Editorial
Measuring childhood asthma control Søren Pedersen, MD, PhD, DMSc
Kolding, Denmark
Key words: Asthma control, assessment, Global Initiative for Asthma, Childhood Asthma Control Test, Asthma Control Test, quality of life, Web-based diary recordings
Several studies have documented the benefits of good asthma control on a variety of outcomes that are important to patients and society, such as no restriction in lifestyle, better physical fitness and quality of life, reductions in asthma burden, health care resource use and lower risk of exacerbations, oral steroid use, hospitalizations, and death.1 Therefore the aims of asthma management focus on achieving and maintaining good asthma control and reducing future risks.2 The problem with this strategy is that correct assessment of asthma control is not straightforward. Several studies have found that the assessment of control varies markedly among health care professionals, as well as patients. Generally, both physicians and patients tend to overestimate the level of asthma control, with a subsequent risk of undertreatment.3 In an attempt to facilitate correct asthma control assessment, several simple and easy-to-use composite asthma control scores have been developed. Most try to capture the level of control in a single numeric value, such as the Asthma Control Test (ACT) and Childhood Asthma Control Test (c-ACT). Because the various tests use the same outcomes (daytime and nighttime symptoms, limitation of activities, and use of rescue medication), it is not unexpected that the results of these tests correlate with each other and with the Global Initiative for Asthma (GINA) definition of asthma control4 to some extent. However, symptoms, limitations of activities, and use of rescue medication are not independent variables. Physical activity is one of the most important causes of symptoms and reliever use in children. Therefore many children with insufficiently controlled asthma avoid strenuous exercise.5-8 The result is fewer daytime symptoms, less rescue use, and apparently controlled asthma. This is achieved at the expense of poorer fitness and a higher risk of obesity. Many parents (and children) are unaware of such changes in lifestyle. The question remains whether the various retrospectively collected tests capture the same information as the prospective but more cumbersome diary recordings and also whether a single cutoff value is sufficient or optimal in distinguishing between controlled and uncontrolled asthma. The study by Voorend-van From the University of Southern Denmark, Paediatric Research Unit, Kolding Hospital. Disclosure of potential conflict of interest: S. Pedersen has received consultancy fees from Bergen, GlaxoSmithKline, Boehringer Ingelheim, and Nycomed; has received research support from GlaxoSmithKline; and has received lecture fees from GlaxoSmithKline and Boehringer Ingelheim. Received for publication October 30, 2013; accepted for publication November 7, 2013. Corresponding author: Søren Pedersen, MD, PhD, DMSc, Paediatric Research Unit, Kolding Hospital, Skovvangen 2-8, 6000 Kolding, Denmark. E-mail: spconsult@ post1.tele.dk. J Allergy Clin Immunol 2013;nnn:nnn-nnn. 0091-6749/$36.00 Ó 2013 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaci.2013.11.003
Bergen9 provided some interesting additional information about this. It was reassuring that the retrospectively collected c-ACT and ACT scores correlated well with the prospectively collected Web-based diary recordings. However, the researchers also used their data to estimate c-ACT and ACT cutoff points for wellcontrolled asthma. This is novel and has been given little attention in the past. Most studies using the control tests have focused on differences in various outcomes between patients with c-ACT or ACT scores of less than 20 and patients with scores of greater than 19. From such studies, we have learned that a score of less than 20 is a significant risk factor for exacerbations, emergency department visits, health care use, poor quality of life, absence from school or work, and limitations in physical and social activities. Therefore, a score of less than 20 has become widely accepted as the level for poor asthma control, which requires treatment or treatment changes. Fewer studies have assessed whether a c-ACT or ACT score of greater than 19 can be used as an indication that the asthma is sufficiently or well controlled. The findings by Voorend-van Bergen et al9 suggest that this is probably not the case. Using sensitivity, specificity, and positive and negative predictive values for different cutoff points of c-ACT and ACT scores, the authors concluded that the cutoff scores for well-controlled asthma were 22 or