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Non-CF Bronchiectasis

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Macrolides as Immunomodulatory Agents

Part of the book series: Progress in Inflammation Research ((PIR,volume 92))

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Abstract

Bronchiectasis is a disease of recurrent wet cough and acute respiratory exacerbations with objective confirmation by abnormal bronchial dilatation on chest computed tomography scans. There is strong evidence that macrolide maintenance therapy reduces the frequency of respiratory exacerbations in both children and adults. This chapter will focus on the clinical use of macrolides in bronchiectasis in both adults and children, in relation to current guidelines, evidence and key recommendations, as well as exploring risks of long-term therapy and future research priorities.

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References

  1. Chang AB, Fortescue R, Grimwood K, Alexopoulou E, Bell L, Boyd J, et al. European Respiratory Society guidelines for the management of children and adolescents with bronchiectasis. Eur Respir J. 2021;58(2):2002990.

    Article  CAS  PubMed  Google Scholar 

  2. 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(3):1700629.

    Article  PubMed  Google Scholar 

  3. Hill AT, Welham SA, Sullivan AL, Loebinger MR. Updated BTS adult bronchiectasis guideline 2018: a multidisciplinary approach to comprehensive care. Thorax. 2019;74(1):1–3.

    Article  PubMed  Google Scholar 

  4. Chang AB, Bush A, Grimwood K. Bronchiectasis in children: diagnosis and treatment. Lancet. 2018;392(10150):866–79.

    Article  PubMed  Google Scholar 

  5. Cohen R, Shteinberg M. Diagnosis and evaluation of bronchiectasis. Clin Chest Med. 2022;43(1):7–22.

    Article  PubMed  Google Scholar 

  6. Chalmers JD, Chotirmall SH. Bronchiectasis: new therapies and new perspectives. Lancet Respir Med. 2018;6(9):715–26.

    Article  CAS  PubMed  Google Scholar 

  7. Chalmers JD, Chang AB, Chotirmall SH, Dhar R, McShane PJ. Bronchiectasis. Nat Rev Dis Primers. 2018;4(1):45.

    Article  PubMed  Google Scholar 

  8. Lin JL, Xu JF, Qu JM. Bronchiectasis in China. Ann Am Thorac Soc. 2016;13(5):609–16.

    Article  PubMed  Google Scholar 

  9. 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(1):186–93.

    Article  PubMed  Google Scholar 

  10. Weycker D, Hansen GL, Seifer FD. Prevalence and incidence of noncystic fibrosis bronchiectasis among US adults in 2013. Chron Respir Dis. 2017;14(4):377–84.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Aksamit TR, O'Donnell AE, Barker A, Olivier KN, Winthrop KL, Daniels MLA, et al. Bronchiectasis research registry consortium. Adult patients with bronchiectasis: a first look at the US bronchiectasis research registry. Chest. 2017;151(5):982–92.

    Article  PubMed  Google Scholar 

  12. Chandrasekaran R, Mac Aogáin M, Chalmers JD, Elborn SJ, Chotirmall SH. Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis. BMC Pulm Med. 2018;18(1):83.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Henkle E, Chan B, Curtis JR, Aksamit TR, Daley CL, Winthrop KL. Characteristics and health-care utilization history of patients with bronchiectasis in US Medicare enrollees with prescription drug plans, 2006 to 2014. Chest. 2018;154(6):1311–20.

    Article  PubMed  Google Scholar 

  14. Ringshausen FC, Rademacher J, Pink I, de Roux A, Hickstein L, Ploner T, et al. Increasing bronchiectasis prevalence in Germany, 2009-2017: a population-based cohort study. Eur Respir J. 2019;54(6):1900499.

    Article  PubMed  Google Scholar 

  15. Aliberti S, Sotgiu G, Lapi F, Gramegna A, Cricelli C, Blasi F. Prevalence and incidence of bronchiectasis in Italy. BMC Pulm Med. 2020;20(1):15.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Araújo D, Shteinberg M, Aliberti S, Goeminne PC, Hill AT, Fardon T, et al. Standardised classification of the aetiology of bronchiectasis using an objective algorithm. Eur Respir J. 2017;50(6):1701289.

