P­ri­me­r

­­­B­ro­nc­hi­ec­ta­si­s­­­­­­­­­­
James D. Chalmers1*, Anne B. Chang2,3, Sanjay H. Chotirmall4, Raja Dhar5 and
Pamela J. McShane6
Abstract | 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.

Bronchiectasis refers to abnormal, usually permanent,
dilatation of the bronchi (Fig. 1). It is a pathological or
radiological term and a disease with its own diagnosis
code (J47.9) in the 10th revision of the International
Statistical Classification of Diseases and Related Health
Problems (ICD-10)1. Bronchiectasis as a disease is a clin-
ical syndrome that usually presents with cough, sputum
production and recurrent chest infections, along with
other symptoms, such as malaise, chest discomfort,
haemoptysis (coughing of blood) and weight loss1. In
terms of pathophysiology, bronchial dilatation leads to
impaired mucociliary clearance, and failure to adequately
clear bacteria and mucus (the layer of gel-​like fluid that
facilitates the trapping of particulate matter and micro-
organisms that enter the airway) from the airways leads
to persistent infection, inflammation and further airway
damage2. Progressive airway damage can lead to impaired
lung function, worsening symptoms and eventually res-
piratory failure and death3. Bronchiectasis can be the final
common pathway of several infectious, inflammatory,
allergic, genetic and degenerative disorders, and, there-
fore, is the result of multiple pathophysiological pro-
cesses and one of the most complex and heterogeneous
*e-​mail: jchalmers@
dundee.ac.uk syndromes in respiratory medicine.
https://doi.org/10.1038/ Bronchiectasis has been recognized as a major
s41572-018-0042-3 clinical problem since its first description by the
French physician René Laennec in 1819 (ref.4). Severe
infections such as pneumonia and tuberculosis were
the predominant causes of bronchiectasis in the pre-​
antibiotic era; thus, once antibiotics became available,
bronchiectasis was expected to disappear as a clinical
problem over time. Perhaps as a result of this assump-
tion, the development of drugs and clinical services
for these patients received few investments, leading
to bronchiectasis being described as an orphan or
neglected disease5.
However, the predicted decline in bronchiectasis has
not occurred, and the number of patients has risen inexor­
ably in the past decade, placing an increasing burden
on global health-​care systems6,7. As a result, there has
been a surge in interest in bronchiectasis8, with the gener­
ation of international guidelines for treatment, the for-
mation of international networks (including registries in
the United States, Europe, India and Australasia), large-​
scale randomized controlled trials and new studies into
mechanisms of disease9–11. Nevertheless, we are a long
way from fully understanding this disease or being able
to offer the evidence-​based practice and personalized
medicine that are now available in conditions such as
cystic fibrosis12.
This Primer provides a comprehensive overview of
the progress that has been made in bronchiectasis, with

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Author addresses
1
Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and
Medical School, Dundee, UK.
2
Child Health Division, Menzies School of Health Research, Charles Darwin University,
Darwin, Northern Territory, Australia.
3
Department of Respiratory and Sleep Medicine, Queensland Children’s Hospital,
Children Centre for Health Research, Queensland University of Technology, Brisbane,
Queensland, Australia.
4
Translational Respiratory Research Laboratory, Lee Kong Chian School of Medicine,
Clinical Sciences Building, Nanyang Technological University, Singapore, Singapore.
5
Department of Pulmonology, Fortis Hospital, Kolkata, India.
6
Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, USA.
a focus on disease mechanisms and their implications
for patient management.
Epidemiology
Prevalence and incidence
The ability to mine large health-​care databases for
disease-​specific codes has provided increased insight
into epidemiological patterns in bronchiectasis. Data
indicate that bronchiectasis prevalence is increasing, and
this trend may be partially influenced by an increased
use of diagnostic CT scans13 and the establishment of
national bronchiectasis registries, both of which enable
the identification of patients with bronchiectasis10,11.
Bronchiectasis can affect individuals of any age,
but the overall prevalence of bronchiectasis increases
with age; the mean age of patients with bronchiecta-
sis across continental Europe and Australia is 65 years
(range 59.4–68.3)14,15. In a US Medicare population
(which includes men and women of >65 years of age),
the annual percentage increase in the prevalence of
bronchiectasis was on average 8.74% from 2000 to 2007
(ref.16). Across all age groups, the incidence of bronchi-
ectasis increased in the United Kingdom from 2004 to
2013 (from 21.24 to 35.17 per 100,000 person-​years in
women and from 18.19 to 26.92 per 100,000 person-​
years in men)6. As a corollary, bronchiectasis-​associated
hospitalizations increased. The overall age-​adjusted
rate of all bronchiectasis-​associated hospitalizations
in Germany increased at an average rate of 2.9% per
year from 2005 to 2011 (refs7,17). Similarly, in Spain,
an increasing incidence of bronchiectasis-​associated
hospitalizations was observed from 2004 to 2013 (ref.18).
In children, bronchiectasis is commonly misdiag-
nosed as asthma19. In one study, 49% of children with
bronchiectasis on CT imaging had been diagnosed
with asthma, and the delay in receiving the correct
diagnosis of bronchiectasis was up to 14.8 years from
symptom onset19. The prevalence of bronchiectasis is
high in regions where children have early and recurrent
respiratory infections20. For example, the prevalence
is estimated at 160 per 100,000 individuals in Māori/
Pacific Islander children in New Zealand and 1,470
per 100,000 individuals in Indigenous Australians of
<15 years of age21,22. Furthermore, a disproportionate
number of US Alaskan native children in the YK Delta
region is affected23. Whether the increased susceptibility
in these populations represents genetic differences or a
more-​limited access to care, particularly for antibiotic
treatment of childhood infections, is unclear.
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Geographical differences. The overall prevalence of bron-
chiectasis varies geographically worldwide. Geographical
variances may be due to several factors, including host
factor susceptibilities, environmental exposures (for
example, bronchiectasis is a common sequelae of tuber-
culosis, and this fact is likely to be a major driver of
differences in prevalences and patient characteristics
among regions), local diagnostic practices and the nature
of available data sets24. In particular, in European and
US populations, the variations in prevalence estimates
may reflect differences in data capture between health-​
care claims databases, primary-​care records and registries,
as much as true differences in prevalence between coun-
tries. European countries report prevalence rates from
67 per 100,000 individuals in Germany to 362 per 100,000
individuals in Spain7,18,25. In 2013, the US prevalence was
estimated to be 139 per 100,000 individuals of >18 years
of age25. In the same year, the UK prevalence was noted to
be 566.1 and 485.5 per 100,000 in adult women and men,
respectively6. The highest prevalence of bronchiectasis
is reported in Asia, at 1,200 per 100,000 individuals of
>40 years of age in China, although this rate is probably
a gross underestimate26. Accurate, reliable epidemiologi­
cal data are lacking for large regions of the world, for
example, Eastern Europe, South America, the Middle
East and Africa.
Sex differences. The reported ratio of affected males to
females is variable. In adults from the United Kingdom,
Spain and the United States, women predominate
(57–79% depending on the population studied)11,15,27. In
Australia, 50.6% of patients are females but only 42% and
45% in China and South Korea, respectively14. Idiopathic
bronchiectasis and non-​tuberculous mycobacteria
(NTM) infection-​associated bronchiectasis are more
frequent in women than in men11,28,29, but the reasons
for the increased susceptibility to bronchiectasis among
women are not well understood, although possible
mechanisms have been reviewed30. In large parts of the
world, smoking is more prevalent in men than in women
and, as a result, bronchiectasis associated with smoking-​
related chronic obstructive pulmonary disease (COPD)
is more frequent in men than in women31. Smoking itself
does not seem to be a risk factor for bronchiectasis, as
the prevalence of radiological bronchiectasis in both
male and female non-​smokers and smokers without
COPD does not seem to be different32.
Mortality
Age-​adjusted mortality for patients with bronchiec­
tasis is more than twice that of the general population6.
Mortality correlates with the severity of disease but is not
strongly influenced by the underlying aetiology, with a
few exceptions, such as rheumatoid arthritis and COPD,
which are associated with worse prognosis3,33–35.
Predictors of mortality that are relevant to all possible
aetiologies include old age, low forced expiratory volume
in 1 second (FEV1; the amount of air a person can force-
fully exhale in 1 second in a forced expiratory volume
test), low body mass index, previous hospitalizations and
frequent exacerbations (that is, unpredictable flare-​ups
of symptoms often caused by infection)3,34–36