greater for the c-ACT and 23 or greater for the ACT. According to the GINA criteria, 20% of their patients had symptoms that were well controlled, and 80% had symptoms that were not controlled (41% partly controlled and 39% uncontrolled). In contrast, only 29% and 25% of the children had symptoms that were uncontrolled according to the c-ACT or ACT (data provided by the authors). Similar differences have been reported in another study10: 85% had uncontrolled symptoms according to GINA criteria (uncontrolled and partly controlled) and only 40% had uncontrolled symptoms with the ACT/c-ACT. Knowledge of these differences between the various ways of defining controlled and uncontrolled asthma is important when comparing results from different studies. Children with uncontrolled asthma according to the GINA criteria are likely to be clinically quite different from children included in studies using a c-ACT or ACT score of less than 20 as a criterion to define uncontrolled asthma. The same will be the case for children defined as having controlled symptoms by using these 2 methods. On the other hand, it seems as if uncontrolled asthma defined by c-ACT or ACT scores is more similar to uncontrolled asthma defined by the GINA definitions. The clinical importance of the additional grading of the level of control used by GINA is less well studied. However, there are some suggestions that the additional grading might be useful. Studies in adults found significant differences between wellcontrolled and partly controlled asthma in a variety of clinically important outcomes,11 and another study reported that an ACT score of greater than 19 was found not to exclude poor asthma control very well.12 Findings of fewer symptoms and more symptom-free days in children with well-controlled asthma than in those with partly controlled asthma and an almost clinical 1
2 PEDERSEN
important difference in c-ACT or ACT scores between wellcontrolled and partly controlled asthma in the study by Voorend-van Borgen et al9 indirectly support that the same will also be the case for children. Quantifying control facilitates interpretation and comparison of clinical trials, as well as patients’ understanding of improvement and deterioration. It allows assessment of a minimal clinically important difference that will reflect a meaningful change for the patient. This is difficult with the GINA definition of control. Thus 77% of 548 children with uncontrolled asthma (GINA) achieved asthma control after treatment, suggesting that the remaining 23% did not benefit from the treatment because their symptoms remained not well controlled at study’s end.13 However, these patients all showed marked improvements in 1 or several control outcomes, and therefore at study’s end, they failed only half the number of the control criteria as at baseline. If the c-ACT or ACT had been used, the majority of these patients would have shown a clinically important improvement according to the criteria suggested by Voorend-van Bergen et al.9 Such useful information would not normally be missed when using the GINA definitions. The problem for all studies assessing asthma control is that we do not have a gold standard with which the various tests can be compared. Voorend-van Bergen et al9 used a change in the Pediatric Asthma Quality of Life Questionnaire or the Pediatric Asthma Caregiver’s Quality of Life Questionnaire results to define a minimally important clinical difference because these tests have previously been validated with respect to this. This is probably the best we can do at present, but it does not necessarily make it a gold standard. (Albert Einstein: ‘‘What counts cannot always be measured and what can be measured does not always count.’’) Both these tools depend heavily on symptoms, and the number of symptom-free days correlates with quality of life.14 Symptoms are subjective and influenced by the children’s level of perception of symptoms and the effect of the disease on the children’s daily activities, including sports and play and social life. Therefore good objective measures that do not depend on these factors would be welcome. In this respect FEV1 and exhaled nitric oxide measurement did not seem useful, but other outcomes, such as exercise challenges, objective measurements of daily physical activity, and specific diary recordings of daily
J ALLERGY CLIN IMMUNOL nnn 2013
activities, might be worth studying. The validity and feasibility of the Web-based diary recordings reported in the study by Voorend-van Bergen et al9 suggest that this tool might be useful in the future for more specific prospective recordings of daily activities and probably more reliable than retrospective recordings and a paper diary.
