Control and severity: complementary approaches to asthma management
Authors: N. Roche, P. Godard
Journal: Allergy (2007)

Assessment of asthma now relies on two concepts, namely control and severity. An influence of severity on asthma-related costs has already been demonstrated (1). In the present issue of Allergy, Sullivan et al. show that, in a given severity stratum (i.e. patients with severe or difficult-to-treat asthma), the degree of control is also a determinant of costs (2). This finding leads to consider conceptual and practical differences between control and severity. It can also stimulate discussions on what the goal of treatment should be, depending on the perspective. Control and severity are both based on symptoms, exacerbations, impact on daily life, use of rescue medications, lung function and its variations. Therefore, factor analysis has been unable to identify distinct constructs of these concepts (3), which both influence healthcare resource utilization (4, 5). However, each has specificities which drive their usage and interpretation. First, severity, but not control, takes into account daily maintenance therapy (Fig. 1) (6). This has significant practical implications, including the difficulty of determining the real level of severity in patients on maintenance treatment who are suspected of being noncompliant. In these patients, assessing and, if necessary, improving compliance with pharmacological prescriptions and environmental measures are the first step to improve asthma control (7) and allow reliable evaluation of severity. Besides, many primary care physicians find it difficult to use Global Initiative for Asthma (GINA) severity classification in routine practice and believe that such a static index is inappropriate for an inherently variable disease such as asthma (8). Accordingly, adherence to treatment guidelines remains relatively poor, in part, due to misclassification of severity (4, 5, 9–12). Therefore, some guidelines now advocate that therapeutic changes are driven by one simple question, i.e. is asthma controlled? (Fig. 2) (7). This appears easier than trying to determine the right severity stage according to symptoms and treatment, with 12 possible combinations of the four levels of symptom severity with the three levels of maintenance treatment (Fig. 1) (6). Severity-based approach of asthma classification and management. Adapted from GINA guidelines (6). Control-based approach of asthma classification and management. Adapted from French guidelines (7). Another major difference between control and severity is the duration of the assessment period: severity is assessed over the preceding 6 months to 1 year, whereas control refers to the preceding weeks (1 week to 3 months): thus, while the level of control has to be evaluated at each visit and may change from one visit to another, reclassification of severity should be envisaged only when a stable level of control has been obtained and maintained during several (e.g. at least 3) months, allowing to decrease the ‘therapeutic pressure’. Besides, assessment of control may be more reliable, due to the shorter recall period. Furthermore, the goal of assessment is not the same for control and severity: control is one of the main treatment targets (together with the prevention of long-term lung function deterioration) and, therefore, might be considered as the main determinant of therapeutic decisions in a patient who is already treated. Severity is a way of (i) appreciating the prognosis and the level of treatment which will probably be necessary to obtain control and (ii) choosing initial treatment in a new patient. It also helps homogenizing communication about patients and may be used to predict asthma-related costs and resource utilization. As a consequence of the above-mentioned differences, determinants and clinical correlates of control and severity may not be identical: for instance, body mass index and obesity are associated with control and quality of life but not with severity (13, 14); conversely, tobacco smoking is associated with both poorer control and increased severity (15,16), although this relationship was not significant in the study by Sullivan et al. (2). In addition, for patients with a given level of severity, control is an additional contributor to quality of life (17). Some studies even suggest that control could be associated more strongly to quality of life than severity (18), thus being closer to the notion of ‘patient-reported outcomes’. However, quality of life may also change significantly in the absence of measurable variation in the degree of control, e.g. with new side-effects or constraints following treatment changes (19). Altogether, in routine practice, control appears to have more operational implications than severity, which might be considered as a more academic way of apprehending asthma. Data presented by Sullivan et al. in this issue of Allergy show that patients with severe asthma are frequently uncontrolled, which increases direct and indirect costs of the disease (2). Such results are not really surprising, but they are strengthened by the large scale of the study, which allows quantifying differences more reliably. In addition, they further emphasize the complementarity of the ‘control’ and ‘severity’ concepts. Repeated measures of control can also be used to estimate probabilities of transition from one state of health to another (e.g. from acceptable to unacceptable control) and determine their contributing factors; such an approach appears especially relevant when considering that a significant proportion of patients (16% in the study by Sullivan et al.) exhibit inconsistent levels of control. Then, medico-economic models (e.g. Markov model) can be built to analyse how these factors influence healthcare costs (14, 20). Such modelling is particularly useful to define treatment targets from both an economic and clinical point of view. Indeed, in patients with severe or difficult-to-treat asthma, an important question is the goal of treatment: should total control be targeted, as defined by the stringent criteria of the Gaining Optimal Asthma Control (GOAL) study (21), or should acceptable control (as defined in the GOAL study or in Canadian and French guidelines) (7, 22) be considered sufficient? It is almost impossible to propose a universally valid answer to this question: it depends on the price that patients, practitioners and payers are willing to pay in terms of therapeutic constraints, costs and side-effects: this explains why the French guidelines on asthma follow-up preferred to define an ‘optimal’ level of control, which can be either total control as in the GOAL study or ‘the best compromise between degree of control (provided that it is at least acceptable), acceptance of treatment and possible side-effects’ (7). One way of defining the most reasonable objective of asthma care could be to examine costs as a function of control: data presented in Fig. 1 of the paper by Sullivan et al. suggest that asthma-related costs begin to rise when the asthma therapy assessment questionnaire (ATAQ) score indicates at least two asthma-related problems. Thus, from an economic perspective, acceptable control would be enough and increasing treatment costs to reach total control would not be cost-effective. But these considerations are largely hypothetic and need to be confronted to results of formal cost-effectiveness studies. In the economic analysis of the GOAL study, increasing the proportion of total asthma control was associated with significant gains in quality-adjusted life years, but the corresponding increase in treatment costs was not fully compensated by the reduction in healthcare utilization (23). Another way of determining which level of control has to be achieved is to assess the relationship between control and quality of life; both types of indices usually correlate well with each other (24, 25). Studies with the ATAQ score found that statistically significant and clinically relevant impairment in quality of life begins when the number of asthma control problems in the past 4 weeks exceeds zero (26). However, using such findings to guide therapeutic decisions is not easy: the impairment in quality of life associated with poorer control could be the consequence of both physical symptoms and lower lung function (which are improved by treatments) and higher therapeutic pressure (which may increase side-effects and patients constraints) (27). A third way of defining the target level of control is to find out whether acceptable control is associated with a greater rate of exacerbations requiring emergency medical care than total control. Peters et al. recently showed that the risk of acute asthma events requiring healthcare utilization increases slightly when ATAQ score rises from 0 to 1–2 and more markedly between scores of 1–2 and 3–4 (28). Altogether, the target of asthma management in terms of level of control obviously depends on both the perspective and the patient. In conclusion, control and severity are complementary approaches to asthma management, with different goals and implications. Both influence asthma-related costs: from an economical point of view, severity may be used to predict these costs while improving control may be the most important goal to reduce them. Although a control-based approach may be quite simple to implement in routine primary care, the level of control to target will always be in part variable between patients: being influenced by many factors (including but not limited to severity), it has to be determined jointly by the patient and the doctor on an individual basis.