What are the differential diagnoses for a productive cough with yellow sputum?

Differential Diagnoses for Productive Cough with Yellow Sputum

Yellow sputum does not indicate bacterial infection and should never guide antibiotic decisions, as the color reflects inflammatory cells from either viral or bacterial causes. 1

Primary Diagnostic Considerations

Acute Viral Bronchitis (Most Common)

• Acute viral bronchitis accounts for more than 90% of acute productive cough in otherwise healthy adults, with cough typically lasting up to 3 weeks and potentially persisting up to 6 weeks. 1
• Yellow or purulent sputum color is not a reliable indicator of bacterial infection—it simply reflects inflammatory cells or sloughed epithelial cells that occur with both viral and bacterial causes. 1, 2
• The sensitivity of yellowish/greenish sputum for bacterial infection is only 0.79, with a specificity of 0.46, yielding a positive likelihood ratio of just 1.46—clinically insufficient to justify antibiotics. 2

Post-Infectious Cough (Subacute, 3–8 Weeks)

• Post-infectious cough is diagnosed when cough persists for 3–8 weeks following an acute respiratory infection, with initial URI symptoms for 3 days followed by persistent cough. 3
• Key features excluding bacterial infection include non-purulent sputum, absence of fever, clear lungs except transient wheezes that clear with coughing, and no crackles suggesting pneumonia. 3
• This condition is driven by post-viral airway inflammation, bronchial hyperresponsiveness, and mucus hypersecretion—not ongoing bacterial infection. 3

Asthma (Including Cough-Variant Asthma)

• Approximately 40% of patients diagnosed with "acute bronchitis" actually have transient bronchial hyperresponsiveness characteristic of asthma. 1
• Asthma accounts for 14.6–41.3% of chronic cough cases and may present with cough as the sole manifestation, even without wheezing or dyspnea. 4
• Consider asthma if cough worsens at night, with cold/exercise exposure, or if there is a history of recurrent "bronchitis" episodes. 1
• Normal spirometry does not exclude asthma-related cough; methacholine challenge is indicated when baseline pulmonary function is normal. 4

Pneumonia (Critical Rule-Out)

• Obtain a chest X-ray immediately if the patient has heart rate >100 bpm, respiratory rate >24 breaths/min, oral temperature >38°C, or focal chest findings (crackles, diminished breath sounds, dullness to percussion). 1
• Special populations—those aged ≥60 years, or those with hemoptysis, cough persisting >3 weeks, or C-reactive protein >100 mg/L—require a lower threshold for imaging. 1
• The presence of focal auscultatory abnormalities raises the probability of pneumonia from 5–10% to approximately 39%. 3

Chronic Bronchitis / COPD with Mucus Hypersecretion

• Smokers with persistent productive cough may be at risk of developing COPD, and a productive cough in patients with established airflow obstruction predicts lung function decline. 5
• Chronic cough and sputum production are significantly more prevalent in patients with COPD and serve as risk factors for exacerbations. 6
• In current smokers, chronic bronchitis should be considered as a contributor to productive cough. 4

Bronchiectasis

• Although usually associated with sputum production, "dry" bronchiectasis can cause persistent cough; the prevalence among specialist cough clinic patients is estimated at 4%. 5
• High-resolution CT of the chest is the definitive diagnostic test for bronchiectasis and should be obtained when chest radiograph and empiric therapies do not identify the cause. 4
• Bronchiectasis is characterized by dilated bronchi due to severe or recurrent lower airway inflammation and typically presents with chronic or recurrent productive cough. 7

Upper Airway Cough Syndrome (UACS)

• UACS accounts for approximately 18.6–81.8% of chronic cough cases and may present without prominent nasal symptoms such as post-nasal drip. 4
• Associated symptoms include frequent throat clearing, nasal congestion, or chronic rhinitis. 4

Gastroesophageal Reflux Disease (GERD)

• GERD is implicated in 4.6–85.4% of chronic cough cases and frequently occurs without typical gastrointestinal symptoms (heartburn, regurgitation). 4
• Cough related to reflux can be the sole manifestation of GERD. 4

Non-Asthmatic Eosinophilic Bronchitis (NAEB)

• NAEB contributes to 6.4–17.2% of chronic cough cases and is characterized by eosinophilic airway inflammation without airway hyperresponsiveness or variable airflow obstruction. 4
• Treatment with inhaled corticosteroids is effective in NAEB. 4

Pertussis (Bordetella pertussis)

• In a series of 180 prospective chronic cough cases, 10% had nasal swabs positive for Bordetella. 5
• Pertussis should be suspected when cough lasts ≥2 weeks with paroxysms, post-tussive vomiting, or inspiratory "whoop" sound. 3

Protracted Bacterial Bronchitis (PBB)

• PBB is defined as cough lasting at least 4 weeks that responds to antibiotic therapy and may occur following a viral respiratory tract infection. 7
• An adult version of the pediatric diagnosis has been proposed for patients with idiopathic chronic productive cough who respond well to low-dose macrolide therapy. 8

Immunodeficiency

• Immunodeficiency is often associated with chronic productive cough and should be considered in the differential diagnosis, particularly when recurrent infections are present. 8

Critical Management Principles

Antibiotic Stewardship

• Antibiotics are explicitly contraindicated for uncomplicated acute bronchitis with yellow sputum, as randomized trials demonstrate no benefit and increased adverse events. 1
• Antibiotics have no role in post-infectious cough unless there is documented bacterial sinusitis or early pertussis infection. 3

Duration-Based Diagnostic Approach

• If cough persists >3 weeks, reconsider the diagnosis and systematically evaluate for UACS, asthma, GERD, bronchiectasis, or pertussis. 1
• If cough extends beyond 8 weeks, it should be reclassified as chronic cough and trigger mandatory baseline investigations: chest radiograph and spirometry. 4

Multiple Simultaneous Etiologies

• Up to 67% of chronic cough patients have multiple concurrent causes; combination therapy is often required rather than sequential monotherapy. 4

Common Pitfalls to Avoid

• Never prescribe antibiotics based solely on yellow or green sputum color in the absence of fever, dyspnea, or radiographic evidence of pneumonia. 1, 2
• Do not assume a single etiology—chronic productive cough frequently has multiple contributing factors that must all be addressed. 4
• Failure to obtain chest radiograph and spirometry when cough persists >8 weeks delays appropriate diagnosis and treatment. 4
• Neglecting medication review—ACE inhibitors cause cough in 5–50% of users, with resolution typically occurring within 26 days (up to 40 weeks) after discontinuation. 4