Polymorphic markers of several immune regulatory genes modulate the susceptibility for eczema and related phenotypes in children.

Background: Eczema is associated with multiple genes regulating epidermal barrier functions and immunological pathways. However, their epistatic interactions are not well studied. This cross-sectional study investigated the relationship between childhood eczema phenotypes and single-nucleotide polymorphisms (SNPs) of immune regulatory genes. Methods: One thousand three hundred and twenty-nine Chinese eczematous children and 1,179 non-allergic controls were recruited. Nine SNPs of immune regulatory genes signal transducer and activator of transcription 3 (STAT3), interleukin-10 (IL10), transforming growth factor-beta 1 (TGFB1), and IL-6 receptor (IL6R) were genotyped by TaqMan genotyping assays. Logistic regression was used to analyze the associations between SNPs and eczema phenotypes. Generalized multifactor dimensionality reduction (GMDR) was used to examine epistatic interactions among these SNPs as well as those reported by our group [filaggrin (FLG) and 11q13] for eczema phenotypes. Results: TGFB1_rs1800469 was found to be associated with eczema [odds ratio (OR), 0.82; 95% confidence interval (CI): 0.73-0.92; P=0.001], atopic eczema (OR, 0.83; 95% CI: 0.72-0.95; P=0.009) and allergic rhinitis (OR, 0.84; 95% CI: 0.74-0.95; P=0.005). We also found a trend between IL10_rs1800872 and increased total immunoglobulin E (IgE) levels (P=0.009). Epistatic interaction among IL10_rs3021094, TGFB1_rs1800469, IL6R_rs2228145, and STAT3_rs4796793 were found for total IgE [testing accuracy (TA), 0.551; cross-validation consistency (CVC), 10; P=0.014]. Mean log-transformed total IgE (logIgE) levels in high-risk cases, low-risk cases, high-risk controls, and low-risk controls were 2.75, 2.60, 1.90, and 1.81 respectively (P=0.019 for trend). Conclusions: Functional TGFB1 polymorphism is associated with both eczema and allergic rhinitis, suggesting the role of TGF-ß1 in allergy susceptibility. IL10 may be associated with increased total IgE levels. Interaction among immune regulatory genes modulates total IgE levels.

A novel infant microbiome formula (SIM03) improved eczema severity and quality of life in preschool children.

Altered gut microbiome composition has been reported in children with eczema and interventions that restore beneficial bacteria in the gut may improve eczema. This open-label pilot study aimed to investigate the efficacy of a novel infant microbiome formula (SIM03) in young children with eczema. Pre-school Chinese children aged 1-5 years old with eczema received SIM03 twice daily for three months. The novelty of SIM03 consists of both the use of a patented microencapsulation technology to protect the viability of unique Bifidobacterium bifidum and Bifidobacterium breve strains identified through big data analysis of large metagenomic datasets of young Chinese children. Paired stool samples at baseline and following SIM03 were analyzed by metagenomics sequencing. Generalized estimating equation was used to analyze changes in eczema severity, skin biophysical parameters, quality of life and stool microbiome. Twenty children aged 3.0 ± 1.6 years (10 with severe eczema) were recruited. Treatment compliance was ≥ 98%. SCORing Atopic Dermatitis score decreased significantly at two months (P = 0.008) and three months (P < 0.001), while quality of life improved significantly at 1, 2, and 3 months. The relative abundance of B. breve and microbial pathways on acetate and acetyl-CoA synthesis were enriched in stool samples at one month (P = 0.0014). Children who demonstrated increased B. bifidum after SIM03 showed improvement in sleep loss (P = 0.045). Relative abundance of B. breve correlated inversely with eczema extent (P = 0.023) and intensity (P = 0.019) only among patients with increased B. breve at Month 3. No serious adverse event was observed. In conclusion, SIM03 is well tolerated. This patented microbiome formula improves disease severity and quality of life in young eczematous children by enhancing the delivery of B. bifidum and B. breve in the gut. SIM03 is a potential treatment option for childhood eczema.

Real-World Sensitization and Tolerance Pattern to Seafood in Fish-Allergic Individuals.

