Approach to chronic cough in children د هالة الرفاعي

INTRODUCTION

Coughing is an important defensive reflex that protects from aspiration of foreign materials, and enhances clearance of secretions and particulates from the airways. Healthy children may cough on a daily basis; one study documented an average of 11 cough episodes every 24 hours

However, a cough may also be the presenting symptom of a serious underlying pulmonary or extrapulmonary disease. The causes of chronic cough in children are quite different from that of adults, so evaluation and management of children should not be based on adult protocols. Adolescents 15 years and older may be evaluated using guidelines for adults

The differential diagnosis of chronic cough in children includes subacute and chronic infections bacterial bronchitis pertussis, mycoplasma, tuberculosis foreign body aspiration, and cough dominant asthma

Gastroesophageal reflux, upper airway cough syndrome (formerly known as postnasal drip syndrome), and sinusitis are sometimes implicated because of associations with chronic cough in adults, but their role in causing chronic cough in children is controversial [

Less common disorders must be excluded if the cough is unusually severe and/or frequent, or when there is evidence of failure to thrive, growth retardation, purulent sputum, exertional dyspnea, hypoxemia, chest pain, or hemoptysis

chronic cough appears to be common, with an estimated prevalence of 5 to 7 percent in preschoolers, and 12 to 15 percent in older children Cough is more common among boys than girls up to 11 years of age and may be less common in developing countries than in affluent countries [

DEFINITION There is no consensus as to the length of time in the definition of chronic cough in children. The American College of Chest Physicians, Thoracic Society of Australia and New Zealand, and many studies have defined chronic cough as one that lasts more than four weeks, because most acute respiratory infections in children resolve within this interva

In comparison, guidelines from the British Thoracic Society define chronic cough as one that lasts more than eight weeks However, these guidelines also describe a "prolonged acute cough" as one that lasts at least three weeks

PHYSIOLOGY Each cough occurs through the stimulation of a complex reflex arc This is initiated by the irritation of cough receptors that exist not only in the epithelium of the upper and lower respiratory tracts, but also in the pericardium, esophagus, diaphragm, stomach, and external ear

Chemical receptors sensitive to acid, heat mechanical cough receptors can be triggered by touch or displacement. The proximal airways (larynx and trachea) are more sensitive to mechanical stimulation, the distal airways more sensitive to chemical stimulation. Irritation at the bronchiolar and alveolar level does not cause cough

Impulses from stimulated cough receptors traverse afferent branches of the vagus nerve to a "cough center" in the medulla and nucleus tractus solitarius, which itself is under control by higher cortical centers. The cough center generates an efferent signal that travels down the vagus, phrenic, and spinal motor nerves to expiratory musculature to produce the cough

The mechanical events of a cough can be divided into three phases

Inspiratory phase: Inhalation, which generates the volume necessary for an effective cough. Compression phase: Closure of the larynx combined with contraction of muscles of chest wall, diaphragm, and abdominal wall result in a rapid rise in intrathoracic pressure. Expiratory phase: The glottis opens, resulting in high expiratory airflow and the coughing sound. Large airway compression occurs. The high flows dislodge mucus from the airways and allow removal from the tracheobronchial tree.

The specific pattern of the cough depends on the site and type of stimulation. Mechanical laryngeal stimulation results in immediate expiratory stimulation (sometimes termed the expiratory reflex), probably to protect the airway from aspiration; stimulation distal to the larynx causes a more prominent inspiratory phase, presumably to generate the airflow necessary to remove the stimulus

Cough is an important defensive reflex that is required to maintain the health of the lungs. Children who do not cough effectively are at risk for atelectasis, recurrent pneumonia, and chronic airways disease from aspiration and retention of secretions

Many disorders can impair a child's ability to cough effectively, resulting in persistent cough. Children with neuromuscular disease and chest wall deformities may not generate a deep enough inspiratory volume or expiratory flow necessary for effective clearance of secretions due to defective "pump" mechanisms

