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Background. Bronchiectasis, a chronic suppurative lung condition, is a largely neglected disease, especially in low- to middle-income
countries (LMICs), from which there is a paucity of data. Post-infectious causes are more common in LMICs, while in high-income
countries, inborn errors of immunity (IEIs), recurrent aspiration, primary ciliary dyskinesia (PCD) and cystic brosis are more common.
Children living with HIV (CLWH), especially those who are untreated, are at increased risk of bronchiectasis. Data on risk factors, diagnosis
and follow-up of children with bronchiectasis are required to inform clinical practice and policy.
Objectives. To describe the demographics, medical history, aetiology, clinical characteristics and results of special investigations in children
with bronchiectasis.
Methods. We undertook a retrospective descriptive study of children aged <16 years with chest computed tomography (CT) scan-conrmed
bronchiectasis in Johannesburg, South Africa, over a 10-year period. Demographics, medical history, aetiology, clinical characteristics and
results of special investigations were described and compared according to HIV status.
Results. A total of 91 participants (51% male, 98% black African) with a median (interquartile range) age of 7 (3 - 12) years were included in
the study. Compared with HIV-uninfected children, CLWH were older at presentation (median 10 (6 - 13) years v. 4 (3 - 9) years; p<0.01),
and more likely to be stunted (p<0.01), to have clubbing (p<0.01) and hepatosplenomegaly (p=0.03), and to have multilobar involvement
on the chest CT scan (p<0.01). All children had a cause identied, and the majority (86%) of these were presumed to be post-infectious,
based on a previous history of a severe lower respiratory tract infection. is group included all 38 CLWH. Only a small proportion of the
participants had IEIs, secondary immune deciencies or PCD.
Conclusion. A post-infectious cause for bronchiectasis was the most common aetiology described in children from an LMIC in Africa,
especially CLWH. With improved access to diagnostic techniques, the aetiology of bronchiectasis in LMICs is likely to change.
Keywords. Bronchiectasis, chronic suppurative lung disease, paediatrics, children living with HIV.
Afr J Thoracic Crit Care Med 2024;30(4):e1899. https://doi.org/10.7196/AJTCCM.2024.v30i4.1899
Study synopsis
What the study adds. In this retrospective descriptive study of children aged <16 years with chest computed tomography scan-conrmed
bronchiectasis in Johannesburg, South Africa (SA), over a 10-year period, we report that a post-infectious cause for bronchiectasis was the
most commonly described, and that HIV was an important contributor. A large proportion of children with bronchiectasis in low- and
middle-income countries such as SA do not benet from an extensive work-up for the non-infectious causes of bronchiectasis.
Implications of the ndings. With improved access to diagnostic techniques, including improvements in early diagnosis and access to
treatment for children living with HIV, the aetiology of bronchiectasis is likely to change in the coming years.
Bronchiectasis, a chronic suppurative lung condition, is characterised
by irreversible bronchial dilation and excessive airway mucus
production.[1] Clinically, children with bronchiectasis may have a
chronic wet or productive cough, exertional dyspnoea, respiratory
exacerbations, poor growth, digital clubbing and chest deformity.[2,3]
e diagnosis is conrmed radiologically by identifying bronchial
dilation on a chest computed tomography (CT) scan.[2-4]
Largely a neglected disease, bronchiectasis has a prevalence ranging
