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Acute Respiratory Infections (ARI) - Structured Note

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1. Definition

• Upper ARI (UARI): Involves the nose, paranasal sinuses, pharynx, larynx - above the epiglottis
• Lower ARI (LARI): Involves the trachea, bronchi, bronchioles, and lung parenchyma

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2. Epidemiology & Public Health Significance

• ARI is the most common acute illness in otherwise healthy adults and children. Past National Health Interview Survey data: ~85.6 illnesses per 100 persons/year; accounts for 54% of all acute conditions (excluding injuries)
• Adults experience 3-5 respiratory illnesses/year; children under age 9 experience 5-9/year
• 44% of illnesses require medical attention; result in 94 days lost from work and 182 school days lost per 100 persons/year
• Children under 5 in developing countries: ~4.5 million deaths/year attributable to ARI; viruses contribute to 20-30% of these deaths
• Upper respiratory tract infections account for at least 50% of absenteeism from schools and workplace
• Common cold: responsible for 26 million missed school days and 23 million lost work days annually
• Acute bronchitis: 9th most common ED diagnosis in the US; one of the 10 most common outpatient diagnoses worldwide
• ARI control programmes have contributed significantly to the decline in global infant and child mortality rates

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3. Etiology - Major Causative Agents

Viruses (predominant cause)

Bacteria

Bacteria detected by PCR in only 6-15.5% of acute bronchitis cases. Viruses account for ~95% of acute bronchitis cases.

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4. Transmission

• Contact route: Direct hand contact with contaminated skin/surfaces followed by self-inoculation of nasal mucosa or conjunctiva (rhinovirus, RSV)
• Large-particle aerosol (droplet): Short range (<1 m) - most respiratory viruses
• Small-particle aerosol (airborne): Influenza, measles, varicella-zoster virus
• Respiratory virus infections alter bacterial colonization patterns, increase bacterial adhesion to epithelium, and reduce mucociliary clearance and phagocytosis - predisposing to secondary bacterial infections

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5. Classification by Clinical Syndrome

A. Common Cold (Coryza)

• Etiology: Rhinovirus (most common), coronavirus, adenovirus
• Incubation: Symptoms begin as early as 10-12 hours after inoculation
• Features: Sore throat, malaise, rhinitis, rhinorrhea, congestion, sneezing, cough; fever more common in children; typical duration up to 7 days
• Diagnosis: Clinical; no routine testing needed
• Differential: Allergic rhinitis, sinusitis, non-viral pharyngitis, EBV, influenza, pertussis, HIV seroconversion
• Treatment: Supportive; decongestants and antihistamines give modest relief in adults; topical oxymetazoline reduces nasal airway resistance; avoid cough/cold preparations in children ≤6 years; vitamin C, zinc, echinacea have inconclusive evidence

B. Pharyngitis

• Viral (more common): Associated with common cold viruses (rhinovirus, coronavirus, parainfluenza), adenovirus (pharyngoconjunctival fever - fever + pharyngitis + bilateral conjunctivitis with types 3 & 7), influenza, EBV (exudative, with lymphadenopathy and hepatosplenomegaly; Monospot positive in week 2), CMV (Monospot negative), HSV-1 (vesicles/ulcers on palate), herpangina (Coxsackievirus - small vesicles on soft palate rupturing to white ulcers)
• Bacterial: Group A Streptococcus (GAS) - most important; fever, tonsillar exudate, tender anterior cervical lymphadenopathy, absence of coryza; scarlatiniform rash suggests scarlet fever
• Features favoring streptococcal etiology: Tonsillar swelling, marked tenderness, enlarged lymph nodes, scarlatiniform rash, absent coryza
• Features favoring viral etiology: Nasal symptoms, conjunctivitis present; age <3 years (predominantly viral)
• Diagnosis: Rapid antigen detection test (RADT) for GAS; throat culture if RADT negative in children
• Treatment (GAS): Penicillin V (drug of choice) or amoxicillin; alternatives: cephalosporins, azithromycin in penicillin-allergic patients

