- Email: [email protected]
Assessment of asthma control and severity
CME review article This feature is supported by an unrestricted educational grant from AstraZeneca LP
Assessment of asthma control and severity William M. Vollmer, PhD
Objective: To provide a conceptual framework for defining severity and control in asthma, to describe recent advances in measuring asthma control, and to discuss the role of severity and control in asthma disease management. Data Sources: MEDLINE was searched for relevant English-language articles published between 1998 and July 2003. Additional sources included key references cited in these articles, national and international guidelines for the diagnosis and management of asthma, and the author’s personal bibliography. Study Selection: All studies that reported on the development and validation of formal measures of asthma control, as well as the few editorials that focused on the distinction between asthma severity and control, were included. The author’s professional judgment was used to select for illustrative purposes from among the many purported measures of asthma severity in the literature. Results: Although several standardized measures of asthma control exist, no direct comparisons of the performance and properties of these control measures have been published. The available instruments appear more similar than dissimilar. All share the common trait of assessing multiple aspects of asthma control, which is believed to provide better discrimination than a single measure. Conclusions: Asthma control is different from asthma severity and may be useful as a clinical vital sign for patients with asthma. Ultimately, no one measure may be better than any of the others or the optimal measure may depend on the intended use of the scale. Ann Allergy Asthma Immunol. 2004;93:409–414. Off-label disclosure: Dr. Vollmer has indicated that this article does not include the discussion of unapproved/investigative use of a commercial product/device. Financial disclosure: Dr. Vollmer has indicated that in the last 12 months he has received research support from Merck & Company Inc. Instructions for CME credit 1. Read the CME review article in this issue carefully and complete the activity by answering the self-assessment examination questions on the form on page 415. 2. To receive CME credit, complete the entire form and submit it to the ACAAI office within 1 year after receipt of this issue of the Annals.
INTRODUCTION Despite the evolution in our understanding of asthma as a chronic inflammatory disease, the development of powerful new drugs for its management, and the dissemination of national treatment guidelines, asthma continues to be a common disease with significant morbidity.1–3 National data indicate that the prevalence of asthma in the United States increased 75% (from 3.1% to 5.4%) between 1980 and 1994 and the annual cost to the US health care system in 1998 was in excess of $11 billion.3 In response to this growing problem, increasing attention is being given to the concept of population-based asthma disease management and to the development of tools to identify patients who are at increased risk for future acute exacerbations. One by-product of this activity has been an emerging Center for Health Research, Kaiser Permanente, Portland, Oregon. Received for publication December 16, 2003. Accepted for publication in revised form April 20, 2004.
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emphasis on the distinction between asthma control and asthma severity4 – 6 and on the development of measures of asthma control that are distinct from asthma severity.7–10 This article provides a conceptual framework for thinking about severity and control in asthma, describes recent advances in measuring asthma control, and discusses the role of severity and control in asthma disease management. MEDLINE was searched for relevant English-language articles published between 1998 and July 2003. Additional sources included key references cited in these articles, national and international guidelines for the diagnosis and management of asthma, and the author’s personal bibliography. All studies that reported on the development and validation of formal measures of asthma control, as well as the few editorials that focused on the distinction between asthma severity and control, were included. The author’s professional judgment was used to select for illustrative purposes from among the many purported measures of asthma severity in the literature.
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ASTHMA SEVERITY VS CONTROL The term severity as used in the asthma literature may have many meanings, ranging from the underlying severity of disease to the severity of symptoms on a day-to-day basis to the clinical severity of an acute exacerbation in a patient who presents to the emergency department. In this article, we use the term to refer to the underlying severity of disease. In this sense, it is a stable personal characteristic that may change, but only slowly over time. In the absence of treatment, severity can be measured by lung function, the intensity and frequency of symptoms, interference with activities, and so on.1 In the presence of treatment, theoretically, it can be measured by the minimum level of treatment required to attain good control. In practice, severity is probably best measured by some combination of the 2 approaches, although no universally agreed on algorithm exists. Level of control, by contrast, may be thought of as a relatively short-term evaluation of the adequacy of patient management.4 In the clinical setting, it can be thought of as the answer to the question, “How is your asthma affecting you today?” and determines whether or not an adjustment to therapy or other clinical intervention is needed. The severity classification used in the Second Expert Panel Report of the National Asthma Education and Prevention Program (NAEPP2)1 is thus seen to reflect the patient’s level of asthma control in the absence of treatment. Although closely related, asthma severity and level of control are nonetheless distinct concepts. A patient with moderate-to-severe asthma can have well-controlled asthma with good management, whereas a patient with relatively mild asthma who is nonadherent to therapy and practices poor allergen control may experience relatively poor control of
symptoms. The interplay among severity, personal management practices (including medication adherence and allergen avoidance), and asthma control is depicted in Figure 1. For any given level of severity, control will tend to improve as management practices improve. Similarly, for any given level of management practices, increasing severity will tend to be associated with worsening control. Obviously, however, other factors, such as genetics, may influence these relationships. Theoretically, Figure 1 could be inverted to define severity based on some combination of level of control and asthma management, which in effect is what most of the existing severity indices try to do. Figure 2 further illustrates the conceptual distinction between severity and control. In this simplified causal model, we see that severity is a determinant of level of control (rather than vice versa) and that its impact is modulated by medical management, patient self-management practices, environmental exposures, and other factors. Level of control, although a legitimate outcome of therapy in its own right, also helps to determine other outcomes, such as health care utilization, quality of life, and functional status. Although severity may influence these outcomes directly, I hypothesize, at least in this model, that it exerts these effects primarily through its influence on level of control. Whether severity or level of control is more important depends on one’s perspective. To the patient, current symptoms and level of control most immediately determine quality of life, although these are, of course, influenced by severity. To the clinician, being able to ascertain the current level of control is most useful in determining if therapeutic adjustments or other interventions are required; an understanding of underlying severity also is needed to determine the proper
Figure 1. Interplay among asthma severity and level of asthma management, depicted along the vertical and horizontal axes, and level of asthma control, depicted by varying shades of gray inside the box. Adapted with permission from Osborne et al.26
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Figure 2. A simplified causal model showing the interplay among asthma severity; medical management; personal self-management practices; environmental and other factors; asthma control; and quality of life, functional status, and short-term asthma health care utilization.
