Expert Review of Respiratory Medicine

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An update on pediatric bronchiectasis

Danielle F Wurzel & Anne B Chang

To cite this article: Danielle F Wurzel & Anne B Chang (2017) An update on
pediatric bronchiectasis, Expert Review of Respiratory Medicine, 11:7, 517-532, DOI:
10.1080/17476348.2017.1335197

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EXPERT REVIEW OF RESPIRATORY MEDICINE, 2017
VOL. 11, NO. 7, 517–532
https://doi.org/10.1080/17476348.2017.1335197

REVIEW

An update on pediatric bronchiectasis

Danielle F Wurzela,b and Anne B Changc,d
a
The Royal Children’s Hospital, Parkville, Australia; bMurdoch Childrens Research Institute, Parkville, Australia; cLady Cilento Children’s Hospital,
Queensland University of Technology, Brisbane, Australia; dMenzies School of Health Research, Charles Darwin University, Darwin, Australia

ABSTRACT ARTICLE HISTORY

Introduction: The prevalence and awareness of bronchiectasis not related to cystic fibrosis (CF) is Received 6 December 2016
increasing and it is now recognized as a major cause of respiratory morbidity, mortality and healthcare Accepted 23 May 2017
utilization worldwide. The need to elucidate the early origins of bronchiectasis is increasingly appre- KEYWORDS
ciated and has been identified as an important research priority. Current treatments for pediatric Bronchiectasis; children;
bronchiectasis are limited to antimicrobials, airway clearance techniques and vaccination. Several new cough; treatment
drugs targeting airway inflammation are currently in development.
Areas covered: Current management of pediatric bronchiectasis, including discussion on therapeutics,
non-pharmacological interventions and preventative and surveillance strategies are covered in this
review. We describe selected adult and pediatric data on bronchiectasis treatments and briefly discuss
emerging therapeutics in the field.
Expert commentary:
Despite the burden of disease, the number of studies evaluating potential treatments for bronchiectasis
in children is extremely low and substantially disproportionate to that for CF. Research into the
interactions between early life respiratory tract infections and the developing immune system in
children is likely to reveal risk factors for bronchiectasis development and inform future preventative
and therapeutic strategies. Tailoring interventions to childhood bronchiectasis is imperative to halt the
disease in its origins and improve adult outcomes.

1. Background modifiable factors that likely influence the disease [14]. Host
innate immune factors (generally non-modifiable) are likely to
Worldwide, bronchiectasis is increasingly diagnosed [1–3].
have additional impact on the likelihood of disease develop-
Thus, elucidating the early origins of the disease has been
ment and its severity.
identified as a research priority in both children [4,5] and
Although significant advancements have occurred with
adults [6]. Indeed, bronchiectasis is regarded by the
respect to our understanding of bronchiectasis risk factors
European Respiratory Society as one of the most neglected
and treatments, major knowledge gaps remain. The paucity
lung diseases [6]. The role of childhood respiratory tract infec-
of clinical trials in pediatric bronchiectasis unrelated to cystic
tions in the etiopathogenesis of chronic suppurative lung
fibrosis (CF) has resulted in extrapolation from adult and CF
diseases (CSLDs) such as bronchiectasis is well known [3,7]
data. In recent years, the pitfalls of this approach have been
and first described as early as the mid twentieth century [8–
recognized [15] although the number of clinical trials specifi-
10]. Until today the exact mechanisms leading to the devel-
cally relating to bronchiectasis treatment in children remains
opment of bronchiectasis remain poorly understood, although
exceptionally low [16,17] and out of proportion to the burden
is believed to be related to persistent infection and inflamma-
of disease worldwide [18]. This review outlines current recom-
tion of the airways [11,12].
mendations on the treatment of bronchiectasis unrelated to
An appreciation of the etiopathogenesis of bronchiectasis
CF in children and highlights the need for further well-
is crucial in order to understand the role of current and
designed interventional studies in this field.
potential future treatments for the disease. In bronchiectasis,
In recent years, as the burden of bronchiectasis is now
a vicious cycle phenomenon is believed to exist, whereby
recognized and larger than that of CF on a global scale, a
impairment in mucociliary clearance facilitates the establish-
concerted effort to abandon the term non-CF bronchiectasis is
ment of airway infection and the subsequent inflammatory
being made. This review focuses on bronchiectasis and, unless
response further impairs mucosal function and mucociliary
specifically mentioned, refers to bronchiectasis unrelated to CF.
clearance creating a feedback loop as first described by Cole
[13]. Treatment for the condition is thus multimodal, with
antibiotics and airway clearance as mainstays. Lifestyle factors 1.1. Diagnosis
such as exercise, nutrition, environmental pollutant (e.g.
Bronchiectasis is a possible late consequence of a large num-
tobacco smoke) exposure, and vaccinations are additional
ber of different pathological conditions resulting in a common

