Many upper- and lower-airway problems cause wheeze and cough, and some conditions coexist with asthma. Here's how to pin down a diagnosis.
Asthma causes more school absence than any other chronic childhood illness and greatly affects patients' quality of life.1 Unfortunately, testing limitations in children younger than 6 years often force physicians 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.
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 inconsistent with asthma include neonatal symptoms, mechanical ventilation in an infant, wheeze associated with feeding or vomiting, sudden onset of cough or choking, steatorrhea, or stridor. Consider a different diagnosis in children with failure to thrive, cardiac murmur, clubbing, or stridor. If airflow obstruction is not reversed by use of a bronchodilator or chest x-ray shows no focal or persistent findings, reconsider your diagnosis. Some differential diagnoses for pediatric asthma are shown in the table below.
Upper- and large-airway disease: Postnasal drip from allergic rhinitis or sinusitis can cause cough similar to that of asthma, especially when the conditions coexist. Often, the asthma cannot be controlled until the rhinitis is also treated.
Upper-airway obstruction can also cause cough and wheeze but usually presents with stridor, or wheeze on inspiration, and may be associated with voice changes. The wheeze of asthma occurs in the expiratory phase of breathing.
Croup inflames the upper and often the lower airways. The seal-like bark may be accompanied by an expiratory wheeze. Foreign-body inhalation is not uncommon in small children. A thorough history usually discovers a choking spell at some point. Clues to foreign-body inhalation are unilateral wheeze and changes of hyperinflation on one side of the chest x-ray only.
Vocal-cord dysfunction is challenging. Continued irritation 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 difficult to sort out. Again, voice changes and stridor should raise suspicions of 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. In bronchiectasis, recurrent infections or systemic diseases cause sacs or pockets in the lungs. Pus or mucus that accumulates in the sacs causes cough and wheeze. CT scans are needed for diagnosis. Other conditions that cause fluid in the lungs can result in wheezing. “Cardiac asthma” describes the wheeze heard in congestive heart failure but is not asthma at all. In bronchiolitis obliterans, the bronchioles start to scar and close up. This can also cause wheeze and is diagnosed only by bronchoscopy.
Other infections, such as pertussis and TB, can cause intractable cough. Accompanying symptoms usually rule out asthma, but these conditions can be quite difficult to diagnose, especially when there is coexistent asthma.
Gamma globulin deficiency, ciliary dysfunction, and cystic fibrosis are also worthy of consideration.
How do you confirm asthma?
Spirometry or standard bronchoprovocational testing is not possible before age 5 or 6. In older patients, though, a 15% increase in forced expiratory volume in one second (FEV1) or a forced vital capacity representing ≥200 mL constitutes a bronchodilator response suggestive of asthma.2 A 20% improvement in peak flow with bronchodilators is diagnostic.
Symptom triggers can assist in diagnosis. Viral infection is the primary trigger in children younger than 4 years. Allergic triggers are more common after the age of 4 years, and testing for inhalant allergies is usually reserved for these children.
Asthma is associated with atopy at all ages,3 although the link is strongest in children and young adults. Atopic patients may have concurrent flexural eczema or hay fever, or they may have a history of these conditions. The prevalence of asthma in different environments correlates with specific immunoglobulin (Ig) E antibody to the specific 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 often have small airways and wheeze only with viral illnesses. This is strictly 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.
Treatment
First, control the environment, i.e., reduce exposure to irritants, e.g., cigarette smoke, or triggers, e.g., pets or dust mites. Understanding whether the medication controls symptoms or the underlying inflammation is essential. Treatment of inflammation5 results in symptom resolution, then normalization of spirometry and, finally, bronchial hyperresponsiveness.
Inhaled corticosteroids (ICS) comprise the single best treatment for inflamed airways in asthma. Chronic uncontrolled lung inflammation may lead to lung remodeling with resulting fibrotic changes. Studies show reduction in asthma symptoms, reduction in asthma exacerbations, and improved exercise tolerance in children who regularly use ICS.
The use of ICS does not result in any long-term airway changes6 or alterations in the course of the disease. Therefore, doses should be the smallest amount needed to control the condition (table, opposite page) and lung function. Small lungs, because of their inspiratory capacity, are exposed only to a smaller amount of the dose given; this is called “autoscaling.”
ICS should be used on a regular basis when patients show signs of persistent inflammation, e.g., recurrent symptoms or exacerbations. There is no evidence that intermittent use of ICS for sporadic wheezing has any effect on symptoms. Also, there is a statistically significant reduction in body-growth velocity when ICS therapy is started.
Within two to three months, the growth velocity is similar to that seen with placebo. In general, ICS therapy should continue until patients attain six months of adequate to complete control. If symptoms are worse during specific times of the year (winter, for example), continuous use during that time, with discontinuation at other times, may be appropriate. Alternate anti-inflammatory treatment with leukotriene modifiers can also be considered.
Patient adherence to treatment tends to be poor, so close monitoring is essential. The consequences of nonadherence include unrelieved symptoms, failure to reach target values, unneeded investigations, unnecessary drug additions and dose changes, patient dissatisfaction, and physician frustration.
Tips on asthma-device use
Metered-dose inhalers (MDIs) are subject to dose variability that evens out if two puffs are used, i.e., two puffs of 125 µg instead of one puff of 250 µg. To estimate the amount of remaining medication, shake the canister (after removing it from the plastic case), or slide your fingers up and down the canister to detect where the medication appears to stop. If the MDI does not have a dose counter, check the label for the number of sprays contained. Calculate how many days the device will last and note a date several days ahead on a daily calendar.
Dry-powder devices have either dose counters or a red line that starts to appear when 20 doses are left (Turbuhaler). Shaking the device is not helpful, as the desiccant for the medication will be heard even when no medication remains.
When to look for another diagnosis
Nonresponsiveness despite appropriate therapy may be due to incorrect diagnosis, noncompliance with medications, improper inhaler use, inadequate control of environmental triggers, and comorbidities, e.g., GERD, rhinosinusitis, and allergic rhinitis. Check for these, and affirm your diagnosis when faced with this dilemma.
Conclusion
Not all that wheezes is asthma. Try to diagnose using objective measurements of airflow. Remember that treatment of the upper airway is needed to adequately control the lower airway. Reconsider the diagnosis when the presentation is atypical or response to therapy is incomplete. Timely referral for appropriate diagnostics or to a practitioner with special interest in asthma can clarify many of these issues.
Treatment of asthma should allow the child to live a normal life with minimal symptoms and infrequent exacerbations.
Dr. Kaplan is a family physician who specializes in respiratory disease. He practices in Richmond Hill, Ontario, where he is chairperson of the Family Physician Airways Group of Canada.
References
1. Mannino DM, Homa DM, Akinbami LJ, et al. Surveillance for asthma — United States, 1980-1999. MMWR. 2002;51(SS1):1-13.
2. National Asthma Education and Prevention Program. Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Md.: National Institutes of Health; 1997. Publication No. 97-4051.
3. Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. N Engl J Med. 1995;332:133-138.
4. Oswald H, Phelan PD, Lanigan A, et al. Childhood asthma and lung function in mid-adult life. Pediatr Pulmonol. 1997;23:14-20.
5. National Asthma Education and Prevention Program. Highlights of the Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Md.: National Institutes of Health; May 1997. NIH Publication No. 97-4051A.
6. Baxter-Jones AD, Helms PJ. Early introduction of inhaled steroids in wheezing children presenting in primary care. Clin Exp Allergy. 2000;30:1618-1626.