a Normal bronchus b Bronchiectasis Loss of cilia
Smooth
muscle cell
Basement
membrane
Goblet cell
Epithelial
Air cell
passageway
Cilia
Mucus
Blood vessel
Wall
Fig. 1 | Morphology of healthy and dilatated bronchi. a | Structure of a healthy bronchus. b | Structure of a bronchus
with bronchiectasis. Note the airway dilatation, with obstruction of the airway with mucus, increased number and size
of mucous glands (goblet cells), bronchial wall damage and loss of cilia. c | Different morphologies of bronchiectasis.
Cylindrical bronchiectasis is the mildest form, whereas cystic dilatation is the most severe form, in which the morphology
of the bronchus is lost entirely.
Geographical variations of aetiologies
Most of the evidence guiding our treatment of bron-
chiectasis has been generated in European adults, and
very little data have been generated from developing
countries or in children. The burden of bronchiectasis
seems to be substantial in countries and populations
with a high incidence of tuberculosis and other respir­
atory infections24 (Fig. 2). There are also clear ethnic and
cultural influences on the prevalence and presentation of
bronchiectasis, as demonstrated by the high incidence
of childhood bronchiectasis in indigenous populations
in Australia22 or the high frequency of Pseudomonas
aeruginosa infections reported in studies from China,
which may reflect different genetic susceptibilities to
infection or different patterns of antibiotic use37. Genetics
are likely to influence what bacteria an individual is most
susceptible to — for example, in patients with cystic
fibrosis, Staphylococcus aureus infection is much more
common than would be expected by chance38. Some
organisms (such as Burkholderia cepacia) are very rare in
bronchiectasis that is not due to cystic fibrosis39. Genetic
susceptibility to bronchiectasis development varies with
ethnic origin: for example, cystic fibrosis is very rare in
Asia compared with Western populations, and higher
frequencies of some primary ciliary dyskinesia (PCD)-
causing mutations have been reported in South Asian
individuals40. As a result of these variations, when using
clinical evidence to guide treatment, it is important to be
mindful of the patient population in which it has been
generated, to ensure that the findings are applied to the
appropriate patients.
International registries should help to unravel some
of these issues of patient representation. The European
Multicentre Bronchiectasis Audit and Research
Collaboration (EMBARC) is currently enrolling and has
enrolled 12,000 European adult patients at the time of
writing, including patients from underrepresented popu­
lations in eastern and southern European countries10,41.
Registries now exist in Europe, the United States, Australia
and most recently in India, and more are expected to be
formed in additional countries in the coming years.
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c
Increased
mucus
Destruction
of wall
Normal
Cylindrical
Varicose
Cystic
Mechanisms/pathophysiology
The pathogenesis of bronchiectasis is complex, poorly
understood and is likely to vary depending on the
underlying aetiology and important modifying factors.
The airway epithelium represents a physical barrier built
to resist infection through tight cellular junctions, mucin
release, efficient ciliary function, antimicrobial peptide
production and active ion transport. All these mech-
anisms are thought to be impaired in bronchiectasis.
It has been postulated that there are two distinct phases
of disease: the first insult to the airway epithelium causes
initial bronchial dilatation and mucociliary impair-
ment2. The disease is hypothesized to be reversible at this
stage, if the original stimulus is controlled or removed42.
However, this initial phase predisposes to infection,
inflammation and failure of microbial clearance through
dysregulated immunity (Fig. 3), and, in some individ­
uals, these insults establish a self-​perpetuating cycle that
results in disease progression1,2.
Most evidence supports this disease model, but
important gaps exist in our understanding. For instance,
inflammation and bronchiectasis may occur in the
absence of infection43.
Microbial colonization and infection
The airway in bronchiectasis is predisposed to microbial
colonization due to mucus inspissation (thickening) and
impaired mucociliary clearance; these features, together
with dysregulated immunity, may render commensal
organisms pathogenic under appropriate circumstances.
Pulmonary infection is a major driver of airway inflam-
mation and bronchiectasis35,44,45 (Fig. 3). Airway damage
from severe or recurrent childhood lung infection may
contribute to the development of bronchiectasis in later
life, and protracted bacterial bronchitis (chronic, persis-
tent bacterial infection of conducting airways character-
ized by the presence of cough for >4 weeks) is implicated
in disease pathogenesis46,47. Bacteria, mycobacteria,
viruses and fungi have all been proposed to promote
the initiation and perpetuation of bronchiectasis, and
bacterial load, rather than the specific pathogen, is the
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100 worsening pathology 11,29,59. Mycobacterium avium

Children
90 complex is the most frequently isolated NTM in bron-
High-income countries
80 chiectasis, and patients with NTM infection are more
Low-income countries
70
likely than patients without NTM to develop Aspergillus
Adults spp.-associated disease, potentially indicating a shared
60
Cohort (%)

Europe and North America susceptibility factor60. Specific roles for viruses and
50 Africa, Asia and South America fungi are emerging but the mechanisms are currently
40 Australasia unclear61,62.
30 Collectively, infective agents contribute to the patho-
20 genesis of bronchiectasis by promoting airway dam-
age and increasing inflammation, and, by evading host
10
immune responses, pathogens can persist in the airway
0
and eventually become resistant to antimicrobial therapy63.
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Aetiology
Fig. 2 | Aetiologies of bronchiectasis grouped by regions and populations. Data
summarized from systematic reviews and publications in adults10,11,36,87,108,114,134 and
children110. However, one paper11 described some of these underlying aetiologies as
comorbidities (for example, primary immunodeficiency and inflammatory bowel
disease); thus, the prevalence data may not be accurate. aUnclear whether these figures
include post-​tuberculosis bronchiectasis. ABPA , allergic bronchopulmonary aspergillosis;
COPD, chronic obstructive pulmonary disease; PCD, primary ciliary dyskinesia.
major determinant of the inflammatory response44.
Most studies to date use traditional culture methods to
identify the causative bacterial pathogen, but molecu-
lar approaches to characterize the microbiota have also
been performed in bronchiectasis, identifying organisms
that are present in low abundance or difficult to detect
by routine culture48,49. The bacteria most frequently iso-
lated from airway secretions of patients with bronchi-
ectasis include Haemophilus influenzae, P. aeruginosa,
Moraxella catarrhalis, Streptococcus pneumoniae and
S. aureus36,44,50. Virulence strategies vary between organ-
isms and include structural-​mediated damage to the host
and inflammatory damage. Pathogens can also evade the
host immune response via several mechanisms, such as
forming a biofilm, which acts as a shield, and undergo-
ing genetic changes (for example, genetic mutations can
confer antimicrobial resistance). Some organisms, such
as H. influenzae, can invade the airway epithelium and
survive intracellularly, thereby circumventing or dysregu-
lating the host immune response51,52. H. influenzae is one
of the most frequent causes of chronic airway infections
in patients with bronchiectasis, but the mechanisms are
poorly characterized3,53,54. To date, such studies of the
lung microbiome using sequencing technologies in bron-
chiectasis have confirmed a key role for Pseudomonas
and Haemophilus genera55,56. Bacteria can evade antibody
responses through cleavage or destruction of immuno-
globulins such as IgA57, whereas P. aeru­ginosa may utilize
host IgG to block the activation of complement as a
virulence strategy58. P. aeruginosa is a key bronchiectasis-​
associated pathogen, associated with poorer clinical out-
come and higher mortality than those associated with
other pathogens35,45.
NTM are intracellular pathogens that can poten-
tially cause bronchiectasis directly or infect patients
with established bronchiectasis, contributing to
is challenging because, paradoxically, both immunodefi-
ciency and immune hyper-​reactivity can lead to disease.
The paradoxical consequence of both hypo-​immune and
hyper-​immune function resulting in bronchiectasis sug-
gests that a single defect or mechanism is improbable,
and the extent of dysregulation also probably differs
among patients with bronchiectasis63–66. Inflammation
and destruction of the small airways can lead to bron-
chiectasis. This is evidenced by data from patients with
common variable immunodeficiency, in whom radio-
logical signs (expiratory air trapping or mosaic attenua-
tion) suggestive of inflammation-​associated alterations
in the small airways appear before bronchiectasis is
­diagnosed and are potentially reversible67.
Excessive immune response. In addition to providing
a mechanical barrier against invading organisms, the
epithelial cells recruit neutrophils by releasing pro-​
inflammatory signals and increasing the expression of
surface glycoproteins that regulate phagocyte adhesion
and transendothelial migration63 (Fig. 3). These host
responses become exaggerated in bronchiectasis, owing
to overwhelming persistent infections that perpetuate the
pathogenic mechanisms68,69. In addition to airway inflam-
mation, there is evidence of systemic inflammation asso-
ciated with increased levels of fibrinogen, a coagulation
factor, which has been proposed as an indirect marker of
disease severity70. The interaction between coagulation
and inflammation is currently an area of intense study and
there is evidence that other systemic inflammatory
pathways are activated, including increased circulating
adhesion molecules and endothelial dysfunction, the
latter a marker of cardiac risk64,70.
Immunodeficiency. Immunodeficiencies, primary or
acquired, are associated with bronchiectasis, and fail-
ure of adequate vaccine responses to S. pneumoniae
or H. influenzae have been described in some patients
with bronchiectasis, indicating that their immune sys-
tems are unable to make coordinated B cell and T cell
responses to specific antigens71. Bronchiectasis is preva-
lent in patients with chronic lymphocytic leukaemia and
transporter associated with antigen presentation defi-
ciency syndrome72. In transporter associated with anti-
gen presentation deficiency syndrome, the expression