from 67 to 566 per 100000 globally, with variability between and within
countries (including indigenous populations in high-income countries
(HICs)).[5-7] Post-infectious causes are more common in low- and middle-
income countries (LMICs), while in HICs, inborn errors of immunity
(IEIs), recurrent aspiration, primary ciliary dyskinesia (PCD) and cystic
brosis (CF) feature more commonly.[2,8] Access to improved diagnostics
Bronchiectasis in children in a high HIV and tuberculosis
prevalence setting
P Juggernath,1 MB BCh ; K Mopeli,1 FC Paed (SA), MMed (Paed) ; R Masekela,2 FC Paed (SA), PhD ; Z Dangor,1,3 FC Paed (SA),
PhD ; A Goga,4,5 FC Paed (SA), PhD ; D M Gray,6 FC Paed (SA), PhD ; C Ver we y,1,3 FC Paed (SA), PhD
1 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
2 Department of Paediatrics and Child Health, School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
3 South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa
4 South African Medical Research Council HIV and other Infectious Diseases Research Unit, Johannesburg, South Africa
5 Department of Paediatrics and Child Health, Faculty of Heath Sciences, University of Pretoria, South Africa
6 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, South Africa
Corresponding author: C Verwey (charl.verwey@wits.ac.za)
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Table 1. Characteristics of children with bronchiectasis, subdivided by HIV status
Var i able Total (N=91),* n (%)†HIV infected (n=38), n (%)†HIV uninfected (n=50), n (%)†p-value
Female 45/91 (49.5) 23/38 (60.5) 21/50 (42.0) 0.09
Black African 89/91 (97.8) 37/38 (97.4) 49/50 (98.0) 0.85
Age (years), median
(IQR); range
7 (3 - 12); 0 - 16 10 (6 - 13); 1 - 16 4 (3 - 9); 0.2 - 14 0.01
Relevant history
HIV positive 38/91 (41.8) 38/38 (100) 0/50 (0) n/a
On ART 34/38 (89.5) 34/38 (89.5) n/a n/a
Home oxygen 10/91 (11.0) 5/38 (13.2) 5/50 (10.0) 0.64
Cough 83/91 (91.2) 35/38 (92.1) 45/50 (90.0) 0.73
Wet cough 65/69 (71.4) 26/27 (96.3) 39/39 (100) 0.50
Exertional dyspnoea 16/89 (17.6) 10/36 (27.8) 6/05 (12.0) 0.06
Previous chest
infections
78/91 (85.7) 38/38 (100) 40/50 (80) <0.01
Previously treated TB 67/89 (73.6) 31/38 (81.6) 35/49 (71.4) 0.27
Anthropometry
Weight (kg), median
(IQR); range
16 (11.5 - 23.5); 3 - 69 20 (15 - 28); 5 - 40 14 (10 - 18.5); 3 - 69 <0.01
Height (cm), mean
(SD); range
109.7 (24.09); 53 - 156 117.4 (21.5); 64 - 149 101.8 (23.8); 53 - 156 <0.01
Underweight 56/82 (61.5) 21/37 (67.6) 34/49 (69.4) 0.92
Stunted 49/82 (53.9) 30/35 (85.7) 17/42 (40.5) <0.01
General examination
Room air oxygen
saturation (%), median
(IQR); range
93 (88 - 96); 60 - 100 93 (87 - 96); 60 - 99 93.5 (89 - 96); 76 - 100 0.60
Digital clubbing 67/91 (73.6) 34/38 (89.5) 31/50 (62.0) <0.01
Oedema 5/90 (5.5) 3/38 (7.9) 1/49 (2.0) 0.20
Otitis media 1/91 (1.1) 1/37 (2.7) 0/50 (0) 0.24
Respiratory
Hyperination 27/91 (29.6) 13/38 (34.2) 14/50 (28.0) 0.53
Crackles 81/89 (89.0) 35/38 (92.1) 44/48 (91.7) 0.94
Bronchial breathing 20/88 (22.7) 11/38 (28.9) 9/50 (18.0) 0.17
Cardiovascular
Displaced apex beat 4/91 (4.4) 1/38 (2.6) 2/50 (4.0) 0.73
Right ventricular
hypertrophy
14/90 (15.3) 8/38 (21.1) 6/49 (12.2) 0.28
Abnormal heart sounds 27/91 (29.7) 14/38 (36.8) 13/50 (26.0) 0.45
Audible murmur 4/91 (4.4) 1/38 (2.6) 3/50 (6.0) 0.27
Pulmonary
hypertension – clinical
19/91 (20.9) 12/38 (31.6) 7/50 (14.0) 0.05
Abdominal
Hepatomegaly 23/90 (25.3) 14/38 (36.8) 8/49 (16.3) 0.03
IQR = interquartile range; n/a = not applicable; ART = antiretroviral therapy; TB = tuberculosis; SD = standard deviation.
*ree patients did not have known HIV status. Denominators vary owing to the variation in available data for specic data captured.
†Except where otherwise indicated.
