Treatment Protocol for Dry Cough

Step 1: Classify by Duration

Step 2: Targeted Etiology-Directed Treatment

1. Upper Airway Cough Syndrome (UACS) / Post-Nasal Drip

• Allergic rhinitis: Topical nasal corticosteroids + antihistamines
• Non-allergic/vasomotor rhinitis: First-generation (anticholinergic) antihistamines + decongestants (note: non-sedating antihistamines are less effective here since they lack anticholinergic activity)
• Sinusitis: Antibiotics + nasal irrigation/saline; nasal anticholinergics (ipratropium nasal spray)
• Response expected within 2-4 weeks

2. Gastroesophageal Reflux Disease (GERD)

• Conservative: Weight reduction, high-protein/low-fat diet, elevate head of bed, avoid coffee and smoking
• Pharmacologic: H2-receptor antagonists or proton pump inhibitors (PPI) for ≥2 months for patients with objective evidence of acid exposure or heartburn
• Prokinetics (domperidone, metoclopramide) have insufficient evidence and potential side effects - not routinely recommended
• Antireflux surgery (laparoscopic fundoplication): evidence is unclear for cough that fails medical therapy
• Murray & Nadel's Textbook of Respiratory Medicine

3. Asthma / Cough-Variant Asthma

• Inhaled corticosteroids (ICS) + long-acting beta2-agonist (LABA): First-line, maintain for 3-6 months
• Short-acting beta2-agonists (SABA): For episodic relief
• Leukotriene receptor antagonists (e.g., montelukast): Effective adjunct in cough-variant asthma
• Oral corticosteroids (prednisolone 40 mg/day for 2 weeks): Trial for patients not responding to adequate inhaled therapy
• Murray & Nadel's Textbook of Respiratory Medicine, p. 874

4. Eosinophilic Bronchitis

• Inhaled corticosteroids: Responds well; leukotriene inhibitors may be added
• Harrison's, p. 317

5. ACE Inhibitor-Induced Cough

• Stop the ACE inhibitor - this is the first and most important step
• Switch to an angiotensin II receptor blocker (ARB): Resolves cough in nearly all cases; ARBs do not accumulate bradykinin/substance P
• Cough usually resolves within days to weeks after discontinuation
• Murray & Nadel's Textbook of Respiratory Medicine, p. 875

6. Post-Infectious Cough

• Macrolide antibiotics or trimethoprim-sulfamethoxazole: Eliminates B. pertussis but does not alter clinical course of established cough
• Inhaled corticosteroids: Often tried, but with variable success
• Oral steroids: May be effective in some patients
• Most cases resolve spontaneously

7. Chronic Bronchitis / COPD

• Smoking cessation: Most effective intervention; cough typically reduces within 4-5 weeks
• SABA/LABA + anticholinergics: For airflow obstruction and dyspnea
• ICS + LABA: For small airway inflammation
• Mucolytics: May reduce exacerbation frequency

8. Idiopathic Pulmonary Fibrosis (IPF)

• Treat comorbid GERD, UACS, and asthma aggressively
• Pirfenidone (anti-fibrotic): Shown in observational studies to reduce cough frequency
• Thalidomide: Small trial showed some benefit
• Conventional opioid antitussives often ineffective in IPF - Murray & Nadel's, p. 875

Step 3: Symptomatic / Antitussive Therapy

Non-Pharmacologic

• Speech and language therapy / cough suppression therapy: Breathing exercises, vocal hygiene, laryngeal retraining, psychoeducational counseling - effective for all chronic cough patients; especially effective in those with concurrent muscle tension dysphonia or vocal cord dysfunction
• Murray & Nadel's, p. 876

Pharmacologic Antitussives

Neuromodulators (for Chronic Refractory Cough Affecting Quality of Life)

Step 4: Investigations if Cough Persists

1. Chest CT - to detect tumors, early ILD, bronchiectasis, atypical mycobacterial infection missed on plain X-ray
2. Spirometry with bronchodilator response - to confirm/exclude asthma
3. Methacholine challenge - if spirometry normal but asthma suspected
4. 24-hour pH monitoring / impedance - to objectively document GERD
5. Sputum eosinophil count - if eosinophilic bronchitis suspected
6. Exhaled nitric oxide (FeNO) - elevated levels predict response to inhaled steroids

Emerging Therapies (2025 Evidence)

• Camlipixant (P2X3 receptor antagonist): Phase 2b SOOTHE trial showed significant reduction in refractory chronic cough - published Am J Respir Crit Care Med 2025
• Nalbuphine ER: Phase 2a RIVER trial showed 56% placebo-adjusted reduction in cough frequency in refractory chronic cough, including IPF patients; most common side effects were constipation, nausea, and somnolence
• Speech therapy + neuromodulation combination: Recommended as standard for unexplained or refractory cough per a 2025 NEJM review

Quick Reference Summary Table

Dry Cough WITH Voice Change - Differential Diagnosis & Treatment Protocol

Red Flags - Urgent Referral Needed

• Hoarseness + dry cough lasting >3 weeks in a smoker or drinker
• Progressive voice change with dysphagia or neck lump
• Stridor (suggests airway compromise)
• Hemoptysis
• Weight loss, night sweats
• History of head/neck irradiation