Children with reduced function of the abdominal wall musculature are particularly at risk for ineffective cough. Children with tracheobronchomalacia ("floppy" airways), or with obstructive airways diseases, often do not generate the high flow rates needed for effective clearance of secretions. Individuals with laryngeal disorders, including those with tracheostomies, may not achieve sufficient laryngeal closure to generate the increased intrathoracic pressures necessary for an effective cough [

DIAGNOSTIC APPROACH Children with chronic cough should be evaluated with a detailed history, physical examination, chest radiograph, and (if the child is able) spirometry This evaluation often provides sufficient information to categorize the cough as specific (ie, caused by an underlying disease) or nonspecific

Specific cough — The causes of specific chronic cough fall into the following general categories

Asthma Persistent bacterial bronchitis Chronic suppurative lung disease and bronchiectasis Airway abnormality (congenital, foreign body, or neoplastic) Aspiration Chronic or less common infections Interstitial lung disease Extrapulmonary causes: cardiac abnormalities, ear conditions

The sequence of evaluation for these disorders is informed by the age and presenting features of the child. Identification of the presenting features and cough characteristics is important because many are easily recognizable and strongly suggestive of a specific cause; this is less true in adults.

Key symptoms and signs — Certain symptoms and signs are highly predictive of a specific cough. These signs or symptoms narrow the diagnostic possibilities and call for further specific testing or referral

Chronic wet cough Wheezing or crepitations Onset after an episode of choking, or sudden onset while eating or playing Abnormal chest radiography or spirometry Associated cardiac or neurologic abnormalities Failure to thrive, feeding difficulties, or hemoptysis

the symptom of a chronic wet cough, with or without production of purulent sputum, is always pathologic and warrants investigations for a persistent endobronchial infection (persistent bacterial bronchitis or chronic suppurative lung disease), retained airway foreign body, or immunodeficiency

Nonspecific cough — If symptoms suggesting specific cough are absent and the chest radiograph and spirometry are normal the possibility of asthma should be considered and pursued with an empiric trial of bronchodilators and other asthma medications

If there is no response, the child should be considered to have a nonspecific cough, and the medication should be stopped. The child and parents should be reassured and the patient observed over time for possible emergence of specific symptoms

HISTORY — The diagnostic approach outlined above requires a detailed history, which should focus on the following key elements Age and circumstances at onset — Neonatal onset of coughing should prompt consideration of congenital malformations (eg, tracheobronchomalacia), conditions predisposing to aspiration

tracheoesophageal fistula, laryngeal cleft, or a neurological disorder), or chronic pulmonary infections (eg, cystic fibrosis or ciliary dyskinesia

A cough that begins suddenly while playing or eating, especially in the toddler age range, should raise suspicion of an aspirated foreign body in the airway. The physician should specifically ask about a history of choking, because this may have occurred weeks before and the family may not voluntarily recall the information. Even if there is no history of choking, a foreign body remains a diagnostic possibility

An episode of severe pneumonia can damage the airways, making the child vulnerable to chronic cough. More rarely, severe pneumonia may cause frank bronchiectasis. A psychogenic or habitual cough also often begins after an upper respiratory infection.

Nature of the cough.

Chronic paroxysmal cough triggered by exercise, cold air, sleep, or allergens is often seen in patients with asthma. Barking or brassy cough suggests a process in the trachea or more proximal airways, such as airway malacia, laryngotracheobronchitis, spasmodic croup, or foreign body

Staccato cough in young infants can be the result of infection with Chlamydia trachomatis. Cough that is honking ("Canadian Gooselike") and disappears at night suggests a psychogenic or habitual cough.

