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Andrew H. Liu, MD,a Robert Zeiger, MD,b Christine Sorkness, PharmD,c Todd Mahr, MD,d Nancy Ostrom, MD,e Somali Burgess, PhD,f Jacqueline Carranza Rosenzweig, PharmD, MS,g and Ranjani Manjunath, MSPHg Denver, Colo, San Diego, Calif, Madison and LaCrosse, Wis, Boston, Mass, and Research Triangle Park, NC Background: For children younger than 12 years old with asthma, there are several quality-of-life instruments, clinical diaries, and questionnaires assessing symptoms; however, a validated tool for assessing asthma control is currently lacking. Objective: To develop and validate the Childhood Asthma Control Test (C-ACT), a self-administered tool for identifying children aged 4-11 years whose asthma is inadequately controlled. Methods: A 21-item questionnaire was administered to 343 patients with asthma and their caregivers, randomly assigning 75% (n 5 257) for development and cross-sectional validation of the tool and 25% (n 5 86) to a confirmatory sample. Stepwise logistic regression was used to reduce the 21 items to those best able to discriminate control as defined by the specialist’s rating of asthma control. From aNational Jewish Medical and Research Center and the University of Colorado School of Medicine, Denver; bKaiser Permanente, San Diego; c the University of Wisconsin School of Pharmacy, Madison; dthe Gundersen Lutheran Clinic, LaCrosse; ethe Allergy and Asthma Medical Group and Research Center, San Diego; fMapi Values, Boston; and g GlaxoSmithKline, Research Triangle Park. Supported by GlaxoSmithKline. Disclosure of potential conflict of interest: A. H. Liu has consulting arrangements with GlaxoSmithKline, AstraZeneca, and Schering-Plough; has received grant support from GlaxoSmithKline, Microlife, Ross, and Novartis; and is on the speakers’ bureau for GlaxoSmithKline, Merck, Schering-Plough, and AstraZeneca. R. Zeiger has consulting arrangements with Aerocrine, AstraZeneca, Dynavax, Genentech, GlaxoSmithKline, Merck, and Novartis; has received grant support from AstraZeneca, GlaxoSmithKline, Merck, Sanofi-Aventis, and Teva Pharmaceuticals; and has lectured for AstraZeneca. C. Sorkness has consulting arrangements with AstraZeneca and GlaxoSmithKline; has received grant support from GlaxoSmithKline; and is on the speakers’ bureaus for GlaxoSmithKline. T. Mahr has received grant support from GlaxoSmithKline, Alcon, AstraZeneca, and Novartis and is on the speakers’ bureau for Alcon, AstraZeneca, GlaxoSmithKline, Merck, Schering-Plough, Novartis, Genentech, Verus, and Sanofi-Aventis. N. Ostrom has received grant support from Alcon, Allux, Altana, AstraZeneca, Clay-Park Labs, Critical Therapeutics, Genentech, GlaxoSmithKline, Hoffman-LaRoche, Medicinova, MedPointe, Merck, Novartis, Pharmaxis, Rigel, Sanofi-Aventis, Schering-Plough, and Wyeth; has consulting arrangements with Aperon Biosystems, AstraZeneca, Genentech, and Verus Pharmaceuticals; and is on the speakers’ bureau for AstraZeneca, Genentech, Novartis, GlaxoSmithKline, IVAX, KOS, Pfizer, Sanofi-Aventis, and Schering-Plough. S. Burgess has received grant support from GlaxoSmithKline. J. C. Rosenzweig and R. Manjunath are employed by GlaxoSmithKline. Received for publication September 8, 2006; revised November 20, 2006; accepted for publication December 13, 2006. Available online March 15, 2007. Reprint requests: Andrew H. Liu, MD, National Jewish Medical and Research Center, 1400 Jackson Street (K1023), Denver, CO 80206. E-mail: liua@ njc.org. 0091-6749/$32.00 Ó 2007 American Academy of Allergy, Asthma & Immunology doi:10.1016/j.jaci.2006.12.662 Results: Seven items were selected from regression analyses of the development sample to comprise the C-ACT. The scores of each item were summed for a total score (0-27), with lower scores indicating poorer control. Summed scores discriminated between groups of patients differing in the specialists’ rating of asthma control (F 5 36.89; P < .0001), the need for change in patients’ therapy (F 5 20.07; P < .0001), and % predicted FEV1 (F 5 2.66; P 5 .0494). A score of 19 indicated inadequately controlled asthma (specificity 74%, sensitivity 68%). These analyses were confirmed in the confirmatory sample. Conclusion: The C-ACT is a validated tool to assess asthma control and identify children with inadequately controlled asthma. Clinical implications: The C-ACT can be valuable in clinical practice and research based on its validation, ease of use, input from the child