Bronchiectasis refers to abnormal dilatation of the bronchi. Airway dilatation can lead to failure of mucus clearance and increased risk of infection. Pathophysiological mechanisms of bronchiectasis include persistent bacterial infections, dysregulated immune responses, impaired mucociliary clearance and airway obstruction. These mechanisms can interact and self-perpetuate, leading over time to impaired lung function. Patients commonly present with productive cough and recurrent chest infections, and the diagnosis of bronchiectasis is based on clinical symptoms and radiological findings. Bronchiectasis can be the result of several different underlying disorders, and identifying the aetiology is crucial to guide management. Treatment is directed at reducing the frequency of exacerbations, improving quality of life and preventing disease progression. Although no therapy is licensed for bronchiectasis by regulatory agencies, evidence supports the effectiveness of airway clearance techniques, antibiotics and mucolytic agents, such as inhaled isotonic or hypertonic saline, in some patients. Bronchiectasis is a disabling disease with an increasing prevalence and can affect individuals of any age. A major challenge is the application of emerging phenotyping and endotyping techniques to identify the patient populations who would most benefit from a specific treatment, with the goal of better targeting existing and emerging treatments and achieving better outcomes.
Subscribe to Journal
Get full journal access for 1 year
only $59.00 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Chalmers, J. D., Aliberti, S. & Blasi, F. Management of bronchiectasis in adults. Eur. Respir. J. 45, 1446–1462 (2015).
Cole, P. J. Inflammation: a two-edged sword — the model of bronchiectasis. Eur. J. Respir. Dis. Suppl. 147, 6–15 (1986).
Chalmers, J. D. et al. The bronchiectasis severity index. An international derivation and validation study. Am. J. Respir. Crit. Care Med. 189, 576–585 (2014). This study described the risk factors for mortality and hospital admissions in multiple European bronchiectasis cohorts and derived a clinical prediction tool that can predict poor outcome across multiple domains, which has now been validated worldwide.
Tomos, I., Karakatsani, A., Manali, E. D. & Papiris, S. A. Celebrating two centuries since the invention of the stethoscope. Rene Theophile Hyacinthe Laënnec (1781–1826). Ann. Am. Thorac Soc. 13, 1667–1670 (2016).
Goeminne, P. C. & De Soyza, A. Bronchiectasis: how to be an orphan with many parents? Eur. Respir. J. 47, 10–13 (2016).
Quint, J. K. 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. 47, 186–193 (2016). An epidemiological study using routinely collected data, demonstrating dramatic increases in bronchiectasis prevalence over 10 years.
Ringshausen, F. C. et al. Bronchiectasis in Germany: a population-based estimation of disease prevalence. Eur. Respir. J. 46, 1805–1807 (2015).
Aliberti, S. et al. Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration. Eur. Respir. J. 48, 632–647 (2016).
McDonnell, M. J. et al. Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts. Thorax 71, 1110–1118 (2016).
Chalmers, J. D. et al. The EMBARC European Bronchiectasis Registry: protocol for an international observational study. ERJ Open Res. https://doi.org/10.1183/23120541.00081-2015 (2016).
Aksamit, T. R. et al. Adult patients with bronchiectasis: a first look at the US Bronchiectasis Research Registry. Chest 151, 982–992 (2017). The first report from a national registry in the United States demonstrating patient characteristics very different from European and Australasian cohorts, including very high rates of NTM infection.
Taylor-Cousar, J. L. et al. Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del. N. Engl. J. Med. 377, 2013–2023 (2017).
Hess, E. P. et al. Trends in computed tomography utilization rates: a longitudinal practice-based study. J. Patient Saf. 10, 52–58 (2014).
Blackall, S. R. et al. Bronchiectasis in indigenous and non-indigenous residents of Australia and New Zealand. Respirology 23, 743–749 (2018).
Lonni, S. et al. Etiology of non-cystic fibrosis bronchiectasis in adults and its correlation to disease severity. Ann. Am. Thorac Soc. 12, 1764–1770 (2015).
Seitz, A. E., Olivier, K. N., Adjemian, J., Holland, S. M. & Prevots, D. R. Trends in bronchiectasis among Medicare beneficiaries in the United States, 2000 to 2007. Chest 142, 432–439 (2012).
Ringshausen, F. C. et al. Bronchiectasis-associated hospitalizations in Germany, 2005–2011: a population-based study of disease burden and trends. PLOS ONE 8, e71109 (2013).
Sanchez-Munoz, G. et al. Time trends in hospital admissions for bronchiectasis: analysis of the Spanish National Hospital discharge data. PLOS ONE 11, e0162282 (2016).
Eastham, K. M., Fall, A. J., Mitchell, L. & Spencer, D. A. The need to redefine non-cystic fibrosis bronchiectasis in childhood. Thorax 59, 324–327 (2004).
Karakoc, G. B., Yilmaz, M., Altintas, D. U. & Kendirli, S. G. Bronchiectasis: still a problem. Pediatr. Pulmonol. 32, 175–178 (2001).
Twiss, J., Metcalfe, R., Edwards, E. & Byrnes, C. New Zealand national incidence of bronchiectasis “too high” for a developed country. Arch. Dis. Child 90, 737–740 (2005).
Chang, A. B., Grimwood, K., Mulholland, E. K. & Torzillo, P. J. Bronchiectasis in Indigenous children in remote Australian communities. Med. J. Aust. 177, 200–204 (2002).
Singleton, R. et al. Bronchiectasis in Alaska native children: causes and clinical courses. Pediatr. Pulmonol. 29, 182–187 (2000).
