What is the differential diagnosis and treatment for a cough triggered by sensitivity to smells?

Cough Triggered by Sensitivity to Smells: Differential Diagnosis and Treatment

Cough triggered by smells represents cough hypersensitivity syndrome, a disorder characterized by troublesome coughing provoked by low-level chemical exposures including scents, perfumes, and aerosols, and should be managed by systematically treating the most common underlying causes: upper airway cough syndrome (UACS), asthma, non-asthmatic eosinophilic bronchitis (NAEB), and gastroesophageal reflux disease (GERD). 1

Understanding the Pathophysiology

The triggering of cough by smells, scents, and aerosols indicates a sensitized or hypersensitive cough reflex, which is central to understanding chronic cough. 1 This hypersensitivity state occurs when chemosensitive receptors in the airways become abnormally responsive to stimuli that would not normally provoke coughing. 1

• Patients typically describe triggering by low-level physical and chemical stimuli including scents, odors, perfumes, sprays, aerosols, changes in air temperature, and exercise. 1
• This feature is often the most troublesome cough-associated problem for patients and significantly impairs their quality of life. 1
• The concept of cough hypersensitivity syndrome parallels neuropathic pain, where cough triggered by relatively inoffensive stimuli (allotussia) is similar to allodynia, and excessive coughing (hypertussia) resembles hyperalgesia. 1

Differential Diagnosis: The "Big Four" Causes

You must systematically evaluate and treat the four most common causes of chronic cough with hypersensitivity features: 1, 2

1. Upper Airway Cough Syndrome (UACS/Postnasal Drip Syndrome)

• Patients may report frequent throat clearing, sensation of postnasal drip, or throat irritation. 1
• The absence of subjective postnasal drip symptoms does NOT rule out UACS as the cause. 1
• Initial treatment: First-generation antihistamine/decongestant combination (not second-generation antihistamines, which are less effective for cough). 1, 2

2. Asthma or Cough-Variant Asthma

• Cough may be worsened by cold air, exercise, or strong odors. 1, 3
• Patients with asthmatic cough more frequently report "cold air" and "fatigue/stress" as triggers compared to non-asthmatic coughers. 3
• The medical history alone is unreliable for diagnosing or excluding asthma. 1
• Diagnostic approach: Spirometry with bronchodilator response; if normal, perform methacholine challenge testing to confirm airway hyperresponsiveness. 1
• Patients marking "cold air" as a trigger show greater airway sensitivity to methacholine and higher exhaled nitric oxide levels. 3

3. Non-Asthmatic Eosinophilic Bronchitis (NAEB)

• Presents with chronic cough and eosinophilic airway inflammation but WITHOUT airflow obstruction or airway hyperresponsiveness. 4
• Responds well to inhaled corticosteroids. 4
• Requires sputum eosinophil count or exhaled nitric oxide measurement for diagnosis. 4

4. Gastroesophageal Reflux Disease (GERD)

• Cough may occur with eating, postprandially (within 10 minutes after meals), or with phonation (talking, laughing, singing). 1
• Patients with "spices" and "meals" as triggers more frequently have GERD-related cough. 3
• The absence of dyspepsia does NOT rule out reflux as the cause of cough. 1
• Cough on phonation suggests GERD due to lack of diaphragmatic closure of the lower esophageal sphincter. 1
• Treatment: Empiric proton pump inhibitor therapy plus dietary/lifestyle modifications. 2

Critical Initial Steps

Medication Review

• Immediately assess for ACE inhibitor use and discontinue if present. 1, 2
• ACE inhibitor-induced cough can take weeks to months to resolve after discontinuation (median 26 days). 1, 2

Smoking Status

• Current smokers should receive counseling and assistance with cessation, as most experience cough resolution within 4 weeks of quitting. 1, 2

Chest Radiograph

• Obtain chest X-ray to exclude malignancy, pneumonia, and other serious pulmonary conditions before embarking on empiric treatment. 1, 2

Treatment Algorithm

Because multiple causes often coexist, therapy must be given in sequential and additive steps: 1

1. Start with first-generation antihistamine/decongestant for presumed UACS (e.g., chlorpheniramine with pseudoephedrine). 1, 2

2. If cough persists after 1-2 weeks, add asthma evaluation and treatment:

   • Perform spirometry ± methacholine challenge. 1
   • Initiate inhaled corticosteroids and bronchodilators if asthma is confirmed or highly suspected. 1

3. If cough continues, add empiric GERD treatment:

   • Proton pump inhibitor twice daily plus dietary modifications (avoid late meals, elevate head of bed, avoid trigger foods). 2
   • GERD treatment may require 2-3 months for full effect. 1

4. Consider NAEB if eosinophilia is present:

   • Check sputum eosinophils or exhaled nitric oxide. 4
   • Treat with inhaled corticosteroids. 4

Refractory Cough Hypersensitivity Syndrome

If cough persists despite treating all common causes, consider neuromodulatory therapy: 1

• The European Respiratory Society conditionally recommends a trial of neuromodulatory drugs (gabapentin, pregabalin, amitriptyline, or morphine) for chronic refractory cough, based on the concept that cough hypersensitivity parallels neuropathic pain. 1
• This recommendation is based on low-quality evidence but reflects the mechanistic understanding of central sensitization. 1

Common Pitfalls to Avoid

• Do not rely on cough character or timing for diagnosis—these features have poor predictive value. 1
• Do not assume a single cause—up to 62% of patients with chronic cough have multiple contributing factors requiring additive treatment. 1
• Do not use second-generation antihistamines (cetirizine, loratadine, fexofenadine) for cough—they are ineffective; first-generation agents with anticholinergic properties are required. 1, 2
• Do not dismiss smell-triggered cough as psychogenic—it represents genuine cough reflex hypersensitivity with neurophysiologic basis. 1
• Do not expect immediate GERD treatment response—reflux-related cough may take 2-3 months to improve. 1
• Female patients exhibit heightened cough responses to chemical stimuli, which may explain the female predominance among chronic cough patients. 1

Special Considerations

• The hypersensitive state may be transient (as with viral infections lasting <3 weeks) or become chronic (>8 weeks). 1
• Resolution of sensitization—whether through natural resolution, medication withdrawal, or effective treatment of underlying causes—is critical to cough improvement. 1
• Patients often describe abnormal sensations including persistent throat tickle, itch, or "lump" sensation. 1