Cough is a common reason for a child's family to seek care from their pediatrician. A cough, whether acute or chronic, can be distressing to the patient and parents. The extensive differential diagnosis can occasionally lead to excessive and unnecessary testing and/or treatment. A systematic approach, including a thorough history and physical examination, can help narrow the differential diagnosis for chronic cough. This article highlights the common differential diagnoses to be considered in the evaluation of children with a chronic cough.
The definition of acute and chronic cough is variable based on the literature. According to the American College of Chest Physicians, in children, an acute cough is defined as a daily cough for less than 4 weeks and chronic cough is defined as a daily cough of greater than 4 weeks.1,2 The threshold of 4 weeks was chosen to permit early diagnosis of serious underlying conditions such as bronchiectasis or foreign body. Alternatively, a cough can be considered acute (<4 weeks), prolonged acute or subacute (4–8 weeks), and chronic (>8 weeks).
The normal cough reflex is a complex multisystem mechanism (Figure 1). The goal of a cough is to remove mucus and other materials from the airway. A cough is a reflex stimulated by sensory receptors located throughout the upper and lower airways from the pharynx to terminal bronchioles. Afferent impulses are sent via glossopharyngeal and vagus nerves to the cough center in the upper brainstem and pons. The efferent signals from the cough center travel via the vagus, phrenic, and spinal motor nerves to the larynx, diaphragm, chest wall, abdomen, and pelvic floor.3,4
The multisystem mechanism of a cough and the reflex involved.
There are three phases of a cough: (1) deep inspiration, (2) closure of the glottis, and respiratory muscle relaxation and contraction, and (3) sudden opening of the glottis with forced exhalation.5,6 The last phase ultimately determines the success of expectoration. Stimuli (irritants) may provoke a cough via pulmonary irritation (central airway or parenchymal), irritation of pleura, diaphragm, or Arnold's nerve, which is stimulated by wax or foreign body in the external ear.5
A detailed history and physical examination are key for determining the etiology of a cough. In identifying an etiology, some details to be attained include onset of cough (since birth or after illness), quality of cough (productive, nonproductive, “barking”), timing of cough during day, quantity and color of any sputum, relation to oral intake, relation to viral illnesses, seasonality, any wheezing, chest pain related to cough, any symptom-free periods, history of structural airway repair, witnessed or unwitnessed choking episode at any time, and presence of nighttime coughing episodes. Other information may be imperative in determining the etiology of cough. In our experience, a patient diary to note frequency and timing of cough can also be helpful.
Etiology and Differential Diagnosis
The differential diagnosis for chronic cough is quite broad. To aid in thinking about the differential diagnosis in an organized fashion, etiologies of cough can be categorized into infectious, inflammatory, and functional/anatomical conditions. Multiple diagnoses can be classified within each category. Table 1 summarizes some of the potential diagnoses in each category. This list is not exhaustive, but it suggests some of the more common etiologies.
Common Diagnoses and Categories for Chronic Cough
Infectious Etiologies and Disease-Specific Treatments
An infectious etiology is usually the most common reason for an acute cough in an otherwise previously well child.6,7 A cough after a viral illness typically can last up to 2 weeks, but in some children it can last as long as 4 weeks.
Viruses. Viruses such as respiratory syncytial virus, rhinovirus/enterovirus, adenovirus, metapneumovirus, influenza/parainfluenza, and others can be the primary cause of cough in younger children.6,7 Viruses typically result in cough associated with upper respiratory signs and symptoms (eg, rhinorrhea and nasal congestion). The cough can linger for weeks. Symptomatic treatment alone is usually all that is required in the absence of concerning secondary signs such as localized findings on auscultation or toxic appearance. Treatment for influenza with antiviral therapy should be initiated as early as possible, especially in those with increased risk of complications.8
Bacterial lung infections. Bacterial lung infections can produce a wet cough due to an increase in mucus production. Bacterial pneumonia can cause cough with high fever and respiratory distress. History and physical examination are often sufficient to make the diagnosis, although a chest radiograph may be helpful in determining the exact location of pneumonia and for evaluating complications such as pleural effusion or empyema. In our opinion, treatment with high-dose amoxicillin, a third-generation cephalosporin, or clindamycin should be considered.
