Successful Management of Pediatric Endobronchial Tuberculosis With Endoscopic Cryotherapy: A Case Series

Endobronchial tuberculosis (EBTB), a form of complicated pulmonary tuberculosis (PTB) affecting the tracheobronchial tree [1], is often underdiagnosed. Incidence rates range from 10% to 38% in pediatric PTB cases [2]. Airway involvement, initially suspected on chest radiography, is typically confirmed with chest computerized tomography (CT) and flexible bronchoscopy (FB). EBTB can present with inflammatory, tumorous, caseous, ulcerative, or fibrostenotic lesions [1]. While most lesions resolve with antituberculous therapy and corticosteroids, significant airway narrowing (> 50%) may necessitate surgical or endoscopic interventions [1]. Cryotherapy has recently proven effective in improving airway patency by enucleating endobronchial lesions in children, but data on its use for pediatric EBTB remains limited [3-5]. We present two cases of successful airway recanalization with cryotherapy in very young children with EBTB. A 19-month-old girl with a productive cough, asthenia, and failure to thrive for 6 months was evaluated for antibiotic-unresponsive left upper lobe (LUL) consolidation. A repeat chest X-ray (CXR) showed cavitary changes. Cultures from gastric aspirates, stool, and urine confirmed susceptible Mycobacterium tuberculosis. Treatment with rifampin, isoniazid, pyrazinamide, and ethambutol was initiated. Follow-up CXR revealed a rightward mediastinal shift, hyperinflation of the left lower lobe (LLL), and significant narrowing of the left mainstem bronchus (LMB) (Figure 1A). A chest CT confirmed compression of the LMB by extensive perihilar partially calcified and necrotic lymph nodes (Figure 1B). FB identified near complete obstruction of the LMB by herniating caseous material (Figure 1C). Endoscopic enucleation with optical alligator forceps and grasping forceps restored about 50% airway patency after a 1.5-h procedure. Three weeks later, a second FB was performed due to the distal location of the residual lesion; because of the size of the forceps, additional tissue could not be removed. Six months later, a control CXR showed decreased but persistent LUL consolidation and recurrence of the LLL hyperinflation. A FB with endobronchial cryorecanalization was performed with a 4.2 mm Olympus bronchoscope and a 1.1 mm cryoprobe for ERBECRYO®2 (Ref.20402-401, Tübingen, Germany). Most of the intraluminal lesion was removed (Figure 1E) with two passes, improving lumen size to > 90% patency (Figure 1F) in a 15-min procedure. Minor bleeding was controlled with cold saline and topical epinephrine. Histopathological analysis of the lesion revealed inflamed granulation tissue and granulomatous inflammation (Figure 1G). Tissue and BAL mycobacterial cultures were negative. The patient completed TB therapy and remains asymptomatic. CXR showed no recurrence of obstruction 3 and 6 months post-procedure. A 4-month-old boy, born preterm at 35 weeks, presented with lethargy, cough, and respiratory distress. Initial CXR showed a prominent superior mediastinum, rightward tracheal deviation, and left lobe hyperinflation, suggesting a ball-valve occlusion of the LMB (Figure 2A). CT revealed consolidation in the LLL, multiple enlarged mediastinal lymph nodes with necrosis and compression of the trachea and LMB (Figure 2B). Rigid bronchoscopy identified an irregular endobronchial lesion occluding 75% of the distal trachea and 90% of the proximal LMB (Figure 2C). The distal tracheal lesion was removed with rigid bronchoscopy and forceps. The proximal LMB lesion was debulked through a 4.2 mm Olympus bronchoscope with a flexible cup forceps, achieving only 25% lumen patency, as cryotherapy was not available in the institution. The lesion in the LLL bronchus could not be addressed due to forceps size. TB workup results included positive AFB in bronchial lavage and tissue biopsy. PCR and culture for Mycobacterium tuberculosis from gastric samples were positive. Rifampin, isoniazid, pyrazinamide, ethambutol, and oral prednisolone 2 mg/kg/day were started. Two weeks later, cryorecanalization was performed using a 1.1 mm cryoprobe for ERBECRYO®2 (Ref.20402-401, Tübingen, Germany), successfully enucleating the lesions in a 20-min procedure. Postprocedure, the LMB had near-normal lumen size with minimal bleeding (Figure 2D). Histology showed granulomatous inflammation with multinucleated giant cells and suppurative inflammation (Figure 2E). The patient's symptoms improved significantly, and he was discharged with a 2-month course of oral steroids. Four months later, he remained asymptomatic while anti-TB treatment. There is no consensus on standard care for pediatric patients with EBTB and significant airway narrowing. Recent trends favor less invasive procedures such as balloon dilation, laser photoresection, argon plasma coagulation, forceps enucleation, and cryotherapy [2, 6]. Cryotherapy has gained particular attention as a novel therapeutic and diagnostic tool, facilitated by the introduction of the 1.1 mm cryoprobe, which allows for its use in infants with small bronchoscopes (2 mm working channels) [3]. The cryotherapy technique for the pediatric population begins with FB to examine airway anatomy and locate EBTB lesions [3, 4]. The cryoprobe is then used to freeze the lesion at temperatures between −80°C and −60°C. Freezing durations vary: cryobiopsies typically require 3–5 s to preserve diagnostic yield, whereas longer durations (5–10 s) are used for managing airway obstruction and improving cryoadhesion in foreign body removal [3]. Based on these findings, we recommend a freezing time of 3–5 s, in line with adult guidelines, to minimize complications. For significant lesions, multiple freeze-rewarm cycles may be necessary, and additional tools like foreign body forceps, baskets, or balloon bronchial blockers may aid in sample retrieval [3]. In the context of EBTB, some authors suggest intralesional isoniazid injections to enhance treatment outcomes [4]. The effectiveness of cryotherapy in the pediatric population was evaluated by Schramm et al. in a prospective multicenter study [3]. Indications included cryobiopsies, airway recanalization, and foreign body management. Of the 30 cryobiopsies performed (24 transbronchial and six endobronchial), all were successful. In 23 patients with airway obstruction, a median increase of 85% in luminal diameter was achieved, accompanied by clinical improvement in all cases. Complications included mucosal bleeding in 43 procedures (11 required topical epinephrine) and pneumothorax in two cases. Endobronchial tuberculosis was diagnosed in only one patient following a procedure initially intended for foreign body removal. Reports on enucleation with cryoprobes for pediatric EBTB are limited [4, 5]. Zhao et al. treated seven patients with CO2 cryotherapy and intralesional isoniazid, achieving resolution of airway obstruction in all, though five required multiple interventions [4]. Complications were minimal, managed with topical epinephrine (1:10,000) or saline. Goussard et al. also successfully treated a 2-year-old with EBTB using cryotherapy, with no significant complications [5]. This case series demonstrates the successful use of endoscopic cryotherapy for pediatric enucleation of EBTB, facilitating sample collection for histology and culture, while restoring airway patency. Our findings are consistent with recent trends favoring less invasive techniques for managing pediatric EBTB and suggest that cryotherapy could be a valuable addition to existing treatment options. Further research and larger studies are needed to standardize protocols and optimize outcomes. Enrique G Villarreal: conceptualization, investigation, writing–original draft, writing–review and editing. Anita Nagy: investigation, writing–review and editing, validation. Ray Lam: investigation, writing–review and editing, validation. Valerie Waters: investigation, writing–review and editing, validation. Ian Kitai: conceptualization, investigation, writing–review and editing, supervision. Fiona Kritzinger: conceptualization, investigation, supervision, writing–original draft, writing–review and editing. This study was exempt from ethics approval by The Hospital for Sick Children Review Ethics Board (REB), as case reports with one or two patients do not meet the Tri-Council Policy Statement definition of research. This study was conducted in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the minor(s)’ legal guardian for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the patient(s)’ legal guardian for the publication of this case report. Written informed consent was obtained from the patient's legal guardians for the publication of this case series and the accompanying images. A copy of the consent is available for review by the Editor-in-Chief of this journal. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.