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and consequent earlier recognition of underlying susceptibility to
recurrent respiratory infections may contribute to the diering aetiology
between settings.[9]
In LMICs, recurrent lower respiratory tract infection (LRTI) in early
childhood, especially cases requiring hospitalisation, is a risk factor for
developing bronchiectasis.[10] Inadequate vaccination against common
respiratory pathogens, inhaled environmental pollutants, and poverty,
associated with overcrowding, poor water supply, macro- and micro-
malnutrition, and limited access to healthcare and antibiotics, are further risk
factors for developing bronchiectasis.[3,11] Children living with HIV (CLWH),
especially those who are untreated, are at increased risk of recurrent and
severe LRTIs, including pulmonary tuberculosis (PTB),[12] which increase
the likelihood of airway damage and eventual bronchiectasis.[13-16]
Data on risk factors, diagnosis and follow-up of children with
bronchiectasis are required to inform local clinical practice and policy.
ere are very limited data in South Africa (SA), or in LMICs generally,
on the prevalence, investigational pathways, management and outcomes
of children with bronchiectasis, despite a high prevalence of known risk
factors for chronic respiratory disease. Available data are predominantly
from high-risk populations, such as cohorts of CLWH, with 43% of
adolescents with perinatally acquired HIV in Malawi and Zimbabwe
being reported to have high-resolution chest CT scan-confirmed
bronchiectasis, but data are limited on all causes of bronchiectasis.[14,17]
We therefore aimed to describe the clinical characteristics, aetiology
and risk factors for disease severity in children with CT-conrmed
bronchiectasis attending the paediatric pulmonology service at Chris
Hani Baragwanath Academic Hospital (CHBAH) in Johannesburg,
SA, over a 10-year period.
Methods
Study design
We undertook a retrospective descriptive study of children aged <16
years with chest CT scan-confirmed bronchiectasis, attending the
paediatric pulmonology specialist clinic at CHBAH over a 10-year
period from February 2011 to December 2020.
is study forms part of the Bronchiectasis in African Children:
Prevalence, Aetiology, and Clinical outcome (BACPAC) study, a
multisite, observational clinical cohort study with the aim of establishing
a national SA paediatric bronchiectasis registry. Study participating sites
are CHBAH (Johannesburg), Inkosi Albert Luthuli Central Hospital
(Durban), Red Cross War Memorial Children’s Hospital (Cape Town),
and Steve Biko Academic Hospital (Pretoria).
Study setting
CHBAH is a tertiary referral hospital for southern Johannesburg,
Gauteng Province. e paediatric pulmonology clinic is set in the
paediatric outpatient department and receives referrals from the
paediatric in-house services and primary and secondary hospitals in
the drainage area, as well as from neighbouring provinces. In-house
referrals are received from one of four acute general paediatric wards
or other subspecialty services, for example the haematology-oncology
unit and the infectious diseases unit, which also runs the hospital’s
paediatric HIV clinic.
In children with CT-conrmed bronchiectasis, investigations to
determine the aetiology of the bronchiectasis are undertaken but are
dependent on the availability of resources. Over the course of the
study, diagnostic capabilities improved with the addition of more
specialised tests, for example nasociliary brushings and transmission
electron microscopy (TEM) for the diagnosis of PCD since May
2019, and improved ability to investigate for IEIs, as experience and
knowledge of the condition have improved. Sweat tests for CF are
conducted o-site at another Johannesburg hospital.
Study denitions
For the purpose of this study, children were enrolled if they had
characteristic radiographic features of bronchiectasis on a chest CT
scan.[1,4,18,19] e diagnosis of CT-conrmed bronchiectasis was made
aer a paediatric pulmonologist or a radiologist who provided a CT scan
report reviewed the CT scans. Radiographic features of bronchiectasis
on the chest CT scan include an increased bronchoarterial ratio (the
diameter of the bronchi divided by the diameter of the accompanying
airway) of >1 - 1.5 in adults, with a proposed cut-o value of 0.8
in children.[1,4,5,20] Corroborating features include one or more dilated
bronchi, the signet ring sign, non-tapering of the bronchi as they
branch towards the periphery, presence of visible bronchi adjacent to
the mediastinal pleura or within the outer 1 - 2 cm of the lung elds,
bronchial wall thickening, and mucus plugging or impaction.
