Chronic cough is estimated to affect 5% of the U.S. adult population (12.3 million individuals).¹ The American College of Chest Physicians (CHEST) defines chronic cough as a persistent cough lasting longer than 8 weeks in adults and 4 weeks in children.^2,3 According to the Centers for Disease Control and Prevention, cough of undifferentiated duration is the second most common reason that patients present to primary care ambulatory settings.⁴ Chronic cough can negatively impact quality of life and daily activities, which can increase the risk of depression and anxiety.^5–7

ASSESSMENT OF CHRONIC COUGH

The initial assessment of chronic cough includes obtaining a comprehensive medical history, performing a physical examination, identifying triggers that may point to common causes (Table 1^2,3,8–13 [corrected]), and evaluating for red flags to rule out serious conditions (Table 2^14,15). Chest radiography and spirometry should be included in the initial workup if the history and physical examination do not identify an apparent cause. Initial treatment should be based on pertinent history and physical examination findings, and response to treatment should be assessed in 4 to 6 weeks. The evaluation and empiric treatment of chronic cough in adults should be based on the most common causes: upper airway cough syndrome, asthma, nonasthmatic eosinophilic bronchitis, gastroesophageal reflux disease (GERD), and laryngopharyngeal reflux (LPR).¹⁴

In select patients with a normal physical examination and negative chest radiography, computed tomography of the chest may be performed, but there are limited clinical benefits, even after ruling out the most common causes.^14,16,17 The initial evaluation of chronic cough in immunocompromised adults is similar to those who are immunocompetent.¹⁸ A suggested approach for the assessment and treatment of adults with chronic cough is shown in Figure 1.^2,8,12,14,19

COMMON CAUSES OF CHRONIC COUGH IN ADULTS

Upper Airway Cough Syndrome

In 2006, the ACCP started using the term upper airway cough syndrome instead of postnasal drip syndrome in patients with chronic cough related to upper airway abnormalities.²⁰ This change reflects the understanding that upper airway cough syndrome can manifest in the absence of postnasal drip. Although the exact mechanism of upper airway cough syndrome is unknown, it is considered to be related to hypersensitivity of the upper or lower airway sensory nerves.²¹

Upper airway abnormalities can be categorized into three conditions: chronic nonallergic rhinitis is the most common, followed by chronic allergic rhinitis and chronic rhinosinusitis.²² Common symptoms of upper airway cough syndrome include rhinorrhea, nasal congestion, and throat clearing; these symptoms are nonspecific for the diagnosis of chronic cough.²² Because upper airway cough syndrome is the most common cause of chronic cough in the United States, it is reasonable to use empiric treatment regardless of nasal symptoms.²⁰

Management strategies include treatment for reducing inflammation and secretions, treatment of infection, and avoiding environmental triggers. First-generation antihistamines can have a useful role in the treatment of upper airway cough syndrome because of the indirect peripheral anticholinergic effects and central nervous system–mediated cough suppression, although adverse effects such as thickening secretions, oral dryness, and drowsiness may limit their tolerability.²³ Management of the underlying conditions of upper airway cough syndrome may vary among countries.^17,24–26 Use of nasal corticosteroids or second- or third-generation antihistamines and decongestants and avoiding allergens are recommended for allergic rhinitis. First-generation antihistamines and decongestants are recommended in patients with nonallergic rhinitis and chronic rhinosinusitis.²⁰ Nasal corticosteroids and antibiotics can be used for chronic rhinosinusitis when appropriate.

