• Extrinsic to airway
  
  
  • Lymphadenopathy
  • Tumor/malignancy
  • Diaphragmatic hernia
    
    
• Intrinsic to airway
  
  
  • Bronchomalacia
  • Endobronchial foreign body
  • Endobronchial tuberculosis
  • Endobronchial tumors
  • Vocal cord dysfunction
  • Bronchopulmonary dysplasia
  • Congestive heart failure/pulmonary edema
  • Pulmonary cysts
  • Congenital lobar emphysema
  • Pulmonary sequestration

• Bronchitis
• Bronchiolitis
  
  
  • Viral bronchiolitis secondary to respiratory syncytial virus (see Bronchiolitis)
    
    
• Pneumonia
  
  
  • Mycoplasma
  • Chlamydia
  • Aspiration
    
    
• Bronchiectasis
• Bronchial papillomas
• Hypersensitivity pneumonitis
• Pulmonary hemosiderosis

• Cystic fibrosis
• Dyskinetic (immotile) cilia syndrome
  
  
  • Kartagener syndrome
    
    
• Metabolic disturbances
  
  
  • Hypocalcemia
  • Hypokalemia

• Asthma (see Asthma)

• Psychosomatic illness
  • Emotional laryngeal wheezing
  • Factitious asthma

• Characterize the type of abnormal breath sounds heard. Determine the timing of sounds in the respiratory cycle (expiratory and/or inspiratory?) and location (unilateral or bilateral?; are sounds heard best in the region of the neck or chest?). The goal is to distinguish between continuous sounds originating from the upper airway (e.g., stridor) including transmitted upper airway sounds, and lower airway (e.g., wheezing).
• In patients identified with wheezing, determine the likely cause.
• The therapy for wheezing is directed toward a specific cause.

Question: What is the pattern, if any, of the wheezing over time? New onset versus recurrent? Intermittent versus persistent? Seasonal pattern?
Significance: Episodes of recurrent wheezing with periods of complete resolution suggests reactive airway disease or asthma. Persistent wheezing suggests anatomic (e.g., intrinsic or extrinsic airway compression) or persistent physiological abnormalities (e.g., bronchopulmonary dysplasia, cystic fibrosis, or immotile cilia syndrome).

Question: What was the age of onset of wheezing?
Significance: Onset at birth or during early infancy suggests a congenital/anatomical disease process. Of the infectious etiologies, younger infants and children (especially less than 1–2 years of age) are more susceptible to lower respiratory tract infection with the common viral pathogens (e.g., respiratory syncytial virus bronchiolitis), while mycoplasma pneumoniae is more commonly identified in school-aged children. Foreign body aspiration is more common in children between the ages 1 and 4 years.

Question: Have any triggers of wheezing been identified?
Significance: Upper respiratory infection symptoms (i.e. nasal congestion, cough, fever) can accompany viral bronchiolitis or a virus-triggered reactive airway disease. Common triggers for asthma include allergens (e.g., house dust mites, pollen, animal dander), irritants (e.g., tobacco smoke, pollution), exercise, and changes in humidity or air temperature.

Question: Did an episode of choking precede the onset of wheezing?
Significance: A history of choking mandates consideration of foreign body aspiration.

Finding: Assess the patient’s degree of respiratory distress and toxicity.
Significance: Look for signs of respiratory distress including tachypnea, retractions, nasal flaring, head bobbing, abdominal breathing, cyanosis, the ability to speak in complete sentences, and the adequacy of air entry. Of note, some patients with significant airway obstruction may exhibit relatively little respiratory distress. Also, wheezing may not be audible in patients with severely restricted air movement.

Finding: Determine the timing of abnormal breath sounds in the respiratory cycle, i.e. inspiratory, expiratory, bi-phasic.
Significance: Inspiratory breaths sounds (i.e. stridor) are associated with extrathoracic narrowing of the airway (see Stridor, Croup, Tracheitis, and Epiglottitis).

Finding: Ratio of inspiratory to expiratory phase
Significance: A prolonged expiratory phase indicates obstructive airway disease. In asthma, a prolonged expiration should occur in conjunction with expiratory wheezing.

Finding: Presence of clubbing
Significance: Clubbing indicates chronic cardiopulmonary disease (e.g., congenital or acquired heart disease, cystic fibrosis, bronchopulmonary dysplasia). Clubbing should not be present in children with asthma.

Finding: Presence of allergic shiners, Dennie lines, nasal crease, the “allergic salute” (i.e. rubbing the nose with the palm of the hand), and atopic dermatitis
Significance: The presence of other atopic diseases increases likelihood of coexisting asthma.

Test: Pulse oximetry measurement of oxygen saturation (SaO₂).
Significance: Pulse oximetry can help gauge the degree of respiratory compromise. In asthma, SaO₂ measurements of less than 92% may be seen in severe exacerbations.

Test: Arterial blood gas (ABG)
Significance: ABGs provide a direct measure of oxygenation (paO₂) and ventilation (paCO₂). A low paCO₂ is expected in a patient with increased work of breathing, therefore, a normal or increasing paCO₂ predicts impending respiratory failure. In general, ABG measurements are not necessary in the vast majority of patients seen in the office setting with wheezing.