BACKGROUND: Seafood is a common cause of food allergy and anaphylaxis, but there are limited published real-world data describing the clinical presentation of fish and shellfish allergies. OBJECTIVE: This study aimed to examine the clinical characteristics, immunological profile, and tolerance pattern to fish, crustaceans, and mollusks in fish-allergic individuals. METHODS: Patients presenting with IgE-mediated fish allergy between 2016 and 2021 were recruited. A comprehensive sensitization profile including specific IgE and skin prick test to various fish and shellfish species and a detailed clinical history including individuals' recent seafood consumption were evaluated. RESULTS: A total of 249 fish-allergic individuals (aged 4.2 ± 5.8 years) were recruited from 6 allergy clinics in Hong Kong, and they had experienced their fish-allergic reaction 2.2 ± 3.4 years before enrollment. Seventy-five subjects (30%) reacted to either grass carp, salmon, grouper, or cod in oral food challenges. We identified an IgE sensitization gradient that corresponded to the level of ß-parvalbumin in fish. In total, 40% of fish-allergic individuals reported tolerance to 1 or more types of fish, more commonly to fish with a lower ß-parvalbumin level such as tuna and salmon, compared with ß-parvalbumin-rich fish such as catfish and grass carp. Despite fish and shellfish cosensitization, 41% of individuals reported tolerance to crustaceans, mollusks, or both, whereas shellfish avoidance occurred in half of the fish-allergic individuals, of whom 33% lacked shellfish sensitization. CONCLUSIONS: Fish allergy commonly presents in early childhood. A considerable proportion of fish-allergic patients are selectively tolerant to certain fish, typically those with lower levels of ß-parvalbumin. There is an unmet need to promote precision medicine for seafood allergies.

Development and validation of assessment tools for food allergy-related knowledge and management confidence.

Background: Given the life-threatening nature of food allergy (FA), it is important to assess the level of knowledge among families with food-allergic patients and their ability to cope with anaphylaxis. This study constructed a FA knowledge questionnaire (FAKQ) and confidence in FA management skills (CIFAMS) questionnaire to assess understanding and attitudes toward FA management in food-allergic families. Methods: Items from literature review and expert panel showing ≥80% content validity index and semantic equivalence were selected for translation into Chinese. These questionnaires underwent feasibility pilot testing followed by cross-sectional validation to assess their psychometric properties of internal consistency, test-retest reliability, and construct validity with a FA quality-of-life questionnaire and discriminant validity. Exploratory factor analysis was performed to confirm their factor structure. Results: A total of 155 subjects (104 patients and 51 parents) completed a 20-item FAKQ and 10-item CIFAMS. Both tools showed acceptable internal consistency in baseline and retest groups. FAKQ and CIFAMS correlated for all subjects (P = .002) and for adults (P = .002), and similarly between CIFAMS and parent-reported FA independent measure (P = .005). Total score of FAKQ was sensitive to within-group differences of patients hospitalized for FA (P < .001). FAKQ and CIFAMS items were factored into 4 and 2 domains, respectively. Subjects scored the lowest on FAKQ items about signs of allergic reaction and CIFAMS items on epinephrine autoinjector use. Conclusion: FAKQ and CIFAMS developed by our group are valid and reliable in assessing knowledge and confidence in FA management in patients and parents. These tools are crucial for formulating education programs and advocacy campaigns for FA.

Human milk oligosaccharides in Chinese lactating mothers and relationship with allergy development in offspring.

BACKGROUND: The health benefits of breastfeeding are partly contributed by human milk oligosaccharides (HMOs), but there is limited data on breast milk (BM) HMO composition in Chinese. OBJECTIVE: This study investigated the association between early-life HMO intake and allergy occurrence in Chinese children. METHODS: 103 healthy Chinese pregnant women regardless of allergy history were recruited into this birth cohort. Their babies were followed until 24 months old. Concentrations of 2'-fucosyllactose (2'-FL), lacto-N-neotetraose (LNnT), -sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) in BM collected at 1-month postpartum were measured by liquid chromatography-mass spectrometry. The associations between these HMOs and allergy occurrence by 24 months were analyzed by multivariate regression analyses. RESULTS: Twenty-nine percent and 19% of participants had eczema at 12 and 24 months old respectively. Eighty BM samples were analyzed, with 2'-FL being the most abundant HMO (median 1447 ppm, interquartile range [IQR] 291-1906 ppm), and median (IQR) levels of LNnT, 6'-SL and 3'-SL in ppm were 738 (580-950), 20.5 (12.7-38.8) and 23.0 (17.8-27.6) respectively. Participants with eczema by 24 months consumed BM with higher 2'-FL concentration at 1-month (P = 0.008), and also lower 6'-SL concentration in exclusively breastfed infants (P = 0.012) but higher 6'-SL concentration for those with mixed feeding at 1 month (P = 0.043). Food allergic children at 12 months consumed BM with higher 2'-FL concentrations at 1 month (P = 0.048). CONCLUSIONS: BM 2'-FL concentration is higher in children who develops eczema by 24 months and food allergy during infancy. The relationship for 6'-SL is divergent depending on mode of feeding in infants.