REFERENCES 1. O’Byrne PM, Pedersen S, Schatz M, Thoren A, Ekholm E, Carlsson LG, et al. The poorly explored impact of uncontrolled asthma. Chest 2013;143:511-23. 2. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, Fitzgerald M, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008;31:143-78. 3. Holgate ST, Price D, Valovirta E. Asthma out of control? A structured review of recent patient surveys. BMC Pulm Med 2006;6(Suppl 1):S2. 4. O’Byrne PM, Reddel HK, Eriksson G, Ostlund O, Peterson S, Sears MR, et al. Measuring asthma control: a comparison of three classification systems. Eur Respir J 2010;36:269-76. 5. Wildhaber J, Carroll WD, Brand PL. Global impact of asthma on children and adolescents’ daily lives: the room to breathe survey. Pediatr Pulmonol 2012;47: 346-57. 6. Haselkorn T, Chen H, Miller DP, Fish JE, Peters SP, Weiss ST, et al. Asthma control and activity limitations: insights from the Real-world Evaluation of Asthma Control and Treatment (REACT) study. Ann Allergy Asthma Immunol 2010; 104:471-7. 7. Vahlkvist S, Pedersen S. Fitness, daily activity and body composition in children with newly diagnosed, untreated asthma. Allergy 2009;64:1649-55. 8. Vahlkvist S, Inman MD, Pedersen S. Effect of asthma treatment on fitness, daily activity and body composition in children with asthma. Allergy 2010;65:1464-71. 9. Voorend-van Bergen S, Vaessen-Verberne AA, Landstra AM, Brackel HJ, van den Berg NJ, Caudri D, et al. Monitoring childhood asthma: web-based diaries and the Asthma Control Test. J Allergy Clin Immunol 2014;nnn:nnn. 10. Carroll WD, Wildhaber J, Brand PL. Parent misperception of control in childhood/ adolescent asthma: the Room to Breathe survey. Eur Respir J 2012;39:90-6. 11. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med 2004;170:836-44. 12. Thomas M, Kay S, Pike J, Williams A, Rosenzweig JR, Hillyer EV, et al. The Asthma Control Test (ACT) as a predictor of GINA guideline-defined asthma control: analysis of a multinational cross-sectional survey. Prim Care Respir J 2009;18: 41-9. 13. Pedersen S, Maspero J, Gul N, Sharma R. Components of asthma control and treatment response of individual control criteria in children: analysis of the PEACE study. Pediatr Pulmonol 2011;46:1182-8. 14. Carranza R Jr, Edwards L, Lincourt W, Dorinsky P, ZuWallack RL. The relationship between health-related quality of life, lung function and daily symptoms in patients with persistent asthma. Respir Med 2004;98:1157-65.
Measuring childhood asthma control Søren Pedersen, MD, PhD, DMSc
Kolding, Denmark
Key words: Asthma control, assessment, Global Initiative for Asthma, Childhood Asthma Control Test, Asthma Control Test, quality of life, Web-based diary recordings
Several studies have documented the benefits of good asthma control on a variety of outcomes that are important to patients and society, such as no restriction in lifestyle, better physical fitness and quality of life, reductions in asthma burden, health care resource use and lower risk of exacerbations, oral steroid use, hospitalizations, and death.1 Therefore the aims of asthma management focus on achieving and maintaining good asthma control and reducing future risks.2 The problem with this strategy is that correct assessment of asthma control is not straightforward. Several studies have found that the assessment of control varies markedly among health care professionals, as well as patients. Generally, both physicians and patients tend to overestimate the level of asthma control, with a subsequent risk of undertreatment.3 In an attempt to facilitate correct asthma control assessment, several simple and easy-to-use composite asthma control scores have been developed. Most try to capture the level of control in a single numeric value, such as the Asthma Control Test (ACT) and Childhood Asthma Control Test (c-ACT). Because the various tests use the same outcomes (daytime and nighttime symptoms, limitation of activities, and use of rescue medication), it is not unexpected that the results of these tests correlate with each other and with the Global Initiative for Asthma (GINA) definition of asthma control4 to some extent. However, symptoms, limitations of activities, and use of rescue medication are not independent variables. Physical activity is one of the most important causes of symptoms and reliever use in children. Therefore many children with insufficiently controlled asthma avoid strenuous exercise.5-8 The result is fewer daytime symptoms, less rescue use, and apparently controlled asthma. This is achieved at the expense of poorer fitness and a higher risk of obesity. Many parents (and children) are unaware of such changes in lifestyle. The question remains whether the various retrospectively collected tests capture the same information as the prospective