CONTACT Danielle F Wurzel danielle.wurzel@rch.org.au Murdoch Children’s Research Institute, Melbourne, Victoria 3052, Australia
© 2017 Informa UK Limited, trading as Taylor & Francis Group
518 D. F. WURZEL AND A. B. CHANG
outcome with respect to airway dilatation and damage. Prior
to the advent of CT in the 1970s, the diagnostic criteria for
bronchiectasis were based on contrast bronchography. Today,
chest CT definitions used by most centers are based on adult
data [19,20]. Indeed, this has remained essentially unchanged
for several decades. The radiological conventional high-resolu-
tion CT (c-HRCT) scan definition of bronchiectasis is irreversible
dilatation of one or more bronchi with bronchi larger than
their accompanying vessel and/or failure of one or more
bronchi to taper within the periphery of lung [20]. However,
in children particularly, there is increasing awareness of the
fact that a diagnosis of bronchiectasis requires clinical and
radiological correlation. Further, the current adult-based radi-
ological criteria for bronchiectasis diagnosis are inappropriate
for children for many reasons [12]. The key reasons, as out-
lined in an Australian guideline [21], were ‘(a) extrapolating
c-HRCT findings of bronchiectasis from adult studies may be
inappropriate for children, as morphology of the airway and
lungs changes with age; (b) at least two c-HRCT scans (sepa-
rated by an undefined period) are required to confirm irrever-
sible airway dilatation; and (c) c-HRCT scans performed in
different clinical states yield different results.’
The applicability of a broncho-arteriolar ratio of 1:1, used to
define airway ectasia in adults, underestimates the presence of
bronchiectasis in children as was demonstrated in a study by
Kapur et al. [22]. Airway measurements in this study were
taken from the inner wall as is the classical approach used
since the 1980s and currently used in adults. Recent studies in
children with CF have suggested that outer wall measure-
ments may be arguably more accurate as these account for
bronchial wall thickening and are less prone to parallax error
[23]. Further, a ratio of 1:1 has been proposed as the optimal
threshold for differentiating CF patients from controls using
this outer wall (AA-ratio) method [24]. The applicability of this
finding to children with bronchiectasis unrelated to CF is
unknown and warrants investigation.
A diagnosis of bronchiectasis is generally made in the
context of clinical symptoms and/or signs of bronchiectasis
in addition to characteristic radiological findings. In pediatrics,
a smaller broncho-arterial ratio (BAR) of >0.8 rather than the
adult definition of 1 is sometimes used [25].
Clinically, recurrent or persistent episodes of wet cough are
the hallmark clinical feature in children with bronchiectasis
[26]. Unlike adults with bronchiectasis, in children with mild
or early bronchiectasis, the wet or productive cough may
resolve after initial treatment and only recur during acute
exacerbations [26]. Other symptoms that may be present
include wheeze (often reflective of the presence of airway
secretions and edema rather than bronchospasm). Increased
sputum production or change in color of sputum, chest pain,
breathlessness, hemoptysis, or auscultatory signs of crackles or
wheeze may also occur during exacerbations of bronchiectasis
[27]. Chronic signs can include growth failure, digital clubbing,
hyperinflation, and chest wall deformity, the later occurring
more frequently with increasing severity of bronchiectasis [28].
The above are common symptoms and signs suggestive of
bronchiectasis. The absence of any of the symptoms (other
than cough) or signs above does not indicate absence of
disease. In addition to these, a child with bronchiectasis may
also have symptoms and signs of the underlying cause of the
bronchiectasis. For example, naso-otitis problems or markers
of heterotaxy may be present in primary ciliary dyskinesia or
dysmorphism associated with genetic syndromes (e.g. Cri du
Chat syndrome or Trisomy 21) may underlie neurological
symptoms with associated dysphagia and aspiration.
Bronchiectasis is diagnosed when a child presents with a
clinical history suggestive of bronchiectasis (e.g. recurrent
episodes of antibiotic responsive protracted wet cough,
usually >3 per year) in conjunction with a HRCT chest showing
abnormal dilatation of one or more bronchi [14]. A child who
presents with clinical symptoms but has a normal CT chest is
usually given a diagnosis of CSLD [14]. CSLD may progress to
bronchiectasis over time if left untreated [29]. In protracted
bacterial bronchitis (PBB), the mildest form of endobronchial
suppuration, while the majority of children with PBB fully
recover [5], there is a small minority where those with recur-
rent (>3 per year) episodes are later diagnosed with bronch-
iectasis [30].
1.2. Burden and prevalence
The prevalence of non-CF bronchiectasis worldwide appears
to be increasing, particularly in adults [1,2]. Studies in high-
income countries have investigated the socio-economic, geo-
graphic and ethnic factors that influence the disparity in
observed rates of bronchiectasis between different popula-
tions [2,31]. Pediatric bronchiectasis is a major health issue
for socially disadvantaged Indigenous populations in devel-
oped countries e.g. Maori and Pacific Islanders in New
Zealand, Australian Aboriginal and Native Alaskan children
living in the US [31–34]. However, it has now been recognized
as a major issue in non-Indigenous settings in affluent
societies.
The global burden of bronchiectasis in children is extremely
difficult to quantify as the diagnosis is dependent on case
ascertainment with radiological confirmation using chest CT
that has limited accessibility outside of major cities in affluent
settings. The prevalence estimates in high-income countries
range from 0.5 child years per 100,000 in Finland (1983–1992)
to 1470 per 100,000 in Aboriginal children (<15 years) from
Central Australia [32] and 1600 per 100,000 in South-West
Alaskan Native children living in the US [35] (data from the
early 2000s). Prevalence in low-income countries is likely to be
substantially higher (although no data is available from these
regions) underlining the association between low socioeco-
nomic status and bronchiectasis. Further, the prevalence of
bronchiectasis appears to be increasing in all populations,
irrespective of the country’s affluence.
In a recent study by Quint et al, from a UK-based primary
care database of predominantly adult patients, a substantial
increase in the incidence and prevalence of bronchiectasis was
observed between 2004 and 2013 [2]. More notably, within
the same population, age-adjusted mortality rates were dra-
matically higher in those with bronchiectasis compared to
those without (e.g. in males, mortality rate was 1914.6 per
100,000 vs. 895.2 per 100,000 in general population,
 EXPERT REVIEW OF RESPIRATORY MEDICINE 519

comparative mortality rate of 2.14) [2]. Further, these data
suggested that bronchiectasis was associated with higher,
rather than lower, socio-economic status [2]. However, this
latter finding may be confounded by access to high-resolution
CT scans. Although data on bronchiectasis in children is scarce,
we have observed an increasing number of children with
bronchiectasis in our clinics over the last 15 years, whereby
the total number of children with bronchiectasis now out-
number those with CF.
A study by Munro et al [36] in Auckland, New Zealand,
reported that in the period between 2000 and 2008, the
number of children with bronchiectasis under active review
had increased 280% [36]. Once again this may be due to
increased use of HRCT scan and heightened recognition of
disease; nevertheless, it is likely that the true burden of disease
is underestimated worldwide. Mortality from bronchiectasis
also occurs in children.
In high-income countries, the overall number of childhood
fatalities from bronchiectasis is low [37] but deaths do occur
(as shown in Figure 1). In a New Zealand study examining
deaths in children with and without CF over a similar period
(in children <14 years) showed no deaths related to CF, com-
pared to several deaths in children with bronchiectasis [38,39].
Similarly, a UK study in 2010 [37] reported mortalities in

