What are the differential diagnoses and treatment options for a patient with bronchitis, considering both infectious and non-infectious causes, including chronic obstructive pulmonary disease (COPD) and occupational exposures?

Differential Diagnosis for Bronchitis

Primary Diagnostic Considerations

The differential diagnosis for bronchitis must distinguish between acute viral bronchitis (which accounts for >90% of cases), acute exacerbations of chronic bronchitis/COPD, asthma or its exacerbation, pneumonia, and less common entities including pertussis, occupational/environmental exposures, and bronchiolitis. 1, 2, 3

Acute vs. Chronic Bronchitis Distinction

• Acute bronchitis presents as cough with or without sputum production lasting 2-3 weeks, typically viral in etiology (89-95% of cases), with constitutional symptoms resolving within 3-7 days 1, 4, 3
• Chronic bronchitis requires cough and sputum expectoration occurring on most days for at least 3 months per year for at least 2 consecutive years, typically caused by cigarette smoke or prolonged irritant exposure 1
• If cough persists beyond 3 weeks, transition to subacute cough warrants reassessment for alternative diagnoses; beyond 8 weeks becomes chronic cough requiring systematic evaluation 2, 4

Critical Differential: Asthma (Most Commonly Missed)

• Asthma is misdiagnosed as acute bronchitis in approximately one-third of patients presenting with acute cough 2, 5
• In retrospective studies, 65% of patients with recurrent "acute bronchitis" episodes (≥2 episodes in past 5 years) actually had undiagnosed mild asthma 2, 5
• Distinguishing features: asthma presents with progressively worsening dyspnea, wheezing, chest tightness, and symptoms that characteristically worsen at night or with triggers, whereas bronchitis manifests predominantly as constant cough 5
• Spirometry or peak expiratory flow measurement is essential: bronchodilator response showing ≥12% and ≥200 mL improvement in FEV1, or ≥20% improvement in PEF, indicates asthma 5

Acute Exacerbations of Chronic Bronchitis (AECB)

• Occurs in patients with established chronic bronchitis who develop acute worsening of symptoms 1
• Bacterial pathogens (H. influenzae, S. pneumoniae, M. catarrhalis) can be isolated from distal airways in 50% of AECB cases 6, 7
• Viruses account for approximately one-third of acute exacerbations, with or without superimposed bacterial infection 6, 7
• Pseudomonas aeruginosa becomes more prevalent in patients with severe underlying disease (FEV1 <50%), advanced age (>65 years), or recurrent exacerbations 6

Pneumonia

• Fever persisting beyond 3 days strongly suggests bacterial superinfection or pneumonia rather than uncomplicated viral bronchitis 4
• Chest radiograph is essential to rule out pneumonia, malignancy, or other structural abnormalities 2

Pertussis (Bordetella pertussis)

• Must be considered if paroxysms of coughing, post-tussive vomiting, or inspiratory whooping sound are present 2
• Diagnosis should be made when cough lasts >2 weeks with these characteristic features unless another diagnosis is proven 2

Upper Airway Cough Syndrome (UACS)

• At 3 months duration, persistent dry cough requires systematic evaluation for UACS as a primary cause 2
• Look for throat clearing, sensation of postnasal drip, nasal discharge, or rhinosinusitis symptoms 2
• Pathogenesis involves persistent inflammation of nose and paranasal sinuses following viral infection 2

Gastroesophageal Reflux Disease (GERD)

• May be triggered or exacerbated by vigorous coughing from initial viral illness 2
• Look for heartburn, regurgitation, or cough worsening after meals or when supine 2

Occupational and Environmental Bronchitis

• Occupational bronchitis has a differential diagnosis including nonoccupational bronchitis and requires comprehensive occupational history 1
• Common exposures include laboratory animal workers (endotoxin exposure), bakers (wheat, egg, enzymes), healthcare workers (natural rubber latex), and workers exposed to acid anhydrides, acrylic compounds, and diisocyanates 1
• Relatively low workplace respiratory irritant exposures may induce cough from mucous membrane irritation (sick building syndrome, bioaerosols, endotoxins, fungal glucans, solvents) 1

Bronchiolitis (Small Airways Disease)

