Lactology Foundation

Approach to wheezing in children

Wheezing is a common presenting symptom of respiratory disease in children

A nationwide survey performed in the United States between 1988 and 1994 showed that the prevalence of wheezing among two to three year olds was 26 percent and among 9 to 11 year olds was 13 percent. One in three children experience at least one acute wheezing illness before the age of three years. Wheezing may be either a benign, self-limited process or the presenting symptom of a significant respiratory disease. The role of the treating clinician is to try to reach the most likely diagnosis as quickly and efficiently as possible so that therapy, if necessary, can be instituted and the parental concerns can be addressed.
The most likely diagnosis in children with recurrent wheezing is asthma, regardless of the age of onset, evidence of atopic disease, precipitating causes, or frequency of wheezing. However, other diseases can present with wheezing in childhood, and patients with asthma may not wheeze. The differential diagnosis of wheezing includes a variety of congenital and acquired conditions.
Clinical history and physical examination often allow accurate diagnosis. However, radiographic examination, pulmonary function testing, bronchoscopy, sweat chloride concentration, and selective laboratory studies are helpful tools in establishing the underlying etiology of wheezing when used appropriately. The initial evaluation of a wheezing child is directed towards the exclusion of alternative diagnoses, followed by a therapeutic trial of bronchodilators if asthma is suspected.
A diagnostic approach to wheezing in childhood is presented in this topic review.

DEFINITION AND PHYSIOLOGY OF WHEEZING
A wheeze is a continuous musical sound heard during chest auscultation that lasts longer than 250 msec. It is produced by the oscillation of opposing walls of an airway narrowed almost to the point of closure. It can be high pitched or low pitched, consist of single or multiple notes, and occur during inspiration or expiration. Wheezes can originate from airways of any size throughout the proximal conducting airways. Wheezing requires sufficient airflow to generate airway oscillation and produce sound in addition to narrowing or compression of the airway. Thus, the absence of wheezing in a patient who presents with acute asthma may be an ominous finding, suggesting impending respiratory failure.
Wheezing caused by a large or central airway obstruction has a constant acoustical character throughout the lung but varies in loudness depending upon the distance from the site of obstruction. It is referred to as monophonic (or homophonous) wheezing. In contrast, the degree of narrowing varies from place to place within the lung in the setting of small airway obstruction. As a result, the sounds generated also vary in quality and acoustical character and are described as polyphonic (or heterophonous) wheezes.
Some experts distinguish between wheezes and rhonchi based on the dominant frequency, or pitch, of the sound. Wheezes have a dominant frequency greater than 400 Hz, whereas rhonchi are of lower frequency. However, the clinical significance of this distinction, if any, is not well defined.
Stridor refers to a monophonic sound that is loudest over the anterior neck. Stridor can be heard during inspiration, expiration, or throughout the respiratory cycle, depending on the location and severity of obstruction. In general, inspiratory stridor is prominent in the setting of extrathoracic obstruction, whereas expiratory stridor suggests intrathoracic obstruction.

