What is the best approach to treat intermittent cough in a patient with Parkinson's disease, considering potential interactions with medications such as levodopa (L-dopa) or dopamine agonists?

Treatment of Intermittent Cough in Parkinson's Disease

In patients with Parkinson's disease experiencing intermittent cough, first systematically evaluate and treat the three most common causes—upper airway cough syndrome (UACS), asthma, and gastroesophageal reflux disease (GERD)—using sequential empiric therapy, as cough characteristics lack diagnostic specificity and multiple causes frequently coexist. 1

Initial Diagnostic Approach

Start with medical history and chest radiograph to exclude serious pathology, then proceed with empiric treatment trials rather than extensive testing. 1

• Determine if the patient is taking ACE inhibitors, as these can cause chronic cough that resolves within days to 2 weeks (median 26 days) after discontinuation, regardless of temporal relationship to cough onset 1
• Assess smoking status, though less relevant in established Parkinson's patients 1
• Obtain chest X-ray to rule out masses, interstitial disease, or infection 1

Sequential Treatment Algorithm

First-Line: Upper Airway Cough Syndrome (UACS)

Begin with a first-generation antihistamine/decongestant combination for postnasal drip, as UACS is the most common cause of chronic cough (44% prevalence). 1

• Trial duration: 2-3 weeks minimum 1
• If partial response, continue while adding next therapy 1
• This approach is supported by decision analysis favoring sequential empirical treatment over extensive upfront testing 1

Second-Line: Asthma or Nonasthmatic Eosinophilic Bronchitis

If UACS treatment fails or provides only partial relief, add inhaled corticosteroids (ICS) with or without bronchodilators for asthma/NAEB. 1

• Asthma is the second most common cause of chronic cough 1
• Cough may be the sole manifestation of asthma without wheezing 1
• Trial duration: 2-4 weeks 1

Third-Line: Gastroesophageal Reflux Disease

For persistent cough despite UACS and asthma treatment, initiate high-dose proton pump inhibitor (PPI) therapy for GERD. 1, 2

• Start with once-daily PPI for 4-8 weeks 2
• If inadequate response, increase to twice-daily dosing 2
• Add prokinetic agent (metoclopramide) if minimal improvement with PPI alone 1, 2
• Critical caveat: Metoclopramide can worsen Parkinson's symptoms through dopamine receptor blockade—use with extreme caution and close monitoring in PD patients 2
• GERD is the third most common cause of chronic cough and may present without typical reflux symptoms 1, 2

Parkinson's-Specific Considerations

Avoid metoclopramide or use only with extreme caution in Parkinson's patients, as it antagonizes dopamine receptors and can precipitate or worsen parkinsonian symptoms. 2

• If prokinetic therapy is necessary for GERD-related cough, consider alternative agents or accept suboptimal GERD control 2
• Levodopa and dopamine agonists do not directly cause cough but may interact with cough treatments 3, 4
• Anticholinergic cough medications may compound anticholinergic burden if patient is on anticholinergic PD medications 5

Refractory Cough Management

If the above sequential approach fails after adequate trials (each 2-8 weeks), consider advanced antitussive therapies. 1

Pharmacologic Options for Refractory Cough:

1. Neuromodulators: Gabapentin or pregabalin have RCT support in chronic unexplained cough 1
2. Opiates: Morphine or codeine derivatives, titrated to acceptable side-effect profile 1
3. Peripherally-acting antitussives: Levodropropizine, moguisteine, or sodium cromoglycate where available 1
4. Local anesthetics: Nebulized lidocaine (5 mL of 0.2% tid) or bupivacaine (5 mL of 0.25% tid), avoiding food/drink for 1 hour post-treatment 1

Non-Pharmacologic Options:

• Speech pathology therapy has RCT support for chronic cough 1
• Physiotherapy interventions 1

Critical Pitfalls to Avoid

• Do not assume single etiology: Chronic cough is multifactorial in 25-62% of cases—maintain all partially effective treatments while adding sequential therapies 1
• Do not use metoclopramide liberally: This prokinetic can worsen Parkinson's motor symptoms through dopamine antagonism 2
• Do not discontinue treatments prematurely: Each empiric trial requires adequate duration (2-8 weeks depending on suspected cause) 1, 2
• Do not overlook ACE inhibitors: Stop these regardless of temporal relationship to cough onset 1
• Do not delay treatment for extensive testing: Sequential empiric therapy is more cost-effective and faster than upfront comprehensive testing 1

When to Pursue Further Investigation

If sequential empiric treatment of UACS, asthma, and GERD fails after adequate trials, obtain high-resolution CT chest to evaluate for bronchiectasis, interstitial lung disease, or occult airway pathology before labeling as unexplained cough. 1

• Consider bronchoscopy if HRCT shows abnormalities or remains unrevealing after complete workup 1
• Evaluate for uncommon causes: nonacid reflux, swallowing disorders, or habit cough based on clinical context 1