A chronic productiv coughe suggests a suppurative process, and may require further investigation to exclude Bronchiectasis cystic fibrosis immune deficiency, or congenital malformation active infection

Acute or subacute paroxysmal cough suggests infection with pertussis or parapertussis; this characteristic cough can be retriggered by subsequent upper respiratory illness

Timing and triggers The timing and triggers associated with cough can help guide diagnosis Cough due to asthma typically occurs following exposure to characteristic asthma triggers (ie, allergens, smoke, exercise, cold air, or viral infection), and typically worsens during sleep

Cough associated with nasal problems typically is worst during changes of position, while cough due to bronchiectasis typically is worst and most productive early in the day. Cough that is triggered during swallowing is suggestive of aspiration, either primary or due totracheoesophageal fistula or laryngeal abnormalities

Cough in the first hour after meals, or which is worse while supine, may reflect gastroesophageal reflux

Associated symptoms A history of dyspnea or hemoptysis should trigger a search for an underlying lung disease Hemoptysis should also raise concerns of bronchiectasis, cavitary lung disease (tuberculosis or bacterial abscesses), heart failure, hemosiderosis, neoplasm, foreign bodies, vascular lesions, endobronchial lesions, catamenial bleeding, and clotting disorders

Cough, with or without symptoms of pancreatic insufficiency, recurrent endobronchial infection, and/or failure to thrive should raise suspicion of cystic fibrosis Cough associated with persistent fever, and/or failure to thrive, or weight loss should raise suspicion of chronic infection and immune deficiency

Children with neurologic impairment or seizures frequently have chronic aspiration Anaphylactic reactions to food can include cough but are unlikely to present with recurrent cough in the absence of other symptoms of anaphylaxis

Past medical history The past medical history should include an account of the pregnancy, labor, and delivery, as well as the neonatal course Low birth weight and/or premature neonates are at risk for developing atopic sensitization and asthma.

The past medical history should also include questions related to eczema and pulmonary infections. In preschool children, a history of infantile eczema is often associated with inhalant allergy

Family history Family history of atopy or asthma increases the risk in offspring, and suggests a diagnosis of either allergic rhinitis or asthma in the child with chronic cough

Family history of cystic fibrosis or primary ciliary dyskinesia should raise suspicion for these disorders. A careful history should be obtained for current illness in family members or close contacts; such individuals with cough, weight loss, and night sweats should arouse suspicion of tuberculosis. In some cases, the possibility of HIV transmission from mother to child should be assessed

Social history and environmental exposures Passive or active exposure to smoke from tobacco marijuana, cocaine or other chemical irritants can result in chronic cough In addition, woodburning stoves cause indoor air pollution and can predispose children to respiratory infection s Gas stoves are also associated with respiratory symptoms in children

It is important to elicit any history of contact with pets or other animals, as cough may be induced by allergy to the animals. Similarly, the location of the child's home and travel history may be relevant. Local epidemiology can inform the diagnostic considerations, especially with respect to endemic fungal and parasitic infections

Histoplasmosis is commonly associated with exposure to birds and bats, and echinococcosis with exposure to dogs and sheep

Medications — Response to prior therapy may yield some diagnostic clues regarding the cause of chronic cough. Previous response to antihistamines suggests a component of rhinitis and postnasal drip, while a response to inhaled bronchodilators suggests possible asthma.

Any medications taken by the patient should be reviewed carefully; angiotensin converting enzyme (ACE) inhibitors are a wellestablished cause of chronic cough. Patients previously treated with cytotoxic drugs or thoracic radiation are at risk of interstitial lung disease.

PHYSICAL EXAMINATION General examination — The physical examination should pay close attention to the following signs of chronic underlying disease

General appearance of chronic illness Poor growth, thinness, or obesity Increased work of breathing, retractions, accessory muscle use, chest wall hyperinflation or deformity, abnormal breath sounds (reduced intensity, asymmetry, wheezing, stridor, crackles) Shiners, swollen nasal turbinates, nasal obstruction, nasal polyps, allergic nasal crease, halitosis, tonsillar hypertrophy, pharyngeal cobblestoning, high arched or cleft palate, hoarseness

Tympanic membrane scarring or frank otorrhea Abnormal heart sounds, abnormal pulses Hepatoand/ or splenomegaly, abdominal masses, bloating, rectal prolapse Edema of the extremities, cyanosis and/or clubbing of the digits Rashes and other skin lesions (eg, scars of healed recurrent impetigo)

