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 of the early-life gut microbiome and associations with eczema in a prospective Chinese cohort.

IMPORTANCE: Eczema is a major allergic disease in children, which is particularly prevalent in Chinese children during their first year of life. In this study, we showed that alterations in the infant gut microbiota precede the development of eczema in a prospective Chinese cohort. In particular, we discovered enrichments of the genera Clostridium sensu stricto 1 and Finegoldia in the cases at 3 and 1 month of age, respectively, which may represent potential targets for intervention to prevent eczema. Besides, we identified a depletion of Bacteroides from 1 to 6 months of age and an enrichment of Clostridium sensu stricto 1 at 3 months in the eczema cases, patterns also observed in C-section-born infants within the same time frames, providing first evidence to support a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema in infancy.

Early-Life Skin Microbial Biomarkers for Eczema Phenotypes in Chinese Toddlers.

Eczema is a common inflammatory skin disorder during infancy. Evidence has shown that skin-microbiome fluctuations may precede eczema development, but their predictive value for eczema phenotypes remains unknown. We aimed to investigate the early-life evolution of the skin microbiome and its temporal associations with different pairs of eczema phenotypes (transient versus persistent, atopic versus non-atopic) in Chinese children. We followed 119 term Chinese infants from birth to 24 months old within a Hong Kong birth cohort. The skin microbes at the left antecubital fossa were serially sampled by flocked swabs at 1, 6, and 12 months for bacterial 16S rRNA gene sequencing. The atopic sensitization at 12 months was strongly associated with eczema persisting to 24 months (odds ratio 4.95, 95% confidence interval 1.29-19.01). Compared with those with non-atopic eczema, the children with atopic eczema had reduced alpha diversity at 12 months (p < 0.001) and transiently higher abundance of the genus Janibacter at 6 months (p < 0.001). Our findings suggest that atopic sensitization at 12 months may predict persistent eczema by 24 months, and atopic eczema at 12 months is associated with unique skin microbiome profiles at 6 and 12 months. Non-invasive skin-microbiome profiling may have predictive value for atopic eczema.

High prevalence of sacroiliitis and early structural changes in the sacroiliac joint in children with enthesitis-related arthritis: findings from a tertiary centre in Hong Kong.

BACKGROUND: Epidemiological studies have demonstrated a wide, unexplained disparity in the prevalence of juvenile idiopathic arthritis (JIA) subtypes depending on geographical location, ethnicity and other factors. Enthesitis-related arthritis (ERA) is more prevalent in Southeast Asia. Axial involvement in ERA patients is increasingly recognised to occur early in the disease course. Inflammation in the sacroiliac joint (SIJ) observed on MRI seems highly predictive of subsequent structural radiographic progression. The resulting structural damage can have significant impacts on both functional status and spinal mobility. This study aimed to evaluate the clinical characteristics of ERA in a tertiary centre in Hong Kong. The primary objective of the study was to provide a comprehensive description of the clinical course and radiological findings of the SIJ among ERA patients. METHOD: Paediatric patients diagnosed with JIA attending the paediatric rheumatology clinic from January 1990 to December 2020 were recruited from our registry based at the Prince of Wales Hospital. RESULTS: In our cohort, 101 children were included. The median age of diagnosis was 11 years, interquartile range (IQR) 8-15 years. The median follow-up duration was 7 years (IQR 2-11.5 years). ERA was the most prevalent subtype (40%), followed by oligoarticular JIA (17%). Axial involvement was frequently reported in our cohort of ERA patients. 78% demonstrated radiological evidence of sacroiliitis. Among those, 81% had bilateral involvement. The median duration from disease onset to confirmation of radiological sacroiliitis was 17 months (IQR 4-62 months). Among the ERA patients, 73% had structural changes of the SIJ. Alarmingly, 70% of these patients had already developed radiological structural changes when sacroiliitis was first detected on imaging (IQR 0-12 months). Erosion was the most common finding (73%), followed by sclerosis (63%), joint space narrowing (23%), ankylosis (7%) and fatty change (3%). The duration from symptom onset to diagnosis was significantly longer in ERA patients with SIJ structural changes (9 vs 2 months, p = 0.009), comparing with those without. CONCLUSION: We found that a high proportion of ERA patients had sacroiliitis and a significant number of them had radiological structural changes during early disease. Our findings illustrate the importance of prompt diagnosis and early treatment in these children.