Test: Pulmonary function testing (PFT)—peak flow meter, spirometry
Significance: PFTs can be used to quantify the degree of airway obstruction. Older children (>6 years old) can cooperate with peak flow measurements, which can be plotted against normal ranges (typically based on height), or personal best (in patients with known asthma).

Test: Microbiologic studies. A variety of cultures, antigen detection, and polymerase chain reaction studies can be performed on nasal washes from infants, for the identification of respiratory viruses (e.g., RSV, adenovirus, parainfluenza virus, influenza), chlamydia, and pertussis. The validity of sputum cultures (especially bacterial cultures) in determining the cause of lower respiratory tract infections in children is limited.
Significance: These tests may allow identification of a specific infectious etiology. However, a delay in getting the results of some of these tests, cost, and a lack of specific therapy for many of the viral agents, may restrict their use and value.

Test: Tuberculosis skin test—Mantoux purified protein derivative (PPD)
Significance: Tuberculosis can produce wheezing through both intrinsic (endobronchial) or extrinsic (lymph node) effects on the airway.

Test: Chest radiography (anteroposterior and lateral)
Significance: Routine chest radiology can demonstrate airway obstruction (e.g., hyperinflation, hyperlucency, flattening of the diaphragms), peribronchial cuffing, infiltrates, atelectasis, bronchiectasis, and radio-opaque foreign bodies. Asymmetry in air-trapping can suggest foreign body aspiration.

Test: Complete blood count including eosinophil count, quantitative immunoglobulins, IgE, complement, HIV testing, allergy skin testing
Significance: Allergy/immunologic evaluation in selected individuals.

• A trial of bronchodilator therapy (e.g., albuterol) may be both therapeutic and diagnostic of reversible airway obstruction in patients suspected of having reactive airway disease.
• Antibiotics may be considered in patients with illnesses compatible with Mycoplasma pneumoniae or Chlamydia pneumoniae, both of which can produce clinical manifestation of wheezing.
• Antiviral agents, such as ribavirin for respiratory syncytial virus, have limited usefulness for the majority of cases.

• Respiratory distress—tachypnea, retractions, nasal flaring, head bobbing, abdominal breathing, cyanosis, inability to speak in complete sentences, inadequate air entry.
• Respiratory insufficiency—cyanosis, fatigue, altered mental status (e.g., confusion, agitation), apnea, normal or rising pCO₂ in the face of respiratory distress.
• Management of respiratory emergencies begin with the ABCs—Airway, Breathing, and Circulation. Determine which patients require assisted ventilation (e.g., bag-mask ventilation or endotracheal intubation). Reassess often.

Q: How common is wheezing in childhood?
A: Wheezing is common in childhood. By 1 year of age, 25% to 30% of infants will have an episode of wheezing. This percentage may increase to 40% by 3 years of age, and nearly one-half by 6 years.

Q: What percent of recurrent wheezing resolves by school age?
A: In one prospective study up to 6 years of age, roughly 40% of children with one or more episodes of wheezing by 3 years of age no longer wheezed by 6 years of age.

Q: Should chest x-rays be routinely obtained in children experiencing their first episodes of wheezing?
A: Admittedly, the decision to obtain a chest x-ray of a patient in this setting is controversial. The reported rate of abnormal x-ray findings (other than those consistent with asthma or reactive airway disease) are in the range of 5% to 6%.

• Patients requiring surgical intervention. Suspected or confirmed foreign body aspiration requires referral to a surgical service (e.g., pediatric surgery, otolaryngology) for rigid bronchoscopy and removal of the foreign body.
• For patients in whom the diagnosis is not clear after initial evaluation, consider referral to a specialist (e.g., pulmonologist) for additional diagnostic evaluation.
• Patients with specific congenital/anatomic malformations and genetic syndromes.
• Patients with asthma who experience a life-threatening episode, poor control, etc. (see Asthma or Expert Panel Report 2, 1997 are recommended to have specialty referral) (e.g., pulmonologist, allergist).
• Patients in whom the identification of specific allergic triggers will help case management may benefit from referral to an allergist for skin testing.

• “All that wheezes is not asthma.” While most episodes of wheezing will represent viral infections or asthma, clinicians need to be mindful of alternative diagnoses. This is especially true in patients with first-time, persistent, or atypical episodes of wheezing.
• A high index of suspicion is necessary to make the diagnosis of foreign body aspiration (FBA). While a history of choking is helpful in supporting the diagnosis, the absence of such a history does not rule out the diagnosis.
  • Toy safety: Families should be aware of the choking hazards that small toys can be for infants and young children. Parents can screen toys for appropriate size by using a tube from a toilet paper roll. With a diameter of about 1.75 inches, a measurement promoted by the Consumer Product Safety Commission (CPSC), toys which can fit inside are too small for children less than 3 years of age.

Consumer Product Safety Commission [http://www.cpsc.gov/].

Expert Panel Report 2. Guidelines for the diagnosis and management of asthma: National Heart, Lung, and Blood Institute. National Asthma Education Program Expert Panel report. NIH Publication No. 97-4051. April 1997.

Holroyd HJ. Foreign body aspiration: potential cause of coughing and wheezing. Pediatr Rev 1988;10(2):59–63.

Marks MB. Differential diagnosis of wheezing in children. Clin Pediatr 1974;13(3):225–228.

Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheeezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995;332(3):133–138.