Causes of chronic cough in children

INTRODUCTION — There are many causes of cough; the majority originate in the lungs, but there are also nonpulmonary etiologies, some proven and others controversial. The causes are presented in the table (table 1).

The causes of chronic cough in children will be reviewed here. The evaluation of a child with chronic cough should include a detailed history [1], physical examination, chest radiograph, and spirometry and follow a child-specific algorithm [2-4]; the clinical approach is summarized in the algorithm (algorithm 1) and discussed in more detail in a separate topic review. (See "Approach to chronic cough in children".)

DEFINITIONS

Chronic cough — Chronic cough in children aged 14 years and younger is typically defined as a cough lasting more than four weeks [2,3,5]. This definition is used by most published international guidelines (American, European, and Australian [3,6-8]) because most acute respiratory infections in children resolve within this interval and evaluation at four weeks permits relatively early diagnosis of serious underlying illnesses. (See "Approach to chronic cough in children", section on 'Chronic cough'.)

Specific cough — Specific cough refers to a chronic cough that is ultimately attributable to an underlying abnormality or disease, which is usually, but not always, of pulmonary origin (table 1). In most cases of specific cough the initial evaluation will identify signs or symptoms suggesting the cause of the cough (known as "specific cough pointers"). These include symptoms such as wet cough or wheeze; timing, such as onset in neonatal period; associated conditions, such as failure to thrive or digital clubbing; abnormalities on chest radiograph or spirometry (table 2); or classically recognizable cough sounds (eg, brassy or croup-like) (table 3). Many of these pointers are easily recognizable and are strong predictors of a specific cause. A specific cause of cough is very unlikely if no pointers are found on the initial evaluation [9]. One of the most important and discriminating pointers is presence of wet or productive cough [9]. A chronic wet cough signifies the presence of airway secretions [10], and in most cases airway infection, and should not be ignored in children [11,12].

The main causes of specific cough are described in the remainder of this topic review.

Nonspecific cough — Conversely, "nonspecific" cough is defined as a chronic cough that does not have an identifiable cause after a reasonable evaluation including history, physical examination, radiography, and spirometry. A chronic cough is likely to be nonspecific if it is dry and there are no abnormalities identified on initial evaluation (ie, no "specific cough pointers" (table 1)). This type of cough usually resolves gradually, but children should be reevaluated periodically for the emergence of signs or symptoms of specific cough. In some cases, nonspecific cough may represent a postviral syndrome.

OVERVIEW OF CAUSES IN CHILDREN — The three most common causes of chronic cough in children are asthma, protracted bacterial bronchitis (PBB), and nonspecific cough that resolves spontaneously, as described in hospital-based multicenter studies and a systematic review [13-15] and supported by a multicenter study in which children were enrolled from primary care or emergency departments [4]. Other causes are outlined in the table (table 1). For some other diagnoses such as tuberculosis, the frequency varies by region [13,16].

Of note, the causes of chronic cough in children are different from that of adults, so evaluation and management of children should be based on child-specific protocols and not those designed for adults [13,17]. As an example, gastroesophageal reflux disease (GERD) and upper airway cough syndrome (formerly known as postnasal drip syndrome) are thought to be common causes of chronic cough in adults but are probably not common causes in children [13,18]. Adult cough guidelines have suggested empirical treatment of asthma, GERD, and upper airway cough syndrome (UACS) because these are the most common causes in this population. By contrast, pediatric guidelines do not recommend empiric therapy [3,6,7], although adolescents 15 years and older may be managed using guidelines for adults [19]. (See "Causes and epidemiology of subacute and chronic cough in adults".)

PULMONARY CAUSES OF CHRONIC COUGH IN CHILDREN

Aspiration — Chronic or recurrent aspiration is an uncommon but important cause of chronic cough. It may be due to a primary swallowing dysfunction or secondary to disorders such as gastroesophageal reflux or achalasia. Other risk factors for aspiration include neurologic and developmental abnormalities, neuromuscular disease, and anatomic airway abnormalities (eg, laryngeal cleft or tracheoesophageal fistula). Some individuals with these disorders have a history of feeding difficulties, or coughing during feeding. However, the absence of cough during swallowing does not exclude aspiration, because aspiration can be "silent," especially if it is chronic [20]. (See "Aspiration due to swallowing dysfunction in children" and "Congenital anomalies of the larynx".)

Asthma — In some children, chronic cough can be the most prominent presenting symptom of asthma. However, isolated cough (cough in absence of other symptoms) is rarely asthma in children [21,22].

●Respiratory symptoms – The cough associated with asthma is typically dry. A wet cough does not exclude asthma but should also raise the possibility of protracted bacterial bronchitis (PBB) or aspirated foreign body (see 'Protracted bacterial bronchitis' below and 'Inhaled retained airway foreign body' below). Typically in asthma there are associated symptoms of wheezing, exertional dyspnea, or atopy, although these features may not be recognized or initially reported by the parents or caregivers.

Asthma in the absence of any of these symptoms, sometimes termed "cough-dominant asthma," or "cough-variant asthma" may present as an apparently nonspecific cough. Most studies have suggested that this is an uncommon cause of cough in children [7,17,23,24]. As an example, a randomized trial in children with nonspecific cough showed no benefit from treatment with beta agonists and steroids [25]. Moreover, observational studies show that nonspecific cough has different risk factors and triggers than classic asthma and that nonspecific cough generally resolves spontaneously [26].

