วันอังคารที่ 3 มีนาคม พ.ศ. 2569

Pulmonary Tuberculosis: clinical & diagnosis

Pulmonary Tuberculosis: clinical & diagnosis

Clinical manifestations, natural history, complications

1) Core clinical concept (High-yield)

  • ปอด = primary site ของ Mycobacterium tuberculosis infection
  • Spectrum ของโรค:
    • Subclinical TB (culture+ ไม่มีอาการ)
    • Active pulmonary TB (symptomatic)
  • การแพร่เชื้อ: airborne aerosol droplets (cough/sneeze/singing)

2) Natural history of pulmonary TB (Pathophysiology เชิงคลินิก)

2.1 หลัง inhalation ของ M. tuberculosis → 3 possible outcomes

1. Immediate clearance

  • innate immunity กำจัดเชื้อก่อน adaptive response

2. TB infection (Latent TB infection; LTBI)

  • เชื้อยังมีชีวิต แต่ถูกควบคุมโดย CMI
  • TST/IGRA (Tuberculin Skin Test/Interferon-Gamma Release Assays) positive
  • ไม่มีอาการ/ไม่มี active disease
  • Global prevalence ~1.7 billion คน

3. Primary TB disease

  • เกิดเมื่อ host ล้มเหลวในการ mount CMI
  • เชื้อ proliferate ใน alveolar macrophage
  • เกิด granuloma → Ghon focus
    • hilar LN = Ghon complex
  • calcified = Ranke complex

2.2 Reactivation (Postprimary TB)

  • Lifetime risk: ~5–10%
    • 5% ภายใน 2–5 ปีแรก
    • อีก ~5% ตลอดชีวิต
  • Predilection: apical & posterior upper lobes
  • มัก localized มากกว่า primary TB

Risk factors for reactivation (ต้อง screen เสมอ)

  • HIV infection
  • DM
  • CKD
  • TNF-alpha inhibitors / steroids
  • Organ transplant
  • Silicosis
  • Malnutrition
  • Older age

3) Transmission risk factors (สำคัญต่อ infection control)

Index case ที่แพร่เชื้อสูง:

  • Pulmonary / laryngeal TB
  • Cavitary disease
  • Smear positive sputum
  • Frequent cough
  • Ineffective treatment

Air travel risk:

  • 8 ชั่วโมงใกล้ผู้ป่วย infectious TB → risk เพิ่ม

4) Clinical manifestations of pulmonary TB

4.1 Reactivation TB (พบบ่อยในผู้ใหญ่) — Classic presentation

Symptoms (insidious, weeks–months)

พบบ่อย:

  • Chronic cough (>2–3 weeks) 50–70%
  • Weight loss
  • Fatigue
  • Fever (low-grade, evening rise)
  • Night sweats
  • Anorexia

พบรองลงมา:

  • Hemoptysis (~25%)
  • Dyspnea
  • Chest pain

ลักษณะสำคัญ:

  • อาการค่อย ๆ เป็น (subacute/chronic)
  • Sputum: yellow/green ± blood-streaked
  • Massive hemoptysis = late disease (cavity erosion)

⚠️ Clinical pitfall:

  • ~1/3 วินิจฉัยจาก admission ด้วยเหตุอื่น
  • Missed diagnosis สูง (~75% มี missed opportunity ≥1 ครั้ง)

4.2 Primary TB (พบมากในเด็ก / immunocompromised)

อาการ:

  • Low-grade fever (70%)
  • Pleuritic chest pain (~25%)
  • Fatigue
  • Mild cough
  • Arthralgia / pharyngitis (rare)

ระยะไข้:

  • Gradual onset
  • Duration ~2–3 สัปดาห์
  • มักหายภายใน 10 สัปดาห์

4.3 Presentation in special populations

Older adults

  • Fever, hemoptysis, cavitation ↓
  • Dyspnea, fatigue ↑
  • Lower lobe involvement ↑
  • Diagnosis delay สูง (symptoms nonspecific)

HIV infection

ขึ้นกับ CD4:

  • CD4 >200 → คล้าย TB ทั่วไป (cavity, upper lobe)
  • CD4 <200:
    • Noncavitary consolidation
    • Diffuse infiltrates
    • Mediastinal lymphadenopathy
    • Miliary/disseminated TB ↑
    • Normal CXR ได้บ่อย

Subclinical TB (HIV): 7–52%

5) Physical examination (มักไม่ specific)

อาจพบ:

  • Post-tussive crackles
  • Dullness (effusion)
  • Amphoric breath sound (cavity) เป่าลมผ่านปากขวด
  • Signs of consolidation:
    • Tubular breath sound (เสียงเหมือน trachea)
    • Whispered pectoriloquy
  • Wheeze (endobronchial TB)
  • Clubbing (chronic disease)

