Clinical features and lymphocyte immunophenotyping analysis in primary immunodeficiency patients with non-transplant lymphoproliferative disorders.

Lymphoproliferative disorders (LPD) comprise a heterogeneous group and are originally classified into the "Disease of immune dysregulation" category. Of 96 Taiwanese patients during 2003-2022, 31 (median 66, range 0.03-675 months) developed LPD, mainly including palpable lymphadenopathy (in 10 patients), intestinal lymphadenopathy associated with refractory inflammatory bowel disease (IBD in 8) and hepatosplenomegaly (in 7) during long-term follow-up (median 144, range 3-252 months). They distributed in the categories of antibody deficiency (2 CVID, 2 TTC37, PIK3CD, PIK3R1 and AICDA each), phagocyte (4 CYBB, 1 STAT1 and 1 IFNRG1), immune dysregulation (2 FOXP3, 2 XIAP and 2 HLH), combined immunodeficiencies (2 IL2RG; CD40L, ZAP70 and unknown each), syndromic features (2 STAT3-LOF, 1 WAS and 1 ATM) and three with anti-IFN-γ autoantibodies. An increased senescent (CD8 + CD57+) and CD21-low, disturbed transitional B (CD38 + IgM++), plasmablast B (CD38++IgM-), memory B (CD19 + CD27+) and TEMRA (CD27-IgD-) components were often observed in cross-sectional immunophenotyping and trended to develop LPD.

Taiwan ocular inflammation society consensus recommendations for the management of juvenile idiopathic arthritis-associated uveitis.

We presented the development of a consensus guideline for managing juvenile idiopathic arthritis-associated uveitis (JIAU) in Taiwan, considering regional differences in manifestation and epidemiology. The Taiwan Ocular Inflammation Society (TOIS) committee formulated this guideline using a modified Delphi approach with two panel meetings. Recommendations were based on a comprehensive evidence-based literature review and expert clinical experiences, and were graded according to the Oxford Centre for Evidence-Based Medicine's "Levels of Evidence" guideline (March 2009). The TOIS consensus guideline consists of 10 recommendations in four categories: screening and diagnosis, treatment, complications, and monitoring, covering a total of 27 items. These recommendations received over 75% agreement from the panelists. Early diagnosis and a coordinated referral system between ophthalmologists and pediatric rheumatologists are crucial to prevent irreversible visual impairment in children with JIAU. However, achieving a balance between disease activity and medication use remains a key challenge in JIAU management, necessitating further clinical studies.

Contribution of genetic variants associated with primary immunodeficiencies to childhood-onset systemic lupus erythematous.

BACKGROUND: A dysregulated immune response is a hallmark of autoimmune disorders. Evidence suggests that systemic autoimmune diseases and primary immunodeficiency disorders (PIDs) may be similar diseases with different clinical phenotypes. OBJECTIVE: This study aimed to investigate the burden of PID-associated genetic variants in patients with childhood-onset systemic lupus erythematosus (cSLE). METHODS: We enrolled 118 cSLE patients regularly followed at Chang Gung Memorial Hospital. Targeted next-generation sequencing identified PID genetic variants in patients versus 1475 unrelated healthy individuals, which were further filtered by allelic frequency and various functional scores. Customized immune assays tested the functions of the identified variants. RESULTS: On filtration, 36 patients (30.5%) harbored rare variants in PID-associated genes predicted to be damaging. One homozygous TREX1 (c.294dupA) mutation and 4 heterozygous variants with possible dominant PID traits, including BCL11B (c.G1040T), NFKB1 (c.T695G), and NFKB2 (c.G1210A, c.G1651A), were discovered. With recessive traits, variants were found across all PID types; one fifth involved phagocyte number or function defects. Predicted pathogenic PID variants were more predominant in those with a family history of lupus, regardless of infection susceptibility. Moreover, mutation loads were greater among cSLE patients than controls despite sex or age at disease onset. While greater mutation loads were observed among cSLE patients with peripubertal disease onset, no significant differences in sex or phenotype were noted among cSLE patients. CONCLUSION: cSLE is mostly not monogenic. Gene-specific analysis and mutation load investigations suggested that rare and predicted damaging variants in PID-related genes can potentially contribute to cSLE susceptibility.