Although cough-dominant asthma is probably uncommon in children, it is still appropriate to consider the possibility of asthma in a child presenting with a chronic dry cough and no other apparent symptoms, primarily because the presence or absence of wheezing is not reliably recognized by the parents or reported on history [27]. Therefore, evaluation for chronic cough in children should include careful questioning about clinical symptoms of wheezing or atopy, with spirometry and response to bronchodilators, and if warranted a trial of anti-asthma medications, as discussed below.

●History – Clues to the presence of asthma include a history of eczema, rhinitis, or bronchiolitis [28]. A family history of atopy or asthma is common. In addition a history of wheeze and paroxysmal cough (that responds to bronchodilators) may be reported [28], although parental reporting of wheeze is often inaccurate [27]. Episodes of asthma are often triggered by acute upper respiratory viral illnesses, exercise, cold, or known allergens.

●Evaluation – Initial evaluation of any child with chronic cough includes a chest radiograph and spirometry (if the child is able). The presence of bilateral hyperinflation on chest radiograph is often, although not always, indicative of asthma. In addition, changes within the right middle lobe are seen in children with asthma (image 1). Spirometry (generally performed in children aged >5 years) that shows an obstructive pattern on the flow volume loop, which reverses with bronchodilators, indicates obstructive airway disease, most commonly asthma.

If the initial evaluation suggests a provisional diagnosis of asthma, the next step is a trial of asthma medications (empiric trial of bronchodilators [short-acting beta-2 agonists] and low-dose inhaled corticosteroids) for two to four weeks, followed by reevaluation (algorithm 1). A clear response to this therapy strongly supports the diagnosis of asthma, but does not fully establish the diagnosis, because nonspecific cough unrelated to asthma frequently resolves spontaneously. Therefore, asthma medication should not be continued unless the diagnosis of asthma can be made with confidence [2]. Lack of response to asthma medications generally is sufficient to exclude asthma. (See "Asthma in children younger than 12 years: Initial evaluation and diagnosis" and "Asthma in children younger than 12 years: Overview of initiating therapy and monitoring control".)

In cases where it is particularly difficult to establish or exclude the possibility of asthma, an airway hyperresponsiveness challenge test in the pulmonary laboratory may be indicated if the child is old enough for testing (≥5 years); this test is not always diagnostic [22]. (See "Asthma in children younger than 12 years: Initial evaluation and diagnosis", section on 'Bronchoprovocation testing'.)

Chronic endobronchial suppurative disease — Chronic endobronchial suppurative disease represents a spectrum ranging from PBB, to chronic suppurative lung disease (CSLD), to bronchiectasis.

While the relationship among these disorders has not been fully established, a pathobiologic model that has been proposed that suggests that PBB, CSLD, and bronchiectasis represent a spectrum of disease, with PBB at one end and irreversible bronchiectasis at the other. The model proposes that some children with PBB will progress to CSLD, then to bronchiectasis (figure 1) [29-31]. All three diseases have similar pathobiology with airway neutrophilia, neutrophilic inflammation (elevated matrix metallopeptidase 9 [MMP-9], interleukin 1 beta [IL1-beta], interleukin 8 [IL-8]) endobronchial infection with typical organisms and impaired mucociliary clearance and efferocytosis (removal of dying cells by macrophages) [32,33].

Support for this model comes from a prospective study of 194 children with PBB, which found that a small percentage of children with PBB (9.6 percent) developed bronchiectasis within five years [34]. Risk factors for development of bronchiectasis were recurrent episodes of PBB and nontypeable Haemophilus influenzae infection. A subsequent study found alveolar macrophages from children with PBB or bronchiectasis demonstrated reduced ability to phagocytose apoptotic airway epithelial cells as well as nontypeable H. influenzae, suggesting that these two conditions have similar pathogenetic mechanisms [35].

Protracted bacterial bronchitis — PBB is one of the most common causes of chronic wet cough, particularly in young children (<5 years of age), accounting for approximately 40 percent of referrals to pediatric pulmonary specialist clinics in resource-abundant countries [15]. This disorder is now incorporated into American, Australian, and European cough guidelines [3,6-8,36]. Identification and treatment of PBB is important because, if untreated, it may be a precursor to bronchiectasis [31,37,38]. (See 'Bronchiectasis' below.)

Diagnosis — PBB is usually diagnosed based on clinical criteria (termed "clinically-based PBB") [32]:

●Chronic wet cough (duration at least four weeks)

●No other symptoms or signs of other causes

●No evidence of an alternative diagnosis after a standard evaluation (including normal spirometry and normal radiograph, other than bilateral peribronchial accentuation) (table 2)

●Resolution of the cough after a two-week course of appropriate antibiotics

PBB is caused by typical respiratory pathogens, such as H. influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis [17,32]. Bronchoscopy is not required for the diagnosis but, if performed, reveals mucopurulent discharge in the bronchi (picture 1). If bronchoscopy is performed and confirms clinically important density of bacteria in the lower airway, the term "microbiologically-based PBB" can be used to distinguish the diagnosis from clinically-based PBB [32].