6) Laboratory findings (practical interpretation)

Routine labs

  • มักปกติใน early disease
  • CRP ↑ (up to 85%)
    Late disease:
  • Normocytic anemia
  • Leukocytosis / monocytosis
  • Hypoalbuminemia
  • Hypergammaglobulinemia
  • Hyponatremia (SIADH หรือ adrenal TB)

7) Radiologic findings (High-yield for diagnosis)

7.1 Reactivation TB (Classic pattern)

CXR:

  • Upper lobe consolidation (70–87%)
  • Cavitation (19–40%)
  • Apical/posterior segments (80–90%)
  • Air-fluid level in cavities (~20%)

CT findings:

  • Tree-in-bud pattern (bronchogenic spread)
  • Cavities
  • Fibrosis
  • Traction bronchiectasis
  • Apicoposterior consolidation

7.2 Primary TB imaging

  • Hilar/mediastinal lymphadenopathy (65%)
  • Pleural effusion (~33%)
  • Homogeneous consolidation
  • Middle/lower lobe involvement

CT hallmark:

  • Necrotic lymph nodes (rim enhancement)
  • Dense consolidation
  • Galaxy sign (cluster granulomas)

7.3 Important imaging pearls

  • CXR อาจปกติได้ (~5%)
  • CT sensitive กว่า CXR โดยเฉพาะ apical lesion
  • Atypical pattern:
    • Lower lobe consolidation
    • Solitary nodule
    • Pleural effusion only
    • Lymphadenopathy only

8) Special pulmonary manifestations

8.1 Endobronchial TB

Pathogenesis:

  • Direct extension จาก cavity
  • Bronchogenic spread

Symptoms:

  • Barking cough (classic)
  • Wheezing (monophonic, localized)
  • Hemoptysis
  • Dyspnea

Complications:

  • Bronchial stenosis (>90%)
  • Atelectasis
  • Bronchiectasis
  • Airway obstruction

Diagnosis:

  • HRCT (tree-in-bud)
  • Bronchoscopy + biopsy + culture (>90% yield)

8.2 Lower lung TB

  • Incidence: 2–9%
  • Mimics:
    • Bacterial pneumonia
    • Lung cancer
    • Bronchiectasis
  • High risk:
    • Elderly
    • HIV
    • DM
    • CKD
    • Steroid use

8.3 Tuberculoma

  • Well-circumscribed pulmonary nodule/mass
  • Upper lobe common
  • Size <1 cm to >10 cm
  • DDx: malignancy
  • Airway culture often negative → biopsy needed

8.4 Laryngeal TB (high infectivity)

Symptoms:

  • Dysphonia (96%)
  • Dysphagia
  • Cough
  • Weight loss
  • Stridor

Complication: vocal cord paralysis, stenosis

9) Major pulmonary complications of TB (Exam + Clinical critical)

9.1 Hemoptysis

  • Occurs ~8%
  • Usually mild blood-streaked sputum
  • Massive hemoptysis causes:
    • Rasmussen aneurysm
    • Bronchial artery dilatation
    • Cavitary erosion

Management:

  • Bronchoscopy (localization)
  • CT angiography
  • Bronchial artery embolization = first-line
  • Surgery if failed

9.2 Pneumothorax

  • Incidence ~1–1.5%
  • Mechanism: rupture of subpleural cavity
  • Treatment: chest tube + anti-TB therapy

9.3 Bronchiectasis (common long-term sequela)

Mechanisms:

  • Lymph node compression (primary TB)
  • Fibrosis + parenchymal destruction (reactivation TB)
  • Endobronchial stenosis

9.4 Severe complications (high mortality)

  • Massive pulmonary destruction
  • Pulmonary gangrene
  • ARDS (mortality 47–80%)
  • Septic shock from TB (mortality ~79%)

9.5 Other important complications

  • Chronic pulmonary aspergillosis (post-cavity)
  • Lung cancer risk ↑ (OR ~2.1)
  • VTE risk ↑ (OR ~2.9)
  • Tracheobronchial stenosis
  • Bronchopleural fistula

10) Differential diagnosis of cavitary lung lesion (must rule out)

Key DDx:

  • Nontuberculous mycobacteria (NTM)
  • Fungal infection (aspergillus, histoplasma)
  • Melioidosis (สำคัญใน Southeast Asia)
  • Lung abscess
  • Septic emboli
  • Lung cancer
  • Lymphoma
  • Sarcoidosis (noncaseating granuloma)

11) Clinical red flags suggestive of pulmonary TB (Practical checklist)

สงสัย TB สูงเมื่อมี:

  • Cough >2–3 weeks
  • Weight loss + night sweats
  • Hemoptysis
  • Upper lobe lesion / cavity
  • Chronic symptoms + normal antibiotics failure
  • Immunosuppression (HIV, DM, steroid)
  • Residence/travel in endemic area
  • Unexplained pleural effusion
  • Tree-in-bud pattern on CT