medication regimen. To a health plan manager or an epidemiologist performing outcomes research, level of control is an outcome of interest, and severity is a confounder for which adjustment may be needed. ASSESSING LEVEL OF CONTROL If control is viewed as a measure of the adequacy of patient management, then a good measure of control should reflect the extent to which the goals of treatment are being met. Although the frequency and severity of asthma symptoms might seem attractive as a measure, such an approach does not capture the full spectrum of treatment goals. In addition, patients are known to vary in their perception and recognition of symptoms.11 Briefly stated, the Global Initiative for Asthma (GINA) guidelines state the goals of therapy as the prevention of troublesome symptoms; the prevention of serious exacerbations; the achievement of normal pulmonary function; and the ability to lead a productive, physically active life.2 Although the GINA documents do not propose a formal measure of control based on these criteria, Bateman et al9 conducted this exercise. They noted that, although the attainment of full control is possible, the proportion of patients achieving full control is much lower than the proportion who can achieve individual elements of control. They concluded that reliance on individual measures of control is likely to result in significant overestimation of true control. Although the authors did not present a rigorous evaluation of the performance characteristics of this measure of control, they did consider the responsiveness characteristics of 3 different thresholds for defining control based on their index. In 1999, the Royal College of Physicians in London proposed a simple measure of control that uses yes-or-no ques-
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tions to evaluate the following 3 dimensions: nocturnal awakening, daytime symptoms, and interference with activities.12 This measure was touted as being useful to the clinician and patient, as well as permitting scores to be aggregated for groups of patients to evaluate quality of care, but it has not, to my knowledge, been validated. A similar index, the Jones Asthma Morbidity Index, has been validated and is one of the bases of the measure proposed by the Royal College of Physicians in London.13,14 The Jones Asthma Morbidity Index also asks 3 yes-or-no questions and determines risk of morbidity by the number of yes answers. Vollmer et al8,15 proposed yet a fourth multidimensional measure of asthma control (the Asthma Therapy Evaluation Questionnaire [ATAQ] control index). Similar to the 2 measures mentioned herein, the ATAQ assesses control based on a brief series of dichotomously scored questions, with the control index being simply the number of control problems identified. The 4 dimensions that comprise the scale are nocturnal wakening, interference with activities, overuse of reliever medications, and self-perception of poor control. Using survey data from more than 5,100 adult asthma patients, the authors demonstrated that the ATAQ control index shows a striking correlation with generic and asthma-specific measures of quality of life and with self-reported, short-term health care utilization.8 In these cross-sectional analyses, each additional control problem was associated with a clinically significant decrement in all of these measures, which supports the concept of using multidimensional measures of asthma control. In prospective analyses, the authors demonstrated the ability of the ATAQ score to stratify patients on the basis of their risk of future acute exacerbations. Individuals who reported 3 to 4 control problems were at 31⁄2-fold
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risk relative to those with no control problems, and those with 1 to 2 control problems were at intermediate risk.15 No data are currently available on the responsiveness characteristics of this measure in clinical trials. Juniper et al7,16 have reported on the Asthma Control Questionnaire (ACQ), which also measures asthma control. Similar to the other measures that have been discussed, the ACQ consists of a limited number of questions (7) that tap multiple dimensions of control, including nocturnal awakening, daytime symptoms, interference with activities, overuse of reliever medication, and lung function. Unlike the previous control measures with dichotomized responses, each of the ACQ questions is coded on a 7-point scale, and these are averaged to obtain an overall score. In a 9-week observational study of adult asthma patients, the ACQ control index was very responsive to changes in clinically measured control, whereas it was stable in those whose asthma remained stable. The latest in the burgeoning field of asthma control indices is the Asthma Control Test (ACT), which is available through QualityMetric Inc (Lincoln, RI). The ACT measures 5 dimensions of asthma control: the impact of asthma on role functioning, patients’ rating of asthma control, shortness of breath, nighttime awakenings, and rescue medication use. Information on the development and performance properties of the ACT was recently published.17 For the most part, these measures of control are all patient centric and do not rely on clinical measurements. This makes them easy to use in epidemiologic surveys or as part of population-based disease management evaluation. Nonetheless, it is reasonable to speculate that their predictive value would be improved by the addition of clinical measurements, such as lung function or markers of inflammation. In this vein, it is interesting to note that Juniper et al18 have reported that the ACQ questions on airway caliber and rescue medication use could be omitted without changing the validity or measurement properties of the instrument. This suggests that the other, more patient-centric measures convey most of the useful information regarding control. This still leaves unresolved the question of whether the patient with evidence of significant airway obstruction or active inflammation in the absence of other signs and symptoms should be regarded as in control. As Fuhlbrigge6 has noted, debate continues on the role biomarkers should play in the evaluation of control. ASSESSING ASTHMA SEVERITY Efforts to develop standardized measures of asthma severity far predate similar efforts to measure asthma control, and numerous measures of asthma severity have been proposed.19 –22 Even so, in many ways far more progress has been made on measures of asthma control. Current national guidelines define severity in terms of the level of control in the unmedicated state.1 Such guidelines do not apply to most patients with asthma, who typically are taking some form of medication. Severity is therefore perhaps best evaluated by some combination of current control, medication use, and past short-term health care utilization. To the extent that