Figure 1. (a) Hospital admissions (2008–2012) and mortality (2006–2010) for New Zealand children and young people with cystic fibrosis by age. Reproduced with
permission from [38], (b) Acute and semi-acute hospital admissions (2006–2010) and deaths (2004–2008) for New Zealand Children and young people with
bronchiectasis by age. Reproduced with permission from [38].
520 D. F. WURZEL AND A. B. CHANG
children with bronchiectasis. In less affluent countries, where
healthcare access is marginal, mortality in children with
bronchiectasis is estimated to be around 10% (unpublished).
Despite this, awareness of, and availability of resources for
children with bronchiectasis is limited and substantially
lower than that related to CF.
In adults with bronchiectasis, mortality is significantly
increased compared to the normal population. A study in
England and Wales showed an increased mortality rate of
3% per year between 2001 and 2007 in those with bronchiec-
tasis [37]. This is compared to a study of hospitalized
Indigenous Australian adults in Central Australia that showed
an 88.5% survival rate at 1-year [40] and further demonstrated
in a Turkish study published in 2007 that showed even lower
survival of 58% at 4 years [41]. Despite these figures, there has
been a significant improvement in survival over time, with a
study of 400 patients with bronchiectasis published in 1940
suggesting that most patients died before the age of 40 years
[42]. This improvement in survival over time is likely due to
factors such as antimicrobials, vaccination and overall
improvements in healthcare.
Overall, the prevalence of bronchiectasis unrelated to CF is
substantially higher than that of CF (US data showed 30,000
[43] with CF compared to an estimated >190,000 cases with
bronchiectasis [44]).
1.3. Pathophysiology
A knowledge of the basic pathophysiological mechanisms
underlying the development of bronchiectasis is necessary in
order to understand its management. This involves an inter-
play between the host (airway and systemic) inflammatory
response, pathogens and the environment [45]. A comprehen-
sive review of the pathophysiology is beyond the scope of this
article. Readers are referred to a recent pediatric review [4].
Histologically, in bronchiectasis, the bronchial walls (elastic
and muscular components) become damaged by an acute or
chronic insult (often infection) leading to progressive bron-
chial wall dilatation and airflow obstruction. As described by
Cole [46] such injury is believed to initiate a vicious cycle
phenomenon whereby muco-ciliary clearance is impaired con-
tributing to ongoing infection, inflammation and bronchial
wall damage. It has been suggested that pediatric bronchiec-
tasis may be reversible when diagnosed early and managed
intensively [4,47–49].
Reversibility of bronchiectasis on imaging has been shown
in several studies in children with cylindrical bronchiectasis
[47–49], questioning the relevance of the current definition
of bronchiectasis to children (that refers to permanent dilata-
tion of the airways). The ability to definitively ascertain rever-
sibility is reliant upon clearly defined imaging protocols to
ensure appropriate image comparison. Radiological features
however are believed to resolve or improve in some cases of
foreign body aspiration (after removal) and when bronchiec-
tasis is mild or post-pneumonia in a segment of atelectatic
lung [47]. In children with an underlying progressive cause for
their bronchiectasis e.g. immunodeficiency, reversibility may
still be seen (Table 1).
Table 1.
Causes of bronchiectasis where Specific treatment of the underlying
underlying disease is treatable disease
Primary or secondary Immunoglobulin replacement
immunodeficiency, e.g. therapy [76,77], anti-retroviral
hypogammaglobulinemia, HIV therapy
Aspiration disease – primary or Dietary modification or non-oral
secondary, including oral disease feeding [78], Nissen’s
fundoplication, improved oral
care, repair of tracheoesophageal
fistula
Foreign body inhalation causing Removal of foreign body –
bronchial obstruction bronchoscopic or surgical [79]
Allergic bronchopulmonary Oral glucocorticoids [80,81] +
aspergillosis antifungal therapy [82]
Autoimmune diseases, e.g. sarcoidosis Oral glucocorticoids [83] and/or
disease modifying antirheumatic
drugs
IgG4-related disease Oral glucocorticoids [84] and/or
disease modifying antirheumatic
drugs
1.4. Impact and significance of bronchiectasis in children
As the prevalence of bronchiectasis diagnoses are rising the
substantial cost of hospitalizations, school and/or work absen-
teeism and declining quality of life (QoL) in children and
families is increasingly appreciated [50–53]. Child-rated QoL
physical health scores are lower in children and adolescents
with bronchiectasis compared to controls [54]. The burden on
parents of children with bronchiectasis, particularly during
exacerbations, has been shown using a parent-proxy cough-
specific QoL (PC-QOL) questionnaire [52] and the depression,
anxiety and stress scale (DASS) [51]. This latter study showed
that younger age of children is associated with impairment in
QOL for parents (using PC-QOL and DASS) and that QOL is
significantly reduced during exacerbations [51]. The strong
correlation between QoL measures and disease severity in
children with bronchiectasis [53] underpins the importance
of early recognition and prompt and aggressive treatment of
bronchiectasis in childhood.
With advancing bronchiectasis, impacts on general health
and QoL increase with breathlessness and fatigue as promi-
nent symptoms. In end-stage disease, chronic hypoxia contri-
butes to the development of pulmonary hypertension that
may progress to cor pulmonale and eventually death from
respiratory failure [55].
1.5. Treatable underlying diseases
Specific underlying disease processes render an individual at
increased risk of bronchiectasis. Such diagnoses should be
sought in all patients known to have bronchiectasis or demon-
strating clinical symptoms of signs of the condition. This is
especially important as treatment of the underlying disease
e.g. immunodeficiency, may alter the natural history of their
lung disease. In children with bronchiectasis, an underlying
disease process is identified in 63% of cases as shown in a
systematic review of 12 studies including 989 children [56].
The most common causes were: infectious (17%), primary
immunodeficiency (16%), aspiration (10%), ciliary dyskinesia
(9%), congenital malformation (3%) and secondary immuno-
deficiency (3%) [56].

The prevalence of an underlying disease causing bronch-
iectasis may be influenced by the setting (e.g. HIV common in
some African countries) and depth of tests available (e.g. nasal
ciliary brushing for primary ciliary dyskinesia [PCD]). In addi-
tion to routine treatment of bronchiectasis, treating an under-
lying disease may reduce the rate of progression of
bronchiectasis. The table below summarizes potentially trea-
table conditions in which bronchiectasis is a complication. This
highlights the importance of investigating for and identifying
an underlying cause of bronchiectasis.
Treatment of bronchiectasis can thus be broadly divided
into: (i) treatment of the underlying disease where possible;
and (ii) generic treatment. There are several recent compre-
hensive reviews on medications for bronchiectasis [57–59].
The remainder of this review focuses primarily on generic
management of bronchiectasis in children. Specific references
to CF or adult-related data are included where relevant.
1.6. The need for early diagnosis
Early management of bronchiectasis, such as prompt initiation
of airway clearance and appropriate antibiotics during exacer-
bations, is likely to reduce the rate of progression in those
with an underlying disease. This was shown in children with
primary immunodeficiency who were treated early [60]. These
reasons underpin the notion that early diagnosis and treat-
ment for bronchiectasis is vital in order to reduce long-term
morbidity and prolong survival of patients with this condition.
Although it is accepted that early recognition and treat-
ment of bronchiectasis ensures the best outcomes for chil-
dren with bronchiectasis, in reality, delays in diagnosis are
common. A recent study in children suggested delays of
several years before diagnosis [61]. Moreover, a study in
adults with newly-diagnosed bronchiectasis showed that
59% had chronic cough dating back to childhood [62]. This
data should be interpreted in the context of evidence sug-
gesting there may be a linear relationship between duration
of wet cough and lung function decline in adults with
bronchiectasis [62]. A study by King et al showed that with
each additional year of wet cough, FEV1 %predicted
decreased by 0.51% in non-smoking adults with bronchiec-
tasis [62]. In children, spirometry data is unavailable but a
Greek study showed that the longer the duration of wet
cough, the more severe the radiological findings, as deter-
mined by CT score [63]. Early recognition of bronchiectasis,
and identification of those at greatest risk, is needed in
order to target primary and secondary prevention strategies.
Awareness amongst primary care physicians regarding
the risk factors for bronchiectasis, and when to refer for
specialist opinion, is important to facilitate early diagnosis.
An Australian multicenter study evaluating the etiology of
chronic cough in children found that 9% of the 346 children
enrolled had bronchiectasis [64]. A recent study suggested
that children with recurrent episodes (>3 per year) of PBB
and those with lower airway infection with H. influenzae
may be at increased risk of a later diagnosis of bronchiec-
tasis [30]. The findings were based upon the hypothesis that
PBB and bronchiectasis represent a common clinical spec-
trum as they share many similarities, e.g. chronic wet cough,
EXPERT REVIEW OF RESPIRATORY MEDICINE 521
lower airway bacterial infection, and neutrophilic inflamma-
tion [12]. Further studies evaluating this hypothesis and
research aimed at identifying key risk factors for bronchiec-
tasis in children are needed to inform monitoring and sur-
veillance interventions.
2. Therapies
After a diagnosis of bronchiectasis is made and an underlying
cause investigated, the aim of treatment is several fold: (i)
improve QoL; (ii) reduce frequency and/or severity of exacerba-
tions; (iii) prevent progression of disease and/or achieve resolu-
tion; and (iv) minimize complications. The justification for early
and aggressive treatment of children with, or at risk of, bronch-
iectasis is that it may preserve lung function [65] and improve or
reverse changes in those with mild disease [47].
2.1. Airway clearance
Regular airway clearance tailored to an individual child by a
physiotherapist with respiratory expertise is considered standard
treatment for bronchiectasis [66]. There are several different
physiotherapy techniques, many of which are age-dependent.
Airway clearance techniques employed may include use of a
device (e.g. an oscillatory positive expiratory pressure (PEP)
device), autogenic drainage, and/or manual techniques such as
chest percussion. Although there are no supportive studies on
optimal frequency of physiotherapy, daily airway clearance is
generally recommended with intensification during exacerba-
tions. Studies comparing physiotherapy techniques are limited.
Readers are referred to a recent review [67].
A Cochrane review published in 2015 showed that airway
clearance techniques employing an oscillating PEP device
improve QoL and symptoms in adults with bronchiectasis
with reductions in cough and sputum volumes, when com-
pared to other airway clearance techniques and controls [68].
Authors reported on seven small studies, six of which were
crossover in design, and only 1 in children [68]. The single
study in children included 9 children enrolled in a randomized
crossover trial comparing an oscillatory PEP (flutter) device
compared to a sham device; however, methodological factors
precluded any robust conclusions from this study [68]. Further
well-designed, interventional studies evaluating airway clear-
ance methods in children are needed. Mucoactive agents are
sometimes used as part of airway clearance technique and are
discussed in Section 2.4.
Aerobic exercise is considered important in the overall man-
agement of bronchiectasis. Although there are no studies in
children with pediatric bronchiectasis, a study of children with
CF showed significant benefit. A randomized controlled trial
compared a 3-year home exercise program to usual care in
children with CF and demonstrated a significant decrease in
lung function (FEV1 and FVC) decline over time compared to
controls [69]. Further, in a small study on 12 children with PCD,
compared to controls without PCD, authors found that exercise
was a more potent broncho-dilator than beta2 agonists [70]. In
light of the additional known health benefits of exercise, children
with bronchiectasis are encouraged to participate in regular
aerobic exercise as part of their overall management plan.
522 D. F. WURZEL AND A. B. CHANG