Chandrasekaran, R., Mac Aogain, M., Chalmers, J. D., Elborn, S. J. & Chotirmall, S. H. Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis. BMC Pulm. Med. 18, 83 (2018).
Weycker, D., Hansen, G. L. & Seifer, F. D. Prevalence and incidence of noncystic fibrosis bronchiectasis among US adults in 2013. Chron. Respir. Dis. 14, 377–384 (2017).
Lin, J.-L., Xu, J.-F. & Qu, J.-M. Bronchiectasis in China. Ann. Am. Thorac Soc. 13, 609–616 (2016).
McDonnell, M. J. et al. Comorbidities and the risk of mortality in patients with bronchiectasis: an international multicentre cohort study. Lancet Respir. Med. 4, 969–979 (2016).
Diel, R. et al. Burden of non-tuberculous mycobacterial pulmonary disease in Germany. Eur. Respir. J. 49, 1602109 (2017).
Koh, W.-J. et al. Outcomes of Mycobacterium avium complex lung disease based on clinical phenotype. Eur. Respir. J. 50, 1602503 (2017).
Vidaillac, C., Yong, V. F. L., Jaggi, T. K., Soh, M.-M. & Chotirmall, S. H. Gender differences in bronchiectasis: a real issue? Breathe (Sheff.) 14, 108–121 (2018).
Vogelmeier, C. F. et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Am. J. Respir. Crit. Care Med. 195, 557–582 (2017).
Tan, W. C. et al. Findings on thoracic computed tomography scans and respiratory outcomes in persons with and without chronic obstructive pulmonary disease: a population-based cohort study. PLOS ONE 11, e0166745 (2016).
De Soyza, A. et al. Bronchiectasis rheumatoid overlap syndrome is an independent risk factor for mortality in patients with bronchiectasis: a multicenter cohort study. Chest 151, 1247–1254 (2017).
Chalmers, J. D. et al. Characterization of the “frequent exacerbator phenotype” in bronchiectasis. Am. J. Respir. Crit. Care Med. 197, 1410–1420 (2018). A large (>2,000 patients), multicentre study describing the clinical effect of exacerbations over time, demonstrating that patients with frequent exacerbations have worse clinical outcomes even after adjustment for potential confounders.
Araujo, D. et al. The independent contribution of Pseudomonas aeruginosa infection to long-term clinical outcomes in bronchiectasis. Eur. Respir. J. 51, 1701953 (2018).
Polverino, E. et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur. Respir. J. 50, 1700629 (2017). The first international guidelines following on from national guidance issued by thoracic societies in Spain, the United Kingdom, Australia and New Zealand.
Mao, B., Yang, J.-W., Lu, H.-W. & Xu, J.-F. Asthma and bronchiectasis exacerbation. Eur. Respir. J. 47, 1680–1686 (2016).
Shah, P. L. et al. Determinants of chronic infection with Staphylococcus aureus in patients with bronchiectasis. Eur. Respir. J. 14, 1340–1344 (1999).
Whitehouse, J. L., Exley, A. R., Foweraker, J. & Bilton, D. Chronic Burkholderia multivorans bronchial infection in a non-cystic fibrosis individual with mannose binding lectin deficiency. Thorax 60, 168–170 (2005).
Shoemark, A. et al. High prevalence of CCDC103 p. His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations. Thorax 73, 157–166 (2018).
Chalmers, J. D. et al. The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration. Breathe (Sheff.) 13, 180–192 (2017).
Donnelly, D., Critchlow, A. & Everard, M. L. Outcomes in children treated for persistent bacterial bronchitis. Thorax 62, 80–84 (2007).
Chalmers, J. D. & Chotirmall, S. H. Bronchiectasis: new therapies and new perspectives. Lancet Respir. Med. 6, 715–726 (2018).
Chalmers, J. D. et al. Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am. J. Respir. Crit. Care Med. 186, 657–665 (2012). A study demonstrating that bacterial clearance through antibiotic therapy results in reduced airway inflammation and in improvements in systemic inflammation, thereby providing strong support for the self-perpetuating cycle hypothesis and the development of inhaled antibiotics as a treatment.
Finch, S., McDonnell, M. J., Abo-Leyah, H., Aliberti, S. & Chalmers, J. D. A. Comprehensive analysis of the impact of Pseudomonas aeruginosa colonization on prognosis in adult bronchiectasis. Ann. Am. Thorac Soc. 12, 1602–1611 (2015).
Wurzel, D. F. et al. Protracted bacterial bronchitis in children: natural history and risk factors for bronchiectasis. Chest 150, 1101–1108 (2016). A detailed description of a cohort of patients with persistent bacterial bronchitis that also identified risk factors for progression to bronchiectasis.
Kantar, A. et al. ERS statement on protracted bacterial bronchitis in children. Eur. Respir. J. 50, 1602139 (2017). A consensus statement from the ERS on the definition, diagnosis, microbiology, treatment and research priorities in persistent bacterial bronchitis.
Faner, R. et al. The microbiome in respiratory medicine: current challenges and future perspectives. Eur. Respir. J. 49, 1602086 (2017).
Taylor, S. L. et al. FUT2 genotype influences lung function, exacerbation frequency and airway microbiota in non-CF bronchiectasis. Thorax 72, 304–310 (2017).
Metersky, M. L. et al. The prevalence and significance of Staphylococcus aureus in patients with non-cystic fibrosis bronchiectasis. Ann. Am. Thorac Soc. 15, 365–370 (2018).