Underweight was dened as a weight for age less than the –2 z-score
and stunting as a height for age less than the –2 z-score. Conrmed
tuberculosis (TB) was dened as either microscopically or culture-
positive TB, or a positive Xpert MTB/RIF assay.
Clinical and risk factor information
Data were collected from the paediatric pulmonology database and
patient records and entered into a RedCAP (Research Electronic
Data Capture, Vanderbilt University, 2022) database developed
by BACPAC investigators and hosted by the University of the
Witwatersrand. e following variables were captured: demographic
data, past medical history, current clinical features, and ndings
on radiological investigations, sputum microbiology, blood
investigations and pulmonary function tests. Data reported were
from the initial time of presentation to the paediatric pulmonology
specialist clinic.
Statistical analysis
Demographics, medical history, aetiology, clinical characteristics and
results of special investigations were described using standard summary
statistics, and data were presented as means and standard deviations
(SDs) for normally distributed and medians and interquartile ranges
(IQRs) for non-normally distributed continuous variables, and as
proportions and percentages for categorical variables. Data were
compared based on sex, HIV status and nutritional status. Comparisons
between these groups were made using Student’s t-test for continuous
variables with normal distribution and the Mann-Whitney U-test for
those without normal distribution, and the χ2 or Fisher’s exact test for
categorical variables. Dierences were considered statistically signicant
when the p-value was <0.05.
Ethical considerations
Ethical clearance was obtained from the University of the Witwatersrand
Human Research Ethics Committee (ref. no. M190529).
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Results
Characteristics of cohort
A total of 91 children (51% male, 98% black African) with a median
(IQR) age of 7 (3 - 12) years were included in the study (Table 1).
Thirty-eight (42%) were HIV positive, of whom 90% were on
antiretroviral therapy at the time of bronchiectasis diagnosis.
e majority (86%) of the participants had a history of previous
chest infections, and 67/89 (74%) had previously been treated for PTB;
5 (7%) of these had conrmed PTB.
At rst presentation, 83 children (91%) were coughing; 65/69 (71%)
reported a productive cough. Sixteen of 89 (18%) reported exertional
dyspnoea and 5/91 (6%) wheezing. On clinical examination, 56/82
(62%) were underweight for age and 49/82 (54%) were stunted. e
majority, 67/91 (74%), had digital clubbing and almost a third, 27/91
(30%), had features of hyperinflation. Predominant auscultatory
ndings were crackles in 81/89 (89%) and bronchial breathing in
20/88 (23%). e median (IQR) room air oxygen saturation was 93%
(88 - 96%). Almost a quarter of the participants, 19/91 (21%), had
clinical evidence of pulmonary hypertension.
CLWH tended to be older at rst presentation than those who were
uninfected (median (IQR) 10 (6 - 13) years v. 4 (3 - 9) years; p<0.01)
and were more likely to be stunted (p<0.01) and to have clubbing
(p<0.01) and hepatosplenomegaly (p=0.03) (Table 1). ere were no
dierences between male and female children with bronchiectasis
(data not shown). Children who were underweight for age were more
likely than those of normal weight to have clinical right ventricular
hypertrophy and hepatomegaly (data not shown).
Investigations
e majority of the children (96%) had chest radiographs available
for review, of which 51% had changes suggestive of multilobar
bronchiectasis, 27% had changes predominantly in the right
hemithorax, and 21% had changes predominantly in the left
hemithorax (Table 2). Chest CT revealed that 38% of children had
bilateral changes suggestive of bronchiectasis, and in those with
unilateral disease, 37% had right hemithorax and 26% le hemithorax
involvement. CLWH had more multilobar involvement on chest CT
than those who were HIV uninfected (p<0.01) (Table 2). ere were
no dierences between male and female children with bronchiectasis
(data not shown).
Only 21/89 children (23%) had upper gastrointestinal contrast
studies performed, with abnormal anatomy reported in one case and
aspiration in one. Fourteen children had radionucleotide-milk scans
or videouoroscopy performed, with reux reported in four cases and
aspiration in one.
