Abstract
Objective
To evaluate relations between health-related quality of life (HRQoL) and clinical symptom presentation in youth with eosinophilic esophagitis (EoE). We hypothesized that presence of dysphagia, reflux, nausea/vomiting, and epigastric pain would be related to poorer HRQoL. In predictive models, it was hypothesized that dysphagia, reflux, nausea/vomiting, and epigastric pain would each significantly and uniquely predict poorer HRQoL.
Methods
This cross-sectional, two-study design included 91 dyads comprised children with EoE and their respective caregivers across two tertiary children’s hospitals, Site 1 in the Midwest (N = 47) and Site 2 in the Deep South (N = 44). Youth and their caregivers both completed questionnaires addressing HRQoL and EoE symptoms during clinic visits.
Results
Per youth self-report, epigastric pain was found to be a significant predictor of poor physical and psychosocial HRQoL. Per caregiver-proxy reports, epigastric pain was found to be a significant predictor of poor physical HRQoL.
Conclusions
The clinical symptoms of EoE, specifically epigastric pain, were found to be predictive of the youth’s HRQoL. Targeted interventions to help youth with EoE better manage their specific symptom experiences could ultimately improve HRQoL.
Keywords: chronic Illness, gastroenterology, pain, quality of life
Introduction
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease marked by clinical symptoms of upper gastrointestinal distress and by pathologic findings of increased eosinophils in the esophagus (Dellon et al., 2013). Specific EoE symptoms commonly include dysphagia, reflux, nausea/vomiting, feeding aversion, food impaction, and epigastric pain (Liacouras et al., 2011). Diagnosis requires clinical presentation of the aforementioned symptoms and eosinophil-predominant inflammation of the esophagus with ≥15 eosinophils/high-power field found during an esophagogastroduodenoscopy (EGD) (Liacouras et al., 2011). EoE is observed in pediatric populations, with initial diagnoses made in individuals as young as 6 months of age (Khan et al. 2003). Incidence of EoE in children are estimated at 0.7–10 cases per 100,000 children per year (Soon, Butzner, Kaplan, & Jennifer, 2013). Treatment for EoE typically includes steroidal slurries aimed at reducing esophageal inflammation and dietary eliminations to reduce the patient’s exposure to possible allergens. Dietary elimination therapy includes elemental diets and specific elimination diets such as the six-food and four-food diets and allergy test-directed eliminations. While these can be effective, food reintroduction requires repeat scopes to assess histologic changes following the addition of each food (Henderson, et al., 2012).
Chronic illnesses such as EoE are often associated with changes in functioning, characterized as health-related quality of life (HRQoL). HRQoL is a multidimensional construct that includes domains related to physical, psychological, and social functioning (Drotar et al., 1998). Youth with chronic gastrointestinal diseases such as EoE often reports poor HRQoL. For instance, Cortina and colleagues found that youth with eosinophilic gastrointestinal disorders including EoE had significantly poorer HRQoL compared with healthy peers (Cortina et al., 2010). In another study examining HRQoL across different pediatric chronic illnesses, youth with eosinophilic gastrointestinal disorders reported significantly lower HRQoL than youth with cystic fibrosis, inflammatory bowel disease, epilepsy, type 1 diabetes, and sickle cell disease based on caregiver-proxy reports (Ingerski et al., 2010).
Despite growing evidence that youth with EoE may experience poor HRQoL, current understanding of the factors that drive this poor HRQoL remains limited. It has been suggested that clinical symptoms, diagnostic procedures, and recommended treatments for EoE may each influence HRQoL (Cortina et al., 2010; Franciosi et al., 2013; Klinnert, 2009). The presence and severity of EoE clinical symptoms may lead to poor HRQoL. To illustrate, Klinnert and colleagues reported results of a longitudinal study indicating that for youth with EoE, a greater number of clinical symptoms at baseline was related to poorer HRQoL at 6-month follow-up (Klinnert et al., 2014). Given that EoE has only recently been recognized and defined as a clinical syndrome in youth, it remains to be determined whether certain clinical symptoms of EoE are more predictive of HRQoL. Although yet to be addressed empirically, clinical experience suggests that recurrent and/or persistent epigastric pain may be an underappreciated, yet important, symptom of EoE that negatively impacts HRQoL. This assertion is supported by mounting evidence showing that in youth with chronically painful medical conditions, greater intensity and frequency of pain are predictive of poorer HRQoL per self- and caregiver-proxy reports (Hunfeld et al., 2001; Jastrowski Mano, Khan, Ladwig, & Weisman, 2011; Palermo, Harrison, & Koh, 2006; Sawyer et al., 2004).