Hilliam, Y. et al. Pseudomonas aeruginosa adaptation and diversification in the non-cystic fibrosis bronchiectasis lung. Eur. Respir. J. 49, 1602108 (2017).
Woo, T. E. et al. Virulence adaptations of Pseudomonas aeruginosa isolated from patients with non-cystic fibrosis bronchiectasis. Microbiology 162, 2126–2135 (2016).
King, P. T. et al. Adaptive immunity to nontypeable Haemophilus influenzae. Am. J. Respir. Crit. Care Med. 167, 587–592 (2003).
Walker, W. T. et al. Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to Haemophilus influenzae biofilm formation. Eur. Respir. J. 50, 1700612 (2017).
Flume, P. A., Chalmers, J. D. & Olivier, K. N. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet 392, 880–890 (2018).
Taylor, S. L. et al. Matrix metalloproteinases vary with airway microbiota composition and lung function in non-cystic fibrosis bronchiectasis. Ann. Am. Thorac Soc. 12, 701–707 (2015).
Chintalacharuvu, K. R. et al. Cleavage of the human immunoglobulin A1 (IgA1) hinge region by IgA1 proteases requires structures in the Fc region of IgA. Infect. Immun. 71, 2563–2570 (2003).
Wells, T. J. et al. Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing. J. Exp. Med. 211, 1893–1904 (2014).
van Ingen, J. et al. Treatment outcome definitions in nontuberculous mycobacterial pulmonary disease: an NTM-NET consensus statement. Eur. Respir. J. 51, 1800170 (2018).
Kunst, H., Wickremasinghe, M., Wells, A. & Wilson, R. Nontuberculous mycobacterial disease and Aspergillus-related lung disease in bronchiectasis. Eur. Respir. J. 28, 352–357 (2006).
Mac Aogain, M. et al. Immunological corollary of the pulmonary mycobiome in bronchiectasis: the CAMEB study. Eur. Respir. J. 52, 1800766 (2018).
Gao, Y.-H. et al. The role of viral infection in pulmonary exacerbations of bronchiectasis in adults: a prospective study. Chest 147, 1635–1643 (2015).
Chalmers, J. D. & Hill, A. T. Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis. Mol. Immunol. 55, 27–34 (2013).
Saleh, A. D., Kwok, B., Brown, J. S. & Hurst, J. R. Correlates and assessment of excess cardiovascular risk in bronchiectasis. Eur. Respir. J. 50, 1701127 (2017).
Frija-Masson, J. et al. Bacteria-driven peribronchial lymphoid neogenesis in bronchiectasis and cystic fibrosis. Eur. Respir. J. 49, 1601873 (2017).
Ruchaud-Sparagano, M.-H. et al. Effect of granulocyte–macrophage colony-stimulating factor on neutrophil function in idiopathic bronchiectasis. Respirology 18, 1230–1235 (2013).
van de Ven, A. A. J. M. et al. A CT scan score for the assessment of lung disease in children with common variable immunodeficiency disorders. Chest 138, 371–379 (2010).
Frick, A. G. et al. Haemophilus influenzae stimulates ICAM-1 expression on respiratory epithelial cells. J. Immunol. 164, 4185–4196 (2000).
Angrill, J. et al. Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. Am. J. Respir. Crit. Care Med. 164, 1628–1632 (2001).
Saleh, A. D. et al. The heterogeneity of systemic inflammation in bronchiectasis. Respir. Med. 127, 33–39 (2017).
van Kessel, D. A., van Velzen-Blad, H., van den Bosch, J. M. M. & Rijkers, G. T. Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology. Eur. Respir. J. 25, 482–489 (2005).
Zimmer, J., Sleiman, M., Poli, A., Michel, T. & Hentges, F. TAP deficiency is also a cause of bronchiectasis. Thorax 68, 490–491 (2013).
Holmes, A. H., Pelton, S., Steinbach, S. & Luzzi, G. A. HIV related bronchiectasis. Thorax 50, 1227 (1995).
Tsikrika, S. et al. The role of non-invasive modalities for assessing inflammation in patients with non-cystic fibrosis bronchiectasis. Cytokine 99, 281–286 (2017).
Watt, A. P. et al. Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis. Thorax 59, 231–236 (2004).
Chalmers, J. D. et al. Neutrophil elastase activity is associated with exacerbations and lung function decline in bronchiectasis. Am. J. Respir. Crit. Care Med. 195, 1384–1393 (2017). A study demonstrating for the first time that a biomarker could predict clinical outcomes in bronchiectasis, supporting a key role of neutrophil elastase in disease progression.
Schleimer, R. P., Benenati, S. V., Friedman, B. & Bochner, B. S. Do cytokines play a role in leukocyte recruitment and activation in the lungs? Am. Rev. Respir. Dis. 143, 1166–1169 (1991).
Mikami, M., Llewellyn-Jones, C. G., Bayley, D., Hill, S. L. & Stockley, R. A. The chemotactic activity of sputum from patients with bronchiectasis. Am. J. Respir. Crit. Care Med. 157, 723–728 (1998).
Schaaf, B., Wieghorst, A., Aries, S. P., Dalhoff, K. & Braun, J. Neutrophil inflammation and activation in bronchiectasis: comparison with pneumonia and idiopathic pulmonary fibrosis. Respiration 67, 52–59 (2000).
Fick, R. B. J. et al. Proteins of the cystic fibrosis respiratory tract. Fragmented immunoglobulin G opsonic antibody causing defective opsonophagocytosis. J. Clin. Invest. 74, 236–248 (1984).
