Bradley Chipps, MD, FAAP

As complex as it is common, chronic cough in children presents diagnostic and treatment challenges that are complicated by a dearth of solid data and, often, the anxieties of well-meaning parents. 

	An important defense mechanism for clearing the airway and signaling the presence of an upper respiratory tract infection (URTI), coughing represents the most common reason for pediatrician visits in the United States.

 However, the search for an underlying etiology often proves fruitless, and in other cases multiple etiologies may overlap, making diagnosis and treatment difficult. However, a practical approach focuses on red-flag symptoms that help point the way toward appropriate management strategies regardless of diagnosis.

 reflex occurs when inhaled, aspirated, or locally produced objects activate sensory nerves located throughout the airway. These afferent nerves communicate with the brainstem, which signals motor nerves that activate respiratory muscles to produce the characteristic cough response.

	Often, coughing is normal. Healthy school-aged children typically cough between 10 and 34 times daily.

 Of concern, however, is chronic cough, which for practical purposes most experts define as cough lasting more than 4 weeks,

 based on the expected duration of acute URTIs, which represent the most common cause of coughing in adults and children. Coughing associated with a typical viral URTI lasts 14 to 21 days.

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	Because most acute (lasting longer than 3 weeks) and subacute (lasting 3 to 8 weeks) coughs in adults and children signal viral URTIs, they do not demand specific diagnostic evaluation. In otherwise healthy children, these coughs stem from transient situations that are likely to be self-limited.

	However, the aftermath of viral respiratory tract infections can include upregulation of cough reflex sensitivity (CRS), which can provoke coughing long after the infection has resolved.

	Other conditions associated with increased CRS include asthma, 

 (GERD, albeit weakly), and angiotensin-converting enzyme inhibitor therapy.

	Children in whom cough reflex hypersensitivity persists beyond 3 weeks may require evaluation. Additionally, all children with cough persisting beyond 8 weeks should be evaluated.

	Outside CRS and garden-variety URTIs, other forms of abnormal, persistent coughing in children can be associated with more severe, progressive underlying illnesses and/or structural abnormalities. Such cases require thorough evaluation to ensure that underlying problems are properly identified and, to the extent possible, addressed. The Table lists cough characteristics and associated symptoms that should raise these red flags.

	Although multiple etiologies can overlap, the following questions

 can help determine the etiology of a particular cough:

	·      Is the cough an isolated symptom; if not, what other symptoms exist?

	·      What is the cough's character or quality? How disruptive is it?

	·      At what time(s) does the cough occur?

	·      Is there a family history of respiratory, allergic, or infectious disease?

	·      Does the child (or do the parents) 

? Is there evidence of environmental pollutants in the home?

	·      What treatments have been tried, and what were their effects?

	·      What medications, if any, does the child take?

 for chronic pediatric cough is quite varied, the child's age can help narrow the investigation. In this regard, the top 3 causes of chronic cough in adults and older children-upper airway congestion syndrome (UACS, formerly called postnasal drip syndrome), asthma, and GERD-rarely afflict preschool-aged children.

	In 2 studies of children whose average ages were 9.2 years and 8.4 years, respectively, UACS, 

, and GERD accounted for a combined 83% and 69% of cases, respectively.

 Conversely, these diagnoses accounted for just 9% of cases in a similar review involving children whose average age was 2.6 years.

 In this study, persistent bacterial bronchitis (PBB), postinfectious causes, and bronchiectasis (irreparable structural damage to the airway wall) accounted for a combined 68% of cases. In the 2 reviews involving older children, the corresponding totals for these 3 diagnoses were 5% and 40% (the latter included PBB, 35%), respectively.

	Additionally, in infants and younger children, causes of coughing more likely include foreign-body aspiration and abnormalities of the upper respiratory, lower respiratory, and gastrointestinal tracts, versus the infectious agents and habit cough that predominate in older children and teenagers.

	Specific etiologies of cough that clinicians are likely to encounter include:

This syndrome encompasses various types of rhinosinus diseases, particularly allergic or nonallergic rhinitis and sinusitis, that can induce cough. Diagnostic criteria include postnasal drip, nasal discharge, and throat clearing caused by rhinosinusitis. Alone or with other entities, UACS is the most common cause of cough in adults and older children. It is particularly associated with nocturnal coughing. Regarding chronic sinusitis, chronic sinus inflammation doesn't always show up on routine x-rays.

The leading cause of emergency department visits in children, this condition provokes signs and symptoms including frequent, intermittent coughing, as well as wheezing or whistling upon exhaling, dyspnea, chest congestion, tightness, or pain.

 When considering asthma in children aged 2 to 4 years, the Modified Asthma Predictive Index

In this variant, which rarely occurs in infants, cough may be the main or sole symptom. In children without history of recurrent wheezing, the condition is frequently underdiagnosed. Because it rarely responds to asthma medications, accurate diagnosis is crucial.

Poorly characterized in medical literature, PBB is underdiagnosed, and frequently misdiagnosed as asthma. Key characteristics include an intense neutrophilic airway inflammatory response, revealed by bronchoscopy.