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of major histocompatibility complex class I molecules eosinophils are usually associated with environmental or
is reduced, resulting in decreased antigen recognition allergic triggers and promote allergic TH2 cell-​mediated
by cytotoxic CD8+ T cells, impaired immune response responses. Airway neutrophilia is observed even in stable
and subsequent microbial persistence. Thus, cytotoxic bronchiectasis, but increases during infection and exacer­
T cells may play a key part in the development and pro- bations69,75,76 and contributes to disease pathogenesis
gression of bronchiectasis. Other congenital or acquired (Fig. 3). Neutrophils are recruited to the airway by chemo­
immunodeficiency states, such as HIV infection, are also attractants77, and cellular migration is regulated by a
associated with the development of bronchiectasis73. series of inter-​related and organized processes, including
altered surface receptor expression, increased cellular sig-
Cellular innate immunity. Airway neutrophilia is a hall- nalling and cytoskeletal manipulation in neutrophils, the
mark of bronchiectasis, although up to one-​quarter of endothelium and extracellular matrix78,79. Once neutro-
patients have eosinophil-​dominant airway inflamma- phils reach the airway, pathogens and the high concen-
tion74,75. The different cell populations may reflect differ- tration of inflammatory mediators trigger phagocytosis,
ent disease triggers, as neutrophils are mainly recruited degranulation and bacterial killing63. However, in bron-
by an infectious trigger and skew T cell responses towards chiectasis, despite their abundance, neutrophils fail at
T helper 1 (TH1) cell-​mediated inflammation, whereas removing bacteria, largely because phagocytosis is hin-
dered through several mechanisms, including cleavage
of receptors by neutrophil elastase and secreted defensins
NE NE NE (primarily released from neutrophils) and dysfunctional
Efferocytosis
intracellular signalling induced by the inflammatory
Macrophage CD35
IgG mileu80–83. Neutrophil elastase also directly cleaves com-
C3b/C4b CD11b/CD18 FcγR plement components bound to pathogens, preventing
• IL-1β • Cathepsin G opsonization and complement activation81. Neutrophil
Pathogen
CD88 • IL-8 • MMPs elastase is normally inhibited by natural anti-​proteinases,
P. aeruginosa • LTB4 • NE
• Proteinase 3
such as α1-antitrypsin and secretory leukocyte proteinase
H. influenzae • TNF
IL-17 • ROS inhibitor, but in the bronchiectasis airway, extensive neu-
NTM VCAM1 trophil recruitment and degranulation cause an excess of
Phagocytosed
C5a ICAM1 pathogen neutrophil elastase, and anti-​elastase defences are hin-
Biofilm
dered by multiple mechanisms, including cleavage and
Mucus TH17 cell CD8+ T cell
inactivation of secretory leukocyte proteinase inhibi-
tor76,84. This imbalance has been reported to damage air-
way epithelia, slow ciliary beat frequency and promote
Blood mucus production76,85–87. Neutrophil elastase levels cor-
Selectin
Goblet cell
vessel relate with disease severity, lung function, radiological
findings and sputum volume and have been evaluated
PSGL-1 Epithelial cell
• IL-8 as a potential inflammatory and prognostic marker in
• MIP-2 Neutrophil Endothelial cell
• TNF stable and exacerbating bronchiectasis that responds to
antibiotic therapy44,76,87.
Fig. 3 | Microbial infection and dysfunctional immunity contribute to the Similar to neutrophils, macrophage numbers are
pathophysiology of bronchiectasis. The respiratory epithelium recruits neutrophils by increased in bronchiectasis airways86,87. Patients with
releasing pro-​inflammatory signals (IL-8, macrophage inflammatory protein 2 (MIP-2; productive cough (with mucus production) seem to have
also known as CXC-​chemokine ligand 2 (CXCL2)) and tumour necrosis factor (TNF)) an increased burden of macrophages and macrophage-​
and increasing cell surface expression of intercellular adhesion molecule 1 (ICAM1) and derived neutrophil chemoattractants88,89. Macrophage
vascular cell adhesion protein 1 (VCAM1). C5a (from circulating complement) stimulates efferocytosis (the process in which apoptotic cells, particu-
airway macrophages to release TNF, IL-8, IL-1β and leukotriene B4 (LTB4), which promote
larly neutrophils, are cleared from the airway) is impaired
neutrophil recruitment77. Expression of CD11a/CD18 integrins on neutrophils (not
shown) and increased expression of selectin on endothelial cells promote neutrophil
in children with bronchiectasis and protracted bacterial
transmigration to the airway , where degranulation occurs. Key mediators of airway bronchitis, a forerunner of bronchiectasis90. Failure of
inflammation and destruction in bronchiectasis include reactive oxygen species (ROS), neutrophil clearance results in increased inflammatory
neutrophil elastase (NE), matrix metalloproteinases (MMPs), proteinase 3 and damage through unopposed granule product release and
cathepsin G, all of which are released by neutrophils56,76. Cleavage of neutrophil surface secondary necrosis of apoptotic cells. Neutrophil elastase
complement (CD35 and CD11b/CD18) and Fcγ receptors (FcγR; CD16 and CD32) by may impair neutrophil clearance by cleaving phosphati-
neutrophil elastase impairs opsonization and the phagocytic ability of neutrophils. The dylserine receptor from the surface of macrophages,
recognition of opsonized immunoglobulin G (IgG) targets and C3b/C4b and iC3b (not which is required for recognition of apoptotic cells91.
shown) complement components on microorganisms is also further compromised63.
Macrophages normally clear neutrophils by efferocytosis, a process impaired by
Impaired mucociliary clearance
neutrophil elastase release from excessive neutrophil degranulation in bronchiectasis.
Other airway immune cells, including lymphocytes, specifically cytotoxic T cells and
Mucociliary clearance is an important physiological
T helper 17 (TH17) cells, have a role in the pathogenesis of bronchiectasis by, respectively, self-​clearing mechanism for the airway. The epithelial
downregulating major histocompatibility complex class I molecules (thereby enabling cells lining the airways have hair-​like structures (cilia)
microbial persistence) and releasing IL-17 , an additional neutrophil chemoattractant207. on the surface; cilia beat in a tightly regulated manner
Ineffective microbial killing, persistent infection and inflammation coupled to to propel material towards the pharynx. Together with
mucus hypersecretion and airway epithelial damage all promote bronchiectasis. overlying mucus, cilia form the mucociliary escalator,
NTM, non-tuberculous mycobacteria; PSGL-1, P-​selectin glycoprotein ligand 1. which ensures that foreign agents entering the airway are

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transported and either swallowed or expelled by cough-
ing92. Damage to cilia and the associated mucociliary
escalator can lead to bronchiectasis. Mucus trapping
causes airway obstruction and dilatation and provides
a suitable environment for infection (Fig. 4).
Multiple factors may cause reduced ciliary beating,
including cyanide produced by P. aeruginosa and neu-
trophil proteases, and deletion of airway cilia results in
non-​inflammatory bronchiectasis and airway hyper-​
reactivity93–95. Structural airway defects can contribute
to impair the function of the mucociliary escalator and,
therefore, airway clearance. Anatomical defects of the
airway, such as tracheomalacia (softening of cartilage
that maintains patency of the trachea), bronchomalacia
(softening of cartilage in the bronchial walls) and tracheo­
bronchomegaly (a rare congenital disorder charac­
terized by a widening of the upper airways), can lead
to bronchiectasis through deficient airway clearance,
excess secretions and recurrent infection96,97.
Genetic conditions affecting cilia and their function
are also implicated in bronchiectasis. PCD is an auto-
somal recessive disease leading to dysfunctional cilia
and impaired mucociliary function54,98,99. In autosomal
dominant polycystic kidney disease, renal cysts develop
because of defective cilia and ciliary polycystin-1 pro-
tein in renal epithelia100. Cilia of the airway epithelia also
express polycystin-1, and radiology from patients with
autosomal dominant polycystic kidney disease reveals
that substantial numbers of these patients have bronchi-
ectasis100. CFTR variants that result in the expression of
dysfunctional cystic fibrosis transmembrane conduct-
ance regulator (CFTR) are also proposed to influence
the pathogenesis of bronchiectasis, even in the absence
of homozygosity for CFTR variants that would result in a
diagnosis of cystic fibrosis101,102. Heterozygosity for these
CFTR variants may have a role in the development of
diffuse bronchiectasis, at least in a subset of patients101,103.
CFTR mutations can result in abnormal ion transport
in the airways, leading to airway dehydration and
• Excessive mucus secretion Dysfunctional
• Airway obstruction and dilatation
• Persistent infections
cilia
Oxidative stress
Hypoxia
Biofilm CFTR variants
Mucus
Blood
Endothelial cell Epithelial cell Goblet cell vessel
Fig. 4 | Airway obstruction, impaired mucociliary clearance and other mechanisms
promoting bronchiectasis. Excess mucus production and the viscosity of mucus in
bronchiectasis promote airway obstruction and, therefore, bronchial dilatation.
Dysfunctional cilia (due to genetic mutations or acquired structural damage) and the
associated impaired mucociliary escalator further contribute to mucus retention and
airway obstruction. Oxidative stress (predominantly from immune cells), hypoxia (from
infection and inflammatory airway damage) and dysfunctional CFTR variants promote
and may lead to the development of bronchiectasis. Together, these mechanisms favour
persistent airway infection, inflammation and bronchial damage, thereby perpetuating
the pathogenetic mechanisms underlying bronchiectasis.
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inflammation. Measurement of transepithelial ion
transport across the nasal epithelium (nasal potential
difference measurement) and CFTR mutation frequency
analyses in non-​cystic fibrosis-​associated bronchiectasis
have suggested, in some cohorts, a higher than expected
frequency of CFTR dysfunction103.
Other mechanisms
Oxidative stress (structural and functional alterations
induced by reactive oxygen species) and hypoxia in
the airway are induced by consumption of nutrients by
inflammatory cells and bacteria and by reduced supply of
oxygenated blood to damaged lung segments. Oxidative
stress is associated with airway damage in bronchiec-
tasis104,105. Activated immune cells in bronchiectasis are
a rich source of reactive oxygen species, and increased
H2O2 levels in exhaled breath correlate with neutro-
phil burden, disease severity and lung function104,105.
Microbial infection further contributes to oxidative
stress and inflammation through phagocyte recruitment,
lipid peroxidation and the release of the stress response
protein haem-​oxygenase-1 (ref.106). Vitamin D deficiency
could also contribute to bronchiectasis pathogenesis;
however, it is unknown whether vitamin D deficiency,
by leading to impaired innate immunity, plays a part in
bronchiectasis or whether it is a result of bronchiectasis,
which can lead to a lack of outdoor sunlight exposure
(owing to more-​severe disease and reduced mobility and
exercise capacity) and, therefore, vitamin D deficiency107.
Diagnosis, screening and prevention
Diagnosis
Diagnosing bronchiectasis requires clinical awareness of
this disease, to prescribe the necessary tests to confirm
or rule out the diagnosis and detect possible underlying
diseases and comorbidities. Early diagnosis enables
earlier achievement of treatment objectives (improving
the quality of life (QOL) of patients and possibly halt-
ing disease progression)36,108, but many patients with
bronchiectasis are diagnosed at an advanced stage.
Chronic wet or productive cough, recurrent respiratory
infections, persistent pneumonia or chest radiography
changes, haemoptysis, digital clubbing and dyspnoea can
occur in both adults and children and should prompt
diagnostic tests for bronchiectasis. The presence of other
symptoms depends on the underlying characteristics of
the aetiology and patient population.
Medical history, symptoms and signs. In adults, the
main symptom of bronchiectasis is chronic cough
with mucopurulent sputum (up to 80% of individuals),
and bronchiectasis should be suspected in individuals
with productive couch and severe COPD or asthma or
chronic fatigue109. As disease severity increases, other
symptoms (for example, dyspnoea, haemoptysis, weight
lost and fatigue) may occur. The relative prevalence of
these symptoms and signs varies among global cohorts,
dependent on the locality, aetiology and severity of
bronchiectasis and comorbidities.
The clinical findings of children with bronchiecta-
sis also vary among global cohorts. Chronic cough is
the most consistent symptom (35–100% of patients)
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At any point in the lung, the internal luminal diameter