Tosi, M. F., Zakem, H. & Berger, M. Neutrophil elastase cleaves C3bi on opsonized pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch. J. Clin. Invest. 86, 300–308 (1990).
Berger, M., Sorensen, R. U., Tosi, M. F., Dearborn, D. G. & Doring, G. Complement receptor expression on neutrophils at an inflammatory site, the Pseudomonas-infected lung in cystic fibrosis. J. Clin. Invest. 84, 1302–1313 (1989).
Voglis, S. et al. Human neutrophil peptides and phagocytic deficiency in bronchiectatic lungs. Am. J. Respir. Crit. Care Med. 180, 159–166 (2009). The most detailed study of neutrophil function and dysfunction in bronchiectasis to date, demonstrating that human neutrophil peptides (defensins) impair neutrophil phagocytosis and contribute to airway inflammation in bronchiectasis.
Weldon, S. et al. Decreased levels of secretory leucoprotease inhibitor in the Pseudomonas-infected cystic fibrosis lung are due to neutrophil elastase degradation. J. Immunol. 183, 8148–8156 (2009).
Amitani, R. et al. Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium. Am. J. Respir. Cell Mol. Biol. 4, 26–32 (1991).
Fischer, B. M. & Voynow, J. A. Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species. Am. J. Respir. Cell Mol. Biol. 26, 447–452 (2002).
Bedi, P. et al. The BRICS (Bronchiectasis Radiologically Indexed CT Score): a multicenter study score for use in idiopathic and postinfective bronchiectasis. Chest 153, 1177–1186 (2018).
Gaga, M. et al. Increases in CD4+ T lymphocytes, macrophages, neutrophils and interleukin 8 positive cells in the airways of patients with bronchiectasis. Thorax 53, 685–691 (1998).
Zheng, L. et al. Macrophages, neutrophils and tumour necrosis factor-alpha expression in bronchiectatic airways in vivo. Respir. Med. 95, 792–798 (2001).
Hodge, S. et al. Is alveolar macrophage phagocytic dysfunction in children with protracted bacterial bronchitis a forerunner to bronchiectasis? Chest 149, 508–515 (2016). A mechanistic study that increases our understanding of persistent bacterial bronchitis in children by demonstrating reductions in alveolar macrophage phagocytosis and efferocytosis (the clearance of apoptotic cells) in children with persistent bacterial bronchitis compared with healthy controls, suggesting a defect that may contribute to persistent neutrophilic inflammation.
Vandivier, R. W. et al. Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J. Clin. Invest. 109, 661–670 (2002).
Houtmeyers, E., Gosselink, R., Gayan-Ramirez, G. & Decramer, M. Regulation of mucociliary clearance in health and disease. Eur. Respir. J. 13, 1177–1188 (1999).
Gilley, S. K. et al. Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways. Am. J. Physiol. Lung Cell. Mol. Physiol. 306, L162–L169 (2014).
Smallman, L. A., Hill, S. L. & Stockley, R. A. Reduction of ciliary beat frequency in vitro by sputum from patients with bronchiectasis: a serine proteinase effect. Thorax 39, 663–667 (1984).
Shoemark, A. et al. Primary ciliary dyskinesia with normal ultrastructure: three-dimensional tomography detects absence of DNAH11. Eur. Respir. J. 51, 1701809 (2018).
Falconer, M., Collins, D. R., Feeney, J. & Torreggiani, W. C. Mounier–Kuhn syndrome in an older patient. Age Ageing 37, 115–116 (2008).
Nishino, M. et al. Excessive collapsibility of bronchi in bronchiectasis: evaluation on volumetric expiratory high-resolution CT. J. Comput. Assist. Tomogr. 30, 474–478 (2006).
Lucas, J. S. et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur. Respir. J. 49, 1601090 (2017).
Goutaki, M. et al. The international primary ciliary dyskinesia cohort (iPCD cohort): methods and first results. Eur. Respir. J. 49, 1601181 (2017).
Driscoll, J. A., Bhalla, S., Liapis, H., Ibricevic, A. & Brody, S. L. Autosomal dominant polycystic kidney disease is associated with an increased prevalence of radiographic bronchiectasis. Chest 133, 1181–1188 (2008).
Fajac, I., Viel, M., Gaitch, N., Hubert, D. & Bienvenu, T. Combination of ENaC and CFTR mutations may predispose to cystic fibrosis-like disease. Eur. Respir. J. 34, 772–773 (2009).
Casals, T. et al. Bronchiectasis in adult patients: an expression of heterozygosity for CFTR gene mutations? Clin. Genet. 65, 490–495 (2004).
Bienvenu, T. et al. Cystic fibrosis transmembrane conductance regulator channel dysfunction in non-cystic fibrosis bronchiectasis. Am. J. Respir. Crit. Care Med. 181, 1078–1084 (2010).
Horvath, I. et al. Increased levels of exhaled carbon monoxide in bronchiectasis: a new marker of oxidative stress. Thorax 53, 867–870 (1998).
Loukides, S., Horvath, I., Wodehouse, T., Cole, P. J. & Barnes, P. J. Elevated levels of expired breath hydrogen peroxide in bronchiectasis. Am. J. Respir. Crit. Care Med. 158, 991–994 (1998).
Willis, D., Moore, A. R., Frederick, R. & Willoughby, D. A. Heme oxygenase: a novel target for the modulation of the inflammatory response. Nat. Med. 2, 87–90 (1996).
Chalmers, J. D., McHugh, B. J., Docherty, C., Govan, J. R. W. & Hill, A. T. Vitamin-D deficiency is associated with chronic bacterial colonisation and disease severity in bronchiectasis. Thorax 68, 39–47 (2013).