In some children the diagnostic criteria listed above are met but the disease is more severe. In these cases the term "PBB-extended" is used if the cough only resolves after an extended course (four weeks) of antibiotics; the term "recurrent PBB" is used when a child has more than three episodes per year [32]. (See 'Recurrent protracted bacterial bronchitis' below.)

Differential diagnosis

●Asthma – The clinical symptoms of PBB can be similar to asthma. Unlike asthma, PBB does not respond to bronchodilators and the cough is wet. However, asthma and PBB can coexist. If a child has a chronic wet cough and apparent asthma, but fails to respond to asthma medications, empiric treatment for PBB should be considered [29].

●Foreign body – The symptoms of PBB may also be indistinguishable from foreign body aspiration. Young children are at risk for unrecognized foreign body aspiration, and should be evaluated if there are suspicious features, such as a history of sudden onset of cough after choking, or while eating or playing. (See 'Inhaled retained airway foreign body' below.)

●Bronchiectasis – Bronchiectasis may be associated with a previous or current respiratory infection or by other conditions that predispose to chronic lung infection, including immunodeficiency, anatomic abnormalities, cystic fibrosis, or primary ciliary dyskinesia (table 4). Evaluation for these disorders is warranted in a child who fails to respond to treatment (four weeks of appropriate antibiotics) or has recurrent episodes of PBB (>3 in one year), growth faltering, or other pointers of specific cough [32,38,39]. (See 'Recurrent protracted bacterial bronchitis' below and "Bronchiectasis in children: Pathophysiology and causes".)

Treatment — Children with a clinical diagnosis of PBB should be treated with a prolonged course of antibiotics, with a minimum course of two weeks [7,40-42]. In a meta-analysis of three randomized controlled trials including 190 children with chronic wet cough, treatment with antibiotics improved cough resolution compared with placebo (odds ratio [OR] for persistent cough 0.15, 95% CI 0.07-0.31). The studies included in the meta-analysis were heterogeneous in the definition of chronic cough, the specific antibiotic used, and duration of therapy [41]. In one of the trials included in this meta-analysis, treatment with a two-week course of amoxicillin-clavulanate was significantly more likely to achieve resolution of cough compared with placebo (48 percent versus 16 percent) [40].

American and European guidelines suggest an additional two weeks of antibiotic therapy (four weeks total) for children whose cough persists after two weeks of treatment [3,7], while the British Thoracic Society recommends a four to six week course of antibiotics for all children with PBB [19].

A multicenter randomized trial compared two weeks with four weeks of amoxicillin-clavulanate; although the four-week course did not improve clinical cure by day 28, it did improve symptom control, with a significantly prolonged time to next wet cough (median 150 versus 36 days) [43]. This supports a retrospective review of children with PBB in the United Kingdom that suggested that there may be an association between longer initial courses of antibiotics and a decrease in the rate of recurrent PBB [44]. Further, it has been shown in another retrospective review that for each month of prior wet cough, it took an extra one day to achieve cough resolution while on antibiotic treatment [45]. Better evidence is needed to determine in which children a prolonged course of antibiotics is beneficial, in view of the inherent risks of antibiotic therapy.

For patients with a first clinical presentation and typical features of PBB, the antibiotics are usually selected empirically, targeted to the most likely causative organisms, or can be based upon the sensitivities of organisms if cultures are available from sputum or bronchoalveolar lavage (BAL). The most widely used antibiotic is oral amoxicillin-clavulanate, as it is active against beta-lactamase-producing strains of H. influenzae. Alternatives include most oral second- or third-generation cephalosporins, trimethoprim-sulfamethoxazole, or a macrolide [36]. Azithromycin is not recommended for this purpose, because of a lack of studies demonstrating efficacy for chronic wet cough, and concerns about increasing resistance of S. pneumoniae and H. influenzae to macrolide antibiotics [36].

Bronchoscopy is appropriate prior to antibiotic treatment for patients with atypical features or suspicion of an inhaled foreign body; and also for patients who fail to respond completely to a four-week course of empiric treatment. Some practitioners elect to perform bronchoscopy with BAL and bacterial culture to guide antibiotic selection, especially in children with a very long duration of cough (eg, ≥12 months) [46].

Recurrent protracted bacterial bronchitis — Children with recurrent PBB (>3 episodes in one year) should undergo an evaluation to evaluate for bronchiectasis or an underlying disorder that predisposes to chronic lung infection (table 4) [34]. Important considerations are a retained foreign body, congenital abnormalities, and disorders that can lead to bronchiectasis such as cystic fibrosis, primary ciliary dyskinesia, and immune deficiencies such as selective antibody deficiency [47]. These further investigations usually involve referral to a specialist for bronchoscopy with BAL and/or high-resolution computed tomography (HRCT) chest scan, sweat test, and an immune evaluation [41]. The need for specialist referral and follow-up was shown by a five-year follow-up study of children with PBB, in which two-thirds of children had ongoing symptoms and 9.6 percent had bronchiectasis [34]. (See 'Differential diagnosis' above and "Bronchiectasis in children: Pathophysiology and causes".)

Chronic suppurative lung disease — CSLD refers to a condition with the clinical characteristics of bronchiectasis, such as a chronic wet cough unresponsive to oral antibiotics, but without the radiologic changes on HRCT chest diagnostic of bronchiectasis [29,30,33]. In the past, the term was used more broadly, to describe any condition with chronic purulent secretions on the lungs, such as empyema, bronchiectasis, or lung abscess [30].