of the bronchus should be smaller than the external diam-
eter of the adjacent blood vessel. A bronchoarterial ratio
(BAR) of >1 is pathological. Lack of tapering of the bron-
chi and the presence of bronchi visible within 1 cm of the
pleura are additional radiological signs indicative of
bronchiectasis (Fig. 5).
However, the diagnostic criteria of bronchiectasis are
not univocal. Most studies define bronchiectasis if BAR
is >1 or >1.5, but using a single ratio irrespective of age
and the lung segment affected is, in the authors’ opinion,
problematic. Pathology-​based data and older studies
found a consistent BAR irrespective of lung inflation
and position, but studies using better CT technologies
reported that this ratio is age dependent and segment
dependent117–121. A study on 85 adults described a sig-
nificant positive correlation between age and BAR, and
41% of those of >65 years of age had a BAR of >1 (ref.122).
Extrapolation of the regression line from this study sug-
gests that the cut-​off BAR for normality should be at
Fig. 5 | Radiological features of bronchiectasis. High-​resolution CT scan slice
(reconstructed from a multi-​detector CT scan) shows bronchiectasis in a 7-year-​old child 0.4–0.5 in infants, and one study in children of 0–5 years
who first presented to the respiratory service with chronic cough. Dilatated bronchi and of age confirmed this value120. Experts have suggested
the adjacent blood vessels are visible, with the typical signet ring shape: cylindrical that a BAR of ≥0.8 should be the cut-​off used to define
bronchiectasis is present in the right lower lobe (blue arrow), and varicose-​to-cystic abnormality in individuals of <18 years of age when the
bronchiectasis is present in the right middle lobe, left lingula (yellow arrow) and lower clinical symptoms suggest bronchiectasis123.
lobe. Non-​tapering of the bronchi is visible in the left lower lobe (black arrow), and visible Several factors, for example, the presence of asthma
bronchi adjacent to the mediastinal pleura or within the outer 1–2 cm of the lung fields and elevated altitude, may increase the BAR and, there-
are present in the left lingula and lower lobe (red arrow). The aetiology of bronchiectasis fore, generate false-​positive results. Furthermore, a study
in this child is primary aspiration.
in adults with COPD described that the increased BAR
was related to a reduced diameter of the blood vessel and
and cough may resolve after treatment110,111. Of note, as not an increased diameter of the bronchus119. Some have
young children usually do not expectorate, the cough argued that the outer diameter of the bronchus should
is wet rather than productive112. Predictors of having be used instead of the inner diameter when measuring
bronchiectasis in children include failure to thrive and the BAR, and most studies do not specify what diam-
chest wall deformity (present in 45% and 95% of cohorts, eter was used120,123. In addition, the radiological bron-
respectively), the presence of recurrent (>3 per year) chial dilatation is probably a gradual process, and the
protracted bacterial bronchitis46 and failure of the wet type of CT may affect the ability to detect bronchiectasis.
cough to resolve with oral antibiotics (adjusted odds Contiguous 1-mm slices (from multi-​detector CT scans)
ratio = 20.9; 95% CI 5.4–81.8)113. Symptoms of dys­ are superior to conventional HRCT images (1-mm slice
pnoea and haemoptysis are generally rare in paediatric every 10 mm)124,125, and not all studies specify what type
cohorts in high-​income countries, where bronchiectasis of CT scans was used.
is generally diagnosed earlier (and hence patients have Thus, the diagnosis of bronchiectasis should not rely
milder disease at diagnosis) than in low-​income coun- on radiology only. For example, mild cylindrical bron-
tries. Cohorts based in low-​income countries generally chiectasis can be observed on CT in the absence of clini­
reported a higher prevalence of wheeze (up to 66%), cal symptoms in up to 20% of individuals of >65 years
haemoptysis (up to 41%) and digital clubbing (up to of age32,122. We propose that, in addition to radiology,
41%) than cohorts from high-​income countries outside the diagnosis includes a clinical phenotype supported by
of indigenous settings46,109–112. airway neutrophilia. A univocal definition of bronchi-
ectasis as a disorder would be particularly important for
Radiology. If bronchiectasis is suspected, radiological consistency across studies and advancement of interven-
examination should be performed. The diagnosis of tions aimed at treating mild bronchiectasis to prevent
bronchiectasis is objectively confirmed with a high-​ disease progression.
resolution CT (HRCT), which is the gold-​standard
diagnostic tool36,108,114 (Fig. 5). Volumetric CT, which ena- Initial evaluation
bles closer examination of the whole lung (that is, more Once bronchiectasis has been diagnosed, on the basis
images are acquired), has improved sensitivity and inter- of radiological findings and clinical presentation, addi-
observer agreement for the diagnosis of bronchiectasis, tional examinations should be performed to assess the
compared with standard HRCT scans115. Guidelines possible underlying aetiology, the severity of the disease
currently recommend the use of HRCT to confirm the and the presence of comorbidities and treatable traits.
diagnosis in patients with clinical symptoms of bronchi- Spirometry (a test to determine lung function by meas-
ectasis, but arguably volumetric CT with HRCT should uring FEV1 and forced vital capacity, which is the total
be the gold standard116. amount of air exhaled during a FEV test) is useful in