Chang, A. B. 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. 202, 21–23 (2015).
Dimakou, K. et al. Non CF-bronchiectasis: aetiologic approach, clinical, radiological, microbiological and functional profile in 277 patients. Respir. Med. 116, 1–7 (2016).
McCallum, G. B. & Binks, M. J. The epidemiology of chronic suppurative lung disease and bronchiectasis in children and adolescents. Front. Pediatr. 5, 27 (2017).
Kapur, N., Masters, I. B. & Chang, A. B. Exacerbations in noncystic fibrosis bronchiectasis: clinical features and investigations. Respir. Med. 103, 1681–1687 (2009).
Chang, A. B., Redding, G. J. & Everard, M. L. Chronic wet cough: protracted bronchitis, chronic suppurative lung disease and bronchiectasis. Pediatr. Pulmonol. 43, 519–531 (2008).
Goyal, V., Grimwood, K., Marchant, J., Masters, I. B. & Chang, A. B. Does failed chronic wet cough response to antibiotics predict bronchiectasis? Arch. Dis. Child 99, 522–525 (2014).
Suarez-Cuartin, G., Chalmers, J. D. & Sibila, O. Diagnostic challenges of bronchiectasis. Respir. Med. 116, 70–77 (2016).
van der Bruggen-Bogaarts, B. A., van der Bruggen, H. M., van Waes, P. F. & Lammers, J. W. Assessment of bronchiectasis: comparison of HRCT and spiral volumetric CT. J. Comput. Assist. Tomogr. 20, 15–19 (1996).
Pasteur, M. C., Bilton, D. & Hill, A. T. British Thoracic Society guideline for non-CF bronchiectasis. Thorax 65, 577 (2010).
Matsuoka, S. et al. Bronchoarterial ratio and bronchial wall thickness on high-resolution CT in asymptomatic subjects: correlation with age and smoking. AJR Am. J. Roentgenol. 180, 513–518 (2003).
Berend, N., Woolcock, A. J. & Marlin, G. E. Relationship between bronchial and arterial diameters in normal human lungs. Thorax 34, 354–358 (1979).
Diaz, A. A. et al. Bronchoarterial ratio in never-smokers adults: implications for bronchial dilation definition. Respirology 22, 108–113 (2017).
Kapur, N., Masel, J. P., Watson, D., Masters, I. B. & Chang, A. B. Bronchoarterial ratio on high-resolution CT scan of the chest in children without pulmonary pathology: need to redefine bronchial dilatation. Chest 139, 1445–1450 (2011).
Chalmers, J. D. Bronchiectasis and COPD overlap: a case of mistaken identity? Chest 151, 1204–1206 (2017).
Kim, S. J. et al. Normal bronchial and pulmonary arterial diameters measured by thin section CT. J. Comput. Assist. Tomogr. 19, 365–369 (1995).
Brody, A. & Chang, A. The imaging definition of bronchiectasis in children: is it time for a change? Pediatr. Pulmonol. 53, 6–7 (2018).
Hill, L. E., Ritchie, G., Wightman, A. J., Hill, A. T. & Murchison, J. T. Comparison between conventional interrupted high-resolution CT and volume multidetector CT acquisition in the assessment of bronchiectasis. Br. J. Radiol. 83, 67–70 (2010).
Dodd, J. D., Souza, C. A. & Muller, N. L. Conventional high-resolution CT versus helical high-resolution MDCT in the detection of bronchiectasis. AJR Am. J. Roentgenol. 187, 414–420 (2006).
Goyal, V., Grimwood, K., Marchant, J. M., Masters, I. B. & Chang, A. B. Paediatric chronic suppurative lung disease: clinical characteristics and outcomes. Eur. J. Pediatr. 175, 1077–1084 (2016).
Colom, A. J., Maffey, A., Garcia Bournissen, F. & Teper, A. Pulmonary function of a paediatric cohort of patients with postinfectious bronchiolitis obliterans. A long term follow-up. Thorax 70, 169–174 (2015).
Pizzutto, S. J. et al. Bronchoscopy contributes to the clinical management of Indigenous children newly diagnosed with bronchiectasis. Pediatr. Pulmonol. 48, 67–73 (2013).
Chang, A. B., Boyce, N. C., Masters, I. B., Torzillo, P. J. & Masel, J. P. Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease. Thorax 57, 935–938 (2002).
Douros, K. et al. Bronchoscopic and high-resolution CT scan findings in children with chronic wet cough. Chest 140, 317–323 (2011).
Martinez-Garcia, M. A. et al. Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score. Eur. Respir. J. 43, 1357–1367 (2014).
Ellis, H. C., Cowman, S., Fernandes, M., Wilson, R. & Loebinger, M. R. Predicting mortality in bronchiectasis using bronchiectasis severity index and FACED scores: a 19-year cohort study. Eur. Respir. J. 47, 482–489 (2016).
Mao, B., Yang, J.-W., Lu, H.-W. & Xu, J.-F. Asthma and risk of bronchiectasis exacerbation: we still need more evidence. Eur. Respir. J. 48, 1247–1248 (2016).
Araujo, D. et al. Standardised classification of the aetiology of bronchiectasis using an objective algorithm. Eur. Respir. J. 50, 1701289 (2017).
Gaillard, E. A., Carty, H., Heaf, D. & Smyth, R. L. Reversible bronchial dilatation in children: comparison of serial high-resolution computer tomography scans of the lungs. Eur. J. Radiol. 47, 215–220 (2003).
