Keywords

Introduction

Involvement of the trachea and major bronchi by tuberculosis was first described by Morton in 1698 [1]. Endobronchial tuberculosis (EBTB), defined as tuberculous infection of the tracheobronchial tree, is not uncommon. Endobronchial involvement was reported in 42 % of 1000 autopsies of patients with tuberculosis [2] and 10–38.8 % of living patients undergoing rigid bronchoscopy [3–5].

EBTB continues to be a major public health problem because its diagnosis is often delayed, and airway stenosis and its attendant complications such as post-obstructive pneumonia, atelectasis, hemoptysis, wheezing, and dyspnea can develop during the course of treatment [6–8]. Owing to HIV infection, poverty, aging population, migration, multidrug resistance, failure in health systems, and rise in diabetes, a resurgence of tuberculosis is observed globally, which accounts for 8.8 million new cases and 1.8 million TB-related deaths each year [9, 10]. It is also likely that HIV may be associated with a higher incidence of EBTB [11, 12]. In this chapter, the pathogenesis, clinical presentation, diagnosis, and current treatment of EBTB are discussed.

Pathogenesis

The pathogenesis of EBTB is not fully understood and is thought to arise from direct implantation of the tubercle bacilli onto the tracheobronchial tree from adjacent pulmonary parenchymal lesion. This theory is supported by finding tuberculosis affecting the bronchus opposite to the airway that drains the tuberculous cavity. Another proposed mechanism is direct airway infiltration by adjacent tuberculous mediastinal lymph node, which is more commonly seen in children. Lymphatic and hematogenous spread to endobronchial tree is rare [13–15]. The clinical course of EBTB can be variable and complex, and is dependent on the interaction between mycobacteria, host immunity, and anti-tuberculous drugs [16, 17].

Clinical Features

EBTB appears to occur more frequently in women in their second and third decades of life even though they have a lower incidence of pulmonary TB [6, 13, 16, 17]. One explanation is the implantation of mycobacteria from infected sputum occurs more frequently in females as they do not expectorate sputum well due to sociocultural circumstances. Clinical features depend on the type and stage of EBTB. Some patients are asymptomatic, while most complain of productive cough, fever, hemoptysis, hoarseness, chest pain, and generalized weakness [6]. Wheezing can be detected by auscultation in a third of patients erroneously managed as asthma with steroids and decreased air entry in a quarter [8, 18–20]. Diagnosis of EBTB is difficult to establish because similar symptoms can occur as part of pulmonary TB or other respiratory diseases.

Radiology

Chest X-ray can be normal as these lesions are not detectable unless airway obstruction has occurred causing distal atelectasis. Interestingly, the lower or middle lung lobes are affected slightly more often than upper lobes which would favor the direct implantation theory of EBTB by gravity (Fig. 8.1) [6, 8, 16, 18]. Pleural effusions and military tuberculosis may be observed [14, 21]. Computed tomography (CT) is more useful in demonstrating bronchial wall irregularities and lymphadenopathy associated with bronchial lesion, and 3D CT reconstruction for degree and the extent of tracheobronchial stenosis especially if surgery or bronchoscopic intervention is planned (Fig. 8.2a–c) [22, 23].

Fig. 8.1
figure 1

CXR showing left lower lobe collapse

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Fig. 8.2
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a CT scan of left main bronchial stricture, distal lingular, and lower lobe collapse. b CT scan of left lower lobe collapse. c 3D CT reconstruction showing LMB stricture with left lung collapse

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Laboratory Tests

Sputum smear for acid-fast bacilli (AFB) is positive in 17 % and increases to 79 % when combined with bronchoscopic specimens [6, 18]. This finding is unexpected as EBTB is presumed to yield higher sputum AFB smear positivity. One possible explanation is that sputum expectoration may be difficult due to mucus entrapment by proximal granulation tissue. Alternatively, mucosal ulceration, which is not seen in every patient with EBTB, may be necessary for positive AFB smear. Polymerase chain reaction (PCR) for mycobacteria tuberculosis is increasingly applied to improve the diagnosis of EBTB [24, 25].