and caregiver, and alignment with asthma guidelines. (J Allergy Clin Immunol 2007;119:817-25.) Key words: Asthma, pediatric, control, health outcomes, healthrelated quality of life, symptom assessment, questionnaire, tool The National Asthma Education and Prevention Program (NAEPP)1 and the the Global Initiative for Asthma (GINA)2 define the goals of asthma control as minimal or no symptoms during the day or night, full physical activity including exertion, prevention of exacerbations, maintenance of (near) normal pulmonary function, decreased use of rescue b2-agonist medication, and minimal or no adverse effects from medications. Reliable assessment of asthma control is essential to manage asthma effectively and to initiate or change pharmacotherapy.3,4 There are fundamental challenges when assessing asthma control in children, including selecting meaningful measures to assess asthma symptoms and determining the most reliable source of the information (parent/caregiver, child, and/or health care provider). Developmental issues are believed to influence the accuracy of a young child’s symptom reporting.5 For example, some children may have difficulty associating time with asthma events and may be reluctant to acknowledge their asthma symptoms, because they do not recognize abnormal symptoms or they want to be perceived as ‘‘normal.’’6,7 As a result, caregivers are often asked to assess their child’s symptoms. However, numerous studies have demonstrated poor correlations between the symptom reports of children and those of their parents.8-12 Indeed, some studies suggest that child symptom reporting should not be discounted or ignored. In a study by Lara et al10 assessing the validity of exercise-related symptom reporting by children with asthma compared with their parents, child-reported 817 Asthma diagnosis and treatment Development and cross-sectional validation of the Childhood Asthma Control Test 818 Liu et al Asthma diagnosis and treatment Abbreviations used AUC: Area under the curve C-ACT: Childhood Asthma Control Test FVC: Forced vital capacity GINA: Global Initiative for Asthma NAEPP: National Asthma Education and Prevention Program NPV: Negative predictive value PAQLQ: Pediatric Asthma Quality of Life Questionnaire PACQLQ: Pediatric Asthma Caregiver’s Quality of Life Questionnaire PPV: Positive predictive value ROC: Receiver operating characteristic coughing and wheezing correlated with FEV1 and observed symptoms due to exercise; in contrast, parentreported symptoms did not correlate. Guyatt et al11 observed in younger children (age <11 years) that their symptom reports correlated strongly with changes in quality-of-life measures, although parents’ ratings of asthma symptoms showed moderate correlations with FEV1 and asthma control but not quality-of-life measures. They concluded that, in younger children, clinicians are likely to obtain important and complementary information from children and their parents. Owing to these challenges, there is a need for a simple yet reliable measurement tool to assess asthma control in children to help them achieve the goals of asthma care.4 Several patient-completed instruments have been developed and validated to assess asthma control13,14 in adults with asthma. For younger (ie, age <12 years) children with asthma, there are several health-related quality-of-life instruments, clinical diaries, and questionnaires assessing symptoms directed towards children or their caregivers6,15-18; however, a standardized, self-administered, and validated tool for assessing asthma control in younger children is currently lacking. The Childhood Asthma Control Test (C-ACT) was developed to assess asthma control in children 4-11 years of age with asthma for use in the clinic and at home. The C-ACT was designed to be self-administered, to incorporate input from parent and child, to capture the multidimensional nature of asthma control, and to demonstrate good predictive properties for assessing asthma control. This article details the development and cross-sectional validation of the C-ACT. METHODS Development of the working questionnaire The initial conceptual framework of domains for ‘‘asthma control’’ was developed from the national NAEPP1 guidelines, the international GINA2 guidelines, and working group input (10 childhood asthma and allergy specialists). To support this framework and determine further concepts, the literature was reviewed for existing generic and asthma-specific