There was no difference in the CDPQOL score when comparing scores derived from all original items and scores derived from the reduced set of items. A comparison of these scores is shown in Figure 3. Figures 4 and 5 show the final validated CDPQOL instruments.
Results of the PedsQL in the Instrument Evaluation Group
Participants completing the CDPQOL in the instrument evaluation phase of development additionally completed the PedsQL generic instrument. Those in the 8- to 12-year group had a mean score of 83.8 and those in the 13- to 18-year group had a mean score of 82.1. A higher score indicates better HRQOL.
The F-K reading grade level for the validated 8- to 12-year instrument was 4.3. An F-K reading grade level of 3.4 was calculated for the 13- to 18-year instrument.
A GFD has been reported to negatively affect children with CD. Olsson et al (9) used focus group discussions with adolescents and reported that they experienced stigmatization from being on a GFD. Rashid et al (11) reported that 63% of children felt left out of social activities to some degree, 54% avoided restaurants all or most of the time, and 28% found it extremely difficult to locate stores with gluten-free foods. Chauhan et al (23) showed that the restrictions of a GFD affected eating out and traveling in Indian children with CD.
Instruments used to measure HRQOL may be generic or disease specific. A generic instrument allows for comparison across disease populations and with normative data, whereas a disease-specific instrument helps identify the most relevant problems pertaining to the disease (12,24). Generic instruments do not assess specific aspects of a disease, such as being on a GFD, which are better assessed through disease-specific instruments that are additionally more sensitive to the issues affecting patients with the disease. In CD, these issues may include the social and financial restrictions because of a GFD. Given these restrictions, a disease-specific HRQOL instrument for CD would allow health care providers to monitor their patients for such dilemmas, thereby allowing for appropriate referrals to address these issues. Because the information obtained from a generic instrument and a disease-specific instrument differs, general HRQOL scores cannot be assumed to reflect one's disease-specific HRQOL. Van Doorn et al (13) found a discrepancy in HRQOL when reviewing results from children using a generic instrument and a CD-specific instrument. When using the CD-specific instrument, children reported a negative or neutral HRQOL, whereas the generic instrument showed the same children to have a positive HRQOL. Van Koppen et al (25) also showed a discrepancy in outcomes when applying a generic instrument and a disease-specific instrument to the same population of subjects with children having a good general HRQOL but neutral or low specific HRQOL. Our study showed that the general HRQOL of the children in this study as assessed by the PedsQL was good, but this result cannot reflect CD-specific HRQOL because its items do not address the issues, which may impair HRQOL in children with CD. Only a dedicated instrument can assess the HRQOL of children with CD as compared with other children with this disease, and until now such an instrument applicable to American children has been lacking.
There are limited data on HRQOL of children with CD (11,13,23,25–29); all but 3 studies (11,26,29) were conducted outside North America, and only 2 (13,25) used a validated disease-specific instrument developed in the Dutch population. In the Dutch pediatric population, van Doorn et al (13) developed a disease-specific 24-item questionnaire (CDDUX) for children 8 to 18 years of age. This validated instrument consists of 12 items on 3 subscales: communication, diet, and having CD. Van Koppen et al (25) used the CDDUX in a study to assess HRQOL in Dutch children diagnosed at 2 to 4 years of age through mass screening. In Canada, Rashid et al (11) used the Canadian Celiac Health survey, which consisted of 76 questions, including 12 that pertained to well-being and lifestyle. In the United States, Bongiovanni et al (26) applied a HRQOL survey of 14 questions to Californian children with CD ages 7 to 17 years; this survey was developed from 4 other validated surveys because, as the authors noted, of the lack of validated pediatric CD-specific HRQOL instruments in the United States. Adherence to a GFD may be socially and financially difficult because of its restrictive nature, which may result in an impaired HRQOL. In Europe, it is possible that CD has less of a social effect given the greater awareness and health resources offered to those with CD. For example, in Britain, those with CD receive prescriptions for gluten-free food products. In Italy, the national health care system covers the expenses related to having CD, including the GFD and medical care (30). In France, patients experiencing CD are reimbursed a certain amount monthly for gluten-free food. In Finland, schools are governmentally mandated to provide gluten-free foods for lunch. Also, given the increased marketing of gluten-free options at some European restaurants and stores, the stigmatization of having CD may be less because of diminished social constraints. Because of the relative lack of such resources in the United States, a CD-specific HRQOL instrument created and used in the European population may not be comparable for use in the US population. Additional hardship may be encountered by children in the United States because of insufficient disease awareness. Associated with this, gluten-free items are difficult to find as well as much more expensive. For many families, the financial burden of additional food costs creates anxiety, which may be perceived by children with CD, possibly affecting HRQOL adversely. In India, where CD is also underdiagnosed, Chauhan et al (23) showed that noncompliance with the GFD was more common when financial burden was considered.
