Managing High-Risk Asthma Patients

Asthma is a heterogeneous syndrome with variable expressivity. The heterogeneity of asthma is governed, in part, by gene-by-environmental influences and gene-by-gene interactions. Therefore, by extrapolation, the heterogeneity of asthma results in variability of responsiveness to pharmacotherapeutic interventions and to environmental control manipulations. Therein lies the basis for individualization of therapeutic interventions in the management of most chronic diseases, asthma representing no exception.

The Expert Panel 3 Guidelines for the Diagnosis and Management of Asthma establishes a new paradigm for assessing and managing asthma within the context of current impairment and future risk.1 Current impairment addresses the tangible and quantifiable parameters of asthma expression, including daytime and nighttime symptoms, the frequency of quick-relief bronchodilator use, the objective assessment of lung function, and the assessment of quality of life as measured with validated questionnaires.

Future risk is less tangible and somewhat nebulous as the future is not easy to predict. Moreover, the risks that one has to anticipate any asthma patient experiencing include not only the risk of an exacerbation, but also the risk of premature loss of lung function in adults, inhibition of lung maturation in growing children, asthma drug interactions, and importantly, adverse effects of asthma medications.

A fundamental question is: How can asthma advance to the point that it becomes a high-risk disease? Underdiagnosis of asthma is common in inner-city populations. Late diagnosis of asthma may be even more common, with symptoms frequently being ignored or ascribed to other phenomena such as a common cold or poor conditioning, especially when there is coexisting obesity.

Education of high risk patientsAnother interesting question worthy of consideration is: Why is asthma poorly controlled even in some patients who are highly adherent to their prescribed respiratory medical regimen and who have successfully controlled for environmental triggers?

High-risk asthma patients include those who have demonstrated a rocky clinical course manifested by major life-threatening exacerbations, and those individuals who require high doses of inhaled or systemic corticosteroids in order to decrease the frequency of exacerbations.

Such high-risk asthma patients often find it hard to avoid exogenous triggers. Some of these individuals have lung inflammation that has escalated to the point that daily systemic corticosteroid use is necessary to attenuate airways lability associated with recurrent asthma destabilization, even while consuming the best medications available for long-term asthma control. Unfortunately, we have no disease-modifying asthma medications.

All high-risk asthma is not severe asthma. Certain demographic features automatically qualify one as having high-risk asthma. For example, in our practice, we consider all African-American women to be high-risk asthma patients because national statistics have demonstrated that they have a disproportionate probability of experiencing a fatal asthma attack. In fact, African-American women with asthma and Puerto Rican asthma patients have the highest mortality due to their disease than any other groups.2

All patients with very poorly controlled asthma do not necessarily have severe asthma. Some of them are simply non-adherent to their asthma medical regimen, while others are regularly exposed to triggers that drive the asthma.

On the other hand, it is apparent that individuals with severe asthma require high-intensity treatment. This group of patients includes some individuals with very poorly controlled asthma, patients with frequent exacerbations despite high-intensity treatment, as well as those who can only be well-controlled while taking high-intensity treatment.

Special considerations

Patients at high risk for an exacerbation require early intervention. A written asthma action plan is essential for all patients who have asthma, especially those who have moderate or severe persistent asthma or a history of severe exacerbations. Obvious interventions include removal or withdrawal of allergens or precipitating irritants in the environment that may be contributing to the exacerbation.

Who is at high risk?

    High-risk asthma patients require special consideration because they are otherwise likely to die prematurely.

    Such high-risk asthma patients include African-American children, African-American women, and Puerto Ricans.

    Other high-risk asthma patients include obese women with adult-onset asthma, especially if they have an idiosyncratic reaction to aspirin and other non-steroidal anti-inflammatory drugs and have nasal/sinus polyposis.

    Special measures must be taken to decrease the statistical probability of asthma attacks in such patient populations with special asthma phenotypes.