Lynch and colleagues (Lynch, Avis, Dimmitt, & Goodin, 2015) have previously suggested that additional research is needed to characterize the HRQoL of youth with EoE, as well as identify potentially modifiable biopsychosocial factors that predict HRQoL. Therefore, the current work sought to determine which clinical symptoms of EoE most significantly predict the HRQoL of youth undergoing treatment at two separate and geographically distinct pediatric hospitals. The first study (Study 1) took place at Site 1, a major hospital in the Midwest, while the second study (Study 2) took place at Site 2, a major hospital in the Deep South. The decision to combine data collected as part of two separate studies was based on the need to increase sample size because of the low occurrence rate of this rare disease, produce broader generalizability (i.e., external validity), and extend findings back to the pediatric EoE population at large. Across both studies, it was hypothesized that dysphagia, reflux, nausea/vomiting, and epigastric pain would each significantly and uniquely predict poorer HRQoL.
Methods
Participants
Study 1
Youth with EoE and their caregivers were consecutively recruited for Study 1 from August 2010 through May 2011 at a tertiary hospital in the Midwest, Site 1. These pediatric patients were restricted to those with a confirmed diagnosis of EoE, defined as the presence of upper gastrointestinal tract symptoms and an endoscopy with ≥15 eosinophils/hpf in the proximal or distal esophageal tissue biopsies as per consensus diagnostic recommendations (Dellon et al., 2013). Youth aged 2–17 years and their caregivers were approached for participation in the study during their new diagnosis, follow-up, and/or problem-related clinical appointments at the Center for Eosinophilic Disorders at Site 1. Forty-nine patient–caregiver dyads were recruited. This study was approved for conduct by the Site 1 institutional review board.
Study 2
Youth with EoE and their caregivers were consecutively recruited for Study 2 from May 2014 through May 2016 at a tertiary hospital in the Deep South, Site 2. These pediatric patients had a confirmed diagnosis of EoE according to the same consensus diagnostic recommendations incorporated in Study 1 (Dellon et al., 2013). Youth aged 4–12 years was approached for participation in the study during clinic visits in the Gastrointestinal Eosinophilic Disease Program at Site 2. Appointments were a mix of new diagnosis, routine follow-up, and problem-focused visits. A total of 58 patient–caregiver dyads were recruited. The study was approved by Site 2’s institutional review board.
Procedures
Study 1
Following informed consent/assent, basic demographic information (e.g., age; sex; race) and medical history for youth with EoE were collected. Patient medical records were accessed to verify EoE diagnosis and determine current EoE treatment regimen including prescribed medications and dietary eliminations. The initial diagnostic EGD date was gathered to calculate approximate duration of illness. Participant dyads were provided with validated measures of HRQoL and EoE-specific clinical symptoms that they completed in clinic. These measures included the PedsQL Quality of Life Inventory, Generic Core Scales, Version 4.0 (Connelly and Rapoff, 2006; Varni, Limbers, & Burwinkle, 2007; Varni, Seid, & Kurtin, 2001) and the PedsQL Eosinophilic Esophagitis Module Symptom Scales I and II (Franciosi et al., 2013).
Study 2
Similar to Study 1, following informed consent/assent, demographic information and medical history for youth with EoE were collected. Medical records were reviewed to confirm each patient’s current EoE treatment regimen, and also to determine approximate duration of illness according to the date of initial diagnostic EGD. In Study 2, HRQoL and EoE clinical symptoms were again assessed using the PedsQL Quality of Life Inventory (Connelly and Rapoff, 2006; Varni, Limbers, & Burwinkle, 2007; Varni, Seid, & Kurtin, 2001) and the PedsQL Eosinophilic Esophagitis Module—Symptom Scales I and II (Franciosi et al., 2013). Participants were sent home from their clinic appointment with study measures and returned them via mail when completed.