Asthma

The prevalence of asthma in patients with chronic cough ranges from 24% to 32%.²⁷ Patients with asthma present with wheezing, dyspnea, and cough, which may be caused by allergens, environmental triggers, or upper respiratory tract infection. Clinical history, physical examination, and pre- and postbronchodilator spirometry are important for diagnosing asthma.²⁸ If findings are nondiagnostic, clinicians can consider performing a bronchial hyperresponsiveness test (e.g., methacholine challenge).²⁷ A fractional exhaled nitric oxide test can be used as adjunct diagnostic testing for those who cannot undergo spirometry accurately, although it is important to note that GERD and allergic rhinitis can increase fractional exhaled nitric oxide levels, leading to a false-positive test result.^29,30 Underdiagnosis and overdiagnosis of asthma is common and may lead to worsened patient outcomes and unnecessary treatment with associated costs.³¹ More information is available in American Family Physician articles and guidelines focusing on asthma management.^32–35

Nonasthmatic Eosinophilic Bronchitis

Nonasthmatic eosinophilic bronchitis is a corticosteroid-responsive chronic cough in a nonsmoking patient with eosinophilic inflammation of the respiratory tract without signs of variable airway obstruction or airway hyperresponsiveness.³⁶ The prevalence is estimated to be approximately 17% in patients with chronic cough.³⁷ Sputum eosinophilia is helpful in the diagnosis of nonasthmatic eosinophilic bronchitis; however, the availability of this test in primary care is limited because it requires saline nebulization or bronchoalveolar lavage.¹⁴

CHEST recommends inhaled corticosteroids (ICS) as first-line treatment in adults and adolescents with nonasthmatic eosinophilic bronchitis. At least 2 months of ICS treatment is effective in reducing relapse.^27,38 If there is no response to treatment with ICS, physicians should consider alternative causes of chronic cough. If nonasthmatic eosinophilic bronchitis is still suspected, a dosage increase of ICS or a therapeutic trial of a leukotriene inhibitor, such as montelukast, can be used.²⁷ Patients with chronic refractory cough should not be treated with ICS empirically, which underlines the importance of determining the diagnosis of asthma or nonasthmatic eosinophilic bronchitis before the initiation of ICS.

Gastroesophageal Reflux Disease and Laryngopharyngeal Reflux

The prevalence of GERD and LPR in adults with chronic cough is estimated to be 2% to 86% among different studies.³⁹ Chronic cough related to GERD and LPR is caused by gastric reflux irritation of the larynx and activation of the afferent limb in the cough reflux. Common manifestations include voice changes, throat clearing, dysgeusia, acid reflux, and regurgitation.⁴⁰ The presence of acid reflux in patients with chronic cough does not necessarily indicate that the cough is due to GERD or LPR⁴¹; therefore, evaluation of symptom resolution in response to an empiric trial of treatment is needed to identify GERD or LPR as the cause of chronic cough. Lifestyle modifications can reduce GERD-related symptoms and include smoking cessation, weight loss, elevation of the head, and avoiding food triggers and late meals.^39,42,43 Although the evidence of benefit for proton pump inhibitors in patients with chronic cough secondary to GERD and LPR remains insufficient, an 8- to 12-week trial of a proton pump inhibitor 30 to 60 minutes before breakfast can be considered after ruling out other common causes of chronic cough. Routine pH monitoring and esophagogastroduodenoscopy should not be performed in patients with only extraesophageal symptoms, including chronic cough.⁴²

ACE Inhibitor–Related Cough

Angiotensin-converting enzyme (ACE) inhibitor–related cough typically presents as a dry cough that develops hours to months after the initiation of therapy. The prevalence is reported from 5% to more than 30%.⁴⁴ The exact mechanism remains unclear, but the most widely accepted theory is that ACE inhibitors prevent the degradation of bradykinin and substance P, leading to bronchoconstriction and cough.⁴⁵ The diagnostic and therapeutic approach is to discontinue the medication and observe for the resolution of cough within 1 to 4 weeks. However, several studies have demonstrated that cough may spontaneously resolve in 25% to 50% of patients, even those who keep taking ACE inhibitors.^46,47 If patients develop chronic cough, ACE inhibitors should be replaced with an alternative, such as an angiotensin receptor blocker. Physicians should also consider other common causes of chronic cough.