    Article  PubMed  Google Scholar 

  17. Boaventura R, Sibila O, Agusti A, Chalmers JD. Treatable traits in bronchiectasis. Eur Respir J. 2018;52(3):1801269.

    Article  PubMed  Google Scholar 

  18. Flume PA, Chalmers JD, Olivier KN. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet. 2018;392(10150):880–90.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Metersky ML, Barker AF. The pathogenesis of bronchiectasis. Clin Chest Med. 2022;43(1):35–46.

    Article  PubMed  Google Scholar 

  20. Shteinberg M, Flume PA, Chalmers JD. Is bronchiectasis really a disease? Eur Respir Rev. 2020;29(155):190051.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Angrill J, Agustí C, De Celis R, Filella X, Rañó A, Elena M, et al. Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. Am J Respir Crit Care Med. 2001;164(9):1628–32.

    Article  CAS  PubMed  Google Scholar 

  22. Chalmers JD, Hill AT. Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis. Mol Immunol. 2013;55(1):27–34.

    Article  CAS  PubMed  Google Scholar 

  23. Osika E, Cavaillon JM, Chadelat K, Boule M, Fitting C, Tournier G, Clement A. Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease. Eur Respir J. 1999;14(2):339–46.

    Article  CAS  PubMed  Google Scholar 

  24. Bedi P, Davidson DJ, McHugh BJ, Rossi AG, Hill AT. Blood neutrophils are reprogrammed in bronchiectasis. Am J Respir Crit Care Med. 2018;198(7):880–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tsikrika S, Dimakou K, Papaioannou AI, Hillas G, Thanos L, Kostikas K, et al. The role of non-invasive modalities for assessing inflammation in patients with non-cystic fibrosis bronchiectasis. Cytokine. 2017;99:281–6.

    Article  CAS  PubMed  Google Scholar 

  26. Watt AP, Brown V, Courtney J, Kelly M, Garske L, Elborn JS, et al. Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis. Thorax. 2004;59(3):231–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chalmers JD, Smith MP, McHugh BJ, Doherty C, Govan JR, Hill AT. Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2012;186(7):657–65.

    Article  CAS  PubMed  Google Scholar 

  28. 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(22):2127–37.

    Article  CAS  PubMed  Google Scholar 

  29. Keir HR, Shoemark A, Dicker AJ, Perea L, Pollock J, Giam YH, et al. Neutrophil extracellular traps, disease severity, and antibiotic response in bronchiectasis: an international, observational, multicohort study. Lancet Respir Med. 2021;9(8):873–84.

    Article  CAS  PubMed  Google Scholar 

  30. Giam YH, Shoemark A, Chalmers JD. Neutrophil dysfunction in bronchiectasis: an emerging role for immunometabolism. Eur Respir J. 2021;58(2):2003157.

    Article  CAS  PubMed  Google Scholar 

  31. Mac Aogáin M, Narayana JK, Tiew PY, Ali NABM, Yong VFL, Jaggi TK, et al. Integrative microbiomics in bronchiectasis exacerbations. Nat Med. 2021;27(4):688–99.

    Article  PubMed  Google Scholar 

  32. Mac Aogáin M, Chotirmall SH. Microbiology and the microbiome in bronchiectasis. Clin Chest Med. 2022;43(1):23–34.

    Article  PubMed  Google Scholar 

  33. Hill AT, Haworth CS, Aliberti S, Barker A, Blasi F, Boersma W, et al. EMBARC/BRR definitions working group. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. Eur Respir J. 2017;49(6):1700051.

    Article  PubMed  Google Scholar 

  34. Sheehan RE, Wells AU, Copley SJ, Desai SR, Howling SJ, Cole PJ, Wilson R, et al. A comparison of serial computed tomography and functional change in bronchiectasis. Eur Respir J. 2002;20(3):581–7.