Our instrument differs from the CDDUX in several important ways, beyond the cultural distinctions of the populations among which they have been validated. First, the CDPQOL is an age- as well as a disease-specific instrument, with separate questionnaires developed for children ages 8 to 12 years and 13 to 18 years, taking into account comprehension differences and experiential distinctions in the questions asked. Through the validation process, we learned that challenges of having CD among different facets of life vary by age. In contrast, the CDDUX was validated among age-specific groups, although the same final instrument was developed. Furthermore, the majority (8/12) of the items contained in the CDDUX specifically refer to diet, whereas the disease-specific implications of living with CD extend beyond these considerations as reflected in the design of our instruments. Items contained in the CDPQOL contain diet-specific questions as well as several related to the emotional and social issues experienced by children diagnosed as having CD. Finally, the development and validation process of the CDDUX had several limitations, acknowledged by the authors, specifically the high proportion of female subjects taking the questionnaire. Our study showed some similarities in this regard among the younger group, whereas the 13- to 18-year-old participants were more equally balanced by sex.
Our study is unique in that it collected disease-specific HRQOL data from US children nationwide. Also, we developed and validated a CD-specific instrument that may be used in future studies on HRQOL in the United States. To validate our instrument, our study was carried out using the PedsQL, developed by Dr James W. Varni, to assess agreement for both convergent and divergent validities. In the United States, the PedsQL is a generic instrument used to evaluate HRQOL in children with various diseases, including sickle cell disease (31), inflammatory bowel disease (32), and systemic lupus erythematosus (33). There was an appropriately moderate agreement between our disease-specific instrument and the generic instrument's Psychosocial dimension confirming convergent validity. When correlating the CDPQOL with the Physical Health Summary dimension of the PedsQL, there was low agreement in the 8- to 12-year-old group, as expected, confirming divergent validity, but more moderate agreement in the 13- to 18-year-old group, although still lower than the agreement with the PedsQL Psychosocial dimension, thus still confirming divergent validity.
In creating the CDPQOL, we initially used those dimensions pertaining to specific aspects of life as determined from the literature, clinicians, and previous insight at CD support group sessions. Dimensions moderated during the focus groups addressed issues that may arise at school, at home, and social settings; however, during focus group discussions, other dimensions became apparent, resulting in the reclustering of items. Given the distinct age groups, it is expected that there would be different dimensions between age groups. For example, the 13- to 18-year-old age group faced issues pertaining to buying their own food and becoming an adult, which resulted in 2 additional dimensions for their age group. After administration and statistical analysis of the CDPQOL, clustering of the items using pattern matrix resulted in restructuring of the items for which the authors renamed the dimensions based on the connotations of the clustered items. Given the distinct age groups, it is not unexpected that the items clustered resulted in dimensions that did not necessarily overlap between age groups. This may limit the ability to compare HRQOL between the 2 age groups.
Readability statistics, specifically the F-K grade level test, were calculated for each instrument. The readability of the instrument geared toward younger patients was rendered at 4.3, indicating best readability for children reading at a 4th-grade level or above. The statistics for the 13- to 18-year instrument was 3.4, indicating that this instrument should be comprehended by those reading at the 3rd-grade level or above. This indicates that these instruments are generally age appropriate as was confirmed by our interactions with the focus groups. The discrepancy may be attributed to the marginal differences in word length between the 2 tools (4.2 characters per word vs 3.6) and perhaps by the shorter length of the 8- to 12-year tool, which may affect the reliability of an F-K score.
Limitations exist in this study. For the focus groups, recruitment was limited to children living in the local New York tristate community because of study constraints in which direct supervision from study personnel was required to conduct each focus group. Although this may influence the questionnaire's development, the distribution of the questionnaire nationwide was designed to overcome this possible bias. In addition, there was a female preponderance in both the development and validation of the CDPQOL. This may be consistent with the greater preponderance of diagnosed CD in female than in male patients, but may also reflect a bias in those patients willing to participate in such studies. Similar issues were encountered during construction of the CDDUX questionnaire (13). Furthermore, although this questionnaire was distributed nationwide, demographic information was not requested from individuals when this tool was administered during the evaluation phase, and as such it is difficult to assume how lack of these data may or may not affect the applicability of this tool for certain populations.