but more cumbersome diary recordings and also whether a single cutoff value is sufficient or optimal in distinguishing between controlled and uncontrolled asthma. The study by Voorend-van From the University of Southern Denmark, Paediatric Research Unit, Kolding Hospital. Disclosure of potential conflict of interest: S. Pedersen has received consultancy fees from Bergen, GlaxoSmithKline, Boehringer Ingelheim, and Nycomed; has received research support from GlaxoSmithKline; and has received lecture fees from GlaxoSmithKline and Boehringer Ingelheim. Received for publication October 30, 2013; accepted for publication November 7, 2013. Corresponding author: Søren Pedersen, MD, PhD, DMSc, Paediatric Research Unit, Kolding Hospital, Skovvangen 2-8, 6000 Kolding, Denmark. E-mail: spconsult@ post1.tele.dk. J Allergy Clin Immunol 2013;nnn:nnn-nnn. 0091-6749/$36.00 Ó 2013 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaci.2013.11.003
Bergen9 provided some interesting additional information about this. It was reassuring that the retrospectively collected c-ACT and ACT scores correlated well with the prospectively collected Web-based diary recordings. However, the researchers also used their data to estimate c-ACT and ACT cutoff points for wellcontrolled asthma. This is novel and has been given little attention in the past. Most studies using the control tests have focused on differences in various outcomes between patients with c-ACT or ACT scores of less than 20 and patients with scores of greater than 19. From such studies, we have learned that a score of less than 20 is a significant risk factor for exacerbations, emergency department visits, health care use, poor quality of life, absence from school or work, and limitations in physical and social activities. Therefore, a score of less than 20 has become widely accepted as the level for poor asthma control, which requires treatment or treatment changes. Fewer studies have assessed whether a c-ACT or ACT score of greater than 19 can be used as an indication that the asthma is sufficiently or well controlled. The findings by Voorend-van Bergen et al9 suggest that this is probably not the case. Using sensitivity, specificity, and positive and negative predictive values for different cutoff points of c-ACT and ACT scores, the authors concluded that the cutoff scores for well-controlled asthma were 22 or greater for the c-ACT and 23 or greater for the ACT. According to the GINA criteria, 20% of their patients had symptoms that were well controlled, and 80% had symptoms that were not controlled (41% partly controlled and 39% uncontrolled). In contrast, only 29% and 25% of the children had symptoms that were uncontrolled according to the c-ACT or ACT (data provided by the authors). Similar differences have been reported in another study10: 85% had uncontrolled symptoms according to GINA criteria (uncontrolled and partly controlled) and only 40% had uncontrolled symptoms with the ACT/c-ACT. Knowledge of these differences between the various ways of defining controlled and uncontrolled asthma is important when comparing results from different studies. Children with uncontrolled asthma according to the GINA criteria are likely to be clinically quite different from children included in studies using a c-ACT or ACT score of less than 20 as a criterion to define uncontrolled asthma. The same will be the case for children defined as having controlled symptoms by using these 2 methods. On the other hand, it seems as if uncontrolled asthma defined by c-ACT or ACT scores is more similar to uncontrolled asthma defined by the GINA definitions. The clinical importance of the additional grading of the level of control used by GINA is less well studied. However, there are some suggestions that the additional grading might be useful. Studies in adults found significant differences between wellcontrolled and partly controlled asthma in a variety of clinically important outcomes,11 and another study reported that an ACT score of greater than 19 was found not to exclude poor asthma control very well.12 Findings of fewer symptoms and more symptom-free days in children with well-controlled asthma than in those with partly controlled asthma and an almost clinical 1
2 PEDERSEN
