Inhaled corticosteroids (ICS) were introduced to control asthma in the 1980s and 1990s and have been a godsend for asthma sufferers. These medications open an asthmatic’s airways quickly, reliably and without the need for medical intervention. They work so well, in fact, that they are often overprescribed and overused. In obstructive lung diseases, inhaled corticosteroids may be overprescribed regularly and result in other comorbidity.1 Even when an inhaler is necessary, for some patients the dosage may not be optimally titrated.
A trip to the ED is the last thing any physician wants for an asthmatic patient. When patients with asthma are hospitalized, typical treatment includes high doses of oral steroids for as long as 5 days. According to National Institutes of Health (NIH) guidelines,2 patients should experience high-dosage events no more than once every 2 years, but many asthma patients experience an exacerbation that requires hospitalization more frequently than the recommendation. As a result, doctors default to the “better safe than sorry” approach and overprescribe the medication rather than risk the consequences of under-prescribing.
Often asthma is diagnosed by clinicians using a binary scale: a patient does or does not have asthma; the disease is severe or it is mild. The reality of the disease, however, is much more nuanced, and an all-or-nothing approach makes it difficult to provide individualized treatment, particularly when it comes to medication. Clinicians initially estimate an effective dose of inhaled steroid for patients with asthma. If symptoms are relieved, the patient remains at that dosage. If symptoms are not relieved, clinicians typically increase the dosage. Decisions regarding dosing of medication to control symptoms are far from scientific.
What if doctors could isolate specific asthma triggers and quantify a patient’s asthma severity? Actually, they can, using two diagnostic tools available today: specific IgE (s-IgE) blood tests and fractional exhaled nitric oxide (FeNO) testing. Both have proven effective and been approved by the Food and Drug Administration (FDA), yet they are woefully underutilized.
Specific IgE Testing To Measure Allergic Sensitization
Allergy-induced asthma is the most common form of asthma3; as many as 60% of adults with asthma and 90% of children with asthma have allergic triggers.4,5 However, in practice, allergy diagnosis frequently represents a missed opportunity in asthma management. NIH guidelines recommend allergy testing for perennial indoor allergens for all patients with persistent asthma.2 Despite consensus in the medical community that allergy treatment is a crucial component of asthma management, too few treatment plans for patients with asthma include diagnostic testing for underlying allergic trigger. It is time for such an oversight to change. As specific IgE (s-IgE) allergy blood tests provide comparable specificity, sensitivity, and positive and negative predictive values to skin prick testing,6 the time for change is now. Some of the advantages of s-IgE blood testing include2:
Does not require knowledge of skin testing technique
Does not require availability of “potent” allergen extracts
Can be performed on patients who are taking medications that suppress the immediate skin prick test (antihistamines, antidepressants)
No risk of systemic reactions
Can be done for patients who have extensive eczema
Easier for most pediatric patients than skin testing
Overcomes poor skin reactivity in very young or old patients
Yields quantitative results with established 95% cutoff values
Allergy test results should always be interpreted in the context of the patient’s history, physical examination and allergen exposure.
Allergy testing is a vital step to identify a patient’s unique “allergy profile,” which can then be incorporated into a comprehensive allergy-asthma treatment plan. Testing for 25 to 30 inhalant allergens, customized to geographic region and pre-selected based on clinical allergy patterns, can reliably detect allergies.7 Identifying the patient’s triggers, for example, dust mites, can lead to easy steps, such as dustproof pillowcases,8 that could improve symptoms enough to lower medication requirements. If medication is required, testing may enable selection of a more appropriate dosage. According to American Academy of Allergy Asthma & Immunology (AAAAI), less than half of asthmatics report being taught how to avoid triggers.9 Knowing the results of s-IgE testing may help motivate patients to avoid their unique triggers.