    Article  CAS  PubMed  Google Scholar 

  35. 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(5):576–85.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Amati F, Simonetta E, Gramegna A, Tarsia P, Contarini M, Blasi F, et al. The biology of pulmonary exacerbations in bronchiectasis. Eur Respir Rev. 2019;28(154):190055.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Lovie-Toon YG, Grimwood K, Byrnes CA, Goyal V, Busch G, Masters IB, et al. Health-resource use and quality of life in children with bronchiectasis: a multi-center pilot cohort study. BMC Health Serv Res. 2019;19(1):561.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Goyal V, McPhail SM, Hurley F, Grimwood K, Marchant JM, Masters IB, et al. Cost of hospitalization for bronchiectasis exacerbation in children. Respirology. 2020;25(12):1250–6.

    Article  PubMed  Google Scholar 

  39. de la Rosa D, Martínez-Garcia MA, Olveira C, Girón R, Máiz L, Prados C. Annual direct medical costs of bronchiectasis treatment: impact of severity, exacerbations, chronic bronchial colonization and chronic obstructive pulmonary disease coexistence. Chron Respir Dis. 2016;13(4):361–71.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Cox NS, Wilson CJ, Bennett KA, Johnston K, Potter A, Chang AB, et al. Health-related quality of life and psychological wellbeing are poor in children with bronchiectasis and their parents. ERJ Open Res. 2019;5(3):00063–2019.

    Article  PubMed  PubMed Central  Google Scholar 

  41. 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(11):1410–20.

    Article  PubMed  Google Scholar 

  42. Visser SK, Bye PTP, Fox GJ, Burr LD, Chang AB, Holmes-Liew CL, et al. Australian adults with bronchiectasis: the first report from the Australian bronchiectasis registry. Respir Med. 2019;155:97–103.

    Article  PubMed  Google Scholar 

  43. Nathan AM, Muthusamy A, Thavagnanam S, Hashim A, de Bruyne J. Chronic suppurative lung disease in a developing country: impact on child and parent. Pediatr Pulmonol. 2014;49(5):435–40.

    Article  PubMed  Google Scholar 

  44. Kapur N, Masters IB, Chang AB. Longitudinal growth and lung function in pediatric non-cystic fibrosis bronchiectasis: what influences lung function stability? Chest. 2010;138(1):158–64.

    Article  PubMed  Google Scholar 

  45. 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(11):1602–11.

    PubMed  Google Scholar 

  46. Chang AB, Boyd J, Bell L, Goyal V, Masters IB, Powell Z, et al. Clinical and research priorities for children and young people with bronchiectasis: an international roadmap. ERJ Open Res. 2021;7(3):00122–2021.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Gao YH, Guan WJ, Xu G, Lin ZY, Tang Y, Lin ZM, et al. The role of viral infection in pulmonary exacerbations of bronchiectasis in adults: a prospective study. Chest. 2015;147(6):1635–43.

    Article  PubMed  Google Scholar 

  48. Kapur N, Mackay IM, Sloots TP, Masters IB, Chang AB. Respiratory viruses in exacerbations of non-cystic fibrosis bronchiectasis in children. Arch Dis Child. 2014;99(8):749–53.

    Article  PubMed  Google Scholar 

  49. Crichton ML, Shoemark A, Chalmers JD. The impact of the COVID-19 pandemic on exacerbations and symptoms in bronchiectasis: a prospective study. Am J Respir Crit Care Med. 2021;204(7):857–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mallia P, Footitt J, Sotero R, Jepson A, Contoli M, Trujillo-Torralbo MB, 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(11):1117–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Loebinger MR, Wells AU, Hansell DM, Chinyanganya N, Devaraj A, Meister M, Wilson R. Mortality in bronchiectasis: a long-term study assessing the factors influencing survival. Eur Respir J. 2009;34(4):843–9.

