855-69. https://doi.org/10.1016/S2213-2600(19)30185-7
  74. Chalmers JD, Cipolla D, Thompson B, Davis AM, O'Donnell A, Tino G, et al. Changes in respiratory symptoms during 48-week treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies. Eur Respir J 2020;56:2000110.
  75. Elborn JS, Blasi F, Haworth CS, Ballmann M, Tiddens HA, Murris-Espin M, et al. Bronchiectasis and inhaled tobramycin: a literature review. Respir Med 2022;192:106728.
  76. Loebinger MR, Polverino E, Chalmers JD, Tiddens HA, Goossens H, Tunney M, et al. Efficacy and safety of TOBI Podhaler in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study. Eur Respir J 2021;57:2001451.
  77. Riveiro V, Casal A, Alvarez-Dobano JM, Lourido T, Suarez-Artime P, Rodriguez-Garcia C, et al. Response to inhaled ceftazidime in patients with non-cystic fibrosis bronchiectasis and chronic bronchial infection unrelated to Pseudomonas aeruginosa. Clin Respir J 2022;16:768-73. https://doi.org/10.1111/crj.13534
  78. Barker AF, O'Donnell AE, Flume P, Thompson PJ, Ruzi JD, de Gracia J, et al. Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIRBX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials. Lancet Respir Med 2014;2:738-49. https://doi.org/10.1016/S2213-2600(14)70165-1
  79. Haworth CS, Floto RA. Antibiotic management in bronchiectasis. Clin Chest Med 2022;43:165-77. https://doi.org/10.1016/j.ccm.2021.11.009
  80. Sibila O, Laserna E, Shoemark A, Keir HR, Finch S, Rodrigo-Troyano A, et al. Airway bacterial load and inhaled antibiotic response in bronchiectasis. Am J Respir Crit Care Med 2019;200:33-41. https://doi.org/10.1164/rccm.201809-1651OC
  81. Guan WJ, Xu JF, Luo H, Xu XX, Song YL, Ma WL, et al. A double-blind randomized placebo-controlled phase 3 trial of tobramycin inhalation solution in adults with bronchiectasis with Pseudomonas aeruginosa infection. Chest 2023;163:64-76. https://doi.org/10.1016/j.chest.2022.07.007
  82. Chalmers JD, Boersma W, Lonergan M, Jayaram L, Crichton ML, Karalus N, et al. Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis. Lancet Respir Med 2019;7:845-54. https://doi.org/10.1016/S2213-2600(19)30191-2
  83. 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. https://doi.org/10.1001/jama.2013.1937
  84. 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. https://doi.org/10.1001/jama.2013.2290
  85. 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. https://doi.org/10.1016/S0140-6736(12)60953-2
  86. Burr LD, Rogers GB, Chen AC, Hamilton BR, Pool GF, Taylor SL, et al. Macrolide treatment inhibits Pseudomonas aeruginosa quorum sensing in non-cystic fibrosis bronchiectasis. an analysis from the bronchiectasis and low-dose erythromycin study trial. Ann Am Thorac Soc 2016;13:1697-703.
  87. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2021 report) [Internet]. Deer Park: GOLD; 2021 [cited 2023 May 26]. Available from: https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf.
  88. Choi Y, Shin SH, Lee H, Cho HK, Im Y, Kang N, et al. Favorable response to long-term azithromycin therapy in bronchiectasis patients with chronic airflow obstruction compared to chronic obstructive pulmonary disease patients without bronchiectasis. Int J Chron Obstruct Pulmon Dis 2021;16:855-63. https://doi.org/10.2147/COPD.S292297
  89. Yang B, Ryu J, Kim T, Jo YS, Kim Y, Park HY, et al. Impact of bronchiectasis on incident nontuberculous mycobacterial pulmonary disease: a 10-year national cohort study. Chest 2021;159:1807-11. https://doi.org/10.1016/j.chest.2020.12.020
  90. Metersky ML, Choate R; Bronchiectasis and NTM Research Registry Investigators. The association of longterm macrolide therapy and nontuberculous mycobacterial culture positivity in patients with bronchiectasis. Chest 2021;160:466-9. https://doi.org/10.1016/j.chest.2021.02.019
  91. Hill AT, Haworth CS, Aliberti S, Barker A, Blasi F, Boersma W, et al. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. Eur Respir J 2017;49:1700051.
  92. Bedi P, Cartlidge MK, Zhang Y, Turnbull K, Donaldson S, Clarke A, et al. Feasibility of shortening intravenous antibiotic therapy for bronchiectasis based on bacterial load: a proof-of-concept randomised controlled trial. Eur Respir J 2021;58:2004388.
  93. Flume PA, Basavaraj A, Garcia B, Winthrop K, Di Mango E, Daley CL, et al. Towards development of evidence to inform recommendations for the evaluation and management of bronchiectasis. Respir Med 2023;211:107217.