Can peak expiratory flow rates, symptom scores, β-agonist use, mast cell biopsy, tryptase levels, or exhaled nitric oxide levels predict an exacerbation event, defined as a 20% decrease in forced expiratory volume in one second (FEV1)?
In an ACRN study by Leone et al,
1 data collected from 313 participants were used to assess these outcomes. Of these participants, only 71 individuals met criteria for having active disease (ie, 20% decrease in FEV
1). In a comparison of the use of albuterol in the active disease group with the nonactive disease group, neither asthma symptom scores, peak flow values, nor diurnal variation of peak flow were able to accurately predict patients who would have a 20% decline in FEV
1.
The ability of peak flow measurement to predict a drop in FEV
1 occurred in only 17% of patients. In viewing the data from the opposite direction, only 19% of patients who had a decrease in FEV
1 also had a decrease in peak flow values. Results of the study by Leone et al
1 suggest that peak flow data, symptoms, and albuterol use may not be sensitive or specific enough (when used alone) to predict an asthma attack.
1
Because of the inability of peak flow values to predict an asthma attack and the lack of patient compliance in using peak flow meters, the NHLBI Guidelines for the Diagnosis and Management of Asthma
2 are flexible regarding the need to monitor peak flow values. The exception to this flexibility is the patient with poor perception of his or her asthma severity. In that cohort, monitoring peak flow—with the goal of intensifying treatment before an exacerbation occurs—is important. An obvious question arises: Are more specific and sensitive tests available for predicting asthma exacerbation? Exhaled nitric oxide (eNO) measurements, sputum eosinophil counts, and challenge tests have been evaluated to determine if these tests could successfully predict asthma exacerbation—especially when altering corticosteroid treatment.
To determine the success of eNO, sputum eosinophil assessments and challenge tests in predicting loss of asthma control, Deykin et al
3 randomized 164 patients to receive an inhaled corticosteroid (ICS), the β-agonist salmeterol, or placebo. Neither the eNO test nor the methacholine challenge was able to predict loss of asthma control, but increasing eosinophil counts in sputum were predictive. Thus, assessment of sputum eosinophils may help predict which patients with asthma need to be restarted on ICS treatment to prevent loss of asthma control. Although monitoring sputum eosinophils may be effective in predicting an impending asthma exacerbation, monitoring techniques are difficult to perform, quality assurance is intense, and interpretation of the slides is complex—all of which limit the use of sputum eosinophil assessments in clinics.
3
Analyzing mast cells and mast cell products (eg, tryptase levels) by bronchoscopy, biopsy, and bronchoalveolar lavage (BAL) can also be used to assess asthma control in patients. In a 28-week trial by Kraft et al,
4 45 patients underwent bronchoscopy, endobronchial biopsy, and BAL after a 6-week period in which all participants received the ICS triamcinolone acetonide. The patients were then randomly assigned to treatment with salmeterol, ICS, or placebo. At the end of the trial, they received a second bronchoscopy.
Similar to sputum eosinophils, mast cells were found by Kraft et al
4 to be an important predictor of asthma exacerbation in patients withdrawn from ICS and in others whose symptoms exacerbated while taking salmeterol or placebo. Patients whose symptoms exacerbated after stopping ICS had higher numbers of mast cells on biopsy despite therapy, and they also had higher levels of tryptase on BAL. Patients whose symptoms exacerbated while taking salmeterol or placebo also had higher levels of tryptase on BAL. These data suggest that assessment of mast cells or their products may help predict individuals who need ICS to maintain well-controlled asthma.
4
Despite the beneficial findings represented by these data, use of sputum eosinophil tests and bronchoscopy are not practical in many clinical settings. The collection of sputum and counting of sputum eosinophils is time-consuming and difficult to perform even in an experienced research laboratory. Adequate collection of sputum requires a well-trained technician and—even with such training—results can be inconsistent. Similarly, the use of bronchoscopy includes inherent risk and cost. Because of these factors, these procedures are unlikely to gain widespread use in the clinical setting.
Patient response to ICSs can be predicted by many parameters. In a dose-ranging study of 2 ICSs by Szefler et al,
5 patients who had a greater than 15% increase in FEV
1 level were more likely to have a high eNO level, a high degree of reversal of FEV
1 with albuterol, and a low FEV
1/forced vital capacity (FVC) ratio, compared to patients who had a minimal response in FEV
1 level. Of particular interest, methacholine suppression, eNO reduction, albuterol rescue use, symptom reduction, peak flow, and FEV
1 level all improved maximally with a low to medium dose of ICS. Increasing the ICS dose further provided only minimal improvement, despite the increase in cortisol suppression. The only parameter that required higher doses of ICS for maximal suppression was sputum eosinophil count.
5
Based on these studies,
1-5 no single parameter or variable that can be assessed routinely in the clinical setting provides sufficient information to determine risk of future asthma exacerbations. Thus, it is necessary to use multiple variables, as outlined by the NHLBI asthma guidelines,
2 to determine asthma severity, control, and treatment for a patient. The NHLBI asthma guidelines
2 suggest the consideration of daytime symptoms, nighttime symptoms, albuterol use, exercise tolerance, exacerbations
in the past year, and spirometry to classify asthma severity (
Figure 1), to assess asthma control options (
Figure 2), and to determine asthma management methods (
Figure 3).
Because of the difficulty of performing sputum eosinophil counts and the poor prediction of risk from using a single variable (eg, spirometry, peak flow, eNO, symptoms, methacholine), the NHLBI guidelines provide the most appropriate tool for managing the patient with asthma in the clinical setting.
2