Immunoglobulin-Induced Aseptic Meningitis in Juvenile Dermatomyositis: A Case Report.

Aseptic meningitis is a known but unusual serious adverse effect of intravenous immunoglobulin (IVIG). It usually resembles infectious meningitis, which makes its diagnosis challenging. In this report, we present the case of a five-and-a-half-year-old Chinese girl with juvenile dermatomyositis (JDM) who presented with signs of meningismus 21 hours after the initiation of IVIG infusion. Her blood work at diagnosis showed neutrophilia and lymphopenia. The cerebrospinal fluid (CSF) analysis demonstrated neutrophilic pleocytosis, hyperproteinorrachia, and normoglycorrhachia. All microbiological tests were negative. The child fully recovered within 72 hours without neurological sequelae. IVIG-induced aseptic meningitis remains a diagnosis of exclusion. Although it is rare, pediatricians should be aware of this complication and avoid unnecessary investigations or treatment.

Prospective study of disease persistence and lung function trajectories of childhood asthma.

BACKGROUND: A proportion of asthmatic children outgrow their disease by adulthood, but there are limited data on predictors for asthma persistence. This prospective study characterized the trajectory of spirometric indices and identified predictors for the persistence of childhood asthma. METHODS: Chinese asthmatic children aged 6-15 years from pediatric allergy clinic underwent annual visits for ≥5 years and until their adulthood. Pre-bronchodilator spirometry and anti-asthma medications were recorded at baseline and then at least annually. Asthma resolution was defined when patients were free from asthma symptoms and use of anti-asthma drugs for ≥2 years. Logistic regression was used to identify predictors for asthma persistence. Generalized estimating equation was used to analyze longitudinal changes in lung function parameters in relation to asthma persistence. RESULTS: 181 asthmatic children aged [mean (SD)] 10.0 (2.7) years were followed for [mean (SD)] 12.5 (2.8) years. One third of them outgrew asthma during follow-up. Female was 3.36 times more likely to have persistent asthma. Inhaled corticosteroid (ICS) treatment ever and frequent asthma exacerbation (AE) predicted asthma persistence with respective odds ratios of 3.19 (95% confidence interval [CI] 1.44-7.09) and 3.05 (95% CI 1.39-6.68). Persistent asthma was inversely associated with baseline forced expiratory volume in 1-second (FEV1 %) with an odds ratio of 0.96 (95% CI 0.93-1.00). Throughout follow-up, patients with persistent asthma had generally lower forced expiratory indices than those with asthma resolution. Children with persistent asthma experienced poorer lung function growth. CONCLUSIONS: Female, ICS ever, and frequent AE predicted persistent asthma. Patients with persistent asthma had lower forced expiratory indices and poorer lung function growth into adulthood.

Identification of predictors for persistence of immediate-type egg allergy in Chinese children.

BACKGROUND: Egg allergy is one of the most common food allergies in childhood with increasing prevalence in Hong Kong. While ample studies were published on its optimal diagnosis, there was limited data on predictors for the natural history of egg allergy in Asian populations. OBJECTIVE: This study aimed to characterize the clinical course and outcome of children with egg allergy and identify its prognostic factors. METHODS: All Chinese children with immediate-type egg allergy being followed since ≥3 years old in allergy clinic of our university-affiliated teaching hospital were reviewed to determine if they outgrew egg allergy at the latest follow-up. The predictive values of clinical and atopic factors for resolution of egg allergy were analyzed on Kaplan-Meier curves, and factors independently associated with persistent egg allergy was analyzed by logistic regression. RESULTS: Seventy-six patients with median (interquartile range) age 8.9 years (6.3-13.0 years) were recruited. They initially presented with egg-allergic reactions at 1.0 years (0.7-1.7 years). Fifty-four children (71%) were able to tolerate egg at a median of 36 months from initial reaction. Patients with concomitant peanut allergy and those with initial reaction at ≥1 year old were more likely to have persistent egg allergy (p = 0.015 and p = 0.027 respectively). Skin prick test wheal ≥6 mm to egg yolk and egg white individually as well as to both egg yolk and egg white were predictors for egg allergy persistence (respective, p < 0.001, p = 0.001, and p = 0.001 by log-rank tests). Logistic regression showed that initial SPT ≥ 6 mm to egg yolk was the only independent predictor for persistent egg allergy (B = 2.59 ± 0.98, p = 0.008). CONCLUSION: Most Chinese children with immediate-type egg allergy can tolerate egg in long run. SPT wheal size to egg, concomitant peanut allergy and initial presentation after infancy may predict egg allergy persistence.