Sputum or bronchoalveolar lavage specimens were sent for analysis
at the time of diagnosis in the majority of cases (81%), with 69%
(n=52/75) having a positive culture; just over half of these (56%)
cultured multiple organisms. Haemophilus influenzae (34%) was
the most commonly cultured organism. ere were no dierences
between CLWH and those who were HIV uninfected.
Investigations for CF, including faecal elastase, sweat conductivity
testing and CF gene analysis, were performed in 30% of the
participants, with no results being suggestive of CF, while nasociliary
brushings with TEM were done in 13/90 children (14%), of whom ve
(38%) were conrmed with PCD, all class 1 defects.
Lung function tests (spirometry) were only performed on 20% of
patients at the time of diagnosis; almost a quarter (22%) displayed
normal pulmonary function, while 44% displayed mixed obstructive/
restrictive pulmonary function, 28% restrictive lung disease, and
only one obstructive lung disease alone. The mean (SD) forced
vital capacity (FVC) z-score was –2.46 (2.32) and the mean forced
expiratory volume in 1 second (FEV1) z-score –2.9 (2.14), with an
FEV1/FVC ratio of 0.79 (0.17), an FEV1/FVC z-score of –1.46 (1.85),
and a forced expiratory ow between 25% and 75% of FVC (FEF25-75)
z-score of –3.09 (1.60). ese ndings were similar for the CLWH and
those who were HIV uninfected.
Bronchoscopy was performed on just over half (53%) of the
children, of whom two showed abnormal anatomy, one a right upper
lobe tracheal bronchus and one narrowing of the le main bronchus.
Aetiology of bronchiectasis
Discernible causes of bronchiectasis are summarised in Table 3. All
the children had a cause identied. e majority (86%) of these were
presumed to be post-infectious based on a history of a severe LRTI.
is was the most likely cause in all 38 CLWH. Only a small proportion
(4%) had IEIs, which included two cases of common variable
immune deficiency and one case each of agammaglobulinaemia
and hypergammaglobulinaemia. Secondary immune deciencies,
excluding HIV, accounted for bronchiectasis in a further four children,
including two with malignancies, receiving immunosuppressive
therapy, one with nephrotic syndrome, and one with microdeletion
of 22q11 (CATCH-22) and tetralogy of Fallot. Five children (6%) were
diagnosed with PCD.
Discussion
In this study we reported data from an LMIC setting in Africa
describing 91 children (median age 7 years) with bronchiectasis, and
compared CLWH with those who were HIV uninfected.
A presumed post-infectious cause for bronchiectasis was the most
common aetiology described, with the majority of children having
previously been treated for a severe LRTI, including all 38 children
who were HIV infected. Furthermore, CLWH were older at diagnosis
of bronchiectasis, which could explain the dierences in basic growth
parameters between the two groups, but they were also more likely
to be stunted, to display digital clubbing, and to have hepatomegaly.
Lastly, CLWH were more likely to present with multilobar disease on
chest CT scan.