Validation of the food allergy quality of life questionnaire series in Chinese families with food-allergic children.

BACKGROUND: Anxiety from accidental exposure and vigilant dietary monitoring impair the quality of life (QoL) of food-allergic patients. A comprehensive food allergy-specific questionnaire allows patients to accurately report their QoL. This study validated the Food Allergy Quality of Life Questionnaire (FAQLQ) series and assessed the QoL of Chinese food-allergic patients and their caregivers. METHODS: FAQLQ series developed by EuroPrevall consists of four separate questionnaires for parents, children, adolescents and adults. All questionnaires were translated into traditional Chinese by standard forward and backward methods. A cross-sectional study was conducted on food-allergic patients and children's parents using an age-appropriate questionnaire. The performance indices of FAQLQ and their correlation with independent measures of food allergy were analyzed, and factor analysis was performed to confirm the factor structure of FAQLQ questionnaires. RESULTS: Cross-sectional validation was performed on 214 participants, with 40 reassessed for test-retest reliability. Overall scores for the FAQLQ series had good internal consistency with Cronbach's α ≥.90. Good construct validity was demonstrated by correlations between FAQLQ-Parent Form, FAQLQ-Child Form, FAQLQ-Teenager Form, FAQLQ-Adult Form and Food Allergy Independent Measure (FAIM) scores, except in 0- to 3-year-old children. Test-retest analyses revealed a significant correlation between total FAQLQ score, parent-reported FAIM and food anxiety domain in 4-6 years, and between total score and FAIM in 7-12 years. Exploratory factor analysis categorized items in the FAQLQ series into three to four domains. CONCLUSION: FAQLQ series provide a valid and reliable measure for QoL in Chinese food-allergic patients and caregivers, except for parents of children aged 0-3 years. Items for all FAQLQ questionnaires are categorized into different functional domains in our population.

Effect of pine-tar bath on disease severity in moderate-to-severe childhood eczema: an investigator-blinded, crossover, randomized clinical trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease associated with pruritus and sleep loss. Pine-tar has long been used for various chronic skin conditions in which its polycyclic aromatic hydrocarbon (PAH) component is anti-inflammatory and its resin acids antiseptic. The null hypothesis of this trial is that there is no difference in clinical efficacy between a pine-tar product and its vehicle for AD. METHODS: A 3-month, investigator-blinded, crossover, randomized control trial (RCT) was conducted in which each patient was assigned to bathing with pine-tar bath oil for one month and vehicle bath oil for another, with a washout period of 1-month in-between. Acceptability and efficacy of the bath products were measured. Disease severity scores (scoring atopic dermatitis (SCORAD) and patient-oriented eczema measure (POEM), quality of life questionnaires, noninvasive skin biophysiological measurements, blood IgE levels, and Staphylococcus aureus (SA) colonization status were assessed before and following bathing. RESULTS: Significant improvements were found in total SCORAD (p = .030), POEM (p = .004), SA colonization status (p = .002), and log-transformed IgE level (p = .009) among patients who bathed with pine-tar in the overall RCT study using intention-to-treat analysis. For per protocol analysis, significant improvements were found in total SCORAD (p = .024), objective SCORAD (p = .011), extent (p = .014), intensity (p = .032), pruritus (p = .047), POEM (p = .044), SA colonization status (p = .035), and log-transformed IgE level (p = .028). Acceptability to both bath-oils was good, and no product-related serious adverse events were recorded. CONCLUSIONS: Bathing with pine-tar is an efficacious and recommendable adjuvant practice for AD patients. Disease improvement is associated with reduction of SA and IgE.