Measures
Pediatric Quality of Life Inventory, Generic Core Scales, Version 4.0 (PedsQL 4.0)
The PedsQL is a 23-item measure that assesses the HRQoL of youth ages 2–18 years over the past month. Caregiver-proxy report forms are available for all ages and are grouped as follows: toddler (2–4 years), young child (5–7 years), child (8–12 years), and teen (13–18 years). Self-report versions are available for youth, aged ≥5 years. The items on this measure relate to four domains: physical, emotional, social, and school functioning (Varni, Seid, & Kurtin, 2001). The PedsQL can be used to derive physical and psychosocial subscales of HRQoL, as well as an overall composite for HRQoL that comprised the physical and psychosocial subscales. The physical and psychosocial HRQoL subscales were examined separately, rather than the overall composite, to determine whether EoE clinical symptoms were differentially related to these two HRQoL domains. For each subscale, scores range from 0 to 100 with higher scores reflecting better HRQOL. The PedsQL has good reliability and validity (Varni, Seid, & Kurtin, 2001). Youth self-reports and caregiver-proxy reports for physical and psychosocial HRQoL possess good agreement (Varni, Limbers, & Burwinkle, 2007).
PedsQL Eosinophilic Esophagitis Module—Symptom Scales I and II
The PedsQL Eosinophilic Esophagitis Module—Symptom Scales I and II are embedded in the 33-item measure assessing aspects of EoE that affect HRQoL. The Symptom Scales consist of the first two sections of the overall module, containing 7–10 items depending on age group. Scale 1 includes three items for children aged 2–7 years and six items for youth ≥8, while Scale 2 includes four items for all participants. For each item, the participant is asked to rate on a Likert scale, from never to almost always, how much of a problem the symptom has been for them over the past month. Caregiver-proxy reports are available for youth aged 2–18 years with self-report forms for youth aged 8–18 years. To allow for analysis of specific symptoms, scores for each EoE clinical symptom were calculated as follows. Individual symptom ratings were gathered for reported reflux. Dysphagia ratings were calculated as an average of the indicators of dysphagia on Symptom Scale II. Nausea/vomiting symptom ratings were averaged for a combined score. Epigastric pain ratings were calculated as an average of the chest pain and abdominal pain scores. Given responses are reverse scored and linearly transformed, results range from 0 to 100 with low scores indicative of more frequent and/or severe symptom experience. The PedsQL Eosinophilic Esophagitis Module (and symptoms scales) has previously been shown to possess good reliability and validity (Franciosi et al., 2013).
Data Reduction and Analysis Across Study 1 and Study 2
Of the 49 youths with EoE and their caregivers who were recruited from Site 1 in Study 1, diagnostic endoscopy results were unavailable for two participants. These two participants were excluded from data analysis because of inability to confirm EoE diagnosis. The final Site 1 sample included for data analysis in Study 1 consisted of 47 caregiver–youth with EoE dyads. Among the 58 youths with EoE and their caregivers recruited from Site 2 in Study 2, three dyads chose to withdraw from the study, seven dyads failed to return study materials by mail, and four dyads completed the study but did not have diagnostic endoscopy results available to confirm EoE diagnosis. Ultimately, 44 dyads representing youth with EoE and their caregivers recruited at Site 2 were included for data analysis in Study 2.
For analytic purposes, data were collapsed across Site 1 and Site 2. This resulted in a final study sample composed of 91 youth–caregiver dyads. Given the age limit of 8 years for valid self-report on the PedsQL EoE module, not all youth with EoE completed self-report measures. For this reason, 37 youths in total met age requirements for the provision of self-report pertaining to both their HRQoL and EoE clinical symptoms. Given the importance of recognizing the youth’s perspective, primary data analyses were conducted using youth self-report data followed by examination of the caregiver-proxy data from the 91 caregivers as secondary analyses.
Before analysis, data were examined for normality and outliers. Continuous data are presented as Ms and SDs, while categorical data are presented as frequencies. Zero-order associations among EoE clinical symptoms, physical HRQoL, and psychosocial HRQoL were examined using Pearson correlations for both self-reports of youth with EoE and caregiver-proxy reports. For self-reports of youth with EoE, the relationship between clinical symptoms and both physical and psychosocial HRQoL were further evaluated using linear multiple regressions. These analyses were then repeated using caregiver-proxy reported data. Site was used as a covariate for all regression analyses. Statistical significance was set at p < 0.05. All data analysis was conducted using SPSS version 22.0 (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp.).