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adults and older children (usually of >4 years of age).
When bronchiectasis is mild (typically with few lobes
affected or only a mildly elevated BAR), lung function is
often completely normal126, particularly in children and
young adults with bronchiectasis living in affluent set-
tings. The classical spirometry abnormality associated
with bronchiectasis is an obstructive profile in which
airway collapse obstructs expiratory airflow, resulting
in a reduced FEV1 but normal lung volumes; a mixed
obstructive–restrictive pattern may also be present, with
both FEV1 and forced vital capacity reduced3,127.
Obtaining a lower airway secretion specimen (usu-
ally sputum) is another necessary component of the
initial evaluation in both adults and children, particu-
larly to guide antibiotic therapy and identify NTM and
P. aeruginosa.
Bronchoscopy is not required routinely in adults who
are able to spontaneously expectorate sputum for micro-
biology assessment, but may be useful if foreign body
obstruction is suspected or to evaluate patients who are
unable to provide good-​quality sputum samples116. Some
centres undertake bronchoscopy in children routinely,
for lower airway assessment and to exclude foreign bod-
ies; information from bronchoscopy helped to guide
antibiotic or corticosteroid treatment in 41% of cases128.
In two systematic analyses of bronchoscopic findings in
children129,130, five airway lesions were described, ranging
from bronchitis to an obliterative lesion, and the extent
of disease on CT correlated to the type of airway lesion.
Severity scores
There are no specific disease severity scoring systems
for children with bronchiectasis, but prognostic and
severity scores have been developed in adults3,9,131. The
two scores that have been most extensively studied are
the Bronchiectasis severity index (BSI) and the FACED
score3,131. The BSI was developed and validated in a pro-
spective multicentre European study of >1,000 patients
and was specifically designed to predict not only mortal-
ity but also hospital admissions and future exacerbations
and to identify patients with worse QOL3,9,132. The BSI
has been shown to be a robust and reproducible marker
of disease severity and adverse outcomes in multiple
studies across Europe, Asia and the United States3,9.
The FACED score is an acronym for FEV1, age, colo­
nization with P. aeruginosa, extension of radiologi­cal
bronchiectasis and dyspnoea. Although it contains
similar variables to the BSI, it attributes a higher propor-
tion of points to age and does not include exacerbations.
The FACED score predicts mortality but has not
performed well as a predictor of morbidity in most
validation studies9.
Evaluation of possible underlying diseases
Upon confirming the presence of bronchiectasis, patients
should also be evaluated for possible underlying dis-
eases3,15,27. Bronchiectasis is a heterogeneous disease
and is associated with multiple underlying aetiologies,
coexisting diseases and overlapping syndromes15,27,33,36,133
(Table 1) that vary among regions (Fig. 2). The search for
the underlying diseases is clinically important, as the
aetiology guides clinical management in children and
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adults36,108,116,134. Nevertheless, despite extensive investiga-
tions, the cause cannot be found in a substantial propor-
tion of patients, who are then diagnosed with idiopathic
bronchiectasis. The European Respiratory Society (ERS)
and Thoracic Society of Australia and New Zealand
guidelines recommend a similar standard set of tests
for adults with bronchiectasis36. The Thoracic Society of
Australia and New Zealand guidelines includes children
and recommends a sweat test for children to identify
cystic fibrosis. Using an algorithm improves the ability to
diagnose an underlying condition that leads to a change
in management134, as shown in a study in which the use
of an algorithm reduced idiopathic bronchiectasis as the
attributed aetiology from 42% to 29%. The additional
tests to be prescribed should be guided by the medical
history (past and present) and clinical findings.
Prognosis
There is a large variation in prognosis, with some
patients having mild bronchiectasis for many years and
others progressing rapidly with frequent exacerbations
and accelerated lung function decline34,76. The reversi-
bility of radiologically defined bronchiectasis (which is
defined when the increased BAR has returned to normal
values) is possible when the cylindrical bronchiectasis
is treated early (Fig. 6). This has been described in chil-
dren but is almost certainly also true in adults. In one
study, bronchial dilatation resolved completely in 6 out
of 21 children with radiologically defined bronchiecta-
sis when HRCT scans were repeated 2–43 months fol-
lowing intensive medical therapy135. In addition, when
primary immunodeficiency disorders are diagnosed
early and optimally managed, bronchiectasis is not a
consequence136, and if already present, bronchiectasis
can improve with optimal treatment (Fig. 6).
Mortality risk in bronchiectasis can be thought of as
an interaction between age, lung damage, lung infection,
disease activity and comorbidities. Thus, assessment of
outcome should take into account the measurement of all
of these components, in both adults and children. Lung
damage may be considered in terms of functional capacity
(which can be measured through the Medical Research
Council Dyspnoea score or other measures of functional
impairment), the extent of disease on CT scan or lung
function testing. Disease activity is best evaluated by the
frequency of exacerbations and severe exacerbations.
Comorbidities may be causes of bronchiectasis (such as
rheumatoid arthritis) or unrelated diseases, such as car-
diac disease3,27,33,45,76. Thus, patients with frequent exacer-
bations, a high symptom burden, old age, more-​extensive
radiological disease and chronic infection, particularly
with P. aeruginosa, are the patients with the most rapid
clinical decline. Among these risk factors, exacerbations
seem to be the most important modifiable risk34.
It is highly likely that factors other than the under­
lying aetiology and the discussed mortality risks also
affect outcomes; examples include access to health care,
the efficacy of (and adherence to) interventions, the
severity of bronchiectasis when first diagnosed43 and
patient and social factors137. This is clearly described in
the paediatric literature, in which early diagnosis and
appropriate interventions can alter the natural history.
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Table 1 | Aetiologies associated with the development of bronchiectasisa

Key features Examples of specific aetiology Key diagnostic test(s)b
Post-infectious
• Largest attributable cause of bronchiectasis in some Tuberculosis Medical history
cohorts1,15,24. Of note, the bias of data recall limits the Pneumonia206 Medical history
validity of this aetiology
• Any severe past infection may lead to bronchiectasis
Immunodeficiency
• The link between immunodeficiency and bronchiectasis Primary: agammaglobulinaemia and hypoglobulinaemia, IgA , IgG and IgM levels
relates to increased susceptibility to pulmonary infections, causing recurrent deep infections
causing recurrent and/or persistent infection, inflammation Primary: selective hyperglobulinaemia (for example, Specific immunoglobulin
and immune dysregulation hyper IgE syndrome and hyper IgM syndrome), causing levels
• Immunodeficiencies are important to identify , as their recurrent deep infections
identification changes clinical management
• Thus, the standard set of baseline tests recommended by Primary: neutrophil abnormalities (function and/or In-​depth immune tests
the European Respiratory Society , the Thoracic Society of movement), causing chronic granulomas and recurrent
Australia and New Zealand and other guidelines includes infections
serum IgG, IgA , IgM and IgE levels Primary: other rare causes (for example, bare Genetic and in-​depth
• There is an increasingly wide array of primary innate, lymphocyte syndrome) immune tests
humoral, phagocytic and complement immune deficiency
and dysregulation identified only through in-​depth immune Secondary: secondary immunodeficiencies (for Serology and medical
tests aided by genetic confirmation208 example, HIV infection and chemotherapy-​induced history
immunosuppression)
Impaired mucociliary clearance
• Primary impaired mucociliary clearance is associated with Cystic fibrosis Sweat test and genotype
genetic diseases, including cystic fibrosis, PCD and Jeune PCD Nasal nitric oxide test, cilia
syndrome)92,209,210 biopsy and motility test, and
• Conditions associated with respiratory muscle weakness genetic analysis
and impaired cough effectiveness (inspiratory and
expiratory forces) Other less common conditions, for example, Various clinical appearances
asphyxiating chest wall abnormality , congenital muscle and genetic tests dependent
dystrophies and myopathies on the condition
Previous lung injury
Wide group of conditions, including: Primary aspiration (due to dysphagia that is often, but Swallowing assessment (for
• Aspiration (the entry of material (such as food, drink or not always, related to neurological abnormality) example, video fluoroscopy)
stomach contents) from the gastrointestinal tract into the Secondary aspiration (due to gastroesophageal reflux). Endoscopy and motility
larynx and lower respiratory tract) Of note, gastroesophageal reflux disease as a cause of testing
• Bronchiolitis obliterans (inflammation of the smallest bronchiectasis is controversial11
airways of the lungs leading to obstruction) Bronchiolitis obliterans (the end product of a large CT scan
number of respiratory conditions, including infections,
graft-​versus-host disease and autoimmune conditions)
Interstitial lung disease (drug induced or due to Medical history
occupational inhalation exposure)
Airway lesions
Structural abnormalities (primary , that is, congenital, Congenital tracheobronchomegaly , primary or Chest CT and bronchoscopy
or secondary , for example, due to injuries) of the airway secondary tracheal stenosis or cartilage abnormalities
can promote the pathophysiological mechanisms of Obstructive (for example, foreign body or external Medical history , chest CT
bronchiectasis compression) and bronchoscopy
Tracheobronchomalacia Bronchoscopy
Concurrent other chronic respiratory diseases
• Both chronic obstructive pulmonary disease (COPD) COPD Lung function and smoking
and bronchiectasis share common features (including history
spirometry abnormality and chronic cough) and aetiologies Asthma Lung function — tests for
(for example, childhood respiratory infections, inhalational airway reactivity
injury and tuberculosis)
• However, some controversy exists121 regarding the Allergic bronchopulmonary aspergillosis should be Elevated anti-​Aspergillus
causative role of COPD in bronchiectasis, as it remains diagnosed according to guidelines212 spp. IgE levels, total IgE
unknown whether one disease precedes another or a supported by raised IgG
previous misclassification occurred and/or Aspergillus spp.
• Adults with COPD and bronchiectasis have a poorer prognosis precipitin and eosinophil
than adults with bronchiectasis without co-​existing COPD32,33 assessment
• Asthma can be a comorbidity , but whether it causes
bronchiectasis is controversial
• One study described that 40% of newly referred adults
with ‘difficult asthma’ (and who had a CT scan) were
found to have bronchiectasis, suggesting that disease
misclassification exists211

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Table 1 (cont.) | Aetiologies associated with the development of bronchiectasisa

Key features Examples of specific aetiology Key diagnostic test(s)b
Connective tissue disease and/or autoimmune
• Important causes in some cohorts, predominantly in Inflammatory bowel disease Colonoscopy
North America (28% of cohort)213 Rheumatoid arthritis Serum autoantibody
• Connective tissue diseases overlap with immunodeficiency assessment
syndromes208
• A wide array of connective tissue diseases can lead to Systemic lupus erythematosus Serum autoantibody
bronchiectasis through the development of interstitial lung assessment
disease, the use of immunosuppressants or other unknown Sjögren syndrome Serum autoantibody
mechanisms assessment
• Bronchiectasis can precede the development of other
features of connective tissue disease
• Inflammatory process in the lungs can provoke
autoimmune responses, such as the generation of
citrullinated peptide antibodies against antigens released
from activated neutrophils
Other syndromes
Bronchiectasis can be associated with conditions that are not Ataxia-​telangiectasia α-​Fetoprotein and genetic
predominantly pulmonary analysis (ATM gene)
Marfan syndrome Clinical characteristics
(defined set exits) with or
without the presence of
fibrillin-1 (FBN1) mutation
Polycystic kidney disease Renal ultrasonography and
genetic analysis
Velocardiofacial syndrome Genetic analysis (22q11
deletion)
Yellow nail syndrome Clinical characteristics. In
some patients, mutations
in FOXC2 may be found
Others
• Being born premature is associated with bronchiectasis in Prematurity Medical history
children and adults200. In a small cohort of adult preterm α1-Antitrypsin deficiency Levels and function of
survivors, 3 of the 46 (6.5%) adults had CT-​defined α1-antitrypsin
bronchiectasis 200

• α1-Antitrypsin deficiency is associated with bronchiectasis

with emphysema; however, guidelines from Europe, Australia
and New Zealand and the United Kingdom do not advocate
screening for it in the absence of emphysema36,108,116
Ig, immunoglobulin; PCD, primary ciliary dyskinesia. aThe table is not a complete list of all possible aetiologies, as some rare diseases have been omitted for brevity.
b
Different guidelines may recommend different diagnostic tests (dependent on the setting and the prevalence of different conditions).