Effects of a self-efficacy theory-based parental education program on eczema control and parental outcomes.

BACKGROUND: Eczema is the most common childhood skin problem worldwide. Education that enhances parental self-efficacy in carrying out appropriate eczema management is crucial to controlling eczema symptoms of their children. However, the lack of such a structured education program hinders everyday lives of eczematous children and their families. This study evaluated the effects of a self-efficacy theory-based parental eczema education program in controlling eczema of Chinese children at three months after commencement of intervention. METHODS: An assessor-blind, 2-arm, randomized controlled trial was conducted at an outpatient clinic of a regional hospital. One hundred and thirty-six Chinese children aged 3 months to 12 years with physician-diagnosed eczema, and their parents were recruited. The intervention was underpinned by the Social Cognitive Theory. Children's disease severity, parental self-efficacy, treatment adherence, and quality of life of family members were assessed by validated tools. Generalized estimating equation model was employed to compare differential change in each outcome across time between different groups. RESULTS: Eczema severity of children and parental self-efficacy in the intervention group were found to show greater improvement at 3-month follow-up with regression coefficient (ß) -16.98 (95% CI, -21.04 to -12.92; P < .001) and ß 29.39 (95% CI, 22.64-36.14; P < .001), respectively. Nearly all parents (97%) receiving the intervention rated this program as useful and helpful. CONCLUSIONS: This program is effective in enhancing parents' self-efficacy in managing their children's eczema and improving their adherence to eczema treatment and quality of life.

Translation and Validation of a Chinese Version of the Parental Self-Efficacy with Eczema Care Index.

BACKGROUND: Parental self-efficacy has been found to be a critical determinant of the efficacy of interventions intended to enhance the parental management of childhood eczema. OBJECTIVES: The psychometric properties of a translated Chinese version of the Parental Self-Efficacy with Eczema Care Index (C-PASECI) were examined. METHODS: The PASECI was translated in a 2-stage process involving both forward and backward translation. Subsequently, the psychometric properties of the C-PASECI were examined in a cohort of 147 Chinese parents or caregivers of children with eczema. Specifically, the internal consistency, 2-day test-retest reliability and construct validity were assessed. RESULTS: The C-PASECI received a Cronbach's αof 0.97, and the intraclass correlation coefficients of each item ranged from 0.93 to 0.99. Negative correlations were observed among the C-PASECI, Children's Dermatology Life Quality Index and Scoring Atopic Dermatitis Scale scores, indicating the acceptable convergent validity of the C-PASECI. The moderate correlation observed between the C-PASECI and General Self-Efficacy Scale (Pearson's r = 0.53, p < 0.001) reflected the acceptable concurrent validity of the C-PASECI. The results of confirmatory factor analysis supported the factorial validity of the C-PASECI. CONCLUSION: The C-PASECI appears to be a reliable and valid measure of parental self-efficacy in Chinese parents or caregivers of children with eczema.

Measuring the quality of life of the families of children with eczema in Hong Kong.

BACKGROUND: Eczema is the most common skin problem among children in Hong Kong. Previous studies have highlighted that the quality of life of the families of children with eczema influences the effects of eczema interventions. However, the Chinese version of the Family Dermatology Life Quality Index (C-FDLQI), a tool for measuring the quality of life of the families of children with eczema, has not yet been validated. OBJECTIVE: This study examined the psychometric properties of the C-FDLQI among parents and caregivers of children with eczema in Hong Kong. METHODS: This study evaluated the internal consistency, test-retest reliability and structural validity of the C-FDLQI and its convergent validity by examining its correlations with the SCORing Atopic Dermatitis (SCORAD) and the Cantonese version of the Children's Dermatology Life Quality Index (C-CDLQI) among 147 Chinese parents/caregivers of children with varying degrees of eczema. RESULTS: Based on the ratings by an expert panel, both the content validity index and semantic equivalence of the C-FDLQI were satisfactory (>0.90). The C-FDLQI showed high internal consistency, with a Cronbach α of 0.95. Its test-retest reliability was good, with weighted kappa values for the items ranging from 0.70 to 1.00. The total scores of the C-FDLQI showed positive correlations with those of the C-CDLQI (Pearson r = 0.75, p < 0.001) and SCORAD (Pearson r = 0.62, p < 0.001). Known-group comparisons of the C-FDLQI between the parents/caregivers of children with mild eczema and those of children with moderate to severe eczema showed a significant difference (t = -7.343, p < 0.001), indicating that the C-FDLQI had acceptable convergent validity. Confirmatory factor analysis supported the one-factor structure of the C-FDLQI. CONCLUSION: The results suggest that the C-FDLQI is a reliable and valid tool for evaluating the quality of life of parents or caregivers of children with eczema in Hong Kong.

