To the editor:
Flexible airway endoscopy is not part of the recommended diagnostic
routine for tuberculosis (TB) in children and adolescents. Most
pediatric pulmonologists will only perform it on an individual case
basis either for sampling bronchoalveolar lavage (BAL) from areas of
localized infiltration or for resecting endobronchial granuloma in cases
with atelectasis. This may contribute to the low bacteriological
confirmation rate in pediatric cases, although mycobacterial detection
remains a diagnostic standard for active TB and a prerequisite for drug
susceptibility testing (DST). Specific challenges in children and
adolescents include the notoriously low sensitivity and specificity of
symptoms and radiological abnormalities, technical issues around sputum
or gastric aspirate sampling and the lower pathogen density in
children’s respiratory samples. Furthermore, thoracic lymphadenopathy
occurs frequently in pediatric TB with minor or no obvious pulmonary
affection. As a targeted approach, transbronchial needle aspiration
(TBNA) guided by endobronchial ultrasound (EBUS) has been addressed by
an ERS statement on interventional bronchoscopy in children1 and a recent literature review 2summarizing smaller case series. We sought to evaluate the safety and
diagnostic yield of a comprehensive endoscopic investigation including
EBUS-TBNA in a prospective pediatric cohort.
Forty-five children and adolescents (mean age 12 years; range 2-17) with
suspected TB were investigated at our regional center between 2014 and
2020. Sputum was collected from 37 subjects, in part after nebulized
hypertonic saline, and gastric aspirate from eight younger children.
Bronchoscopy was considered when repeated samples were microscopically
negative for acid-fast bacilli. The study group consisted of 8
preschoolers (2-5 years), 10 schoolchildren (6-11 years) and 27
adolescents (12-17 years); 36 were foreign-born with a wide range of
Eastern European, African or Asian nationalities. Diagnostic work-up had
been triggered by suspicious symptoms in nine patients, by health
screening of asylum seekers in 20 patients and by active case finding
after exposure to infectious TB in 16 patients. DST results were
available for 16 of 19 contact persons, with multiple or extensive
resistance in five index cases.
After appropriate risk assessment and consent/ assent, all subjects
underwent flexible bronchoscopy through the largest possible laryngeal
mask airway under general anesthesia. Following inspection and
bronchoalveolar lavage, EBUS (EXERA II BF-UC180F, Olympus, Hamburg,
Germany) served to visualize thoracic lymph node stations with sampling
of nodes >10 mm by repeated TBNA (ViziShot 22G, Olympus).
Tissue specimens were minced and suspended in phosphate buffer for both
fluorescence microscopy using auramine-O stain and for molecular
diagnostics of Mycobacterium tuberculosis DNA and
resistance-conferring mutations in the rpoB , inhA ,katG , embB and gyrA genes. Mycobacterial cultures
in liquid (Mycobacterial growth indicator tubes, Becton Dickison, Sparks
MD, USA) and solid media (Loewenstein-Jensen and Stonebrink plates) were
incubated at 30/ 37 degrees for 8 weeks.
In line with previous reports 2-5 and contrary to most
pediatricians’ intuition, investigation with a flexible EBUS-scope of
6.9 mm outer diameter including a convex-array ultrasound transducer and
needle aspiration under assisted ventilation was universally feasible
and well tolerated by all our patients, even toddlers of 12 kg body
weight. During endoscopy and 24-hour follow-up monitoring, no patient
experienced complications such as dyspnea, fever, hypoxemia, bleeding,
sustained coughing, pain, pneumothorax or feeding difficulties.
After reviewing all diagnostic findings, an alternative diagnosis was
established in four subjects (one each with post-infectious lobar
bronchiectasis, chronic suppurative bronchitis with segmental
atelectasis, mucoid impaction with retention pneumonia and cryptogenic
organizing pneumonia). The remaining 41 patients were started on
antituberculous combination treatment according to guidelines and DST
results from an index case where available.
Microscopic evaluation was negative in all additional respiratory
specimens but BAL and TBNA from one patient in this smear-negative
cohort. After a median of 15 days, cultures from 17 subjects grewMycobacterium tuberculosis . In three additional cases, TB was
confirmed by positive PCR testing (two sputum samples, one BAL and one
TBNA). Thus, total bacteriological confirmation rate amounted to 20 of
41 patients (49%). Only seven of these cases would have been diagnosed
based on sputum samples alone (confirmation rate 17%), all gastric
aspirates were culture-negative. BAL cultures were positive in four
cases, two had positive sputum cultures as well (combined confirmation
rate 9 of 41 = 22%). Processing of TBNA samples yielded 14 positive
cultures and four positive PCR results. In 11 of 20 cases with
bacteriological confirmation (55%), mycobacterial infection was
exclusively secured by lymph node biopsy. The sampling site of an
individual’s first positive culture was TBNA in 13 of 17 cases (76%),
sputum in three (18%) and BAL in one (6%). The detailed patterns of
samples and test results are specified in table 1 .
All isolates were fully susceptible using phenotypic and molecular
methods. Medication could be changed to oral first-line drugs in the
case of a 6-year-old Chechnian girl upon growth of a sensitive strain
from the TBNA-based culture after 14 days. After previous treatment for
pulmonary disease in her home country, she had been diagnosed with
paratracheal lymph node TB and empirically started on a second-line
regimen including intravenous amikacin.
EBUS-guided TBNA is an established diagnostic tool in adults, but still
infrequently applied in pediatric respiratory medicine due to the
requirement of a large-diameter bronchoscope. Our single-center
experience in 45 consecutive subjects, the largest case series reported
to date, expands current evidence on the procedure’s efficacy and safety
as recently reviewed by Madan et al.2 Our use of EBUS
and lymph node biopsy almost tripled the bacteriological confirmation
rate in comparison to sputum- or gastric aspirate-based testing alone.
Bronchoscopic BAL only increased the confirmation rate by a factor of
1.3 relative to standard testing, and additional TBNA resulted in a
further doubling of the diagnostic yield. More than half of our cases
were only confirmed by results from the TBNA sample, and the first
positive culture was based on TBNA in 76% of cases.
These findings were important for establishing a timely and definite
diagnosis, excluding drug-resistant TB and guiding long-term management.
We therefore recommend the inclusion of bronchoscopy and EBUS-TBNA into
a comprehensive diagnostic protocol for smear-negative pediatric
patients with suspected TB.
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