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severity is evaluated based on measures of short-term control, it will inevitably reflect short-term control and not true severity. It would be better to try to define severity based on medication use and/or measures of longer-term control. For instance, questions about symptom severity or control “over the past year” or “on average” are more likely to measure true severity, especially in the presence of medication use, than are questions about control in the past week or month. Blanc et al19 proposed a 29-point severity scale that includes information on prior hospitalizations, intubation, frequency of symptoms, and medication use. Although this scale has been shown to be useful in categorizing patients, the level of gradation of the scale may limit its clinical utility for clinicians who seek to make treatment decisions. For instance, is there a natural grouping of scores that would correspond roughly to the NAEPP2 classification system? Baker et al23 recently highlighted the difficulty in assessing asthma severity by asking 24 board-certified pediatric allergists and pulmonologists to rate the severity of each of 8 case summaries according to national guidelines. They reported a low level of interrater agreement and suggested the need for a refined classification system that would help ensure a more reliable application of the guidelines. In a companion editorial, Colice24 noted that despite the “seductive” appeal of the asthma severity classification system for clinicians, clinicians are unable to apply it. He noted that asthma control is probably more relevant than severity in helping clinicians evaluate the risks and benefits of asthma pharmacotherapy. IMPLICATIONS FOR USE OF MEASURES OF ASTHMA CONTROL Clinically, measures of asthma control have several natural uses. They in some sense measure the ultimate outcome of patient management (including pharmacologic management, adherence, and allergen control). Thus, a measure of asthma control taken in the clinic setting can provide a good “vital sign,” analogous to a blood pressure reading for hypertension or a glucose level for diabetes. As noted previously, a measure such as the ATAQ index provides a simple way to identify patients potentially at risk. It also can identify specific problem areas (nocturnal wakening, interference with activities, overuse of reliever medications) that can serve as a basis for discussion with the patient. Specialty offices that see a higher volume of asthma patients may find even more elaborate evaluations to be feasible and beneficial.25 On a population level, measures of asthma control can be useful disease management tools. Overall level of asthma control of a population can be evaluated on a regular basis and compared across facilities or administrative units (ideally with some adjustment for severity case mix). In addition, such measures can be used as part of proactive disease management activities. My own institution is currently conducting a study of using speech recognition software to make computerized calls to members of its asthma registry to ask about their current level of asthma control. The brief evaluation asks ATAQ questions about whether the patient was
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recently hospitalized or seen in the emergency department for asthma and about current medication use. Patients receive tailored feedback, and those identified as being at high risk are flagged for follow-up by a clinician (typically by telephone). This 1-year randomized trial is currently under way. In the context of clinical trials (for instance, short-term trials of pharmaceutical agents), control can almost always be viewed as an outcome of interest (along with lung function and quality of life), whereas severity serves as a potentially confounding factor. These constructs should presumably be evaluated in this framework exactly as they are evaluated in any other setting. SUMMARY As noted, asthma control is a concept distinct from asthma severity and may be useful as a clinical vital sign for patients with asthma. Although several standardized measures of asthma control exist, to my knowledge no head-to-head comparisons of the performance and properties of these control measures have yet been published. The available instruments appear more similar than dissimilar. All share the common trait of assessing multiple different measures of asthma control, which is believed to provide better discrimination than a simple measure of, for example, current asthma symptoms. Not yet determined is the clinical relevance of significant lung function impairment or evidence of airways inflammation in the absence of other signs or symptoms. Ultimately, no one measure of asthma control may be better than any of the others or the optimal measure may depend on the intended use of the scale. ACKNOWLEDGMENT The author thanks Ms. Martha Swain for her invaluable editorial assistance in the preparation of the manuscript. REFERENCES 1. National Institutes of Health, National Asthma and Education and Prevention Program. Clinical Practice Guidelines: Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Institutes of Health; 1997. 2. National Institutes of Health, Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health; 1995. 3. National Institutes of Health. NHLBI Data Fact Sheet: Asthma Statistics. Bethesda, MD: National Institutes of Health; 1999:1– 4. 4. Cockcroft DW, Swystun VA. Asthma control vs. asthma severity. J Allergy Clin Immunol. 1996;98:1016 –1018. 5. Bateman ED. Measuring asthma control. Curr Opin Allergy Clin Immunol. 2001;1:211–216. 6. Fuhlbrigge AL. Asthma severity and asthma control: symptoms, pulmonary function, and inflammatory markers. Curr Opin Pulm Med. 2004;10:1– 6. 7. Juniper EF, O’Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999;14:902–907.