CSLD should be suspected in children with recurrent PBB or chronic wet cough that persists despite four weeks of oral antibiotics. Such children should be evaluated with chest HRCT, to help identify any underlying cause, and determine if bronchiectasis has developed [46]. Management of CSLD is not well established, but is similar to that for bronchiectasis, including repeated courses of antibiotics and airway clearance therapies. (See 'Bronchiectasis' below.)

Bronchiectasis — Bronchiectasis is defined by abnormal radiographic signs on chest HRCT. The major sign on chest HRCT is an increase in the bronchial-arterial ratio, and dilatation of peripheral airways with bronchial wall thickening and lack of peripheral airway tapering [48].

Bronchiectasis is likely in a child with a chronic wet cough that persists despite four weeks of antibiotics [46]. In older children, the cough may be productive of mucopurulent sputum. Other symptoms may include recurrent episodes of PBB or other chest infections, exertional dyspnea, hemoptysis, or digital clubbing [30,48]. Children with any of these features should be evaluated with chest HRCT, which will determine if bronchiectasis is present and in some cases may help identify an underlying cause. This is important if bronchiectasis is suspected because early manifestations of bronchiectasis can be reversible if treated optimally [38,49].

Patients with CSLD or bronchiectasis should be evaluated for underlying causes such as trachea-bronchomalacia, cystic fibrosis, immunodeficiency (primary or secondary), ciliary dyskinesia, or recurrent aspiration. Referral to a specialist for further investigation is suggested as investigations include bronchoscopy, sweat chloride testing and genetic testing to evaluate for cystic fibrosis, chest magnetic resonance imaging (if vascular ring is suspected), detailed evaluation of immune function, and tests to evaluate for primary ciliary dyskinesia. (See "Bronchiectasis in children: Clinical manifestations and evaluation".)

The management of bronchiectasis involves a multidisciplinary approach, including antibiotics based on lower airway cultures (oral, or parenteral if oral therapy is inadequate), personalized self-management plans, and airway clearance techniques including respiratory physiotherapy advice, as well as regular physical activity and nutritional advice [50]. Multicenter randomized controlled trials in children have demonstrated that oral amoxicillin-clavulanate is superior to placebo for nonsevere exacerbations, and this remains first choice for empirical therapy in the absence of lower airway cultures [51,52]. Children should receive vaccinations as per national schedule, including pneumococcal vaccination and annual influenza vaccination where available [53]. (See "Bronchiectasis in children without cystic fibrosis: Management".)

Chronic pneumonia — In areas in which tuberculosis (TB) is endemic, it is a common cause of chronic cough in children and adults. Eight countries account for two-thirds of new cases: India (27 percent), China (9 percent), Indonesia (8 percent), the Philippines (6 percent), Pakistan (6 percent), Nigeria (4 percent), Bangladesh (4 percent), and South Africa (3 percent) [54]. Hence, it is important to consider TB in any child with chronic cough in these or other countries where the disease is prevalent, or in those who are at risk of exposure due to travel or infected contacts. Children who have completed TB treatment may also have a chronic cough [55], which may be associated with bronchiectasis, a common manifestation of post-TB lung disease in adults [56]. On examination, children with TB may have a monophonic wheeze due to hilar lymphadenopathy or tuberculoma. Investigations include standard tests such as tuberculin skin test, interferon-gamma release assay, or other available microbiologic investigation such GeneXpert test (detects deoxyribonucleic acid [DNA] to TB bacteria in sputum sample). Imaging with a chest radiograph and chest CT may reveal mediastinal widening, lung collapse, or findings of secondary bronchiectasis. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis".)

Other chronic infections that have a significant role in certain geographical areas or in immunocompromised individuals include nontuberculous mycobacteria, fungi (histoplasmosis or Coccidioides), Legionella, and Chlamydia pneumoniae. As an example, Toxocara canis infection is common in Hungarian children with chronic cough [57]. Investigations such as bronchoscopy, BAL, and chest CT are warranted if atypical chronic infection is suspected. Further investigations for one of these infections are guided by the clinical suspicion, based on the geographical area or exposures (eg, serum T. canis immunoglobulin G [IgG]), and age or immune status of the child. These and any other type of chronic pneumonia may cause a chronic cough. (See "Pneumonia in children: Epidemiology, pathogenesis, and etiology" and "Nontuberculous mycobacterial pulmonary infections in children" and "Zoonoses: Dogs", section on 'Toxocara canis'.)

In young infants, infections with Chlamydia trachomatis, cytomegalovirus, or other agents may cause a chronic pneumonia, sometimes known as "afebrile pneumonia of infancy." (See "Pneumonia in children: Epidemiology, pathogenesis, and etiology", section on 'In neonates' and "Chlamydia trachomatis infections in the newborn", section on 'Pneumonia'.)

Eosinophilic lung disease — The possibility of eosinophilic lung disease should be considered in children with elevated eosinophils in peripheral blood and chronic cough [58]. Pediatric eosinophilic pneumonia is characterized by infiltration of alveolar spaces, resulting in local or diffuse pulmonary infiltrates on radiography [58]. The diagnosis relies on the finding of elevated eosinophils in fluid from BAL. Elevation is often defined as eosinophils >20 percent of total cell count, although the cut-off is controversial, as a disorder known as "nonasthmatic eosinophilic bronchitis" in adults in defined as airway eosinophilia of >3 percent [59]. (See "Causes and epidemiology of subacute and chronic cough in adults", section on 'Nonasthmatic eosinophilic bronchitis'.)