A post-infectious aetiology has been reported as one of the
leading causes of bronchiectasis, especially in LMICs.[3,20] Severe or
recurrent chest infections, PTB and HIV have been documented as
signicant risk factors in the development of bronchiectasis.[13-15,21]
More than two-thirds (60 - 90%) of CLWH globally reside in sub-
Saharan Africa, and the World Health Organization reports that
12% of newly diagnosed PTB cases in children aged <15 years occur
in Africa, providing a large potential reservoir of children with an
increased incidence of bronchiectasis.[21-23] CLWH are also more
likely to develop LRTI, to have more recurrent LRTIs and to have
more severe LRTI, which is likely to explain the increased presence of
multilobar lung involvement in CLWH.[12] Ferrand et al.[14] reported
that 43% of their cohort of highly active antiretroviral therapy
(HAART)-naive adolescents living with HIV (ALWH) in Zimbabwe
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Table 2. Investigations in children with bronchiectasis, subdivided by HIV status
Variabl e Total (N=91),* n (%)†
HIV infected (n=38), n
(%)†
HIV uninfected (n=50),
n (%)†p-value
Imaging
Chest X-ray done 87/91 (95.6) 37/38 (97.4) 47/50 (94.0) 0.45
Multilobar involvement 42/83 (50.6) 19/34 (55.9) 23/47 (48.9) 0.38
Location of ndings of bronchiectasis on
CT chest 91/91 (100) 38/38 (100) 50/50 (100) n/a
Multilobar involvement 63/91 (69.2) 32/38 (84.2) 29/50 (58.0) <0.01
Mainly le lung involvement 23/91 (26.1) 9/36 (25.0) 14/47 (2.6) 0.40
Mainly right lung involvement 32/91 (36.6) 11/36 (30.5) 18/47 (36.7) 0.31
Bilateral lung involvement 33/91 (37.5) 16/36 (44.4) 17/47 (34.7) 0.30
Contrast studies
Upper gastrointestinal study done 21/89 (23.1) 5/36 (13.9) 16/50 (32.0) 0.05
Abnormal anatomy 1/21 (4.8) 1/5 (20.0) 0/16 (0) 0.07
Aspiration 1/21 (4.8) 1/5 (20.0) 0/16 (0) 0.07
Reux 12/21 (57.1) 2/5 (40.0) 10/16 (62.5) 0.38
Milk scan/videouoroscopy done 14/89 (15.4) 0/37 (0) 14/49 (28.6) n/a
Aspiration 1/14 (7.1) 0/38 (0) 1/14 (7.1) n/a
Reux 4/14 (28.6) 0/38 (0) 4/14 (28.6) n/a
Sputum
Sputum/BAL sent 74/91 (81.3) 30/37 (79.0) 43/50 (86.0) 0.38
Microscopy sent 74/91 (81.3) 29/37 (78.4) 44/49 (89.8) 0.14
Culture sent 75/91 (82.4) 29/37 (78.4) 45/50 (90.0) 0.13
Positive culture 52/75 (69.3) 20/29 (69) 32/45 (71.1) 0.84
Multiple organisms 29/52 (55.7) 12/20 (60.0) 17/32 (53.1) 0.90
Fungal culture sent 13/88 (13.2) 6/36 (16.7) 7/49 (14.3) 0.76
Positive fungal culture 5/13 (38.5) 1/6 (16.7) 4/7 (57.1) 0.39
TB work-up
TB microscopy positive 3/75 (3.3) 1/28 (3.6) 2/45 (4.4) 0.86
TB culture positive 4/75 (4.4) 1/28 (3.6) 3/45 (6.7) 0.57
Xpert MTB/RIF assay positive 2/76 (2.6) 0/28 (0) 2/45 (4.4) 0.26
CF work-up
Faecal elastase done 22/91 (24.2) 1/38 (2.6) 20/50 (40.0) n/a
Faecal elastase <100 µg/g 0/22 (0) 0/1 (0) 0/20 (0) n/a
Sweat test (conductivity) done 27/91 (29.7) 1/38 (2.6) 27/50 (54.0) n/a
Sweat conductivity >80 mmol/L 0/27 (0) 0/1 (0) 0/27 (0) n/a
CF gene done 16/91 (17.6) 0/38 (0) 15/50 (30.0) n/a
CF gene positive 0/16 (0) 0 (0) 0/17 (0) n/a
Lung function
Spirometry done 18/91 (19.8) 8/38 (21.1) 10/50 (20.0) 0.90
FVC z-score, mean (SD); range –2.46 (2.33); –5.23 - 2.19 –2.44 (2.87); –5.23 - 2.19 –2.48 (1.99); –5.21 - 0.43 0.98
FEV1 z-score, mean (SD); range –2.93 (2.14); –5.73 - 1.79 –2.62 (2.62); –5.73 - 1.79 –3.19 (1.80); 4.85 - 0.16 0.65
FEV1/FVC, mean (SD); range 0.78 (017); 0.44 - 0.98 0.81 (0.16); 0.51 - 0.93 0.76 (0.18); 0.44 - 0.98 0.61
FEF25-75 z-score, mean (SD); range –3.09 (1.60); –6.12 - 0.31 –2.94 (1.53); –5.18 - 1.55 –3.21 (1.78); –6.12 - 0.31 0.77
Other tests
Nasal brushing done 13/90 (14.4) 0/37 (0) 9/50 (18.0) <0.01
PCD conrmed 5/13 (38.5) 0/5 (0) 5/5 (100) n/a
Lung biopsy done 2/87 (2.2) 1/36 (2.8) 1/48 (2.1) 0.84
Bronchoscopy done 48/89 (52.8) 15/36 (41.7) 30/50 (60.0) 0.09
Abnormal anatomy 2/48 (4.2) 1/15 (6.7) 1/30 (3.3) 0.61
CT = computed tomography; n/a = not applicable; BAL = bronchoalveolar lavage; TB = tuberculosis; CF = cystic brosis; FVC = forced vital capacity; FEV1 = forced expiratory volume in 1 second;
FEF25-75 = forced expiratory ow between 25% and 75% of FVC; SD = standard deviation; PCD = primary ciliary dyskinesia.