    Article  CAS  PubMed  Google Scholar 

  52. 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;71(12):1110–8.

    Article  CAS  PubMed  Google Scholar 

  53. Goyal V, Chang AB. Bronchiectasis in childhood. Clin Chest Med. 2022;43(1):71–88.

    Article  PubMed  Google Scholar 

  54. Kapur N, Stroil-Salama E, Morgan L, Yerkovich S, Holmes-Liew CL, King P, et al. Factors associated with "frequent Exacerbator" phenotype in children with bronchiectasis: the first report on children from the Australian bronchiectasis registry. Respir Med. 2021;188:106627.

    Article  PubMed  Google Scholar 

  55. Gaillard EA, Carty H, Heaf D, Smyth RL. Reversible bronchial dilatation in children: comparison of serial high-resolution computer tomography scans of the lungs. Eur J Radiol. 2003;47(3):215–20.

    Article  CAS  PubMed  Google Scholar 

  56. Eastham KM, Fall AJ, Mitchell L, Spencer DA. The need to redefine non-cystic fibrosis bronchiectasis in childhood. Thorax. 2004;59(4):324–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Haidopoulou K, Calder A, Jones A, Jaffe A, Sonnappa S. Bronchiectasis secondary to primary immunodeficiency in children: longitudinal changes in structure and function. Pediatr Pulmonol. 2009;44(7):669–75.

    Article  PubMed  Google Scholar 

  58. Foo CT, Karia S, Herre J. Reversible bronchiectasis. Thorax. 2022;77(7):733–4.

    Article  PubMed  Google Scholar 

  59. Zhang J, Wang S, Shao C. Reversible bronchial dilatation in adults. Clin Exp Pharmacol Physiol. 2021;48(7):966–70.

    Article  CAS  PubMed  Google Scholar 

  60. Goeminne PC, Cox B, Finch S, Loebinger MR, Bedi P, Hill AT, et al. The impact of acute air pollution fluctuations on bronchiectasis pulmonary exacerbation: a case-crossover analysis. Eur Respir J. 2018;52(1):1702557.

    Article  PubMed  Google Scholar 

  61. Smith D, Du Rand I, Addy CL, Collyns T, Hart SP, Mitchelmore PJ, et al. British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease. Thorax. 2020;75(5):370–404.

    Article  PubMed  Google Scholar 

  62. Grimwood K, Bell SC, Chang AB. Antimicrobial treatment of non-cystic fibrosis bronchiectasis. Expert Rev Anti-Infect Ther. 2014;12(10):1277–96.

    Article  CAS  PubMed  Google Scholar 

  63. Koh YY, Lee MH, Sun YH, Sung KW, Chae JH. Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study. Eur Respir J. 1997;10(5):994–9.

    Article  CAS  PubMed  Google Scholar 

  64. 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(9842):660–7.

    Article  CAS  PubMed  Google Scholar 

  65. Henkle E, Aksamit TR, Barker AF, Curtis JR, Daley CL, Anne Daniels ML, et al. Pharmacotherapy for non-cystic fibrosis bronchiectasis: results from an NTM Info & Research Patient Survey and the bronchiectasis and NTM research registry. Chest. 2017;152(6):1120–7.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Haworth CS, Johnson C, Aliberti S, Goeminne PC, Ringhausen F, Boersma W, et al. Management of bronchiectasis in Europe: Data from the European bronchiectasis registry (EMBARC). Eur Respir J. 2016;48(60):OA273.

    Google Scholar 

  67. 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(4):1113–22.

    Article  PubMed  Google Scholar 

  68. Martinez-García MA, Villa C, Dobarganes Y, Girón R, Maíz L, García-Clemente M, Sibila O, et al. RIBRON: the Spanish online bronchiectasis registry. Characterization of the first 1912 patients. Arch Bronconeumol. 2021;57(1):28–35.