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8. Vollmer WM, Markson LE, O’Connor EA, et al. Association of asthma control with health care utilization and quality of life. Am J Respir Crit Care Med. 1999;160:1647–1652. 9. Bateman ED, Bousquet J, Braunstein GL. Is overall asthma control being achieved? A hypothesis-generating study. Eur Respir J. 2001;17:589 –595. 10. Bateman ED. Using clinical measures of disease control to reduce the burden of asthma. Pharmacoeconomics. 2001;19:7–12. 11. Stahl E. Correlation between objective measures of airway calibre and clinical symptoms in asthma: a systematic review of clinical studies. Respir Med. 2000;94:735–741. 12. Pearson MG, Bucknall CE. Measuring Clinical Outcome in Asthma: A Patient-Focused Approach. Sarum, Salisbury, UK: Royal College Physicians of London; 1999. 13. Jones K, Cleary R, Hyland ME. Predictive value of a simple asthma morbidity index in a general practice population. Br J Gen Pract. 1999;49:23–26. 14. Jones K, Cleary R, Hyland ME. Associations between an asthma morbidity index and ideas of fright and bother in a community population. Respir Med. 1999;93:515–519. 15. Vollmer WM, Markson LE, O’Connor EA, Frazier EA, Berger M, Buist AS. Association of asthma control with health care utilization. Am J Respir Crit Care Med. 2002;165:195–199. 16. Juniper EF, O’Byrne PM, Ferrie PJ, King DR, Roberts JN. Measuring asthma control: clinic questionnaire or daily diary? Am J Respir Crit Care Med. 2000;162:1330 –1334. 17. Nathan RA, Sorkness C, Li JT, et al. Development of the Asthma Control Test (ACT). J Allergy Clin Immunol. 2003;111:S214. 18. Juniper EF, O’Byrne PM, Roberts JN. Measuring asthma control in group studies: do we need airway calibre and rescue 2-agonist use? Respir Med. 2001;95:319 –323. 19. Blanc PD, Jones M, Besson C, Katz P, Yelin EH. Work disability among adults with asthma. Chest. 1993;104:1371–1377. 20. Wahlgren DR, Hovell MF, Matt GE, Meltzer SB, Zakarian JM, Meltzer EO. Toward a simplified measure of asthma severity for applied research. J Asthma. 1997;34:291–303. 21. Bailey WC, Higgins DM, Richards BM. Asthma severity: a factor analytic investigation. Am J Med. 1992;93:263–269. 22. Busse WW, Calhoun WF, Sedgwick JD. Mechanism of airway inflammation in asthma. Am Rev Respir Dis. 1993;147: S20 –S24. 23. Baker KM, Brand DA, Hen J Jr. Classifying asthma: disagreement among specialists. Chest. 2003;124:2156 –2163. 24. Colice GL. The seduction of asthma severity categorization. Chest. 2003;124:2054 –2056. 25. Jose B, Bukstein D. Development and clinical use of the asthma profile. Am Group Pract Assoc Qual Source Group Pract. 1996;4:1– 6. 26. Osborne ML, Vollmer WM, Pedula KL, Wilkins J, Buist AS, O’Hollaren M. Lack of correlation of symptoms with standard measures of severity. Chest. 1999;115:85–91. Requests for reprints should be addressed to: William M. Vollmer, PhD Center for Health Research Kaiser Permanente 3800 N Interstate Ave Portland, OR 97227-1110 E-mail: [email protected]
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Objectives: After reading this article, participants should be able to demonstrate an increased understanding of their knowledge of allergy/asthma/ immunology clinical treatment and how this new information can be applied to their own practices. Participants: This program is designed for physicians who are involved in providing patient care and who wish to advance their current knowledge in the field of allergy/asthma/immunology. Credits: ACAAI designates each Annals CME Review Article for a maximum of 2 category 1 credits toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity. The American College of Allergy, Asthma and Immunology is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.
CME Examination 1–5, Vollmer WM. 2004;93:409-414. Self-Assessment Exam Questions 1. The term asthma severity has been used in the literature to characterize which of the following? a. the underlying pathophysiologic features of a patient’s asthma b. the clinical acuity of asthma in patients who present to the emergency department c. the frequency or intensity of day-to-day asthma symptoms d. a and b only e. a, b, and c 2. The underlying severity of a patient’s asthma can, in theory, be evaluated by a. the minimum level of pharmacologic treatment needed to attain good control b. the percent predicted forced expiratory volume in 1 second following administration of a bronchodilator c. a patient’s level of asthma control in the absence of treatment d. a and c only e. a, b, and c 3. Which of the following is an accurate statement about asthma control? a. it is a stable characteristic that changes only slowly over time b. patients may exhibit good control of asthma in one area, such as nocturnal awakening, whereas still experiencing problems in other aspects of asthma control, such as interference with daily activities c. regular use of controller medications is indicative of good control
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d.
4.
5.
even a one-time evaluation of current asthma control can be used to identify patients at risk for subsequent short-term asthma health care utilization in the coming year e. all of the above f. b and d Which of the following statements about asthma severity and control are true? a. severity and level of control are distinct concepts that can be readily evaluated and distinguished from one another in practice b. level of control can be viewed as a measure of the extent to which treatment goals are being met c. level of severity directly influences level of asthma control from a causal perspective d. the level of patient adherence to medications is more likely to affect asthma severity than it is to affect asthma control e. a and b f. b and c Which of the following are currently published indices or questionnaires designed to measure level of asthma control? a. St. George’s Respiratory Symptom Questionnaire b. Asthma Therapy Evaluation Questionnaire c. Eichorn Asthma Control Index d. Juniper Asthma Control Questionnaire e. b and d f. all of the above Answers found on page 492.
