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Indian J Pediatr (October 2015) 82(10):938–944

DOI 10.1007/s12098-015-1866-4

REVIEW ARTICLE

Non Cystic Fibrosis Bronchiectasis


Anand K. Gupta 1 & Rakesh Lodha 1 & Sushil K. Kabra 1

Received: 11 May 2015 / Accepted: 28 July 2015 / Published online: 27 August 2015
# Dr. K C Chaudhuri Foundation 2015

Abstract Bronchiectasis is a pathological abnormality of the Introduction


airways in which there is permanent dilatation and thickening
of the airways. Precise incidence/prevalence in India is not Bronchiectasis is a pathological term which denotes perma-
known. Recent data suggests that about 1 % young children nent dilated and thickened airways as a result of chronic in-
admitted in a hospital with pneumonia may develop bronchi- flammation and recurrent infection due to multiple underlying
ectasis. Due to significant burden of pneumonia in young illnesses.
children in developing countries including India, it may be a Precise burden of bronchiectasis is not known. Various esti-
significant problem that is possibly under recognized. Causes mates indicate variation in incidence and underlying illness in
of bronchiectasis depend on the burden of respiratory infec- different geographic regions. Data from England and Wales
tions and availability of the investigations for identification of suggests that between 2001 and 2007, mortality rates due to
the underlying cause. Post infectious causes are common in bronchiectasis in adults increased at 3 %/year [1]. Reports from
countries where infections are more common; however, since New Zealand and Australia suggest an increasing health burden
these countries are usually resource constrained and therefore, of chronic suppurative lung disease in children as well as adults.
are not able to appropriately diagnose the other causes, leading A survey in New Zealand estimated an overall incidence of 3.7
to more than real overrepresentation of infections as a cause. per 100 000 in under 15-y-old children per year [2]. In Central
In countries with less of infectious illnesses and good diag- Australian indigenous population, prevalence in children below
nostic facilities, malformations of airways, immune deficiency 15 y was estimated to be 1470/100,000 [3].
disorders and primary ciliary dyskinesia are common causes There is no data on magnitude of problem of bronchiectasis
of bronchiectasis. High resolution CT scan of chest confirms from the developing countries. General impression is that it is a
the diagnosis. Treatment is supportive care and consists of common cause of morbidity and mortality in the developing
maintenance of nutrition, airway clearance and antibiotics countries.
for exacerbations. Medical treatment is successful in the A systematic review on long term sequal of pneumonia es-
majority. timated bronchiectasis in 0.9 % (0.7–8.7 %) children hospital-
ized with pneumonia [4]. In a systematic review in India, num-
ber of children between 0 and 4 y were calculated as 12,79,60,
Keywords Aspiration syndrome . Bronchiectasis . FENO . 004 and a total of 3,53,61,230 episodes of pneumonia were
Primary ciliary dyskinesia estimated per year. Out of this about 11 % progressed to severe
pneumonia [5]. It may have resulted in severe pneumonia in 38,
89,735 children. The incidence of bronchiectasis may vary
from 27,22,814 to 3,38,40,694 per year due to pneumonia
* Sushil K. Kabra alone. It gives a figure of 212 to 2646 children developing
skkabra@hotmail.com bronchiectasis per one million children below 4 y of age.
These calculations are based on estimates and assumptions,
1
Department of Pediatrics, All India Institute of Medical Sciences, may not indicate real life scenario, but suggest that bronchiec-
New Delhi 110029, India tasis is not uncommon and is possibly underdiagnosed.
Indian J Pediatr (October 2015) 82(10):938–944 939

