Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 https://doi.org/10.1186/s12955-022-01955-5 RESEARCH Open Access Measurement properties of the EQ‑5D‑Y administered through a smartphone app in children with asthma: a longitudinal questionnaire study Karina Mayoral1,2,3, Olatz Garin1,3,4, Catalina Lizano‑Barrantes1,5,4, Angels Pont1,3, Araceli M. Caballero‑Rabasco6,2, Manuel Praena‑Crespo7,8, Laura Valdesoiro‑Navarrete9, María Teresa Guerra10,8, José Antonio Castillo11,8, Inés de Mir12, Eva Tato13, Jordi Alonso1,3,4, Vicky Serra‑Sutton14,3, Yolanda Pardo3,1,15, Montse Ferrer1,3,4* and ARCA Group Abstract Background: Asthma impacts children’s physical, emotional, and psychosocial Health-Related Quality of Life (HRQL). The EQ-5D-Y is a generic econometric instrument developed to measure HRQL in children. Objective: Evaluation of feasibility, validity, reliability, and responsiveness of EQ-5D-Y descriptive system and util‑ ity index to allow the assessment of HRQL in children with asthma, aged 8–11 years (self-response version) or under 8 years old (proxy-response version). Methods: We used data from baseline to 10 months of follow-up of an observational, prospective study of children with persistent asthma recruited by pediatricians in Spain (2018–2020). HRQL instruments were administered through a smartphone application: ARCA app. The EQ-5D-Y is composed of a 5-dimension descriptive system, a utility index ranging from 1 to − 0.5392, and a general health visual analogue scale (EQ-VAS). The Pediatric Asthma Impact Scale (PROMIS-PAIS) includes 8 items, providing a raw score. Construct validity hypotheses were stated a priori, and evalu‑ ated following two approaches, multitrait–multimethod matrix and known groups’ comparisons. Reliability and responsiveness subsamples were defined by stability or change in EQ-VAS and the Asthma Control Questionnaire (ACQ), to estimate the intraclass correlation coefficient (ICC) and the magnitude of change over time. Results: The EQ-5D-Y was completed at baseline for 119 children (81 self-responded and 38 through proxy response), with a mean age of 9.1 (1.7) years. Mean (SD) of the EQ-5D-Y utility index was 0.93 (0.11), with ceiling and floor effects of 60.3% and 0%, respectively. Multitrait–multimethod matrix confirmed the associations previously hypothesized for the EQ-5D-Y utility index [moderate with PROMIS-PAIS (0.38) and weak with ACQ (0.28)], and for the EQ-5D-Y dimension “problems doing usual activities” [moderate with the ACQ item (0.35) and weak with the PROMIS- PAIS item (0.17)]. Statistically significant differences were found in the EQ-5D-Y between groups defined by asthma control, reliever inhalers use, and second-hand smoke exposure, with mostly moderate effect sizes (0.45–0.75). The *Correspondence: mferrer@imim.es 1 Health Service Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona Biomedical Research Park, office 144. Doctor Aiguader, 88, 08003 Barcelona, Spain Full list of author information is available at the end of the article © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 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Health and Quality of Life Outcomes (2022) 20:51 Page 2 of 16 ICC of the EQ-5D-Y utility index in the stable subsamples was high (0.81 and 0.79); and responsiveness subsamples presented a moderate to large magnitude of change (0.68 and 0.78), though without statistical significance. Conclusions: These results support the use of the EQ-5D-Y as a feasible, valid, and reliable instrument for evaluating HRQL in children with persistent asthma. Further studies are needed on the responsiveness of the EQ-5D-Y in this population. Keywords: Health-Related Quality of Life, Asthma, EQ-5D-Y, Validity, Reliability, Responsiveness, Smartphone app Introduction a self-administered version and a proxy version (chil- Asthma is a chronic condition that affects more than 300 dren 5–12 years old), but its administration burden is million people worldwide [1], and it is the most com- substantially greater than for the EQ-5D-Y. The inter- mon chronic disease during childhood, affecting around viewer-administered EQ-5D-Y showed high feasibility 14% of children globally [2]. Patient-reported outcome and agreement with the CHU-9D among 6–7 years old measures (PROMS), such as symptom control or Health- children [31], and several studies supported the accept- Related Quality of Life (HRQL), have been shown to be ability [32], feasibility [32, 33], reliability [33], validity useful for clinical management, in combination with [33, 34], and responsiveness [35] of the EQ-5D-Y self- clinical measures, providing relevant information to administered version in children and adolescents from understand the impact of the disease on patients’ func- the general population aged 8–18 years. Furthermore, tional status and well-being [3–5]. Given its heterogene- the psychometric properties of the EQ-5D-Y have already ous nature and symptoms burden, asthma has physical, been tested in several pathologies, such as chronic kid- emotional, and psychosocial impact on children’s lives, as ney disease [36], cystic fibrosis [37], juvenile idiopathic has been shown through diverse generic HRQL instru- arthritis [38], type 1 diabetes mellitus [39], idiopathic ments [6–10]. The most affected dimensions of asthma- scoliosis [40], and chronic or acute conditions [41]. As specific HRQL instruments are peer relationships, feeling far as we know, there is only one study centered on the of dependence on medication, shortness of breath, and psychometric properties of the EQ-5D-Y in patients with activity limitations [11–13]. There is consistent evidence asthma [42], supporting its feasibility and its convergent that HRQL and asthma control are independent pre- validity with the Pediatric Asthma Quality of Life Ques- dictors of future exacerbation [14–17]. Furthermore, a tionnaire. Other studies in heterogeneous samples that systematic review [18] found that asthma severity was included children and adolescents with asthma [43, 44] significantly related to the child’s HRQL in most of the also supported the EQ-5D-Y’s feasibility, reliability, and studies. International guidelines [19–22] have empha- construct validity. sized that treatment goals should focus on improving the There is extensive evidence on the reliability [45], con- day-to-day symptoms of the patient, preventing exacer- struct validity [45, 46] and responsiveness [47] of EQ-5D bations, and improving patients’ HRQL. in adults, both for the descriptive system and the utility HRQL instruments are generic or specific according to index. However, all previous studies on EQ-5D-Y in chil- their target population, and they can in turn be classified dren evaluated only the dimensions of the descriptive as psychometric profiles or econometric indexes accord- system, or an equally weighted summary score. None ing to their measurement model [23]. Psychometric of them evaluated the EQ-5D-Y utility index, because instruments generate scores on different dimensions in the value set for children has just been published [48]: order to describe them (profiles). Econometric measures first for the Slovenian [49] and then for the Spanish [50] provide a single global score (index) which incorporates population. societal preferences for health states (utilities) that can To the best of our knowledge, this is the first study be used to calculate quality-adjusted life years for use in evaluating the psychometric properties of the EQ-5D-Y economic evaluations [24]. The EQ-5D has probably been utility index, and also the first one assessing