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Assessment of asthma control and severity William M. Vollmer, PhD
Objective: To provide a conceptual framework for defining severity and control in asthma, to describe recent advances in measuring asthma control, and to discuss the role of severity and control in asthma disease management. Data Sources: MEDLINE was searched for relevant English-language articles published between 1998 and July 2003. Additional sources included key references cited in these articles, national and international guidelines for the diagnosis and management of asthma, and the author’s personal bibliography. Study Selection: All studies that reported on the development and validation of formal measures of asthma control, as well as the few editorials that focused on the distinction between asthma severity and control, were included. The author’s professional judgment was used to select for illustrative purposes from among the many purported measures of asthma severity in the literature. Results: Although several standardized measures of asthma control exist, no direct comparisons of the performance and properties of these control measures have been published. The available instruments appear more similar than dissimilar. All share the common trait of assessing multiple aspects of asthma control, which is believed to provide better discrimination than a single measure. Conclusions: Asthma control is different from asthma severity and may be useful as a clinical vital sign for patients with asthma. Ultimately, no one measure may be better than any of the others or the optimal measure may depend on the intended use of the scale. Ann Allergy Asthma Immunol. 2004;93:409–414. Off-label disclosure: Dr. Vollmer has indicated that this article does not include the discussion of unapproved/investigative use of a commercial product/device. Financial disclosure: Dr. Vollmer has indicated that in the last 12 months he has received research support from Merck & Company Inc. Instructions for CME credit 1. Read the CME review article in this issue carefully and complete the activity by answering the self-assessment examination questions on the form on page 415. 2. To receive CME credit, complete the entire form and submit it to the ACAAI office within 1 year after receipt of this issue of the Annals.
INTRODUCTION Despite the evolution in our understanding of asthma as a chronic inflammatory disease, the development of powerful new drugs for its management, and the dissemination of national treatment guidelines, asthma continues to be a common disease with significant morbidity.1–3 National data indicate that the prevalence of asthma in the United States increased 75% (from 3.1% to 5.4%) between 1980 and 1994 and the annual cost to the US health care system in 1998 was in excess of $11 billion.3 In response to this growing problem, increasing attention is being given to the concept of population-based asthma disease management and to the development of tools to identify patients who are at increased risk for future acute exacerbations. One by-product of this activity has been an emerging Center for Health Research, Kaiser Permanente, Portland, Oregon. Received for publication December 16, 2003. Accepted for publication in revised form April 20, 2004.
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emphasis on the distinction between asthma control and asthma severity4 – 6 and on the development of measures of asthma control that are distinct from asthma severity.7–10 This article provides a conceptual framework for thinking about severity and control in asthma, describes recent advances in measuring asthma control, and discusses the role of severity and control in asthma disease management. MEDLINE was searched for relevant English-language articles published between 1998 and July 2003. Additional sources included key references cited in these articles, national and international guidelines for the diagnosis and management of asthma, and the author’s personal bibliography. All studies that reported on the development and validation of formal measures of asthma control, as well as the few editorials that focused on the distinction between asthma severity and control, were included. The author’s professional judgment was used to select for illustrative purposes from among the many purported measures of asthma severity in the literature.
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ASTHMA SEVERITY VS CONTROL The term severity as used in the asthma literature may have many meanings, ranging from the underlying severity of disease to the severity of symptoms on a day-to-day basis to the clinical severity of an acute exacerbation in a patient who presents to the emergency department. In this article, we use the term to refer to the underlying severity of disease. In this sense, it is a stable personal characteristic that may change, but only slowly over time. In the absence of treatment, severity can be measured by lung function, the intensity and frequency of symptoms, interference with activities, and so on.1 In the presence of treatment, theoretically, it can be measured by the minimum level of treatment required to attain good control. In practice, severity is probably best measured by some combination of the 2 approaches, although no universally agreed on algorithm exists. Level of control, by contrast, may be thought of as a relatively short-term evaluation of the adequacy of patient management.4 In the clinical setting, it can be thought of as the answer to the question, “How is your asthma affecting you today?” and determines whether or not an adjustment to therapy or other clinical intervention is needed. The severity classification used in the Second Expert Panel Report of the National Asthma Education and Prevention Program (NAEPP2)1 is thus seen to reflect the patient’s level of asthma control in the absence of treatment. Although closely related, asthma severity and level of control are nonetheless distinct concepts. A patient with moderate-to-severe asthma can have well-controlled asthma with good management, whereas a patient with relatively mild asthma who is nonadherent to therapy and practices poor allergen control may experience relatively poor control of
symptoms. The interplay among severity, personal management practices (including medication adherence and allergen avoidance), and asthma control is depicted in Figure 1. For any given level of severity, control will tend to improve as management practices improve. Similarly, for any given level of management practices, increasing severity will tend to be associated with worsening control. Obviously, however, other factors, such as genetics, may influence these relationships. Theoretically, Figure 1 could be inverted to define severity based on some combination of level of control and asthma management, which in effect is what most of the existing severity indices try to do. Figure 2 further illustrates the conceptual distinction between severity and control. In this simplified causal model, we see that severity is a determinant of level of control (rather than vice versa) and that its impact is modulated by medical management, patient self-management practices, environmental exposures, and other factors. Level of control, although a legitimate outcome of therapy in its own right, also helps to determine other outcomes, such as health care utilization, quality of life, and functional status. Although severity may influence these outcomes directly, I hypothesize, at least in this model, that it exerts these effects primarily through its influence on level of control. Whether severity or level of control is more important depends on one’s perspective. To the patient, current symptoms and level of control most immediately determine quality of life, although these are, of course, influenced by severity. To the clinician, being able to ascertain the current level of control is most useful in determining if therapeutic adjustments or other interventions are required; an understanding of underlying severity also is needed to determine the proper
Figure 1. Interplay among asthma severity and level of asthma management, depicted along the vertical and horizontal axes, and level of asthma control, depicted by varying shades of gray inside the box. Adapted with permission from Osborne et al.26
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Figure 2. A simplified causal model showing the interplay among asthma severity; medical management; personal self-management practices; environmental and other factors; asthma control; and quality of life, functional status, and short-term asthma health care utilization.