Bronchoscopy and Histopathology

EBTB affects the trachea, main bronchi, and upper bronchi (Fig. 8.3). The presence of caseating granuloma or acid-fast bacilli is diagnostic for EBTB. Biopsy specimens are diagnostic for EBTB. In some instances, endobronchial biopsies show non-caseating granuloma, but the presence of Langhan’s giant cells in these cases is helpful in establishing the underlying diagnosis and in excluding sarcoidosis, fungal, or other granulomatous diseases (Fig. 8.4). Chung and coworkers classified EBTB into 7 categories (% prevalence): non-specific bronchitis (8 %), actively caseating (43 %), granular (11 %), edematous hyperemic (14 %), ulcerative (3 %), tumorous (10.5 %), and fibrostenotic (10.5 %). Serial bronchoscopy was performed from the diagnosis of EBTB to the completion of anti-tuberculous treatment, and actively caseating, edematous-hyperemic, tumorous, and fibrostenotic lesions (Fig. 8.3) demonstrated higher risk of progression to tracheobronchial stenosis usually within 3 months [6, 26].

Fig. 8.3
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a, b Actively caseating EBTB of trachea and left main-stem bronchus. c Tumorous EBTB of right upper lobe. d Fibrostenotic EBTB of left main bronchus

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Fig. 8.4
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a Mycobacteria stain bright red with Ziehl–Neelsen stain bronchial aspirate. b Histology of tumorous EBTB. Medium power view: bronchial wall cartilage and several granulomas with some associated necrosis

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The classification of EBTB can be explained pathologically by disease progression. The initial lesion is characterized by erythema and lymphocytic infiltration which corresponds to non-specific bronchitis. As the disease advances, submucosal tubercles develop giving it a granular appearance (granular), while marked mucosal edema describes the edematous-hyperemic type. It can undergo caseous necrosis (actively caseating) or becomes ulcerative if the inflammation continues. The actively caseating or ulcerative lesion can either evolve into hyperplastic–inflammatory polyp (tumorous type) or heal by fibrostenosis [15, 27, 28]. Moreover, the associated intrathoracic tuberculous lymph node can erode and protrude into the airway akin to tumorous EBTB [11, 14, 28]. Rikimaru and coworkers have further divided the ulcerative type into active (stage A), healing (stage H), and scarring (stage S). Only stage A lesions were observed before anti-tuberculous treatment. During 1 and 2 months of therapy, 76 % of ulcerative lesions were in stage A or H, and thereafter, 63 % were in stage S of which one-third of patients developed inflammatory polyps [29].

Treatment

Active and fibrous subtypes must be differentiated. Fibrous disease is considered as inactive TB, but it can lead to bronchial stenosis which can be a challenging sequel to EBTB during or after treatment.

Active EBTB

The most important goal of treatment is in the eradication of tubercle bacilli without selecting drug-resistant mycobacteria. The second most important goal is in the prevention of tracheobronchial stenosis. Chemotherapy eradicates tubercle bacilli except for multidrug-resistant TB, while the sequel of tracheobronchial stricture is atelectasis with dyspnea or obstructive pneumonia. Tracheobronchial strictures can develop despite prompt anti-tuberculous therapy [6, 8, 16, 26], and previously topical silver nitrate application has been attempted for ulcerative EBTB [30, 31] and electrosurgery via rigid bronchoscopy for tumorous or polypoidal lesions [32]. A recent systematic review and meta-analysis conclude that steroids could be effective in reducing mortality for all forms of tuberculosis including PTB [33]. However, the role of corticosteroids in preventing fibrostenosis consequent to EBTB remains controversial. Two prospective, randomized, placebo-controlled studies of children with endobronchial obstruction from enlarged tuberculous hilar lymph nodes demonstrated the significant improvement in the group treated with steroids [34, 35]. However, only one such randomized study is available in adults which did not show any difference in the rate of bronchial strictures between the steroid-treated and placebo groups. It was a small study, and timing of initiation of systemic steroids could contribute to the negative results. There are case reports that show favorable response to both systemic and endoscopic injection of steroids [36].

Shim recommends steroids for the edematous-hyperemic, actively caseating, and tumorous types as these tend to progress to tracheobronchial stenoses. Prednisolone at 1 mg/kg is prescribed for 4–6 weeks followed by slow taper for the same duration [37]. In 1963, Nemir et al. [38] observed that short course of prednisone of less than 4 months was effective adjunct to the anti-tuberculous therapy for EBTB. Song et al. [39] also observed good response if steroids were initiated within 3 months of symptoms and concluded that steroids were beneficial in early-phase EBTB, but had no impact on bronchial stenosis. Rikumaru et al. [40] observed that heal time for ulcerative EBTB was shorter, and bronchial stenosis less severe if patients were treated with twice daily aerosol therapy of streptomycin 100 mg, dexamethasone 0.5 mg, and naphazoline 0.1 mg in addition to anti-tuberculous therapy. Um et al. [41] found that age >45 years, fibrostenotic subtype, and >90 days between symptom onset and the initiation of anti-tuberculosis chemotherapy were independent predictors of persistent airway stenosis, and oral corticosteroids (prednisolone equivalent ≥30 mg/d) did not reduce the frequency of airway stenosis. It is apparent that steroids do not affect the regression of fibrostenotic lesions, but ameliorate inflammation and edema in the early phase of EBTB.

