Asthma causes more school absence than any other chronic childhood illness. The tremendous morbidity associated with this disease greatly affects patients’ quality of life.1 Prompt diagnosis and treatment could alleviate symptoms, but testing limitations in children younger than six often force clinicians to make presumptive diagnoses and try various therapies. Recognition of other disorders with similar symptoms can aid in choosing the correct diagnosis and treatment over time.

What else could it be?

Children are not just small adults. The most common — but certainly not the only — cause of wheeze is asthma. Atypical presentation or responses to therapy that are inconsistent with expectations require consideration of other conditions.

Historic features that are inconsistent with asthma include neonatal symptoms, infants who have required mechanical ventilation, wheeze associated with feeding or vomiting, sudden onset of cough or choking, steatorrhea, or stridor. On examination, consider a different diagnosis in children who have failure to thrive, cardiac murmur, clubbing, or stridor. If airflow obstruction is not reversed by use of a bronchodilator or no focal or persistent findings are seen on chest x-ray, reconsider your diagnosis.

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Upper- and large-airway disease: Postnasal drip from allergic rhinitis or sinusitis can cause cough that is often confused with the cough due to asthma, especially when the conditions coexist. Oftentimes, the asthma cannot be effectively controlled until the rhinitis is also treated.

Upper-airway obstruction can also cause cough and wheeze. The tip-off here is that the wheeze of upper-airway obstruction usually presents with stridor, or wheeze on inspiration, and, depending on the level of obstruction, may be associated with voice changes. The wheeze of asthma occurs in the expiratory phase of breathing.

Croup is a viral infection that inflames the upper and often the lower airways. This usually causes the characteristic seal-like bark, which may also be accompanied by an expiratory wheeze.

Foreign-body inhalation is not uncommon in small children. It is usually, if you search hard enough in the history, associated with a choking spell at some point. Findings suggestive of foreign-body inhalation are unilateral wheeze and changes of hyperinflation seen on one side only on the chest x-ray.

Vocal-cord dysfunction is particularly challenging, as it often occurs in patients with asthma. Continued irritation of the vocal cords from asthma, rhinitis, and gastroesophageal reflux disease (GERD) can cause paradoxical vocal-cord closure during breathing as well as stridor and cough. But these patients, often younger females, will also have wheeze from asthma, making the cause quite difficult to sort out. Again, voice changes and stridor should alert you to suspect something other than asthma.

Lower-airway conditions: Many lower-airway problems can cause wheeze and cough. Infections of the airways (bronchitis) and the lungs (pneumonia) may be to blame. Bronchiectasis is a structural condition of the lung in which recurrent infections or systemic diseases cause sacs or pockets in the lungs. Pus or mucus that accumulates in the sacs cause cough and wheeze. While chest x-ray may hint at this diagnosis, CT scans of the lungs are needed for diagnosis. Other conditions that cause fluid in the lungs can result in wheezing. “Cardiac asthma” is the term used to describe wheeze in patients with congestive heart failure. In fact, this is not asthma at all. In bronchiolitis obliterans, the bronchioles start to scar and close up. This condition may also present with wheeze; it is diagnosed only by bronchoscopy.

Other infections such as pertussis and TB can cause intractable cough and other symptoms. There are usually accompanying clues that rule out asthma, but these conditions can be quite difficult to diagnose, especially when there is co-existent asthma.

Frequent pulmonary infections, especially in children, lead to consideration of a variety of conditions. Gamma globulin deficiency can be confirmed by protein immunoelectrophoresis. Ciliary dysfunction is often a manifestation of ciliary damage due to smoking.

Cystic fibrosis, which causes respiratory difficulties, wheeze, and digestive problems, is an inherited, progressive, chronic condition that can also be misdiagnosed as asthma (see below: “A genetic cause of wheeze”).

How do you confirm asthma?

Objective pulmonary function testing with spirometry or standard bronchoprovocational testing is not possible in children younger than 5-6 years of age. However, in older children or adults, a 15% increase in the forced expiratory volume in one second (FEV1) or a forced vital capacity representing ≥200 mL constitutes a significant bronchodilator response suggestive of a diagnosis of asthma.2 Alternatively, a 20% improvement in peak-flow readings with bronchodilators or treatment is considered significant and diagnostic.

Consideration of symptom triggers can assist in diagnosis. In children younger than 4 years, the primary trigger is viral infection. Allergic triggers are more common after the age of 4 years, and the use of allergy testing for inhalant allergies is generally reserved for these older children.

Asthma is associated with atopy in patients of all ages,3 although the link is strongest in children and young adults. Atopic individuals may also have flexural eczema or hay fever concurrently, or they may have had these conditions in the past. The prevalence of asthma in different environments correlates with specific immunoglobulin (Ig) E antibody to the particular allergens present. For example, in U.S. cities, asthma is associated in affluent areas with IgE specific to house-dust mite and cat hair and in poor areas with IgE specific to house-dust mite and cockroach. Furthermore, the severity of asthma correlates with the concentration of specific allergens to which individuals are sensitized.

Persistent wheezers4 who have early-onset asthma usually have associated atopy, bronchial hyperreactivity, and significant deterioration in lung function by age 6. Transient wheezers are those children, often with small airways, who wheeze only with viral illnesses. This is strictly a matter of mechanics, as flow is very dependent on the radius of the tube, and when it is narrowed by swelling due to viral infection, flow decreases and wheeze occurs.