Pathophysiology Diagnosis

Bronchiectasis is dilatation and thickening of the airways. In Diagnosis of bronchiectasis should be suspected in children
pre-existing abnormalities (congenital or acquired), recurrent presenting with any of the following clinical symptoms:
infection and inflammation leads to bronchial wall destruc- Persistent wet/moist cough lasting for more than 8 wk and
tion. Recurrent infection/inflammation may result in impaired persisting in between colds, asthma not responding to appro-
mucociliary clearance of purulent and inflammatory material. priate treatment, persistence or recurrence of symptoms of
Bronchoscopic biopsies and bronchoalveolar lavage analysis pneumonia, pertussoid cough not resolving even after 6 mo,
has helped in understanding the mechanisms of development persistent crepitations in the chest without obvious explanation,
of bronchiectasis [6, 7]. It has been suggested that the key recurrent respiratory problems with associated esophagus and
factor in the development of bronchiectasis is bronchial infec- upper respiratory illnesses and unexplained hemoptysis [16].
tion and inflammation. It has been identified that infection Imaging has remained a diagnostic tool for bronchiectasis.
leads to mucosal infiltration by neutrophils and T lympho- A few decades ago, bronchiectasis was suspected on abnormal
cytes; which in turn results in increased concentrations of findings in X-ray film and confirmed by bronchography. X-
inflammatory elements such as neutrophil elastase, interleu- ray film of chest (CXR) lacks specificity. Abnormalities on X-
kin-8, tumor necrosis factor-alpha, and prostanoids. A com- ray film suggestive of bronchiectasis include: prominent
plex interaction between these mediators results in permanent bronchovascular markings, dilated bronchus, loss of lung vol-
dilatation and thickening of the airways i.e., bronchiectasis ume and peribronchial thickening. Now high resolution CT
[6–8]. It is suggested that underrecognition and (HRCT) has replaced bronchography and is considered gold
undertreatment of protracted bacterial bronchitis (PBB) which standard [17, 18]. Contrast enhanced chest CT (CECT) may
is persistence of bacterial infection of airways in children for be considered if reactivation of tuberculosis or mass lesion in
more than 4 wk may be responsible for the development of mediastinum, including lymphnodes are suspected.
bronchiectasis in the developing countries as well as vulnera- Findings in HRCT suggesting bronchiectasis include: dilata-
ble children in the developed countries [9]. tion of airway lumen more than nearby vessel; lack of tapering
towards periphery; bronchial wall thickening; cylindrical, vari-
cose, and/or saccular changes with local or diffuse disease [19,
20]. Findings on HRCT may give clue about underlying illness.
Etiology/Underlying Illnesses in Children Central bronchiectasis suggests allergic bronchopulmonary as-
pergillosis (ABPA), cystic fibrosis or recurrent aspirations.
There are many causes underlying the development of bron- With advanced technology, HRCT may detect subtle ab-
chiectasis. They can be classified into two major groups: con- normalities, including dilatation of airways during acute pneu-
genital problems and acquired problems [10–15]. A list of monia, aspiration or foreign body aspiration. These changes
underlying illnesses is given in Table 1 and comparison of may resolve in repeat HRCT after 6–8 wk [21, 22]. In some
various underlying causes from different parts of the world patients bronchial dilatation may persist static or may show
is described in Table 2. resolution; [11, 23] though it is difficult to differentiate natural
resolution or resolution due to aggressive treatment of bron-
chiectasis. It is suggested that the term prebronchiectasis may
be used in those which resolve over the period of time [24].
Clinical Manifestations Performance of Magnetic resonance imaging (MRI) of
chest and HRCT chest in picking up findings like
Clinical manifestations of bronchiectasis are variable and de- peribronchial wall thickening, mucous plugging and bronchi-
pend on the causes and extent of the illness. There is no uni- ectasis was assessed to be similar [25]. MRI is not associated
form reporting of the clinical symptoms. A comparison of with exposure to radiation but needs longer duration of seda-
presenting clinical symptoms is given in Table 3. A recent tion or general anesthesia. HRCT can be done quickly with
study from India [15] reported 80 children with bronchiecta- minimal or no sedation but is associated with radiation expo-
sis. Common manifestations were: Cough (96 %), breathless- sure. With more experience and improvement in technology,
ness (81 %), expectoration (66 %), fever (62 %), wheezing MRI may find a place in imaging of pediatric chest diseases.
(52 %), repeated pneumonia (46 %) hemoptysis (16 %)
and failure to thrive (70 %). Common manifestations
include: Chronic cough, wheezing, exercise intolerance Investigations for Identification of Underlying Cause
and recurrent chest infections. Advanced disease may
manifest with failure to thrive, clubbing and pulmonary The aim of laboratory investigations for confirmation of the
arterial hypertension. underlying cause is to administer specific treatment.
940 Indian J Pediatr (October 2015) 82(10):938–944