questionnaires as well as relevant literature for developing age-appropriate questions for younger children with asthma.13,19-26 J ALLERGY CLIN IMMUNOL APRIL 2007 The questions, including recall periods and response formats, were created and refined based on information gathered from 4 rounds of interviews with 22 children with asthma and 14 caregivers who were white (45%), African American (32%), or of other ethnicity (23%). Patients interviewed were also of different levels of caregiverassessed asthma severity, with 36% considered to have ‘‘very mild or mild’’ asthma, 32% considered to have ‘‘moderate’’ asthma, and 28% considered to have ‘‘severe or very severe’’ asthma. Differing recall periods and Likert scales were chosen for the caregiver and child questions based on the literature on age-appropriate question formats for younger children5 and feedback from child and caregiver interviews. The child questions ask about the present, without reference to recall period, because interviewed children 4-6 years of age had difficulty recalling beyond 1 day. We also learned in the patient interviews that younger children often require more guidance in responding to the child-reported questions, perhaps to the extent of the parent/caregiver reading the questions aloud to the child. Acknowledging that there are developmental differences in children’s abilities to understand and respond to items rated on Likert scales, a scale using a child’s face was developed to facilitate comprehension by younger children. Several types of faces were tested, including a generic face, a boy’s face, and a girl’s face; the young boy’s face was preferred by the majority of children. It was also found that younger children tended to use more extreme responses and had difficulties understanding a neutral state, ie, ‘‘neither happy or unhappy.’’ Consequently, a 4-point Likert scale was chosen (ie, ‘‘very bad,’’ ‘‘bad,’’ ‘‘good,’’ or ‘‘very good’’) to address this issue. For the caregiver questions, a standard recall period of 4 weeks was selected. Based on these interviews, a working questionnaire was generated containing a total of 21 questions (8 child-completed and 13 caregiver-completed questions) (see Fig E1 in this article’s Online Repository at www.jacionline.org). Questions related to asthma symptoms and impact on everyday functioning and quality of life were directed to the children and caregivers; questions pertaining to asthma exacerbations, health care resource utilization (including medication), and missed school or daycare were directed only to the caregivers. Cross-sectional study design A 3-month, cross-sectional, nonrandomized study of 343 children and their parents/caregivers was conducted to identify the optimal child and caregiver questions to comprise the final C-ACT questionnaire from the 21-item working questionnaire. Children 4-11 years of age were identified and enrolled from 9 specialist asthma clinics at their usual care visit, including those who may have experienced or were experiencing an exacerbation. Patients were required to have a diagnosis of asthma without other respiratory conditions, have experienced symptomatic improvement to a short-acting b-agonist bronchodilator, and/or had a history of documented reversible airway disease. Institutional Review Board approval was granted by local committees, and signed informed consent/assent was obtained from children and parents/caregivers. Study forms, the working questionnaire, and supplemental health status questionnaires (Pediatric Asthma Quality of Life Questionnaire [PAQLQ]22; Pediatric Asthma Caregiver’s Quality of Life Questionnaire [PACQLQ]27) were completed by children and their caregivers during a routine previously scheduled physician office visit. Caregivers were instructed to help the child understand and to read the question if needed, but to allow the child to select the responses himself. Specialists were blinded to patient questionnaire responses. Following completion of questionnaires by parents/caregivers and their children, pediatric asthma and allergy specialists assessed the patient’s asthma severity, control, and medication regimen by history, physical exam, and spirometry (FEV1 and FEV1/FVC) in a routine manner. Spirometry was performed pre- and postbronchodilator in study participants who were older and able to comply with American Thoracic Society standards28 (n 5 270). Data analyses Data from the cross-sectional study were analyzed to develop and