McCallum, G. B. & Chang, A. B. “Good enough” is “not enough” when managing indigenous adults with bronchiectasis in Australia and New Zealand. Respirology 23, 725–726 (2018).
Aliberti, S. et al. Quality standards for the management of bronchiectasis in Italy: a national audit. Eur. Respir. J. 48, 244–248 (2016).
Kwak, H. J. et al. High prevalence of bronchiectasis in adults: analysis of CT findings in a health screening program. Tohoku J. Exp. Med. 222, 237–242 (2010).
Flude, L. J., Agent, P. & Bilton, D. Chest physiotherapy techniques in bronchiectasis. Clin. Chest Med. 33, 351–361 (2012).
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. 51, 1701926 (2018).
Wong, C., Sullivan, C. & Jayaram, L. ELTGOL airway clearance in bronchiectasis: laying the bricks of evidence. Eur. Respir. J. 51, 1702232 (2018).
Lee, A. L., Burge, A. T. & Holland, A. E. Airway clearance techniques for bronchiectasis. Cochrane Database Syst. Rev. 11, CD008351 (2015).
Nicolson, C. H. H. et al. The long term effect of inhaled hypertonic saline 6% in non-cystic fibrosis bronchiectasis. Respir. Med. 106, 661–667 (2012).
Lee, A. L., Hill, C. J., McDonald, C. F. & Holland, A. E. Pulmonary rehabilitation in individuals with non-cystic fibrosis bronchiectasis: a systematic review. Arch. Phys. Med. Rehabil. 98, 774–782 (2017).
Kuehni, C. E., Goutaki, M. & Kobbernagel, H. E. Hypertonic saline in patients with primary ciliary dyskinesia: on the road to evidence-based treatment for a rare lung disease. Eur. Respir. J. 49, 1602514 (2017).
Bilton, D. et al. Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial. Thorax 69, 1073–1079 (2014).
Guan, W.-J., Huang, Y., Chen, C.-L., Chen, R.-C. & Zhong, N.-S. Macrolides, mucoactive drugs and adherence for the management of bronchiectasis. Eur. Respir. J. 51, 1701987 (2018).
Chalmers, J. D. & Polverino, E. Macrolides, mucoactive drugs and adherence for the management of bronchiectasis. Eur. Respir. J. 51, 1702033 (2018).
O’Donnell, A. E., Barker, A. F., Ilowite, J. S. & Fick, R. B. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. rhDNase Study Group. Chest 113, 1329–1334 (1998). One of the first large-scale trials in bronchiectasis in the modern era, showing that a drug known to be beneficial in cystic fibrosis bronchiectasis was ineffective or potentially harmful in non-cystic fibrosis bronchiectasis; the knowledge that cystic fibrosis and bronchiectasis behave differently has made a major impact on the field.
Wills, P. J. et al. Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability. Am. J. Respir. Crit. Care Med. 154, 413–417 (1996).
Mustafa, M.-H. et al. Acquired resistance to macrolides in Pseudomonas aeruginosa from cystic fibrosis patients. Eur. Respir. J. 49, 1601847 (2017).
Kelly, C. et al. Macrolide antibiotics for bronchiectasis. Cochrane Database Syst. Rev. 3, CD012406 (2018).
Serisier, D. J. 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 309, 1260–1267 (2013).
Wong, C. et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet 380, 660–667 (2012). The first-published of three important macrolide studies conducted in adults, demonstrating consistent reductions in exacerbation frequency with long-term low-dose macrolide versus placebo.
Altenburg, J. et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA 309, 1251–1259 (2013).
Valery, P. C. 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. 1, 610–620 (2013). A multicentre randomized controlled trial demonstrating reduced exacerbations in Indigenous children treated with azithromycin compared with placebo.
van Ingen, J. et al. Poor adherence to management guidelines in nontuberculous mycobacterial pulmonary diseases. Eur. Respir. J. 49, 1601855 (2017).
Haworth, C. S., Foweraker, J. E., Wilkinson, P., Kenyon, R. F. & Bilton, D. Inhaled colistin in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. Am. J. Respir. Crit. Care Med. 189, 975–982 (2014).
Barker, A. F. et al. Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials. Lancet Respir. Med. 2, 738–749 (2014). At the time, the largest inhaled antibiotic trial in bronchiectasis; this study found that aztreonam, which is licensed for use in cystic fibrosis, did not improve QOL in bronchiectasis and was associated with increased adverse events.
De Soyza, A. 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. 51, 1702052 (2018). One of two studies describing the largest inhaled antibiotic development programme in bronchiectasis; this study found no consistent improvements in exacerbation frequency or QOL with inhaled antibiotics, questioning their role as a therapy for patients with bronchiectasis.
Aksamit, T. 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. 51, 1702053 (2018).
Chotirmall, S. H. & Chalmers, J. D. RESPIRE: breathing new life into bronchiectasis. Eur. Respir. J. 51, 1702444 (2018).
Barker, A. F. et al. Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Am. J. Respir. Crit. Care Med. 162, 481–485 (2000).
Drobnic, M. E., Suñé, P., Montoro, J. B., Ferrer, A. & Orriols, R. Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa. Ann. Pharmacother. 39, 39–44 (2005).
Vendrell, M., Muñoz, G. & de Gracia, J. Evidence of inhaled tobramycin in non-cystic fibrosis bronchiectasis. Open Respir. Med. J. 9, 30–36 (2015).
Brodt, A. M., Stovold, E. & Zhang, L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: a systematic review. Eur. Respir. J. 44, 382–393 (2014).