the psycho- the most widely used econometric instrument in adults, metric properties of the EQ-5D-Y proxy version for chil- and the EuroQol Group developed in 2010 the EQ-5D-Y dren with asthma < 8 years of age. We have found only to enable young individuals from 8 years onwards to self- two studies supporting the reliability and construct valid- report their health [25–28]. An EQ-5D-Y proxy version ity of the EQ-5D-Y proxy version, both performed in the was also developed [29] for children under 8 years old. general population [29, 51]. There are few other econometric questionnaires for Our aim was to evaluate the feasibility, validity, reli- children, such as the Health Utility Index (HUI) and the ability, and responsiveness of the EQ-5D-Y descrip- Child Health Utility 9D (CHU-9D). The HUI [30] has tive system and utility index to allow the assessment of Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 3 of 16 Health-Related Quality of Life in children with asthma “looking after myself ”, “doing usual activities”, “hav- aged 8–11 years old (self-response version) or under ing pain or discomfort” and “feeling worried, sad 8 years old (proxy-response version). or unhappy” with 3-level Likert response scales (no problems, moderate problems, and serious problems). Methods The EQ-VAS ranges from 0, worst health possible, to Participants and study design 100, best health possible. The time frame for both the The Asthma Research in Children and Adolescents dimensions and the EQ-VAS is “today”. The EQ-5D-Y (ARCA) is a longitudinal prospective multicenter obser- proxy version 1, which asked proxies to rate the child’s vational study (NCT04480242), designed to provide HRQL in their own opinion, has the same characteris- evidence about the evolution of young patients with per- tics as the self-reported version. Evidence on the Span- sistent asthma through a regular follow-up. ish EQ-5D-Y’s validity, feasibility, and reliability has Patients were recruited in 3 outpatient pediatric pul- been reported [33]. monology hospital units and 8 primary care pediatric From the three digital versions of the EQ-5D-Y, laptop/ centers in Spain, from January 2018 to July 2020. Fami- desktop, tablets, and PDA/smartphone, we administered lies were informed about the project and asked to par- the latter through a smartphone app [52] with its origi- ticipate if their children fulfilled the following inclusion nal generic content, without including any expression criteria: aged 6–14, with clinical diagnosis of asthma, for asthma-specific attribution. The preference value set undergoing treatment with inhaled corticosteroids (alone to generate the EQ-5D-Y utility index for Spain [48] was or combined with long-acting beta-agonists) for more obtained from adults thinking as a hypothetical 10-year- than 6 months in the previous year, and with access to a old child, as recommended in the international protocol. smartphone (their own, or their parents’). Exclusion cri- A single preference-based index was calculated ranging teria were: chronic obstructive pulmonary disease, cystic from 1 (the best health state) to negative values (health fibrosis, pulmonary fibrosis, bronchiectasis, active tuber- states valued by society as worse than death), where 0 is culosis, or/and immunodeficiency associated with alpha equal to death. 1 antitrypsin deficiency, ciliary diseases. The Patient-Reported Outcomes Measurement Infor- mation System (PROMIS) developed a disease-specific Study variables item bank to measure the HRQL of children with asthma The ARCA study collects information through different [53]: the Pediatric Asthma Impact Scale (PROMIS- sources: medical records, computer-assisted telephone PAIS). The short form 8a version of the PROMIS-PAIS interviews performed by trained interviewers, and the (v2.0) contains the item set that provides the maximum ARCA smartphone application [52]. The EQ-5D-Y and test information with the least items [52]. It has dem- the Patient-Reported Outcomes Measurement Informa- onstrated a higher precision [53] than other asthma- tion System-Pediatric Asthma Impact Scale (PROMIS- specific instruments [54, 55], while presenting a lower PAIS) were administered through the ARCA app, while administration burden. Each item of the PROMIS-PAIS all the variables to define known groups for validity is attributed to asthma with the expression “because assessment were collected through telephone interviews, of my asthma”, except for the last one which states “My and clinical characteristics came from medical records. asthma bothered me”. The items [56] ask about the past The ARCA app development has been described else- seven days in a 5-level Likert response scale (1–5) with where [52]. Briefly, HRQL questionnaires are admin- the options: never, almost never, sometimes, often, istered every 6 months: the EQ-5D-Y at baseline and and almost always. It is available for self-response in ages month 6 of follow-up, and the PROMIS-PAIS at months 8–17, and for proxy response in children starting at age 5. 4 and 10. The ARCA app is available in 3 age versions The total raw score is calculated by adding the values of (6–7, 8–11, and ≥ 12 years old) following the EQ-5D age the response to each question, the lowest possible score cut-off points. The version for the younger age group was is 8 and the highest is 40. Missing items were imputed by designed to be answered by parents or guardians (proxy a simple allocation method from the mean of those items response), and the other two versions for children’s and that were available in each dimension of the question- adolescents’ self-response. For the evaluation of the EQ- naire [57]. 5D-Y, 12–14 years old adolescents were excluded because The information collected through telephone inter- the EQ-5D-5L is administered in this age version. views included, among other, the Asthma Control Ques- The EQ-5D-Y was developed to measure HRQL in tionnaire (ACQ), exacerbations occurring in the previous children [25]. It includes a descriptive system [26] of 6 months, treatments for asthma, and secondhand smoke 5 dimensions and a visual analogue scale (EQ-VAS) exposure. Two versions of telephone interviews were of general health. The dimensions measure “mobility”, developed, one designed to be answered by parents or Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 4 of 16 guardians of children under 8 years old (proxy response) consent was required from the parents or legally author- and the other for self-response (participants aged 8 and ized representatives of all participants, and additionally older). oral consent was obtained from children. The Asthma Control Questionnaire ACQ-symptoms only [58] assesses the frequency of 5 asthma symp- Analytical strategy toms (night-time waking, symptoms on waking, activ- Considering the ARCA sample of 119 patients, a statisti- ity limitation, shortness of breath, and wheeze) during cal power of 80% (using a two-side test with a type I error the previous week on a 7-level Likert scale from 0 (no of 5%) was calculated to detect moderate differences (0.5 impairment) to 6 (maximum impairment). The overall SD) in the EQ-5D-Y utility index between two equally score, calculated as the mean of item responses, ranges distributed known groups, or to detect moderate to large from 0 to 6. Cut-off points of 1.5 and 0.75 are established differences (0.65 SD) between two known groups une- to define not well- and well-controlled asthma, respec- qually distributed into 85% and 15% of the sample [63]. tively [59]. Results generated by this short version have Characteristics