Results
Participant Characteristics
Within the overall sample, youth with EoE was primarily Caucasian and male, with a mean age of 8.69 years and illness duration of 1.77 years. The youth with EoE was primarily treated with either medication alone or a combination of medication and dietary restrictions. Table I displays several significant differences in participant characteristics across the two study sites. For example, Site 2 comprised a significantly greater proportion of female and African-American youth with EoE. Further, youth with EoE from Site 1 was more likely to be treated with dietary restrictions only, while youth with EoE from Site 2 was more likely to be treated with medication only.
Table I.
Demographic and Medical Characteristics for Study Participants
| Overall N = 91 caregivers, 58 youths | Site 1 N = 47 caregivers, 36 youths | Site 2 N = 44 caregivers, 22 youths | Site comparisons |
||
|---|---|---|---|---|---|
| Characteristics | n (%),M (SD) | n (%),M (SD) | n (%),M (SD) | Significance | Cohen’s d |
| Sex | .001 | ||||
| Male | 76 (83.50) | 45 (95.70) | 31 (70.50) | – | |
| Female | 15 (16.50) | 2 (4.30) | 13 (29.50) | – | |
| Race | .001 | ||||
| Caucasian | 79 (86.80) | 46 (97.90) | 33 (75.00) | – | |
| African-American | 12 (13.20) | 1 (2.1) | 11 (25.00) | – | |
| Age (years) | 8.69 (3.41) | 8.26 (4.19) | 9.23 (2.30) | .216 | −0.29 |
| Illness duration (years) | 1.77 (1.98) | 2.16 (1.68) | 1.38 (2.18) | .053 | 0.40 |
| Treatment | .001 | ||||
| No active treatment | 8 (8.80) | 5 (10.60) | 3 (6.80) | – | |
| Medication only | 36 (39.60) | 11 (23.40) | 25 (56.80) | – | |
| Dietary restrictions only | 15 (16.50) | 14 (29.80) | 1 (2.30) | – | |
| Both medication and dietary restrictions | 32 (35.20) | 17 (36.20) | 15 (34.10) | – | |
| PedsQL: Generic | |||||
| Youth Self-Report | |||||
| Physical HRQoL | 83.55 (14.02) | 86.69 (10.51) | 79.26 (16.44) | .053 | 0.54 |
| Psychosocial HRQoL | 74.25 (17.39) | 79.93 (15.30) | 66.18 (16.19) | .002 | 0.87 |
| PedsQL: Generic | |||||
| Caregiver Proxy | |||||
| Physical HRQoL | 80.62 (17.17) | 82.14 (17.57) | 79.45 (16.88) | .384 | 0.16 |
| Psychosocial HRQoL | 74.25 (17.90) | 78.24 (16.37) | 69.95 (18.51) | .030 | 0.47 |
| PedsQL: EoE Symptoms | |||||
| Youth Self-Report | |||||
| Epigastric pain | 59.46 (25.07) | 66.25 (19.91) | 51.47 (28.60) | .084 | 0.60 |
| Reflux | 67.57 (26.26) | 73.75 (28.65) | 60.29 (21.76) | .122 | 0.53 |
| Dysphagia | 68.92 (26.04) | 75.31 (19.18) | 61.40 (31.27) | .106 | 0.54 |
| Nausea/vomiting | 75.23 (22.26) | 82.08 (19.73) | 67.16 (22.91) | .040 | 0.70 |
| PedsQL: EoE Symptoms | |||||
| Caregiver Proxy Report | |||||
| Epigastric pain | 55.69 (28.55) | 60.58 (26.21) | 50.57 (30.26) | .096 | 0.35 |
| Reflux | 70.56 (29.17) | 73.37 (27.08) | 67.61 (31.24) | .352 | 0.20 |
| Dysphagia | 69.19 (25.24) | 72.42 (22.58) | 65.82 (27.62) | .217 | 0.26 |
| Nausea/vomiting | 73.52 (26.25) | 75.18 (26.03) | 71.78 (26.67) | .542 | 0.13 |
Note. χ2 tests were used to examine site differences in categorical variables, while t-tests were completed for continuously measured variables. Effect sizes indicate site differences on continuous variables as Cohen’s d. HRQoL = health-related quality of life.
