Bronchiectasis: literature review for preparation of 2024 clinical guidelines

Bronchiectasis, ICD-10 – J47, (BE) is a chronic respiratory disease characterized clinically by cough, sputum production and bronchial infection, and radiographically by abnormal and persistent dilation of the bronchi. Common causes include cystic fibrosis, primary ciliary dyskinesia, immune disorders, systemic inflammatory diseases and infections, and other factors. However, some cases are idiopathic, when the cause cannot be identified. In practice, patients with bronchiectasis are divided into two groups: associated and not associated with cystic fibrosis. The prevalence of the disease varies significantly worldwide; it is not reliably known in the Russian Federation.

The aim of the review is to analyze the literature data on modern approaches to the diagnosis of BE and to familiarize readers with diagnostic methods and basic approaches to the treatment.

Methods. Data from 77 articles and the expert opinion of specialists providing care to patients with BE were used.

Results. The main causes, frequency of occurrence, clinical phenotypes and treatment approaches for BE are described. There are many clinical, laboratory, instrumental and radiological features that provide insight into the etiology of BE. The European consensus is that the goal of treating BE is to restore or maintain normal lung function. There are no randomized trials on the treatment of BE, so all treatment guidelines are based on very low-level evidence or extrapolated from cystic fibrosis guidelines. Recommendations for mucolytic, antibacterial and anti-inflammatory therapy for BE are described, taking into account international and national experience.

Conclusion. The development of a new version of clinical guidelines with modern relevant information will improve the diagnosis and treatment of BE in the Russian Federation.

1. Laennec R.T.H. A treatise on the disease of the chest: with plates. New York: Academy Medicine; 1962. Available at: https://archive.org/details/treatiseondiseas0000laen/page/n1/mode/2up

2. Cole P.J. Inflammation: a two-edged sword – the model of bronchiectasis. Eur .J. Respir. Dis. Suppl. 1986; 147: 6–15.

3. Pembridge T., Chalmers J.D. Precision medicine in bronchiectasis. Breathe (Sheff). 2021; 17 (4): 210119. DOI: 10.1183/20734735.0119-2021.

4. Rachinsky S.V., Tatochenko V.K., eds. [Respiratory diseases in children]. Moscow: Meditsina; 1988 (in Russian).

5. Rozinova N.N., Mizernitsky Yu.L. eds. [Chronic lung diseases in children]. Moscow: Praktika; 2011 (in Russian).

6. Tatochenko V.K., ed. [Respiratory diseases in children]. Moscow: Pediatr; 2012 (in Russian).

7. Eber E., Midulla F., eds. ERS handbook paediatric respiratory medicine. 2nd Edn. Sheffield: ERS; 2021. DOI: 10.1183/9781849841313.eph01.

8. Lowe D.M., Hurst J.R. Primary immunodeficiency. In: Chalmers J.D., Polverino E., Aliberti S., eds. Bronchiectasis. Sheffield: ERS; 2018: 153–166. DOI: 10.1183/2312508X.10015917.

9. Polverino E., Goeminne P.C., McDonnell M.J. et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur. Respir. J. 2017; 50 (3): 1700629. DOI: 10.1183/13993003.00629-2017.

10. Chang A.B., Fortescue R., Grimwood K. et al. European Respiratory Society guidelines for the management of children and adolescents with bronchiectasis. Eur. Respir. J. 2021; 58 (2): 2002990. DOI: 10.1183/13993003.02990-2020.

11. Weycker D., Edelsberg J., Oster G., Tino G. Prevalence and economic burden of bronchiectasis. Clin. Pulm. Med. 2005; 12 (4): 205–209. DOI: 10.1097/01.cpm.0000171422.98696.ed.

12. Feng J., Sun L., Sun X. et al. Increasing prevalence and burden of bronchiectasis in urban Chinese adults, 2013-2017: a nationwide population-based cohort study. Respir. Res. 2022; 23 (1): 111. DOI: 10.1186/s12931-022-02023-8.

13. Bilton D., Jones A.L. Bronchiectasis: epidemiology and causes. In: Floto R.A., Haworth C.S., eds. Bronchiectasis (out of print). Sheffield: ERS; 2011. Vol. 52: 1–10. DOI: 10.1183/1025448x.erm5210.

14. Flume P.A., Chalmers J.D., Olivier K.N. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet. 2018; 392 (10150): 880–890. DOI: 10.1016/S0140-6736(18)31767-7.