*ree patients did not have known HIV status. Denominators vary owing to the variation in available data for specic data captured.
†Except where otherwise indicated.
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Table 3. Aetiology of bronchiectasis in children
Underlying aetiology Total (N=91), n (%)
HIV infected
(n=38), n (%)
HIV uninfected
(n=50), n (%) p-value
Post-infectious (presumed) 78 (85.7) 38 (100) 40 (80) <0.01
Primary ciliary dyskinesia 5 (5.5) 0 5 (10) 0.06
Cystic brosis 0 0 0 n/a
Inborn error of immunity 4 (4.4) 0 4 (8.0) 0.09
Secondary immune deciency (excluding HIV) 4 (4.4) 1 (2.6) 3 (6.0) 0.47
Aspiration 2 (2.2) 1 (2.6) 1 (2.0) <0.01
had bronchiectasis. e increased availability and early use of HAART
and sulfamethoxazole-trimethoprim prophylaxis have signicantly
reduced the number and severity of LRTIs in CLWH, as has the
availability of multiple vaccines against childhood LRTI, for example
measles, pertussis and BCG, as well as the more recently introduced
pneumococcal conjugate vaccine.[24-26] The burden of paediatric
bronchiectasis in CLWH now lies with those patients with perinatally
acquired HIV diagnosed later in childhood.
Although older age at diagnosis of bronchiectasis in CLWH
could account for the dierences in growth parameters between the
two groups, the increased burden of stunting, digital clubbing and
hepatomegaly is more likely to be due to the potential presence of
multiple chronic disease processes in CLWH and delayed initiation
of ARVs, and has been well described in previous studies.[27,28] More
than half of the children in our cohort were underweight for age and
a similar proportion were also stunted, with a signicantly higher
prevalence of stunting in CLWH (86% v. 41%; p<0.01).
Malnutrition, a condition much more prevalent in Africa and LMICs
than in HICs, has been implicated as a risk factor in the development of
bronchiectasis and chronic lung disease.[29] Furthermore, CLWH, and
those with a prior history of PTB, are at increased risk of developing
malnutrition, and bronchiectasis itself may also lead to a catabolic
state in children, resulting in a higher energy demand that cannot be
sustained, leading to malnutrition.
The most common symptom in our cohort was a chronic
productive cough (71%), with 18% also experiencing exertional
dyspnoea. This finding is similar to those in studies describing
CLWH from Zimbabwe and Malawi, as well as studies performed
in HICs, denoting that irrespective of the underlying aetiology and
socioeconomic background, the symptomatology of bronchiectasis
is similar in children whether HIV infected or uninfected.[5,14,16] e
majority of our cohort had digital clubbing and crackles on chest
auscultation, and 38% had radiological changes of bronchiectasis on
both hemithoraces on the chest CT scan. ese ndings are similar to
those in studies from Africa and globally, and are valuable pointers for
referral from primary settings for investigation.[14,16,30,31]
Surveillance of airway-colonising organisms is essential for all
patients with bronchiectasis. e majority of the children in our study
had a positive culture on sputum/bronchoalveolar lavage, with more
than half of the children (56%) culturing multiple organisms and H.
inuenzae (34%) being the most common organism cultured. is
nding is similar to those of multiple studies investigating the sputum
of children with bronchiectasis unrelated to CF.[15,32]
Only a small proportion of our cohort were worked up for CF,
PCD and IEI, with 10% being conrmed with either PCD or IEI.