Atypical bacterial infections. Atypical bacterial infections such as Mycoplasma pneumoniae or Bordetella pertussis should be considered in patients with prolonged cough or classic whooping cough. Bordetella pertussis should be considered in a patient with frequent paroxysms of cough without increased inspiratory effort, who then has a “whoop” or noise of forced inspiratory effort.9 The whoop noise may not be present in older children and adolescents. Post-tussive emesis may also be an indicator of pertussis. Young infants with presumed pertussis may require hospitalization due to the risk of complications such as apnea, secondary pneumonia, or neurologic complications. Treatment should be with a macrolide antibiotic.6,7 Patients infected with Mycoplasma pneumoniae may have a more gradual onset of symptoms and less respiratory distress. Mycoplasma and Chlamydia can cause wheezing, and Chlamydia can also cause a classic staccato cough.9,10 Radiologic imaging may show peri-bronchial pneumonia and streaks of interstitial infiltrates (often bibasilar). Treatment is also with a macrolide antibiotic.
Mycobacterial infections. Mycobacterial infections such as tuberculosis should be considered in the appropriate clinical context (history of travel to or immigration from high-risk regions or exposure to an adult with tuberculosis) or in association with symptoms of high fever, night sweats, weight loss, and/or hemoptysis. Tuberculosis may present more subtly with a chronic cough that lasts longer than 4 weeks. Children with suspected tuberculosis should undergo chest imaging (chest X-ray or chest computed tomography scan) to evaluate for the extent of disease and location of any lesions. Sputum culture, gastric aspirate, and/or bronchoscopy may help to identify the organism and guide treatment. Treatment is based on the extent of disease and sensitivities of any specific organism identified.
Chronic sinusitis. Children with chronic sinusitis may develop a chronic wet cough due to persistent mucopurulent drainage and postnasal drip. Patients with chronic sinusitis may also complain of headache, facial pain, and/or loss of sense of smell. These patients are at increased risk of developing nasal polyps due to chronic inflammation. Appropriate treatment should be initiated early as complications of orbital cellulitis or cavernous sinus thrombosis can occur. Prolonged antibiotics (eg, beta-lactam or broad-spectrum) for as long as 6 weeks may be indicated in certain circumstances.11
Protracted bacterial bronchitis. Protracted bacterial bronchitis (PBB) is an increasingly recognized cause of chronic wet cough in children. Symptoms include chronic wet cough without any other signs or symptoms and no response to bronchodilators.10 It is caused by the usual upper respiratory pathogens (Haemophilus influenzae [nontypable], Moraxella catarrhalis, Streptococcus pneumoniae, and Staphylococcus aureus). Diagnostic criteria include presence of chronic wet cough, resolution of cough within 2 weeks of antibiotic (amoxicillin-clavulanate) use, and presence of lower airway infection (respiratory pathogens ≥104 CFUs/mL on bronchoalveolar lavage or absence of other causes for cough.10 Treatment is at least 2 weeks of antibiotics, such as amoxicillin-clavulanic acid, third-generation cephalosporin, macrolide, or trimethoprim-sulfamethoxazole.10 PBB-associated cough should start to improve after 2 weeks of antibiotics.
Inflammatory Etiologies and Disease-Specific Treatments
Asthma. Asthma is a leading cause of cough in children.2,12 The cough in asthma is usually associated with wheezing or dyspnea. Patients may present only with cough initially, but with time demonstrate other symptoms. Cough-variant asthma is uncommon in children. Asthma should be considered in a patient with chronic cough who has a history of atopy (eg, allergic rhinitis, eczema) or a family history of asthma or atopy. Asthma can worsen with viral illnesses, exercise, and exposure to cold air, dust, mold, or perfumes. An obstructive pattern on spirometry testing or airway hyperreactivity on methacholine challenge would support this diagnosis. Treatment options include bronchodilators, inhaled corticosteroids, leukotriene modifiers, or combinations of these medications.