15. Contarini M., Finch S., Chalmers J.D. Bronchiectasis: a case-based approach to investigation and management. Eur. Respir. Rev. 2018; 27 (149): 180016. DOI: 10.1183/16000617.0016-2018.

16. Altenburg J., Wortel K., van der Werf T.S., Boersma W.G. Non-cystic fibrosis bronchiectasis: clinical presentation, diagnosis and treatment, illustrated by data from a Dutch Teaching Hospital. Neth. J. Med. 2015; 73 (4): 147–154. Available at: https://www.njmonline.nl/article.php?a=1561&d=1036&i=182

17. Smith M.P. Diagnosis and management of bronchiectasis. CMAJ. 2017; 189 (24): E828–835. DOI: 10.1503/cmaj.160830.

18. Ullmann N., Porcaro F., Petreschi F. et al. Noncystic fibrosis bronchiectasis in children and adolescents: Follow-up over a decade. Pediatr. Pulmonol. 2021; 56 (9): 3026–3034. DOI: 10.1002/ppul.25553.

19. Pasteur M.C., Bilton D., Hill A.T.; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010; 65 (7): 577. DOI: 10.1136/thx.2010.142778.

20. Krasovsky S.A., Starinova M.A., Voronkova A.Yu. et al., eds. [Register of patients with cystic fibrosis in the Russian Federation. 2021]. St. Petersburg: Blagotvoritel’nyy fond “Ostrova”»; 2023. Available at: https://mukoviscidoz.org/doc/registr/registr_systicfibrosis_brochure_19_10.pdf (in Russian).

21. King P.T., Holdsworth S.R., Freezer N.J. et al. Microbiologic follow-up study in adult bronchiectasis. Respir. Med. 2007; 101 (8): 1633–1638. DOI: 10.1016/j.rmed.2007.03.009.

22. Cummings S., Nelson A., Purcell P. et al. A comparative study of polymicrobial diversity in CF and non-CF bronchiectasis. Thorax. 2010; 65 (4): A13–A14. DOI: 10.1136/thx.2010.150912.23.

23. Foweraker J.E., Wat D. Microbiology of non-CF bronchiectasis. In: Floto R.A., Haworth C.S., eds. Bronchiectasis (out of print). Sheffield: ERS; 2011. Vol. 52: 68–96. DOI: 10.1183/1025448x.10003610.

24. Finch S., McDonnell M.J., Abo-Leyah H. et al. A Comprehensive analysis of the impact of pseudomonas aeruginosa colonization on prognosis in adult bronchiectasis. Ann. Am. Thorac. Soc. 2015; 12 (11): 1602–1611. DOI: 10.1513/AnnalsATS.201506-333OC.

25. Pasteur M.C., Helliwell S.M., Houghton S.J. et al. An investigation into causative factors in patients with bronchiectasis. Am. J. Respir. Crit. Care Med. 2000; 162 (4, Pt 1): 1277–1284. DOI: 10.1164/ajrccm.162.4.9906120.

26. Reid L.M. Reduction in bronchial subdivision in bronchiectasis. Thorax. 1950; 5 (3): 233–247. DOI: 10.1136/thx.5.3.233.

27. Angrill J., Agusti C., De Celis R. et al. Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. Am. J. Respir. Crit. Care Med. 2001; 164 (9): 1628–1632. DOI: 10.1164/ajrccm.164.9.2105083.

28. Chang A.B., Masel J.P., Boyce N.C. et al. Non-CF bronchiectasis: clinical and HRCT evaluation. Pediatr. Pulmonol. 2003; 35 (6): 477–483. DOI: 10.1002/ppul.10289.

29. Remy Jardin M., Amara A., Campistron P. et al. Diagnosis of bronchiectasis with multislice spiral CT: accuracy of 3-mm-thick structured sections. Eur. Radiol. 2003; 13 (5): 1165–1171. DOI: 10.1007/s00330-003-1821-z.

30. Naidich D.P., McCauley D.I., Khouri N.F. et al. Computed tomography of bronchiectasis. J. Comput. Assist. Tomogr. 1982; 6 (3): 437–444. DOI: 10.1097/00004728-198206000-00001.

31. Hill T.A., Sullivan L.A., Chalmers D.J. et al. British Thoracic Society Guideline for bronchiectasis in adults. Thorax. 2019; 74 (Suppl. 1): 1–69. DOI: 10.1136/thoraxjnl-2018-212463.