of the sample were described by cal- shown to be very similar to those of the complete ACQ, culating percentages, or means and standard deviations, as were its measurement properties (reliability, respon- according to the type of variable. To evaluate the feasi- siveness, internal consistency, construct validity, and bility of the EQ-5D-Y, we calculated the completion rate, interpretability) [58]. The ACQ has been validated [60] the distribution of the response options, and the pro- using self-administration in children 11 years and older portion of missing values. Distribution of the EQ-5D-Y and interviewer-administration in 6- to 10-year-olds. utility index, EQ-VAS, and the PROMIS-PAIS raw score Asthmatic exacerbations during the last 6 months were were examined by calculating the observed range, the assessed through three questions constructed applying floor and ceiling effects (proportion of participants with the definitions by the American Thoracic Society and the the worst and best possible score, respectively), and sta- European Respiratory Society [61]: Did you visit or phone tistics of central tendency and dispersion. your family doctor or outpatient emergency department Construct validity of the EQ-5D-Y was assessed by because your asthma got worse? Did you call an ambu- applying two different approaches: multitrait-multi- lance or go to the hospital because of your asthma? Did method matrix, and comparison of known groups. The you take steroids tablets or syrup (such as Prednisolone or multitrait-multimethod matrix between the EQ-5D-Y, Deltacortril) for at least 2 days because of your asthma? If the PROMIS-PAIS, and the ACQ was constructed with the participant answers “yes” to at least one of the three Spearman correlations due to the scores’ distribution. questions, an asthma exacerbation is confirmed. Besides their scores, the dimension or item on activities To measure the frequency of Short-Acting Beta-Ago- was also included in the matrix, since it was covered by nists (SABA) inhaler use during the previous 4 weeks, the all three questionnaires. The strength of the correlations following question was asked to patients with SABA ther- was defined [64] as weak (≤ 0.30), moderate (0.31–0.60), apy prescription: How often have you usually taken your or strong (0.61–0.90). “reliever medication” (brand name) in the past 4 weeks? The relationships between instruments can be catego- (Every day; almost every day; once or twice every week; rized as convergent (different instruments measuring a less than once a week; or I don’t know). similar concept) or discriminant (different instruments Secondhand smoke exposure was measured through measuring different traits or constructs). For convergent a single question taken from the High School Risk Fac- validity, we hypothesized a moderate correlation between tors Survey [62]: How many people out of those who stay the PROMIS-PAIS raw score and the EQ-5D-Y utility in your house regularly smoke indoors? (No one smokes index, since both instruments intend to measure HRQL indoors; 1 person; 2; 3; 4; 5 people and more than 5 though from different perspectives (generic and asthma- people). specific). Also, we expect moderate correlations between the EQ-5D-Y dimension “problems doing usual activi- Ethics considerations ties”, and the ACQ item “how limited were you in your The study was approved by the ethics committee of par- activities because of your asthma?”. On the other hand, ticipant centers in accordance with national and interna- for divergent validity, we expected a weak correlation tional guidelines (code of ethics, Helsinki Declaration) between the EQ-5D-Y utility index and the ACQ, since as well as legislation on data confidentiality (Spanish they differ on the construct being measured (HRQL and Organic Law 3/2018 of December 5 on the Protection of disease control). A weak correlation was also expected Personal Data and the Guarantee of Digital Rights). The between the EQ-5D-Y dimension “problems doing usual collection and transfer of data was carried out according activities” and the PROMIS-PAIS item “it was hard for to strict security and data encryption. Written informed Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 5 of 16 me to play sports or exercise because of my asthma”, due measured by the effect size coefficient (mean of change/ to differences in the type of activities considered. SD of change) for the worsening and improvement sub- Known groups were defined according to the ACQ samples analyzed together. IBM SPSS Statistics software, (well-controlled, intermediate, and not well-controlled version 22, was used to analyze the data. asthma) [59], asthmatic exacerbation during the last 6 months (yes or no), frequency of SABA inhaler use dur- Results ing the previous 4 weeks (less than once vs once or more Of the 189 participants recruited (see Fig. 1), 55 patients per week), and secondhand smoke exposure (exposed or aged 12–14 years were excluded because they were not). The hypotheses raised a priori, based on available administered the EQ-5D-5L, 15 did not download the evidence, were that patients with worse control of asthma ARCA app, and 119 in total were included in the study: [65], asthmatic exacerbations [66], higher frequency of 81 were 8–11 years old children who completed the SABA use [65], and second-hand smoke exposure [67] self-response version, and 38 were 6–7 years old chil- present worse HRQL. In particular, we expected the EQ- dren whose parents or guardians completed the proxy 5D-Y to present worse discriminant capacity than the response version of the EQ-5D-Y. Table 1 shows the char- disease-specific PROMIS-PAIS because of its generic acteristics of the sample at baseline. Around 60% of the nature. To assess differences among groups we used Chi- participants were boys and had well-controlled asthma. square test for proportions of participants with problems, Differences between age groups were only found for asth- and U-Mann Witney or Kruskall-Wallis nonparametric matic exacerbation, which was more frequent among 6 to test for the HRQL scores. The magnitude of the differ- 7-year-olds. ences between groups was assessed by the Cohen effect Very few patients reported problems in the EQ-5D-Y size (difference of mean/pooled SD) [68]. General guide- dimensions (Table 2), especially for “mobility” (5.1%) lines define an effect size of 0.2 as small, 0.5 as moderate, and “looking after myself ” (2.6%). The dimension show- and 0.8 as large [69]. ing the highest percentage of participants with prob- To assess reliability and responsiveness, patients were lems was “doing usual activities” (28.8%) where there divided into three subsamples defined according to sta- was 1 participant reporting “a lot of ” problems. Very few bility, worsening or improvement between the two missing values were observed in some EQ-5D-Y dimen- administrations of the EQ-VAS and the ACQ. On one sion (“mobility”, “looking after myself ”, and “doing usual hand, patients who changed in EQ-VAS ± 0.3 SD or less activities”). (small magnitude) were included in the stable subsample, At month 4 after recruitment (when the PROMIS- and those with a change larger than 0.3 SD (moderate or PAIS was administered through the app), 44 participants large magnitude) in the negative and positive direction were lost to follow-up, and 75 answered the PROMIS- were considered for the worsening and improvement PAIS. Table 3 shows the results of the participants who subsamples respectively. The cut-off point of 0.3 SD [69] answered the PROMIS-PAIS (self-response n = 59; proxy was