CLINICAL HISTORY
When a patient presents with a history of wheezing, it is crucial to ask the patient or the parents to describe what they are actually experiencing or hearing. On many occasions, the word "wheezing" is used as a general term to describe noisy breathing, including snoring, congestion, rattling, gurgling noises, or stridor. It is essential to try to validate the symptom of wheezing if parental report is the only source of information and no wheezing is heard on examination of the child.
There are few studies that compare parent-reported respiratory illness in infants with clinical diagnosis. In another study, parental report of wheezing in 139 infants and children was compared with clinical findings of wheezing and diagnosis of asthma. There was a less than 50 percent agreement between a clinician's finding of wheeze and asthma and parents' report of wheeze. Fourteen percent of parents use the term "wheeze" to describe other noises, mainly upper airway noises.
Two important aspects of the medical history include the patient's age at the onset of wheezing and the course of onset (acute versus gradual).
Acute onset of wheezing raises the possibility of foreign body aspiration, particularly if there is a history of choking. In addition, it is helpful to distinguish between intermittent and persistent wheezing. Persistent wheezing presenting very early in life suggests a congenital or structural abnormality. In contrast, paroxysmal or intermittent wheezing is a characteristic finding in patients with asthma.
Persistent wheezing with sudden onset is consistent with foreign body aspiration, whereas the slowly progressive onset of wheezing may be a sign of extraluminal bronchial compression by a growing mass or lymph node. Less frequently, patients with interstitial lung disease can present with persistent wheezing.
Cough is a symptom commonly associated with wheezing. The nature of the associated cough (wet versus dry) may be helpful in determining the underlying etiology. Wet cough typically results from excessive mucus production, mostly due to infection or inflammation (eg, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, asthma, and chronic aspiration). In contrast, pure bronchoconstriction or structural causes for airway narrowing (eg, asthma, airway malacia or compression, foreign body, vascular ring) are usually associated with a dry cough. However, the underlying etiology of a dry cough can be complicated by a secondary process, making this distinction difficult (eg, mechanical obstruction can lead to impaired mucus clearance resulting in infection and a wet cough).
Among children younger than two years of age, the incidence of wheezing with respiratory illnesses is approximately 30 percent and peaks between two and six months. Typically, these infants present with classic coryzal symptoms that progress to coughing, wheezing, and, occasionally, respiratory distress over a period of three to five days; resolution is gradual over approximately two weeks. These episodes are variably responsive to bronchodilators and systemic glucocorticoids but not antibiotics, expectorants, or antihistamines. A symptom-free period typically follows, followed by recurrent wheezing with subsequent viral illnesses in as many as 50 percent of babies.

Features in the history that favor the diagnosis of asthma include:
●Intermittent episodes of wheezing that usually are the result of a common trigger (ie, upper respiratory infections, weather changes, exercise, or allergens)
●Seasonal variation
●Family history of asthma and/or atopy
●Good response to asthma medications
●Positive asthma predictive index
Clinical features that suggest a diagnosis other than asthma include the following:
●Poor response to asthma medications.
A history of neonatal or perinatal respiratory problems and wheezing since birth suggests a congenital abnormality.
●Wheezing associated with feeding or vomiting can result from gastroesophageal reflux or impaired swallowing complicated by aspiration.
●A history of choking, especially with associated coughing or shortness of breath, suggests foreign body aspiration, even if it does not immediately precede the onset of wheezing symptoms.
●Wheezing with little cough suggests a purely mechanical cause of obstruction, such as small airways, airway malacia, and vascular ring, since cough is a prominent component of asthma in children.
●Symptoms that vary with changes in position may be caused by tracheomalacia, bronchomalacia, or vascular rings.
●Poor weight gain and recurrent ear or sinus infections suggest cystic fibrosis, immunodeficiency, or ciliary dysfunction.
●History of progressive dyspnea, tachypnea, exercise intolerance, and failure to thrive suggest interstitial lung disease.