Table 1 Underlying causes of


bronchiectasis in children Congenital causes Acquired causes

Malformations Post infectious following


Airway abnormalities: Severe pneumonia
Laryngotracheobronchomalacia Measles
H-type tracheoesophageal fistula Pertussis
Laryngeal cleft Tuberculosis
Congenital cartilage abnormalities
Pulmonary sequestration Obstruction of airways
Foreign body aspiration
Problems of airway clearance Intra or extra luminal compression
Primary ciliary dyskinesia Lymphnode
Cystic fibrosis Tumor mass
Alpha-1 antitrypsin deficiency Cysts
Vascular ring
Primary immune deficiency
B cell deficiencies Allergy and inflammation
Pan hypogammaglobulinemia Allergic bronchopulmonary aspergillosis (ABPA)
Common variable immune deficiency Rheumatic and autoimmune disorders
Phagocytic defects: CGD
Hyper IgE syndrome Environmental causes
Ataxia telengiectasia Toxic inhalation

Acquired immune deficiency disorders


HIV infection
Chemotherapy
Long term steroids

CGD Chronic granulomatous disease

Bronchoscopy: 3–15 % of underlying causes are Work-up for immune deficiency disorders: 6–34 % of un-
malformations of airways. Fiber optic bronchoscopy helps in derlying causes are immune deficiency. Common causes are
identification of airway abnormalities and obtaining samples pan hypogammaglobulinemia (common variable immune de-
from the airways. It can identify airway abnormalities like ficiency, X-linked hypogammaglobulinemia or isolated IgA
laryngotracheomalacia very well [26]. deficiency). Therefore, serum immunoglobulin profile (IgG,

Table 2 Underlying illnesses of non Cystic fibrosis bronchiectasis

Li et al. 2005 [10] Karakoc Eastham Nikolaizik Karadag Kumar


et al. 2001 [11] et al. 2004 [12] et al. 1994 [13] et al. 2005 [14] et al. 2015 [15]

Total numbers studied 138 23 93 41 111 80


Location UK Turkey UK London Turkey India
Post infectious 3.7 35 30 29.7 23.8
Primary ciliary dyskinesia 14 13 1 17 6.3 15
Allergic bronchopulmonary - - - - - 7.5
aspergillosis
Immune deficiency 33.8 17.4 21 27 15.3 6.2
Aspiration syndrome 18.4 3 5
Congenital malformations 3.7 5 15 3.7
Others - 17.41 92 3.63 4.84
Idiopathic 25.7 18 37 37.8 36.2
1
Asthma, 2 Obliterative bronchiolitis, 3 Foreign body aspiration, 4 Includes asthma, HIV, foreign body (FB) aspiration
Indian J Pediatr (October 2015) 82(10):938–944 941

