Is It Asthma or Something Else?

Looking out for asthma comorbidities

by Eli Hendel, M.D. Medical Reviewer

Asthma doesn’t always respond to conventional therapies, but before you consider a severe asthma diagnosis, you must rule out other conditions that mimic it. A 2017 article in the Journal of Asthma and Allergy highlighted the possibility that the comorbidities of asthma may require a very different therapeutic approach. As a pulmonary physician, I face this diagnostic challenge every day.

The common approach when asthma doesn’t initially respond, is to intensify the current treatment. For example, a physician might keep increasing the dose of inhaled corticosteroids (ICS). Higher dosing could cause negative side effects and it might not be the best treatment.

Uncontrolled asthma is defined by poor symptoms control, frequent exacerbations, or one serious exacerbation that requires hospitalization. It’s often assumed that treatment should be intensified to prevent complications. The problem is that, although symptoms are similar in each case, considering them a sign of severe asthma doesn’t always identify the actual mechanisms that are provoking the symptoms. Therefore, an opportunity may be missed to make the correct diagnosis.

It’s important then to identify the difference between severe asthma and asthma with co-morbidities, which are the culprits making the asthma resistant to treatment. Once those co-morbidities are identified, managing them effectively will result in improvement of asthma symptoms without the need to intensify the asthma treatment.

What are some of those co-morbidities?


There are some asthmatics who are also diagnosed with obesity and are (unfortunately) treated only with standard therapy. Treating those patients, without accounting for the co-morbid obesity, can result in poor control. A study of patients who had the characteristics of asthma and were also obese, used questionnaires to assess quality of life and the subjective test of breathlessness (St. George Respiratory Questionnaire). Findings showed that subjective breathlessness persisted even though objective parameters improved with the treatment.

It’s clear that if the patients continued to complain about symptoms, physicians might be inclined to increase dosages of asthma medications. What really needs treatment is the diagnosis of obesity with weight loss implemented through personalized diet, exercise, and other lifestyle recommendations. If the patient has severe obesity, then bariatric surgery might be a consideration.

High body mass index (BMI) negatively affects breathing and could easily lead to a misdiagnosis of severe or intractable asthma. Doctors need to focus on dealing with the status of obesity directly, without assuming the asthma is simply getting worse.

Chronic rhinosinusitis

Studies have shown that both medical and surgical treatment of chronic rhinosinusitis (CRS) are associated with clinical improvements of asthma control. This approach may not follow the current guidelines of step-by-step treatment for asthma but will be effective in patients with CRS and asthma. There are also some treatments for asthma that will treat CRS and they are typically not the first line of treatment for asthma. These include Singulair (montelukast), which works as an inhibitor of the mediators of asthma called leukotrienes. There are also newer biological agents that target interleukins IL5, IL4, ad IL13. These therapies will help to treat the CRS and therefore, the asthma symptoms.

It should be noted that these are unconventional treatments and these biologicals can also be expensive. It’s therefore important to identify the group of patients who will most benefit from these treatments. In certain cases, it may be beneficial to do a CT scan of the sinuses and an examination of the nasal mucosa to look for anatomical changes and nasal polyps associated with CRS. Those may need specific targeted treatments.

Vocal cord dysfunction (VCD)

This is a potentially dangerous condition where the vocal cords come closer together (adduction) in response to irritation of the larynx. Frequently, people affected by vocal cord dysfunction (VCD) go to emergency rooms and demonstrate wheezing on examination, so they are assumed to have asthma.

What needs to be identified by the doctor is that the wheezing in VCD is on inspiration – caused by the narrowing of the vocal cords. In “pure” asthma, the wheezing is during expiration, as the airways close during forceful expiration.

A pulmonary function test called flow volume loop will show a characteristic flat inspiratory curve in the case of VCD, but this test may not be readily available in the emergency room setting.

Sometimes these symptoms are also triggered by emotional stimuli. The treatment of the acute episode of wheezing due to VCD consists of providing heavy dense gas - a mixture of oxygen and helium (heliox). Chronic preventive management of VCD should include referral to a speech therapist.

What’s important to note is that if a patient presents with wheezing caused by co-morbid VCD - high dose intravenous corticosteroids will not help – and that is often the go to treatment in this presentation.

Asthmatics who smoke

Some smokers have a genomic variant that’s associated with a reduced expression of an enzyme called histone deacetylase (HDAC2). This enzyme regulates the protein that mediates the action of steroids. Reduced activity of the enzyme means a patient will have a poor response to corticosteroid therapy. These individuals will therefore frequently receive higher doses, given their poor response, and that will ultimately result in more (negative) side effects. Awareness of this phenomenon in smokers should alert the treating doctors to choose options other than steroid therapy to treat the asthma symptoms, including muscarinic or anti-cholinergic agents like Spiriva or Tudorza.

Other conditions

Gastroesophageal reflux disease, fluid overload due to heart failure, and obstructive sleep apnea are other conditions that deserve attention in the context of asthma that responds poorly to treatment, since each requires specific treatments. Much has been written about identifying these conditions, especially heart failure, since frequent use of fast-acting bronchodilators may incite dangerous cardiac arrhythmias.

Being aware that severe resistant asthma does not always require intensifying traditional treatments, but rather looking into other conditions that require different assessments and treatments may be another important way to prevent the consequences of severe unresponsive asthma.

Eli Hendel, M.D.
Meet Our Writer
Eli Hendel, M.D.

Eli Hendel, M.D., is a board-certified internist/pulmonary specialist with board certification in Sleep Medicine. An Assistant Clinical Professor of Medicine at Keck-University of Southern California School of Medicine, and Qualified Medical Examiner for the State of California Department of Industrial Relations, his areas include asthma, COPD, sleep disorders, obstructive sleep apnea, and occupational lung diseases. Favorite hobby? Playing jazz music.