    Article  PubMed  Google Scholar 

  69. Pollock J, Chalmers JD. The immunomodulatory effects of macrolide antibiotics in respiratory disease. Pulm Pharmacol Ther. 2021;71:102095.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sun J, Li Y. Long-term, low-dose macrolide antibiotic treatment in pediatric chronic airway diseases. Pediatr Res. 2022;91(5):1036–42.

    Article  CAS  PubMed  Google Scholar 

  71. Cramer CL, Patterson A, Alchakaki A, Soubani AO. Immunomodulatory indications of azithromycin in respiratory disease: a concise review for the clinician. Postgrad Med. 2017;129(5):493–9.

    Article  PubMed  Google Scholar 

  72. Parnham MJ, Erakovic Haber V, Giamarellos-Bourboulis EJ, Perletti G, Verleden GM, Vos R. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Ther. 2014;143(2):225–45.

    Article  CAS  PubMed  Google Scholar 

  73. Oliver ME, Hinks TSC. Azithromycin in viral infections. Rev Med Virol. 2021;31(2):e2163.

    Article  CAS  PubMed  Google Scholar 

  74. El Boustany P, Gachelin E, Colomban C, Cernoia J, Sudour P, Carsin A, Dubus JC. A review of non-cystic fibrosis bronchiectasis in children with a focus on the role of long-term treatment with macrolides. Pediatr Pulmonol. 2019;54(4):487–96.

    Article  PubMed  Google Scholar 

  75. Steinkamp G, Schmitt-Grohé S, Döring G, Worlitzsch D, Staab D, Schubert R, et al. Clinical and immunomodulatory effects of once weekly azithromycin treatment in Cystic Fibrosis patients chronically infected with Pseudomonas aeruginosa. J Cyst Fibros. 2006;5:S25.

    Article  Google Scholar 

  76. Buyck JM, Plésiat P, Traore H, Vanderbist F, Tulkens PM, Van Bambeke F. Increased susceptibility of Pseudomonas aeruginosa to macrolides and ketolides in eukaryotic cell culture media and biological fluids due to decreased expression of oprM and increased outer-membrane permeability. Clin Infect Dis. 2012;55(4):534–42.

    Article  CAS  PubMed  Google Scholar 

  77. Fouka E, Lamprianidou E, Arvanitidis K, Filidou E, Kolios G, Miltiades P, et al. Low-dose clarithromycin therapy modulates Th17 response in non-cystic fibrosis bronchiectasis patients. Lung. 2014;192(6):849–55.

    Article  CAS  PubMed  Google Scholar 

  78. Liu J, Zhong X, He Z, Wei L, Zheng X, Zhang J, et al. Effect of low-dose, long-term roxithromycin on airway inflammation and remodeling of stable noncystic fibrosis bronchiectasis. Mediat Inflamm. 2014;2014:708608.

    Article  Google Scholar 

  79. 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(10):1697–703.

    PubMed  Google Scholar 

  80. Wang J, Xu L, Lv Y, Sun L. Azithromycin inhibits the production of MUC5AC in the airway mucosa of patients with bronchiectasis induced by Pseudomonas aeruginosa. Pak J Pharm Sci. 2021;34(3 Special):1179–85.

    CAS  PubMed  Google Scholar 

  81. Keir H, Shoemark A, Crichton ML, Dicker A, Pollock J, Giam A, et al. T6 Sputum proteomics identifies mechanisms of disease severity and treatment response in bronchiectasis. Thorax. 2021;76(1):A3.

    Google Scholar 

  82. 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(12):1251–9.

    Article  CAS  PubMed  Google Scholar 

  83. 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(12):1260–7.

    Article  CAS  PubMed  Google Scholar 

  84. Valery PC, Morris PS, Byrnes CA, Grimwood K, Torzillo PJ, Bauert PA, et al. Long-term azithromycin for indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (bronchiectasis intervention study): a multicentre, double-blind, randomised controlled trial. Lancet Respir Med. 2013;1(8):610–20.