Eosinophilic lung diseases can be classified as primary or secondary. Primary conditions are those in which no other cause is determined. Secondary conditions can be due to infectious causes such as parasites (eg, Ascaris lumbricoides, Strongyloides stercoralis) or fungus (eg, allergic bronchopulmonary aspergillosis, pulmonary coccidioidomycosis, pulmonary histoplasmosis), or rarely drugs [60]. Investigations include peripheral bloods for eosinophil count, bronchoscopy with BAL, and serologic assessment for secondary causes where warranted. (See "Overview of pulmonary eosinophilia".)

Inhaled retained airway foreign body — The possibility of a retained airway foreign body should always be considered in young children (aged <5 years) with a chronic cough. The cough is typically wet-sounding, but may be dry; and there may be associated wheezing or halitosis. The first step is a focused history, specifically asking about an episode of choking, even if weeks before, or sudden onset of the cough in a young child while eating or playing. Even if there is no such history, a foreign body remains a possibility and should be considered in any young child with a chronic cough. (See "Airway foreign bodies in children", section on 'Presentation'.)

The evaluation should also include a careful and sometimes prolonged auscultatory assessment. Findings suspicious for bronchial obstruction include asymmetry in aeration, and focal adventitious sounds, most commonly unilateral low-pitched monophonic wheeze. Only approximately 10 percent of objects aspirated by children are radio-opaque. Therefore, it is important to review the radiograph closely for findings suspicious for bronchial obstruction, particularly unilateral lung hyperinflation (lucency of the lung field distal to the obstruction) (image 2). If possible, chest radiographs should be taken in both inspiration and expiration when foreign body aspiration is suspected because the unilateral hyperinflation may be more apparent on the expiratory film (image 3). (See "Airway foreign bodies in children", section on 'Imaging'.)

If the history, examination, or radiograph is suspicious for a foreign body, the child should always be evaluated with bronchoscopy, which also permits removal of the foreign body. (See "Airway foreign bodies in children", section on 'Bronchoscopy'.)

Uncommonly, an aspirated foreign body may go undiagnosed for months or even years, and can cause focal bronchiectasis. This possibility should be considered in otherwise healthy individuals with focal bronchiectasis. The foreign body may not be evident on chest radiograph or even chest CT; bronchoscopic evaluation may be necessary to make the diagnosis. (See 'Bronchiectasis' above and "Bronchiectasis in children: Pathophysiology and causes".)

Interstitial lung disease — Interstitial lung disease (ILD), also known as "diffuse lung disease," is a group of disorders that involve the pulmonary parenchyma and interfere with gas exchange. These disorders are classified together because of similar clinical, radiographic, physiologic, or pathologic manifestations, but the underlying causes are diverse and include genetic, autoimmune, and acquired/infectious disorders. They tend to present with tachypnea, cough, fine crackles on auscultation, or hypoxemia; failure to thrive or clubbing of the digits may be present. A plain chest radiograph is usually abnormal, but rarely specific. Spirometry (in children >5 years) typically shows a restrictive pattern. The presence of ILD is confirmed by HRCT. Further investigation to determine the type of ILD may include genetic testing or lung biopsy. (See "Classification of diffuse lung disease (interstitial lung disease) in infants and children" and "Approach to the infant and child with diffuse lung disease (interstitial lung disease)".)

Noninfective bronchitis — Exposure to environmental pollutants can trigger noninfective bronchitis and chronic cough in children. Worldwide, indoor air pollution is a major contributor to respiratory health, with the largest burden falling in resource-limited settings; children are more susceptible than adults due to developing lungs and immune systems [61]. The most important indoor air pollutants include environmental tobacco smoke, biologic pollutants (eg, dust mite, mold, pets), nitrogen dioxide from unvented gas heating, and particulate matter from wood stoves and cooking [62]. The importance of environmental tobacco smoke in respiratory health of children is well established and should always be addressed in children with chronic cough [62]. (See "Secondhand smoke exposure: Effects in children".)

Similarly, hazardous outdoor air pollutants can be a contributing factor to chronic cough and bronchitis in children. As an example, a study in Tennessee found an association between toxicity-weighted emissions and the prevalence of chronic bronchitis in children [63]. Another found that exposure to volcanic acid air pollution in Hawaii was associated with chronic cough in children [64].

Identification and mitigation of environmental tobacco smoke and other environmental pollutants is an important step in management of chronic cough. In most cases, these exposures contribute to the development or persistence of chronic cough, but are unlikely to be the sole cause [13].

Postinfection (self-resolving)

Viral infections — Respiratory viral infections are the most common cause of acute cough, and also likely the most common cause of "nonspecific" chronic cough. These children have dry cough and do not have any specific cough "pointers" (table 2) [9]. These cases resolve without any therapies, and can be managed with reassurance and observation. (See 'Nonspecific cough' above and "Approach to chronic cough in children", section on 'Nonspecific cough'.)