selected following the established interpretation of response n = 16). Patients reported more frequently “my the magnitude of change. On the other hand, according asthma bothered me” and “it was hard to play sports or to the ACQ, patients that remained in the same asthma exercise because of asthma”. The PROMIS-PAIS was control category were included in the stable subsam- completed entirely by the responders, with no missing ple, while those which moved to a worse or better cat- values for any of the items. egory were included in the worsening or improvement As shown in Table 4, the mean (SD) of the EQ-5D-Y subsample. utility index in the total sample was 0.93 (SD = 0.11). This Since our hypothesis was that a stable EQ-VAS or ACQ high mean is explained by the accumulation of patients indicates health stability over time, test–retest reproduc- in 1, the highest score (best HRQL). This ceiling effect ibility of the EQ-5D-Y and PROMIS-PAIS was assessed of 60.3% is caused by the high number of participants in the stable subsamples by measuring the agreement reporting “no problems” in all dimensions. Despite this between the two administrations with the Intra-class accumulation in the highest score, the observed range Correlation Coefficient (ICC). Regarding responsiveness, (1–0.5095) indicates a high variance. The EQ-VAS mean our hypothesis was that the EQ-5D-Y is able to detect (SD) was 84.3 (17.1) among the whole sample. There were change over time, though with a lower sensitivity than three patients with a missing value in the EQ-5D-Y utility the asthma-specific instrument PROMIS-PAIS. Respon- index, while the EQ-VAS was completed by all respond- siveness was evaluated in the worsening and improve- ers. The PROMIS-PAIS raw score mean (SD) was 11.9 ment subsamples by testing differences between the two (4.9), and its ceiling effect was 32%. administrations in the EQ-5D-Y or PROMIS-PAIS with Table 5 presents the multitrait-multimethod matrix the Wilcoxon paired test. The magnitude of change was between EQ-5D-Y, PROMIS-PAIS, and ACQ. For the Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 6 of 16 189 patients recruited 41 were 6–7 years old 93 were 8–11 years old 55 were 12–14 years old (EQ-5D-Y proxy version) (EQ-5D-Y self-response) (EQ-5D-5L) 15 did not download the ARCA app App: 119 answered the EQ-5D-Y Baseline Telephone interviews: 119 completed App: 75 answered the PROMIS-PAIS Month 4 44 lost to follow up App: 62 answered the EQ-5D-Y 5 answered the EQ-5D-5L 52 lost to follow up Month 6 Telephone interviews: 116 completed Telephone interviews: 3 not completed App: 67 answered the PROMIS-PAIS Month 10 52 lost to follow up Fig. 1 Flow chart of the study from recruitment to month 10 two correlations previously hypothesized as moderate asthma”. The correlation of the EQ-VAS with the other (convergent validity) we obtained a coefficient of 0.38 two asthma-specific instruments was lower than that between the PROMIS-PAIS’ raw score and the EQ-5D-Y obtained with the EQ-5D-Y utility index. utility index, and of 0.35 between the EQ-5D-Y dimen- Table 6 shows statistically significant differences in sion “problems doing usual activities” and the ACQ item some dimensions of the EQ-5D-Y, the utility index, and “how limited were you in your activities because of your the EQ-VAS, among known groups defined by their asthma?”. Regarding discriminant validity, the two rela- asthma control with the ACQ, frequency of SABA use in tionships hypothesized as weak obtained a correlation the last 4 weeks, and second-hand smoke exposure. The of 0.28 between the ACQ and the EQ-5D-Y utility index, effect size of almost all these differences in both the EQ- and 0.17 between the EQ-5D-Y dimension “problems 5D-Y utility index and the EQ-VAS was ≥ 0.5, indicat- doing usual activities” and the PROMIS-PAIS item “it ing moderate magnitude. The largest magnitude of the was hard for me to play sports or exercise because of my Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 7 of 16 Table 1 Demographic and clinical characteristics of participants at baseline All EQ-5D-Y EQ-5D-Y P value (n = 119) Self response Proxy response (n = 81) (n = 38) Age, mean (SD) 9.1 (1.7) 10.1 (1.1) 7.0 (0.6) < .001 6–7 38 (31.9%) 0 (0.0%) 38 (100.0%) < .001 8–11 81 (68.1%) 81 (100.0%) 0 (0.0%) Sex Girls 48 (40.3%) 29 (35.8%) 19 (50.0%) .14 Boys 71 (59.7%) 52 (64.2%) 19 (50.0%) Asthma control .99 ACQa, mean (SD) 0.81 (0.93) 0.81 (0.88) 0.81 (1.06) Well controlled (< 0.75) 68 (58.6%) 43 (54.4%) 25 (67.6%) .37 Intermediate (0.75–1.5) 23 (19.8%) 18 (22.8%) 5 (13.5%) Not well controlled (> 1.5) 25 (21.6%) 18 (22.8%) 7 (18.9%) Asthmatic exacerbations (last 6 months) Yes 53 (44.5%) 27 (33.3%) 26 (68.4%) < .001 No 66 (55.5%) 54 (66.7%) 12 (31.6%) Number of prescribed SABAb 0 9 (7.8%) 6 (7.6%) 3 (8.1%) .72 1 103 (88.8%) 71 (89.9%) 32 (86.5%) 2 4 (3.4%) 2 (2.5%) 2 (5.4%) Frequency of SABA inhaler use (previous 4 weeks) No use 9 (7.8%) 6 (7.6%) 3 (8.1%) .99 Less than once per week 62 (53.4%) 43 (54.4%) 19 (51.4%) Once or twice per week 29 (25.0%) 19 (24.1%) 10 (27.0%) Almost every day/Every day 16 (13.8%) 11 (13.9%) 5 (13.5%) Secondhand smoke exposure Not exposed 81 (83.5%) 55 (84.6%) 26 (81.3%) .92 Exposed 16 (16.5%) 10 (15.4%) 6 (18.7%) Missing 22 16 6 a ACQ: Asthma Control Questionnaire b SABA: Short-Acting β-Agonists Table 2 Distribution of EQ-5D-Y dimensions in the entire sample at baseline EQ-5D-Y dimensions No problems Some problems A lot of problems Missing values n (%) n (%) n (%) n (%) Mobility 111 (94.9%) 6 (5.1%) 0 (0.0%) 2 (1.7%) Looking after myself 114 (97.4%) 3 (2.6%) 0 (0.0%) 2 (1.7%) Doing usual activities 84 (71.2%) 33 (28%) 1 (0.8%) 1 (0.8%) Having pain or discomfort 98 (82.4%) 21 (17.6%) 0 (0.0%) 0 (0.0%) Feeling worried, sad or unhappy 110 (92.4%) 9 (7.6%) 0 (0.0%) 0 (0.0%) difference with the PROMIS-PAIS raw score was 1.11 the EQ-VAS or the ACQ. Of the 62 participants who among asthma control groups (p = 0.02). answered the EQ-5D-Y twice, after excluding three for Table 7 shows test–retest reproducibility results for missing values, 59 were finally distributed into the sub- the subsamples of stable patients and responsiveness samples (24 stable, 17 worsened and 18 improved). Only results for the subsamples of patients with worsening 46 participants answered both the PROMIS-PAIS and and improvement, defined according to the changes on the EQ-5D-Y twice. The subsamples defined according Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 8 of 16 Table 3 Distribution of the Pediatric Asthma Impact Scale (PROMIS-PAIS) items’ responses at month 4 after recruitment PROMIS-PAISa items Never Almost never Sometimes Often Almost always n (%) n (%) n (%) n (%) n (%) I felt scared that I might have trouble breathing because of my asthma 60 (80.0%) 8 (10.7%) 6 (8.0%) 1 (1.3%) 0 (0.0%) My chest felt tight because of my asthma 53 (70.7%) 13 (17.3%) 7 (9.3%) 1 (1.3%) 1 (1.3%) I felt wheezy because of my asthma 52 (69.3%) 8 (10.7%) 14 (18.7%) 1 (1.3%) 0 (0.0%) I had trouble breathing because of my asthma 52 (69.3%) 12 (16.0%) 9 (12.0%) 2 (2.7%) 0 (0.0%) I had trouble sleeping at night because of my asthma 56 (74.7%) 9 (12.0%) 10 (13.3%) 0 (0.0%) 0 (0.0%) It was hard for me to play sports or exercise because of my asthma 48 (64.0%) 12 (16.0%) 9 (12.0%) 5 (6.7%) 1 (1.3%) It was hard to take a deep breath because of my asthma 52 (69.3%) 13 (17.3%) 8 (10.7%) 2 (2.7%) 0 (0.0%) My asthma bothered me 46 (61.3%) 14 (18.7%) 13 (17.3%) 2 (2.7%) 0 (0.0%) a PROMIS-PAIS: Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale Table 4 Distribution of Health-Related Quality