Although the proportion of children with underlying causes for
bronchiectasis, other than post-infectious, is relatively small, this
finding clearly demonstrates that all cases of bronchiectasis in
childhood warrant full aetiological investigation, as a definitive
diagnosis aects the management of the bronchiectasis. In a study
from Turkey, it was reported that with increased access to further
investigations, an increased number of children with an identied
cause for the bronchiectasis, other than post-infectious, can be
found, with increased cases of PCD and a decreased number of
idiopathic cases.[9] In our study, additional signicant aetiological
results were found in the small number of patients who did undergo
full investigation. is nding suggests that we have much more to
learn regarding the aetiology of bronchiectasis in our setting, and an
increased proportion of other causes may be uncovered if all cases are
thoroughly investigated. However, in LMICs, nasociliary brushings
and TEM for the diagnosis of PCD, and any testing modality for the
diagnosis of CF, are not readily available outside of specialist centres,
and IEI investigations are costly, leaving many cases of bronchiectasis
deemed post-infectious or idiopathic.[17]
Spirometry was only performed on 20% of patients, with 44%
displaying a mixed obstructive/restrictive picture. Attia et al.[13]
reported that 45% of ALWH, of whom 43% had bronchiectasis on the
chest CT scan, had abnormal FEV1, while Chang et al.[30] reported that
children with bronchiectasis from LMICs had lower FEV1 and FVC
than those from HICs.
ere are notable limitations to our study. Firstly, it was a retrospective
observational study, with all the inherent shortcomings of a study of
this type, including incomplete data capturing. Furthermore, it was a
single-centre study with a strict denition of CT scan conrmation of
bronchiectasis. In resource-limited settings, this denition may miss
many children, and an alternative LMIC-based approach previously
proposed by this group may be more appropriate.[17] e CF data
presented in this study may be misleading, as there is a dedicated CF
centre in Johannesburg to which children may have been referred
directly from the drainage area of our hospital, and it is therefore
possible that cases of CF were missed. Children were investigated
based on the tests that were available at their time of presentation and
attendance at the clinic, with children who presented in the later years
having more extensive testing to identify causes of bronchiectasis than
those in the earlier years. At the time of enrolment into the study, the
majority of CLWH had not been investigated any further to look for
AJTCCM VOL. 30 NO. 4 2024 163
ORIGINAL RESEARCH: ARTICLES
additional contributing causes of their bronchiectasis, which could
inadvertently have led to underdiagnosis of certain aetiologies of
bronchiectasis in this subgroup. At the time of enrolment, further data
on the immunological status of the CLWH, including their viral load,
CD4 count and antiretroviral status, were not available. ese data
could have better described the CLWH population.
e strength of the study is that we describe in detail children with
chest CT scan-conrmed bronchiectasis, thereby ensuring minimal
possible misdiagnosis of the clinical syndrome, providing novel data
from an LMIC in Africa.
Conclusion
A post-infectious cause was the most common aetiology described
in children with bronchiectasis from an LMIC in Africa, especially
in CLWH. With improved access to diagnostic techniques and
improvements in early diagnosis and management of childhood HIV,
the aetiology of bronchiectasis in LMICs is likely to change in the
coming years, to more closely resemble that in HICs.
Data availability. e datasets generated and analysed during the present
study are available from the corresponding author (CV) on reasonable
request. Any restrictions or additional information regarding data access
can be discussed with the corresponding author.
Declaration. RM and CV are members of the editorial board. The
research for this study was done in partial fulfilment of the
requirements for PJ’s MMed (Paed) degree at the University of the
Witwatersrand.
Acknowledgements. None.
Author contributions. PJ and CV conceptualised this project,
analysed the data, wrote the manuscript and approved the final
version. ZD, KM, DMG, AG and RM reviewed and revised the
manuscript and approved the final version. CV, DMG, AG and RM
conceptualised and implemented the BACPAC group and database on
which this study is based.
Funding. None.
Conflicts of interest.None.
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Received 30 January 2024. Accepted 18 October 2024. Published 10 December 2024..