    Article  CAS  PubMed  Google Scholar 

  85. Spencer S, Felix LM, Milan SJ, Normansell R, Goeminne PC, Chalmers JD, Donovan T. Oral versus inhaled antibiotics for bronchiectasis. Cochrane Database Syst Rev. 2018;3(3):CD012579.

    PubMed  Google Scholar 

  86. Shi ZL, Peng H, Hu XW, Hu JG. Effectiveness and safety of macrolides in bronchiectasis patients: a meta-analysis and systematic review. Pulm Pharmacol Ther. 2014;28(2):171–8.

    Article  CAS  PubMed  Google Scholar 

  87. Gao YH, Guan WJ, Xu G, Tang Y, Gao Y, Lin ZY, Lin ZM, Zhong NS, Chen RC. Macrolide therapy in adults and children with non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis. PLoS One. 2014;9(3):e90047.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Wu Q, Shen W, Cheng H, Zhou X. Long-term macrolides for non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis. Respirology. 2014;19(3):321–9.

    Article  PubMed  Google Scholar 

  89. Zhuo GY, He Q, Xiang-Lian L, Ya-Nan Y, Si-Te F. Prolonged treatment with macrolides in adult patients with non-cystic fibrosis bronchiectasis: meta-analysis of randomized controlled trials. Pulm Pharmacol Ther. 2014;29(1):80–8.

    Article  CAS  PubMed  Google Scholar 

  90. Fan LC, Lu HW, Wei P, Ji XB, Liang S, Xu JF. Effects of long-term use of macrolides in patients with non-cystic fibrosis bronchiectasis: a meta-analysis of randomized controlled trials. BMC Infect Dis. 2015;15:160.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Kelly C, Chalmers JD, Crossingham I, Relph N, Felix LM, Evans DJ, et al. Macrolide antibiotics for bronchiectasis. Cochrane Database Syst Rev. 2018;3(3):CD012406.

    PubMed  Google Scholar 

  92. Wang D, Fu W, Dai J. Meta-analysis of macrolide maintenance therapy for prevention of disease exacerbations in patients with noncystic fibrosis bronchiectasis. Medicine (Baltimore). 2019;98(17):e15285.

    Article  CAS  PubMed  Google Scholar 

  93. Lee E, Sol IS, Kim JD, Yang HJ, Min TK, Jang GC, et al. Long-term macrolide treatment for non-cystic fibrosis bronchiectasis in children: a meta-analysis. Sci Rep. 2021;11(1):24287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Baldwin DR, Wise R, Andrews JM, Ashby JP, Honeybourne D. Azithromycin concentrations at the sites of pulmonary infection. Eur Respir J. 1990;3(8):886–90.

    Article  CAS  PubMed  Google Scholar 

  95. Rodvold KA, George JM, Yoo L. Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antibacterial agents. Clin Pharmacokinet. 2011;50(10):637–64.

    Article  CAS  PubMed  Google Scholar 

  96. Kryfti M, Bartziokas K, Papaioannou AI, Papadopoulos A, Kostikas K. Clinical effectiveness of macrolides in diseases of the airways: beyond the antimicrobial effects. Pneumonologie. 2013;26(1):33–46.

    Google Scholar 

  97. Parnham MJ, Erakovic HV, Giamarellos-Bourboulis EJ, Perletti G, Verleden GM, et al. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Ther. 2014;143(2):225–45.

    Article  CAS  PubMed  Google Scholar 

  98. Lee E, Hong SJ. Pharmacotherapeutic strategies for treating bronchiectasis in pediatric patients. Expert Opin Pharmacother. 2019;20(8):1025–36.

    Article  CAS  PubMed  Google Scholar 

  99. Tembo T, Higgins J, Mohammed R, Greenhalgh L, Francis H, Kwong NM. Primary care review of patients on long-term azithromycin for chronic lung conditions. Thorax. 2019;74(2):A232.