C. Acute Bronchitis ("Chest Cold")

• Definition: Self-limited infection causing large airway inflammation, characterized by cough without evidence of pneumonia
• Etiology: Viral (influenza A & B, parainfluenza, RSV, coronavirus, adenovirus, rhinovirus); atypical bacteria in prolonged cases (M. pneumoniae, C. pneumoniae); B. pertussis in adults with cough >3 weeks
• Incidence: Highest in children <5 and elderly; seasonal peak in midwinter
• Clinical Features:
  • Prodrome: ≥24 hours of common cold and pharyngitis symptoms
  • Cough (dry evolving to mucopurulent) persisting >5 days, up to 3-4 weeks
  • Fever, headache, myalgias, retrosternal chest pain
  • Tracheal tenderness; coarse crackles and occasional wheezes on auscultation
  • Yellow/green sputum does NOT predict bacterial infection
• Diagnosis: Clinical; cough >5 days + no evidence of pneumonia; reversible decrease in FEV1 may be seen on PFTs
  • Chest X-ray: if pneumonia suspected (fever, tachycardia, tachypnea, hypoxia, abnormal auscultation)
  • Procalcitonin: studied as antibiotic guide but large RCTs failed to show reduction in unnecessary prescriptions
• Treatment:
  • Antibiotics NOT recommended routinely - benefit <0.5 days, significant adverse effects outweigh
  • Reserve antibiotics for strong suspicion of specific treatable pathogen (e.g., pertussis)
  • Beta-2 agonists: avoid routine use; consider in patients with wheeze/airflow obstruction
  • Oral corticosteroids: not supported in patients without COPD/asthma
  • Antitussives, benzonatate, guaifenesin: may provide modest cough relief
• Cough >3 weeks differential: Post-nasal drip, asthma, GERD, ACE inhibitor cough, pertussis (>90% of causes)

D. Influenza

• Epidemiology: 9-60 million infections/year in the US; 12,000-56,000 deaths/year (CDC); pandemic potential (H1N1 pandemic 2009)
• Transmission: Antigenic drift (minor) and antigenic shift (major) drive epidemic and pandemic cycles
• Clinical Features: Sudden onset fever, myalgias, severe fatigue, headache, cough, pharyngitis
• Treatment: Oseltamivir, zanamivir, baloxavir - best within 48 hours of symptom onset; recommended in high-risk patients (elderly, immunocompromised, pregnant, severe illness)
• Prevention: Annual influenza vaccination

E. Acute Sinusitis

• Upper respiratory infection predisposing to bacterial superinfection of sinuses
• Most commonly maxillary sinuses; caused by S. pneumoniae, H. influenzae, M. catarrhalis
• Symptoms >10 days or worsening after initial improvement suggest bacterial etiology

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6. Pathogenesis

• Site of initial infection differs by virus: rhinovirus primarily upper tract; influenza and coronaviruses commonly invade lower airways and parenchyma
• Epithelial damage: Extensive in influenza (characteristic); minimal in rhinovirus (cold symptoms driven mainly by inflammatory mediators and neurogenic reflexes)
• Bradykinin and lysyl bradykinin: Elevated in nasal secretions during rhinovirus colds; potent stimulators of pain nerve endings - explains sore throat and nasal symptoms
• Secondary bacterial infection risk: Respiratory viruses alter bacterial colonization patterns, increase bacterial adhesion to respiratory epithelium, impair mucociliary clearance and phagocytosis
• Lower airway: epithelial infection causes bronchial mucosal inflammation/thickening, airflow obstruction, and bronchial hyperresponsiveness (decreased FEV1, wheeze, dyspnea)

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7. Diagnostic Approach Summary