Study 1
Youth with EoE in Study 1 was primarily male and Caucasian. Participants had a mean age of 8.26 years with a mean illness duration of 2.16 years. The proportion of Caucasian and African American children was similar to samples reported elsewhere (DeBrosse et al., 2011; Hommel et al., 2012; Noel and Putnam, 2004). Treatment method was fairly evenly distributed between medication only, dietary restrictions only, and a combination of medication and dietary restrictions for youth with EoE in Study 1.
Study 2
Youth with EoE in Study 2 was primarily Caucasian and male with an average age of 9.23 years and mean duration of illness of 1.38 years. The proportion of Caucasian and African-American children matched the racial composition of the U.S. Deep South (United States Census Bureau, 2015), with a greater proportion of African-American children compared with samples reported elsewhere (DeBrosse et al., 2011; Hommel et al., 2012; Noel and Putnam, 2004). Participants were primarily treated with either medication only or a combination of medication and dietary restrictions.
Relationships Among Clinical Symptom Severity and HRQoL
Self-Reports of Youth With EoE
Pearson correlations among self-reported clinical symptoms in youth with EoE and their respective HRQoL domains indicated that participant age (r = .299, p < .05) and race (r = −.271, p < .05) were significantly correlated with psychosocial HRQoL, while no demographics were correlated with physical HRQoL (Table II). However, the severity of epigastric pain (r = .658, p < .01), reflux (r = .336, p < .05), and nausea/vomiting (r = .531, p < .01) were significantly correlated with physical HRQoL. With regard to psychosocial HRQoL, severity of epigastric pain (r = .595, p < .01), reflux (r = .338, p < .05), and nausea/vomiting (r = .452, p < .01) were each significantly related to psychosocial HRQoL. Specifically, experiencing more problems with each of the symptoms (lower PedsQL EoE Module score) was associated with poorer physical and psychosocial HRQoL as shown in Table II.
Table II.
Correlation Matrix, All Variables of Interest
| Variable | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1. | Age | – | −.109 | .005 | −.043 | .130 | .299* | .383* | .410* | .186 | −.297 |
| 2. | Illness duration | −.109 | – | .146 | −.150 | .119 | .168 | .094 | −.116 | −.068 | .142 |
| 3. | Gendera | .005 | .146 | – | −.177 | .073 | .091 | .271 | .115 | .137 | .454** |
| 4. | Raceb | −.043 | −.150 | −.177 | – | −.192 | −.271* | −.133 | −.068 | −.002 | −.268 |
| 5. | Physical HRQoL | –.025 | .141 | .082 | −.206* | – | .689** | .658** | .336* | .251 | .531** |
| 6. | Psychosocial HRQoL | −.129 | .174 | .097 | −.269* | .612** | – | .595** | .338* | .290 | .452** |
| 7. | PedsQL Epigastric Pain | .069 | .069 | .195 | −.035 | .355** | .272** | – | .453** | .536** | .535** |
| 8. | PedsQL Reflux | −.221* | .147 | .137 | .145 | .048 | .170 | .516** | – | .389* | .429** |
| 9. | PedsQL Dysphagia | −.013 | .163 | −.014 | −.015 | .173 | .287** | .466** | .395** | – | .472** |
| 10. | PedsQL Nausea/Vomiting | −.089 | .146 | .098 | −.113 | .160 | .283** | .452** | .523** | .445** | – |
Note. Data above the diagonal reflect correlations with youth self-reported HRQoL and symptom presentation. Data below the diagonal reflect correlations with caregiver-proxy reported HRQoL and symptom presentation. HRQoL = health-related quality of life.
0 = Female, 1 = Male.
1 = White, 2 = Non-white.
p < .05; **p < .01.
Study site was included as a covariate in all linear regression models because of the differences found in physical and psychosocial HRQoL between Site 1 and Site 2 (Table I). As shown in Table III, results revealed that severity of self-reported epigastric pain significantly predicted poorer physical HRQoL (β = .608, p < 0.01) as well as poorer psychosocial HRQoL (β = .486, p < 0.01) in youth with EoE. None of the other clinical symptoms self-reported by youth with EoE were found to significantly predict either physical or psychosocial HRQoL.
Table III.
