What is the best course of treatment for a patient with a persistent cough, considering potential underlying respiratory conditions such as asthma (Asthma), chronic obstructive pulmonary disease (COPD), or pneumonia, and taking into account their medical history, including recent illnesses, smoking history, and exposure to environmental irritants?

Management of Persistent Cough

Begin by systematically evaluating and treating the four most common causes of chronic cough—upper airway cough syndrome (UACS), asthma, gastroesophageal reflux disease (GERD), and non-asthmatic eosinophilic bronchitis (NAEB)—using sequential and additive empiric therapy, as multiple causes frequently coexist. 1

Initial Critical Assessment

Immediately determine if this represents a life-threatening condition requiring urgent intervention:

• Rule out pneumonia by assessing for fever, tachypnea (respiratory rate >25/min), tachycardia (heart rate >110/min), dyspnea, inability to complete sentences, chest pain, and new infiltrates on imaging 1, 2, 3
• Evaluate for lung cancer, particularly in smokers with finger clubbing, pleural effusion, or lobar collapse on examination, as cough is the fourth most common presenting feature 1
• Assess for COPD exacerbation by evaluating increased dyspnea, increased sputum volume and purulence, respiratory rate >25/min, and heart rate >110/min 2
• Check medication history for ACE inhibitor use, as this causes cough in a significant proportion of patients and resolves with cessation (median 26 days, but may take up to 40 weeks) 1

Essential History and Physical Examination Elements

Document these specific findings:

• Smoking history and current status, as smokers with persistent cough are at risk for developing COPD 1
• Occupational and environmental exposures to workplace sensitizers, dust, chemicals, or irritants that can cause chronic cough 1
• Sputum characteristics: purulent versus mucoid, volume changes 2
• Respiratory rate, oxygen saturation, ability to speak in full sentences 2
• Chest auscultation for wheezes (suggesting asthma), coarse crackles (bronchiectasis), or fine late inspiratory crackles (diffuse parenchymal lung disease) 1, 2

Baseline Investigations

Obtain chest radiograph to rule out tuberculosis, chronic fungal infection, bronchiectasis, lung abscess, bronchogenic carcinoma, or pneumonia 3, 4

Perform spirometry to identify obstructive patterns (asthma, chronic bronchitis, bronchiectasis) or restrictive defects (pulmonary fibrosis, sarcoidosis, pneumoconiosis) 4, 5

Sequential Empiric Treatment Algorithm

Because more than one cause is frequently present, use additive therapy rather than switching between treatments: 1

Step 1: Discontinue ACE Inhibitors

• Switch to angiotensin II receptor blocker if ACE inhibitor is being used, as most patients tolerate this alternative 1
• Wait 26 days to 40 weeks for cough resolution after discontinuation 1

Step 2: Treat Upper Airway Cough Syndrome (UACS)

• Initiate first-generation antihistamine/decongestant combination (not newer non-sedating antihistamines, which are ineffective) 3, 5
• Evaluate for chronic rhinosinusitis, even if physical examination and sinus radiographs are normal, as this is one of the most common causes 4

Step 3: Treat Asthma or NAEB

• Start inhaled bronchodilators and inhaled corticosteroids as initial therapy 3
• Add leukotriene receptor antagonist for refractory cases before escalating to systemic corticosteroids 3
• For NAEB specifically, inhaled corticosteroids are first-line treatment 3

Step 4: Treat GERD

• Initiate empiric proton pump inhibitor therapy without testing if reflux symptoms are present 5
• Continue treatment for adequate duration (4-6 weeks minimum) before determining response 6

Special Considerations for Specific Underlying Conditions

COPD Exacerbation with Productive Cough

• Administer nebulized salbutamol 2.5-5 mg every 4-6 hours as first-line bronchodilator therapy 2
• Add ipratropium bromide 250-500 µg every 4-6 hours for severe exacerbations or poor response 2
• Prescribe systemic corticosteroids (prednisone 30-40 mg orally daily for 5-7 days) for COPD exacerbation, monitoring blood glucose 2
• Initiate antibiotic therapy (amoxicillin-clavulanate 875/125 mg twice daily plus azithromycin 500 mg daily for 5-7 days) if increased sputum purulence is present 2
• Target oxygen saturation to 88-92% to prevent hypercapnic respiratory failure 2

Pertussis Infection

• Consider pertussis as 10% of chronic cough cases have positive nasal swabs for Bordetella 1

Bronchiectasis

• Evaluate for "dry" bronchiectasis even without sputum production, though prevalence in specialist cough clinics is only 4% 1

Critical Medications to AVOID

Do not use cough suppressants (including dextromethorphan), expectorants, mucolytics, antihistamines alone, or inhaled corticosteroids alone for productive cough, as they have no clear benefit and may impair secretion clearance 2, 3, 7

Avoid excessive oxygen administration in COPD patients to prevent hypercapnic respiratory failure 2

Do not extend corticosteroids beyond 5-7 days due to significant side effect risk in elderly patients 2

Indications for Hospital Admission

Admit if any of the following are present:

• Age >65 with COPD, diabetes, heart failure, confusion 2
• Pulse >100, temperature >38°C, respiratory rate >30, blood pressure <90/60 2
• Inability to maintain oxygenation, worsening dyspnea, or pH <7.26 with rising PaCO2 2

When Initial Treatment Fails

If cough persists after 4-6 weeks of appropriate empiric treatment for the five most common causes:

• Consider bronchoscopy to evaluate for occult airway disease (endobronchial tumor, sarcoidosis, suppurative infection, eosinophilic or lymphocytic bronchitis) 1
• Evaluate for uncommon causes: non-acid reflux disease, swallowing disorder, congestive heart failure, habit cough 1
• Consider high-resolution CT scan and bronchoscopic evaluation 3
• Refer to pulmonologist or cough specialist before labeling as unexplained/idiopathic cough 1

Refractory Chronic Cough Management

For patients who remain undiagnosed or refractory after complete workup:

• Initiate low-dose morphine (preferred), gabapentin, or pregabalin for neuromodulatory therapy 6
• Refer for speech pathology/cough control therapy 8, 6

Common Pitfalls to Avoid

Do not rely on cough timing or characteristics for diagnosis, as these have little diagnostic value 1, 3

Do not treat only one potential cause—remember that multiple factors frequently contribute and sequential additive therapy is essential 1, 3

Do not use newer non-sedating antihistamines for cough, as they are ineffective 3

Do not forget to reassess smoking cessation and environmental irritant avoidance at every visit 1, 5