Murray, M. P. et al. A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am. J. Respir. Crit. Care Med. 183, 491–499 (2011).
Haworth, C. et al. Inhaled liposomal ciprofloxacin in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection: results from two parallel phase III trials (ORBIT-3 and -4) [abstract]. Am. J. Respir. Crit. Care Med. 195, A7604 (2018).
Contoli, M. et al. Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD. Eur. Respir. J. 50, 1700451 (2017).
Kapur, N., Petsky, H. L., Bell, S., Kolbe, J. & Chang, A. B. Inhaled corticosteroids for bronchiectasis. Cochrane Database Syst. Rev. 5, CD000996 (2018).
De Soyza, A. et al. A randomised, placebo-controlled study of the CXCR2 antagonist AZD5069 in bronchiectasis. Eur. Respir. J. 46, 1021–1032 (2015).
Stockley, R. et al. Phase II study of a neutrophil elastase inhibitor (AZD9668) in patients with bronchiectasis. Respir. Med. 107, 524–533 (2013).
Bedi, P. et al. A randomized controlled trial of atorvastatin in patients with bronchiectasis infected with Pseudomonas aeruginosa: a proof of concept study. Chest 152, 368–378 (2017).
Mandal, P. et al. Atorvastatin as a stable treatment in bronchiectasis: a randomised controlled trial. Lancet Respir. Med. 2, 455–463 (2014).
Konstan, M. W. et al. A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis. J. Cyst. Fibros 13, 148–155 (2014).
Fan, L.-C., Liang, S., Lu, H.-W., Fei, K. & Xu, J.-F. Efficiency and safety of surgical intervention to patients with non-cystic fibrosis bronchiectasis: a meta-analysis. Sci. Rep. 5, 17382 (2015).
Birch, J. et al. Outcomes of lung transplantation in adults with bronchiectasis. BMC Pulm. Med. 18, 82 (2018).
Hill, A. T. et al. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. Eur. Respir. J. 49, 1700051 (2017). A global consensus document on the definition of exacerbation for use in clinical research; this paper is notable for the involvement of investigators from Europe, North America, Australasia and Africa in a global task force.
O’Leary, C. J. et al. Relationship between psychological well-being and lung health status in patients with bronchiectasis. Respir. Med. 96, 686–692 (2002).
Ryu, Y. J., Chun, E.-M., Lee, J. H. & Chang, J. H. Prevalence of depression and anxiety in outpatients with chronic airway lung disease. Korean J. Intern. Med. 25, 51–57 (2010).
Joish, V. N., Spilsbury-Cantalupo, M., Operschall, E., Luong, B. & Boklage, S. Economic burden of non-cystic fibrosis bronchiectasis in the first year after diagnosis from a US health plan perspective. Appl. Health Econ. Health Policy 11, 299–304 (2013).
Kapur, N., Masters, I. B., Newcombe, P. & Chang, A. B. The burden of disease in pediatric non-cystic fibrosis bronchiectasis. Chest 141, 1018–1024 (2012).
Murray, M. P., Turnbull, K., MacQuarrie, S., Pentland, J. L. & Hill, A. T. Validation of the Leicester cough questionnaire in non-cystic fibrosis bronchiectasis. Eur. Respir. J. 34, 125–131 (2009).
Guan, W.-J. et al. Inflammatory responses, spirometry, and quality of life in subjects with bronchiectasis exacerbations. Respir. Care 60, 1180–1189 (2015).
Courtney, J. M. et al. Quality of life and inflammation in exacerbations of bronchiectasis. Chron. Respir. Dis. 5, 161–168 (2008).
Coulter, T. I. et al. Clinical spectrum and features of activated phosphoinositide 3-kinase delta syndrome: a large patient cohort study. J. Allergy Clin. Immunol. 139, 597–606 (2017).
Goeminne, C. P. et al. The impact of acute air pollution fluctuations on bronchiectasis pulmonary exacerbation. A case-crossover analysis. Eur. Respir. J. 52, 1702557 (2018).
Chalmers, J. D. et al. Cross-infection risk in patients with bronchiectasis: a position statement from the European Bronchiectasis Network (EMBARC), EMBARC/ELF patient advisory group and European Reference Network (ERN-Lung) Bronchiectasis Network. Eur. Respir. J. 51, 1701937 (2018).
Blasi, F., Chalmers, J. D. & Aliberti, S. COPD and bronchiectasis: phenotype, endotype or co-morbidity? COPD 11, 603–604 (2014).
Aliberti, S. et al. Clinical phenotypes in adult patients with bronchiectasis. Eur. Respir. J. 47, 1113–1122 (2016).
Pasteur, M. C. et al. An investigation into causative factors in patients with bronchiectasis. Am. J. Respir. Crit. Care Med. 162, 1277–1284 (2000).
Agustí, A. et al. Precision medicine in airway diseases: moving to clinical practice. Eur. Respir. J. 50, 1701655 (2017).
Agusti, A. et al. Treatable traits: toward precision medicine of chronic airway diseases. Eur. Respir. J. 47, 410–419 (2016).
Vedel-Krogh, S., Nordestgaard, B. G., Lange, P., Vestbo, J. & Nielsen, S. F. Blood eosinophil count and risk of pneumonia hospitalisations in individuals with COPD. Eur. Respir. J. 51, 1800120 (2018).
Kerkhof, M. et al. Blood eosinophil count and exacerbation risk in patients with COPD. Eur. Respir. J. 50, 1700761 (2017).
Southworth, T., Beech, G., Foden, P., Kolsum, U. & Singh, D. The reproducibility of COPD blood eosinophil counts. Eur. Respir. J. 52, 1800427 (2018).
