Causes of Chronic Cough
In adults with chronic cough (lasting >8 weeks), four conditions account for over 90% of cases: upper airway cough syndrome (UACS), gastroesophageal reflux disease (GERD), asthma, and nonasthmatic eosinophilic bronchitis (NAEB). 1
Primary Etiologies
The dominant causes of chronic cough form a predictable pattern in nonsmokers with normal chest radiographs who are not taking ACE inhibitors:
The "Big Four" Causes
Upper Airway Cough Syndrome (UACS) - previously called postnasal drip syndrome - represents the most common single etiology, accounting for a significant proportion of cases across multiple international studies 2, 1
Asthma - including cough variant asthma where cough is the sole presenting symptom without wheezing or dyspnea - is a leading cause that may present with circadian variations in airway responsiveness 1, 3
Gastroesophageal Reflux Disease (GERD) - can present as "silent GERD" with cough as the only symptom in up to 75% of cases, without any heartburn or typical gastrointestinal symptoms 1, 4
Nonasthmatic Eosinophilic Bronchitis (NAEB) - characterized by eosinophilic airway infiltration, normal spirometry, and absence of bronchial hyperresponsiveness - is frequently overlooked but represents an important cause 1, 5
Additional Common Causes
ACE inhibitor use - alters cough reflex sensitivity and should be identified early in the evaluation 4, 3
Current cigarette smoking - one of the most common causes of persistent cough, with prevalence increasing in a dose-related manner 2, 4
Chronic bronchitis/COPD - particularly in patients with smoking history, though less common than the "big four" in nonsmokers 2, 1
Critical Diagnostic Considerations
Common Pitfalls to Avoid
Do not rely on cough characteristics for diagnosis - the character, timing, or presence/absence of sputum production has no diagnostic value 2, 1
Never assume absence of typical symptoms rules out a diagnosis - patients can have "silent GERD" without heartburn, "cough variant asthma" without wheezing, or "silent UACS" without obvious nasal symptoms 2, 1, 4
Even significant sputum production does not change the differential - in nonsmokers not on ACE inhibitors with normal chest radiographs, bronchorrhea still typically results from UACS, asthma, GERD, or combinations thereof 2
Failing to consider NAEB early is a frequent diagnostic error that delays appropriate treatment 1
Multiple Simultaneous Causes
In up to 25% of patients, multiple disorders contribute simultaneously to chronic cough, requiring treatment of all identified conditions 6
The combination of two or even all three of the dominant etiologies (UACS, asthma, GERD) commonly coexist in the same patient 2
Essential Historical Elements
While cough characteristics are unhelpful, specific historical factors are crucial:
Geographic exposure - areas where tuberculosis or endemic fungal diseases are prevalent 2
Past medical history - previous cancer, tuberculosis, or AIDS 2
Systemic symptoms - fever, night sweats, or unintentional weight loss suggesting serious underlying disease 2, 5
Special Populations
- Women, particularly middle-aged women, have higher prevalence of chronic cough and more sensitive cough reflex compared to men 1, 4
Less Common But Important Causes
Obstructive sleep apnea 3
Bronchiectasis and cystic fibrosis 7
Chronic infectious respiratory diseases - particularly in endemic areas 2, 7
Refractory Chronic Cough
When the common causes have been adequately treated without resolution, consider cough hypersensitivity syndrome - a condition characterized by heightened cough reflex sensitivity to normally innocuous stimuli 5, 8, 7
This represents a distinct pathophysiologic entity requiring neuromodulatory therapy (gabapentin or pregabalin) and/or speech pathology therapy rather than continued pursuit of traditional etiologies 5, 7