Obstructive Sleep Apnea

Approximately 15% of the U.S. adult population has sleep apnea.⁴⁸ In a retrospective study, more than 40% of patients with chronic cough were found to have obstructive sleep apnea (OSA).⁴⁹ A prospective cohort study demonstrated that patients with OSA had a higher burden of chronic cough and LPR symptoms compared with people without OSA.⁵⁰ Continuous positive airway pressure therapy can improve cough-related quality of life in patients with chronic cough and OSA compared with sham therapy.⁵¹ Evaluation of OSA, such as administering the STOP-BANG (snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck circumference, gender) questionnaire and a sleep study if indicated, should be considered early during management of chronic cough in an ambulatory setting.⁵²

CHRONIC REFRACTORY COUGH

Up to 10% of patients with chronic cough can be categorized as having chronic refractory cough.¹⁹ It is defined as a clinically significant chronic cough that persists despite appropriate intervention and treatment.² Physicians should complete a comprehensive evaluation for common etiologies and confirm adherence to optimal therapy before referral to a specialist.²

Physicians should avoid using ICS as empiric treatment for chronic refractory cough. It is critical to perform a comprehensive assessment for asthma and nonasthmatic eosinophilic bronchitis before initiation of ICS. Multimodality speech pathology therapy, including education about chronic cough, psychoeducational counseling, and techniques for cough control, can improve cough frequency and severity and cough-related quality of life.^2,53–55

Neuromodulators can be effective for the treatment of chronic refractory cough by acting directly on cough hyper-sensitivity. After discussing the potential benefits and risks, a trial of gabapentin (initial dosage: 300 mg twice per day; maximum dosage: 1,800 mg per day) or amitriptyline (initial dosage: 10 mg at bedtime; maximum dosage: 100 mg) can be considered in addition to physiotherapy and speech and language therapy to improve cough-related quality of life.^2,17,56–58 Reassessment of the risk-benefit profile is recommended 6 months after initiating gabapentin or amitriptyline. When initial test findings are unremarkable, further diagnostic tests, such as bronchoscopy and nasendoscopy, are often warranted through referral to a pulmonologist and otolaryngologist.

CHRONIC COUGH IN CHILDREN

Chronic cough in children can lead to impaired quality of life, multiple medical visits, and a substantial burden on caregivers.^59,60 The most common etiologies include protracted bacterial bronchitis, asthma, bronchiectasis, upper airway cough syndrome, and GERD.^3,60–62 Other common etiologies of chronic cough in children include foreign body inhalation, ear conditions, and medications.⁶³ Approximately 20% of children with chronic cough were found to have serious underlying conditions such as bronchiectasis, aspiration lung disease, and cystic fibrosis.⁶⁰ Early identification and optimal treatment are critically important to prevent further lung injury.

Physicians should also evaluate tobacco smoke exposure and caregivers’ expectations and concerns.⁶³ Because of the high likelihood of spontaneous resolution, a 2-week watchful waiting approach can be used for children with dry cough without any other signs, including wheezing, exertional dyspnea, chest pain, and digital clubbing.⁶⁴ For wet cough, a 2-week course of antibiotics (amoxicillin/clavulanate or erythromycin) is reasonable because of the prevalence of protracted bacterial bronchitis and the effectiveness for clinical recovery from chronic cough.^65,66 The suggested primary care approach for the assessment and treatment of children with chronic cough is shown in Figure 2.^61,63,64

This article updates previous articles on this topic by Michaudet and Malaty⁶⁷; Benich and Carek⁶⁸; Holmes and Fadden⁶⁹; and Lawler.⁷⁰

Data Sources: A PubMed search was completed in Clinical Queries using the key term chronic cough. The search included meta-analyses, randomized controlled trials, guidelines, and reviews. The Agency for Healthcare Research and Quality Effective Healthcare Reports, the Cochrane database, DynaMed, and Essential Evidence Plus were also searched. We critically reviewed studies that used patient categories such as race and/or gender but did not define how these categories were assigned, stating their limitations in the text. Search date: October 6, 2023, and June 8, 2024.