An additional limitation pertains to focus group participants reporting a >99% compliance with the GFD. If true, this may be a function of the general motivation of this group, because a willingness to participate in such research studies may be related to behavior making one more adherent to medical therapy. This may bias the questionnaire's development; however, we did not require confirmation of dietary adherence with serology for children to participate in these focus groups, making it possible that the participants may not have been as diligent with the diet as they stated. Furthermore, the focus groups were moderated in such a fashion as to facilitate discussion of issues or concerns that a child may face in various settings by being on a GFD, regardless of GFD compliance.
Despite the nationwide recruitment, another limitation of this study was the small sample size, particularly in the 13- to 18-year-old group. In addition, inclusion of children who were not proven by biopsy to have CD may bias the development of this tool. Changes in the way in which CD is being diagnosed should be considered here. Recent guidelines for the diagnosis of CD in children published by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition have opened the door for diagnosis of CD under certain circumstances without a small bowel biopsy (34), and some of these children may have been diagnosed based on serology alone. Given that we did not confirm diagnoses with medical records, it is feasible that some of these patients may actually have gluten intolerance rather than CD. This should not affect the overall goal of the CDPQOL to capture the HRQOL of American children on a GFD who are doing so on the basis of having CD, proven by biopsy or not, although separate issues may exist in those who truly have CD versus those presumed to but who actually do not have CD. In actuality, there may be more similarities experienced by children with symptomatic CD and gluten intolerance versus between children with silent CD and symptomatic CD. These are issues that should be addressed in a future study.
Another limitation is that completion of the questionnaires was not supervised directly by study personnel during the questionnaire validation process, prohibited by the widespread locations of participating children and impracticability of dispatching study personnel to each participant's location. As a result, we cannot confirm absence of parental involvement in the completion of these questionnaires. Although clinical questions regarding presenting complaints and biopsy history were asked alongside the CDPQOL questionnaire, likely requiring parental involvement in many, the development of the questionnaire was designed so that children in either age group would not require parental assistance or direct supervision to complete the CDPQOL. We admit that this may further have affected the result of the questions regarding compliance with the GFD (likely resulting in an overestimate of compliance), although in effect this limitation may have improved the diversity of the patients included in the validation phase because inclusion of children with suboptimal dietary compliance would improve the quality of this tool. Whether in research or clinical practice, even when patients are faced with persistently elevated serologies, it is often difficult to unearth a history of poor dietary compliance from a child. Lastly, use of exploratory factor analysis has its own limitations in that orphan items that may be important to children with CD may be excluded; however, expert review was used to limit this bias.
In summary, studies on HRQOL in American children with CD are lacking, and this is the first validated disease-specific HRQOL instrument for use in these children who may experience different social and financial pressures compared with children with CD living under other circumstances. A generic instrument is insufficient to assess CD-specific HRQOL in children. With continued use of this validated disease-specific instrument, further objective data on the HRQOL of children with CD may be obtained. Potential areas for future study include evaluating the effect of socioeconomic status, geographical location, and delay in diagnosis upon CD-specific HRQOL. This instrument will also enable assessment of HRQOL among asymptomatic children with CD, as well as the effect of future nondietary therapies for CD upon HRQOL. Collection of such information may affect how CD is viewed in the United States, among practitioners, and the public.
1. Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease
: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr
2. Ravelli A, Bolognini S, Gambarotti M, et al. Variability of histologic lesions in relation to biopsy site in gluten-sensitive enteropathy. Am J Gastroenterol
3. Leffler DA, Dennis M, Edwards George JB, et al. A simple validated gluten-free diet
adherence survey for adults with celiac disease
. Clin Gastroenterol Hepatol
2009; 7:530–536.536 e531–e532.