2.2. Antimicrobials Table 2. Antibiotic selection for management of bronchiectasis exacerbations in

children [11].
Antibiotic therapy is a key component in the management of Mild-to-moderate
patients with bronchiectasis. This is based upon recognition of exacerbation Severe exacerbation (intravenous
the role of bacterial infection in bronchiectasis pathogenesis. (oral therapy)b therapy)b
Historically, there has been a paucity of research into optimal Initial empiric Amoxycillin, Ampicillin, cefotaxime, or
therapya amoxycillin- ceftriaxone (amoxycillin,
antibiotic prescribing in bronchiectasis, although there has clavulanate amoxycillin-clavulanate, or
been a recent surge in trials in this area, particularly in adults. ciprofloxacin if cefuroxime)
Bacterial load is directly related to neutrophilic airway P. aeruginosa in piperacillin-tazobactam or
recent cultures. ceftazidime + tobramycinc if
inflammation in children with bronchiectasis [71]. The aim of severe or P. aeruginosa in
antimicrobial therapy is to reduce pathogen load and attenu- recent cultures.
ate the infection-inflammation cycle. Antibiotics reduce mor- Specific pathogens
H.influenzae Amoxycillin Ampicillin (amoxycillin)
bidity and the risk of exacerbations while also improving QoL β-lactamase–ve Amoxycillin- cefotaxime, or ceftriaxone
in adults with bronchiectasis [72]. A recent review [57] pro- β-lactamase+ve clavulanate or (amoxycillin-clavulanate or
vides an in-depth summary of antimicrobials in adults and Doxycyclined cefuroxime)
S. pneumoniae Amoxycillin Benzylpenicillin G, ampicillin
children with bronchiectasis. Antibiotic selection is based (amoxycillin)
upon many factors including known or presumed lower airway M.catarrhalis Amoxycillin- Cefotaxime or ceftriaxone
pathogen, patient factors, e.g. age and severity of lung disease clavulanate (amoxycillin-clavulanate or
cefuroxime)
and clinical response to therapy. methicillin-resistant Di-/flucloxacillin Flucloxacillin
However, there are inherent challenges in antimicrobial S. aureus Seek specialist Seek specialist advicee
prescribing for bronchiectasis in children. As most young chil- (MRSA) advicee
P.aeruginosa Ciprofloxacin (max Piperacillin-tazobactam or
dren are unable to produce sputum, pathogen identification 14 days) ceftazidime + tobramycinc
and susceptibilities are often unknown. CF studies have shown Nontuberculous Seek specialist Seek specialist advicee
that upper airway sampling is a poor predictor of lower airway mycobacteria advicee
(NTM)
microbiota [73,74] and is thus not routinely used in children a
Initial empiric therapy is guided by previous lower airway cultures (e.g. from
with bronchiectasis unrelated to CF. Lower airway sampling sputum or broncho-alveolar lavage) and local antibiotic susceptibilities. In
via bronchoalveolar lavage (BAL) is relatively invasive and children without a lower airway sample, antibiotic therapy should be targeted
generally undertaken at the time of diagnosis [75] and later toward H. influenzae, S. pneumoniae, and M. catarrhalis.
b
Local specialist advice should be sought for known or suspected antibiotic
reserved for children who are nonresponsive to empiric anti- hypersensitivity, significant drug side effects or possible drug interactions.
biotics. Where possible, sputum induction should be used. British guidelines recommend clarithromycin as second-line agent for
However, in the absence of knowledge of an individual child’s infections with S. pneumoniae, H. influenzae, and Methicillin sensitive S.
aureus.
lower airway bacteriology, empirical antibiotic selection is fre- c
Of note, there is no proven additional benefit of dual antipseudomonal anti-
quently employed (Table 2). biotics for respiratory infections, as opposed to a single beta-lactam alone.
Choice of empirical therapy is based upon studies of the Combination therapy should still be used for multiresistant P. aeruginosa
strains.
lower airways of children with bronchiectasis (Table 2). These d
Doxycycline is only used in children over 8 years of age.
e
have shown H. influenzae (NTHi), S. pneumoniae, and M. catar- Specialist advice is recommended for treatment of MRSA and NTM. The
rhalis to be the major infecting lower airway organisms [71,85]. decision of when to treat NTM is complicated by high rates of antibiotic
resistance, requirement for prolonged courses, and risk of serious toxicity and
One pediatric study showed that H. influenzae was identified drug interactions.
on BAL in significant bacterial loads (defined as ≥105 colony Table adapted from: Chang et al. [11] © Copyright 2015, The Medical Journal of
forming units per ml) being present in 32%, while 14% cul- Australia – reproduced with permission.
tured S. pneumoniae, 8% M. catarrhalis, and 5% harbored S.
aureus as the major bacterial pathogen in BAL culture [71]. In
contrast to adults with bronchiectasis, in whom Pseudomonas
aeruginosa is often identified, P. aeruginosa is uncommonly bronchiectasis) has also been shown [89]. In this study, chil-
isolated in children with bronchiectasis (approximately 6% of dren with adenovirus were more likely to have bacteria (pri-
newly diagnosed children [71]), and, if present, raises suspicion marily H. influenzae, most were non-typeable Haemophilus
of CF or more advanced lung disease. influenzae (NTHi)) coinfecting their lower airways, compared
In addition to bacteria, viruses, most commonly human rhi- to those without adenovirus, raising the possibility of viral–
novirus (HRV), have also been shown to be associated with bacterial interaction [89].
exacerbations of pediatric bronchiectasis [86]. However, in this Use of antimicrobials for bronchiectasis is generally divided
study, assessment in the non-acute state was not undertaken into short- and long-term use. Table 2 provides a general
and as HRVs are commonly found in children [87], it remains overview of the approach to treating exacerbations (short-
unknown whether HRV triggers exacerbations of bronchiectasis term use), adapted from Australia and New Zealand guide-
or whether its presence simply represents asymptomatic car- lines, also in keeping with recommendations from the British
riage. Identification of viruses in the nasopharynx is reported in Thoracic Society [3]. Readers should tailor antimicrobial selec-
up to 45% of asymptomatic hospitalized children [88]. tion to their local context. Although there is a paucity of
An association between adenovirus species C (genotypes 1 evidence for optimal duration, antibiotics are usually contin-
and 2) and chronic endobronchial suppuration (PBB and ued for 14 days and dosing is as per severe infection [3,90].