Pediatric post-coronavirus disease (COVID) syndrome (post-acute sequelae of SARS-CoV-2) is uncommon; symptoms may include chronic cough, but this is less common than other symptoms (eg, exertional dyspnea) [65,66]. The overall prognosis for respiratory symptoms in these children is good, and there is no evidence that their clinical course differs from any other post-viral syndrome, based on limited data. (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'Post-COVID-19 condition ("long COVID")'.)

Bordetella pertussis infection — In young children, Bordetella pertussis or parapertussis infection can present with a typical paroxysmal whooping cough. In infants and older children, the classic features may not be seen. A cough post-pertussis infection may persist for weeks after the infection has cleared. As an example, in a prospective cohort study, 37 percent of children with chronic cough had serologic evidence of a recent pertussis infection, although most of the subjects had been fully immunized [67]. Thus, post-pertussis cough should be considered in children with chronic cough regardless of immunization status. (See "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis" and "Pertussis infection in infants and children: Clinical features and diagnosis", section on 'Clinical features'.)

If B. pertussis infection is suspected, evaluation depends on the patient's age and duration of cough:

●For children one year and older with chronic cough, the primary purpose of laboratory testing is to confirm the diagnosis and void further invasive work-up since antimicrobial therapy usually is not indicated three weeks or more after symptom onset, and the chronic cough will usually resolve gradually without treatment.

●For infants, different strategies are used for laboratory confirmation, and antimicrobial therapy may be indicated up to six weeks after symptom onset. Details of laboratory testing and indications for treatment are discussed separately.

(See "Pertussis infection in infants and children: Clinical features and diagnosis", section on 'Laboratory confirmation' and "Pertussis infection in infants and children: Treatment and prevention", section on 'Indications'.)

Other infections — Infections such as Mycoplasma pneumoniae and C. pneumoniae also may cause chronic cough, with or without evidence of an antecedent pneumonia. This chronic cough tends to resolve with time and usually does not require antimicrobial therapy in otherwise healthy children. Laboratory confirmation of these organisms is difficult and patients with pneumonia are often treated empirically; the diagnosis sometimes can be made by serology, polymerase chain reaction (PCR), or antigen detection. (See "Mycoplasma pneumoniae infection in children" and "Pneumonia caused by Chlamydia pneumoniae in children".)

Space-occupying lesions — A rare cause of chronic cough in children is a mediastinal mass (eg, due to cancer), which may be evident on initial chest radiograph. Children with findings suspicious for cancer should be further evaluated with chest CT or magnetic resonance imaging and referred to an oncology specialist.

EXTRAPULMONARY CAUSES OF CHRONIC COUGH IN CHILDREN

Cardiac — Rarely, chronic cough in children is caused by underlying cardiac disease, particularly pulmonary hypertension or cardiogenic pulmonary edema. Pulmonary arterial hypertension may be idiopathic, or secondary to congenital heart disease, connective tissue disease, or HIV infection (see "Pulmonary hypertension in children: Classification, evaluation, and diagnosis"). Cardiogenic pulmonary edema is most often caused by left-sided heart disease. (See "Approach to cyanosis in children", section on 'Pulmonary edema'.)

The possibility of underlying cardiac disease may be raised by focused history and examination, as well as chest radiograph, during evaluation of a child with chronic cough. When evaluation raises suspicion for cardiac disease, consultation with a pediatric cardiologist (where available) and investigation with an echocardiogram and electrocardiogram are warranted.

Ear disease (otogenic cough) — A rare cause of chronic cough in children is the otogenic reflex (also known as the ear-cough reflex) [7]. In a minority of individuals, the external ear is innervated by a branch of the vagus nerve. In this case, irritants (eg, cerumen) can cause chronic cough and removal of the irritants may improve the symptom [68,69]. Although this reflex is common among adults with chronic cough, its prevalence in children with chronic cough is similar to that in healthy children [70].

Tic cough (habit cough) and somatic cough disorder (psychogenic cough)

●Tic cough (also known as habit cough) describes a cough with repetitive and habitual features similar to a vocal tic, especially suppressibility, distractibility, suggestibility, variability, and the presence of a premonitory sensation [7,71].

●Somatic cough disorder (previously known as psychogenic cough) is a diagnosis of exclusion after evaluation for other causes of cough and tic cough are excluded and the child fulfills criteria for somatic disorder as outlined in the Diagnostic and Statistical Manual of Mental Disorders, 5^th edition (DSM-5) [71].

Although these types of cough have distinct definitions, they may not always be easily distinguished clinically and the initial approach to management is similar, unless clear markers of somatic cough disorder are present. The cough characteristics vary among patients but may consist of short, single, dry coughs (tics) or may be loud and repetitive (barking/honking in nature). The cough is typically more prominent during office visits and absent during sleep; a history of an antecedent initial upper respiratory tract illness is common and may be a triggering event [71,72]. The physical examination is normal apart from the cough. Although typical clinical characteristics are often evident on first consultation, this remains a diagnosis of exclusion after other possible causes have been evaluated [71]. The typical age range for children with these disorders is 4 to 18 years, with a median of 10 years [73]. The prevalence varies substantially among different populations and also depends on awareness of this diagnosis among clinicians. In a study of patients referred for chronic cough in Australia, the prevalence of tic cough was 4.3 percent overall and 8 percent in a pulmonology clinic in Sydney [15].