Allergies. Allergies to dust, pet dander, or other environmental agents can contribute to cough in children. Allergic cough is often associated with other symptoms such as rhinorrhea, epiphora, allergic “shiners,” and/or allergic salute.13 Treatment options include antihistamines, nasal corticosteroids, and in some instances, allergy immunotherapy.
Postinfectious inflammation. Postinfectious inflammation may contribute to the development of chronic cough.7 An ongoing cough after a viral infection may last up to 4 weeks. Recurring viral infections, especially during the fall and winter, can result in an ongoing cough for months. This may be a diagnosis of exclusion in an otherwise healthy child who continues to grow and thrive despite the cough. Symptoms typically resolve with time, although oral corticosteroids may hasten the recovery.
Allergic bronchopulmonary aspergillosis. Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus that may occur in patients with asthma or cystic fibrosis (CF). ABPA can manifest as persistent or recurrent cough and/or cause frequent asthma exacerbations that do not respond to the standard of care treatment.14 Diagnosis can be confirmed by measuring serum immunoglobulin E levels, immunoglobulin E-specific antigens, and typical radiographic findings. ABPA is typically treated with prolonged oral corticosteroids.
Functional/Anatomic and Disease-Specific Treatments
Chronic aspiration. Chronic aspiration may be a cause of chronic cough. Chronic aspiration may be due to upper airway anatomic anomalies such as laryngeal cleft, vocal cord paralysis/paresis, tracheoesophageal fistula, or baseline neurologic abnormality/swallow immaturity. Children with chronic cough with a history that could suggest aspiration should undergo a video-fluoroscopic swallow study to evaluate their swallowing function. Speech therapy or otorhinolaryngology consultation may also be useful diagnostically and therapeutically.
Gastroesophageal reflux disease. Gastroesophageal reflux disease (GERD) has been thought to cause chronic cough in children due to reflux of gastric contents into the esophagus, larynx, or toward the airway. Gastric contents can be irritating to mucosa and stimulate the cough receptors. Relaxation of the lower esophageal sphincter or incomplete emptying of gastric contents can increase the risk of reflux and manifest as regurgitation and/or recurrent spitting up in younger children.6,15 In older children, frequent throat clearing, heartburn, and/or globus sensation could suggest GERD. However, there is no consistent evidence that GERD causes isolated cough in otherwise asymptomatic children. Treatment includes antacids, H2 receptor antagonists/blockers, proton pump inhibitors, or prokinetic agents.
Foreign body aspiration. Foreign body aspiration may cause cough if retained in an airway. Aspiration should be considered, especially if the onset of the cough is sudden, as many aspiration events are unwitnessed. Peanuts, nuts, popcorn, coins, seeds, and toys are a few of the more common objects that are aspirated in young children and may cause cough, localized wheezing, and/or recurrent pneumonia. Many of these items are not radio-opaque and may not be identified on radiographic imaging; therefore, a high index of suspicion should be employed if symptoms are unexplained. If not identified in a timely manner, foreign bodies can cause localized bronchiectasis; therefore, diagnostic and therapeutic bronchoscopy should be considered in any child with suspected foreign body aspiration.
Tracheomalacia or bronchomalacia. Tracheomalacia or bronchomalacia can be a cause of chronic cough due to dynamic collapse of airway. The cough of tracheomalacia or bronchomalacia is typically barky and croup-like, often with associated monophonic wheezing or stridor.16 In most cases, the malacia should improve without treatment as the patient grows.
Congenital airway anomalies. Congenital airway anomalies such as congenital lobar overinflation, congenital cystic adenomatoid malformation/congenital pulmonary airway malformation, or bronchogenic cysts should be considered in the evaluation of chronic cough and may be seen on radiographic imaging. Other symptoms such as recurrent pneumonia, noisy breathing, or increased work of breathing may also occur. Vascular rings or slings may encircle the trachea and esophagus leading to chronic cough due to airway narrowing. Treatment, if needed, is surgical.