PHYSICAL EXAMINATION
General examination of a wheezy child should include measurement of weight and height, vital signs including oxygen saturation, and digital inspection for the presence of cyanosis or clubbing. The latter findings suggest the presence of a wheezing illness other than asthma.
Chest examination should focus on the following features:
Inspection for the presence of respiratory distress, tachypnea, retractions, or structural abnormalities. Pertinent findings include an increased anteroposterior (AP) diameter associated with chronic hyperinflation, pectus excavatum caused by chronic airway obstruction and exaggerated swings in intrathoracic pressure, or scoliosis complicated by airway compression.
●Palpation to detect supratracheal lymphadenopathy or tracheal deviation.
●Percussion can define the position of the diaphragm and detect differences in resonance among lung regions and is the most underperformed part of the examination.
●Auscultation allows identification of the characteristics and location of wheezing, as well as variations in air entry among different lung regions. A prolonged expiratory phase suggests airway narrowing. Wheezing caused by a large or central airway obstruction (eg, vascular ring, subglottic stenosis, tracheomalacia) has a constant acoustic character throughout the lung but varies in loudness depending upon the distance from the site of obstruction. In contrast, the degree of narrowing varies from place to place within the lung in the setting of small airway obstruction (eg, asthma, cystic fibrosis, primary ciliary dyskinesia, aspiration). The presence of focal wheezing is usually indicative of a localized and mostly structural airway abnormality, and, therefore, airway evaluation by imaging or bronchoscopy is warranted.
●Crackles can be present in conjunction with wheezing in asthma and in a variety of other conditions, such as those leading to bronchiectasis (eg, cystic fibrosis, primary ciliary dyskinesia, immune deficiency). Early inspiratory crackles are often present in patients with asthma due to air flowing through secretions or slightly closed airways during inspiration. Late inspiratory crackles are usually associated with interstitial lung disease and early congestive heart failure. Thus, the presence of crackles does not exclude the diagnosis of asthma.
●Decreased wheezing after bronchodilator therapy is suggestive of asthma but does not rule comorbid conditions if clinically suspected.
The remainder of the examination should focus on cardiac findings, including murmurs and signs of heart failure. Examination of the skin for eczema (common in atopic patients) or other cutaneous lesions may assist in diagnosis. Nasal examination may reveal signs of allergic rhinitis, sinusitis, or nasal polyps. The presence of nasal polyps in children necessitates an evaluation for cystic fibrosis.

RADIOGRAPHY
A chest radiograph (anteroposterior [AP] and lateral films) should be considered in children with new-onset wheezing of undetermined etiology or chronic persistent wheezing not responding to therapies. It is not necessary to obtain a chest radiograph with every exacerbation in children with asthma, unless there is a specific indication.
In most cases, a plain chest radiograph provides a good image of the large airways, including the tracheal air column and mainstem bronchi. Plain films can also help differentiate between diffuse and focal disease. The presence of generalized hyperinflation suggests diffuse air trapping and airway disease, seen in asthma, cystic fibrosis, primary ciliary dyskinesia, and aspiration. In contrast, localized findings suggest structural abnormalities or foreign body aspiration. A chest radiograph can also detect parenchymal lung disease, atelectasis, and in some cases, areas of bronchiectasis.
In addition, chest radiographs may reveal cardiomegaly, enlarged pulmonary vessels, pulmonary edema, or other signs of cardiac failure. Plain radiographs are also helpful in detecting mediastinal masses or enlarged lymph nodes and may suggest the presence of vascular rings (eg, right aortic arch).
Other radiologic studies may be helpful in selected cases. Chest computed tomography (CT) can provide detailed anatomy of the mediastinum, large airways, and lung parenchyma. Magnetic resonance imaging (MRI) with contrast (magnetic resonance angiography [MRA]) or multidetector computed tomography (MDCT) should be considered when a vascular problem is suspected.
Barium swallow may help in identifying vascular rings, swallowing dysfunction, aspiration syndromes including gastroesophageal reflux, and some cases of tracheoesophageal fistula; however, this study is indicated only when these conditions are suspected.

PULMONARY FUNCTION TESTS
Pulmonary function tests (PFTs) are an important component of the diagnostic evaluation of a wheezy child.
Infant pulmonary function testing, if available, is helpful in assessing airway obstruction. Moreover, this test can be used to quantify the response to bronchodilators. Airway resistance and functional residual capacity can also be measured using gas dilution or body plethysmography and can help quantify airway obstruction and the response to bronchodilators.
In older children who are cooperative, pulmonary function testing with inspiratory and expiratory flow-volume loops is helpful in determining the presence, degree, and location of airway obstruction, as well as the response to bronchodilators. Methacholine challenge testing and exercise testing can confirm airway hyperreactivity in patients for whom the diagnosis of asthma is still in question.

RESPONSE TO TREATMENT
For patients with diffuse wheezing, a trial of inhaled bronchodilators can be used to confirm the presence of reversible airway disease. However, a partial or negative response may not rule out asthma. Inflammation and airway swelling may contribute to wheezing, in addition to bronchoconstriction, especially in infants and young children. Thus, if asthma is still suspected in a patient with chronic or persistent symptoms, the combination of inhaled glucocorticoids and bronchodilators for at least two weeks (or five to seven days of oral glucocorticoids if the patient has more severe symptoms) may result in significant improvement in symptoms and help in making the diagnosis of asthma. Further work-up is indicated if the response to this therapy is inadequate or if a comorbid condition is still suspected in a patient who had a positive response to bronchodilator.

