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PE 28.18 - Lower Respiratory Tract Infections in Children

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OVERVIEW

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I. BRONCHIOLITIS

Definition

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Etiopathogenesis

Etiology

• RSV infection does not confer lasting immunity - reinfection is common
• Seasonal: November to April (winter/early spring in temperate climates; monsoon in India)
• Transmission: fomites (hand-to-nose) and respiratory droplets; incubation 2-8 days; viral shedding continues 2-3 weeks

Pathogenesis

1. Viral replication begins in upper airway epithelium, spreads to lower respiratory mucosa
2. Infected epithelial cells are destroyed by lysis/apoptosis → desquamation + release of inflammatory mediators
3. Histological findings: epithelial cell necrosis, monocytic peribronchial inflammation, edema, mucus and fibrin plugging of distal airways
4. These cause: wheeze + lower airway obstruction
5. Air trapping → hyperinflation + atelectasis → ventilation-perfusion mismatch → hypoxemia
6. Smaller caliber airways in young infants + absence of active immunity → more severe disease
7. Severe obstruction → respiratory muscle fatigue → hypercarbia + respiratory failure
8. Virus-specific IgE production triggers release of bronchoconstriction mediators (leukotriene C4) - explains bronchospasm component

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Clinical Features

• Nasal congestion, copious rhinorrhea, low-grade fever, mild cough

• Tight cough (hallmark)
• Wheeze (audible or on auscultation)
• Tachypnea, tachycardia
• Increased work of breathing: intercostal/subcostal/suprasternal retractions, nasal flaring, grunting
• Feeding difficulties (first sign of hypoxia in infants)
• Apnea (especially in very young infants and ex-premature babies - may precede typical symptoms)
• Cyanosis in severe disease

• Tachypnea (RR > 60/min in infants)
• Bilateral diffuse wheeze (expiratory >> inspiratory in severe)
• Fine end-inspiratory crackles (shifting)
• Prolonged expiration
• Hyperinflated chest (barrel chest appearance)
• Hepatomegaly (from pushed-down diaphragm - does NOT indicate cardiac failure)

Severity Assessment (Bronchiolitis Score)

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Diagnosis

• CXR: hyperinflation, peribronchial thickening, patchy atelectasis, flattened diaphragm - not routinely required
• SpO₂: essential in moderate-severe disease
• Rapid antigen test/PCR for RSV: reserved for hospitalized patients (cohorting) or immunocompromised
• Blood gas: only if severe respiratory failure suspected
• CBC: not routinely required

Key point (Ghai): No single sign reliably predicts hypoxia - a combination of signs (RR > 60, altered sensorium, poor feeding) should be used.

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Management

Supportive Care (mainstay)

• Positioning: upright/semi-prone, head elevated 30°
• Oxygen: via nasal cannula/face mask for SpO₂ < 92% (or < 94% in severe cases)
• Hydration: oral/nasogastric if able to tolerate; IV fluids if unable to feed or SpO₂ < 92%
• Nasal suctioning: gentle suction before feeds to relieve congestion
• Monitor: respiratory rate, SpO₂, hydration, feeding

Pharmacotherapy (largely NOT recommended routinely)

Respiratory Support

• High-flow nasal cannula (HFNC): may prevent need for intubation in moderate-severe cases; evidence limited
• CPAP/BiPAP: for impending respiratory failure
• Mechanical ventilation: for apnea, respiratory failure (rising PaCO₂, severe hypoxemia)

Indications for Hospitalization

• Age < 3 months
• SpO₂ ≤ 92-94% on room air
• RR > 70/min
• Poor oral intake (< 50% usual feeds)
• Dehydration
• Apnea
• Social concerns
• Comorbidities (CHD, CLD, prematurity)

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Prevention

• Palivizumab (monoclonal antibody against RSV F protein): IM monthly injections during RSV season for high-risk infants (premature < 32-35 weeks, CHD, chronic lung disease) - not a vaccine
• Nirsevimab (newer long-acting monoclonal antibody): single dose, now recommended for all infants in their first RSV season (2023 ACIP/WHO)
• RSV maternal vaccine (mResvia/Abrysvo): given to pregnant women 32-36 weeks gestation - passive antibody transfer to neonate
• Hand hygiene and contact precautions in hospital settings
• Breast feeding - protective
• Avoid exposure to tobacco smoke, crowding

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II. WHEEZE-ASSOCIATED LRTI (WALRI)

Definition

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Etiopathogenesis

• Pathogen: Rhinovirus (most common trigger in children > 1 year), RSV, hMPV, PIV
• Virus infects airway epithelium → triggers bronchospasm via IgE-mediated mechanisms + direct epithelial damage
• Background factors: atopy, small airway caliber, parental smoking, daycare attendance