The most successful therapy for these types of cough in children has been suggestion therapy, which employs a distractor, such as sipping warm water, as an alternative behavior to the cough (table 5) [72,73]. In a systematic review, suggestion therapy was successful in resolving cough in 96 percent of patients with tic cough [74]. An explanation and reassurance (directed primarily to the child) also may be effective [75]. Children with somatic cough disorder may require referral to a psychologist and/or psychiatrist if unresponsive to suggestion therapy.

Cases of Tourette syndrome presenting with chronic cough have been reported; children with other vocal or motor tics should be further evaluated for this or another tic disorder [76,77]. (See "Hyperkinetic movement disorders in children", section on 'Tic disorders' and "Tourette syndrome: Pathogenesis, clinical features, and diagnosis".)

Medications — A small number of medications are known to cause a chronic cough. In particular, cough is a well-recognized side effect of angiotensin-converting enzyme (ACE) inhibitors [78]. Any inhaled medications, proton pump inhibitors, and a few other medications may occasionally cause cough as an idiosyncratic side effect. If suspected, the medication should be withdrawn and the cough usually resolves.

Other medications can cause lung disease that results in chronic cough, such as interstitial lung disease (ILD) with cytotoxic drugs.

Causal role unlikely — A preponderance of evidence suggests that gastroesophageal reflux and upper airway pathology are unlikely sole causes of chronic cough in children:

Esophageal disorders/gastroesophageal reflux — Gastroesophageal reflux disease (GERD) rarely causes chronic cough in children, although some children with chronic cough have GERD. Most experts suggest that GERD is not a common cause of isolated chronic cough, except in children with neurologic abnormalities predisposing to aspiration [13,15,18]. This is supported by many prospective studies that report that GERD is not a common cause of cough in children, as summarized in a systematic review [13].

Data from ambulatory monitoring of esophageal pH also suggest that acid reflux is not a common cause of chronic cough. In one such study, more than 80 percent of coughs were independent of a reflux event and when the events coincided, reflux was no more likely to precede than to follow cough [79]. There is somewhat better evidence to suggest a role for nonacid reflux in triggering chronic cough. In a few studies that used impedance manometry (a technique that can detect both acid and nonacid reflux), a temporal association between reflux events and some of the episodes of cough was noted in approximately 50 percent of children with chronic unexplained cough, suggesting a possible association in some individuals [80-83].

Therefore, GERD treatments should not be used in children <14 years old with chronic cough when no clinical features of GERD are present, as stated in an expert-panel systematic review [84]. (See "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents", section on 'Clinical manifestations'.)

For children with chronic cough and without underlying lung disease who do have gastrointestinal GERD symptoms (such as recurrent regurgitation, dystonic neck posturing in infants, and heartburn in older children), we suggest further investigation and treatment when appropriate, following current GERD guidelines for children [85,86]. Importantly, for these children with chronic cough and gastrointestinal GERD symptoms, it is recommended that a treatment trial of four to eight weeks of appropriate therapy be used, with reevaluation for response and cessation of therapy if there is no therapeutic benefit.

Upper airway pathology — Upper airway disorders are probably not a cause of chronic cough in children; the main considerations are:

●Upper airway cough syndrome (UACS) – UACS, also known as "postnasal drip," is probably an uncommon cause of chronic cough in children, although there is some controversy on this question [13,18]. In a systematic review, only two of the ten included studies reported that UACS was a common cause of cough in children; both of these studies were from Turkey [13]. By contrast, UACS is thought to be a common cause of chronic cough in adults. (See "Causes and epidemiology of subacute and chronic cough in adults", section on 'Upper airway cough syndrome'.)

●Chronic rhinosinusitis – Similarly, chronic noninfectious rhinitis is probably not a common cause of cough in children, although it is a recognized cause of UACS in adults. Nonetheless, if a child has chronic cough and symptoms of a chronic noninfectious or allergic rhinitis (eg, because of chronic clear nasal drainage and boggy or edematous nasal mucosa), a trial of intranasal glucocorticoids is appropriate. (See "An overview of rhinitis".)

●Chronic sinusitis – Chronic sinusitis is not a common cause of chronic cough in children except in association with an immune defect predisposing to chronic infection [7,13]. Typical symptoms of chronic sinusitis are a thick and colored chronic nasal discharge. It is common practice to treat patients empirically with antibiotics, and in some cases both the discharge and cough improve with treatment. However, this response does not prove an association between sinusitis and cough. This is because patients with protracted bacterial bronchitis (PBB) may present with identical symptoms, and would respond to antibiotics. Moreover, many other cases of chronic cough will improve or resolve over time regardless of the intervention. (See "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis", section on 'Clinical features'.)

●Obstructive sleep apnea (OSA) – No convincing evidence exists to suggest a clear relationship between OSA and chronic cough in children, although it is a reported cause in adults [13,87]. A prospective cohort study investigating children with chronic cough using a standardized chronic cough algorithm also evaluated for sleep-disordered breathing (including observed apneas in sleep, daytime somnolence, large tonsils) and found that a small number with OSA diagnosed on polysomnography had chronic cough that resolved with surgical treatment of their OSA [88]. Hence children with suspected OSA should be treated separately for both conditions according to sleep and cough guidelines, respectively.