of Life (HRQL) Discussion scores We found the EQ-5D-Y to be feasible and easy to admin- Distribution of EQ-5D-Y Utility EQ-VASa PROMIS- ister via a smartphone application, but with a high ceil- scores Index PAISb Raw ing effect (60.3% of participants reported no problem in score any dimension). This generic preference-based instru- Sample 119 119 75 ment showed good validity, considering the moderate Theoretical Range + 1, − 0.5392 100, 0 8, 40 correlation between the EQ-5D-Y utility index and the Best–worst Best–worst Best–worst PROMIS-PAIS raw score, and the discrimination among Observed Range + 1, + 0.5095 100, 25 8, 29 known groups based on the ACQ, frequency of Short- Floor effect 0.0% 0.0% 0.0% Acting Beta-Agonists (SABAs), and second-hand smoke Ceiling effect 60.3% 23.5% 32.0% exposure. Test–retest reproducibility among the stable Mean (SD) 0.93 (0.11) 84.3 (17.1) 11.9 (4.9) subsamples indicated high reliability; and the magnitude Missing 3 (2.5%) 0 (0.0%) 0 (0.0%) of change observed between the first and second evalu- a ation in the worsening or improvement subsamples may EQ-VAS: EuroQol-Visual Analogue Scale b suggest its responsiveness, but the differences were not PROMIS-PAIS: Patient-Reported Outcomes Measurement Information System- Pediatric Asthma Impact Scale statistically significant. Feasibility of the EQ-5D-Y was indicated by its high response rate at baseline (97.5%): of the 119 participants to the ACQ were smaller, since we excluded nine patients who downloaded the app, 116 responded the EQ-5D-Y whose telephone interview was more than 90 days apart entirely. These results are similar to the 96% response rate from their app response. For the stable EQ-VAS subsam- reported in the abovementioned cross-sectional Swedish ple, the mean change was of 0.01 in the EQ-5D-Y utility study on children and adolescents with asthma [42]. The index and -0.5 in the PROMIS-PAIS raw score with ICCs flexibility of the administration through the app benefits of 0.81 and 0.89 respectively, indicating high agreement our completion results, especially for the EQ-VAS with between both evaluations (reproducibility). Regarding a completion rate of almost 100%, compared with 91% responsiveness, though change of means was not statisti- and 86.2% reported in studies where the EQ-5D-Y was cally significant, the effect size was of moderate and large administered in paper format to children with chronic magnitude for the EQ-5D-Y utility index and PROMIS- conditions [43] and schoolchildren [44], respectively. The PAIS raw score (0.68 and 1.08 respectively) among losses to follow-up (44 participants who downloaded the patients in the worsening or improvement subsamples, app but did not follow until month 6) are likely related analyzed together. to major misunderstandings regarding the app, such us The agreement (reproducibility) in the stable subsam- patients thinking that it only had to be answered once ple defined according to ACQ for the EQ-5D-Y utility and then deleted [52]. On the other hand, 8 patients who index, EQ-VAS and the PROMIS-PAIS raw score meas- continued using the app did not answer the EQ-5D-Y ured with the ICC was 0.79, 0.70 and 0.68, respectively; at month 6, which is a response rate of 88.5%. This high and regarding responsiveness, the effect size of change level of completion in both administrations could be was large (0.78, 1.15 and 1.28) among patients from explained by its low response burden: response times the worsening or improvement subsamples, analyzed have been estimated on 1.25 min for EQ-5D-Y web together. Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 9 of 16 Table 5 Multitrait-multimethod matrix between the EQ-5D-Y, the Pediatric Asthma Impact Scale and the Asthma Control Questionnaire EQ-5D-Y EQ-VASc EQ-5D-Y ACQd ACQ Item Utility index Visual Analogue Scale Dimension (Problems Global Score (Limited in activities doing usual activities) because of asthma) PROMIS-PAIS Global Score 0.38a 0.16 0.33 0.37 0.29 n = 74 n = 75 n = 75 n = 73 n = 73 (p = .001) (p = .158) (p = .003) (p = .001) (p = .014) CI CI [0.38 to 0.06] CI [0.12 to 0.52] CI CI [0.06 to 0.48] [0.56 to 0.16] [0.15 to 0.55] PROMIS-PAISe Item 0.25 0.16 0.17b 0.31 0.30 (Hard to play sports or exercise because of n = 74 n = 75 n = 75 n = 73 n = 73 asthma) (p = .033) (p = .158) (p = .151) (p = .008) (p = .011) CI CI [0.38 to 0.06] CI [ 0.06 to 0.38] CI CI [0.07 to 0.49] [0.45 to 0.02] [0.08 to 0.50] ACQ Global Score 0.28b 0.26 0.30 1 0.79 n = 113 n = 116 n = 115 n = 116 (p = .002) (p = .004) (p = .001) (p = .000) CI CI [0.43 to 0.09] CI [0.12 to 0.46] CI [0.71 to 0.85] [0.44 to 0.10] ACQ Item 0.36 0.26 0.35a 0.79 1 (Limited in activities because of asthma) n = 113 n = 116 n = 115 n = 116 (p = .000) (p = .005) (p = .000) (p = .000) CI CI [0.42 to 0.08] CI [0.18 to 0.50] CI [0.71 to [0.51 to 0.18] 0.85] Correlation coefficients are presented without a sign, since it only reflects that instruments’ scores are in the same or in the opposite direction a Correlation hypothesized as moderate (0.31–0.60) b Correlation hypothesized as weak (≤ 0.30) c EQ-VAS: EuroQol-Visual Analogue Scale d ACQ: Asthma Control Questionnaire e PROMIS-PAIS: Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale version [34]. These results support the feasibility of the “having pain or discomfort” (18.1%) are consistent with EQ-5D-Y when it is administered through a smartphone previous studies [42, 44, 73] where the EQ-5D-Y has been application. used to describe the impact of asthma on children and Regarding the distribution of EQ-5D-Y results, the adolescents. Studies using the Pediatric Asthma Qual- ceiling effect in the sample was high for the utility index ity of Life Questionnaire (PAQLQ) [42, 74] or the Child (60.3%) and for three out of its five dimensions, which Health Questionnaire (CHQ-CF87) [8] also highlighted measuring HRQL with the PedsQL™ [10] concludes that exceeded 90% of participants reporting no problem the physical activity limitation, while another study (“mobility”, “looking after myself ”, and “feeling worried/ sad/unhappy”). This high ceiling effect in our sample asthma has an impact on physical, emotional, and school could be partly explained by the considerable proportion performance. In our study, participants reported a low of participants with well-controlled symptoms of asthma percentage of problems in the dimension of “Feeling wor- (58.6%). Furthermore, a similar ceiling effect, above 80%, ried, sad or unhappy” (7.6%). has been also reported for the “mobility” and “looking Construct validity of the EQ-5D-Y was evaluated by after myself ” dimensions in other studies with children exploring its relationships as a generic measure with or adolescents with asthma [42] and other chronic condi- the asthma-specific PROMIS-PAIS, as there is no gold tions [43, 44]. These ceiling effects are very high consid- standard for HRQL assessment in pediatric asthma. The ering the established recommendation of 15% for HRQL correlation between the EQ-5D-Y utility index and the scores [70]. However, this is a general standard, as there PROMIS-PAIS raw score is moderate in our study, show- are none specifically for children. A higher ceiling effect ing that both instruments are capturing the HRQL impact could be expected in children, taking into account their of asthma although not similarly, mainly due to differ- capacity of adaptation to chronic diseases and treatment ences between generic and asthma-specific approaches, routines, known as the well-being paradox or response and to a lesser extent due to differences between the psy- shift