Dealing With Death Taboo: Discussion of Do-Not-Resuscitate Directives With Chinese Patients With Noncancer Life-Limiting Illnesses.

BACKGROUND: Noncancer patients with life-limiting diseases often receive more intensive level of care in their final days of life, with more cardiopulmonary resuscitation performed and less do-not-resuscitate (DNR) orders in place. Nevertheless, death is still often a taboo across Chinese culture, and ethnic disparities could negatively affect DNR directives completion rates. OBJECTIVES: We aim to explore whether Chinese noncancer patients are willing to sign their own DNR directives in a palliative specialist clinic, under a multidisciplinary team approach. DESIGN: Retrospective chart review of all noncancer patients with life-limiting diseases referred to palliative specialist clinic at a tertiary hospital in Hong Kong over a 4-year period. RESULTS: Over the study period, a total of 566 noncancer patients were seen, 119 of them completed their own DNR directives. Patients had a mean age of 74.9. Top 3 diagnoses were chronic renal failure (37%), congestive heart failure (16%), and motor neuron disease (11%). Forty-two percent of patients signed their DNR directives at first clinic attendance. Most Chinese patients (76.5%) invited family caregivers at DNR decision-making, especially for female gender (84.4% vs 69.1%; P = .047) and older (age >75) age group (86.2% vs 66.7%; P = .012). Of the 40 deceased patients, median time from signed directives to death was 5 months. Vast majority (95%) had their DNR directives being honored. CONCLUSION: Health-care workers should be sensitive toward the cultural influence during advance care planning. Role of family for ethnic Chinese remains crucial and professionals should respect this family oriented decision-making.

Supportive & palliative interventions in motor neurone disease: what we know from current literature?

Although there is no cure for motor neurone disease (MND), the advent of supportive interventions including multidisciplinary care (MDC) has improved treatment interventions and enhanced quality of life (QOL) for MND patients and their carers. Our integrative review showed evidence-based MDC, respiratory management and disease-modifying therapy that have improved the outcomes of patients diagnosed with MND. Supportive approaches to nutritional maintenance and optimization of symptomatic treatments, including management of communication and neuropsychiatric issues, improve the QOL for MND patients. Notwithstanding improvement to care and QOL, survival benefit has become evident with the advent of a MDC framework, early treatment with non-invasive ventilation (NIV). In addition, weight maintenance remains critical, as weight loss is associated with more rapid disease progression. The endof- life phase is poorly defined in MND patients and treatment remains challenging, yet effective symptom control through palliative care (PC) is achievable and essential.

End-of-life Characteristics and Palliative Care Provision for Patients With Motor Neuron Disease.

Motor neuron disease (MND) is a neurodegenerative disease and manifested as progressive decline in physical, respiratory, swallowing and communication function, and ultimately death. Traditional model of care was fragmented and did not match with multifacet needs of patients and carers. Furthermore, there could be lack of integrated care at end of life for patients with MND in most lower- and middle-income countries or in places with inadequate palliative care (PC) coverage. In view of this, a special workgroup for patients with MND, which includes neurologist, respiratory physician, rehabilitation specialist, and PC physician was formed in Hong Kong since year 2011. In various disease phase, each specialty team plays a leading role in coordinated care of patients with MND. From July 2011 to June 2017, a total of 52 patients with MND were referred for PC; 41 deceased patients with MND were included into data analysis. Major cause of death remains pneumonia (54.8%) and respiratory failure (40.5%). Most of the patients with MND (66.7%) died in acute ward and neurology units, with only 11.9% dying in PC units and hospices. The PC team plays a major role in advance care planning (ACP), and most patients had their ACP documented at second or third PC clinic visit (93.8%). Patients with MND often have limitations in mobility, swallowing difficulty, respiratory insufficiency requiring ventilator support, and various psychosocial needs. This highlighted the importance of early PC referral.