validate the final C-ACT based on the 21-item working questionnaire. The total sample (n 5 343) was randomly divided into a 75% development sample (n 5 257) and a 25% confirmatory sample (n 5 86). The development sample was used for item selection, evaluation of the questionnaire’s psychometric properties (ie, construct, concurrent, clinical, and predictive validities), and determination of the scoring algorithm. Analyses of the confirmatory sample were used to verify the 75% sample results. All analyses were performed using SAS Version 9.1.3 for Windows or Multitrait/Multi-item Analysis Program– Revised for Windows, Version 1.0 (SAS Institute, Cary, NC). Item selection. Stepwise logistic regression was performed to reduce the 21-item working questionnaire to the set of items that were most predictive in determining asthma control. A P value of .10 was selected a priori as the criterion for item retention. The criterion measure was the specialist’s rating of asthma control, dichotomized as ‘‘controlled’’ (including ‘‘well controlled’’ and ‘‘completely controlled’’) versus ‘‘uncontrolled’’ (including ‘‘not controlled at all,’’ ‘‘poorly controlled,’’ and ‘‘somewhat controlled’’). Formal conservative tests were then used to evaluate the goodness of fit of the final model consisting of the most predictive child and parent/caregiver items. The overall performance of the model was evaluated using area under the curve (AUC) from the receiver operating characteristic (ROC) curves. The Hosmer-Lemeshow goodness-of-fit test was used to determine how well the data fit a logistic model.29 Validation. Demographic and clinical characteristics were examined using descriptive statistics. Internal consistency reliability was also evaluated using Cronbach a. Concurrent validity of the instrument was calculated using the Pearson correlations between the score on the final C-ACT instrument and the scores on the PAQLQ and PACQLQ. The clinical validity of the C-ACT was evaluated (ie, the extent to which the C-ACT can discriminate among clinically diverse groups) by percentage predicted FEV1 and FEV1/FVC ratio (<60%, 60% to 79%, 80% to 99%, and 100%), specialist’s assessment of control and change in therapy (step up, no change, and step down). Analysis of variance methods were used to evaluate the ability of the C-ACT score to discriminate between these groups derived from the clinical measures. Known-group validity and ROC analyses were performed to discriminate ‘‘uncontrolled’’ versus ‘‘controlled’’ patients based on the C-ACT score cut points. The odds ratios, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), percentage correctly classified, and AUC (or c-statistic) were estimated for each scoring option drawn at different cut points. The 25% confirmatory sample was used to verify the results. A P value of .05 was selected a priori and used for all the analyses of the reduced instrument. All tests of significance were 2-sided. RESULTS The sample characteristics of the children (n 5 343) are presented in Table I. The mean age was 8.1 years; 61% were male; and 74.34% were in ‘‘good to very good’’ health based on parent/caregiver report. Approximately 63% of caregivers had a college or graduate degree and about 63% were employed either part or full time. Specialists characterized 62% of the participants with mild, 36% with moderate, and 2% with severe asthma. Liu et al 819 Specialists concluded that 70.5% of their patients had asthma that was well to completely controlled (ie, ‘‘controlled’’). No change in therapy was necessary for 69%, and a step up in therapy was recommended for 21% of patients. Item selection Seven of 21 items (4 child-reported and 3 caregiverreported) were selected based on their ability to predict asthma control (see Fig E2 in this article’s Online Repository at www.jacionline.org). Maximum likelihood estimates based on logistic regression are provided for the 7 most predictive items (Table II). The 7-item model showed good statistical fit, with an AUC of 0.798 and percentage concordant and percentage tied results of 79.5 and 0.5, respectively. The Hosmer-Lemeshow goodness-of-fit test indicated sufficient fit (0.5322) to the 7-item logistic model. The child-completed items use a 4-point response scale and the parent/caregiver-completed items use a 6point response scale, with lower scores indicating poorer control. The items were summed to obtain a total score for the C-ACT, with a potential range in score from 0-27. Construct