effect [71, 72]. The prevalence of problems reported chometric and econometric development. In our study, in the dimensions of “doing usual activities” (29.6%) and these questionnaires were administered at different Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 10 of 16 Table 6 Comparison of Health-Related Quality of Life (HRQL) between known groups measured at baseline % of participants reporting problems in each dimension EQ-5D-Y EQ-VASa PROMIS ­PAISb raw (n of participants with problems/n of participants without Utility Index Score problems) Mobility Looking Doing Having Feeling Mean (SD) Mean (SD) Mean (SD) after usual pain/ worried/sad/ n = 116 n = 119 n = 75 myself activities discomfort unhappy Asthma control—ACQc Well controlled 4.4% 1.5% 20.6% 14.7% 7.4% .94 (.12) 88.2 (14.4) 10.9 (4.4) (3/65) (1/67) (14/54) (10/58) (5/63) Intermediate 0.0% 4.3% 39.1% 21.7% 8.7% .91 (.11) 78.6 (20.6) 11.3 (3.3) (0/23) (1/22) (9/14) (5/18) (2/21) Not well controlled 13.0% 4.3% 45.8% 24.0% 8.0% .89 (.12) 77.9 (18.5) 16.2 (6.2) (3/20) (1/22) (11/13) (6/19) (2/23) P value .12 .64 .04 .52 .98 .06 < .006 .002  ­ESd N/Af N/Af N/Af N/Af N/Af − 0.38 0.66 1.11 [95% ­CIe] [− 0.87 to 0.1] [0.19 to 1.13] [0.45 to 1.76] Asthmatic exacerbations (last 6 months) No 6.3% 1.5% 23.1% 13.6% 6.1% 0.94 (0.11) 84.6 (18.3) 11.3 (4.8) (4/60) (1/64) (15/50) (9/57) (4/62) Yes 3.8% 3.8% 35.8% 22.6% 9.4% 0.91 (0.12) 84.0 (15.6) 12.9 (5.0) (2/51) (2/50) (19/34) (12/41) (5/48) P value .55 .43 .13 .20 .49 .12 .46 .15 ES N/Af N/Af N/Af N/Af N/Af − 0.24 0.03 0.35 [95% CI] [− 0.61 to 0.13] [− 0.33 to 0.4] [− 0.13 to 0.82] Frequency of SABAg use reported by patients (last 4 weeks) Less than once per 4.3% 1.4% 18.6% 11.3% 5.6% 0.95 (0.09) 88.4 (14.2) 11.4 (4.9) week (3/66) (1/69) (13/57) (8/63) (4/67) Once or more per 6.7% 4.5% 46.7% 28.9% 11.1% 0.88 (0.14) 77.2 (19.4) 12.7 (5.0) week (3/42) (2/42) (21/24) (13/32) (5/40) P value .59 .31 .001 .02 .28 .004 .001 .27 ES N/Af N/Af N/Af N/Af N/Af − 0.59 0.68 0.26 [95% CI] [− 0.98 to − 0.2] [0.30 to 1.07] [− 0.21 to 0.73] Second-hand smoke exposure Not exposed 5.1% 1.3% 27.5% 17.3% 9.9% 0.92 (0.11) 85.6 (15.4) 11.6 (4.7) (4/75) (1/79) (22/58) (14/67) (8/73) Exposed 12.5% 13.3% 43.8% 37.5% 6.3% 0.87 (0.16) 73.5 (19.7) 13.7 (6.6) (2/14) (2/13) (7/9) (6/10) (1/15) P value .27 .01 .20 .07 .65 .35 .02 .21 ES N/Af N/Af N/Af N/Af N/Af − 0.45 0.75 0.42 [95% CI] [− 1.01 to 0.1] [0.21 to 1.30] [− 0.23 to 1.07] a EQ-VAS: EuroQol-Visual Analogue Scale b PROMIS-PAIS: Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale c ACQ: Asthma Control Questionnaire d ES: effect size e CI: interval confidence f N/A: not applicable g SABA: Short-Acting β-Agonists periods (EQ-5D-Y at baseline and PROMIS-PAIS at [75, 76], with a high correlation between them (0.78) month 4), which may have produced an underestimation [76], proposing generic HRQL instruments to add of their correlations. Previous studies have remarked that broader domains which are also important to patients asthma-specific HRQL instruments measure similar con- with asthma [77]. However, in our study the correlation tents to those covered by asthma control questionnaires of the ACQ with the PROMIS-PAIS was moderate (0.37, Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 11 of 16 Table 7 Evaluation of reproducibility and responsiveness of EQ-5D-Y’s utility index and PROMIS-PAIS Stable subsample Worsening subsample Improvement subsample Subsamples defined according to the EQ-VASa EQ-5D-Y utility Index n 24 17 18 1st administration, mean (SD) 0.94 (0.11) 0.98 (0.04) 0.90 (0.12) 2nd administration, mean (SD) 0.95 (0.09) 0.95 (0.10) 0.94 (0.10) Change, mean (SD) 0.01 (0.08) − 0.04 (0.09) 0.04 (0.11) P value .50 .12 .18 Effect size 0.14 0.68d  ­ICCb 0.81 N/Ac N/Ac PROMIS-PAIS raw ­scoree n 19 12 15 1st administration, mean (SD) 39.0 (7.4) 41.4 (7.8) 38.0 (6.6) 2nd administration, mean (SD) 39.5 (9.8) 36.5 (5.8) 37.6 (6.0) Change, mean (SD) − 0.5 (5.5) 5.0 (8.7) 0.4 (10.1) P value .71 .07 .88 Effect size 0.09 1.08d  ­ICCb 0.89 N/Ac N/Ac f Subsamples defined according to the ACQ EQ-5D-Y utility Index n 29 6 16 1st administration, mean (SD) 0.94 (0.10) 0.92 (0.15) 0.95 (0.08) 2nd administration, mean (SD) 0.96 (0.09) 0.88 (0.14) 0.95 (0.08) Change, mean (SD) 0.02 (0.08) − 0.04 (0.13) 0.00 (0.11) P value .31 .50 .94 Effect size 0.19 0.78d  ­ICCb 0.79 N/Ac N/Ac a EQ-VAS n 30 6 16 1st administration, mean (SD) 88.9 (14.1) 78.5 (22.3) 80.4 (16.3) 2nd administration, mean (SD) 90.8 (11.7) 83.0 (19.3) 83.1 (18.1) Change, mean (SD) 2.0 (12.5) 4.5 (24.0) 2.7 (20.2) P value .40 .67 .59 Effect size 0.16 1.15d  ­ICCb 0.70 N/Ac N/Ac e PROMIS-PAIS raw ­score n 25 6 11 1st administration, mean (SD) 36.5 (4.0) 48.0 (10.1) 42.1 (9.0) 2nd administration, mean (SD) 36.7 (5.2) 46.6 (11.8) 38.5 (7.1) Change, mean (SD) − 0.2 (4.6) 1.4 (13.8) 3.7 (10.3) P value .83 .82 .27 Effect size 0.04 1.28d  ­ICCb 0.68 N/Ac N/Ac a EQ-VAS: EuroQol-Visual Analogue Scale b ICC: Intra-class Correlation Coefficient c N/A: not applicable d Effect size of change calculated for the worsening and improvement subsamples together e PROMIS-PAIS: Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale f ACQ: Asthma Control Questionnaire Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 12 of 16 95% CI 0.15–0.55), and not significantly stronger than test and retest in these two studies was short (7–10 days that of the ACQ with the EQ-5D-Y index (0.28, 95% CI and 48 h). In our case, a 6-month time interval between 0.44–0.10). evaluations could underestimate the reproducibility, but As we hypothesized, the correlation of the EQ-5D-Y this effect could be compensated by the selection of sta- dimension “problems doing usual activities” with the ble patients. Reproducibility of the PROMIS-PAIS raw ACQ item “how limited were you in your activities score was high in the stable subsample defined with the because of your asthma?” was moderate, and with the EQ-VAS (ICC of 0.89) and acceptable in the subsam- PROMIS-PAIS item “it was hard for me to play sports ple defined with the ACQ (ICC of 0.68). We did not or exercise because of my asthma” was insignificant. find previous studies evaluating reproducibility of the This was similar to the correlation of 0.21 between PROMIS-PAIS. “mobility” (EQ-5D-Y) and “physical wellbeing” (KID- Regarding responsiveness of the EQ-5D-Y utility index, SCREEN) reported in children with diabetes [39], argu- we obtained a moderate to large capacity of the instru- ing that some KIDSCREEN items consider high energy ment to detect change over time. As expected, a larger activities such as “have you been physically active (e. g. capacity of detecting change was observed with the running, climbing, biking)?”