Phenotypes (important for Ghai)

1. Transient early wheezers: wheezing starts before age 3, resolves by age 6 - associated with reduced lung function at birth (maternal smoking), NOT atopic
2. Persistent wheezers: wheezing that continues beyond age 6 - associated with atopy, family history of asthma, elevated IgE
3. Late-onset wheezers: begin after age 3

Predictive Index (Modified Asthma Predictive Index - mAPI)

• 1 major criterion: parental asthma OR eczema in child
• 2 minor criteria: allergic rhinitis, wheeze without cold, eosinophilia > 4% → High probability of persistent asthma

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Clinical Features

• Episodic wheeze triggered by viral URTI
• Tachypnea, increased work of breathing
• Bilateral expiratory wheeze ± crackles
• Mild-moderate fever
• Inter-episode: completely well (distinguishes from asthma which may have residual symptoms)

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Diagnosis

• Clinical diagnosis
• CXR: hyperinflation, peribronchial thickening
• Peak flow/spirometry: not feasible in < 5 years
• Allergy tests (IgE, skin prick test): to assess atopic status for predicting persistence

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Management

Acute Episode

• Salbutamol (albuterol) MDI with spacer or nebulization: 0.15 mg/kg (minimum 2.5 mg) every 20 minutes x 3, then reassess - first line
• Oxygen for hypoxia
• Ipratropium bromide: add in moderate-severe wheeze (first 24 hours)
• Oral prednisolone (1-2 mg/kg/day for 3-5 days): in moderate-severe episodes, evidence less clear in pre-schoolers vs older children
• IV magnesium sulfate (50 mg/kg over 20 min): in severe/refractory wheeze

Prevention/Maintenance

• Identify and avoid triggers
• Intermittent ICS (budesonide/beclomethasone): prescribed at onset of viral URTI in high-risk children (not all WALRI children)
• Montelukast: may reduce episode severity; modest evidence in preschool wheeze
• Continuous ICS: only if high frequency of episodes (≥4/year) and significant mAPI - anticipates asthma
• Environmental control: secondhand smoke, allergen reduction

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III. PNEUMONIA

Definition

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Classification (Ghai/WHO)

By Etiology

• Bacterial (most common cause of severe pneumonia in developing countries)
• Viral (most common overall cause in children)
• Atypical (Mycoplasma, Chlamydia)
• Fungal (immunocompromised)
• Aspiration

By WHO Clinical Severity (Field Classification - key for Ghai/IAP)

By Causative Agent by Age (Ghai emphasis)

Streptococcus pneumoniae = most common bacterial cause across all age groups > 1 month

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Etiopathogenesis

Routes of Infection

1. Aspiration of nasopharyngeal secretions (most common) - organisms colonize upper airway
2. Inhalation of infected aerosols/droplets
3. Hematogenous spread (e.g., sepsis, infective endocarditis)
4. Direct spread from adjacent infection

Pathogenesis

1. Pathogen overcomes host defenses (mucociliary clearance, alveolar macrophages, secretory IgA, cough reflex)
2. Bacteria/virus reach alveoli → inflammatory exudate fills alveolar spaces
3. Consolidation (bacterial) - alveolar flooding with PMNs, fibrin, RBCs
4. Interstitial infiltration (viral) - lymphocytic infiltration of alveolar walls
5. V/Q mismatch → hypoxemia
6. Systemic inflammatory response → fever, tachycardia

Lobar Pneumonia (classical bacterial - pneumococcal) - 4 stages:

1. Congestion (12-24 hrs): vascular engorgement, alveolar edema
2. Red hepatization (2-3 days): alveoli filled with fibrin, RBCs, PMNs - lung lobe becomes firm/red
3. Grey hepatization (4-6 days): RBCs lyse, fibrin, macrophages - grey appearance
4. Resolution (7-10 days): enzymatic digestion of exudate, lung architecture restored

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Clinical Features

Symptoms

• Fever: usually present, may be high (39-40°C) in bacterial; lower grade in viral/atypical
• Cough: initially dry, becomes productive
• Fast breathing (tachypnea) - most sensitive sign
• Chest pain (older children - pleurisy)
• Abdominal pain (referred from lower lobe pneumonia - may mimic appendicitis)
• Feeding difficulty, lethargy in young infants
• Cyanosis (severe)
• Rigors in older children (bacterial)