Cystic fibrosis. CF is an autosomal recessive genetic disorder of the cystic fibrosis transmembrane conductance regulator (CFTR) gene that can manifest as failure to thrive, chronic sinopulmonary infections with chronic cough, nasal polyps, clubbing, rectal prolapse, steatorrhea, and gastrointestinal disease.17 CF is more common in white people, but it can occur in patients from any ethnic background.6,18 Genetic screening for CF is included as part of newborn screening; however, CF can be missed on initial screening. CF can be diagnosed by sweat chloride testing and/or the presence of two abnormal CFTR gene mutations. Treatment is based on a multisystem approach, and referral to a specialized CF center is recommended for access to best practice care guidelines and improved outcomes. CF center physicians should work in concert with, and not to the exclusion of, the primary care pediatrician.
Primary ciliary dyskinesia. Primary ciliary dyskinesia (PCD) is a heterogeneous disorder of cilia affecting mucociliary clearance in airways. In this disease, cilia are either unable to beat (immotility), unable to beat properly (dyskinesia), or absent (aplasia). Patients typically suffer from chronic cough, recurrent pneumonias that can develop into bronchiectasis, chronic sinusitis, and chronic otitis media.19 Patients may also have situs inversus and PCD, known as Kartagener's syndrome.19,20 Symptoms can present at a younger age or not until patients are older. Infants may have respiratory distress, tachypnea, and/or require supplemental oxygen. Mucopurulent sputum, copious constant nasal discharge, and frequent otitis media are highlights of this disease. Genetic testing is available to diagnose certain causes of PCD. The treatment approach is multisystem based on symptoms.
Immunodeficiency. Immunodeficiency should also be considered in a patient with chronic cough. Defects in B-cell or T-cell function can present with frequent bacterial or fungal infections. Immune disorders could include X-linked agammaglobulinemia, common variable immunodeficiency, immunoglobulin A immunodeficiency, severe combined immunodeficiency, and chronic granulomatous disease. Prolonged cough with respiratory illnesses and frequent infections could suggest possible immune deficiency. Patients may not present until age 4 to 6 months when maternal antibodies wane.21 Children with immunodeficiencies are at risk for pulmonary complications, including bronchiectasis and interstitial lung disease. Treatment depends on the type of immunodeficiency.
Somatic cough syndrome. Somatic cough syndrome (habit or “hyperreflexive” cough) was previously thought of as a diagnosis of exclusion, but it is now being diagnosed with increased frequency based on its classic symptoms.22 This cough is typically loud, honking, brassy, or barky and can be disruptive to those around the child.12,22,23 The cough is often repetitive and may be accompanied by classic chin-on-chest posture. The child may cough frequently during daytime hours when awake and it may increase when he or she is around others. The cough, however, will be absent during sleep or when the patient is alone or distracted. This cough may be preceded by a viral illness or stressful event. Treatments include behavioral therapies (eg, suggestion therapy) and/or specialized speech therapy.
As discussed previously, a detailed history and physical examination are key in determining the etiology of a chronic cough. Aside from those details previously discussed, other questions include the following: has the child had similar symptoms previously? Were there any ill contacts with similar symptoms? Was there any travel corresponding with the onset of cough?
Physical examination is often normal. Physical findings that can be helpful may include nasal mucosal edema with or without pallor, posterior pharyngeal “cobblestoning,” which could suggest allergic/nonallergic rhinitis or chronic sinusitis. Wheezing, with or without retractions, could suggest asthma. Clubbing, poor growth, and failure to thrive could suggest CF, ciliary dyskinesia, or immunodeficiency. Elevated respiratory rate and low oxygen saturation could suggest an underlying pulmonary intestinal abnormality or cardiac abnormality.4 A dry, honking, barky cough that calms with distraction in clinic and a history of improving with sleep could suggest somatic cough syndrome.