MANAGEMENT — In the management of chronic cough, the key principles are:

●Specific cough – Targeted treatment for the suspected or confirmed cause, as determined by a systematic evaluation. The approach to treatment for several of these disorders is included in the discussion above:

•Asthma (see 'Asthma' above and "Asthma in children younger than 12 years: Overview of initiating therapy and monitoring control")

•Protracted bacterial bronchitis (PBB) (see 'Protracted bacterial bronchitis' above)

•Tic cough or somatic cough disorder (see 'Tic cough (habit cough) and somatic cough disorder (psychogenic cough)' above)

●Nonspecific cough – For patients with nonspecific cough (chronic dry cough with no specific cough pointers (table 1)), management focuses on watchful waiting. Drug trials are occasionally warranted. Details of management and monitoring are discussed separately. (See "Approach to chronic cough in children", section on 'Nonspecific cough'.)

●Counseling – In addition, management of any type of chronic cough should include counseling to [7]:

•Identify and mitigate exacerbating factors, such as exposure to environmental tobacco smoke

•Avoid over-the-counter cough suppressants

•Define the burden of the cough on the child and parent(s), and manage their expectations

These steps are discussed in detail in the linked topic. (See "Approach to chronic cough in children", section on 'Other management considerations'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic cough in children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Cough in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Chronic cough in children is defined as a cough lasting more than four weeks. "Specific cough" refers to a chronic cough that is ultimately attributable to an underlying abnormality or disease, which is usually, but not always, of pulmonary origin (table 1). Conversely, "nonspecific cough" is defined as a chronic cough that does not have an identifiable cause after a reasonable evaluation. (See 'Definitions' above.)

●Evaluation – The evaluation of a child with chronic cough should include a detailed history, physical examination, chest radiograph, and spirometry (when possible in children aged >5 years) using algorithmic approach (algorithm 1). Signs and symptoms suggesting a specific cause of cough are outlined in the table (table 2). If the initial evaluation provides clues suggesting a specific cause of cough, further evaluation is focused on that diagnostic possibility. (See "Approach to chronic cough in children".)

●Major causes of chronic cough and initial management

•Protracted bacterial bronchitis (PBB) – PBB is a common cause of chronic cough in young children (<5 years of age) in Australia, Europe, and similar populations.

-A provisional diagnosis of PBB can be made in a child presenting with chronic wet cough, no other symptoms, and no evidence of an alternative diagnosis (eg, retained airway foreign body or pneumonia) after a standard clinical evaluation. (See 'Protracted bacterial bronchitis' above.)

-For patients with a provisional diagnosis of PBB, we suggest antibiotic therapy (Grade 2B). Small, randomized trials have shown that, compared with placebo, antibiotics improve cough resolution in children with chronic wet cough. We typically treat with oral amoxicillin-clavulanate for two weeks. Alternatives include oral second- or third-generation cephalosporins, trimethoprim-sulfamethoxazole, or a macrolide. Azithromycin should not be used in this setting, due to lack of demonstrated efficacy and concerns of inducing antibiotic-resistant organisms. (See 'Treatment' above.)

-For children who continue to cough after two weeks of antibiotics, we suggest prolonging the course of antibiotics (up to four weeks) (Grade 2C). This is based on our clinical experience and a randomized trial that found that four weeks of treatment improved some but not all outcomes; further clinical trial data are required. (See 'Treatment' above.)

-If a wet cough fails to improve after a four-week course of antibiotics, or if PBB recurs frequently (>3 times in 12 months), the patient should be further evaluated for other causes, including a retained foreign body, congenital abnormalities, and bronchiectasis and its causative disorders such as cystic fibrosis, primary ciliary dyskinesia, and immune deficiencies. (See 'Recurrent protracted bacterial bronchitis' above and 'Bronchiectasis' above.)

•Asthma – Asthma is a common cause of chronic cough in children of all ages, and the cough is typically dry, except if there is a concurrent respiratory infection. It usually is associated with symptoms of wheezing, but some children may have cough as their primary or only symptom of asthma. Therefore, evaluation for chronic cough in children should include careful questioning about clinical symptoms of exertional dyspnea, recurrent wheezing, or atopy, with spirometry and evaluation of response to bronchodilators. If the initial evaluation suggests a provisional diagnosis of asthma, the next step is a trial of asthma medications (empiric trial of bronchodilators [short-acting beta-2 agonists] and/or low-dose inhaled corticosteroids) for two to four weeks, followed by reevaluation (algorithm 1). Asthma medication should not be continued unless the diagnosis of asthma can be made with confidence. (See 'Asthma' above.)

•Foreign body – The possibility of an inhaled foreign body should always be considered in young children with a chronic cough who have a history of sudden onset after a choking episode or began after eating or playing. These children should be evaluated with a chest radiograph as a first step but should also be referred to a specialist for evaluation and urgent bronchoscopy, regardless of radiographic findings. (See 'Inhaled retained airway foreign body' above and "Airway foreign bodies in children".)

•Tic cough – Tic cough (also known as habit cough) describes a cough with repetitive and habitual features similar to a vocal tic. Key characteristics are suppressibility, distractibility, suggestibility, variability, and presence of a premonitory sensation. Many cases can be successfully managed with suggestion therapy (table 5). (See 'Tic cough (habit cough) and somatic cough disorder (psychogenic cough)' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Roni Grad, MD, who contributed to earlier versions of this topic review.