medication regimen. To a health plan manager or an epidemiologist performing outcomes research, level of control is an outcome of interest, and severity is a confounder for which adjustment may be needed. ASSESSING LEVEL OF CONTROL If control is viewed as a measure of the adequacy of patient management, then a good measure of control should reflect the extent to which the goals of treatment are being met. Although the frequency and severity of asthma symptoms might seem attractive as a measure, such an approach does not capture the full spectrum of treatment goals. In addition, patients are known to vary in their perception and recognition of symptoms.11 Briefly stated, the Global Initiative for Asthma (GINA) guidelines state the goals of therapy as the prevention of troublesome symptoms; the prevention of serious exacerbations; the achievement of normal pulmonary function; and the ability to lead a productive, physically active life.2 Although the GINA documents do not propose a formal measure of control based on these criteria, Bateman et al9 conducted this exercise. They noted that, although the attainment of full control is possible, the proportion of patients achieving full control is much lower than the proportion who can achieve individual elements of control. They concluded that reliance on individual measures of control is likely to result in significant overestimation of true control. Although the authors did not present a rigorous evaluation of the performance characteristics of this measure of control, they did consider the responsiveness characteristics of 3 different thresholds for defining control based on their index. In 1999, the Royal College of Physicians in London proposed a simple measure of control that uses yes-or-no ques-
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tions to evaluate the following 3 dimensions: nocturnal awakening, daytime symptoms, and interference with activities.12 This measure was touted as being useful to the clinician and patient, as well as permitting scores to be aggregated for groups of patients to evaluate quality of care, but it has not, to my knowledge, been validated. A similar index, the Jones Asthma Morbidity Index, has been validated and is one of the bases of the measure proposed by the Royal College of Physicians in London.13,14 The Jones Asthma Morbidity Index also asks 3 yes-or-no questions and determines risk of morbidity by the number of yes answers. Vollmer et al8,15 proposed yet a fourth multidimensional measure of asthma control (the Asthma Therapy Evaluation Questionnaire [ATAQ] control index). Similar to the 2 measures mentioned herein, the ATAQ assesses control based on a brief series of dichotomously scored questions, with the control index being simply the number of control problems identified. The 4 dimensions that comprise the scale are nocturnal wakening, interference with activities, overuse of reliever medications, and self-perception of poor control. Using survey data from more than 5,100 adult asthma patients, the authors demonstrated that the ATAQ control index shows a striking correlation with generic and asthma-specific measures of quality of life and with self-reported, short-term health care utilization.8 In these cross-sectional analyses, each additional control problem was associated with a clinically significant decrement in all of these measures, which supports the concept of using multidimensional measures of asthma control. In prospective analyses, the authors demonstrated the ability of the ATAQ score to stratify patients on the basis of their risk of future acute exacerbations. Individuals who reported 3 to 4 control problems were at 31⁄2-fold
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risk relative to those with no control problems, and those with 1 to 2 control problems were at intermediate risk.15 No data are currently available on the responsiveness characteristics of this measure in clinical trials. Juniper et al7,16 have reported on the Asthma Control Questionnaire (ACQ), which also measures asthma control. Similar to the other measures that have been discussed, the ACQ consists of a limited number of questions (7) that tap multiple dimensions of control, including nocturnal awakening, daytime symptoms, interference with activities, overuse of reliever medication, and lung function. Unlike the previous control measures with dichotomized responses, each of the ACQ questions is coded on a 7-point scale, and these are averaged to obtain an overall score. In a 9-week observational study of adult asthma patients, the ACQ control index was very responsive to changes in clinically measured control, whereas it was stable in those whose asthma remained stable. The latest in the burgeoning field of asthma control indices is the Asthma Control Test (ACT), which is available through QualityMetric Inc (Lincoln, RI). The ACT measures 5 dimensions of asthma control: the impact of asthma on role functioning, patients’ rating of asthma control, shortness of breath, nighttime awakenings, and rescue medication use. Information on the development and performance properties of the ACT was recently published.17 For the most part, these measures of control are all patient centric and do not rely on clinical measurements. This makes them easy to use in epidemiologic surveys or as part of population-based disease management evaluation. Nonetheless, it is reasonable to speculate that their predictive value would be improved by the addition of clinical measurements, such as lung function or markers of inflammation. In this vein, it is interesting to note that Juniper et al18 have reported that the ACQ questions on airway caliber and rescue medication use could be omitted without changing the validity or measurement properties of the instrument. This suggests that the other, more patient-centric measures convey most of the useful information regarding control. This still leaves unresolved the question of whether the patient with evidence of significant airway obstruction or active inflammation in the absence of other signs and symptoms should be regarded as in control. As Fuhlbrigge6 has noted, debate continues on the role biomarkers should play in the evaluation of control. ASSESSING ASTHMA SEVERITY Efforts to develop standardized measures of asthma severity far predate similar efforts to measure asthma control, and numerous measures of asthma severity have been proposed.19 –22 Even so, in many ways far more progress has been made on measures of asthma control. Current national guidelines define severity in terms of the level of control in the unmedicated state.1 Such guidelines do not apply to most patients with asthma, who typically are taking some form of medication. Severity is therefore perhaps best evaluated by some combination of current control, medication use, and past short-term health care utilization. To the extent that