Usually the history and physical examination are sufficient to narrow down the possible etiologies for chronic cough. Other testing that might be appropriate could include pulmonary function testing (looking for obstruction, restriction, air trapping, and/or bronchodilator reversibility), chest radiograph (especially for those with a chronic wet cough or focal lung findings on physical examination), sputum culture/cough swab (low diagnostic yield), and Bordetella pertussis and/or Mycoplasma pneumoniae screening. Additional testing may include sweat test/CF genetics and/or immune testing (if history or physical examination raise concerns for these diagnoses), flexible fiberoptic bronchoscopy and bronchoalveolar lavage (if concerned about airway anatomical issues, foreign body, chronic infection, or PBB), chest computed tomography scan (eg, if persistent changes on chest radiograph), video-fluoroscopy (aspiration) with or without pH probe (for GERD), and ciliary biopsy with PCD genetics (for PCD).2,19 Referral to a pulmonary specialist would be advisable for some of these more sophisticated diagnostic tests that are not readily available to a busy pediatrician.
Initial Treatment Approach Based on Suspected Category
For suspected infectious etiologies, a trial of antibiotics, such as beta-lactams (eg, amoxicillin), cephalosporins, other broad-spectrum antibiotics (eg, amoxicillin-clavulanate), or macrolide antibiotics (if Bordetella pertussis and/or Mycoplasma pneumoniae are suspected) for 5 to 10 days or as long as 3 to 6 weeks (if chronic sinusitis or PBB are suspected) would be appropriate.2,6
For suspected inflammatory causes, a trial of asthma medications (bronchodilators, inhaled steroids, or leukotriene inhibitors) and/or allergy medications (eg, antihistamines, nasal corticosteroids) could be considerations. A minimum of 4 weeks should be given before determining that they are not beneficial. In our opinion, a 5- to 7-day course of oral corticosteroids (eg, prednisolone 1–2 mg/kg daily) would provide a quicker determination if the source of the cough is inflammatory in nature. If the child's cough resolves (eg, postinfectious inflammation) or improves and then recurs, this would suggest an inflammatory etiology. If there is little or no response to the oral corticosteroids, this would suggest that the etiology lies elsewhere.
Treatment of functional/anatomical etiologies could include a trial of anti-GERD therapy for 1 month, speech/swallow therapy (if aspiration is suspected), multidisciplinary/specialty clinic referral and treatment (for CF, immunodeficiencies, or primary ciliary dyskinesia), surgery (for anatomical etiologies or foreign bodies), and suggestion therapy or specialized speech therapy (for somatic cough syndrome).
The differential diagnosis for chronic cough includes many possible etiologies to be considered in the appropriate clinical context. Some of these diagnoses would warrant extensive testing and others would not. Usually a thorough history and physical examination with appropriate laboratory testing is sufficient. Categorizing the etiologies of chronic cough into infectious, inflammatory, or functional/anatomical conditions can help narrow the differential diagnosis and help guide testing or treatment.
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- Wilmott RW. Kendig and Chernick's Disorders of the Respiratory Tract in Children. Philadelphia, PA: Elsevier; 2019:2–25.
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- Heinonen S, Silvennoinen H, Lehtinen P, et al. Early oseltamivir treatment of influenza in children 1–3 years of age: a randomized controlled trial. Clin Infect Dis. 2010;51(8):887–894. doi:. doi:10.1086/656408 [CrossRef]
- Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin Microbiol Rev. 2005;18(2):326–382. doi:. doi:10.1128/CMR.18.2.326-382.2005 [CrossRef]
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- Tolia V., Vandenplas Y. Systematic review: the extra-oesophageal symptoms of gastro-oesophageal reflux disease in children. Aliment Pharmacol Ther. 2009;29:258–272. doi:10.1111/j.1365-2036.2008.03879.x [CrossRef]
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Common Diagnoses and Categories for Chronic Cough
||Viral (respiratory syncytial virus, rhinovirus, influenza, adenovirus, metapneumovirus)
Atypical bacteria (including Bordetella pertussis, Mycoplasma pneumoniae, tuberculosis)
Protracted bacterial bronchitis
Allergic bronchopulmonary aspergillosis
Gastroesophageal reflux disease
Congenital airway abnormalities
Primary ciliary dyskinesia
Somatic cough syndrome