Palmer, R. et al. Dipeptidyl peptidase 1 inhibitor AZD7986 induces a sustained, exposure-dependent reduction in neutrophil elastase activity in healthy subjects. Clin. Pharmacol. Ther. https://doi.org/10.1002/cpt.1053 (2018).
Harding, R. & Maritz, G. Maternal and fetal origins of lung disease in adulthood. Semin. Fetal Neonatal Med. 17, 67–72 (2012).
Maritz, G. S. & Harding, R. Life-long programming implications of exposure to tobacco smoking and nicotine before and soon after birth: evidence for altered lung development. Int. J. Environ. Res. Public Health 8, 875–898 (2011).
Caskey, S. et al. Structural and functional lung impairment in adult survivors of bronchopulmonary dysplasia. Ann. Am. Thorac Soc. 13, 1262–1270 (2016).
Valery, P. C. et al. Hospital-based case–control study of bronchiectasis in Indigenous children in central Australia. Pediatr. Infect. Dis. J. 23, 902–908 (2004).
Jayes, L. et al. SmokeHaz: systematic reviews and meta-analyses of the effects of smoking on respiratory health. Chest 150, 164–179 (2016).
Walker, C. L. F. et al. Global burden of childhood pneumonia and diarrhoea. Lancet 381, 1405–1416 (2013).
Chang, A. B. et al. Protracted bacterial bronchitis: the last decade and the road ahead. Pediatr. Pulmonol. 51, 225–242 (2016).
Sjogren, P., Nilsson, E., Forsell, M., Johansson, O. & Hoogstraate, J. A systematic review of the preventive effect of oral hygiene on pneumonia and respiratory tract infection in elderly people in hospitals and nursing homes: effect estimates and methodological quality of randomized controlled trials. J. Am. Geriatr. Soc. 56, 2124–2130 (2008).
Singleton, R. J. et al. Indigenous children from three countries with non-cystic fibrosis chronic suppurative lung disease/bronchiectasis. Pediatr. Pulmonol. 49, 189–200 (2014).
Tan, H.-L. et al. The Th17 pathway in cystic fibrosis lung disease. Am. J. Respir. Crit. Care Med. 184, 252–258 (2011).
Picard, C. et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J. Clin. Immunol. 35, 696–726 (2015).
Zemanick, E. T. et al. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur. Respir. J. 50, 1700832 (2017).
Paff, T. et al. A randomised controlled trial on the effect of inhaled hypertonic saline on quality of life in primary ciliary dyskinesia. Eur. Respir. J. 49, 1601770 (2017).
Gupta, S. et al. Qualitative analysis of high-resolution CT scans in severe asthma. Chest 136, 1521–1528 (2009).
Agarwal, R. et al. A randomised trial of glucocorticoids in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur. Respir. J. 47, 490–498 (2016).
McShane, P. J., Naureckas, E. T. & Strek, M. E. Bronchiectasis in a diverse US population: effects of ethnicity on etiology and sputum culture. Chest 142, 159–167 (2012). A detailed description of a US-based cohort that reveals differences in aetiology and microbiology based on ethnicity, a finding that has become increasingly important as more global data on bronchiectasis become available.
J.D.C. is supported by the GSK/British Lung Foundation Chair of Respiratory Research. A.B.C. is supported by an Australian National Health and Medical Research Council Practitioner Fellowship (grant 105821). S.H.C. is supported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award (NMRC/TA/0048/2016), the Lee Kong Chian School of Medicine, Nanyang Technological University Start-Up Grant and would like to acknowledge the Academic Respiratory Initiative for Pulmonary Health (TARIPH).
Nature Reviews Disease Primers thank L.-A. Daniel, K. Olivier, E. Polverino, H. Tiddens and the other anonymous reviewer(s) for their contribution to the peer review of this work.
J.D.C. has been an investigator, advisory board member or trial steering committee member for several bronchiectasis clinical trials, including for Aradigm, Bayer, Grifols, Novartis and Zambon. He is chair of the European Bronchiectasis Registry. A.B.C. is a member of the data safety monitoring board for an unlicensed vaccine study (for GlaxoSmithKline) and an adviser for study design of an unlicensed product for cough (for Merck). She declares no financial conflicts of interest regarding the content of this manuscript. P.J.M. has served on the advisory committee to the FDA for Bayer and is an advisory board member for Aradigm, Bayer, Grifols, Hill Rom and Insmed. She declares no financial conflicts of interest regarding the content of this manuscript. S.H.C. and R.D. declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): www.bronchiectasis.eu
About this article
Cite this article
Chalmers, J.D., Chang, A.B., Chotirmall, S.H. et al. Bronchiectasis. Nat Rev Dis Primers 4, 45 (2018). https://doi.org/10.1038/s41572-018-0042-3
Network Pharmacology Analysis of the Therapeutic Mechanisms Underlying Beimu-Gualou Formula Activity against Bronchiectasis with In Silico Molecular Docking Validation
Evidence-Based Complementary and Alternative Medicine (2021)
Bronchiectasis and increased mortality in patients with corticosteroid-dependent severe asthma: a nationwide population study
Therapeutic Advances in Respiratory Disease (2020)
New-onset nontuberculous mycobacterial pulmonary disease in bronchiectasis: tracking the clinical and radiographic changes
BMC Pulmonary Medicine (2020)
ERS International Congress, Madrid, 2019: highlights from the Airway Diseases, Asthma and COPD Assembly
ERJ Open Research (2020)