and concurrent validity In the development sample (n 5 257), the observed C-ACT score ranged from 6 to 27. No floor or ceiling effects were observed. Multitrait analysis showed that the item convergent validity of the C-ACT score was good (Pearson item-scale correlation corrected for overlap; range, 0.41-0.68). The Cronbach coefficient alpha for the C-ACT score was 0.79 and satisfied the minimum recommended level of 0.70. The concurrent correlations between the C-ACT score and the PAQLQ and PACQLQ domains were moderate to strong (0.47 and 0.68, respectively). The results of the construct validity analyses were similar in the subgroups of children 4 to 8 years of age and in children 9 to 11 years of age (data not shown). Clinical validity In the development sample, mean C-ACT scores were lowest in children with pre-bronchodilator FEV1 lower than 60% of predicted (16.33) and FEV1/FVC ratios lower than 60% (17.20) (Table III). Conversely, mean C-ACT scores were highest in children with prebronchodilator FEV1 higher than 80% of predicted (20.51) and FEV1/ FVC ratios higher than 80% (20.42), without differentiation seen between the 2 highest categories. For specialist’s rating of asthma control, 29.5% were considered inadequately controlled in the development sample and 28% in the confirmatory sample. The mean scores were significantly different between groups (P < .0001), ordered in an expected manner with the highest mean score (22.27) found among children who where rated as ‘‘completely controlled’’ by their specialists and the lowest mean score (13.62) found among children whose asthma was rated as ‘‘poorly controlled’’ (Table III). None of the children had their asthma rated as ‘‘not controlled at all’’ by their specialist, so 4 categories were included for this analysis: ‘‘poorly controlled,’’ Asthma diagnosis and treatment J ALLERGY CLIN IMMUNOL VOLUME 119, NUMBER 4 820 Liu et al J ALLERGY CLIN IMMUNOL APRIL 2007 TABLE I. Sample characteristics in the cross-sectional validation study (n 5 343) Asthma diagnosis and treatment Demographic characteristics Age (y), mean (SD) Female, n (%) Ethnicity, n (%)* Afro-Caribbean/African American Asian/Indian Hispanic/Latino/Spanish American North American/European/white Native American Other Caregiver education level, n (%) Some high school High school diploma or GED Some college College degree (2-year or 4-year) Graduate degree Other Caregiver work status, n (%) Working full- or part-time (paid employment) Full-time homemaker Unemployed Student Retired Other Clinical characteristics General health, n (%) Excellent Very good Good Fair Poor Specialist-assessed asthma severity, n (%)* Mild Moderate Severe % predicted FEV1, mean (SD)* Albuterol use (no. of puffs), mean (SD) Daytime* Nighttime* Asthma symptom score, n (%)* 0: No symptoms 1: Symptoms for 1 short period during the past 4 wk 2: Symptoms for 2 or more short periods during the past 4 wk 3: Symptoms for most of the time which did not affect normal activities 4: Symptoms for most of the time with did affect normal activities 5: Symptoms so severe that work or normal activities could not be performed Specialist global assessment of control,* n (%) Not controlled at all Poorly controlled Somewhat controlled Well controlled Completely controlled Specialist-assessed change in therapy,* n (%) Step down No change Step up 8.1 (2.39) 132 (38.60) 38 15 20 233 2 34 (11.11) (4.39) (5.85) (68.13) (0.58) (9.94) 13 45 51 137 80 16 (3.80) (13.16) (14.91) (40.06) (23.39) (4.67) 216 93 12 6 1 15 (62.97) (27.11) (3.50) (1.75) (0.29) (4.37) 59 129 126 26 3 (17.20) (37.61) (36.73) (7.58) (0.87) 211 123 7 94.04 (61.88) (36.07) (2.05) (19.81) 1.20 (2.27) 0.86 (3.25) 108 116 59 28 23 4 (31.49) (33.82) (17.20) (8.16) (6.70) (1.17) 1 24 76 178 63 (0.29) (7.02) (22.22) (52.05) (18.42) 34 (10.06) 234 (69.23) 70 (20.71) *Missing data: ethnicity (n 5 1), specialist-assessed asthma severity (n 5 2), % predicted FEV1 (n 5 69), daytime albuterol use (n 5 20), nighttime albuterol use (n 5 18), asthma symptom score (n 5 5), specialist global assessment of control (n 5 1) and change in therapy (n 5 5). Liu et al 821 J ALLERGY CLIN IMMUNOL VOLUME 119, NUMBER 4 TABLE II. Item selection: analysis of maximum likelihood estimates Estimate Child-completed How is your asthma today? How much of a problem is your asthma when you run, exercise, or play sports? Do you cough because of your asthma? Do you wake up during the night because of your asthma? Parent/caregiver-completed