32. UpToDate. Barker A.F. Clinical manifestations and diagnosis of bronchiectasis in adults. 2023. Available at: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-bronchiectasis-in-adults/print [Accessed: December 05, 2023].

33. Martinez-Garcia M.Á., Oscullo G., Garcia-Ortega A. Towards a new definition of non-cystic fibrosis bronchiectasis. J. Bras. Pneumol. 2022; 48 (1): e20220023. DOI: 10.36416/1806-3756/e20220023.

34. Hill A.T., Haworth C.S., Aliberti S. et al. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. Eur. Respir. J. 2017; 49 (6): 1700051. DOI: 10.1183/13993003.00051-2017.

35. Castellani C., Simmonds N.J. Identifying undiagnosed cystic fibrosis in adults with bronchiectasis. In: Chalmers J.D., Polverino E., Aliberti S., eds. Bronchiectasis. Sheffield: ERS; 2018: 29–44. DOI: 10.1183/2312508X.10015317.

36. Patel I.S., Viahos I., Wilkinson T.M. et al. Bronchiectasis, exacerbation indices and inflammation in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2004; 170 (4): 400–407. DOI: 10.1164/rccm.200305-648oc.

37. Ellis D.A., Thornley P.E., Wightman A.J. et al. Present outlook in bronchiectasis: clinical and social study and review of factors influencing prognosis. Thorax. 1981; 36 (9): 659–664. DOI: 10.1136/thx.36.9.659.

38. Martínez-García M.Á., de Gracia J., Vendrell Relat M. et al. Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score. Eur. Respir. J. 2014; 43 (5): 1357–1367. DOI: 10.1183/09031936.00026313.

39. Lee A.L., Burge A.T., Holland A.E. Airway clearance techniques for bronchiectasis. Cochrane Database Syst. Rev. 2015; 2015 (11): CD008351. DOI: 10.1002/14651858.cd008351.pub3.

40. Mizernitskiy Yu.L., Novak A.A., Shudueva A.R. [Experience of inhaled hypertonic saline use in pediatric pulmonology]. Meditsinskiy sovet. 2022; (12): 36–39. DOI: 10.21518/2079-701X-2022-16-12-36-39 (in Russian).

41. Nicolson C.H., Stirling R.G., Borg B.M. et al. The long term effect of inhaled hypertonic saline 6% in non-cystic fibrosis bronchiectasis. Respir. Med. 2012; 106 (5): 661–667. DOI: 10.1016/j.rmed.2011.12.021.

42. Gao Y.H., Guan W.J., Xu G. et al. Macrolide therapy in adults and children with non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis. PLoS One. 2014; 9 (3): e90047. DOI: 10.1371/journal.pone.0090047.

43. White L., Mirrani G., Grover M. et al. Outcomes of Pseudomonas eradication therapy in patients with non-cystic fibrosis bronchiectasis. Respir. Med. 2012; 106 (3): 356–360. DOI: 10.1016/j.rmed.2011.11.018.

44. Polverino E., Perez-Miranda J. Antibiotic management and resistance. In: Chalmers J.D., Polverino E., Aliberti S., eds. Bronchiectasis. Sheffield: ERS; 2018. Vol. 81: 312–330. DOI: 10.1183/2312508x.erm8118.

45. UpToDate. Goyal V., Chang A.B. Bronchiectasis in children without cystic fibrosis: Management. Available at: https://www.uptodate.com/contents/management-of-bronchiectasis-in-children-without-cystic-fibrosis [Accessed: September 21, 2021].

46. Shapiro A.J., Zariwala M.A., Ferkol T. et al. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review. Pediatr. Pulmonol. 2016; 51 (2): 115–132. DOI: 10.1002/ppul.23304.

47. Brodt A.M., Stovold E., Zhang L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: a systematic review. Eur. Respir. J. 2014; 44 (2): 382–393. DOI: 10.1183/09031936.00018414.

48. Choi S.H., Kim E.Y., Kim Y.J. Systemic use of fluoroquinolone in children. Korean J. Pediatr. 2013; 56 (5): 196–201. DOI: 10.3345/kjp.2013.56.5.196.

