Asthma: Calming the AirwaysPage 6 of 11

4. Differential Diagnosis and Comorbidities

Healthcare professionals working in the emergency department, on medical and surgical floors of the hospital, in clinics and private offices, and other locations where clients are seen, are aware of the axiom “All that wheezes is not asthma.” When wheezing and other symptoms commonly associated with asthma do not respond to traditional therapies, the reason may be that the client has another disease that mimics asthma, or a comorbidity that is complicating it.

Differential Diagnosis

Differential diagnosis is the use of a systematic process of elimination, comparing and contrasting clinical findings to determine the cause of an illness. Use of a well-defined, systematic approach in assessing for asthma increases the likelihood that the disease will be correctly identified and classified according to established criteria.

The history and examination must be sufficiently comprehensive to include an investigation of potential comorbidities and precipitating factors, which can exert a strong influence on the course of the disease or cloud the diagnosis. When the diagnosis of asthma is not clear—as may be the case in intermittent disease (especially between exacerbations)—diseases with symptoms that mimic asthma must be considered and properly managed to improve overall quality of life.

Infants and Children

In children under age 5, the assurance with which one can determine the diagnosis of asthma is complicated by the fact that these young clients are typically not able to comply with the instructions necessary to perform spirometry. Coughing and wheezing can occur for a variety of reasons; however, recurrent episodes of cough and wheezing is most often due to asthma in both children and adults.

Under-diagnosis of asthma in children occurs frequently—particularly if the child is seen by a variety of providers in numerous sites—and the child may receive a diagnosis of bronchitis, bronchiolitis, or possibly pneumonia, even though the signs and symptoms are compatible with a diagnosis of asthma. However, when a child does not respond to treatment, and there is a reasonable certainty that treatments are being administered correctly, other causes of airway disease should be considered. A partial list is as follows.

Upper airway diseases

  • Allergic rhinitis and sinusitis

Obstructions involving large airways

  • Foreign body in trachea or bronchus
  • Vocal cord dysfunction
  • Vascular rings or laryngeal webs
  • Laryngotracheomalacia, tracheal stenosis, or bronchostenosis
  • Enlarged lymph nodes or tumor

Obstructions involving small airways

  • Viral bronchiolitis or obliterative bronchiolitis
  • Cystic fibrosis
  • Bronchopulmonary dysplasia
  • Heart disease

Other causes

  • Recurrent cough not due to asthma
  • Aspiration from swallowing mechanism dysfunction or gastroesophageal reflux (GERD)


Adults also sometimes have conditions that can be confused with asthma, and these should be evaluated using appropriate diagnostic testing to rule them in or out. A partial list of common conditions in adults includes:

  • COPD (chronic bronchitis or emphysema)
  • Congestive heart failure
  • Pulmonary embolism
  • Mechanical obstruction of the airways (benign and malignant tumors)
  • Pulmonary infiltration with eosinophilia
  • Cough secondary to drugs (eg, ACE inhibitors)
  • Vocal cord dysfunction
  • Gastroesophageal reflux disease (GERD)
  • Allergic rhinitis, sinusitis


Several comorbid chronic conditions have been demonstrated to impede asthma management. If these conditions are identified and treated properly, asthma control usually improves. Some of the more common comorbid conditions include gastroesophageal reflux disease (GERD), obesity, obstructive sleep apnea, rhinitis/sinusitis, and underlying mental health problems including stress and depression. Clients with severe forms of mental illness may experience complications due to an inability to follow instructions for medication use.

When considering comorbidities, they often act as a complicating factor, and exacerbate the underlying asthma symptoms until they are identified and managed. In this case, the overall picture of asthma may improve significantly. Any time clients display symptoms that suggest asthma, but their symptoms are not responding to treatment, they should be evaluated for other conditions known to affect breathing.

To clarify the role that a differential diagnosis or comorbidity may be playing relative to respiratory symptoms and asthma, the clinician must first assess whether the recommended treatment for asthma is being taken as ordered. The following questions may be helpful in determining whether asthma is being refractory to treatment of whether an alternate/additional diagnosis needs to be explored:

  • Can you tell me which medications you use and when you use them?
  • Who told you that you had asthma?
  • Can you show or describe your technique for using medication?
  • How many places do you go to receive healthcare? (Clients who receive advice from multiple locations or providers may become confused about which medication regimen to follow.)
  • Do you use more than one pharmacy for your medications? (Verify dates of initial fill and refills.)

Adequate treatment of the comorbid condition may lead to an improvement in asthma symptoms, with corresponding improvement in the severity classification and medication routine. Asthma therapy may be stepped down if symptoms remain stable for several months.

If respiratory symptoms are successfully treated and if other symptoms abate, the client may not have asthma at all and the differential diagnosis should be reviewed.

Let’s return to our theoretical client, Tom, to see how this might work.

Based on Tom’s symptoms—nighttime waking 3 times a week, an FEV1 of 75% (5% below reference), daily asthma symptoms, and missed classes—his severity was classified as “moderate persistent.”

Tom was given a short course of oral prednisone, started on a moderate-strength inhaled corticosteroid (ICS), instructed to use inhaled albuterol (SABA) 2 puffs twice daily, advised on abatement strategies for cat dander exposure, and told to return in 4 weeks or as needed if his symptoms got worse.

After 2 weeks he called the office to report that he was continuing to have nighttime coughing that had increased to every night, and he was using up to 8 puffs of his albuterol every day to try to control his symptoms. He had complied with all abatement measures recommended to minimize exposure to animal dander. He was instructed to come to the office immediately for further evaluation.

During questioning about additional changes since moving from the dorm to an apartment, Tom reports that there have been notable changes to his diet. He is eating more fast foods, eating later at night, and snacking as he studies. He is drinking 1 to 2 beers at night while socializing with his roommate. He frequently awakens in the morning with poor appetite and doesn’t eat until lunchtime. He drinks several cups of very strong coffee during the day, and also drinks caffeinated sodas. He is experiencing some esophageal reflux.

Based on his symptoms, Tom is provided with instructions on diet and lifestyle measures designed to reduce symptoms of GERD and begins empiric treatment with a proton pump inhibitor (PPI) at night. He is instructed to continue with the recommended medications for his asthma and return to the office in 7 to 10 days—sooner if the symptoms continue to worsen.

When Tom returns for his scheduled visit he reports that he is following recommendations for GERD, has not needed his PPI for the last 2 nights, and only requires his albuterol once a day, usually shortly after returning to his apartment in the evening.

Tom’s case illustrates the importance of obtaining a full history when initiating therapy. When the client appears refractory to reasonable control measures, the clinician must proceed to questions and testing that focus on conditions suggested by the client’s history and physical examination. GERD, in particular, is well known to exacerbate asthma because the backflow of stomach acid into the esophagus causes additional irritation to the airways and lungs.

Obesity can also be associated with GERD and obstructive sleep apnea, which are known to complicate asthma. Rhinitis, or postnasal drip, may indicate that the client has an underlying sinus infection requiring treatment. A productive cough with mucopurulent sputum should not be treated as asthma even though it has lasted more than the 7 to 10 days typical for a viral infection.

Regardless of what additional conditions may be contributing to the client’s symptoms, if the diagnosis of asthma has been made using the classical characteristics of the disease—symptoms, airway obstruction, inflammation, and hyper-responsiveness—it is of vital importance to determine if the client is using his medications properly before subjecting him to the time and expense of pursuing other diagnoses.

We will return to Tom later to see what additional measures may assist him in gaining control over his symptoms. Although Tom is a young college student in his first independent living situation, he is an ideal subject for study because he is unusually cooperative and amenable to education.

Back Next