What are the different diagnoses and treatments for cough?

Differential Diagnosis and Treatment of Cough

Classification by Duration

Cough should be classified by duration to guide your diagnostic approach: acute (<3 weeks), subacute (3-8 weeks), or chronic (>8 weeks), as this fundamentally determines your evaluation strategy. 1

Initial Assessment for All Cough Types

Start by identifying three critical historical factors that immediately narrow your differential:

• ACE inhibitor use - Stop the medication regardless of temporal relationship; cough typically resolves within days to 2 weeks (median 26 days) 1, 2
• Current smoking status - Counsel on cessation; most smokers experience cough resolution within 4 weeks 1
• Signs of serious/life-threatening disease - Look for hemoptysis, weight loss, fever, breathlessness, or recurrent pneumonia requiring immediate workup 1, 3

Note that cough characteristics (timing, quality, productive vs. nonproductive) have poor diagnostic sensitivity and specificity, so don't rely on them for diagnosis. 1

Acute Cough (<3 Weeks)

Most Common Causes

• Upper respiratory tract infections (common cold, lower respiratory tract infection) 1
• Exacerbations of pre-existing conditions (COPD, asthma, bronchiectasis) 1
• Pneumonia or pulmonary embolism (life-threatening - rule out first) 1
• Environmental/occupational irritant exposure 1

Treatment Approach

• First-generation antihistamine/decongestant combination (e.g., brompheniramine with sustained-release pseudoephedrine) - proven in double-blind placebo-controlled trials to decrease cough severity and hasten resolution 1, 3
• Naproxen can favorably affect cough symptoms 1, 3
• Dextromethorphan for symptomatic relief when other measures fail 3, 4
• Avoid newer-generation nonsedating antihistamines - they are ineffective for cough 1

Important Caveat

Don't diagnose bacterial sinusitis during the first week of symptoms, as viral URIs can mimic bacterial infection with similar imaging abnormalities. 1

Subacute Cough (3-8 Weeks)

Diagnostic Algorithm

First determine if the cough is postinfectious or non-infectious. 1, 2

If Postinfectious:

Consider these mechanisms in order:

• Persistent upper airway cough syndrome (UACS) from postnasal drip 1, 2
• Transient bronchial hyperresponsiveness 1
• Asthma exacerbation 1
• Bordetella pertussis (look for paroxysmal cough with post-tussive vomiting or inspiratory whooping) 5
• Acute exacerbation of chronic bronchitis 1

If Non-infectious:

Manage as chronic cough (see below). 1, 2

Treatment Approach

• Inhaled ipratropium bromide as first-line for postinfectious cough 5
• First-generation antihistamine/decongestant for UACS 2, 5
• Inhaled corticosteroids if cough adversely affects quality of life and persists despite ipratropium 5
• Oral prednisone 30-40 mg daily for short period in severe paroxysms after ruling out other common causes 5
• Macrolide antibiotics (erythromycin, clarithromycin, roxithromycin) if pertussis suspected - must be given early 5
• Central-acting antitussives (codeine, dextromethorphan) when other measures fail 5

Chronic Cough (>8 Weeks)

The "Big Four" Causes (Account for ~90% of Cases)

Systematically treat these in sequential and additive steps, as multiple causes often coexist: 1, 6

1. Upper Airway Cough Syndrome (UACS) - formerly called postnasal drip syndrome
2. Asthma (including cough-variant asthma)
3. Non-asthmatic eosinophilic bronchitis (NAEB)
4. Gastroesophageal reflux disease (GERD)

Diagnostic Workup

Initial Studies (Obtain in All Patients):

• Detailed history and physical examination 1, 7
• Chest radiograph 1, 6
• Spirometry 6, 7
• Exhaled nitric oxide 7
• Blood eosinophil count 7
• Validated cough severity and quality of life instruments 7

Sequential Empiric Treatment Protocol

Start with first-generation antihistamine/decongestant for presumed UACS before extensive workup. 1

Step 1: UACS Treatment

• First-generation antihistamine/decongestant (not newer nonsedating antihistamines) 1, 2
• If no response, obtain sinus imaging - chronic sinusitis can be clinically silent with nonproductive cough 1
• Treat specific identified rhinosinus disease 1

Step 2: Asthma Evaluation (If UACS Treatment Fails)

• Medical history is unreliable for ruling in/out asthma 1
• Bronchoprovocation challenge (BPC) if spirometry doesn't show reversible airflow obstruction 1, 2
• If BPC unavailable, give empiric trial of inhaled bronchodilators plus inhaled corticosteroids 1, 2
• Diagnosis confirmed only by cough resolution with treatment 1

Step 3: NAEB Evaluation (If UACS and Asthma Ruled Out/Treated)

• Induced sputum test for eosinophils (properly performed) 1, 2
• If unavailable, empiric trial of inhaled corticosteroids 1, 2
• Note: Steroid response doesn't distinguish between asthma and NAEB 1

Step 4: GERD Treatment

• Empiric proton pump inhibitor therapy plus diet/lifestyle modifications 2, 6
• Consider 24-hour pH probe if diagnosis uncertain 8

Maintain Partially Effective Treatments

Because multiple causes frequently coexist, continue all treatments that provide partial benefit while adding new therapies. 1

When Initial Workup Fails

If cough persists after 4-6 weeks of empiric treatment: 7

Advanced Imaging and Procedures:

• High-resolution chest CT scan 1, 2
• Bronchoscopy 1
• ENT examination for upper airway pathology 8

Uncommon Causes to Consider:

• Tuberculosis (especially in high-prevalence areas) - obtain sputum smears/cultures for acid-fast bacilli 1
• Endemic fungal or parasitic infections 1
• Airway foreign body (abrupt onset) 1
• Bronchiectasis 6, 9
• Lung cancer 3
• Pulmonary edema 1

Refractory Chronic Cough

For patients with persistent cough despite negative evaluation and optimal treatment of identified causes, consider cough hypersensitivity syndrome. 7, 10

Treatment Options:

• Low-dose morphine (preferred) 7
• Gabapentin 7, 10
• Pregabalin 7, 10
• Speech therapy trial 10
• Emerging P2X3 receptor antagonists (gefapixant, camlipixant) currently under investigation 7

Special Populations

Immunocompromised Patients

• Use same initial algorithm but expand differential based on immune defect type 1
• HIV patients with CD4+ <200 cells/μL or those with unexplained fever/weight loss/thrush: suspect Pneumocystis pneumonia, tuberculosis, opportunistic infections 1

Peritoneal Dialysis Patients

Evaluate for increased prevalence of: 1

• GERD
• ACE inhibitor-induced cough
• Pulmonary edema
• Asthma exacerbated by β-blockers
• Infection

Critical Pitfalls to Avoid

• Don't make a diagnosis of "unexplained cough" or "idiopathic cough" until you've completed thorough evaluation for uncommon causes 1
• Don't use antibiotics for viral postinfectious cough - they have no role unless bacterial infection is documented 5
• Don't stop partially effective treatments when adding new therapies - multiple simultaneous causes are common 1
• Don't delay stopping ACE inhibitors - even if cough preceded the medication, the drug may now be perpetuating it 1
• Don't use cough suppressants in patients with reduced consciousness due to aspiration risk 5