New asthma guidelines emphasize control, regular monitoring

Validated tests are available to assess control

Asthma control is multidimensional⁹ and can be assessed by use of validated tests such as the Asthma Control Questionnaire (ACQ), Asthma Therapy Assessment Questionnaire (ATAQ), and the Asthma Control Test (ACT) (Table 3). These tests were designed to gauge asthma control over time in a user-friendly fashion. They are valid, reliable, and responsive to asthma control over time.^9–13

In the case of the ACT (Table 4), the patient answers five questions (each on a scale of 1 to 5) about symptoms and the use of rescue medications in the previous 4 weeks. In general, the higher the score (range 5–25), the better the control of the asthma; a cut-point of 19 yields the best balance of sensitivity (71%) and specificity (71%) for classifying asthma as well controlled or not well controlled.¹³

Serial testing as a quality indicator

Serial ACT scores give an objective measure of the degree to which the goals of management¹ are being achieved, and in so doing can encourage optimal outcomes.¹⁴

Another use of these tests is to document whether asthma control improves over time when patients receive care from a particular physician or group. This use may become increasingly important in view of efforts underway to implement a pay-for-performance model for asthma care, in which providers will be financially rewarded for improved patient care outcomes and adherence to standards of practice based on Health Plan Employer Data and Information Set measures.¹⁵

We have used the ACT in the Section of Allergy/Immunology at Cleveland Clinic for 3 years on a routine basis. All patients with asthma being seen either for the first time or as follow-up complete the ACT, which has been entered in a flow sheet in our electronic medical record, at the same time they undergo spirometry. We have shown that care in the Section of Allergy/Immunology is associated with improvement in asthma control over time, in patients who have completed serial ACT measurements at initial visits and at follow-up visits (Figure 2).

Objective measurement of lung function is also important

Serial monitoring of lung function at every patient visit with spirometry is also important, as some patients may be “poor perceivers,”¹⁶ ie, they may have little or no subjective awareness of moderate or even severe ventilatory impairment. A number of studies^17,18 support the contention that symptoms and lung function are separate and independent dimensions of asthma control, and that both of them need to be assessed.

Responding to changes in control

If the disease is well controlled, the provider, in collaboration with the patient, may consider continuing the current regimen or “stepping down” to a less aggressive treatment. If the patient’s asthma is not well controlled, it is appropriate to “step up” the treatment. The EPR3 guidelines outline a stepwise approach to therapy (Table 5), from intermittent asthma (step 1) to severe persistent asthma (steps 5 and 6).⁹ If asthma is poorly controlled, the patient is at risk of exacerbation of asthma and on this basis is clearly a candidate for intervention.^11–13,19

THE STEP 3 CONTROVERSY

Salmeterol Multicenter Asthma Research Trial

In the Salmeterol Multicenter Asthma Research Trial (SMART), patients randomized to the long-acting beta agonist (LABA) salmeterol (Serevent)—particularly African Americans—had a statistically significant increase in the risk of untoward asthma care outcomes.²⁰

SMART was launched in 1996. Patients were randomized in a double-blind fashion to receive either salmeterol 42 μg twice a day or placebo in addition to their usual asthma therapy for 28 weeks. The rate of the primary outcome (respiratory-related deaths or life-threatening experiences) was not significantly different with salmeterol than with placebo (relative risk [RR] = 1.40, 95% confidence interval [CI] 0.91–2.14). However, in 2003, the study was halted prematurely because of difficulty enrolling the targeted number of 60,000 patients, and an interim analysis that revealed significantly higher rates of secondary outcomes in subjects randomized to salmeterol. Compared with the placebo group, the salmeterol group had significantly higher rates of respiratory-related deaths (RR 2.16, 95% CI 1.06–4.41), asthma-related deaths (RR = 4.37, 95% CI = 1.25–15.34), and combined asthma-related deaths or life-threatening experiences (RR = 1.71, 95% CI 1.01–2.89). There were 13 asthma-related deaths and 37 combined asthma-related deaths or life-threatening experiences in the salmeterol group, compared with 3 and 22, respectively, in the placebo group. Of the 16 asthma deaths in the study, 13 (81%) occurred in the initial phase of SMART, when patients were recruited via print, radio, and television advertising; afterward, patients were recruited directly by investigators.

Statistically significant differences in outcomes occurred primarily in African Americans. African Americans who received salmeterol had higher rates of respiratory death or life-threatening experiences (RR = 4.10, 95% CI 1.54–10.90), the primary end point for the study, as well as higher rates of combined asthma-related deaths or life-threatening experiences (RR = 10.46, 95% CI 1.34–81.58), a secondary end point. No statistically significant differences were observed in white patients randomized to salmeterol with respect to the primary end point (RR = 1.05, 95% = 0.62–1.76); the secondary end point of combined asthma-related deaths or life-threatening experiences (RR = 1.08, 95% CI 0.55–2.14); or other end points.

Medication exposures were not tracked during the study, and allocation to inhaled corticosteroids combined with salmeterol was not randomized, so the effect of concomitant inhaled corticosteroid use cannot be determined from these data.

As a result of SMART, medications that contain either of the two LABAs, salmeterol or formoterol (Foradil), carry a black-box warning.