 Organisms most commonly responsible include 

Streptococcus pneumoniae, Haemophilus influenzae, 

. Children with PBB have normal adaptive immune function but heightened reactivity of the innate immune system.

 If untreated, some children with PBB will progress to chronic suppurative lung disease, the precursor of bronchiectasis.

Theoretically, intraesophageal reflux, laryngopharyngeal reflux, and microaspiration all may provoke cough. Moreover, GERD and 

 occur commonly in infants and, to a lesser degree in the case of aspiration, children. However, the link between reflux and cough in children, particularly younger children, is tenuous at best. There is little convincing evidence that GERD commonly causes isolated chronic cough in children.

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This harsh, dry, honking, repetitive cough usually appears after a trivial viral infection. Although adults may consider habit cough disruptive, affected children typically remain unperturbed. Habit cough disappears with distraction and during sleep.

Pertussis, pertussis-like, and mycoplasma infections-

A cough (with or without other symptoms) lasting more than 6 weeks may signal 1 of these entities, the 3 leading infectious causes of cough. Ruling them out, which is especially important with 

 that has been near epidemic for the past 2 decades, requires laboratory testing.

Collapse of the tracheal walls or the bronchi creates symptoms such as airflow obstruction and wheezing, stridor, or both.

Signs include breathing problems, persistent cough, wheezing, and lung infections, as well as developmental abnormalities such as finger clubbing, rectal prolapse, and nasal or sinus polyps.

Stemming from allergic reaction, this entity manifests as a corticosteroid-responsive chronic cough in nonsmokers, with evidence of airway inflammation but lacking airflow abnormalities characteristic of asthma.

	The concept of specific versus nonspecific cough underpins American College of Chest Physicians guidelines for diagnosing and treating chronic cough in children.

 If nonspecific, the typically dry cough is the sole or predominant symptom. The child exhibits no markers of more troublesome etiologies. Viral infections and increased CRS account for many cases of nonspecific cough.

	Fortunately, most cases of nonspecific cough resolve spontaneously.

 Specific cough, on the other hand, is associated with underlying respiratory or systemic disease that requires further investigation, typically following the direction suggested by the coexisting symptoms, 

, and laboratory results. Among these markers, a frequent (daily) wet cough is the most reliable clinical hallmark of specific cough.

	In pediatric reports, a wet or moist (also called productive) cough has been associated with asthma, 

 exposure, and endobronchial bacterial infection.

 Similarly, a barking or brassy cough in infancy or childhood may signal croup (or, in infancy only, tracheomalacia or other anatomic abnormalities of the respiratory or gastrointestinal tract).

	Additional indicators of specific cough in children based on history and physical examination include auscultatory findings (wheezing or crackling), cardiac abnormalities (including murmurs), and immune deficiencies.

	A previously published algorithm (Figure 1 and Figure 2) for evaluating children with chronic cough relies on signs, symptoms, and history to guide the investigation toward either a specific or nonspecific cause and, wherever possible, appropriate treatment.

	Regarding diagnostic strategies and procedures, all children with chronic cough should undergo the following measures:

	·      A careful, systematic examination, including a thorough history, seeking possible causes of allergy or chronic infection;

	·      A chest x-ray to check for abnormalities of the heart, lungs, and other structures.

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	The following tests also may be indicated, at the pediatrician's discretion:

If one suspects bronchiectasis or interstitial lung disease, supporting either diagnosis requires a chest CT without contrast. For patients with persistent upper airway symptoms, a limited CT scan of the sinuses, if normal, is most helpful to rule out intrinsic sinus disease. Interpret results carefully, however, because abnormal sinus scans routinely occur in asymptomatic children.

Most children aged 6 years and older-and some as young as 3 years-can successfully undergo spirometry.

 When performed with a bronchodilator, spirometry showing reversible airway obstruction (at least 12% improvement in forced expiratory volume in 1 second) suggests asthma. Conversely, patients with normal spirometry require more advanced testing such as the methacholine challenge, which is most helpful when negative. If patients with abnormal pulmonary function fail to respond to a bronchodilator or inhaled corticosteroids (ICS), consider the following etiologies:

	·      Structural airway abnormalities;

Findings of more than 2% eosinophils per high-power field (using induced sputum samples for most reliable results) can support a diagnosis of asthma and predict response to ICS.

 Conversely, children without history of wheezing, reversible airflow obstruction, or elevated markers of airway inflammation probably do not have asthma.

Experts consider laboratory studies useful in ruling out infectious causes, immunodeficiency, and CF in pediatric chronic cough. One should measure quantitative immunoglobulins in all children with persistent cough secondary to recurrent bacterial infections. Conversely, a pH probe study may help diagnose gastroesophageal reflux (with or without aspiration), and impedance studies are increasingly recommended to evaluate non–acid reflux. Flexible bronchoscopy may help highlight airway abnormalities, chronic infection, or aspiration (with or without retained foreign body) in children. Finally, always investigate children with chronic productive purulent cough for bronchiectasis, and to identify treatable underlying causes such as CF and immune deficiency.