FeNO Testing to Assess Airway Inflammation
Measuring exhaled nitric oxide (NO) is a highly accurate method for assessing the severity of inflammation of the airways. While peak flow meters estimate the extent of inflammation in a patient’s airways by measuring the force of an exhalation, FeNO testing measures swelling based on levels of NO emitted by inflamed tissue. FeNO testing is more precise than spirometry, which measures lung volume as a surrogate for asthma severity. The FeNO device measures the amount of NO in a patient’s lungs in parts-per-billion (ppb) as exhaled over the course of 15 seconds. Clinical experience demonstrates that FeNO measurements correlate well with eosinophilic, Th2-mediated airway inflammation.10
Some of the ways in which FeNO testing can be used in a clinical setting include11:
To assist in assessing the etiology of respiratory symptoms
To help identify the eosinophilic asthma phenotype
To assess potential response or failure to respond to anti-inflammatory agents, notably inhaled corticosteroids
To establish a baseline FeNO during clinical stability for subsequent monitoring of chronic persistent asthma
To guide changes in doses of anti-inflammatory medications: step-down dosing, step-up dosing, or discontinuation of anti-inflammatory medications
To assist in the evaluation of adherence to anti-inflammatory medications
To assess whether airway inflammation is contributing to poor asthma control, particularly in the presence of other contributors (such as rhinosinusitis, anxiety, gastroesophageal reflux, obesity, or continued allergen exposure)
*Adapted from the full American Thoracic Society guideline.
Higher FeNO values may indicate atopy and a positive response to ICS. FeNO testing more consistently predicts potential response to steroids than spirometry, bronchodilator response, peak flow measurements or airway hyperresponsiveness to methacholine.11 Regular FeNO testing also facilitates monitoring of a symptomatic patient with asthma, who is being treated with ICS, by tracking dynamic changes in airway inflammation. A significant increase in FeNO calls for a review of treatment, including medication. Falling or sustained low FeNO levels support a reduced ICS dose or even withdrawal. In patients on ICS who have persistent symptoms and elevated FeNO levels, infection or overwhelming allergen exposure are areas that may warrant investigation.
The Clinical Challenge
While ICSs offer effective treatment, every medication carries the risk of potential adverse events. Recent evidence suggests that some patients can experience significant adverse effects from ICS therapy. Adverse events linked to ICSs include temporary reduction in growth velocity in prepubertal children,12 cataracts, adrenal insufficiency and osteoporosis. Additionally, in 2010 in response to safety concerns regarding long-acting beta agonists (LABAs) and an increased risk for asthma-related death, the FDA mandated a boxed warning be included in all labeling for combination controller medications that contain ICSs and LABAs. Label changes include instructions that once asthma control is achieved and maintained, step-down therapy of combination medications be initiated.2 A better diagnosis and a personalized management plan can help limit the long-term exposure of patients to these medications.
Given the obvious benefits of testing to differential diagnosis, why are proven diagnostic tools such as s-IgE testing and FeNO testing not used universally? The answer begins with education. Although asthma management has progressed dramatically since asthma cigarettes were prescribed in the 1880s,13 medical schools still devote too few hours to contemporary allergy and asthma diagnosis. At the same time, some in the medical community are slow to incorporate newer diagnostic tests as part of their asthma treatment protocols. Adopting diagnostic tests, like s-IgE and FeNO, requires a new way of thinking, but the benefits are clear.
Asthma currently affects 26 million Americans and costs an estimated $25.6 billion annually.14 To fundamentally improve asthma management, I invite you to join me in rethinking the diagnostic process. Together, we can revolutionize asthma management by making relatively simple changes to incorporate s-IgE testing to identify allergic triggers and FeNO testing to help assess airway inflammation.
Inderpal Randhawa is an assistant professor of Clinical Pediatrics at UC Irvine School of Medicine and an assistant professor of Medicine at UCLA School of Medicine. He also holds several positions at Miller Children’s Hospital – Long Beach Memorial, including: program director, Pediatric Pulmonology Fellowship; director, Gallegos Food Allergy Center; associate director, Pediatric Pulmonary Services; director, Adult Cystic Fibrosis Center; Pulmonary, Clinical Immunology & Allergy.
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14. American College of Allergy, Asthma & Immunology. Asthma facts. http://www.acaai.org/allergist/news/Pages/Asthma_Facts.aspx.