During the last 4 weeks, how many days did your child have any daytime asthma symptoms? During the last 4 weeks, how many days did your child wheeze during the day because of asthma? During the last 4 weeks, how many days did your child wake up during the night because of asthma? SE 0.43 0.19 0.24 0.28 0.24 0.21 0.26 0.24 20.39 20.33 20.13 0.18 0.19 0.17 TABLE III. Comparison of mean C-ACT scores across groups differing in asthma control (75% development sample, n 5 257) Clinical Parameter % Predicted FEV1 (n 5 212) FEV1/FVC (n 5 212) Specialist-assessed change in child’s therapy (n 5 250) Specialist assessment of asthma control (n 5 254) Category n Mean score SD F* <60% 60% to 79% 80% to 99% 100% <60% 60% to 79% 80% to 99% 100% Step up No change Step down Poorly controlled Somewhat controlled Well controlled Completely controlled 9 36 87 78 5 47 151 7 26 167 57 21 54 134 45 16.33 19.47 20.51 20.19 17.20 19.08 20.42 20.14 17.00 20.99 20.08 13.62 17.89 21.14 22.27 6.59 4.60 4.36 4.11 5.26 5.11 4.22 3.98 4.59 3.87 4.41 4.90 3.98 3.46 3.28 2.66 P value* .0494 1.76 .1554 20.07 <.0001 36.89 <.0001 *Because the assumptions of normality were met, the P value has been calculated with parametric 1-way analysis of variance test for differences. Prebronchodilator. ‘‘somewhat controlled,’’ ‘‘well controlled,’’ and ‘‘completely controlled.’’ For specialist-assessed change in therapy, differences in the C-ACT scores were significant (P < .0001), with a lower mean score (17.00) found in the group whose treatment was recommended for ‘‘step up’’ compared with those whose treatment was recommended for ‘‘no change’’ (20.99) or ‘‘step down’’ (20.08). These results were verified in the 25% confirmatory sample (Table IV). C-ACT score cut points Cut-point scores of 18 to 22 demonstrated the highest area under the ROC curve (range 0.672 to 0.713), with sensitivity (ie, patients classified by C-ACT as uncontrolled for those who are uncontrolled by specialist assessment) ranging from 63% to 92% and specificity (ie, patients classified by C-ACT as controlled for those who are controlled by specialist assessment) ranging from 42% to 80% (Fig 1 and Table V). The selection of a cut-point score was based on the following factors: (1) balance between sensitivity and specificity; (2) high sensitivity for adequate accuracy in identifying those patients who are uncontrolled; (3) high AUC and percentage correctly classified; and (4) clinical validity. A cut point of 19 demonstrates a sensitivity of 68% and a specificity of 74%. At scores of 19, approximately 52% of those classified by the C-ACT as uncontrolled were actually uncontrolled (PPV 52%), and 84.6% of those classified by the C-ACT as controlled were actually controlled (NPV 85%)—such that 72% of the children were correctly classified. These findings were strongly verified in the 25% confirmatory sample with, at scores of 19, PPV 70%, NPV 88%, and 83% correctly classified (Table VI). The clinical validity results further support a cut point of 19 or less in the C-ACT as indicative of inadequate asthma control. The C-ACT mean scores are less than 19 for patients characterized as somewhat (18) or poorly (14) controlled, requiring step up in therapy (17), and with <60% FEV1 (16) (Fig 2). DISCUSSION The cross-sectional validation of the C-ACT demonstrates the reliability and predictive properties of the tool Asthma diagnosis and treatment Items 822 Liu et al J ALLERGY CLIN IMMUNOL APRIL 2007 TABLE IV. Confirmation of results relevant to the comparison of mean C-ACT scores across groups differing in asthma control (25% confirmatory sample, n 5 86) Grouping variable Asthma diagnosis and treatment % Predicted FEV1 (n 5 58) FEV1/FVC (n 5 58) Specialist-assessed change in child’s therapy (n 5 83) Specialist assessment of asthma control (n 5 83) Group n Mean score SD x 2* <60% 60% to 79% 80% to 99% <80% 80% to 99% 100% Step up No change Step down Poorly controlled Somewhat controlled Well controlled Completely controlled 9 28 21 14 41 3 10 65 8 4 19 43 17 16.33 21.21 22.00 18.14 21.58 21.33 17.10 20.77 21.87 17.00 17.42 20.95 23.29 4.03 3.15 2.85 4.33 3.05 4.16 3.57 3.86 1.25 3.46 3.45 3.49 2.28 14.07 .0009 8.07 .0176 11.36 .0034 31.29 <.0001 P value* *Because of violation of assumptions of normality, the P value has been calculated with nonparametric Kruskal-Wallis test for differences. Prebronchodilator. FIG 1. C-ACT receiver operating characteristic curves. Sensitivity versus 1 2 specificity