Characterization of ocular and nasopharyngeal microbiome in allergic rhinoconjunctivitis.

BACKGROUND: Allergic rhinoconjunctivitis (ARC) is a prevalent allergic condition in the pediatric population. Microbial dysbiosis has increasingly been recognized to influence on host immunity and allergic diseases. However, the microbial profile of ARC has not been characterized. This cross-sectional study aims to evaluate the changes in nasal and ocular surface microbiome of children with ARC. METHODS: Ocular and nasopharyngeal swabs were collected from controls and pediatric ARC cases for 16S rRNA amplicon sequencing. The bacterial community profile was analyzed. The correlation of the microbial diversity with the ARC-related clinical scores was studied. RESULTS: A total of 23 patients with ARC and 17 healthy controls were recruited;30 were ocular samples (15 controls vs 15 ARC), while 40 were nasal samples (17controls vs 23 ARC) The alpha diversity of nasopharyngeal microbiome was significantly higher in ARC patients than healthy controls (P < 0.01), but not for ocular microbiome. The clinical scores in all subjects were negatively correlated with the Shannon diversity for ocular (P = 0.014) and positively correlated with nasopharyngeal (P = 0.010) microbiome. While the ocular microbiome remained significantly distinct from nasopharyngeal microbiome in terms of both alpha and beta diversity in both healthy subjects and ARC patients, significant differences of relative abundance of certain phyla (Bacteroidetes, Cyanobacteria, and Deinococcus-Thermus) and genera (Dolosigranulum and Moraxella) between nasal and ocular surfaces were only detected in healthy controls, but not in the ARC subjects, suggesting the microbial composition at both body sites becoming more similar at disease state. CONCLUSION: This study reported (a) a higher alpha diversity in ocular than nasopharyngeal microbiome in both ARC patients and controls, and (b) nasopharyngeal microbiome became more diverse in ARC patients than in controls. Our results suggested an interaction of the microbiome between ocular and nasal compartments in patients with ARC.

Do we need another symptom score for childhood eczema?

AIM: It is important to objectively measure the severity of atopic dermatitis (AD). This study aims to investigate correlations among various clinical severity scores and determine how a severity score based on symptoms alone performs. METHODS: A Chinese-translated symptom score based on Patient-Oriented Eczema Measure (POEM, a short-term subjective-symptom score), Scoring Atopic Dermatitis (SCORAD, a short-term subjective-symptom and objective-sign score), Nottingham Eczema Severity Score (NESS, a long-term subjective symptoms + objective signs), Children Dermatology Life Quality Index (CDLQI, a short-term subjective-symptom score), skin hydration (SH) and transepidermal water loss (TEWL) were compared and Spearman's rho correlations was evaluated. RESULTS: 126 sets of clinical scores from eczema patients (mean age: 11.4 ± 5.6 years; 34.7% male) were evaluated. The modified-POEM, objective SCORAD, NESS and CDLQI correlated well with each other. All round, best correlations were obtained with POEM: Objective SCORAD (rho = 0.7, p < 0.001), NESS (rho = 0.69, p < 0.001), SCORAD symptom of itch (rho = 0.75, p < 0.01), SCORAD symptom of sleep loss (rho = 0.64, p < 0.01), CDLQI (rho = 0.77, p < 0.001) and SH (rho= -0.043, p < 0.05). Linear stepwise-backward regression demonstrated that POEM was independently associated with CDLQI parameters of pruritus (B: 2.16; p = 0.018), activities (B: 1.80; p = 0.009), sleep disturbance (B: 2.78; p < 0.001) and NESS parameter of sleep disturbance (B: 1.02; p = 0.003). CONCLUSION: Clinical scores for acute, chronic, subjective symptoms and objective signs correlated well with each other. The symptom measures by modified POEM is easy to perform by parents or patients and correlated better with most other clinical scores, making it an all-round ideal symptom-based severity score for research.