2.2.1. Short-term (acute exacerbations)
Exacerbations of bronchiectasis invariably occur during follow-
up. Exacerbations are important as they impact on QoL and
are associated with financial cost. Further, frequency of exacer-
bations requiring hospitalization predicts future lung function
decline in childhood [91] which is also seen in adult patients
[92]. Aggressive and timely therapy for exacerbations, with
antibiotics and airway clearance, helps to preserve lung func-
tion into adulthood [60,65,93].
There is no universally accepted definition of a bronchiec-
tasis exacerbation but a study by Kapur et al. validated a
clinical definition in children. This was based on a cohort of
69 children with pediatric bronchiectasis prospectively fol-
lowed for 900 child-months [26]. In this study, most children
had a wet cough with increased severity of cough over at least
a 72-hour period. Other common signs of an exacerbation
included: a change in sputum color, chest pain, shortness of
breath, hemoptysis, and auscultatory findings [26].
A recent study by Chalmers et al. of 433 adult patients with
bronchiectasis showed that sputum neutrophil elastase was a
good biomarker of severe exacerbations. Elevated neutrophil
elastase was associated with FEV1 decline and neutrophil elas-
tase activity increased significantly during exacerbations
(p = 0.001) responding to antibiotic treatment [94]. Studies
identifying potential biomarkers for exacerbations in children
are needed.
There are no published randomized controlled trials (RCTs)
evaluating the optimal antibiotic regimen for the treatment of
exacerbations of pediatric bronchiectasis. A multicenter study
comparing amoxicillin-clavulanate, azithromycin, and placebo
in children with mild–moderate exacerbations is currently
underway [16]. Currently, treatment choice is based upon
local susceptibility profiles and specialist opinion. Similarly,
optimal antibiotic duration is unclear. Compared to duration
of antibiotics for acute infections in otherwise well children,
longer courses of antibiotics are sometimes needed.
Pathogens tend to persist in damaged (bronchiectatic) lungs.
In addition, microbiological factors such as biofilm formation
[95] and hypermutations [96] further contribute to this. Longer
term antibiotic therapy in bronchiectasis aims to reduce bac-
terial loads with resultant (presumed) reduction in airway
inflammation and less frequent exacerbations [97] while pro-
tecting airway mucosa from further proteolytic and oxidative
damage. Suppression rather than eradication of bacterial
pathogens is usually the aim of treatment, with the exception
of certain pathogens, e.g. P. aeruginosa and methicillin-resis-
tant S. aureus (MRSA) [3].
Oral antibiotics are usually prescribed in an acute exacer-
bation if it is mild–moderate in severity. Amoxycillin-clavula-
nate is often used as a first-line oral agent due to its beta-
lactamase inhibiting effect. If there is failure to improve an oral
agent or if an exacerbation is more severe, then intravenous
antibiotics are prescribed. A single agent, such as a third-
generation cephalosporin, is often considered first line.
Although there is a paucity of evidence for duration, antibio-
tics are usually continued for 14 days [90]. In general, anti-
pseudomonal agents are only used if the child has isolated
pseudomonas (Table 2.)
EXPERT REVIEW OF RESPIRATORY MEDICINE 523
2.2.2. Long-term therapy
Recent guidelines suggest that long-term antibiotics should
only be considered in patients with three or more exacerba-
tions of bronchiectasis per year [3,98]. A recent Cochrane
review examining the utility of long courses of antibiotics
(4 weeks to 1 year) in adults and children with bronchiectasis
showed a small benefit in reduced exacerbations and hospi-
talization rates at the expense of increased bacterial resistance
[99]. There are different antibiotic types used for long-term
therapy. Prior to commencement of long-term antibiotics,
respiratory or infectious diseases specialist consultation is
usually obtained.
2.2.2.1. Macrolides. Macrolides act as both antimicrobial
and anti-inflammatory agents. In simplistic terms, macrolides
attenuate host inflammatory responses providing an anti-
inflammatory effect without immune system suppression
[100]. Their anti-inflammatory effects range from inhibition of
biofilm production to modulation of leukocyte recruitment
and function [100]. The rationale for their use in bronchiectasis
is based upon attenuation of the inflammatory component of
the vicious cycle.
Recently, the role of long-term oral macrolides in bronch-
iectasis has been investigated in a number of RCTs in children
[101,102] and adults [103–105]. Three multicenter trials
showed significant reductions in exacerbation frequency in
adult patients receiving macrolides; however, this was
balanced by an increase in adverse effects, e.g. diarrhea and
macrolide-resistant bacteria in sputum. A New Zealand-based
RCT (EMBRACE study) [103] involved participants receiving
500 mg azithromycin, three times per week, as compared to
placebo. The second RCT was the Bronchiectasis and Long-
Term Azithromycin Treatment (BAT) [105] study where
patients were given daily azithromycin (250 mg) for 12 months
compared to placebo. Both showed similar benefit in the
azithromycin group with respect to significantly fewer exacer-
bations (EMBRACE: rate ratio 0.38, 95% CI 0.26–0.54;
p < 0.0001; BAT: absolute risk reduction 33.5% 95% CI 14.1–
52.9). A third, Australian study (BLESS) [104], showed that
400 mg of erythromycin twice daily for 48 weeks results in a
reduction in frequency of pulmonary exacerbations, lung func-
tion decline, and sputum production; however, in all studies, a
significant increase in macrolide resistance was
observed [104].
An international multicenter trial of macrolides in children
with bronchiectasis has shown similar results to adult studies.
The Bronchiectasis Intervention Study [101] included 89 indi-
genous children from Australia and New Zealand. Children
received once-weekly azithromycin (30 mg/kg) for a mean
duration of 20.7 months with resultant 50% (95% CI 35–71)
reduction in exacerbation frequency compared to placebo
(p < 0.0001). Mean weight-for-age was also significantly higher
in the azithromycin group compared to placebo (1.03 vs. 0.20,
p = 0.003). Similar to findings from adult studies, nasophar-
yngeal carriage of macrolide-resistant bacteria was increased
in those receiving azithromycin [101]. A subsequent study
examined the determinants of macrolide resistance in these
524 D. F. WURZEL AND A. B. CHANG
children and showed that poor adherence (<70%) and the
remote Australian setting were major independent risk factors
for macrolide resistance in those receiving azithromycin and
hence improved adherence may reduce the likelihood of
emergence of some macrolide-resistant strains [102]. Once
weekly dosing, as opposed to daily or second-daily dosing,
may also impact upon likelihood of emergence of macrolide
resistance; however, this remains unstudied. Of note, macro-
lide-resistant S. pneumoniae declined significantly by the 6-
month post-intervention follow-up [102].
The Australian and New Zealand guidelines on the man-
agement of bronchiectasis currently recommend a therapeutic
trial of daily or second-daily azithromycin (e.g. up to
12–24 months) in selected patients (e.g. ≥3 exacerbations
and/or ≥2 hospitalizations in the previous 12 months) [11].
Readers should be cognizant that exclusion of nontuberculous
mycobacterium infection is recommended prior to initiation of
long-term macrolide therapy to avoid emergence of macro-
lide-resistant strains [90].
2.2.2.2. Inhaled antibiotics. Nebulized or dry-powder
administration of antibiotics in CF bronchiectasis has been
well studied in adults with good evidence for their role, parti-
cularly tobramycin, in the acute eradication of Pseudomonas
aeruginosa and in decreasing bacterial density in the airways,
reducing exacerbation frequency and improving QoL and lung
function in patients with chronic P. aeruginosa infection [106].
The evidence in pediatric bronchiectasis is less convincing
however and adverse respiratory effects are reported to be
more common than in CF [107,108].
A recent meta-analysis [109] of published trials examining
the efficacy and safety of six inhaled antibiotics (amikacin,
aztreonam, ciprofloxacin, gentamicin, colistin, or tobramycin)
in the treatment of adults and children with stable bronchiec-
tasis treated for 4 weeks to 12 months. Benefits of inhaled
antibiotics compared to placebo were seen with respect to
reduction in bacterial load (5 trials), eradication of bacteria
from sputum (6 trials), and reduced risk of acute exacerbations
(5 trials). Bronchospasm was significantly more likely in the
intervention, compared to the control group (7 trials) however
and no studies included children [109].
Long-term inhaled antibiotics are thus not currently con-
sidered part of routine management in children [11] with the
exception of children with P. aeruginosa infection.
2.3. Bronchodilators and inhaled steroids
Airway hyper-responsiveness and bronchiectasis often coexist
especially in those with more advanced disease [110].
Differentiating asthma from bronchiectasis in children can
sometimes be difficult as both can present with wheeze. In
bronchiectasis, wheeze is more often caused by airway secre-
tions and edema than bronchospasm [59]. Several studies in
adults examine use of inhaled corticosteroids and/or bronch-
odilators in bronchiectasis; however, findings are conflicting.
These are summarized in a Cochrane review published in 2009
[111]. A subsequent prospective double-blinded RCT found no
significant benefit of inhaled corticosteroids compared to pla-
cebo in the management of bronchiectasis in adults [112].
There are no RCTs on this topic in children with bronchiectasis.
Current practice in children is to only use inhaled steroids and/
or bronchodilators in children with comorbid asthma; it is thus
not a recommended practice to use these medications for
children with bronchiectasis alone.
With the exception of patients with coexistent asthma or
allergic bronchopulmonary aspergillosis (ABPA), there is no
clear evidence that oral corticosteroids alter the rate of lung
function decline in adults with bronchiectasis. They are thus
not routinely used in treating isolated bronchiectasis in adults
or children without asthma or ABPA [92].
2.4. Mucoactive agents
Mucoactive agents aim to assist in mobilizing airway secre-
tions to relieve small and large airway obstruction and/or
reduce mucus hypersecretion. There are different types of
mucoactive medications. These are generally divided into
expectorants, mucoregulators, mucolytics, and mucoki-
netics [113].
There is possibly some benefit associated with using expec-
torants such as inhaled hyperosmolar agents. Earlier studies
suggested a benefit in assisting mucous clearance in patients
with impairment of muco-ciliary function [114] and in an
animal study [115]. However, a single-center double-blinded
RCT over 12 months in adults with bronchiectasis compared
6% hypertonic saline to isotonic saline used in conjunction
with chest physiotherapy and showed no significant difference
between groups for the outcomes of exacerbations, QOL,
sputum colonization, and respiratory function [103].
However, the study was small (n = 40) and likely under-pow-
ered [116]. Nevertheless, inhaled hyperosmolar agents, e.g. 6%
hypertonic saline, are sometimes used in conjunction with
chest physiotherapy in pediatric bronchiectasis.
In contrast, mannitol were initially promising in CF with
good overall safety and efficacy profile [117,118]; however,
two RCTs of mannitol use for at least 12 weeks were recently
published in adults with bronchiectasis with less optimistic
findings [119,120]. The first was a phase 3 study [119] where
subjects aged 15–80 years with FEV1 ≥ 50% predicted received
either inhaled dry powder mannitol (320 mg twice daily,
n = 231) or placebo (n = 112) for 12 weeks, followed by
open-label for 52 weeks in a subset. Mannitol provided mini-
mal benefit at 12 weeks and sputum expectoration in the
placebo group was significantly less than those receiving the
intervention (mean difference = 4.5 g, 95% CI 1.64–7.00;
p = 0.002) [119]. A subgroup (n = 82) had HRCT scans which
showed significantly reduced mucous plugging in the manni-
tol group [119]. There were, however, no between-group dif-
ferences in exacerbation frequency, St. George respiratory
questionnaire (SGRQ) score, spirometry, microbiology, or
inflammatory parameters [119]. The second RCT involved 461
patients randomized to 400 mg twice daily of mannitol or low-
dose mannitol control [120]. In this longer RCT with a higher
dose (same as CF studies), use of mannitol did not significantly
reduce exacerbation rate but increased the time to first
exacerbation (HR 0.78, p = 0.022) and improved SGRQ score
(−2.4 units, p = 0.046) [120]. This contrasts with data in CF
where 24 weeks of mannitol improved FEV1 and reduced