Screening and prevention
As disease confirmation requires a CT scan (thus expo-
sure to radiation), population screening is not advocated
when symptoms are absent. However, one Korean-​based
study that included screening for bronchiectasis as part
of a health-​screening programme reported that 9.1% of
the 1,409 adults (23–88 years of age) examined had radio­
logical bronchiectasis138. Although they were previously
undiagnosed, 54% of the individuals that were identi-
fied to have bronchiectasis had respiratory symptoms,
which may indicate that the bronchiectasis was clinically
relevant, and 15% had a previous history of tuberculo-
sis. These results suggest that screening with CT could
identify unrecognized bronchiectasis in adults, and the
increasing use of CT for other screening programmes
(such as lung cancer screening) is likely to identify bron-
chiectasis in a high proportion of patients. No interna-
tional guidelines currently suggest population screening
for bronchiectasis.
Since the 1940s, clinicians have recognized that bron-
chiectasis is reversible when treated early. Nevertheless,
in the absence of evidence from randomized controlled
trials, some believe that little can be done to prevent
the disease and its progression. Preventive strategies
largely relate to preventing acute respiratory infections
(summarized in Box 1).
Management
The treatment of bronchiectasis aims at stopping the
self-​p erpetuating pathogenetic mechanisms. This
approach includes strengthening the mucociliary esca-
lator, redu­cing airway inflammation and eradicating
bacterial infections (if present)36. As bronchiectasis can
result from several specific conditions (Table 1), the first
key step in treatment is identifying and treating the
underlying disorder, while also optimally managing
comorbid conditions.
Airway clearance methods
The rationale for promoting airway clearance is removing
purulent secretions from the airways, which ameliorates
the inflammation and improves control of symptoms
such as sputum production and mucus plugging92,139–141.
Several studies have demonstrated the benefits of

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a is another mucoactive agent that has been tested in bron-
b
Fig. 6 | Resolution of bronchiectasis in a child. a | Two slices of the initial chest CT scan
of a 5-year-​old child who had had common variable immunodeficiency for >3 years and
was receiving intravenous immunoglobulin every 4 weeks. The CT scan, undertaken at
the first consultation with a paediatric respiratory physician, shows areas of cylindrical
(blue arrow) and varicose (yellow arrow) bronchiectasis in the left lower lobe. b | The
follow-​up corresponding chest CT scan slices of the same child 8 years later. The CT was
taken as the child was clinically less stable (more exacerbations, although spirometry
values were stable), but shows improvement from the initial scan with resolution of
cylindrical bronchiectasis and improvement of the varicose bronchiectasis changes
(yellow arrows). When well, the child did not have a daily cough.
clearance methods, which include physiotherapy tech-
niques and inhaled agents (see below)142,143. Techniques
used worldwide can be self-​performed, require assistance
of another person, such as a physiotherapist, or require
devices that generate positive expiratory pressure to
mobilize secretions. The ERS guidelines for bronchiec-
tasis recommend daily physio­therapy techniques, such as
active cycle of breathing techniques, autogenic drainage
and oscillating posi­tive expiratory pressure, which are all
techniques that patients can conduct independently in
their own homes36. For example, the active cycle technique
includes breathing control (a period of relaxed breath-
ing) and thoracic expansion exercises (deep breathing,
which expands the alveoli and increases expiratory flow
behind secretions) followed by huffing, which forces
the sputum into the larger airways for expectoration. The
ERS guidelines also strongly advocate pulmonary rehabil-
itation for adult patients, as it improves exercise tolerance
and health-​related QOL (HRQOL) 144. Pulmonary
rehabilitation is not used in children.
Adjuvant inhaled agents. Inhaled mucolytics (which loosen
the mucus) and hyperosmolar agents (which incre­­ase the
hydration of the airway) can facilitate mucus clearance
and are adjuvant therapies for airway clearance, that
is, they are used alongside physiotherapy techniques.
Hypertonic saline hydrates airway mucus and increases
ciliary beat frequency, thereby improving airway clear-
ance143,145. A small trial showed that inhalation of hyper-
tonic saline or isotonic saline has a similar effect on risk
of exacerbation, QOL and respiratory function tests over
12 months143, although larger trials are needed. Mannitol
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chiectasis, but a study in 461 patients with bronchiectasis
concluded that inhaled mannitol did not reduce exacer-
bation frequency, although there were improvements in
time to first exacerbation and QOL146.
Although mucolytics such as N-​acetylcysteine and
carbocysteine are used widely in clinical practice, there is
no published evidence of benefit from these agents147,148.
International guidelines for bronchiectasis do not rec-
ommend use of recombinant DNase in adults or chil-
dren, because a multicentre randomized controlled trial
in adult patients with bronchiectasis and P. aeruginosa
infection showed no benefit and the possibility of harm
in terms of increased frequency of exacerbations and
more-​rapid decline in FEV1 (ref.149). Recombinant DNase
is effective in patients with cystic fibrosis, and reasons
for the discrepancy in the response to DNase between
patients with bronchiectasis and patients with cystic
fibrosis have been the subject of much debate but have
never been clearly explained. One study suggested that
DNase treatment of sputum from patients with bron-
chiectasis made the sputum more-​difficult to transport
along the mucociliary escalator150.
Low-​dose macrolide therapy
Macrolides are a class of orally administered antibiotics
that have both anti-​inflammatory and immunomodula-
tory properties and, therefore, are beneficial to patients
with chronic pulmonary diseases, such as diffuse pan
bronchiolitis, cystic fibrosis and bronchiectasis151,152.
A series of pivotal studies have provided strong evidence
(in both adults and children) in favour of prescribing
low-​dose macrolide for the reduction of the frequency
of exacerbations in patients with bronchiectasis. In the
BLESS randomized controlled trial, long-​term low-​
dose erythromycin significantly reduced the frequency
of protocol-​defined pulmonary exacerbation and also
reduced 24-hour sputum production and lung function
decline153. In the EMBRACE study, azithromycin was
associated with a significant 62% reduction in exacer-
bation rates compared with placebo, with no significant
changes in pulmonary function154.
Similar results were observed in the BAT study, in
which azithromycin significantly reduced the time to
first exacerbation and the number of patients experienc-
ing exacerbations, with improvements in QOL and lung
function also observed. However, gastrointestinal adverse
effects were observed in 40% of individuals in the azithro-
mycin group, and the macrolide resistance rate was 88%
in sputum bacteria in the azithromycin group, compared
with 26% in the placebo group155. In a randomized con-
trolled trial in 89 Indigenous Australian children, azithro­
mycin reduced the exacerbation rate by half; however,
similarly to the studies in adults, increased numbers of
children carrying nasopharyngeal bacteria resistant to
macrolides were observed with azithromycin treatment156.
These randomized controlled trials suggest that
macro­lides are beneficial in the treatment of bronchiecta-
sis for patients with frequent exacerbations in both adults
and children. Important considerations in prescribing
macrolides are that a substantial number of patients will
develop gastrointestinal adverse effects, which are likely
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to be dose related155. In addition, NTM infection should
be excluded before macrolide treatment, to avoid the
risk of inducing macrolide-​resistant NTM157. The pos-
sibility of less common adverse effects, such as hearing
loss and cardiovascular adverse effects, should also be
considered152. The development of antibiotic resistance
in oropharyngeal or sputum bacteria is a concern, but
no data are yet available on whether macrolides lose effi-
cacy in patients with bronchiectasis with time as a result
of long-​term use. Studies with a follow-​up time >1 year
would be required to verify this hypothesis.
Inhaled antibiotics
The main objective of using inhaled antibiotics in bron-
chiectasis is the reduction of bacterial load, as high bac-
terial loads increase the local and systemic inflammatory
response, which worsens symptoms of the disease and
Box 1 | Major preventive measures for the development of bronchiectasis
In utero strategies
• Improving fetal health: improves in utero lung development, thereby preventing
intrauterine growth restriction, fetal intrathoracic space, intrauterine infection or
inflammation198; in utero alterations in lung structure and function can influence
future respiratory outcomes198
• Preventing tobacco smoke exposure: improves in utero lung development, alters
immune development and programming, thereby reduces the risk of acute respiratory
infections (ARIs)199; infants born to mothers who smoked during pregnancy have
diminished lung function, altered respiratory chemoreception and increased risk of ARIs
• Preventing prematurity: prematurity is associated with increased ARIs, reduced lung
function and increased risk of chronic obstructive pulmonary disease (COPD), and is a
risk factor for the development of bronchiectasis200
Postnatal strategies
• Encouraging breastfeeding: passive transfer of immunoglobulins through breast milk
reduces ARIs; a case–control study found that breastfeeding was a protective factor
for bronchiectasis201
• Preventing tobacco smoke exposure and active smoking: reduction of passive smoke
reduces the risk of ARIs, asthma, impaired lung development and the risk of COPD.
Systematic reviews have shown increased risk of COPD in adults who smoke and
increased risk of ARIs and reduced lung function in children exposed to smoke202
• Reducing exposure to pollution (for example, biomass combustion and other air
pollution): reduces the risk of respiratory disorders, COPD, respiratory infections and
possible bronchiectasis exacerbations187
• Reducing overcrowding: overcrowding is a risk factor for ARIs203
• Vaccinations (influenza and pneumococcal): prevent early and/or recurrent ARIs.
Reduction in the prevalence of bronchiectasis with childhood vaccines (for example,
measles and pertussis)203
• Optimizing nutrition: poor nutrition is associated with defective immune function
and susceptibility to infections203. Vitamin D supplementation protects against ARIs,
especially those who have deficiency107
• Early treatment of chronic wet or productive cough: reduces the effects of chronic
airway infection and inflammation; chronic cough duration correlates with reduced
lung function and worse radiology bronchiectasis scores in children and adults. Early
treatment arrests processes leading to bronchiectasis47,204
• Early detection of aetiologies that can lead to bronchiectasis: in children at risk of
bronchiectasis, early treatment of their risk factor (such as ARIs) prevents the
development of pneumonia and bronchiectasis
• Improving oral health: reduces aspiration of oral bacteria and, therefore, reduces
ARIs. Improving oral hygiene reduced pneumonia-​related mortality and non-​fatal
episodes in hospitalized elderly people and nursing home residents205
• Improving socioeconomic determinants: bronchiectasis has a higher prevalence in
less-​affluent settings206. Low socioeconomic status is associated with chronic
respiratory disease
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increases the rate of exacerbations44. Inhaled antibiotics
are only used in patients with confirmed bacterial air-
way infection and are often restricted to patients with
P. aeruginosa infection158–162. Tobramycin, colistin and
gentamicin are the most commonly used in clinical prac-
tice. However, randomized trials have given conflicting
data on the effectiveness of inhaled antibiotics. All of the
trials discussed below were conducted in adults.
In a double-​blind randomized controlled study
on 74 patients with bronchiectasis and P. aeruginosa
infection163, P. aeruginosa was eradicated in 35% of the
patients who received tobramycin solution for inhalation,
whereas there was no change in the placebo group. The
adverse effects, such as cough, dyspnoea, wheezing and
non-​cardiac chest pain, were more frequent in patients
receiving tobramycin solution for inhalation, but these
symptoms did not limit therapy. Increased respiratory
symptoms with tobramycin have been reported in other
trials164,165. Approximately 10% of patients treated with
inhaled antibiotics seem to experience bronchospasm,
with rates reported in trials of tobramycin or gentamicin
higher than those reported for other drugs166.
In a randomized controlled study of colistin in
patients with bronchiectasis and chronic P. aeruginosa
infection, the primary end point was not met, as the
median time to first exacerbation was not significantly
different between the colistin and placebo groups
(165 days and 111 days, respectively)158. P. aeruginosa
density was reduced after 4 weeks and 12 weeks, and
the QOL was improved after 26 weeks in the colis-
tin group compared with those receiving placebo158.
Although the study failed to meet its primary end point,
colistin is widely used in Europe and worldwide for the
control of chronic P. aeruginosa infection in patients
with bronchiectasis158.
A randomized controlled trial of nebulized gen-
tamicin in patients with bronchiectasis showed that,
after 1 year, there was reduced sputum bacterial density
in the gentamicin arm, with a 30.8% eradication rate in
patients with P. aeruginosa infection and 92.8% eradi-
cation rate in those with other pathogens. Thus, long-​
term gentamicin therapy provides substantial benefit in
bronchiectasis, but ongoing efficacy requires continu-
ous treatment, as clinical parameters deteriorated after
stopping the drug, during the 3 months off-​treatment
follow-​up period167. This relapse is probably explained
by the fact that studies consistently show that inhaled
antibiotics do not completely eradicate the infection and
bacterial loads return to baseline levels within 1 month
of discontinuing the drugs.
Efficacy of aztreonam solution for inhalation was
assessed in two double-​blind, multicentre, placebo-​
controlled phase III trials designated AIR-​BX1 and
AIR-​BX2 (ref.159). The primary outcome of both studies
was the QOL score, as measured by a newly developed
bronchiectasis-​specific QOL measure: the QOL ques-
tionnaire bronchiectasis respiratory symptoms score
(QOL-​B-RSS)159. The difference between aztreonam
and placebo for the adjusted mean QOL-​B-RSS change
from baseline score was not clinically meaningful in
either AIR-​BX1 or AIR-​BX2 studies. Increased adverse
effects were observed in the aztreonam arm compared