49. Gardner R.A., Davis S.D., M. Rosenfeld M. et al. Therapies used for primary ciliary dyskinesia in North American children. Am. J. Respir. Crit. Care Med. 2021; 203: A3380. DOI: 10.1164/ajrccm-conference.2021.203.1_MeetingAbstracts.A3380.

50. Mizernitsky Yu.L., Melnikova I.M. [Role of combined mucolytic therapy in infectious and inflammatory diseases of the respiratory system in children]. Meditsinskiy sovet. 2019; (11): 56–59. DOI: 10.21518/2079-701X-2019-11-56-59 (in Russian).

51. Belevskiy A.S., Knyazheskaya N.P. [Thiamphenicol glycinate acetylcysteinate for the treatment of acute and chronic pulmonary diseases]. Prakticheskaya pul’monologiya. 2017: (3): 123–126. Available at: https://atmosphere-ph.ru/modules/Magazines/articles/pulmo/pp_3_2017_122.pdf (in Russian).

52. Tarrant B.J., Le Maitre C., Romero L. et al. Mucoactive agents for chronic, non-cystic fibrosis lung disease: a systematic review and meta-analysis. Respirology. 2017; 22 (6): 1084–1092. DOI: 10.1111/resp.13047.

53. Kellett F., Robert N.M. Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis. Respir. Med. 2011; 105 (12): 1831–1835. DOI: 10.1016/j.rmed.2011.07.019.

54. Herrero-Cortina B., Alcaraz V., Vilaro J. et al. Impact of hypertonic saline solutions on sputum expectoration and their safety profile in patients with bronchiectasis: a randomized crossover trial. J. Aerosol Med. Pulm. Drug Deliv. 2018; 31 (5): 281–289. DOI: 10.1089/jamp.2017.1443.

55. Daviskas E., Anderson S.D., Gonda I. et al. Inhalation of hypertonic saline aerosol enhances mucociliary clearance in asthmatic and healthy subjects. Eur. Respir. J. 1996; 9 (4): 725–732. DOI: 10.1183/09031936.96.09040725.

56. Elkins M.R., Robinson M., Rose B.R. et al. A controlled trial of longterm inhaled hypertonic saline in patients with cystic fibrosis. N. Engl. J. Med. 2006; 354 (3): 229–240. DOI: 10.1056/NEJMoa043900.

57. Wark P., McDonald V.M. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2018; (9): CD001506. DOI: 10.1002/14651858.CD001506.pub4.

58. Michon A.L., Jumas-Bilak E., Chiron R. et al. Advances toward the elucidation of hypertonic saline effects on Pseudomonas aeruginosa from cystic fibrosis patients. PLoS One. 2014; 9 (2): e90164. DOI: 10.1371/journal.pone.0090164.

59. Garantziotis S., Brezina M., Castelnuovo P., Drago L. The role of hyaluronan in the pathobiology and treatment of respiratory disease. Am. J. Physiol. Lung Cell Mol. Physiol. 2016; 310 (9): L785–795. DOI: 10.1152/ajplung.00168.2015.

60. Qi Q., Ailiyaer Y., Liu R. et al. Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial. Respir. Res. 2019; 20 (1): 73. DOI: 10.1186/s12931-019-1042-x.

61. Hart A., Sugumar K., Milan S.J. et al. Inhaled hyperosmolar agents for bronchiectasis. Cochrane Database Syst. Rev. 2014; (5): CD002996. DOI: 10.1002/14651858.CD002996.pub3.

62. Wilkinson M., Sugumar K., Milan S.J. et al. Mucolytics for bronchiectasis. Cochrane Database Syst. Rev. 2014 (5): CD001289. DOI: 10.1002/14651858.CD001289.pub2.

63. Wills P., Greenstone M. Inhaled hyperosmolar agents for bronchiectasis. Cochrane Database Syst. Rev. 2002; (1): CD002996. DOI: 10.1002/14651858.cd002996.

64. Redding G.J. Bronchiectasis in children. Pediatr. Clin. North Am. 2009; 56 (1): 157–171. DOI: 10.1016/j.pcl.2008.10.014.

65. Chalmers J.D., Polverino E., Crichton M.L. et al. Bronchiectasis in Europe: data on disease characteristics from the European Bronchiectasis registry (EMBARC). Lancet Respir. Med. 2023; 11 (7): 637–649. DOI: 10.1016/S2213-2600(23)00093-0.