Chest examination Polyphonic wheezing (ie, many different pitches) with cough is typical of asthma; the wheezing occurs on expiration and sometimes also on inspiration Many children with asthma are also atopic and exhibit signs of rhinitis, conjunctivitis, and/or eczema

Other causes of polyphonic wheezing include viral bronchiolitis, obliterative bronchiolitis, bronchiectasis (cystic fibrosis, allergic bronchopulmonary aspergillosis, primary ciliary dyskinesia), bronchopulmonary dysplasia, heart failure, immunodeficiency, bronchomalacia, and aspiration syndromes.

Monophonic wheezing Monophonic wheezing (a single, distinct noise of one pitch and starting and stopping at one discrete time) and cough should always raise suspicion of large airway obstruction caused by foreign body aspiration or malacia and/or stenosis of the central airways

lymphadenopathy, and mediastinal tumors can cause extrinsic large airway obstruction. Tuberculosis should always be considered in a child with a monophonic wheeze, particularly in areas where the disease is prevalent

CHEST RADIOGRAPHY In addition to a thorough history and physical examination, a chest radiograph should be obtained. If foreign body aspiration is suspected because of the age, clinical presentation or history, frontal films should be obtained during both inspiration and expiration, to evaluate for unilateral lung hyperinflation that would suggest airway obstruction. Similar information can be obtained from the combination of frontal, right lateral decubitus, and left lateral decubitus radiograph

PULMONARY FUNCTION TESTS Spirometry will show signs of obstruction in diseases that obstruct the airways, and restriction in interstitial or chest wall restrictive processes. Suboptimal effort on the part of the child will also result in a restrictive picture; thus, spirometry should be conducted by a technician proficient in testing children

If an obstructive pattern is seen on the expiratory flowvolume loop, the reversibility of the obstruction can be assessed by measuring FEV1 before and after inhalation of a bronchodilating agent. A positive response to bronchodilators establishes the presence of airway reactivity, and is suggestive of asthma but does not rule out other disorders

BRONCHOSCOPY The primary indication for urgent bronchoscopy in children with chronic cough is for suspected foreign body aspiration. Bronchoscopy is also valuable in the evaluation of suspected airway malacia, tracheoesophageal fistula, or stenosis

Patients with presumed infectious etiologies in whom a sputum sample is not obtained or yields negative results can be evaluated with flexible bronchoscopy to perform bronchoalveolar lavage for bacterial, fungal, and mycobacterial cultures. Bronchial brushings can also be taken for patients with suspected ciliary dyskinesia, although nasal brushings also may be used

OTHER TESTS Esophageal pH monitoring — Whether gastroesophageal reflux disease (GERD) is an important cause of isolated chronic cough in children is controversial. Most authorities suggest that this is not a common Sinus imaging

Tuberculin testing Allergy testing

SUMMARY AND RECOMMENDATIONS There is no consensus definition of the time frame for chronic cough in children. Chronic cough is often defined as a cough lasting more than four weeks, because most acute respiratory infections in children resolve within this interval. Other schemes define chronic cough as one that last more than eight weeks but also recognize that a relentlessly progressive cough often warrants evaluation prior to eight weeks

Chronic cough can be a symptom of congenital anomalies, genetic disease, airway obstruction, infection, airway inflammation without infection (as in asthma), neoplasia, or psychogenic processes

The evaluation of a child with chronic cough should include a detailed history, physical examination, chest radiograph, and spirometry (when possible

Symptoms and signs that are highly predictive of a specific cough include chronic wet cough, wheezing or crepitations, onset after a choking episode, abnormal chest radiography or spirometry, associated cardiac or neurologic abnormalities, and failure to thrive, feeding difficulties, or hemoptysis. These signs or symptoms narrow the diagnostic possibilities and call for further specific testing or referral

The symptom of a chronic wet cough in a young child, usually indicates persistent bacterial sinusitis or retained foreign body

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