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severity is evaluated based on measures of short-term control, it will inevitably reflect short-term control and not true severity. It would be better to try to define severity based on medication use and/or measures of longer-term control. For instance, questions about symptom severity or control “over the past year” or “on average” are more likely to measure true severity, especially in the presence of medication use, than are questions about control in the past week or month. Blanc et al19 proposed a 29-point severity scale that includes information on prior hospitalizations, intubation, frequency of symptoms, and medication use. Although this scale has been shown to be useful in categorizing patients, the level of gradation of the scale may limit its clinical utility for clinicians who seek to make treatment decisions. For instance, is there a natural grouping of scores that would correspond roughly to the NAEPP2 classification system? Baker et al23 recently highlighted the difficulty in assessing asthma severity by asking 24 board-certified pediatric allergists and pulmonologists to rate the severity of each of 8 case summaries according to national guidelines. They reported a low level of interrater agreement and suggested the need for a refined classification system that would help ensure a more reliable application of the guidelines. In a companion editorial, Colice24 noted that despite the “seductive” appeal of the asthma severity classification system for clinicians, clinicians are unable to apply it. He noted that asthma control is probably more relevant than severity in helping clinicians evaluate the risks and benefits of asthma pharmacotherapy. IMPLICATIONS FOR USE OF MEASURES OF ASTHMA CONTROL Clinically, measures of asthma control have several natural uses. They in some sense measure the ultimate outcome of patient management (including pharmacologic management, adherence, and allergen control). Thus, a measure of asthma control taken in the clinic setting can provide a good “vital sign,” analogous to a blood pressure reading for hypertension or a glucose level for diabetes. As noted previously, a measure such as the ATAQ index provides a simple way to identify patients potentially at risk. It also can identify specific problem areas (nocturnal wakening, interference with activities, overuse of reliever medications) that can serve as a basis for discussion with the patient. Specialty offices that see a higher volume of asthma patients may find even more elaborate evaluations to be feasible and beneficial.25 On a population level, measures of asthma control can be useful disease management tools. Overall level of asthma control of a population can be evaluated on a regular basis and compared across facilities or administrative units (ideally with some adjustment for severity case mix). In addition, such measures can be used as part of proactive disease management activities. My own institution is currently conducting a study of using speech recognition software to make computerized calls to members of its asthma registry to ask about their current level of asthma control. The brief evaluation asks ATAQ questions about whether the patient was
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recently hospitalized or seen in the emergency department for asthma and about current medication use. Patients receive tailored feedback, and those identified as being at high risk are flagged for follow-up by a clinician (typically by telephone). This 1-year randomized trial is currently under way. In the context of clinical trials (for instance, short-term trials of pharmaceutical agents), control can almost always be viewed as an outcome of interest (along with lung function and quality of life), whereas severity serves as a potentially confounding factor. These constructs should presumably be evaluated in this framework exactly as they are evaluated in any other setting. SUMMARY As noted, asthma control is a concept distinct from asthma severity and may be useful as a clinical vital sign for patients with asthma. Although several standardized measures of asthma control exist, to my knowledge no head-to-head comparisons of the performance and properties of these control measures have yet been published. The available instruments appear more similar than dissimilar. All share the common trait of assessing multiple different measures of asthma control, which is believed to provide better discrimination than a simple measure of, for example, current asthma symptoms. Not yet determined is the clinical relevance of significant lung function impairment or evidence of airways inflammation in the absence of other signs or symptoms. Ultimately, no one measure of asthma control may be better than any of the others or the optimal measure may depend on the intended use of the scale. ACKNOWLEDGMENT The author thanks Ms. Martha Swain for her invaluable editorial assistance in the preparation of the manuscript. REFERENCES 1. National Institutes of Health, National Asthma and Education and Prevention Program. Clinical Practice Guidelines: Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Institutes of Health; 1997. 2. National Institutes of Health, Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health; 1995. 3. National Institutes of Health. NHLBI Data Fact Sheet: Asthma Statistics. Bethesda, MD: National Institutes of Health; 1999:1– 4. 4. Cockcroft DW, Swystun VA. Asthma control vs. asthma severity. J Allergy Clin Immunol. 1996;98:1016 –1018. 5. Bateman ED. Measuring asthma control. Curr Opin Allergy Clin Immunol. 2001;1:211–216. 6. Fuhlbrigge AL. Asthma severity and asthma control: symptoms, pulmonary function, and inflammatory markers. Curr Opin Pulm Med. 2004;10:1– 6. 7. Juniper EF, O’Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999;14:902–907.
