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ENDOBRONCHIAL TUBERCULOSIS

(15-Mark MD Examination Answer)

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INTRODUCTION & DEFINITION

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EPIDEMIOLOGY

• Autopsy prevalence: 3%–72% (most series ~40%)
• Bronchoscopic prevalence: 10%–20% of active TB patients in older studies; lower in recent times due to effective chemotherapy
• Current prevalence may be as low as 0.18% in non-endemic areas
• Age: Most common between 21–40 years; also reported in elderly
• Sex: Female preponderance — due to voluntary cough suppression (socio-cultural reasons) and smaller calibre airways in women

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PATHOPHYSIOLOGY — MECHANISMS OF ENDOBRONCHIAL INFECTION

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PATHOLOGY

Macroscopic Appearances

• Earliest sign: Erythematous mucous membrane
• Discrete tubercles → shallow ulcers → deep ulcers involving bronchial wall
• Extensive granulation tissue may form tumour-like growth (mimics neoplasm)
• Healing → stenosis secondary to fibrosis
• Stenosis may also result from oedema or extrinsic lymph node compression
• Ulcers most common at carina and posterior tracheobronchial tree; size 1–5 mm, axes parallel to cartilaginous rings
• Rare: diffuse stenosis of small bronchi distal to 4th generation, mimicking bronchiolitis obliterans

Microscopic Appearances

• Early: Small, oval/round foci of epithelioid granulomas, with/without central caseation, in subepithelial region and near mucous glands
• Advanced: Foci also in adventitia; cartilage involvement in very extensive disease
• Rupture of submucosal foci → ulceration → wall destruction
• Zone of caseation surrounded by vascular granulation tissue, occasionally covered by pseudo-membrane of fibrin
• Healing: Granulation tissue replaces caseation → regenerating epithelium covers ulcer → connective tissue replaces granulation tissue → if circumferential, fibrotic stenosis develops

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CLINICAL FEATURES

• Diminished breath sounds
• Localised fixed wheeze — low-pitched, constantly present, same area of chest wall; disappears with progressive narrowing
• Partial obstruction → one-way valve → tension pneumothorax (rare)

• Bronchostenosis — most significant complication; develops in 50%–90% despite effective therapy
• Atelectasis, post-obstructive pneumonia, bronchiectasis
• Rare: expectoration of bronchial cartilages, bronchopleural fistula between right and left main bronchi
• Pseudomembranous tracheobronchial aspergillosis on stenotic area
• Concomitant laryngeal (60%) and intestinal (82%) TB in autopsy series

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INVESTIGATIONS

1. Sputum for AFB

• Low yield: only 15%–20% — because proximal granulation tissue traps mucus, and ulceration required for positive smear
• A negative smear does not exclude EBTB

2. Chest Radiograph

• Normal in 10%–20% of patients
• Findings include:
  • Patchy infiltrates
  • Collapse (25%–35%) or consolidation (35%–60%)
  • Hyperinflation, cavitation, pleural effusion, miliary infiltrates, mediastinal lymphadenopathy

3. CT Chest (Very Important)

• Poorly defined nodules, centrilobular nodules
• Bronchial wall thickening
• "Tree-in-bud" pattern — peripheral centrilobular nodules connected to branching linear opacities; corresponds histologically to plugging of small airways with mucus/pus and dilated bronchioles

• Stenosis/obstruction of major airways
• Peribronchial cuff of soft tissue
• Active stage: irregular, circumferential luminal narrowing
• Fibrotic stage: smooth and irregular narrowing, less wall thickening
• Aneurysmal dilatation of medium bronchi, intraluminal polypoid mass
• CT cannot reliably differentiate endobronchial, submucosal, or peribronchial disease
• Virtual bronchoscopy (3D helical CT): better tracheobronchial assessment; useful to determine stenosis length and involvement beyond stenosis

4. Spirometry

• Most common pattern: Restriction (47%)
• Mixed pattern 23.5%, Obstruction 5.9%, Normal 23.5%
• Unlike asthma, no bronchial hyperreactivity to inhaled histamine

5. Bronchoscopy — GOLD STANDARD

• Site: Main stem and upper lobe bronchi most commonly involved; left main stem most common in recent series
• Biopsies: Non-necrotic epithelioid granulomas to necrotic granulomas with AFB
• Brushings + biopsy increases diagnostic yield
• Bronchostenosis develops in 50%–90% despite effective therapy

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BRONCHOSCOPIC CLASSIFICATION (Chung & Lee, 2000)

Correlation: Non-specific bronchitic → erythema/oedema/lymphocytic infiltration → granular (submucosal tubercle) → oedematous-hyperaemic → actively caseating (mucosal granulomas) → ulcerative → tumourous → fibrostenotic

All forms lie between two ends of spectrum: healing ↔ fibrostenosis. Fibrostenotic type does not transform into others.

Predictors of Bronchostenosis Progression:

• Age >45 years
• Anti-TB treatment initiated >90 days after initial symptoms
• Type of lesion (oedematous-hyperaemic and tumourous worst prognosis)
• Elevated IFN-γ, TGF-β, and increased matrix metalloproteinase-1 activity

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SPECIAL SITUATIONS

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DIFFERENTIAL DIAGNOSIS

• Asthma (most common misdiagnosis)
• Foreign body aspiration (especially in children)
• Lung cancer / bronchogenic carcinoma
• Atypical mycobacteria (NTM), sarcoidosis, actinomycosis, papillomatosis
• Focal stenosis: post-intubation stenosis, Crohn's disease, Behçet's syndrome
• Diffuse central stenosis: Wegener's granulomatosis, relapsing polychondritis, amyloidosis, tracheobronchopathia osteochondroplastica, rhinoscleroma
• Anthracofibrosis — elderly non-smoking women exposed to biomass fuel; can co-exist with TB; multiple lobar/segmental bronchi involved (spares central airways, unlike EBTB)

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TREATMENT

1. Anti-TB Chemotherapy

• Same regimen as pulmonary TB (HRZE/HR standard regimen)
• Inhaled streptomycin and inhaled isoniazid reported to improve outcomes (not yet validated in large RCTs)

2. Corticosteroids

• Empirically used with anti-TB drugs
• May suppress cough but do not reliably prevent bronchostenosis
• A prospective randomised trial in adults failed to show benefit
• Some benefit in children with lymph node TB causing bronchial obstruction (double-blind studies)
• Not recommended for routine use

3. Bronchoscopic Modalities (for airway stenosis)

4. Airway Stents

• Stents left in place for 6–18 months in benign stenosis
• Stent removal fails in 44%–76% of EBTB patients
• Silicone stent complications: granulation tissue 65–76%, migration 52–70%, mucostasis 17–18%
• EBUS radial probe: useful to assess cartilage damage before stent placement

5. Surgery

• Preferred when patient no longer has active disease
• Minimal lung resection; objective: restore pulmonary function
• Techniques: sleeve resection with end-to-end anastomosis (bronchoplasty); very low mortality with modern techniques
• Lobectomy for lobar/segmental bronchial lesions
• Pneumonectomy — last resort only (extensive bronchiectasis or completely obliterated main-stem bronchus)

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MULTIDISCIPLINARY MANAGEMENT

1. Three negative smears in TB suspects
2. Intractable symptoms: refractory cough, localised wheeze, persistent/worsening dyspnoea
3. Diminished breath sounds
4. Radiographic atelectasis/collapse or tracheobronchial involvement
5. Lack of clinical/radiological response to anti-TB treatment

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SUMMARY TABLE

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