plotted for the development (75% of study cohort) and validation (25% of cohort) samples. to assess asthma control in children 4-11 years of age. The tool shows good ROC characteristics relative to the specialists’ ratings of asthma control, as well as good performance of C-ACT scores in their ability to discriminate based on various levels of clinical variables, including spirometry and specialist’s recommendation of a change in therapy. In addition, correlation of the C-ACT with PAQLQ22 and PACQLQ27 assessments indicates that the C-ACT captures asthma-related quality-of-life parameters. Findings were further verified in the 25% confirmatory sample, indicating good reproducibility and consistency of the results. The specialist’s assessment of asthma control as the criterion measure was considered to be the most complete and clinically meaningful outcome for item selection in the absence of a ‘‘gold standard’’ by which asthma control Liu et al 823 J ALLERGY CLIN IMMUNOL VOLUME 119, NUMBER 4 Cut-point score 18 19 20 21 22 Sensitivity Specificity PPV (%) NPV (%) Correctly classified (%) AUC 0.63 0.68 0.73 0.83 0.92 0.80 0.74 0.63 0.59 0.42 56.6 52.0 45.5 45.6 40.1 83.6 84.6 85.0 89.0 92.7 74.8 72.0 66.1 65.7 57.1 0.713 0.709 0.682 0.707 0.672 TABLE VI. Summary of the performance of the C-ACT score for each scoring option at different cut points in predicting specialist’s assessment of uncontrolled asthma (25% confirmatory sample, n 5 86) Cut-point score 18 19 20 21 22 Sensitivity Specificity PPV (%) NPV (%) Correctly classified (%) AUC 0.56 0.70 0.91 0.96 0.96 0.90 0.88 0.72 0.50 0.42 68.4 69.6 55.3 42.3 38.6 84.4 88.3 95.6 96.8 96.2 80.7 83.1 77.1 62.7 56.6 0.733 0.789 0.815 0.728 0.687 can be assessed. This criterion measure has been used to develop other well accepted questionnaire tools that are often used to assess asthma control in adults and older children.13,14 To reduce the subjective nature of the criterion measure, specialists used clinical evaluation (spirometry, physical exam) with patient history (eg, symptoms, exacerbations, quality of life, and activity limitations) to assess a patient’s asthma control and were blinded to patient responses on the questionnaires. Lung function measures were not incorporated as an item for potential inclusion in the C-ACT, because this would limit its use to clinical settings and to older children capable of performing spirometry. For a validated asthma control assessment instrument in adults, the omission of FEV1 made minimal difference in the validity, reliability, and responsiveness of the instrument.30 Instead, in the present study, spirometry was used as a component in the specialist’s assessment of asthma control. Remarkably, the 4 child-reported questions regarding daytime and exercise-induced asthma symptoms, nighttime awakenings due to asthma, and self-report of asthma (ie, ‘‘how is your asthma today?’’), as well as the caregiver questions on daytime and nighttime symptoms, are consistent with NAEPP1 and GINA2 assessment guidelines. The statistical predictive properties found during validation yielded both the child and caregiver reports of nighttime awakenings. Because of concern that these items may be redundant, statistical correlations were conducted and shown to be imperfect (r 5 2.50). This weak correlation is consistent with other studies revealing divergence between child-reported and parent-reported daytime, nighttime, and exercise-induced symptoms,10,12,31 thereby highlighting the importance of incorporating both child and caregiver perspectives when assessing asthma control. This study captured a relatively mild and controlled sample of children with asthma, which may limit the generalizability of these findings to other cohorts. We did not aim to recruit children who were ethnically diverse or from inner-city settings that may have a high burden of moderate to severe disease and higher resource utilization (eg, emergency department [ED] visits and hospitalizations). However, we conducted clinical validity analyses among all groups of children in our sample (poorly controlled to completely controlled). The clinical validity findings demonstrate that the tool is able to discriminate among various levels of control, even in those children characterized by clinicians as being poorly controlled or somewhat controlled. Future studies can refine our understanding of the optimal application of this tool in specific populations of interest (eg, inner-city