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8. Vollmer WM, Markson LE, O’Connor EA, et al. Association of asthma control with health care utilization and quality of life. Am J Respir Crit Care Med. 1999;160:1647–1652. 9. Bateman ED, Bousquet J, Braunstein GL. Is overall asthma control being achieved? A hypothesis-generating study. Eur Respir J. 2001;17:589 –595. 10. Bateman ED. Using clinical measures of disease control to reduce the burden of asthma. Pharmacoeconomics. 2001;19:7–12. 11. Stahl E. Correlation between objective measures of airway calibre and clinical symptoms in asthma: a systematic review of clinical studies. Respir Med. 2000;94:735–741. 12. Pearson MG, Bucknall CE. Measuring Clinical Outcome in Asthma: A Patient-Focused Approach. Sarum, Salisbury, UK: Royal College Physicians of London; 1999. 13. Jones K, Cleary R, Hyland ME. Predictive value of a simple asthma morbidity index in a general practice population. Br J Gen Pract. 1999;49:23–26. 14. Jones K, Cleary R, Hyland ME. Associations between an asthma morbidity index and ideas of fright and bother in a community population. Respir Med. 1999;93:515–519. 15. Vollmer WM, Markson LE, O’Connor EA, Frazier EA, Berger M, Buist AS. Association of asthma control with health care utilization. Am J Respir Crit Care Med. 2002;165:195–199. 16. Juniper EF, O’Byrne PM, Ferrie PJ, King DR, Roberts JN. Measuring asthma control: clinic questionnaire or daily diary? Am J Respir Crit Care Med. 2000;162:1330 –1334. 17. Nathan RA, Sorkness C, Li JT, et al. Development of the Asthma Control Test (ACT). J Allergy Clin Immunol. 2003;111:S214. 18. Juniper EF, O’Byrne PM, Roberts JN. Measuring asthma control in group studies: do we need airway calibre and rescue 2-agonist use? Respir Med. 2001;95:319 –323. 19. Blanc PD, Jones M, Besson C, Katz P, Yelin EH. Work disability among adults with asthma. Chest. 1993;104:1371–1377. 20. Wahlgren DR, Hovell MF, Matt GE, Meltzer SB, Zakarian JM, Meltzer EO. Toward a simplified measure of asthma severity for applied research. J Asthma. 1997;34:291–303. 21. Bailey WC, Higgins DM, Richards BM. Asthma severity: a factor analytic investigation. Am J Med. 1992;93:263–269. 22. Busse WW, Calhoun WF, Sedgwick JD. Mechanism of airway inflammation in asthma. Am Rev Respir Dis. 1993;147: S20 –S24. 23. Baker KM, Brand DA, Hen J Jr. Classifying asthma: disagreement among specialists. Chest. 2003;124:2156 –2163. 24. Colice GL. The seduction of asthma severity categorization. Chest. 2003;124:2054 –2056. 25. Jose B, Bukstein D. Development and clinical use of the asthma profile. Am Group Pract Assoc Qual Source Group Pract. 1996;4:1– 6. 26. Osborne ML, Vollmer WM, Pedula KL, Wilkins J, Buist AS, O’Hollaren M. Lack of correlation of symptoms with standard measures of severity. Chest. 1999;115:85–91. Requests for reprints should be addressed to: William M. Vollmer, PhD Center for Health Research Kaiser Permanente 3800 N Interstate Ave Portland, OR 97227-1110 E-mail: [email protected]
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Objectives: After reading this article, participants should be able to demonstrate an increased understanding of their knowledge of allergy/asthma/ immunology clinical treatment and how this new information can be applied to their own practices. Participants: This program is designed for physicians who are involved in providing patient care and who wish to advance their current knowledge in the field of allergy/asthma/immunology. Credits: ACAAI designates each Annals CME Review Article for a maximum of 2 category 1 credits toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity. The American College of Allergy, Asthma and Immunology is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.
CME Examination 1–5, Vollmer WM. 2004;93:409-414. Self-Assessment Exam Questions 1. The term asthma severity has been used in the literature to characterize which of the following? a. the underlying pathophysiologic features of a patient’s asthma b. the clinical acuity of asthma in patients who present to the emergency department c. the frequency or intensity of day-to-day asthma symptoms d. a and b only e. a, b, and c 2. The underlying severity of a patient’s asthma can, in theory, be evaluated by a. the minimum level of pharmacologic treatment needed to attain good control b. the percent predicted forced expiratory volume in 1 second following administration of a bronchodilator c. a patient’s level of asthma control in the absence of treatment d. a and c only e. a, b, and c 3. Which of the following is an accurate statement about asthma control? a. it is a stable characteristic that changes only slowly over time b. patients may exhibit good control of asthma in one area, such as nocturnal awakening, whereas still experiencing problems in other aspects of asthma control, such as interference with daily activities c. regular use of controller medications is indicative of good control
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d.
4.
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even a one-time evaluation of current asthma control can be used to identify patients at risk for subsequent short-term asthma health care utilization in the coming year e. all of the above f. b and d Which of the following statements about asthma severity and control are true? a. severity and level of control are distinct concepts that can be readily evaluated and distinguished from one another in practice b. level of control can be viewed as a measure of the extent to which treatment goals are being met c. level of severity directly influences level of asthma control from a causal perspective d. the level of patient adherence to medications is more likely to affect asthma severity than it is to affect asthma control e. a and b f. b and c Which of the following are currently published indices or questionnaires designed to measure level of asthma control? a. St. George’s Respiratory Symptom Questionnaire b. Asthma Therapy Evaluation Questionnaire c. Eichorn Asthma Control Index d. Juniper Asthma Control Questionnaire e. b and d f. all of the above Answers found on page 492.
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