exacerbation frequency by 29% [121]. Until further pediatric
studies become available, mannitol is not recommended in
the routine management of pediatric bronchiectasis.
Mucolytic agents aim to reduce mucus viscosity by altering
the mucin-containing components and enable more effective
mucociliary clearance. These agents include anti-DNaseB,
N-acetylcysteine, erdosteine, and ambroxol. RCTs of these
agents in bronchiectasis have shown equivocal or no benefit
[4], with the exception of anti-DNaseB which, in a study by
O’Donnell et al., showed detrimental effect in adult patients
with bronchiectasis unrelated to CF, with increased exacerba-
tions, hospitalization rate, and accelerated pulmonary decline
[122]. Anti-DNase B is therefore not recommended in the
routine management of children with bronchiectasis.
2.5. Anti-inflammatories
Nonsteroidal anti-inflammatories (NSAIDs), such as indo-
methacin, inhibit neutrophil function and chemotaxis [123]
and may reduce neutrophil elastase release thus potentially
reducing progression of bronchiectasis. There is limited evi-
dence that NSAIDs may be beneficial in adults with pediatric
bronchiectasis. A Cochrane review examining nebulized
NSAIDs included a single study in adults that showed inhaled
indomethacin reduces sputum production and dyspnea in
adults with chronic lung diseases characterized by chronic
sputum production (including bronchiectasis) [124]. A second
Cochrane review examined the use of oral NSAIDS and found
that there were no randomized controlled trials examining
their utility in the management of bronchiectasis [125].
Other anti-inflammatories currently under investigation
include phosphodiesterase-4 inhibitor roflumilast, currently
licensed in the United States for use in severe chronic obstruc-
tive pulmonary disease (COPD) and chronic bronchitis [126]
Figure 2. A simplified schematic diagram of the factors contributing to the development of bronchiectasis. Reproduced with permission from [59].
EXPERT REVIEW OF RESPIRATORY MEDICINE 525
and CXC chemokine receptor 2 antagonists that inhibit neu-
trophil-mediated pulmonary damage and other lung-injury-
induced cellular responses such as angiogenesis [127]; how-
ever, a recent phase 2 study of this drug was discontinued due
to insignificant benefits and concerns regarding adverse
effects [59,128].
A comprehensive overview of current and emerging ther-
apeutics in pediatric bronchiectasis has recently been pub-
lished (Figure 2 extracted from this manuscript summarizes
these interventions) [59].
2.6. Surgical management
In a small highly select group of children with localized severe
disease, who either do not tolerate conventional therapies or
fail to respond surgical evaluation for lobectomy or segmental
lung resection may be appropriate. The evaluation is usually
undertaken in specialized, tertiary care facilities involving
respiratory and infectious diseases consultation. A retrospec-
tive study by Otgun et al. in 2004, of 54 children undergoing
open lung resection for bronchiectasis, found that most ben-
efitted from surgery (approximately 85%) although the mor-
tality rate was high (5.6%) from open surgery [129]. More
recent studies advocate a thorascopic approach which has
been shown to minimize post-op recovery in adults, with no
intraoperative mortality [130–132]. Similar studies in children
are unavailable.
3. Preventative measures and lifestyle
3.1. Exercise
Regular exercise improves exercise capacity and QoL in adult
patients [133,134]. Reasons for this include improved sputum
526 D. F. WURZEL AND A. B. CHANG