. asthma-specific instrument PROMIS-PAIS. The EQ- Furthermore, the results on discrimination capacity 5D-Y unweighted summary score has demonstrated its of the EQ-5D-Y utility index and EQ-VAS among most ability to detect improvement of a moderate magnitude of the selected known groups confirm the hypothesized in children and adolescents with type 1 diabetes mellitus direction. Although these groups are well known in (n = 58) [39]. A study of children with idiopathic scolio- adults, as far as we know there are no EQ-5D-Y stud- sis (n = 110) [40] demonstrated the responsiveness of the ies evaluating them in children: the EQ-5D was able to EQ-5D-Y index constructed with adult value sets, obtain- detect differences between groups defined by the ACQ ing a large worsening and a small improvement in sub- [65], and presented a significant association with second- samples defined according to the global rating of health hand smoke exposure [67]. These findings provide evi- scale. dence of the EQ-5D-Y’s ability to detect differences in these known groups, indicating a good construct validity Strengths and limitations of the instrument, which presented a similar discrimi- The Asthma Research in Children and Adolescents nant capacity to the PROMIS-PAIS among groups except (ARCA) study provides a complete database with for those defined by the ACQ. The PROMIS-PAIS raw repeated administration of HRQL instruments and dis- score showed, as expected, greater differences than EQ- ease-related variables that allow the assessment of EQ- 5D-Y between patients with well- and not well-controlled 5D-Y’s (self-response and proxy version) psychometric asthma defined by ACQ (large effect size of 1.11). properties. The administration of the PROMIS-PAIS Regarding content validity, it is important to mention allowed us to assess the construct validity of the generic that the EQ-5D-Y does not cover key aspects of children’s EQ-5D-Y, comparing it with an asthma-specific HRQL HRQL such as social, emotional, or school impact, unlike instrument. To the best of our knowledge, this is the first other generic HRQL instruments that do include them. study evaluating the psychometric properties of the EQ- For example, the KIDSCREEN [78] considers “autonomy 5D-Y using the value sets for children, and also the first and relationships with parents”, “social support”, “rela- one including the proxy version to collect HRQL of chil- tionship with friends”, and “school environment”; the dren with asthma younger than 8 years old. Child Health Questionnaire [79] includes “role/social The effect of the SARS-CoV-2 pandemic on this study emotional and behavioral functioning”; and the Child deserves a comment. Of the 119 patients included in Health Utility 9D [80] asks about “school, daily routine this study, there were only 8 patients recruited after the and activities”. SARS-CoV-2 lockdown (between March 2020 and the Our study shows good reproducibility of the EQ-5D-Y closing of the data base in June 2020). Of the patients utility index and EQ-VAS according to the established recruited before lockdown, 19 should have responded the standard [70] (ICC equal or greater than 0.70), which 6-month follow-up during this 4-month period, but only was consistent with the ICC of the EQ-5D-Y unweighted 6 answered the EQ-5D-Y. Considering the low number of summary score (0.83) reported in a study with children participants who had to answer during the SARS-CoV-2 with type 1 diabetes mellitus for the EQ-5D-Y summary lockdown, results are not likely to be affected by the score [39]. Two studies reported from poor to substan- pandemic. On the other hand, 18 participants reported tial agreement according to the EQ-5D-Y dimension, during the telephone interviews having suffered SARS- with Kappa coefficients ranging from 0.003 to 0.67 [33] CoV-2, but only two had been diagnosed before closing and from 0.199 to 0.653 [41]. The period of time between the data base of this analysis. Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 13 of 16 Some limitations should be mentioned. First, this is quality-adjusted life-years (combining both the quantity a secondary objective of the ARCA study, primarily and quality of life) for economic evaluations, since it is a designed for purposes other than the evaluation of the preference-based health status measure. It is a promising psychometric properties of EQ-5D-Y. Second, the small instrument to compare the efficiency of different pro- sample size in the proxy response (n = 38) prevented an grams or treatment strategies, helping prioritization and independent, complete analysis for self-response and investment at different levels. Given its short and easy proxy-response versions. However, the examination of administration, the EQ-5D-Y is a practical instrument the distribution of each version showed a similar pat- to be used for monitoring patients through the use of tern (see Tables S1 and S2 in the Additional file 1). Third, smartphone applications. the skewness (high ceiling effect) of the EQ-5D-Y utility index could have affected the construct validity results Abbreviations and also hinder the detection of improvement. The Euro- ARCA​: Asthma Research in Children and Adolescents; HRQL: Health-Related Qol research foundation’s younger populations working Quality of Life; ACQ: Asthma Control Questionnaire; CHQ-CF87: Child Health group recently developed the new version with 5 lev- Questionnaire; CHU-9D: Child Health Utility 9D; EQ-VAS: EuroQol-Visual Ana‑ logue Scale; HUI: Health Utility Index; SMS: Short Message Service; ICC: Intra- els (EQ-5D-Y-5L) [81], since expanding the number of class Correlation Coefficient; PedQL: Pediatric Quality of Life Inventory; PROMIS severity levels might reduce ceiling effects and improve PAIS: Patient-Reported Outcomes Measurement Information System-Pediatric sensitivity. Fourth, responsiveness results should be Asthma Impact Scale; PROMS: Patient-Reported Outcome Measures; SABA: Short-Acting β-Agonists; SD: Standard deviations; PAQLQ: Pediatric Asthma interpreted with caution considering the low number of Quality of Life Questionnaire. participants evaluated due to the classification into two subsamples (stable and changed), and also in part the Supplementary Information losses to follow-up (n = 44). The latter could have intro- The online version contains supplementary material available at https://​doi.​ duced an attrition bias; in fact, differences found in the org/​10.​1186/​s12955-​022-​01955-5. asthmatic exacerbations in the last 6 months reported at Additional file 1: Table S1. Distribution of Health-Related Quality of Life baseline suggest that the participants could be healthier (HRQL) scores, self-response version (n=81). Table S2. Distribution of Health-Related Quality of Life (HRQL) scores, proxy-response version (n = than those who dropped out (see Table S3 in the Addi- 38). Table S3. Demographic characteristics of participants who completed tional file 1). Fifth, because the ARCA project only the 6-month follow-up evaluation and those who did not. included patients with mild-to-moderate persistent asthma, the generalizability of our results to those with Acknowledgements intermittent or severe persistent asthma is uncertain. Financial support for this study was provided through grants by the Instituto Its generalizability is also uncertain to other chronic de Salud Carlos III FEDER: Fondo Europeo de Desarrollo Regional (PI15/00449 and FI16/00071), University of Costa Rica (OAICE-85-2019) and DIUE of conditions. Generalitat de Catalunya (2017 SGR 452). The funding agreements ensure the authors’independence in designing the study, interpreting the data, and writ‑ ing and publishing the report. The authors would like to acknowledge Aurea Martin for her help in the English editing and proofreading process and in Conclusion finalizing this manuscript, and to the technical team at "STAR​TCA​T APP DEVEL‑ Despite the limitations discussed above, our results pro- OPMENT, S.L." in charge of the development of the mobile application ARCA. vide considerable evidence supporting the appropriate ARCA Group: Montse Ferrer, Karina Mayoral, Catalina Lizano, Olatz Garin, Yolanda Pardo, Àngels Pont (IMIM, Institut Hospital del Mar d’Investigacions psychometric properties of the EQ-5D-Y in children with Mèdiques); Maria Araceli Caballero (Pediatric Service. Hospital del Mar); persistent asthma. In conclusion, these findings suggest Manuel Praena (Centro de Salud la Candelaria); Laura