What are the potential causes and management options for a patient with a chronic cough, considering underlying conditions such as gastroesophageal reflux disease (GERD), asthma, chronic obstructive pulmonary disease (COPD), and infections, particularly in those with a history of smoking or exposure to environmental toxins?

Chronic Cough: Causes and Management

Most Common Causes in Nonsmoking Adults

In immunocompetent nonsmoking adults with chronic cough (>8 weeks) and normal chest radiograph, three conditions account for 92-100% of cases: upper airway cough syndrome (UACS), asthma, and gastroesophageal reflux disease (GERD), either alone or in combination. 1, 2

Upper Airway Cough Syndrome (UACS)

• UACS is the most common single cause of chronic cough and can be completely "silent" with no nasal symptoms, caused by rhinosinusitis, allergic rhinitis, vasomotor rhinitis, or other rhinosinus conditions 1, 2
• The character, timing, or productivity of cough has no diagnostic value and should not be used to rule in or rule out any diagnosis 2

Asthma

• Asthma is the second most common cause and may present as "cough variant asthma" with cough as the only symptom—no wheezing or dyspnea is required for diagnosis 1, 2
• Diagnosis should be confirmed based on clinical response to empiric therapy with inhaled bronchodilators or corticosteroids 3

Gastroesophageal Reflux Disease (GERD)

• GERD is the third most common cause and can be "silent GERD" without heartburn or regurgitation, with cough as the sole manifestation 1, 2
• Up to 75% of patients with GERD-induced cough have no typical GI symptoms like heartburn, making the diagnosis easily missed 4
• Nocturnal symptoms are characteristic: cough exacerbated by meals, positional worsening when lying down, and improvement with head-of-bed elevation 4

Nonasthmatic Eosinophilic Bronchitis (NAEB)

• NAEB is an increasingly recognized important cause that should be considered early in evaluation, as it responds predictably to inhaled corticosteroids 1, 2

Critical Initial Screening

Medication History

• ACE inhibitors cause chronic cough in 2-17% of patients and should be discontinued first if the patient is taking one 4
• Cough can occur anytime within the first year of ACE inhibitor therapy 2
• Resolution typically occurs within a few days to 2 weeks of stopping the drug, but the median time is 26 days 1, 4

Smoking Status

• Cigarette smoking is commonly associated with chronic cough that typically meets the definition of chronic bronchitis 1
• Smoking cessation is almost always effective, with the majority of patients experiencing cough resolution within 4 weeks, though those with severe COPD may have persistent symptoms 1, 4

Chest Radiography

• A chest radiograph is essential to exclude malignancy, interstitial lung disease, tuberculosis (in endemic areas), or infection 1, 2
• If a specific cause is suggested from the chest radiograph (e.g., mass suggestive of lung cancer), this should be directly investigated 1

Algorithmic Management Approach

Step 1: Empiric Treatment for UACS

• Initiate a trial of a decongestant and first-generation antihistamine if UACS is suspected 3
• Assess response within 1-2 weeks 1

Step 2: Empiric Treatment for Asthma

• Trial of inhaled bronchodilators or corticosteroids if asthma is suspected 3
• Assess response within 1-2 weeks 1

Step 3: Empiric Treatment for GERD

• For patients fitting the clinical profile for GERD-related cough, initiate intensive antireflux therapy without testing first 1
• Intensive medical regimen includes: 1
  • Antireflux diet: no more than 45g fat in 24 hours, no coffee, tea, soda, chocolate, mints, citrus products (including tomatoes), or alcohol, no smoking, and limiting vigorous exercise that increases intra-abdominal pressure
  • Acid suppression with a proton pump inhibitor (PPI)
  • Prokinetic therapy (either initially or if no response to first two therapies)
  • Efforts to mitigate comorbid conditions like obstructive sleep apnea
• Response should be assessed within 1 to 3 months 1
• Minimum treatment duration is 8-12 weeks for extraesophageal GERD symptoms 4

Step 4: If Empiric Treatment Fails

• If empiric GERD treatment fails, it cannot be assumed that GERD has been ruled out; rather, objective investigation with 24-hour esophageal pH monitoring is recommended because empiric therapy may not have been intensive enough or medical therapy may have failed 1
• Proton pump inhibition may be effective when H2-antagonism has been ineffective 1
• Prokinetic therapy and diet, when added to proton pump inhibition, may be effective when proton pump inhibition alone has been ineffective 1

Step 5: Refractory Cases

• In patients with chronic cough due to GERD that has failed maximal medical therapy, antireflux surgery may be the only option for improvement or elimination of cough 1
• Antireflux surgery is recommended when: 1
  • 24-hour esophageal pH monitoring before treatment is positive
  • Patient fits the clinical profile suggesting GERD is the likely cause
  • Cough has not improved after minimum 3 months of intensive therapy
  • Serial pH monitoring or other objective studies show intensive medical therapy has failed to control reflux
  • Patient expresses that persisting cough does not allow satisfactory quality of life

Multiple Contributing Diagnoses

Up to 25% of patients have multiple contributing diagnoses, and all three common causes (UACS, asthma, GERD) must be considered in every patient regardless of symptoms. 2

Special Populations

Smokers with COPD

• If the patient has COPD, determine whether cough is part of an exacerbation versus chronic cough associated with stable COPD 1
• If exacerbation, therapy with antibiotics or corticosteroids needs to be considered 1

Endemic Areas

• Determine whether the patient is from an endemic area where tuberculosis or other diseases that can cause cough are more prevalent 1
• Ascertain any systemic signs such as fever, sweats, or weight loss 1
• History of cancer, tuberculosis, or AIDS is important to determine 1

Critical Pitfalls to Avoid

• Do not rule out GERD based on absence of heartburn—75% of reflux-related cough patients have no GI symptoms 4, 2
• Do not stop GERD treatment prematurely—extraesophageal GERD symptoms require minimum 8-12 weeks of intensive therapy, much longer than typical GERD 4
• Do not use short-term PPI trials (1-4 weeks) to diagnose GERD-related cough—these are inadequate for extraesophageal symptoms 4
• Do not forget to address comorbid sleep apnea, which can exacerbate both GERD and respiratory symptoms 4
• Do not assume nocturnal cough equals poorly controlled asthma—objective measurements show cough is suppressed during true sleep, and most "nocturnal" coughing occurs during brief awakenings 4

When to Refer

If cough persists after sequential empiric therapy for UACS, asthma, and GERD, or if red flags are present (fever, weight loss, hemoptysis, recurrent pneumonia), consider referral to pulmonologist or otolaryngologist and proceed to high-resolution CT scan and bronchoscopy if indicated. 1, 2