66. Jayaram L., King P.T., Hunt J. et al. Evaluation of high dose N-acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: a randomised placebo-controlled pilot study. Pulm. Pharmacol. Ther. 2023; 84: 102283. DOI: 10.1016/j.pupt.2023.102283.

67. Minov J., Stoleski S., Petrova T. et al. Effects of a long-term use of carbocysteine on frequency and duration of exacerbations in patients with bronchiectasis. Open Access Maced. J. Med. Sci. 2019; 7 (23): 4030–4035. DOI: 10.3889/oamjms.2019.697.

68. Liao Y., Wu Y., Zi K. 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 (1): 401. DOI: 10.1186/s12890-022-02202-9.

69. Bradley J.M., Anand R., O’Neill B. et al. A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52weeks in adults with bronchiectasis: a protocol for the CLEAR clinical trial. Trials. 2019; 20 (1): 747. DOI: 10.1186/s13063-019-3766-9.

70. Chang A.B., Morgan L.C., Duncan E.L. et al. Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, double-dummy, 2×2 partial factorial, randomised controlled trial. BMJ Open Respir. Res. 2022; 9 (1): e001236. DOI: 10.1136/bmjresp-2022-001236.

71. Serra A., Schito G.C., Nicoletti G., Fadda G. A therapeutic approach in the treatment of infections of the upper airways: thiamphenicol glycinate acetylcysteinate in sequential treatment (systemic-inhalatory route). Int. J. Immunopathol. Pharmacol. 2007; 20 (3): 607–617. DOI: 10.1177/039463200702000319.

72. Blasi F., Page C., Rossolini G.M. et al. The effect of N-acetylcysteine on biofilms: Implications for the treatment of respiratory tract infections. Respir Med. 2016; 117: 190–197. DOI: 10.1016/j.rmed.2016.06.015.

73. Olofsson A.C., Hermansson M., Elwing H. N-acetyl-L-cysteine affects growth, extracellular polysaccharide production, and bacterial biofilm formation on solid surfaces. Appl. Environ. Microbiol. 2003; 69 (8): 4814–4822. DOI: 10.1128/aem.69.8.4814-4822.2003.

74. Ivanchik N.V., Sukhorukova M.V., Chagaryan A.N. et al. [In vitro activity of thiamphenicol against Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes clinical isolates]. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2021; 23 (1): 92–99. DOI: 10.36488/cmac.2021.1.92-99 (in Russian).

75. Bilton D., Tino G., Barker A.F. et al. Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial. Thorax. 2014; 69 (12): 1073–1079. DOI: 10.1136/thoraxjnl-2014-205587.

76. Lee A.L., Gordon C.S., Osadnik C.R. Exercise training for bronchiectasis. Cochrane Database Syst. Rev. 2021; 4 (4): CD013110. DOI: 10.1002/14651858.cd013110.pub2.

77. Etienne T., Spiliopoulos A., Megevand R. [Bronchiectasis: indication and timing for surgery]. Ann. Chir. 1993; 47 (8): 729–735 (in French).

78. Yu J.A., Pomerantz M., Bishop A. et al. Lady windermere revisited: treatment with thoracoscopic lobectomy/segmentectomy for right middle lobe and lingular bronchiectasis associated with non-tuberculous mycobacterial disease. Eur. J. Cardiothorac. Surg. 2011; 40 (3): 671–675. DOI: 10.1016/j.ejcts.2010.12.028.

79. Weill D., Benden C., Corris P.A. et al. A consensus document for the selection of lung transplant candidates: 2014 – an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J. Heart Lung Transplant. 2015; 34 (1): 1–15. DOI: 10.1016/j.healun.2014.06.014.

80. Fujimoto T., Hillejan L., Stamatis G. Current strategy for surgical management of bronchiectasis. Ann. Thorac Surg. 2001; 72 (5): 1711–1715. DOI: 10.1016/s0003-4975(01)03085-5.

81. Kutlay H., Cangir A.K., Enon S. et al. Surgical treatment in bronchiectasis: analysis of 166 patients. Eur. J. Cardiothorac. Surg. 2002; 21 (4): 634–637. DOI: 10.1016/s1010-7940(02)00053-2.

82. Leard L.E., Holm A.M., Valapour M. et al. Consensus document for the selection of lung transplant candidates: An update from the International Society for heart and lung transplantation. J. Heart Lung Transplant. 2021; 40 (11): 1349–1379. DOI: 10.1016/j.healun.2021.07.005.