Table 3 Clinical manifestations of children with bronchiectasis Diagnosis of PCD is confirmed by demonstration of
Li et al. Karadag Kumar abnormal ciliary structure on electron microscopy [28].
2005 [10] et al. et al. Identification of genetic mutation may be alternative di-
2005 [14] 2015 [15] agnostic test in future. At present, it is expensive as
there are a high number of PCD genes and only 60 %
Total numbers studied 138 111 80
of cases can be identified by genetic testing. Diagnostic
Geographic region UK Turkey India
facilities may not be available at all the centers, there-
Chronic cough 34.6 96.9 96 fore it is advisable to refer a suspected patient to cen-
Recurrent wheeze 10.3 46.9 52 ters that have diagnostic facilities [28].
GERD 8.1 - - For diagnosis of allergic bronchopulmonary aspergillosis,
Rhinitis 5.1 - - recently a combination of clinical and lab parameters has been
Recurrent otitis media 5.1 - - suggested [30].
Failure to thrive 4.4 - -
Exercise intolerence 1.5 49 81
Recurrent chest infection 77.2 - 46
Hemoptysis - 10 16 Investigations for Monitoring of Bronchiectasis
Expectoration - 80.6 66
It is important to monitor children with bronchiectasis to as-
GERD Gastroesophageal reflux disease
sess progression of the illness and effect of the treatment. In
All figures are in percentages
older children, spirometry gives objective evidence of airways
and may be repeated every 3–6 mo. In younger children, clin-
IgM, IgA) should be estimated in suspected immune deficien- ical monitoring including symptom relief and weight gain
cy disorders. Other investigations may be considered depend- may be used. Pulmonary function test in pre- school children
ing on the suspicion of underlying illness. Hyper IgE syn- are emerging methods and may be available in future.
drome can be confirmed by documenting high levels of serum Periodic sputum examination may give clear idea about
IgE. Human immunodeficiency virus infection can be con- colonization of the airways. It may also help in deciding about
firmed by ELISA test in children above 18 mo of age. If antibiotic regimen for pulmonary exacerbations.
combined immunodeficiency or chronic granulomatous dis- Imaging such as x-ray film of the chest and computerized
ease is suspected, flowcytometry based investigations may tomography (CT) scan is not required routinely. These may be
confirm diagnosis. obtained in pulmonary exacerbations that are not responding
Cystic fibrosis (CF), once considered a disease of to the treatment. If patient has pulmonary hemorrhage that
Caucasian population, is being diagnosed more frequently does not respond to supportive care, a CT angiography for
from other parts of the world including India [27]. It is impor- demonstration of systemic to pulmonary collaterals may be
tant to suspect CF on clinical features and confirm by sweat considered.
test or mutation studies.
Primary ciliary dyskinesia (PCD) is reported to be 1–17 %
in different studies [10–15]. Diagnostic tests for PCD include
screening test and confirmation of the diagnosis. Screening Treatment
test includes saccharine clearance test, rate of clearance of
radiolabelled aerosol from the airways and nasal NO [28]. In Majority of children with bronchiectasis can be managed with
saccharine clearance test, a crystal of saccharine is placed medical treatment. The aim of the treatment includes nutri-
below inferior turbinate bone and the time taken for appreci- tional support, keeping airways clear and treatment of individ-
ation of sweet taste is recorded. It requires cooperation from ual episode of exacerbation with antibiotics.
the child and normal value for children is not available. It is no
more being used. Delayed clearance of radiolabelled aerosol
from the airways has been used in children above 5 y of age General Measures
and results may not be reliable in the presence of cough [29].
The test is associated with exposure to radiation and reference These include maintaining good hydration, adequate nu-
values for children are not available. trition, vaccination against common respiratory patho-
Nasal NO measurement is standard practice in older chil- gens like pertussis, measles, influenza, pneumococcal
dren and adults. Disorders of Mucociliary Clearance infection and HiB infection. Children with bronchiecta-
Consortium (GDMCC) in North America recommend nasal sis should be protected against smoke (biomass burning,
NO measurement as a screening tool for PCD in children [28]. tobacco) and irritants.
942 Indian J Pediatr (October 2015) 82(10):938–944

Medical Treatment antibiotics is part of treatment regimen in Cystic Fibrosis. There