Fibrous EBTB

An important sequel of EBTB is bronchial stenosis which causes atelectasis and secondary obstructive pneumonia. Patients present with dyspnea and wheezing. As steroids are unable to reverse stenosis, airway patency must be restored by surgery or bronchoscopic intervention. Surgical resection of an atelectatic lung with stenotic main-stem bronchus (pneumonectomy) has been normal practice (Fig. 8.5a, b), but lung-sparing surgery such as sleeve resection, carina resection, and end-to-end anastomosis is increasingly performed [42–44]. Bronchoscopic techniques that include laser, electrosurgery, argon plasma coagulation, cryotherapy, and balloon bronchoplasty have been applied singly or in combination to restore airway patency (Fig. 8.6a–h) [45–54]. Silicon stents are deployed following airway recanalization and dilatation as adjunct to the management of complex strictures (Fig. 8.7a, b) [55–57]. Metallic stents should be avoided since they are difficult to remove due to airway epithelization [57, 58]. Complications after dilatation and stenting include airway perforation, stent migration, and stent-related obstructing granuloma, which can cause subcutaneous emphysema, pneumothorax, pneumomediastinum, mediastinitis, dyspnea, and hemoptysis [58]. A patient who received silicon stent for post-TB complex stricture developed obstructing granuloma that was successfully treated with laser and topical mitomycin C application [59]. It is challenging to determine who will respond to interventional procedures and who will need surgery. Lee and coworkers reported that with interventional treatment, only 30 % of patients experienced successful re-expansion defined as recovery of lung volume >80 % of estimated original volume; these patients were younger median age 22 years versus 34 years. The presence of parenchymal calcification as well as bronchiectasis within the atelectasis showed higher tendency for failure, while mucus plugging, extent of airway narrowing, volume loss on CT, and endobronchial TB activity at the time of intervention did not affect lung re-expansion [60].

Fig. 8.5
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a Chest radiograph after left pneumonectomy. b Surgical specimen shows lung atelectasis with areas of caseous necrosis

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Fig. 8.6
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a Actively caseating EBTB left main bronchus. b Bronchoscopy after 3 months of anti-tubercular treatment showed progression to tumorous EBTB of left main bronchus. c After completion of anti-tubercular treatment, bronchoscopy showed tumorous EBTB with stricture of left main bronchus. d Balloon bronchoplasty of left main bronchus was performed. e Pre-dilation chest radiograph showed left lower lobe collapse–consolidation. f Chest computed tomography with 3D reconstruction showed left main bronchial stricture. g Fluoroscopy during balloon bronchoplasty of left main bronchial stricture. h Chest radiograph post-balloon bronchoplasty shows re-expansion of left lower lobe

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Fig. 8.7
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a Fibrostenotic left main stricture, b radial cuts applied with electrosurgical knife, dilated with balloon bronchoplasty and silicon stent placement

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Conclusions

Diagnosis of EBTB is often delayed as it is difficult to detect on chest radiograph. Symptoms of hemoptysis, wheezing, and dyspnea as well as chest X-ray finding of atelectasis should alert the physician of EBTB. EBTB is divided into 7 categories based on bronchoscopic appearances, and actively caseating, edematous-hyperemic, tumorous, and fibrostenotic lesions demonstrate higher risk of progression to tracheobronchial stenosis. Airway strictures occur in up to two-thirds of EBTB, and steroids when instituted early can prevent progression to tracheobronchial stenosis. Aerosol therapy comprising of streptomycin and corticosteroid is also an effective adjunct to anti-tuberculous treatment. 3D reconstruction CT is not only useful in the planning of bronchoscopic intervention or surgery and it can also be a means to follow-up EBTB during therapy instead of bronchoscopy. Patients with airway strictures consequent to EBTB will require surgery or bronchoscopic procedures which may include laser, electrocautery, argon plasma coagulation or cryotherapy, balloon bronchoplasty, or stent.