4. Olsson C, Hornell A, Ivarsson A, et al. The everyday life of adolescent coeliacs: issues of importance for compliance with the gluten-free diet
. J Hum Nutr Diet
5. Casellas F, Rodrigo L, Vivancos JL, et al. Factors that impact health-related quality of life
in adults with celiac disease
: a multicenter study. World J Gastroenterol
6. Nachman F, Maurino E, Vazquez H, et al. Quality of life in celiac disease
patients: prospective analysis on the importance of clinical severity at diagnosis and the impact of treatment. Dig Liver Dis
7. Ukkola A, Maki M, Kurppa K, et al. Diet improves perception of health and well-being in symptomatic, but not asymptomatic, patients with celiac disease
. Clin Gastroenterol Hepatol
8. Lee A, Newman JM. Celiac diet: its impact on quality of life. J Am Diet Assoc
9. Olsson C, Lyon P, Hornell A, et al. Food that makes you different: the stigma experienced by adolescents with celiac disease
. Qual Health Res
10. Hauser W, Gold J, Stein J, et al. Health-related quality of life
in adult coeliac disease in Germany: results of a national survey. Eur J Gastroenterol Hepatol
11. Rashid M, Cranney A, Zarkadas M, et al. Celiac disease
: evaluation of the diagnosis and dietary compliance in Canadian children
12. Borgaonkar MR, Irvine EJ. Quality of life measurement in gastrointestinal and liver disorders. Gut
13. van Doorn RK, Winkler LM, Zwinderman KH, et al. CDDUX: a disease-specific health-related quality-of-life questionnaire for children
with celiac disease
. J Pediatr Gastroenterol Nutr
14. Fishman DS, Chumpitazi BP, Ngo PD, et al. Small bowel intussusception in celiac disease
: revisiting a classic association. J Pediatr Gastroenterol Nutr
15. Kitzinger J. Qualitative research. Introducing focus groups
16. Powell RA, Single HM. Focus groups
. Int J Qual Health Care
17. Varni JW, Seid M, Rode CA. The PedsQL: measurement model for the pediatric quality of life inventory. Med Care
18. Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care
19. Varni JW, Seid M, Knight TS, et al. The PedsQL 4.0 Generic Core Scales: sensitivity, responsiveness, and impact on clinical decision-making. J Behav Med
20. Varni JW, Burwinkle TM, Seid M, et al. The PedsQL 4.0 as a pediatric population health measure: feasibility, reliability, and validity. Ambul Pediatr
21. Chan KS, Mangione-Smith R, Burwinkle TM, et al. The PedsQL: reliability and validity of the short-form generic core scales and Asthma Module. Med Care
22. Varni JW, Limbers CA. The PedsQL 4.0 Generic Core Scales Young Adult Version: feasibility, reliability and validity in a university student population. J Health Psychol
23. Chauhan JC, Kumar P, Dutta AK, et al. Assessment of dietary compliance to gluten free diet and psychosocial problems in Indian children
with celiac disease
. Indian J Pediatr
24. Yacavone RF, Locke GR 3rd, Provenzale DT, et al. Quality of life measurement in gastroenterology: what is available? Am J Gastroenterol
25. van Koppen EJ, Schweizer JJ, Csizmadia CG, et al. Long-term health and quality-of-life consequences of mass screening for childhood celiac disease
: a 10-year follow-up study. Pediatrics
26. Bongiovanni TR, Clark AL, Garnett EA, et al. Impact of gluten-free camp on quality of life of children
and adolescents with celiac disease
27. Kolsteren MM, Koopman HM, Schalekamp G, et al. Health-related quality of life
with celiac disease
. J Pediatr
28. Wagner G, Berger G, Sinnreich U, et al. Quality of life in adolescents with treated coeliac disease: influence of compliance and age at diagnosis. J Pediatr Gastroenterol Nutr
29. de Lorenzo CM, Xikota JC, Wayhs MC, et al. Evaluation of the quality of life of children
with celiac disease
and their parents: a case-control study. Qual Life Res
30. Ciacci C, De Florio M. Evaluation of an instrument for the surveillance of adult gluten intolerance diagnosis: report of the first year of activity of the Campania Celiac Network for Adult Celiac Disease
. Dig Liver Dis
31. Panepinto JA, Pajewski NM, Foerster LM, et al. The performance of the PedsQL generic core scales in children
with sickle cell disease. J Pediatr Hematol Oncol
32. Marcus SB, Strople JA, Neighbors K, et al. Fatigue and health-related quality of life
in pediatric inflammatory bowel disease. Clin Gastroenterol Hepatol
33. Brunner HI, Higgins GC, Wiers K, et al. Health-related quality of life
and its relationship to patient disease course in childhood-onset systemic lupus erythematosus. J Rheumatol
34. Husby S, Koletzko S, Korponay-Szabo IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr
Keywords:© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
celiac disease; children; focus groups; gluten-free diet; health-related quality of life