Clinical Features and Genetic Analysis of Taiwanese Primary Immunodeficiency Patients with Prolonged Diarrhea and Monogenetic Inflammatory Bowel Disease.

PURPOSE: Diarrhea lasting longer than 14 days which fails to respond to conventional management is defined as severe and protracted diarrhea and might overlap with inflammatory bowel disease (IBD). METHODS: The prevalence, associated pathogens, and prognosis of severe and protracted diarrhea without IBD (SD) and with monogenetic IBD (mono-IBD) in primary immunodeficiency patients (PID) were investigated in Taiwan. RESULTS: A total of 301 patients were enrolled between 2003 and 2022, with predominantly pediatric-onset PID. Of these, 24 PID patients developed the SD phenotype before prophylactic treatment, including Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG1 (one each), CVID (two), and SCID (one) without identified mutations. The most detectable pathogens were pseudomonas and salmonella (six each), and all patients improved after approximately 2 weeks of antibiotic and/or IVIG treatments. Six (25.0%) mortalities without HSCT implementation were due to respiratory failure from interstitial pneumonia (3 SCID and 1 CGD), intracranial hemorrhage (WAS), and lymphoma (HIGM). In the mono-IBD group, seventeen patients with mutant TTC7A (2), FOXP3 (2), NEMO (2), XIAP (2), LRBA (1), TTC37 (3), IL10RA (1), STAT1 (1), ZAP70 (1), PIK3CD (1), and PIK3R1 (1) genes failed to respond to aggressive treatments. Nine mono-IBD patients with TTC7A (2), FOXP3 (2), NEMO (2), XIAP (2), and LRBA (1) mutations were fatal in the absence of HSCT. The mono-IBD group had a significantly earlier age of diarrhea onset (1.7 vs 33.3 months, p = 0.0056), a longer TPN duration (34.2 vs 7.0 months, p < 0.0001), a shorter follow-up period (41.6 vs 132.6 months, p = 0.007), and a higher mortality rate (58.9 vs 25.0%, p = 0.012) compared with the SD group. CONCLUSION: When compared to those with the SD phenotype, the mono-IBD patients had significant early-onset and poor responses to empiric antibiotics, IVIG, and steroids. Anti-inflammatory biologics and suitable HSCT still have the potential to control or even cure the mono-IBD phenotype.

Effect of national curriculum reform on medical students' preparedness for practice: a prospective cohort study from undergraduate to postgraduate periods.

BACKGROUND: In recent years, a national curriculum reform was implemented in undergraduate medical education in Taiwan to reduce clinical rotation training from 3 years to 2 years. The last generation of the old curriculum and the first generation of the new curriculum both graduated in 2019. This study aimed to compare the learning outcomes of the medical students in these two curriculum groups in terms of preparedness for practice during the transition from undergraduate to postgraduate study. METHODS: This was a 3-year prospective, longitudinal, comparative cohort study between 2017 and 2020. Medical students from both the 7-year and 6-year curriculum groups received biannual questionnaire surveys starting 18 months before graduation and running until 11 months after graduation. The measurement tools were the Preparedness for Hospital Practice Questionnaire (PHPQ) and Copenhagen Burnout Inventory (CBI). Personal demographic information was also collected. Linear mixed models were used to determine the effect of curriculum change on learners' preparedness and burnout levels. RESULTS: A total of 130 medical students from the two cohorts provided 563 measurements during the study period. Compared to their counterparts following the old curriculum, the participants following the new curriculum showed a lower level of preparedness when first entering clinical rotation (p = 0.027) and just after graduating (p = 0.049), especially in the domains of clinical confidence (p = 0.021) and patient management p = 0.015). The multivariate linear mixed model revealed gradual increases in preparedness and burnout in serial measurements in both curriculum groups. Students following the new curriculum, which involved a shortened clinical rotation, showed a slightly lower overall preparedness (p = 0.035) and the same level of burnout (p = 0.692) after adjustment. The factor of year of change did not show a significant effect on either preparedness (p = 0.258) or burnout (p = 0.457). CONCLUSION: Shortened clinical rotation training for medical undergraduates is associated with a decrease in preparedness for practice during the transition from undergraduate to postgraduate study. Clinical confidence and patient management are the main domains affected.