Signs

• Tachypnea (most important clinical sign)
• Tachycardia
• Chest indrawing (lower chest wall in-drawing = severity marker in young children)
• Grunting (in neonates/young infants)
• Nasal flaring
• Percussion: dullness over consolidated area
• Auscultation:
  • Bronchial breathing (consolidation)
  • Crepitations/crackles (fine in early/resolving, coarse in consolidation)
  • Reduced air entry
  • Pleural friction rub (pleurisy)
• Vocal resonance/fremitus increased over consolidated lobe

Features by Causative Organism

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Diagnosis

Clinical Criteria (WHO/Ghai)

• Tachypnea alone is sufficient to diagnose pneumonia in a febrile child
• Chest indrawing = severe pneumonia

Investigations

1. Chest X-ray (CXR) - gold standard for confirmation
   • Lobar/segmental consolidation → bacterial (esp. pneumococcal)
   • Patchy bilateral infiltrates/interstitial pattern → viral or atypical
   • Round pneumonia → pneumococcal in young children
   • Pleural effusion → consider empyema
   • Important caveat: CXR not required in mild outpatient pneumonia (Ghai/WHO field classification)
2. CBC:
   • WBC > 15,000/µL with neutrophilia → bacterial
   • WBC 5,000-15,000 with lymphocytosis → viral
   • However, overlap is significant - cannot distinguish reliably
3. Blood culture (gold standard for bacterial etiology): positive in only 10-20%; essential in hospitalized/severe cases before antibiotics
4. Sputum culture: rarely feasible in young children
5. CRP/Procalcitonin: elevated in bacterial; helps guide antibiotic therapy
6. Serology: Mycoplasma IgM (cold agglutinins - positive in 50-60% Mycoplasma), Chlamydia serology
7. Rapid antigen tests: for RSV, influenza, adenovirus (nasopharyngeal wash)
8. Blood gas/SpO₂: to assess oxygenation
9. Pleural fluid analysis: if effusion present (to rule out empyema)

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Management

Antibiotic Selection (Ghai/IAP guidelines)

• Duration: 5-7 days for mild; 10-14 days for severe/S. aureus; 14 days for Mycoplasma

Supportive Care

• Oxygen: for SpO₂ < 90-92%; target ≥ 94%
• IV fluids: if unable to take orally (calculate for maintenance + 10% for fever)
• Antipyretics: paracetamol for comfort
• Positioning: nurse upright
• Nutritional support: nasogastric feeds if needed
• Avoid: cough suppressants, antihistamines (not helpful)

Indications for Hospitalization

• Age < 2 months
• SpO₂ < 90-92% on room air
• Moderate-severe respiratory distress
• Unable to take oral medications
• Vomiting, dehydration
• Complications (effusion, empyema, abscess, pneumatocele)
• Toxic appearance, altered sensorium
• Failure to respond to outpatient antibiotics in 48-72 hours
• Social/family concerns

Complications

• Pleural effusion / empyema
• Lung abscess
• Pneumatocele (especially S. aureus)
• Bronchopleural fistula
• Septicemia, meningitis
• Respiratory failure
• ARDS

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Prevention of Pneumonia

1. Immunization (most effective intervention - Ghai emphasis):
   • PCV (Pneumococcal Conjugate Vaccine): PCV13/PCV15 - 3 doses + booster (NIS schedule: 6, 10, 14 weeks + booster at 9 months)
   • Hib vaccine (DPT-Hib-HepB): protects against H. influenzae type b pneumonia
   • Influenza vaccine: annual, for children with chronic disease
   • Measles vaccine: reduces measles-associated pneumonia
   • COVID-19 vaccine: adolescents
2. Nutritional interventions:
   • Exclusive breastfeeding for 6 months (most important preventive measure)
   • Adequate nutrition/correction of malnutrition
   • Vitamin A supplementation
   • Zinc supplementation (reduces incidence in developing countries)
3. Environmental measures:
   • Reduce indoor air pollution (biomass fuels - smokeless chulhas)
   • Avoid passive smoking
   • Reduce overcrowding
4. Handwashing: proven to reduce LRTI incidence by 40-50%
5. Treatment of predisposing conditions: malnutrition, HIV, malaria

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IV. EMPYEMA THORACIS

Definition

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Etiopathogenesis

Etiology

• S. pneumoniae: most common in children after PCV era (serotype 1, 3, 19A)
• S. aureus (including MRSA): common in infants and younger children; associated with pneumatocele
• S. pyogenes (Group A Strep)
• S. milleri group
• Gram-negative organisms (Klebsiella, E. coli): in neonates, immunocompromised
• Anaerobes: in aspiration pneumonia
• M. tuberculosis: causes serous to frank empyema (rupture of subpleural focus)

Pathogenesis - Three Stages (Light's Classification)

• Free-flowing serous/serosanguineous fluid
• Pleural inflammation → increased vascular permeability
• Low viscosity, low cell count, normal pH and glucose
• Responds to antibiotics alone (no drainage needed)