	Wherever possible, treating pediatric cough requires addressing the underlying etiology. For chronic nonspecific cough, however, physicians frequently try empiric therapies.

Unlike in adults, antihistamines (alone or combined with decongestants, 

, or codeine) have little if any effect on pediatric cough or sleep disturbances associated with nocturnal cough. In allergic rhinitis, however, pediatric reports have revealed significant improvements from use of oral cetirizine, terfenadine, and mometasone nasal spray.

 If a patient with chronic sinusitis responds to oral antibiotics but symptoms return after treatment stops, consider a 3-week to 4-week dose rather than the typical 10 days.

Therapy for asthma-associated cough mirrors age-based therapeutic guidelines for asthma.

 No data support empiric use of beta-adrenergic 

, anticholinergics, theophylline, or leukotriene modifiers for chronic, nonspecific cough in children. Therefore, establishing the diagnosis of asthma is crucial. For children with isolated, dry cough suspicious for asthma, experts recommend an empiric trial of ICS (fluticasone, 200 µg/d to 400 µg/d; or budesonide or equivalent, 400 µg/d to 800 µg/d) lasting from 2 to 12 weeks. With proper inhalation technique, most patients respond within 4 weeks. The presence of multiple cough etiologies may delay response to therapy if all causes are not treated appropriately. Additionally, one must periodically reassess therapy and discontinue it in nonresponsive patients.

Here, the drug of choice is either amoxicillin and clavulanate-90 mg/kg/d of the amoxicillin component-or a 

 (dosing depends on the product). Because of a high incidence of bacterial reemergence requiring a second course of therapy, initial therapy should last at least 3 weeks.

Helpful therapies in children include proton pump inhibitors, prokinetic agents, and H2 antagonists.

 However, data regarding the efficacy of treating chronic nonspecific cough in children with empiric GERD therapy remain inconclusive.

Although a different entity from psychogenic cough and cough tic, habit cough commonly responds to behavioral therapies such as self-hypnosis, biofeedback, or suggestion therapy. It is also important to halt any unnecessary medications for asthma, for which habit cough is often mistaken.

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Laboratory tests involving cultures, serology, and polymerase chain reaction methods can confirm the diagnosis of 

. In infants, and for others with highly suggestive clinical histories, strongly consider treating while awaiting results. Recommended agents include azithromycin, clarithromycin, and erythromycin. Trimethoprim sulfamethoxazole also can be used.

Most children outgrow tracheomalacia. Most cases require only conservative management: air humidification, physical therapy, slow feedings, and antibiotics to control infections.

This condition requires lifelong, multidisciplinary management to address respiratory, digestive, and 

This cough generally responds to ICS, however, occasionally patients may need long-term prednisone.

	If history or examination reveals the presence of exacerbating factors such as allergens or smoking, patients' families should eliminate or minimize these factors wherever possible. Likewise, over-the-counter cough medicines have shown little, if any, benefit beyond the placebo effect in children. Because dextromethorphan and codeine have been linked with significant morbidity and, rarely, mortality, the American Academy of Pediatrics advises against treating any type of cough with these drugs. Often, clinicians also must educate parents about the need for patience. Even with appropriate therapies, some patients with chronic cough require up to 12 weeks' treatment to experience relief.

	Common in children, coughing usually reflects a self-limited respiratory infection. However, cough that lasts beyond 8 weeks or that perhaps points to a serious underlying diagnosis requires thorough evaluation including, at the very least, a thorough history and physical examination, chest x-ray, and (in able children) spirometry.

	When a specific diagnosis emerges, this etiology should drive treatment decisions. For nonspecific cough, let available evidence guide an empiric trial. In such cases, it may help to characterize the cough as wet (suggesting antibiotics for possible PBB or sinusitis) or dry (suggesting ICS for possible asthma). With any chronic cough, one also must consider and, if necessary, address the impact of environmental factors and 

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	2. Munyard P, Bush A. How much coughing is normal? 

	3. Chang AB, Glomb WB. Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. 

	4. Khoshoo V, Edell D, Mohnot S, Haydel R Jr, Saturno E, Kobernick A. Associated factors in children with chronic cough. 

	5. Asilsoy S, Bayram E, Agin H, et al. Evaluation of chronic cough in children. 

	6. Marchant JM, Masters IB, Taylor SM, Cox NC, Seymour GJ, Chang AB. Evaluation and outcome of young children with chronic cough. 

	7. Mayo Clinic. Childhood asthma. Available at: 

http://www.mayoclinic.org/diseases-conditions/childhood-asthma/basics/symptoms/con-20028628

. Published March 5, 2013. Accessed February 13, 2015.

	8. Guilbert TW, Morgan WJ, Zeiger RS, et al. Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma. 

Articles

As complex as it is common, chronic cough in children presents diagnostic and treatment challenges that are complicated by a dearth of solid data and, often, the anxieties of well-meaning parents.

Bradley Chipps, MD, FAAP

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