clearance, reduced dyspnea, and fatigue with fewer exacerba- of acute and chronic respiratory disease in children [140]. Studies
tions over a 12-month period as shown in an adult study [134]. in adults have described an association between Vitamin D
There are however no comparable studies in children. deficiency and worse outcomes in bronchiectasis [141].
Nevertheless, due to the known benefits of exercise with However, there are no current studies in children and there is
respect to general health, children should be encouraged to discordance between data from association studies and that
participate in sports and exercise unless specific contra-indica- from RCTs for other chronic respiratory diseases [142,143].
tions exist (e.g. coexistent cardiac abnormality).
3.4. Environmental pollutant avoidance
3.2. Vaccines Tobacco smoke exposure and other environmental pollutants
are known to exacerbate chronic respiratory diseases [144,145]
Current evidence in pediatric literature indicates that the sin-
and accelerate lung function decline [146]. Preventing children
gle predictor of lung function decline in children with bronch-
with bronchiectasis from taking up tobacco smoke is impera-
iectasis is frequency of exacerbations requiring hospitalization
tive. Adolescents and all parents and guardians should be
[91]. Each hospitalization is associated with a reduction in lung
educated on the deleterious effects of secondary smoke expo-
function (as measured by drop in percentage predicted forced
sure. Referral to services facilitating smoking cessation should
expiratory volume in one second FEV1% adjusted for time) of
be undertaken where children or parents smoke.
1.95% [91]. Vaccines aim to prevent acute respiratory infec-
tions and reduce exacerbations and consequently acute hos-
pitalizations. Readers are referred to a recent review for a 3.5. Self- or parent-management
comprehensive overview of the subject [135].
Parent and patient education via provision of resources and
Several currently licensed vaccines that confer protection
literature regarding online websites and support groups for
against respiratory infections are currently recommended for
families of children with bronchiectasis is an important com-
children with bronchiectasis. These include Streptococcus
ponent of holistic management. Pictorial-based education flip-
pneumoniae, Bordetella pertussis, and influenza virus vaccines.
charts are available and may assist in education [147]. A self-
There are a number of candidate vaccines under develop-
or parent-management approach encourages autonomy and
ment including those targeting Haemophilus influenzae,
promotes awareness among patients, families, and their
Moraxella catarrhalis, additional serotypes of Streptococcus
extended communities to assist patients in managing their
pneumoniae, and respiratory syncytial virus [135,136]. These
condition. Provision of bronchiectasis management plans by
organisms are common respiratory tract pathogens in chil-
respiratory specialists may assist families regarding when to
dren; hence, vaccine development is an important priority as
seek medical assistance and guide primary care physicians in
it has potential to further reduce exacerbation frequency. A
ensuring optimal management of a child with bronchiectasis.
recent study [137] found that children with bronchiectasis
who received ≥ 3 doses of a pneumococcal conjugate vac-
cine containing protein D from H. influenzae produced sig- 4. Monitoring
nificantly more IFN-gamma than children who received the
Monitoring of children with pediatric bronchiectasis should con-
alternative vaccines without protein D (median 939 versus
sist of regular (e.g. 3 monthly) review by a respiratory physician,
338 pg/ml; p = 0.007). The amount of IFN-gamma produced
with lung function assessment when appropriate (most children
by those vaccinated approached the levels observed in cells
≥ 6 years are able to perform spirometry). Monitoring should
from healthy children [137]. An interventional study (not yet
include assessment of: exercise tolerance; symptoms of cough,
published) in children with CSLD and bronchiectasis has
sputum, dyspnea, and wheeze; frequency of exacerbations; QoL
shown benefit from this vaccine with a reduction in fre-
measures and presence of clinical signs, e.g. persistent crepita-
quency of exacerbations.
tions, clubbing, or chest deformity, complications and overall
In the long-term, it is likely that improvements in vaccine
psychosocial aspects of caring for a child with a chronic illness.
uptake among children with bronchiectasis will improve clin-
Growth and development are important clinical indicators of
ical outcomes. However, to advance the field of vaccinology
disease severity and should be monitored closely [3].
for chronic lung diseases, further understanding of the differ-
While spirometry is widely used, it is important to acknowl-
ent genotypes of bacteria is also required. For example, in
edge that FEV1 is a poor marker of disease severity in children
NTHi, the most common bacteria cultured from the airways
with early bronchiectasis, i.e. a child can have radiological
of children with bronchiectasis and PBB [89,138], NTHi from
bronchiectasis even when spirometry is within population
the lower airways has recently been found to be genomically
normal values. This observation was documented in CF litera-
(on whole gene sequencing) different to that of the upper
ture more than 15 years ago [148]. In the early stages of
airways, i.e. the NTHi in the lower airways are more likely to
bronchiectasis, FEV1 is entirely normal; this is assumed to be
lack the gene that codes for protein D [139].
due to disease being mild and/or localized [32,149]. In con-
trast, when bronchiectasis is diffuse, spirometric abnormalities,
although insensitive to disease activity, better reflect disease
3.3. Nutrition
severity [150].
Macro- and micro-nutrient deficiencies may be a risk factor for Frequency of chest imaging is clinician-dependent but may
exacerbations of bronchiectasis and are an important predictor be indicated if there is clinical evidence of disease progression.

