STANFORD, CALIF. – Therapy-resistant asthma usually isn’t.

Often it’s asthma that’s not really resistant to therapy, but a result of poor adherence to therapy, poor inhalation technique, or poor asthma control due to exposure to smoke or allergens.

And sometimes, it’s not even asthma. So, for a child with apparently severe asthma, first confirm the diagnosis and ensure that basic management strategies are in place and being followed, Dr. John D. Mark said at a pediatric update sponsored by Stanford University.

If you can improve the patient’s adherence to treatment, drug delivery, and exposure to environmental triggers, "you could fix nearly all ‘treatment-resistant asthma,’ " said Dr. Mark, a pediatric pulmonologist at Lucile Packard Children’s Hospital at Stanford.

He said he sees many patients referred for therapy-resistant asthma, but noted that there are not a lot of data on how to manage them.

Only 55 of 292 children with moderate to severe asthma, despite being prescribed at least 400 mcg/day of budesonide plus a long-acting beta-2 agonist, could be randomized after eligibility assessment in one treatment trial. Among the 237 who didn’t qualify, children either were nonadherent to treatment (38%) or were found to have mild or no asthma (25%) (J. Allergy Clin. Immunol. 2008;122:1138-44).

In a separate study of 780 patients aged 12-20 years with "severe asthma," the focus on basic asthma management during the run-in period of the trial improved symptoms so much that no clinically significant gains were achieved during the main part of the study by the use of exhaled nitric oxides as an indicator of control, even though this measure increased corticosteroid use (Lancet 2008;372:1065-72).

Another study found that 86% of 100 adults with chronic obstructive pulmonary disease or asthma were misusing their metered-dose inhaler (MDI) and 71% were misusing their Diskus dry powder inhaler (J. Gen. Intern. Med. 2011;26:635-42). A separate study of 127 children and adults found incorrect use of inhaler devices in 64% of MDI users and 26% of patients using the Rotahaler dry powder inhaler. Spacer devices seldom were used (J. Assoc. Physicians India 2005;53:681-4).

Dr. Mark said "therapy-resistant asthma" may fall into one of four categories:

• The wrong diagnosis. This is common, so do a diagnostic re-evaluation, he said.

• Asthma plus. Mild asthma exacerbated by one or more comorbidities is another common scenario. Some studies suggest that up to 15% of patients with severe or persistent asthma have dysfunctional breathing, such as vocal cord dysfunction. Rhinosinusitis, obesity, and food allergy can affect asthma control. Treating gastroesophageal reflux disorder usually does not improve asthma control much, Dr. Mark said.

• Difficult-to-treat asthma. This is a very common category in which poor treatment adherence or poor inhalation technique is the root of the problem. It often overlaps with the previous category.

• True resistance. Probably not common, this is severe therapy-resistant asthma that remains refractory to treatment even after dealing with reversible factors.

For diagnostic testing, start with lung function tests, he said. Spirometry is helpful, but the results may be normal even in cases of severe asthma. Longitudinal spirometry can be helpful, and bronchial responsiveness testing is helpful if the patient has persistent airflow limitation. Consider checking exhaled nitric oxide if that’s available and ordering complete lung function tests to evaluate lung volume and gas trapping. Look for markers of inflammation in induced sputum if the patient’s 1-second forced expiratory volume is more than 70% of predicted. An exercise challenge test also may be appropriate.

Perform an ear, nose, and throat or upper airway evaluation to look for vocal cord dysfunction. Assess tobacco smoke exposure by measuring cotinine in saliva or urine. If the patient has been prescribed theophylline, measure levels, Dr. Mark said.

Evaluate allergies by both skin prick testing and radioallergosorbent testing, looking for aeroallergens, fungi, and food allergens.

The role of bronchial challenge is not clear, and it can be dangerous if bronchial lability is present. There is no evidence to recommend routine high-resolution CT scans even in true severe, therapy-resistant pediatric asthma, he said.

For these tough cases, put on your Marcus Welby hat and make a home visit. "A home visit can be most rewarding," Dr. Mark said, because you can more accurately assess adherence to treatment, smoke exposure, allergens, and psychosocial factors such as acute and chronic stress, which are known to amplify the airway eosinophilic response to an allergen challenge.

A home visit helped solve the mystery of one 8-year-old boy with severe persistent asthma. Scans revealed no chronic sinusitis or bronchiectasis. But testing showed he was allergic to at least 32 substances, and a home inspection revealed mold throughout the house. Social services helped the family move to a new home, and Dr. Mark added itraconazole to the boy’s treatment regimen.

"You can figure it out," Dr. Mark said. "It took me around 3 years for this guy."

Dr. Mark reported having no relevant financial disclosures.

Therapy-Resistant Asthma May Be Neither