    Aggressive treatment with ICS and/or combination therapy, along with control of environmental triggers is essential in decreasing these patients’ likelihood of experiencing premature asthma death and severe asthma exacerbations.

The patient always should be instructed to promptly communicate to a clinician any serious deterioration in asthma symptoms or peak flow, any decreased responsiveness to short-acting beta-agonist (SABA) treatment, or decreased duration of effect of treatment with SABA. Rapid reversal of airflow obstruction should be attempted with repetitive or continuous administration of SABA. Appropriate intensification of therapy to match the level of intensity of disease expression is essential to preclude progression of an asthma flare-up to a severe exacerbation.

This circumstance almost always entails administering a short course of “burst” therapy with a systemic corticosteroid early in the course of treatment, especially if the patient fails to respond promptly and completely to SABA treatment.3-5

Short courses of oral corticosteroids (OCS) reduce the duration of an exacerbation and may prevent hospitalizations and relapse following an acute asthma exacerbation. Doubling the dose of an inhaled corticosteroid (ICS) in those patients already receiving ICS therapy has not been effective in reducing the severity of an exacerbation or in preventing progression of exacerbations.6-9 However, preliminary evidence indicates that quadrupling the dose of ICS for a period of seven days, starting at the first appearance of worsening symptoms, may prevent exacerbations requiring OCS and thereby reduce OCS requirements.10

In an emergency setting, it is important to classify the severity of asthma exacerbations in order to determine the appropriate course of action based on clinical assessment of the patient and some form of objective assessment of lung function in those who can carry out this action.

Recovery from an exacerbation varies, with symptom relief in one to two days being common for moderate exacerbations, but for three or more days for severe exacerbations. It is important to understand that even when symptoms have resolved, there is evidence of residual inflammatory foci within the airways for up to two to three weeks.11 In most cases, the gradual onset of an exacerbation requires protracted treatment to establish asthma stabilization.

Latest research

Asthma morbidity and mortality are increased in African-Americans. Some evidence is growing to suggest that gene-by-environmental influences are conducive to poor asthma outcomes in this population. Also, adolescent and teenage African-American asthma patients demonstrate resistance to ICS in comparison with their white cohorts.

In a retrospective review of adolescents with difficult-to-control asthma, researchers revealed a higher prevalence in steroid-insensitive asthma among African-American adolescents. They also were more likely to have a nonchaotic spirometry pattern, demonstrating greater fixed airflow obstruction with little diurnal variation, and a greater likelihood of significant airway remodeling at a younger age with a delay in asthma diagnosis and administration of corticosteroids.12

Other investigators conducted a cross-sectional study to ascertain whether African-American children and adults, with and without asthma, displayed diminished T-lymphocyte response to glucocorticoids in vitro compared to their white counterparts. They showed that the log-transformed concentration of dexamethasone required to suppress phytohemagglutinin-induced T-lymphocyte proliferation by 50 percent (logû0IC50) was greater in African-Americans with and without asthma in comparison to their white counterparts with asthma.13

These findings raise the question of a racial predisposition to diminished glucocorticoid responsiveness in African-Americans, which may possibly contribute to their heightened asthma morbidity and mortality.

Another team conducted a cross-sectional study including three ethnic populations (Mexican-Americans, Puerto Ricans, and African-Americans) with chronic persistent asthma.14 The percent change in FEV1 was compared in patients who used ICS versus those who used SABA as their only medication. While ICS use was associated with improvement in the percent change in FEV1 after albuterol administration in Mexican-Americans and Puerto Ricans, the augmented bronchodilator responsiveness to albuterol did not occur in African-Americans.

All of these studies collectively demonstrate the need for improved understanding of ethnic-specific, drug interactions and responses, particularly in those high-risk subgroups that experience the highest burden of asthma morbidity and mortality in the U.S.

View a list of references.

Michael B. Foggs, MD, FAAAAI, FACAAI, FCCP, is chief of allergy and immunology for Advocate Health Care, Chicago.