• In patients with cough and incomplete or irreversible airflow limitation, direct or indirect signs of small airways disease on HRCT scan, or purulent secretions on bronchoscopy, nonbronchiectatic suppurative airways disease (bronchiolitis) should be suspected 1
• The top two causes of bronchiolitis are infection and aspiration 8
• Direct HRCT signs include dilation or airway wall thickening with nodular branching (2-4 mm) and "tree-in-bud" abnormalities 1
• Indirect HRCT signs include air-trapping (mosaic attenuation on expiration scans) or subsegmental atelectasis 1
• Specific causes include: infectious bronchiolitis (viral or bacterial), toxic/antigenic exposure, drug-related, post-transplant, collagen-vascular disease-associated, or hypersensitivity pneumonitis 1, 9

Hypersensitivity Pneumonitis

• Consider in patients with appropriate exposure history (organic dusts, birds, mold) and cellular bronchiolitis pattern 1
• Histologic features include small airway distribution, cellular interstitial inflammation consisting mostly of lymphocytes, and poorly formed non-necrotizing granulomas 1

Diagnostic Algorithm

Initial Assessment

• Complete exposure history: cigarette/cigar/pipe smoke, passive smoke, occupational hazards, environmental irritants 1
• Temporal classification: acute (<3 weeks), subacute (3-8 weeks), or chronic (>8 weeks) 2, 4
• Recurrence pattern: ≥2 similar episodes in past 5 years suggests asthma rather than repeated infections 2, 5

Objective Testing

• Chest radiograph to exclude pneumonia, malignancy, structural abnormalities 2
• Spirometry to evaluate for asthma or obstructive lung disease; normal baseline does not exclude asthma if FEV1 ≥70% predicted and clinical suspicion remains high 5
• HRCT with expiratory cuts if bronchiolitis suspected based on incomplete airflow limitation or purulent secretions 1
• Bronchoscopy required before excluding bacterial suppurative airways disease when more common causes have been excluded 1

When to Pursue Specific Diagnoses

• Pertussis testing: cough >2 weeks with paroxysms, post-tussive vomiting, or whooping 2
• Surgical lung biopsy: when combination of clinical syndrome, physiology, and HRCT findings do not provide confident diagnosis of bronchiolitis 1
• Sinus aspiration: for patients with suspected bacterial sinusitis who fail to respond after 72 hours of antimicrobial therapy 1

Treatment Implications Based on Diagnosis

Acute Viral Bronchitis

• Routine antibiotic therapy is NOT indicated as viruses cause >90% of cases 5, 3
• Antibiotics reduce cough duration by only approximately 0.5 days while exposing patients to adverse effects 4, 3
• Symptomatic treatment only; antitussives provide short-term relief 1
• Patient education: expect cough to persist 10-14 days after visit, resolving by 3 weeks 4

Asthma Exacerbation

• Oral corticosteroids (prednisone 40-60 mg daily for 5-7 days) for inadequate response to bronchodilators 5
• Classify severity immediately using objective lung function measures to determine treatment intensity 5

Acute Exacerbations of Chronic Bronchitis

• Prolonged antibiotic therapy improves cough in infectious bacterial bronchiolitis 1
• Fluoroquinolones should be first-line for patients with complicated chronic bronchitis (FEV1 <50%, age >65 years, recurrent exacerbations, co-morbid illness) 6

Toxic/Antigenic Exposure or Drug-Related Bronchiolitis

• Cessation of exposure or medication plus corticosteroid therapy for those with physiologic impairment 1

Critical Pitfalls to Avoid

• Do not assume persistent cough at 3 months is still "postinfectious cough"—this diagnosis is only valid for 3-8 weeks post-infection 2, 4
• Do not miss underlying asthma, which is the most commonly overlooked diagnosis in patients with recurrent "bronchitis" 2, 5
• Do not prescribe antibiotics for uncomplicated acute bronchitis unless bacterial sinusitis or pertussis is specifically suspected 2, 3
• Purulent sputum does NOT indicate bacterial infection in acute bronchitis—it occurs in 89-95% of viral cases and does not alter natural course 4
• Do not overlook occupational exposures—take comprehensive occupational history as almost every nonoccupational respiratory disease has an occupational equivalent 1