Chest X-ray is very insensitive and rarely used for monitoring.
While there is potential promise for the future use of chest MRI
as a means of monitoring small airways diseases such as
bronchiectasis, its current utility is limited.
CT scan is considered the gold-standard for diagnosis and
monitoring of bronchiectasis. However, its current use is judi-
cious in children due to the potential (albeit low) increased
cancer risk associated with exposure to ionizing radiation.
However, in the absence of an alternative imaging modality,
the risk of CT must be balanced against the risks of delayed
diagnosis and management of bronchiectasis [151].
The use of CT chest as a monitoring modality is generally
confined to patients with an underlying diagnosis, e.g. CF or
PCD. In these children, bronchiectasis progression is usually
more rapid and in CF, life expectancy is reduced. Hence, the
potential benefits of regular CT scans, in terms of tailoring
treatment strategies and optimizing management of lung dis-
ease, often outweigh the radiation risks associated with reg-
ular scanning. The frequency of CT scanning for children with
bronchiectasis needs to be tailored to the individual child. This
includes consideration of the child’s age, the severity and rate
of progression of their lung disease, and any other relevant
risk factors.
Further management and investigations in children with
bronchiectasis is guided by clinical symptoms and/or signs. If
there is chronic deterioration with no clear cause then inves-
tigations such as induced sputum or BAL in the non-expector-
ating child may assist in identifying new lower airway infection
with pathogens such as P. aeruginosa or NTM. Investigation for
ABPA should also be considered.
Ideally a multidisciplinary team should be involved in the
care of a child with bronchiectasis. Effective communication
with the child’s family doctor is essential to achieve optimal
care. Those with an underlying immunodeficiency require joint
care between a respiratory physician and immunologist [3].
5. Prognosis
Bronchiectasis severity scores, e.g. FACED score [152] and
bronchiectasis severity index [153], have been shown to accu-
rately predict morbidity and mortality as well as hospitaliza-
tions, exacerbations, and QoL in adults with bronchiectasis
[154]. Poor prognostic indicators in adults include decline in
lung function, presence of P. aeruginosa infection, and
reduced health questionnaire activity scores [155]. These scor-
ing systems were developed in adults and are not likely
applicable to children as they incorporate sputum and pul-
monary function testing and most children <6 years of age
cannot expectorate sputum or perform spirometry. There are
currently no scoring systems available for children.
6. Conclusion
Bronchiectasis is an important cause of respiratory morbidity
in children but remains a neglected field in research and
allotment of clinical resources worldwide. The approach to
management is based largely upon evidence extrapolated
from CF and adult data and involves a combination of anti-
biotics, airway clearance techniques, and vaccination. Well-
EXPERT REVIEW OF RESPIRATORY MEDICINE 527
conducted interventional trials in children with bronchiectasis
are urgently needed to develop treatments to target the dis-
ease in its origins and to reduce childhood morbidity and
future adult disease.
7. Expert commentary
In tailoring management of bronchiectasis to children, as first
priority, we need to revise our current definition of pediatric
bronchiectasis.
Since the advent of CT in the 1970s, an adult-based defini-
tion of bronchiectasis has been extended to children and
continues to be employed by most radiologists for the diag-
nosis of pediatric bronchiectasis. BAR and bronchial wall thick-
ness (diagnostic criteria) are both age-dependent [156]; hence,
the lack of pediatric-specific criteria may be contributing to an
underestimation and underappreciation of bronchiectasis,
especially in its early stages.
The importance of developing a pediatric-specific definition
of bronchiectasis is highlighted by mounting evidence to
suggest that adult lung disease begins early in life [62,157].
This is particularly important in view of current knowledge of
the potential reversibility of bronchiectasis in its early stages
[47–49]. A relationship between duration of wet cough and
lung function decline in adults with bronchiectasis has been
shown [62]. Further, early initiation of treatment for bronch-
iectasis may halt or even potentially reverse the disease [47–
49]. Despite this knowledge, the current armamentarium for
managing pediatric bronchiectasis remains very limited.
Antibiotics and airway clearance remain major strategies
for managing pediatric bronchiectasis; however, there is only
one RCT currently underway (the first) comparing options for
oral antibiotic use in acute exacerbations [16] and a single
pediatric trial comparing a PEP device to a placebo as the
optimal airway clearance technique. There is promise with
respect to future vaccine development in preventing or redu-
cing bronchiectasis exacerbations [135]; however, currently no
promising therapeutic interventions exist.
A clinical spectrum uniting PBB, CSLD, and bronchiectasis,
based upon clinical and laboratory characteristics in common
between these entities, has been proposed [12]. Chronic wet
cough is the hallmark symptom uniting all three conditions.
Hence, early recognition of children with recurrent episodes of
protracted wet cough, who may be at risk of bronchiectasis
[30], must be achieved at primary-care level. The pediatric
population needs to become a major priority for further
research into bronchiectasis. Elucidating the early origins of
bronchiectasis in children will likely inform the development
of future novel interventions to improve outcomes from this
important disease.
8. 5-year review
There is increasing recognition of the significance of early life
events and interest and focus on the early origins of chronic
respiratory disease, a major cause of morbidity and mortality
worldwide. Hence, we anticipate that there will be an increas-
ing number of studies on people with bronchiectasis and
additional interventional and patho-biological studies are
528 D. F. WURZEL AND A. B. CHANG
likely to become available over the next 5 years. These will
substantially improve the evidence base in this field and pro-
vide novel ways to achieve better clinical outcomes for indivi-
duals with bronchiectasis. Targeted interventions will include
the introduction of bronchiectasis-specific management plans
and QoL measures for pediatric bronchiectasis and multicenter
RCTs will provide further insight into effective treatments.
Previous RCT data on rhDNAse clearly depicted that blind
extrapolation of CF management to bronchiectasis can be
harmful [122] and more recent data on inhaled aztreonam
[108] has reinforced this. However, concerted work and sup-
port from pharmaceutical companies in the research and
development arena will be required to advance knowledge
and further improve management options.
The discordance between pediatric and adult bronchiecta-
sis is currently only largely appreciated by pediatric-focused
clinicians. With time, an understanding of the key differences
will become more widespread. The importance of prevention
and early treatment in children, in whom bronchiectasis is
reversible when mild [12], will gain greater momentum, parti-
cularly as appreciation of the early origins of chronic lung
diseases affecting adults increases.
The global epidemiology of bronchiectasis is unknown and
the establishment of bronchiectasis registries is needed to
estimate the prevalence and burden of disease across
continents.
The importance of tackling health issues in childhood and
the impact with respect to improving health outcomes in
adulthood is already gaining recognition [158]. Indeed, future
studies in adults may prove that bronchiectasis may be rever-
sible with early diagnosis and treatment. This would necessi-
tate intense education of both the public and health
professionals of the potential significance of chronic wet or
productive cough and the need for aggressive and timely
management. Earlier diagnosis would also require an age-
specific adjustment of the definition of the main HRCT feature
of bronchiectasis (increased broncho-arterial ratio) as opposed
to a single cutoff throughout life that is used currently, as
broncho-arterial ratio increases with age in healthy adults. The
link between childhood and adult respiratory diseases needs
further research.
Bronchiectasis shares many common features with neutro-
philic asthma, COPD, and PBB, suggesting that therapies
developed for one of these diseases could be beneficial for
others. PBB is now being recognized in adults [159] and with
increased interest from adult-based researchers, major
advancement will likely ensue.
A concerted, global approach to childhood bronchiectasis
will likely have significant and far-reaching effects into the
future with potential to improve our understanding of adult
bronchiectasis and provide insights into future preventative
and therapeutic interventions for this increasingly common
condition [45].
Key issues
● Heightened recognition and improved access to high-resolu-
tion CT has likely contributed to the increase in bronchiectasis
diagnoses worldwide; further research into the early origins
and predictors of bronchiectasis are urgently needed
● Recognition of the need for a pediatric-specific definition of
bronchiectasis is paramount to facilitate earlier diagnosis,
timely management and improved clinical outcomes in
children with bronchiectasis
● There is a current deficiency in randomized controlled trials
in pediatric bronchiectasis unrelated to CF; extrapolating
findings from adult and CF studies can have limitations
and may be detrimental
● Development of new vaccines for children and adults with
bronchiectasis is needed to achieve primary prevention goals
Funding
A. Chang is supported by a NHMRC practitioner fellowship [grant
1058213].
Declaration of interest
A. Chang holds multiple grants awarded from the NHMRC related to
diseases associated with pediatric cough and bronchiectasis. The views
expressed in this publication are those of the authors and do not reflect
the views of the NHMRC. D. Wurzel holds a current grant awarded from
Murdoch Childrens Research Institute related to respiratory disease. The
authors have no other relevant affiliations or financial involvement with
any organization or entity with a financial interest in or financial conflict
with the subject matter or materials discussed in the manuscript apart
from those disclosed.
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