• Increased WBCs, bacteria in fluid
• Fibrin deposition on pleural surfaces → loculations form
• pH ↓ (< 7.2), glucose ↓ (< 40 mg/dL), LDH ↑ (> 1000 IU/L)
• Requires drainage (chest tube) + antibiotics

• Dense fibrin "peel" encases lung → trapped lung
• Fibroblast proliferation
• Lung cannot re-expand
• Requires surgical decortication

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Clinical Features

• Fever: persistent/recurrent despite antibiotics (key clinical clue)
• Cough: usually productive, purulent
• Chest pain: pleuritic, sharp, worsens with breathing
• Dyspnea: progressive
• Toxic appearance, weight loss (subacute)
• Tracheal deviation (large effusion - away from affected side)
• Reduced chest expansion on affected side
• Stony dullness on percussion
• Absent/markedly reduced breath sounds
• Decreased vocal resonance/fremitus
• Pleural friction rub (early, before effusion accumulates)

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Diagnosis

Imaging

1. CXR (PA + lateral):
   • Blunting of costophrenic angle (> 200-300 mL fluid)
   • Homogeneous opacity with concave upper border (Ellis-Damoiseau line)
   • Mediastinal shift (large effusion)
   • Loculated collections (stage II) - fixed opacity, not shifting with posture
   • Hydropneumothorax (bronchopleural fistula)
2. Ultrasound thorax (preferred - Ghai recommends):
   • More sensitive than CXR for detecting/quantifying effusion
   • Identifies loculations (echogenic strands)
   • Guides diagnostic/therapeutic thoracocentesis
   • Can differentiate consolidation from effusion
3. CT thorax: for complex/loculated empyema, lung abscess, planned surgery

Diagnostic Thoracocentesis - Pleural Fluid Analysis

• Pleural LDH/serum LDH > 0.6
• Pleural protein/serum protein > 0.5
• Pleural LDH > 2/3 upper limit of normal serum LDH

Other Investigations

• Blood culture (positive in ~25% bacterial empyema)
• CBC: neutrophilic leukocytosis, elevated CRP/ESR
• Blood glucose, LFT, RFT: baseline
• Mantoux/IGRA: to rule out TB empyema

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Management

Principles

1. Antibiotics (treat underlying pneumonia)
2. Drain the pus (imperative - pus under tension must be drained)
3. Re-expand the lung
4. Nutritional support (high-protein diet)

Antibiotic Therapy

• Community-acquired (Pneumococcal/Strep):
  • IV amoxicillin-clavulanate OR IV ceftriaxone (50-100 mg/kg/day)
  • Duration: 2-4 weeks total (IV until afebrile, then oral)
• S. aureus suspected (infant, pneumatocele on CXR):
  • IV cloxacillin (100-200 mg/kg/day) + IV gentamicin
  • If MRSA: IV vancomycin (15 mg/kg/dose 6 hourly) or linezolid
• Anaerobes/aspiration: add metronidazole

Drainage Procedures

• Insert in 5th/6th ICS, mid-axillary line (safe triangle: anterior axillary line, posteriorly by latissimus dorsi, inferiorly by nipple line)
• Connect to underwater seal drainage
• Remove when drainage < 50 mL/day AND lung fully re-expanded on CXR

Intrapleural Fibrinolytics

• Urokinase: 40,000 IU in 40 mL normal saline twice daily x 3-6 days (preferred in children)
• Clamp tube for 4 hours after instillation
• Reduces need for surgery in Stage II empyema

Surgical Management

• VATS: for organized empyema, direct visualization, breakdown of loculations, decortication
• Earlier VATS has equivalent outcomes to fibrinolytics in Stage II (MIST1/MIST2 trials)
• Open decortication: reserved for failed VATS or severe chronic empyema with trapped lung

Monitoring and Discharge

• Clinical improvement (fever settling) within 48-72 hours of drainage
• Serial CXR/USS to assess fluid drainage and lung re-expansion
• ICD removal criteria: < 50 mL/day drainage, full lung expansion, afebrile
• Oral antibiotics continued for 2-4 weeks after discharge
• Follow-up CXR at 6-8 weeks (most resolve completely in children)

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Prevention of Empyema

• Early recognition and treatment of pneumonia (prevent progression)
• Pneumococcal vaccination (PCV13 - reduces empyema by ~75%)
• Appropriate antibiotic therapy (adequate dose and duration)
• Drainage of significant parapneumonic effusion before loculation occurs

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SUMMARY TABLE: Key Differentiating Features

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QUICK RECALL MNEMONICS (for Exams)

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