children with asthma). In addition, the C-ACT does not include a direct measure of exacerbations. Although the initial pool of items in the working questionnaire (see Fig E1 in this article’s Online Repository at www.jacionline.org) included multiple caregiver questions assessing asthma exacerbations (ie, asthma attack in past 4 weeks, ED visit in past year, unscheduled visit in past year, and hospitalization in past year), these items were not selected, based on logistic regression. However, caregivers reported relatively high frequencies of attacks (37%), ED visits (29%), unscheduled visits (58%), and hospitalizations (5%). An explanation for this finding may be that exacerbations were captured or embedded within other symptom-related questions underlying the specialist’s determination of asthma control. Because the inherent variability of asthma in children is such that some may appear to have good control in the clinic, and subsequently develop a severe exacerbation, it is prudent to recognize that this cross-sectional study is unable to determine if the C-ACT can predict exacerbation risk. Ongoing longitudinal studies using the C-ACT may determine if this tool is helpful in this regard. Asthma diagnosis and treatment TABLE V. Summary of the performance of the C-ACT score for each scoring option at different cut points in predicting specialist’s assessment of uncontrolled asthma (75% development sample, n 5 257) 824 Liu et al J ALLERGY CLIN IMMUNOL APRIL 2007 Asthma diagnosis and treatment FIG 2. C-ACT cut-point score of 19 compared with clinical measures. The utility of a patient-based assessment tool in clinical practice is suggested to be dependent on the easy interpretability of the score and the minimization of false negatives.30 In selecting a score cut point, there is always a tradeoff of sensitivity vs. specificity: moving to a higher cutoff value improves sensitivity (the percentage of truly uncontrolled patients who are correctly classified as such), but this also results in a larger number of false positives which reduces specificity. For the C-ACT, selection of a cut point was determined based on the idea of using the tool as an indicator for uncontrolled asthma to encourage communication between parents/caregivers, children, and clinicians while taking into account the tradeoffs associated with false-positive misclassifications versus falsenegative misclassifications. Overall, to minimize the chance of false negatives, a cut point of 19 was selected on a continuous scale to indicate uncontrolled asthma. Two other studies have suggested that an intermediate area of control may exist.32,33 For the Asthma Control Test, scores >19 were also associated with ‘‘well controlled’’ or ‘‘totally controlled’’ asthma, scores of <16 were considered ‘‘poorly controlled’’ or ‘‘not controlled at all,’’ and scores of 16-19 corresponded to ‘‘somewhat controlled’’ asthma.33 Similarly, using the Asthma Control Questionnaire in adults, Juniper et al32 found that to be confident that a patient has well controlled asthma, the optimal cut point is 0.75, but to be confident that the patient has inadequately controlled asthma the optimal cut point is 1.50, with the meaning of values 0.75-1.50 being less certain. The development of any predictive tool and its cut points is an ongoing process that involves further validation studies of the C-ACT in varying samples (eg, demographic and clinical differences). As a result, we are conducting a longitudinal validation study of the C-ACT to determine its test-retest reliability and responsiveness. Within that study, we will assess the tool’s ability to measure change in asthma control over time and evaluate a spectrum of cut points that may aid clinicians in being able to further distinguish a child’s asthma control (eg, somewhat controlled vs. poorly controlled asthma). In conclusion, the C-ACT is an accurate and reliable way to assess asthma control in children 4-11 years old. As a simple self-administered questionnaire, it is suitable for clinical practice and research settings. It is intended to complement pulmonary function testing and other assessments by health care providers and is consistent with NAEPP1 and GINA2 guidelines. It is designed to enhance communication of asthma control between children and their parents/caregivers to quickly provide health care providers with a complete picture of the child’s level of asthma control. 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