with placebo, including dyspnoea, cough and increased
sputum. In conclusion, aztreonam did not provide sub-
stantial benefit in patients with bronchiectasis in this
trials; by contrast, aztreonam therapy is successful in
cystic fibrosis, suggesting the need for further placebo-​
controlled studies to establish the clinical benefit of this
inhaled antibiotic159.
Two inhaled ciprofloxacin preparations have recently
been evaluated: a dry powder formulation and a lipo-
somal formulation. Two randomized controlled trials
(RESPIRE 1 and RESPIRE 2) of dry powder ciprofloxa-
cin failed to show consistent significant benefits in terms
of the primary outcomes of frequency of exacerbations
or time to first exacerbation160–162. Two trials of cyclical
treatment with ARD-3150 (an inhaled formulation of
ciprofloxacin containing liposome-​encapsulated cipro-
floxacin and free ciprofloxacin) also had inconsistent
results in terms of their primary end point of time to first
exacerbation, with one trial showing a significant pro-
longation of time to first exacerbation but no significant
difference in the replicate trial. Pooled data from both
trials showed a significant reduction in the more-​relevant
clinical end point of frequency of exacerbation 168.
Treatment was safe and well tolerated.
In conclusion, inhaled antibiotics may be beneficial
in some patients with bronchiectasis, but the optimal
patient population has not been identified. Although
the ability of antibiotics to reduce bacterial load has
been demonstrated for all inhaled antibiotics, this effect
is not consistently associated with an improvement in
symptoms or exacerbations.
Inhaled corticosteroids and inhaled bronchodilators
Whereas inhaled corticosteroids and bronchodilators
have an established role in the management of asthma
and COPD169, their use in bronchiectasis is currently
controversial. The ERS and the Thoracic Society of
Australia and New Zealand guidelines suggest consider-
ing bronchodilators in patients with bronchiectasis with
symptoms of breathlessness or features consistent
with asthma36,108. Both guidelines recommend against
the use of inhaled corticosteroids, except in patients
with coexisting asthma or COPD; nevertheless, inhaled
corticosteroids are commonly used in clinical practice.
An updated Cochrane review of seven randomized con-
trolled trials in adults with bronchiectasis found that
inhaled corticosteroids did not improve lung function,
exacerbation frequency or QOL170.
Anti-​inflammatories
Although bronchiectasis is an inflammatory disorder,
our understanding of the inflammatory processes lead-
ing to bronchiectasis is limited, and this is probably
the reason why anti-​inflammatory therapy has been
unsuccessful to date171–174. In a randomized controlled
trial assessing the role of atorvastatin in adult patients
with clinically significant bronchiectasis and ≥2 exacer­
bations in the past year, high-​dose atorvastatin was
associated with a significant improvement in cough174.
However, in a similar trial in patients with P. aeruginosa
infection, there was no improvement in cough173. Many
anti-​inflammatory approaches have attempted to
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P­r i­m e­r
reduce neutrophilic inflammation by reducing neutro-
phil recruitment to the lung, for example, with antago­
nists of C-​X-C chemo­kine receptor type 2 (CXCR2).
This approach did reduce sputum neutrophil count
but seemed to increase the risk of infections in a small
randomized controlled trial171. Approaches that aim to
reduce neutrophil numbers are unlikely to be success-
ful, as neutrophils are required for the control of air-
way infection — removing these cells leads to increased
infections, as demonstrated by a trial of a leukotriene
B4 antagonist in patients with cystic fibrosis, in which
the drug increased the number of infections and caused
FEV1 decline175. Alternative approaches that modulate
rather than inhibit inflammatory functions may be
more successful. Inhibitors of neutrophil elastase have
been tested in a small proof-​of-concept study and a
significant improvement in FEV1 was observed, with
trends towards improvement in QOL, but larger studies
are required172.
Surgery and transplantation
Although surgical resection of affected lung sections was
used extensively in the past, its role is now limited to
severe localized bronchiectasis in which medical man-
agement has failed or to specific complications, such
as severe haemoptysis36. In a meta-​analysis of carefully
selected patients with localized bronchiectasis and who
were assessed as being suitable for surgery, the pooled
mortality was 1.4%, with a postoperative morbidity
rate of 16.2%. Surgery completely alleviated symptoms
in 71.5% of patients176. Close collaboration between
expert physicians and surgeons is mandatory if surgery
is considered.
The success of medical therapy means that bronchiec-
tasis is now an infrequent indication for lung transplan-
tation. A report from a UK transplant centre identified
42 patients with bronchiectasis receiving transplanta-
tion over a 23-year period. Consistent with indication
for transplant in other respiratory diseases, the major
characteristics of this bronchiectasis cohort were severe
lung function impairment (mean 22% FEV1 predicted)
with severe disability. Outcomes were favourable, with
survival of 74% at 1 year and 48% at 10 years177.
Quality of life
Daily symptoms and fatigue, shortness of breath and
productive cough with unexpected exacerbations are a
detriment to the physical and mental health of patients
with bronchiectasis178,179. Symptoms also interfere with
both work and social events; in particular, the produc-
tive cough is often reported by patients to be publicly
embarrassing. Finally, the progressive and incurable
nature of bronchiectasis is a source of stress and anx­
iety180. Medical care utilization and expenditures are also
a burden for patients with bronchiectasis, as they incur
more frequent outpatient visits, longer hospitalizations
and more antibiotic therapy than age-​matched controls
with other chronic diseases (for example, diabetes mel-
litus, coronary disease and HIV infection)181. Of note,
bronchiectasis also imposes a substantial burden on
caretakers of patients; compared with the general popu­
lation, mothers of children with bronchiectasis report
P­r i­m e­r
increased anxiety, stress and depression, which worsen
during exacerbations and are independent of the severity
of disease182.
Patient-​reported outcome (PRO) questionnaires are
self-​administered tools that measure the HRQOL from
the perspective of the patient. PRO questionnaires can be
completed at different time points to measure the effect
of an intervention (for example, an antibiotic), event (for
example, exacerbation) or disease feature (for example,
the presence of P. aeruginosa infection). In contrast to
diseases (such as hypertension or diabetes mellitus) that
can be monitored by parameters that can be measured
objectively, bronchiectasis symptoms are overall sub-
jective. Thus, HRQOL measurements through PRO
questionnaires have enabled clinicians and research-
ers to measure the adverse effects of these subjective
symptoms and gauge which ones are most important to
the patient. The US FDA and the European Medicines
Agency embrace the use of PRO measures. Several PRO
questionnaires have been validated and used as primary
and secondary outcomes in clinical trials of bronchiecta-
sis drugs. The QOL-​B questionnaire and the St George’s
Respiratory Questionnaire can be used to assess overall
QOL, and the Parent-​proxy cough-​specific QOL and the
Leicester cough questionnaire can be used to assess
the effect of cough183.
Small studies investigating the effect of exacerbations
on patients with bronchiectasis demonstrate a measur­able
decrement in HRQOL scores during exacerbations184.
After treatment with an antibiotic, HRQOL improves
beyond steady-​state scores159,184 and remains above
steady-​state levels even when inflammatory markers
rise again185. However, in large clinical trials of inhaled
antibiotics, HRQOL performance has been inconsist-
ent. For example, in the RESPIRE trials160–162, the treat-
ment arms that showed reduction in exacerbations did
not measure improvement in HRQOL scores. In some
instances, the St George’s Respiratory Questionnaire and
QOL-B questionnaire yielded discordant results160,161.
The under­lying reason for these varying results probably
represents more than a difference in medications. Rather,
it may be the heterogeneous nature of the population of
patients with bronchiectasis1. In addition, the influence
of socioeconomic and/or ethnic differences on HRQOL
has not yet been addressed in bronchiectasis. There are
currently no FDA-​approved therapies for bronchiec-
tasis, in part because HRQOL results are mixed, and
the lack of approved therapies probably compounds the
HRQOL problem.
Outlook
Several questions in bronchiectasis, from pathophysio­
logy to long-​term management, remain unanswered; in
2016, the EMBARC published a list of 55 key research
priorities identified from a survey of bronchiectasis
experts and >700 patients from across Europe8.
Pathophysiology
Research into the pathophysiology of the disease is
greatly limited by the lack of an available animal model
that reproduces key features of the syndrome; however,
the study of patients with early bronchiectasis using
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modern ‘omics’ technologies is beginning to identify
key pathological and microbial changes. Although
20–40% of patients are still diagnosed with idiopathic
bronchiectasis15, the increasing availability of exome and
whole-​genome sequencing is enabling the identification
of genetic variants that cause bronchiectasis, including
PIK3CD mutations that cause the primary immuno-
deficiency known as activated PI3Kδ syndrome 186.
A key question is how the immune response becomes
dysregulated in bronchiectasis. Airway innate immune
responses are rapid and respond to foreign invasion
in tandem with pathogen-​specific adaptive responses. In
healthy individuals, inflammation resolves and the patho­
gen is cleared; however, in bronchiectasis, an exagger-
ated response, coupled to resolution and repair failure,
results in the accrual of a harmful mixture of mucus,
pathogens and immune cells in the airway, further
damaging host tissue and creating an environment that
favours perpetuation of the pathogenetic mechanisms.
Patient selection
One of the greatest challenges in bronchiectasis, as out-
lined in this Primer, is that the majority of clinical trials
of this condition have failed. Mortality is not a useful
clinical end point for bronchiectasis trials, and more-​
relevant clinical end points that could be modified with
therapy (such as the frequency of pulmonary exacerba-
tions and hospital admissions and QOL) could better
reflect the severity of disease43,160–162,187. The failure of
previous clinical trials in patients with bronchiectasis
could also reflect an inability to correctly select those
patients who are most likely to benefit from the treat-
ment (for example, those most likely to experience an
exacerbation or whose underlying aetiology is likely
to respond to that specific treatment)43. To address
this issue, large international registries, such as the
European Bronchiectasis Registry at the EMBARC, are
providing key data on the natural history of bronchiec-
tasis that will be required to validate clinical trial end
points, such as QOL and exacerbations10,41,178,188. The
identification of clinical phenotypes (groups of patient
characteristics that are associated with a specific clini­
cal outcome) will help to selectively include in trials
the patients who are more likely to have bronchiectasis-​
associated events for example, the frequent exacerbator
phenotype includes patients who consistently exacer-
bate over time and have poor clinical outcomes as a
result34,189,190. However, multiple underlying biological
processes may be responsible for a specific pheno-
type34,74,191,192. Endotyping refers to identifying under­
lying biological processes that can be measured and are
associated with specific clinical outcomes or treatment
response192,193. Examples of candidate endotypes include
patients with increased neutrophil elastase levels in spu-
tum, who have worse clinical outcomes with faster lung
function decline and may theor­etically be more likely
to respond to antibiotic treatment or to direct inhibi-
tion of elastase77. Other endotypes are represented by
patients with elevated airway bacterial load, who may
be more likely to respond to inhaled antibiotics, or those
with increased blood eosinophil counts, who may be
more likely to respond to inhaled cortico­steroids194–196.
 P­r i­m e­r