Valdesoiro (Hospital Uni‑ that the EQ-5D-Y is a feasible, valid, and reliable instru- versitario Parc Taulí); Ines de Mir (Hospital Vall d’Hebron); Gimena Hernandez (CAP Vila Olimpica); Alberto Bercedo (Centro de Salud Dobra); Jose Antonio ment for evaluating HRQL in children and adolescents Castillo (Hospital Infantil Universitario Miguel Servet); María Teresa Guerra with mild-to-moderate persistent asthma when it is self- (Centro de Salud Jerez Sur), Eva Tato (Hospital Universitario Araba); Pilar Ortiz responded by 8–12 years old patients and through proxy (Centro de Salud Dos de Mayo), María Ángela Carrasco (Consultorio Sevilla la Nueva), Isabel Moneo (Centro de Salud Torre Ramona); Alexandra L. Dima, Eric response by parents of children under 8 years old. How- van Ganse (University Claude Bernard Lyon), Marijn de Bruin (Radboud Univer‑ ever, the EQ-5D-Y’s high ceiling effect found in our sam- sity Medical Center, Radboud Institute for Health Sciences, IQ Healthcare). ple suggests that it may be more suitable for patients with Authors’ contributions severe asthma and a higher presence of problems. Fur- K.M. contributed to the conception and design of the article and wrote the ther head-to-head comparisons of the three-level and the article; M.F. conceived the study, oversaw all aspects, contributed to the new five-level version of the EQ-5D-Y in children with conception and design of the article, contributed to the statistical analyses, carried out the interpretation of data, and contributed to the writing of the asthma are needed to examine to what extent expand- article; O.G., C.L.B. contributed to the conception and design of the article, ing the number of response levels decreases ceiling conceptualized and oversaw analyses, and contributed to the interpretation of effect and increases responsiveness. The recent develop- data; A.P. contributed to the analysis and provided statistical support; A.C.-R., M.P., L.V.-N., M.T.G., J.A.C., I.dM., E.T., participated in the design of the study and ment of the value sets for Spanish children [50] follow- carried out the fieldwork; J.A., Y.P., V.S.S., revised important intellectual content ing the international protocol [48] will allow calculating and the draft versions of the manuscript. All the co-authors critically revised Mayoral et al. Health and Quality of Life Outcomes (2022) 20:51 Page 14 of 16 the manuscript and approved the final draft before submission, and can attest 6. Hossny EM, El-owaidy RH, Abdel BM. Original article Health-related qual‑ to the validity and legitimacy of the data in the manuscript and agree to be ity of life assessment using EQ-5D-Y questionnaire in a group of Egyptian named as author of the manuscript. asthmatic children. Egypt J Pediatr Allergy Immunol. 2020;18(1):25–34. 7. Otto C, Barthel D, Klasen F, Nolte S, Rose M, Meyrose AK, et al. Predictors Funding of self-reported health-related quality of life according to the EQ-5D-Y in Financial support for this study was provided through grants by the Instituto chronically ill children and adolescents with asthma, diabetes, and juve‑ de Salud Carlos III FEDER: Fondo Europeo de Desarrollo Regional (PI15/00449 nile arthritis: longitudinal results. Qual Life Res. 2017;27(4):879–90. https://​ and FI16/00071), University of Costa Rica (OAICE-85-2019), and Generalitat doi.​org/​10.​1007/​s11136-​017-​1753-8. de Catalunya (2017 SGR 452). The funding agreements ensure the authors’ 8. Merikallio VJ, Mustalahti K, Remes ST, Valovirta EJ, Kaila M. Comparison independence in designing the study, interpreting the data, and writing and of quality of life between asthmatic and healthy school children. Pediatr publishing the report. Allergy Immunol. 2005;16(4):332–40. 9. Sawyer MG, Reynolds KE, Couper JJ, French DJ, Kennedy D, Martin J, et al. Availability of data and materials Health-related quality of life of children and adolescents with chronic The datasets used and/or analysed during the current study are available from illness—a two year prospective study. Qual Life Res. 2004;13(7):1309–19. the corresponding author upon reasonable request. 10. Kouzegaran S, Samimi P, Ahanchian H, Khoshkhui M, Behmanesh F. Qual‑ ity of life in children with asthma versus healthy children. Open Access Maced J Med Sci. 2018;6(8):1413–8. Declarations 11. van den Bemt L, Kooijman S, Linssen V, Lucassen P, Muris J, Slabbers G, et al. How does asthma influence the daily life of children? Results of Ethical approval and consent to participate focus group interviews. Health Qual Life Outcomes. 2010;8(5):1–10. The study has the approval of the Parc de Salut Mar ethical committee of 12. Reichenberg K, Broberg AG. Quality of life in childhood asthma : use of clinical research (nº 2015/62/12l), and it was conducted in accordance with the Paediatric Asthma Quality of Life Questionnaire in a Swedish sample the ethical standards of the institutional research committee and the 2000 of children 7 to 9 years old. Acta Paediatr. 2000;89(8):989–96. revision of the Declaration of Helsinki. Informed consent was obtained from 13. Rydstro I, Holritz-rasmussen B, Mo C. Asthma-quality of life for Swedish the parents or legally authorized representatives of participants, as well as children. J Clin Nurs. 2005;14:739–49. from the children. 14. Chipps BE, Haselkorn T, Rosén K, Mink DR, Trzaskoma BL, Luskin AT. Asthma exacerbations and triggers in children in TENOR: impact on qual‑ Consent for publication ity of life. J Allergy Clin Immunol Pract. 2018;6(1):169-176.e2. https://​doi.​ Not applicable. org/​10.​1016/j.​jaip.​2017.​05.​027. 15. Luskin AT, Chipps BE, Rasouliyan L, Miller DP, Haselkorn T, Dorenbaum A. Competing interests Impact of asthma exacerbations and asthma triggers on asthma-related The authors declare that they have no competing interests. quality of life in patients with severe or difficult-to-treat asthma. J Allergy Clin Immunol Pract. 2014;2(5):544-552.e2. https://​doi.​org/​10.​1016/j.​jaip.​ Author details 2014.​02.​011. 1 Health Service Research Group, IMIM (Hospital del Mar Medical Research 16. Zeiger RS, Yegin A, Simons FER, Haselkorn T, Rasouliyan L, Szefler SJ, et al. Institute), Barcelona Biomedical Research Park, office 144. Doctor Aiguader, 88, Evaluation of the National Heart, Lung, and Blood Institute guidelines 08003 Barcelona, Spain. 2 Department of Paediatrics, Obstetrics and Gynaecol‑ impairment domain for classifying asthma control and predicting asthma ogy and Preventive Medicine, Universitat Autònoma de Barcelona, Barcelona, exacerbations. Ann Allergy Asthma Immunol. 2012;108(2):81-87.e3. Spain. 3 CIBER en Epidemiología y Salud Pública, CIBERESP, Madrid, Spain. https://​doi.​org/​10.​1016/j.​anai.​2011.​12.​001. 4 Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 17. Meltzer EO, Busse WW, Wenzel SE, Belozeroff V, Weng HH, Feng J, et al. Barcelona, Spain. 5 Department of Pharmaceutical Care and Clinical Pharmacy, Use of the asthma control questionnaire to predict future risk of asthma Faculty of Pharmacy, Universidad de Costa Rica, San José, Costa Rica. 6 Paedi‑ exacerbation. J Allergy Clin Immunol. 2011;127(1):167–72. https://​doi.​org/​ atric Pulmonology and Allergy Unit, Paediatric Department, Hospital Del Mar, 10.​1016/j.​jaci.​2010.​08.​042. Barcelona, Spain. 7 Centro de Salud La Candelaria. Servicio Andaluz de Salud, 18. Everhart RS, Fiese BH. Asthma severity and child quality of life in pediatric Sevilla, Spain. 8 Grupo de Vías Respiratorias de La Asociación Española de asthma: a systematic review. Patient Educ Couns. 2009;75(2):162–8. 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