Multiple Regressions Predicting Youth Self-Reported HRQoL as a Function of Symptoms
| Physical HRQoL |
Psychosocial HRQoL |
|||||||
|---|---|---|---|---|---|---|---|---|
| R2 | B | SE B | β | R2 | B | SE B | β | |
| Variables | .521** | .520** | ||||||
| Sitea | .499 | 3.821 | .018 | 12.461 | 4.449 | .379** | ||
| Epigastric pain | .350 | 0.094 | .608** | 0.326 | 0.110 | .486** | ||
| Reflux | .011 | 0.079 | .021 | 0.016 | 0.092 | .026 | ||
| Dysphagia | −.127 | 0.085 | −.235 | −0.092 | 0.099 | −.147 | ||
| Nausea/vomiting | .208 | 0.103 | .319 | 0.111 | 0.120 | .147 | ||
Coded variable (1 = Site 1, 2 = Site 2). HRQoL = health-related quality of life.
p < 0.05; **p < 0.01.
Caregiver-Proxy Reports
Severity of epigastric pain was significantly associated with poorer physical HRQoL according to caregiver-proxy reports (r = .355, p < .01). Furthermore, caregiver proxy-reported epigastric pain (r = .272, p < .01), dysphagia (r = .287, p < .01), and nausea/vomiting (r = .283, p < .01) were also significantly correlated with poorer psychosocial HRQoL (Table II).
In a series of linear regression models adjusting for study site differences in HRQoL, it was revealed that caregiver-proxy reports of epigastric pain significantly predicted poorer physical HRQoL (β = .414, p < 0.01) above (Table IV) and beyond the other clinical symptoms. None of the other EoE clinical symptoms were significantly predictive of physical HRQoL. Similarly, none of the caregiver proxy-reported EoE clinical symptoms were found to predict psychosocial HRQoL.
Table IV.
Multiple Regressions Predicting Caregiver Proxy-Reported HRQoL as a Function of Symptoms
| Physical HRQoL |
Psychosocial HRQoL |
|||||||
|---|---|---|---|---|---|---|---|---|
| R2 | B | SE B | β | R2 | B | SE B | β | |
| Variables | .157* | .157* | ||||||
| Sitea | 1.391 | 3.495 | .041 | 6.340 | 3.649 | .177 | ||
| Epigastric pain | 0.250 | 0.076 | .414** | 0.076 | 0.080 | .121 | ||
| Reflux | −0.129 | 0.075 | −.219 | −0.041 | 0.078 | −.066 | ||
| Dysphagia | 0.020 | 0.081 | .029 | 0.109 | 0.085 | .152 | ||
| Nausea/vomiting | 0.047 | 0.082 | .072 | 0.126 | 0.086 | .184 | ||
Coded variable (1 = Site 1, 2 = Site 2).
p < 0.05; **p < 0.01.
HRQoL = health-related quality of life.
Discussion
The goal of this study was to characterize the associations among clinical symptom presentation and HRQoL in youth with EoE. This study has several notable strengths including the incorporation of updated consensus recommendations for the diagnosis of EoE (Liacouras et al., 2011), the large sample size of this rare disease because of the inclusion of two geographically distinct samples of youth with EoE, and the assessment of disease-specific clinical symptoms to better document the impact of EoE on HRQoL. Previous studies have indicated that youth with EoE experience poorer HRQoL compared with healthy peers (Cortina et al., 2010; Ingerski et al., 2010). The HRQoL of youth with EoE in the current study appeared to be modestly better than that reported by other pediatric EoE samples in the literature; however, HRQoL was still appreciably worse than what has been reported by healthy controls in previous studies on this topic (Cortina et al., 2010; Ingerski et al., 2010).
There are several limitations that must be considered when interpreting these findings. First, Study 1 and Study 2 were each conducted as unique, individual research studies at different time points. Therefore, differences were observed in study procedures and data collected by site. Furthermore, each study incorporated a cross-sectional study design. Although we used statistical models to predict the HRQoL of youth with EoE, we cannot rule out the bidirectional or co-occurring nature of clinical symptoms and HRQoL. Additionally, common method variance attributed to the use of comparable study measures may have contributed to the associations between EoE symptoms measured by the PedsQL EoE Module and HRQoL measured by the PedsQL Inventory, Generic Core Scales.