The concepts of phenotypes and endotypes require
prospective testing in trials.
Management
Multiple new therapies are in development for bronchi-
ectasis, including new antibiotics, but also new appro­
aches, such as inhibition of dipeptidyl peptidase 1,
which activates neutrophil serine proteases in the bone
marrow197. Drugs designed to improve mucociliary
clearance include CFTR modulators or correctors and
epithelial sodium channel inhibitors43, whereas immuno-
modulators currently being tested include granulocyte–
macrophage colony-​stimulating factor, neutrophil
elastase inhibitors, roflumilast (a phosphodiesterase
type 4 inhibitor) and vitamin D supplementation66,107.
The possible role of these therapies has recently been
extensively reviewed43.
New pathogenetic pathways, particularly of inflam-
matory and ciliary dysfunction, are being identified and
are likely to lead to many new therapeutic opportunities.
Unravelling the heterogeneity of bronchiectasis is the
key research priority in bronchiectasis, as none of the
therapies in current development is likely to be appropri-
ate for all patients, and even antibiotics, which have been
the mainstay of therapy since their widespread availa-
bility in the 1950s, are only required for some patients
and their use in patients who do not need them could
contribute to the development of antibiotic resistance
without giving clinical benefits. Personalized medicine
is required and will be achieved by the development of
biomarkers and stratification tools that can be used in
clinical practice and preferably at the point of care43,192,193.
Finally, therapeutic development in bronchiectasis
has, until now, focused exclusively on end-​stage disease.
However, bronchiectasis and even ‘pre-​bronchiectasis’
(in which the clinical syndrome is evident before the
development of radiological bronchial dilatation) can
be recognized early, and the airway dilatation that
defines bronchiectasis is likely to be a consequence of
the under­lying pathology rather than the cause of the
disease. Patients with an initial inflammatory process
associated with airway infection and neutrophilia can
increasingly be recognized and treated before airway
dilatation develops. Prevention is better than cure, and
ultimately, the solution to the increase in bronchiectasis
prevalence may be to refocus efforts towards effective
recognition and prevention.
In summary, bronchiectasis is a common, disabling
chronic lung disease caused by a wide range of under-
lying disorders. The renewed interest in bronchiectasis
has brought new understanding to its pathophysiology,
new clinical trials and better ways of evaluating QOL
and patient prognosis. All clinicians should be aware of
the principles of managing this disorder in adults and
children, and scientists should view this disease as a field
ripe for new discoveries in pathogenesis and therapy.
Published online xx xx xxxx

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Acknowledgements
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).
Author contributions
Introduction (J.D.C.); Epidemiology (P.J.M.); Mechanisms/
pathophysiology (S.H.C.); Diagnosis, screening and preven-
tion (A.B.C.); Management (R.D.); Quality of life (P.J.M.);
Outlook (J.D.C.); Overview of Primer (J.D.C.).
Competing interests
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 inter-
est 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 inter-
est regarding the content of this manuscript. S.H.C. and R.D.
declare no competing interests.
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Reviewer information
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.
Related links
European Multicentre Bronchiectasis Audit and Research
Collaboration (EMBARC): www.bronchiectasis.eu