    Google Scholar 

  100. Kricker JA, Page CP, Gardarsson FR, Baldursson O, Gudjonsson T, Parnham MJ. Nonantimicrobial actions of macrolides: overview and perspectives for future development. Pharmacol Rev. 2021;73(4):233–62.

    Article  CAS  PubMed  Google Scholar 

  101. Chang AB, Bell SC, Byrnes CA, Grimwood K, Holmes PW, King PT, et al. Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand. Med J Aust. 2010;193(6):356–65.

    Article  PubMed  Google Scholar 

  102. Bush A. Lung development and aging. Ann Am Thorac Soc. 2016;13(5):S438–46.

    Article  PubMed  Google Scholar 

  103. Masekela R, Anderson R, Gongxeka H, Steel HC, Green RJ. Lack of efficacy of erythromycin in children with human immunodeficiency virus-related bronchiectasis–A randomised controlled trial. Paediatr Respir Rev. 2013;14:S82.

    Google Scholar 

  104. Barker A, Stoller J, Dieffenbach P. Bronchiectasis in adults: maintaining lung health. In: UpToDate post TW (Ed), UpToDate, Waltham, MA. Accessed May 04, 2022.

    Google Scholar 

  105. Goeminne PC, Soens J, Scheers H, De Wever W, Dupont L. Effect of macrolide on lung function and computed tomography (CT) score in non-cystic fibrosis bronchiectasis. Acta clinica belgica. 2012;67(5):338–46.

    CAS  PubMed  Google Scholar 

  106. Terpstra LC, Altenburg J, Mohamed Hoesein FA, Bronsveld I, Go S, van Rijin PA, et al. The effect of maintenance azithromycin on radiological features in patients with bronchiectasis–analysis from the BAT randomized controlled trial. Respir Med. 2022;192:106718.

    Article  PubMed  Google Scholar 

  107. 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(10):845–54.

    Article  CAS  PubMed  Google Scholar 

  108. Kobbernagel HE, Buchvald FF, Haarman EG, Casaulta C, Collins SA, Hogg C, et al. Efficacy and safety of azithromycin maintenance therapy in primary ciliary dyskinesia (BESTCILIA): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2020;8(5):493–505.

    Article  CAS  PubMed  Google Scholar 

  109. Milito C, Pulvirenti F, Cinetto F, Lougaris V, Soresina A, Pecoraro A, et al. Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies. J Allergy Clin Immunol. 2019;144(2):584–593.e7.

    Article  CAS  PubMed  Google Scholar 

  110. Chellew N, Chang AB, Grimwood K. Azithromycin prescribing by respiratory pediatricians in Australia and New Zealand for chronic wet cough: a questionnaire-based survey. Front Pediatr. 2020;8:519.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Hare KM, Grimwood K, Chang AB, Chatfield MD, Valery PC, Leah AJ, et al. Nasopharyngeal carriage and macrolide resistance in indigenous children with bronchiectasis randomized to long-term azithromycin or placebo. Eur J Clin Microbiol Infect Dis. 2015;34(11):2275–85.

    Article  CAS  PubMed  Google Scholar 

  112. Davidson RJ. In vitro activity and pharmacodynamic/pharmacokinetic parameters of clarithromycin and azithromycin: why they matter in the treatment of respiratory tract infections. Infect Drug Resist. 2019;12:585–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Patel A, Meesters K. Macrolides in children: judicious use, avoiding resistance and reducing adverse effects. Arch Dis Child Educ Pract Ed. 2021;106(4):216–9.

    PubMed  Google Scholar 

  114. Renna M, Schaffner C, Brown K, Shang S, Tamayo MH, Hegyi K, et al. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection. J Clin Invest. 2011;121(9):3554–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Bell SC, Elborn JS, Byrnes CA. Bronchiectasis: treatment decisions for pulmonary exacerbations and their prevention. Respirology. 2018;23(11):1006–22.