Emergency & ICU pearls (สำคัญสำหรับแพทย์ฉุกเฉิน)

ต้องนึกถึง TB ใน:

  • Hemoptysis ไม่ทราบสาเหตุ
  • Chronic pneumonia ไม่ตอบสนอง ATB
  • ARDS + risk factors TB
  • Septic shock + weight loss + anemia + low WBC
  • Hyponatremia + chronic respiratory symptoms
  • Post-COVID + steroid history + chronic cough

Diagnosis of Pulmonary Tuberculosis (Adult)

1) Epidemiology & Clinical importance (Context ที่ควรรู้)

  • ประมาณ ~1/4 ของประชากรโลก (~2 พันล้านคน) ติดเชื้อ M. tuberculosis
  • ปี 2024:
    • TB incidence ≈ 10.7 ล้านราย
    • Death ≈ 1.23 ล้านราย
  • Early diagnosis →
    ✔ ลด mortality
    ✔ ลด transmission (public health impact สูงมาก)

2) Core diagnostic principle (High-yield)

Gold standard

Isolation of M. tuberculosis จาก clinical specimen
เช่น:

  • Sputum
  • BAL
  • Pleural fluid
  • Tissue biopsy

3) Terminology ที่ต้องแยกให้ชัด

Term

Meaning

TB infection (LTBI)

Immune sensitization, no active disease

Active TB disease

Symptomatic + microbiologic/radiologic evidence

Microbiologic confirmation

Culture / NAAT positive

Clinical TB diagnosis

ไม่มี culture ยืนยัน (พบได้ 15–20%)

4) Stepwise Diagnostic Approach (Practical Algorithm for Physicians)

4.1 Step 1 — Clinical suspicion (ด่านสำคัญที่สุด)

4.1.1 Symptoms suggestive TB

  • Cough >2–3 weeks
  • Fever
  • Night sweats
  • Weight loss
  • Hemoptysis
  • Lymphadenopathy
    (⚠️ บางราย asymptomatic ได้)

4.1.2 Epidemiologic risk factors

  • Previous TB
  • TB contact
  • Residence/travel in endemic area (เช่น Southeast Asia, Thailand)
  • HIV
  • Immunosuppression
  • Healthcare exposure

ผู้ป่วยที่มี clinical suspicion + transmission risk →
Admit + Airborne isolation (negative pressure)

4.2 Step 2 — Initial investigations

Mandatory baseline workup

1.       Chest X-ray

2.       Sputum microbiology (key step)

5) Specimen collection (High-yield clinical details)

5.1 Sputum (First-line specimen)

Standard recommendation:

  • ≥3 specimens
  • ห่างกัน ≥8 ชั่วโมง
  • อย่างน้อย 1 specimen = early morning sputum
  • ปริมาณที่เหมาะสม: 5–10 mL
  • ต้องเป็น lower respiratory secretion (ไม่ใช่ saliva)

Methods:

  • Spontaneous sputum (preferred)
  • Induced sputum (hypertonic saline)
    • Yield ≈ BAL
    • Safer + cheaper

5.2 When sputum not available

ใช้:

  • Induced sputum
  • Bronchoscopy + BAL (indications):
    • Cannot produce sputum
    • Smear negative but high suspicion
    • Alternative diagnosis needed
    • Urgent diagnosis

Post-bronchoscopy sputum → ส่งตรวจเพิ่ม (เพิ่ม yield)

6) Core microbiologic tests (Key diagnostic tools)

6.1 AFB smear microscopy

Role

  • Rapid
  • Cheap
  • Screening tool

Performance

  • Sensitivity: ~45–80%
  • Specificity: >90%
  • ต้องมี bacilli ~10,000/mL จึงตรวจพบ

Important clinical pearls

  • Smear+ ≠ TB เสมอ (อาจเป็น NTM)
  • HIV → sensitivity ลด (low bacillary load)
  • Fluorochrome stain > Ziehl-Neelsen (more sensitive)

6.2 Nucleic Acid Amplification Test (NAAT) — Modern standard

เช่น:

  • Xpert MTB/RIF
  • Xpert Ultra
  • Truenat MTB

Clinical role

  • Rapid diagnosis (24–48 hr; Xpert ~2 hr)
  • Detect MTB DNA
  • Detect rifampicin resistance (rpoB gene)

Interpretation (very important)

Result

Interpretation

Smear+ + NAAT+

Sufficient for TB diagnosis

NAAT+ (risk present)

Strongly supports active TB

NAAT-

Cannot rule out TB

Smear+ + NAAT-

Think NTM

Sensitivity

  • Smear+: ~95%
  • Smear-: ~75–88%
  • Specificity: ~95–98%

⚠️ Limitation:

  • Detects dead bacilli → not for treatment monitoring

6.3 Mycobacterial culture (Gold standard)

Strengths

  • Most sensitive (detect as low as 10 bacilli/mL)
  • Sensitivity ~80%
  • Specificity ~98%
  • Required for:
    • Definitive diagnosis
    • Species identification
    • Drug susceptibility testing (DST)

Culture time

  • Liquid media: 1–3 weeks
  • Solid media: 3–8 weeks

7) Drug resistance evaluation (Critical in modern TB)

7.1 Suspect drug-resistant TB when:

  • Previous TB treatment
  • Treatment failure/progression
  • Contact with MDR-TB
  • High-resistance endemic area

7.2 Required tests

  • Culture-based DST (gold standard)
  • Molecular resistance testing:
    • Rifampin resistance → Xpert MTB/RIF
    • INH resistance → line probe assay
    • XDR panel (where available)

8) Role of imaging in diagnosis

8.1 Chest X-ray (initial tool)

Classic reactivation TB:

  • Upper lobe infiltration
  • Cavitation
  • Fibrosis
  • Bilateral or unilateral lesions

Atypical findings:

  • Lower lobe consolidation
  • Pleural effusion
  • Miliary pattern
  • Lung mass (tuberculoma)

⚠️ Active vs inactive TB cannot be distinguished by CXR alone

8.2 CT chest

  • More sensitive for early disease
  • Indications:
    • Equivocal CXR
    • Alternative diagnosis suspected
    • Subtle nodal/parenchymal disease

Not routine for all suspected TB.

9) Role of IGRA / TST (Common misconception)

Key point (Exam & clinical):

  • Detect immune sensitization
  • NOT diagnostic for active TB

Test

Use

IGRA

TB infection (LTBI)

TST

TB infection

Positive result

Supports but does NOT confirm active TB

Negative result

Does NOT exclude active TB

10) Diagnosis without microbiologic confirmation (Clinical TB)

พบได้ ~15–20% ของผู้ป่วย

Diagnosis based on:

  • Epidemiologic risk
  • Symptoms
  • Imaging suggestive TB
  • Positive IGRA/TST
  • Histopathology (granuloma ± caseation)
  • Response to therapy

ใน high suspicion →
สามารถเริ่ม empiric anti-TB therapy ได้

11) Special population: HIV patients (Very high-yield)

Diagnostic challenges

  • Smear sensitivity ↓
  • Atypical CXR
  • Low bacillary load

Additional tests recommended

  • Blood mycobacterial culture
  • Urine culture
  • Urine LAM test (especially CD4 <100–200)

Urine LAM (lipoarabinomannan) ตรวจ TB antigen (WHO recommended)

Indications:

  • HIV + TB symptoms
  • CD4 <200
  • Seriously ill
  • Cannot produce sputum

Key:

  • Positive LAM → start empiric TB treatment
  • Negative LAM ≠ rule out TB

12) Tissue biopsy & histopathology

When useful:

  • Sputum negative
  • Extrapulmonary TB
  • Mass lesion (DDx malignancy)

Typical pathology:

  • Caseating granuloma
  • Epithelioid macrophages
  • Langhans giant cells

⚠️ Not pathognomonic → culture still required

13) Tests that should NOT be used

❌ Serologic antibody tests

  • WHO strongly recommends against use
  • Poor accuracy & cost-ineffective

14) WHO 2024 Diagnostic shift (Very important update)

WHO now prioritizes:

Rapid molecular tests (NAAT)
over smear microscopy as initial diagnostic test
in most settings

Preferred initial tests:

  • Xpert MTB/RIF
  • Xpert Ultra
  • Truenat MTB/MTB Plus

15) Screening strategy in high-burden countries (เช่น ไทย)

Best screening combination:

  • Symptom screening + CXR
    Sensitivity:
  • Symptoms alone ≈ 71%
  • CXR ≈ 95%
  • Combined ≈ 99%

16) Infection control & public health (Clinical duty)

  • TB = Reportable disease
  • Suspected/confirmed TB → report to public health
  • Initiate:
    • Contact tracing
    • Community control
    • Case management support

17) Ultra–high yield clinical checklist (สำหรับ ER/OPD)

Suspect pulmonary TB if:

  • Cough >2–3 weeks
  • Weight loss + night sweats
  • Hemoptysis
  • Upper lobe lesion on CXR
  • Pneumonia not responding to antibiotics
  • HIV/immunocompromised
  • TB endemic exposure

Immediate orders (practical order set)

  • Airborne isolation
  • CXR
  • Sputum AFB smear ×3
  • NAAT (Xpert MTB/RIF)
  • Mycobacterial culture
  • HIV test
  • Baseline labs (CBC, LFT)
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