Any hoarseness lasting >3 weeks warrants flexible nasolaryngoscopy to exclude malignancy - Bailey and Love's Short Practice of Surgery 28th Ed

Differential Diagnosis: Dry Cough + Voice Change

Top Causes (Most Common First)

Mandatory First Investigation

• Posterior laryngeal erythema/edema (LPR)
• Vocal cord nodules, polyps, or granulomas
• Vocal cord paralysis/paresis
• Laryngeal mass or lesion
• Bailey and Love's; Textbook of Family Medicine 9e

Cause-Specific Treatment Protocol

1. Laryngopharyngeal Reflux (LPR) - MOST COMMON CAUSE

• Weight reduction
• Avoid late meals (no food 3 hours before lying down)
• Elevate head of bed
• Eliminate: coffee, alcohol, chocolate, fatty/spicy foods, carbonated drinks, peppermint
• Stop smoking

• PPI (e.g., omeprazole, lansoprazole, esomeprazole) twice daily, 30-60 min before meals - note: must be taken before meals for maximal efficacy
• Duration: minimum 3-4 months (LPR requires longer treatment than GERD)
• For non-acid reflux: alginates (e.g., Gaviscon) after meals and at bedtime
• H2-receptor antagonists (ranitidine, famotidine): secondary option or add-on at bedtime
• Patients not responding to max-dose PPI: refer for 24-hour pH-impedance monitoring
• Cummings Otolaryngology; K.J. Lee's Essential Otolaryngology, p. 224

• Adequate systemic hydration (≥8 glasses/day - "pee pale" principle) - reduces mucus viscosity and improves vocal fold vibration
• Avoid caffeine (diuretic effect)
• Guaifenesin (expectorant) may thin secretions in some patients
• Avoid tobacco
• Cummings Otolaryngology, p. 812

2. Vocal Cord Nodules / Polyps

1. Voice therapy (primary treatment): counseling, vocal reeducation, relative voice rest, psychotherapeutic rehabilitation - response expected over 12-18 months
2. Control acid reflux (PPI/lifestyle)
3. Avoid cigarette smoke and other irritants
4. Surgery (endoscopic removal): only for patients failing voice therapy; always followed by postoperative voice therapy

• Textbook of Family Medicine 9e, p. 441

3. Recurrent Laryngeal Nerve (RLN) Palsy

• Bronchial/lung tumors (most common cause of left RLN palsy)
• Thyroid tumors or goiter
• Esophageal tumors
• Mediastinal lymphadenopathy
• Neck surgery or trauma (iatrogenic)
• Aortic aneurysm
• Bailey and Love's, p. 686; Textbook of Family Medicine 9e

• Treat the underlying cause
• Unilateral palsy: ~20-25% recover spontaneously; if compensation does not occur, consider medialization thyroplasty or vocal fold injection (injection laryngoplasty)
• Bilateral palsy: surgical options - cordotomy or arytenoidectomy (ideally endoscopic with CO2 laser); tracheostomy in emergency

4. Laryngeal Carcinoma

• Direct laryngoscopy + biopsy (confirms histology)
• CT and MRI (extent and nodal involvement)

• Early (T1/T2): Single modality - radiotherapy OR transoral laser resection (similar ~95% local control); surgery preferred (day case, faster, preserves function)
• Advanced (T3/T4): Combined surgery + radiotherapy ± chemotherapy; total laryngectomy may be needed for large tumours

5. ICS-Induced Dysphonia

• Gargle and rinse mouth with water after each dose
• Use a spacer device
• Reduce dose if possible
• Switch to a different ICS formulation
• Discontinue if hoarseness persists and clinical status allows

6. Vocal Cord Dysfunction (VCD) / Inducible Laryngeal Obstruction

• Speech and language therapy (primary treatment)
• Breathing retraining techniques
• Address underlying anxiety/psychological factors
• Heliox may help during acute episodes

Diagnostic Approach Summary

Dry cough + voice change
         |
         v
History: Duration? Smoking? Reflux? Drug history (ACE-i, ICS)? 
         Vocal use? Progressive? Red flags?
         |
         v
FLEXIBLE NASOLARYNGOSCOPY (mandatory)
         |
    _____|_____________________________
    |                                  |
Normal larynx                  Abnormal larynx
    |                                  |
Consider:                     Refer to ENT:
- LPR (treat empirically)     - Malignancy workup
- GERD                        - Nodule/polyp therapy
- Post-nasal drip             - RLN palsy workup
- ACE inhibitor               - Laryngoscopic biopsy
- Subglottic/tracheal lesion
    |
If normal + no response to empiric LPR treatment:
→ 24-hr pH impedance study
→ CT chest/neck (RLN palsy, mediastinal mass)
→ Thyroid function tests

Key Practical Points

1. Never dismiss hoarseness >3 weeks - flexible nasolaryngoscopy is non-negotiable
2. LPR is the most common benign cause of this symptom pair; empiric PPI BID × 3 months is reasonable in low-risk patients
3. ACE inhibitors cause dry cough that can traumatize vocal cords secondarily - always check drug history
4. Left-sided RLN palsy should raise suspicion for a thoracic/mediastinal cause (long left RLN course around the aortic arch)
5. ICS are a frequently missed drug cause of voice change - always ask about inhalers