    Article  PubMed  Google Scholar 

  116. Ikeda AK, Prince AA, Chen JX, Lieu JEC, Shin JJ. Macrolide-associated sensorineural hearing loss: a systematic review. Laryngoscope. 2018;128(1):228–36.

    Article  CAS  PubMed  Google Scholar 

  117. Wong AYS, Chan EW, Anand S, Worsley AJ, Wong ICK. Managing cardiovascular risk of macrolides: systematic review and meta-analysis. Drug Saf. 2017;40(8):663–77.

    Article  CAS  PubMed  Google Scholar 

  118. Thomas D, McDonald VM, Simpson JL, Smith A, Gupta S, Majellano E, et al. Patterns of azithromycin use in obstructive airway diseases: a real-world observational study. Intern Med J. 2022;52(6):1016–23.

    Article  PubMed  Google Scholar 

  119. Espadas D, Castillo S, Moreno M, Escribano A. Lack of effect of azithromycin on QT interval in children: a cohort study. Arch Dis Child. 2016;101(11):1079.

    Article  PubMed  Google Scholar 

  120. Goyal V, Grimwood K, Ware RS, Byrnes CA, Morris PS, Masters IB, et al. Efficacy of oral amoxicillin-clavulanate or azithromycin for non-severe respiratory exacerbations in children with bronchiectasis (BEST-1): a multicentre, three-arm, double-blind, randomised placebo-controlled trial. Lancet Respir Med. 2019;7(9):791–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Goyal V, Grimwood K, Byrnes CA, Morris PS, Masters IB, Ware RW, et al. Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in children with bronchiectasis (BEST-2): a multicentre, double-blind, non-inferiority, randomised controlled trial. Lancet. 2018;392(10154):1197–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. O'Sullivan B. What's BEST for children with non-cystic fibrosis bronchiectasis? Lancet Respir Med. 2019;7(9):729–30.

    Article  PubMed  Google Scholar 

  123. Sibila O, Laserna E, Shoemark A, et al. Heterogeneity of treatment response in bronchiectasis clinical trials. Eur Respir J. 2022;59(5):2100777.

    Article  CAS  PubMed  Google Scholar 

  124. O'Sullivan B. Raising new questions on best care for bronchiectasis. Lancet Respir Med. 2019;7(10):828–9.

    Article  PubMed  Google Scholar 

  125. Wurzel DF, Chang AB. An update on pediatric bronchiectasis. Expert Rev Respir Med. 2017;11(7):517–32.

    Article  CAS  PubMed  Google Scholar 

  126. Goyal V, Grimwood K, Marchant JM, Masters IB, Chang AB. Paediatric chronic suppurative lung disease: clinical characteristics and outcomes. Eur J Pediatr. 2016;175(8):1077–84.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Respiratory and Sleep Medicine, Children’s Hospital, Brisbane, QLD, Australia

    Dustin Mills, Anne B. Chang & Julie M. Marchant

  2. School of Medicine, The University of Queensland, Brisbane, QLD, Australia

    Dustin Mills & Julie M. Marchant

  3. Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, QLD, Australia

    Anne B. Chang & Julie M. Marchant

  4. Child Health Division, Menzies School of Health Research, Darwin City, NT, Australia

    Anne B. Chang

Authors
  1. Dustin Mills
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  2. Anne B. Chang
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  3. Julie M. Marchant
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Correspondence to Dustin Mills .

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Editors and Affiliations

  1. School of Medicine, Virginia Commonwealth University, Richmond, VA, USA

    Bruce K. Rubin

  2. Clinical Trial Develop & Research Center, Tokyo Shinagawa Hospital, Tokyo, Japan

    Masaharu Shinkai

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Mills, D., Chang, A.B., Marchant, J.M. (2024). Non-CF Bronchiectasis. In: Rubin, B.K., Shinkai, M. (eds) Macrolides as Immunomodulatory Agents. Progress in Inflammation Research, vol 92. Springer, Cham. https://doi.org/10.1007/978-3-031-42859-3_5

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