Second, given the low base-rate of pediatric EoE in the United States, children as young as 2 years (Study 1) and 4 years (Study 2) in addition to their caregivers were recruited to ensure adequate sample sizes across studies. Youth with EoE <8 years of age did not provide self-report information regarding their experiences of EoE clinical symptoms, given that the symptom scales of the PedsQL Eosinophilic Esophagitis Module have not been validated for use in children <8 years of age. As a result, the clinical symptoms of the youngest children in Study 1 and Study 2 were not fully realized according to self-report.
Third, all study participants were recruited during clinic visits, and the clinics at Site 1 and Site 2 may operate somewhat differently for a variety of reasons such as health-care providers’ preferences. The patients also appear to highlight slightly different symptoms and express differing levels of HRQoL at the two sites. As such, it is possible that unmeasured site differences between these two pediatric hospitals may have affected our results. Additionally, information pertaining to the number of eligible patients, who could have participated, and caregiver demographics was not gathered. Therefore, conclusions based on caregiver data may have limited generalizability. Despite these limitations, we have provided an initial characterization of the associations between specific clinical symptoms and HRQoL in youth with EoE. Further, there is now preliminary evidence for the role of epigastric pain in overall patient functioning in youth with EoE.
Gastrointestinal distress in the form of epigastric pain, reflux, nausea/vomiting, and dysphagia each has the potential to impair the ability of youth with EoE to complete daily physical tasks (e.g., walking; personal hygiene tasks; playing sports) as well as their psychological and social functioning (e.g., feeling sad, having trouble getting along with other children). However, empirical support attesting to the negative impact of EoE clinical symptoms on HRQoL in youth populations is lacking. Whether certain clinical symptoms are more predictive of poorer HRQoL for youth with EoE compared with others remains largely unexplored. This study is the first of its kind to examine self-reports and caregiver-proxy reports of EoE clinical symptoms in relation to HRQoL.
Consistent with our hypotheses, youth self-report results suggest that epigastric pain represents an important clinical symptom that must be considered when treating youth with EoE. Further evidence supporting the salience of epigastric pain as a clinical symptom with HRQoL implications in youth with EoE comes from their caregivers, such that epigastric pain was again found to be the only significant predictor of poor physical HRQoL per caregiver proxy-reports. Contrary to our hypotheses, symptoms of reflux, dysphagia, and nausea/vomiting were not significantly predictive of physical or psychosocial HRQoL according to either youth self-report or caregiver proxy-report in adjusted multiple regression models. While epigastric pain was significantly predictive of both physical and psychosocial HRQoL according to youth self-report, epigastric pain was only predictive of physical HRQoL by caregiver proxy report. It is possible that this discrepancy is a result of caregiver’s under recognition or under appreciation of the child’s pain experience, and the impact pain has on the day-to-day psychosocial functioning of their youth.
Youth with EoE consistently identified their epigastric pain experiences to be related to the ability to complete age-appropriate daily physical activities. The experience of epigastric pain appears to have a broad impact, given that it was also associated with reported difficulty of youth with EoE to maintain engagement in school, interact with peers, and regulate emotions. There are multiple potential ways in which the epigastric pain experiences (i.e., frequency; severity; duration; qualitative description) of youth with EoE could negatively impact their physical and psychosocial HRQoL. For instance, experiences of epigastric pain may impair sleep quality and lead to depressed and/or anxious mood as previously outlined by Lynch and colleagues (Lynch et al., 2015).
In conclusion, it has been established that pediatric patients and their families coping with chronic illnesses are at risk for poor HRQoL across the developmental continuum (DeBrosse et al., 2011; Klinnert et al., 2014); it appears that youth with EoE is no exception. Furthermore, our findings now suggest that EoE clinical symptoms, especially epigastric pain experience, may be detrimental to HRQoL. Recognition and improved medical management of all symptoms, especially epigastric pain, in youth with EoE have the potential to improve their day-to-day functioning. Importantly, pain is a modifiable clinical symptom that has previously been shown in pediatric populations to respond favorably to nonpharmacologic treatment modalities such as cognitive-behavioral therapy (Palermo, Eccleston, Lewandowski, Williams, & Morley, 2010). Whether treatments that mitigate epigastric pain translate into improved HRQoL for youth with EoE is worthy of consideration and future research.
Funding
This work has been generously supported by NIH (R01 DK076893-03S1); the Campaign Urging Research for Eosinophilic Disease (CURED); the Buckeye Foundation; and the Food Allergy Research and Education (FARE).
Conflicts of interest: None declared.
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