LABORATORY STUDIES
There are few laboratory investigations that are useful in the initial evaluation of the wheezy child. In most cases, the probable diagnosis is suspected on the basis of the clinical history and physical examination. The role of laboratory tests, when indicated, is either to confirm the diagnosis or to rule out other less likely diagnoses. Complete blood counts are important in patients with chronic or systemic symptoms and may reveal anemia, leukocytosis, or leukopenia. Eosinophilia in this setting supports an underlying allergic process or possible parasitic infection. Further studies should be obtained based on the suspected diagnosis.

Testing for infection — Viral infection is an important cause of wheezing in children and is mediated through numerous mechanisms. The interrelationship of viral infection, wheezing, and the development of asthma in children is complex and changes according to the patient's age, the presence of atopy, and environmental factors.
Viruses in the Paramyxoviridae family (eg, respiratory syncytial virus and parainfluenza virus) and picornavirus family (eg, human rhinovirus) are important precipitants of wheezing in young children. Metapneumovirus, another member of the Paramyxoviridae family, is a newly recognized human pathogen that can result in upper and lower respiratory tract infection and may present with wheezing. Thus, viral studies can be helpful in confirming the etiology of wheezing in young children presenting with symptoms suggestive of bronchiolitis. However, they are not routinely recommended. Sputum stain and cultures may be useful in a setting suggestive of bacterial infections, including atypical infections (eg, mycobacterial or fungal infections), that can result in wheezing. Tuberculin skin testing and specific serologic assays can be helpful if these infections are suspected. Serologic testing for Mycoplasma may be considered if such an infection is suspected since Mycoplasma is an increasingly recognized cause of wheezing and may predispose children to the subsequent development of asthma.

Sweat chloride test — The sweat chloride test allows clinicians to assess physiological changes associated with cystic fibrosis and is indicated in children with chronic lung problems, including wheezing. It is expected that the majority of patients with cystic fibrosis will be diagnosed at birth due to newborn screening for cystic fibrosis. However, false negatives can occur. Thus, obtaining a sweat test is appropriate if clinical suspicion of the disease remains.
The presence of diarrhea, failure to thrive, and/or clubbing should raise the suspicion for cystic fibrosis and warrant further evaluation. One should also have a low threshold to obtain this test in a patient with persistent or recurrent pulmonary symptoms that are unresponsive to asthma therapies, especially when wheezing is associated with a chronic productive cough, since identifying a patient with cystic fibrosis has major implications for the patient, the family, and future reproductive decisions. The sweat chloride test should be undertaken at a facility with substantial experience, and clinicians interpreting the results should be aware of other conditions that result in elevated sweat chloride concentrations.
Other studies — Immunoglobulin levels can be used to screen for immunodeficiencies. Elevated immunoglobulin E (IgE) can be indicative of an allergic process. If there is a high suspicion of immunodeficiency, then a more detailed immunological work-up is appropriate.

ENDOSCOPY
Endoscopy is a diagnostic tool used in patients with suspected foreign body aspiration, persistent symptoms, or inadequate response to therapy. Rigid bronchoscopy is used in patients with sudden onset of wheezing and suspected foreign body aspiration. Flexible bronchoscopy performed under conscious sedation is used to evaluate the airways during spontaneous breathing and to exclude tracheomalacia. Nasopharyngoscopy, which allows visualization of the vocal cords and larynx without lower airway endoscopy, is a less invasive alternative in infants and children with evidence of extrathoracic obstruction. This approach provided a diagnosis in 75 of 82 cases (91 percent) in one series, without evidence of lower airway disease during a mean follow-up interval of six years. Bronchoscopy with bronchoalveolar lavage should be obtained if infection, aspiration, or interstitial lung disease is suspected.