are not many reports of use of inhaled antibiotics in non CF
Medical treatment is mainstay of management and consists of bronchiectasis. Preliminary report suggests beneficial role of
airway clearance, use of bronchodilators and inhaled steroids, inhaled tobramycin in non CF bronchiectasis [33].
mucolytic agents and administration of systemic and inhaled Prophylactic systemic antibiotics, specifically cotrimoxazole
antibiotics as indicated. has been used in immune deficiency disorders with benefit. A
recent review on use of prophylactic antibiotics in antibody
Airway Clearance deficiency disorder conclude that well-designed multicenter
prospective trials are required to compare benefit of antibiotics
Airway clearance is mainstay of non pharmacologic treatment with other management options [34]. Observational studies
and is underutilized. To keep secretions thin, child should be using long term oral macrolides (erythromycin, azithromycin)
encouraged to drink plenty of liquids. If there is reactive air- in patients with frequent pulmonary exacerbations have docu-
ways disease, bronchodilators before chest physiotherapy mented beneficial effects [35, 36]; there is a need for random-
may help to keep the airways clean. ized controlled trials to confirm their utility.
Mucolytic agents to improve airway clearance has been Chronic respiratory problems may be associated with gas-
advocated for CF as well as Non CF bronchiectasis. troesophageal reflux disease and may benefit with H2 blockers
However, there is not much data about their beneficial role or proton pump inhibitors.
in children. A systematic review including children and adults
with bronchiectasis looked into the efficacy of various inter- Surgical Treatment
ventions and concluded that there is inconclusive evidence on
the use of long-term antibiotics and nebulised hypertonic sa- Majority of the patients respond well to medical treatment.
line for reducing exacerbation frequency and similarly no con- Localized disease that is uncontrolled with medical treatment
clusive evidence to prove that human deoxyribonuclease or localized bleed may be an indication for resection of a lobe
(RhDNase) increases exacerbation frequency [31]. Similarly, or whole lung. In a recent report from India, 17.7 % children
there was no conclusive evidence to support role of hypertonic with bronchiectasis required surgery [15].
saline or mannitol for non CF bronchiectasis. In the same
review, a small (clinically not relevant) beneficial effect was Specific Treatment
observed with inhaled steroids [31].
Traditional chest physiotherapy has four components: Children in whom cause is not identified or there is no specific
Postural drainage, percussion, vibration of the chest wall, and treatment (post infectious, malformations etc) should be treat-
coughing. A systematic review comparing various techniques ed with supportive care. Children with aspiration syndrome
of physiotherapy including active cycle of breathing techniques may benefit with surgical intervention (fundal plication in
(ACBT), forced expiration techniques (FET), autogenic drain- gross gastroesophageal reflux unresponsive to medical treat-
age, postural drainage, oscillating positive expiratory pressure ment). Those with hypogammaglobulinemia may be treated
(OPep) and high frequency chest wall oscillation (HFCWO) with intravenous gamma globulin every 3–4 wk.
did not find any randomized controlled trial (RCT) on the
subject. They observed that all the methods worked well
to improve pulmonary function test and health related Prognosis
quality of life. There is need for RCTs to compare these
techniques in children with non CF bronchiectasis [32]. With better understanding of pathophysiology and diagnostic
In view of current evidence, parents of children diagnosed workup, prognosis of bronchiectasis has improved. In a recent
with bronchiectasis should be encouraged to maintain good report from India [15], 11 % patients died of pulmonary in-
hydration of children, perform daily chest physiotherapy, use fections during follow up. Significant proportion of children
bronchodilators and inhaled steroids if there is an evidence of had morbidity such as poor growth in 61 (76.3 %), pulmonary
reactive airway disease. As of now, there is no conclusive hemorrhage in 13 (16.2 %), chronic hypoxemia in 8 (10 %),
evidence to support use of mucolytic agents (bromhexin), and pulmonary hypertension in 3 (3.8 %). Surgical interven-
hypertonic saline or other osmotic agents. tion was needed in 14 (17.5 %) children.

Antibiotics
Conclusions
Antibiotics should be used with an evidence of pulmonary
exacerbations as indicated by increased expectoration, fever, Bronchiectasis is relatively a common cause of respira-
weight loss, decrease in FEV1 (if available). Long term inhaled tory morbidity. Causes are varied and depend on the
Indian J Pediatr (October 2015) 82(10):938–944 943

geographic region and availability of diagnostic work up 10. Li AM, Sonnappa S, Lex C, et al. Non-CF bronchiectasis: does
knowing the aetiology lead to changes in management? Eur
of underlying illness. In developing countries, post in-
Respir J. 2005;26:8–14.
fectious causes are common while in countries with less 11. Karakoc GB, Yilmaz M, Altintas DU, Kendirli SG. Bronchiectasis:
burden of infection, other causes like malformations, still a problem. Pediatr Pulmonol. 2001;32:175–8.
immune deficiency disorders and primary ciliary dyski- 12. Eastham KM, Fall AJ, Mitchell L, Spencer DA. Paediatric lung
nesia are more common. Bronchiectasis should be disease: the need to redefine non-cystic fibrosis bronchiectasis in
childhood. Thorax. 2004;59:324–7.
suspected in children presenting with long term wet
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uncontrolled bleeding due to systemic to pulmonary col-
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laterals is an indication for surgery. Pediatr. 2015;52:35–7.
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summary of the British thoracic society guideline on the manage-
Contributions AKG: Involved in literature search, manuscript writing; ment of non-cystic fibrosis bronchiectasis. Prim Care Respir J.
RL: Involved in manuscript writing; SKK: Involved in literature search, 2011;20:135–40.
manuscript writing and will act as guarantor for manuscript. 17. Swensen SJ, Aughenbaugh GL, Brown LR. High-resolution com-
puted tomography of the lung. Mayo Clin Proc. 1989;64:1284–94.
18. Kuhn JP, Brody AS. High-resolution CT of pediatric lung disease.
Conflict of Interest None. Radiol Clin N Am. 2002;40:89–110.
19. Barker AF. Medical progress: bronchiectasis. N Engl J Med.
2002;346:1383–93.
Source of Funding None.
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