Why Your Patient’s Chronic Cough Isn’t Always Acid Reflux

Unmasking the Real Culprits Behind a Persistent Symptom
When a patient walks into the clinic complaining of a cough that has overstayed its welcome—lingering for weeks or even months—the reflex diagnosis in many practices is gastroesophageal reflux disease (GERD). It’s easy to see why. GERD is prevalent, elusive, and often shows up without the classic symptoms.

However, if the cough continues despite acid suppression therapy, it’s time for the clinician to reconsider. Chronic cough is frequently misdiagnosed, and GERD—though common—is only one of several contenders. This article unpacks the often-missed causes of persistent cough, guides clinicians through diagnostic strategies, and explains why proton-pump inhibitors (PPIs) might not be the cure-all many believe.

Written for physicians and advanced medical trainees, this is your practical and evidence-informed manual for approaching one of primary care’s most frustrating complaints.

Redefining Chronic Cough
Chronic cough is medically defined as a cough lasting more than eight weeks in adults. It may be dry or productive, intermittent or unrelenting, worse at night or constant throughout the day. Crucially, the lungs may sound clear, and the chest X-ray may look normal—adding to the diagnostic conundrum.

This isn’t a rare phenomenon. Chronic cough affects nearly 10% of the adult population, with a marked female predominance in middle-aged patients. Its consequences are far from benign: sleep disruption, fatigue, social embarrassment, urinary incontinence, and even rib fractures can result from unaddressed or misdiagnosed chronic cough.

The Big Three: Common, But Not Exclusive
In non-smoking adults who are not on ACE inhibitors and have normal chest X-rays, the traditional “big three” causes of chronic cough are:

• Upper Airway Cough Syndrome (UACS), previously called postnasal drip
  
  
• Asthma or cough-variant asthma
  
  
• GERD
  

These account for more than 90% of cases in outpatient care. But if your patient doesn’t improve after antihistamines, inhalers, or PPIs—it’s time to dig deeper.

When It’s Not GERD: Red Flags and Pitfalls
GERD is often blamed for chronic cough, but it’s not always the real cause—even if symptoms slightly improve with a PPI. Clinicians should watch for the following red flags:

• No heartburn or other hallmark GERD symptoms
  
  
• No significant change after 8–12 weeks of high-dose PPI therapy
  
  
• Cough worsens when lying flat, but there's no regurgitation
  
  
• Productive cough or associated wheezing
  

These signs suggest that something other than classic GERD might be driving the cough. Consider airway hypersensitivity, microaspiration, or non-acid reflux as possible culprits.

Postnasal Drip vs. Upper Airway Cough Syndrome (UACS)
The outdated term “postnasal drip” doesn’t do justice to the full spectrum of UACS. Patients may not report actual dripping or nasal congestion. Instead, clues include:

• A throat tickle or urge to clear the throat
  
  
• Repeated throat clearing
  
  
• Dry cough that worsens at night
  
  
• A sensation of something being stuck
  

Empirical treatment with intranasal corticosteroids, first-generation antihistamines (such as diphenhydramine or chlorpheniramine), or saline nasal irrigation can be both diagnostic and therapeutic.

Cough-Variant Asthma and Eosinophilic Bronchitis
Asthma doesn’t always present with wheezing. In some patients, particularly adults, chronic cough may be the only manifestation—a variant known as cough-variant asthma. When spirometry is inconclusive but suspicion remains high, consider:

• Methacholine challenge testing
  
  
• A therapeutic trial with inhaled corticosteroids and bronchodilators
  

A related condition, non-asthmatic eosinophilic bronchitis (NAEB), mimics asthma but lacks bronchial hyperresponsiveness. It is identified by:

• Eosinophilia in induced sputum
  
  
• Good response to inhaled corticosteroids
  

Both conditions can cause significant coughing and are often overlooked.

The Overlooked Giant: Non-Acid or Alkaline Reflux
GERD treatment failure doesn't always mean GERD isn't the cause. Non-acid or weakly alkaline reflux may still trigger coughing by irritating the larynx or activating vagal reflex arcs.

This condition, often labeled laryngopharyngeal reflux (LPR), can occur without heartburn. Clues that point in this direction include:

• Hoarseness
  
  
• Persistent throat clearing
  
  
• Globus sensation
  
  
• Bitter taste in the mouth
  

If LPR is suspected, consider advanced diagnostics like 24-hour multichannel intraluminal impedance-pH monitoring—especially in patients unresponsive to standard GERD treatment.

ACE Inhibitor-Induced Cough
ACE inhibitors remain a widely prescribed class of antihypertensives, but their cough-inducing potential is often forgotten. This adverse effect affects up to 20% of users and can emerge weeks or even months after starting the drug.

Common offenders include:

• Enalapril
  
  
• Lisinopril
  
  
• Ramipril
  

Switching the patient to an angiotensin receptor blocker (ARB) like losartan typically resolves the issue within weeks.

Interstitial Lung Disease (ILD) and Bronchiectasis
Even with a normal chest X-ray, don’t rule out structural lung diseases. If the patient has additional signs such as:

• Dyspnea
  
  
• Finger clubbing
  
  
• Velcro-like crackles
  
  
• Unexplained weight loss
  

…a high-resolution chest CT should be ordered. Look for:

• Interstitial lung disease
  
  
• Bronchiectasis
  
  
• Chronic aspiration
  

These conditions, though less common, are clinically significant—especially in individuals with systemic disease, occupational exposures, or chronic unexplained symptoms.

Psychological and Habit Coughs: Yes, They Exist
In some cases, especially among children and adolescents, chronic cough can be psychogenic or habitual in nature. Features that may raise suspicion include:

• Barking or bizarre-sounding cough
  
  
• Absence during sleep or distraction
  
  
• No improvement despite comprehensive therapy
  

Management may include cognitive-behavioral therapy, cough suppression techniques, or referral to a speech-language pathologist.

Chronic Cough in Smokers and Ex-Smokers
In smokers, chronic cough is often dismissed as “normal.” But persistent cough with daily sputum production for three months per year over two consecutive years defines chronic bronchitis—an early form of COPD.

Management must go beyond symptom control:

• Encourage smoking cessation
  
  
• Perform pulmonary function tests
  
  
• Consider inhaled bronchodilators
  

Cough in this population should always prompt proactive pulmonary evaluation.

A Rational Diagnostic and Therapeutic Approach
Here’s a step-by-step clinical strategy to tackle chronic cough:

• Comprehensive history and physical exam
  
  
• Chest X-ray and spirometry
  
  
• Trial treatments for UACS, asthma, and GERD
  

If there's no improvement within 6–8 weeks, escalate with:

• High-resolution CT of the chest
  
  
• ENT referral for laryngoscopy
  
  
• 24-hour pH or impedance-pH monitoring
  
  
• Sputum eosinophil analysis
  
  
• Possibly bronchoscopy
  

Don’t forget to screen for red flags like hemoptysis, unexplained fever, or significant weight loss.

Conclusion: Think Outside the Stomach
GERD may be one of the most cited causes of chronic cough, but it’s far from the only one—and certainly not always the most accurate. When acid suppression fails, remember to expand your diagnostic lens.

From nasal inflammation to eosinophilic bronchitis, from silent reflux to psychogenic triggers, chronic cough is a symptom that requires curiosity and clinical humility. A structured, evidence-based, and open-minded approach will not only yield answers—but significantly improve your patient’s quality of life.