important difference in c-ACT or ACT scores between wellcontrolled and partly controlled asthma in the study by Voorend-van Borgen et al9 indirectly support that the same will also be the case for children. Quantifying control facilitates interpretation and comparison of clinical trials, as well as patients’ understanding of improvement and deterioration. It allows assessment of a minimal clinically important difference that will reflect a meaningful change for the patient. This is difficult with the GINA definition of control. Thus 77% of 548 children with uncontrolled asthma (GINA) achieved asthma control after treatment, suggesting that the remaining 23% did not benefit from the treatment because their symptoms remained not well controlled at study’s end.13 However, these patients all showed marked improvements in 1 or several control outcomes, and therefore at study’s end, they failed only half the number of the control criteria as at baseline. If the c-ACT or ACT had been used, the majority of these patients would have shown a clinically important improvement according to the criteria suggested by Voorend-van Bergen et al.9 Such useful information would not normally be missed when using the GINA definitions. The problem for all studies assessing asthma control is that we do not have a gold standard with which the various tests can be compared. Voorend-van Bergen et al9 used a change in the Pediatric Asthma Quality of Life Questionnaire or the Pediatric Asthma Caregiver’s Quality of Life Questionnaire results to define a minimally important clinical difference because these tests have previously been validated with respect to this. This is probably the best we can do at present, but it does not necessarily make it a gold standard. (Albert Einstein: ‘‘What counts cannot always be measured and what can be measured does not always count.’’) Both these tools depend heavily on symptoms, and the number of symptom-free days correlates with quality of life.14 Symptoms are subjective and influenced by the children’s level of perception of symptoms and the effect of the disease on the children’s daily activities, including sports and play and social life. Therefore good objective measures that do not depend on these factors would be welcome. In this respect FEV1 and exhaled nitric oxide measurement did not seem useful, but other outcomes, such as exercise challenges, objective measurements of daily physical activity, and specific diary recordings of daily
J ALLERGY CLIN IMMUNOL nnn 2013
activities, might be worth studying. The validity and feasibility of the Web-based diary recordings reported in the study by Voorend-van Bergen et al9 suggest that this tool might be useful in the future for more specific prospective recordings of daily activities and probably more reliable than retrospective recordings and a paper diary.
REFERENCES 1. O’Byrne PM, Pedersen S, Schatz M, Thoren A, Ekholm E, Carlsson LG, et al. The poorly explored impact of uncontrolled asthma. Chest 2013;143:511-23. 2. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, Fitzgerald M, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008;31:143-78. 3. Holgate ST, Price D, Valovirta E. Asthma out of control? A structured review of recent patient surveys. BMC Pulm Med 2006;6(Suppl 1):S2. 4. O’Byrne PM, Reddel HK, Eriksson G, Ostlund O, Peterson S, Sears MR, et al. Measuring asthma control: a comparison of three classification systems. Eur Respir J 2010;36:269-76. 5. Wildhaber J, Carroll WD, Brand PL. Global impact of asthma on children and adolescents’ daily lives: the room to breathe survey. Pediatr Pulmonol 2012;47: 346-57. 6. Haselkorn T, Chen H, Miller DP, Fish JE, Peters SP, Weiss ST, et al. Asthma control and activity limitations: insights from the Real-world Evaluation of Asthma Control and Treatment (REACT) study. Ann Allergy Asthma Immunol 2010; 104:471-7. 7. Vahlkvist S, Pedersen S. Fitness, daily activity and body composition in children with newly diagnosed, untreated asthma. Allergy 2009;64:1649-55. 8. Vahlkvist S, Inman MD, Pedersen S. Effect of asthma treatment on fitness, daily activity and body composition in children with asthma. Allergy 2010;65:1464-71. 9. Voorend-van Bergen S, Vaessen-Verberne AA, Landstra AM, Brackel HJ, van den Berg NJ, Caudri D, et al. Monitoring childhood asthma: web-based diaries and the Asthma Control Test. J Allergy Clin Immunol 2014;nnn:nnn. 10. Carroll WD, Wildhaber J, Brand PL. Parent misperception of control in childhood/ adolescent asthma: the Room to Breathe survey. Eur Respir J 2012;39:90-6. 11. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med 2004;170:836-44. 12. Thomas M, Kay S, Pike J, Williams A, Rosenzweig JR, Hillyer EV, et al. The Asthma Control Test (ACT) as a predictor of GINA guideline-defined asthma control: analysis of a multinational cross-sectional survey. Prim Care Respir J 2009;18: 41-9. 13. Pedersen S, Maspero J, Gul N, Sharma R. Components of asthma control and treatment response of individual control criteria in children: analysis of the PEACE study. Pediatr Pulmonol 2011;46:1182-8. 14. Carranza R Jr, Edwards L, Lincourt W, Dorinsky P, ZuWallack RL. The relationship between health-related quality of life, lung function and daily symptoms in patients with persistent asthma. Respir Med 2004;98:1157-65.
