What is the differential diagnosis for a cough with yellow sputum?

Differential Diagnosis for Cough with Yellow Sputum

Yellow or purulent sputum does NOT indicate bacterial infection and should not guide antibiotic decisions—the color reflects inflammatory cells or sloughed epithelial cells from either viral or bacterial causes. 1

Primary Diagnostic Considerations

1. Acute Viral Bronchitis (Most Common)

• Accounts for >90% of acute cough with sputum in otherwise healthy adults 1
• Caused by influenza A, influenza B, parainfluenza, RSV, or other respiratory viruses 1
• Cough typically lasts up to 3 weeks, may persist up to 6 weeks 1
• Sputum color (yellow, green, or clear) has NO diagnostic value for distinguishing viral from bacterial infection 1, 2
• Key point: A study of 241 patients showed yellowish/greenish sputum had sensitivity of 0.79 but specificity of only 0.46 for bacterial infection, with positive likelihood ratio of only 1.46—clinically unhelpful 2

2. Pneumonia (Must Be Excluded First)

Pneumonia can be ruled out if ALL of the following are absent: 1

• Heart rate >100 beats/min
• Respiratory rate >24 breaths/min
• Oral temperature >38°C (100.4°F)
• Focal chest findings (consolidation, egophony, fremitus, or rales)

If any of these findings are present, obtain chest X-ray immediately 1, 3

Special populations requiring lower threshold for imaging: 3

• Age ≥60 years (pneumonia more common, higher mortality risk)
• Hemoptysis present
• Cough persisting >3 weeks
• C-reactive protein >100 mg/L

3. Acute Asthma or Asthma Exacerbation

• Approximately 40% of patients diagnosed with "acute bronchitis" actually have transient bronchial hyperresponsiveness 1
• Consider asthma if: 1
  • Cough worsens at night or with cold/exercise exposure
  • History of recurrent "bronchitis" episodes (65% have undiagnosed mild asthma) 1
  • Wheezing present on examination
  • Reversible airflow obstruction (FEV1 improvement >15%) 1
• Transient hyperresponsiveness from viral infection typically resolves within 2-6 weeks 1

4. Acute Exacerbation of Chronic Bronchitis/COPD

• Must have underlying chronic lung disease (not "uncomplicated" acute bronchitis) 1
• Increased sputum volume, purulence, or dyspnea beyond baseline 1
• Rhonchi commonly present on examination 4, 5

5. Pertussis (Bordetella pertussis)

Suspect when: 1

• Severe paroxysmal cough
• Post-tussive vomiting
• Characteristic "whooping" sound
• Known exposure to confirmed pertussis case
• Cough persisting >3 weeks without improvement

This is the ONE bacterial cause where early antibiotics reduce transmission 6

6. Atypical Bacterial Infections

• Mycoplasma pneumoniae or Chlamydophila pneumoniae 1
• Consider in outbreak settings (military personnel, college students) 1
• These organisms show lower FEV1 values and greater reversibility than viral causes 1
• However, routine testing is NOT recommended as the organism is rarely identified 1

7. Bronchiectasis (Chronic Condition)

• Chronic productive cough with large sputum volumes (>30 mL/day) 1
• Physical exam may show rhonchi, crackles, clubbing—or be completely normal 1, 5
• Sputum cultures often positive for H. influenzae, S. aureus, S. pneumoniae, or P. aeruginosa 1
• Diagnosis requires HRCT scan showing bronchial dilation (signet ring sign) 1, 5

8. Upper Airway Cough Syndrome (UACS/Post-nasal Drip)

• Accounts for 40% of chronic productive cough cases 1
• Associated rhinorrhea, throat clearing, sensation of post-nasal drainage 1
• May present with yellow sputum from nasal/sinus secretions 1

9. Gastroesophageal Reflux Disease (GERD)

• Accounts for 15% of chronic productive cough 1
• May lack typical heartburn symptoms 1
• Consider if cough persists >3 weeks without other explanation 1

Critical Clinical Pitfalls

Common Misdiagnosis Patterns

• One-third of patients diagnosed with "acute bronchitis" actually have acute asthma 1
• Purulent sputum leads to inappropriate antibiotic prescribing in 65-80% of acute bronchitis cases despite lack of benefit 1
• The common cold is often mislabeled as bronchitis—use of term "chest cold" reduces patient antibiotic expectations (44% expect antibiotics for "bronchitis" vs. 11% for "chest cold") 1

When Antibiotics Are NOT Indicated

Do NOT prescribe antibiotics for uncomplicated acute bronchitis with yellow sputum 1, 6

• No benefit demonstrated in randomized trials 1
• Increased adverse events with antibiotic use 1
• Macrolides (azithromycin) cause significantly more adverse events than placebo 1

When to Reassess

If cough persists >3 weeks, reconsider diagnosis: 1

• Evaluate for asthma, UACS, GERD, bronchiectasis, or pertussis
• Consider chest imaging if not already obtained 3
• Assess for chronic conditions rather than continuing to treat as "acute bronchitis" 1