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8. Treatment Principles

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9. Complications

• Otitis media - especially in children with URTI
• Acute bacterial sinusitis - following viral URTI
• Pneumonia - bacterial superinfection (esp. post-influenza: S. pneumoniae, S. aureus, H. influenzae)
• Croup (laryngotracheobronchitis) - especially parainfluenza types 1 & 2 in young children
• Bronchiolitis - RSV, hMPV, parainfluenza type 3 in infants
• Peritonsillar / retropharyngeal abscess - complication of bacterial pharyngitis
• Rheumatic fever - complication of untreated GAS pharyngitis (thus importance of antibiotic treatment)
• Post-infectious cough - persistent cough after URTI due to airway hyperresponsiveness

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10. Prevention

• Hand hygiene - reduces contact transmission (rhinovirus, RSV)
• Respiratory etiquette - covering coughs/sneezes; masks in outbreaks
• Vaccination:
  • Annual influenza vaccine (all persons >6 months)
  • Pertussis (Tdap) booster in adults and adolescents
  • Pneumococcal vaccines (prevent secondary bacterial pneumonia)
  • RSV vaccine (now available for elderly and maternal protection)
• Antibiotic stewardship - critical to prevent overuse; most ARI is viral and does not benefit from antibiotics

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11. Key Distinguishing Points (Clinical Pearls)

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Classification of Acute Respiratory Infections (ARI)

1. Anatomical Classification - based on site of infection
2. WHO/IMCI Severity Classification - used in child health programmes (for under-5 children)

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I. Anatomical Classification

A. Upper Respiratory Tract Infections (URTI)

B. Lower Respiratory Tract Infections (LRTI)

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II. WHO/IMCI Severity-Based Classification (for Children)

A. Child Aged 2 Months up to 5 Years

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Grade I: Very Severe Disease

• Not able to drink
• Convulsions
• Abnormally sleepy or difficult to wake
• Stridor in a calm child
• Severe malnutrition

• Refer URGENTLY to hospital
• Give first dose of antibiotic
• Treat fever if present
• Treat wheezing if present
• If cerebral malaria possible: give antimalarial

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Grade II: Severe Pneumonia

• Chest indrawing (lower chest wall goes IN on breathing IN)
• May also have: nasal flaring, grunting, cyanosis
• Note: Fast breathing may be absent if child is exhausted
• Children with recurrent wheezing and chest indrawing are classified differently (treat as asthma first)

• Refer URGENTLY to hospital
• Give first dose of antibiotic
• Treat fever and wheeze if present
• If referral not feasible: treat with antibiotic and follow closely

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Grade III: Pneumonia (Not Severe)

• No chest indrawing
• Fast breathing present:
  • ≥50 breaths/min if aged 2-12 months
  • ≥40 breaths/min if aged 12 months to 5 years

• Advise mother on home care
• Give oral antibiotic (co-trimoxazole or amoxicillin)
• Treat fever and wheeze if present
• Reassess in 2 days (or earlier if worsening)

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Grade IV: No Pneumonia - Cough or Cold

• No chest indrawing
• No fast breathing
  • <50 breaths/min if aged 2-12 months
  • <40 breaths/min if aged 12 months to 5 years

• No antibiotic required
• Advise mother on home care
• Treat fever and wheeze if present
• If cough persists >30 days: refer for further assessment
• Assess and treat ear problems or sore throat if present

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B. Young Infant (Age < 2 Months)

• Mild chest indrawing is normal (soft chest wall bones)
• Breathing is erratic (periodic breathing is common)
• Cut-off for fast breathing: ≥60 breaths/minute
• Any pneumonia in a young infant is considered severe
• Must be referred immediately to hospital

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III. Fast Breathing Cut-offs Summary Table

Note: Count respiratory rate for a full minute. Repeat count in young infants if ≥60/min (breathing is erratic in this age group). Increased respiratory rate is significant only if it persists.

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IV. Additional Classification Systems

By Etiology

By Duration

By Host

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V. Key Clinical Signs Used in Classification (WHO)

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