Developing a competency-based framework for resident-as-teacher.

BACKGROUND/PURPOSE: Residents play an important role as teachers of junior colleagues and medical students. Clinical teaching also helps residents in clinical learning. However, the skills required for residents to be competent teachers are rarely described systemically. Beyond the widely adopted six core competencies for postgraduate training by the Accreditation Council for Graduate Medical Education (ACGME), the teaching competencies should be further developed, and the milestones should be clearly defined to serve as better references for resident training programs. METHODS: Twenty members, including five experts from major teaching hospitals across Taiwan and 15 from a public medical center, were invited to a workgroup to collaboratively develop a competency-based framework. The development process was similar to that suggested by the ACGME. The teaching competencies framework were drafted by an experienced physician educator. The draft was sent to each group member, and feedback was collected. Two workgroup meetings were held for consensus formation. The contents of the teaching competencies of residents were confirmed after two rounds of revision. The outline of the framework was also reported at an international meeting in September 2019. RESULTS: Two core competencies, instruction and assessment, with three sub-competencies and 37 milestones, were adopted in the final edition of resident-as-teacher competencies. The sub-competencies were "dissemination of knowledge" and "teaching of procedural skills" for instruction, and "direct observation and feedback" for assessment. CONCLUSION: A competency-based framework for resident-as-teacher was developed. The framework can be applied in combination with other existing competencies for holistic postgraduate training programs.

Clinical Features of Female Taiwanese Carriers with X-linked Chronic Granulomatous Disease from 2004 to 2019.

PURPOSE: Female carriers with X-linked chronic granulomatous disease (XL-CGD) who have < 10% reactive oxygen species (ROS) production due to profound X-chromosome inactivation (XCI or lyonization) are more susceptible to infections. We assessed ROS production in Taiwanese female carriers with XL-CGD to investigate whether the level of ROS correlated to their clinical features of infection, autoimmunity, and autoinflammation. METHODS: Clinical course, ROS production, flavocytochrome b558 (Cyto b558) expression, and genetic analysis in carriers were investigated after identifying their index cases between 2004 and 2019. RESULTS: A total of 19 mothers (median 27 years; range 25-60 years) and three of four girls (range 4-6 years) relative to 22 male index XL-CGD cases from 19 unrelated families were enrolled. Approximately half (8/19, 42%) of the mothers had novel one-allele mutations. Twenty-two of the 23 females were carriers. One carrier with de novo [Arg290X]CYBB who suffered from refractory salmonella sepsis and chorioretinitis as an XL-CGD phenotype had extreme XCI, absent Cyto b558 expression, and only 8% ROS production. The remaining carriers had bimodal patterns of Cyto b558 expressions (median 40.2%, 26.8-52.4%) and ROS production (38.3%, range 28.2-54.2%) sufficient to prevent significant infections, although neck lymphadenitis recurred in one mother and sister who had ROS expressions of 28.2% and 38.0%, respectively. However, none of the carriers had manifestations of autoimmunity or autoinflammation (e.g., photosensitivity, aphthous stomatitis, or joint disorders), of which each was seen in approximately one-third of XL-CGD carriers from the Western world. CONCLUSION: One carrier had undetectable Cyto b558 expression and an extremely low ROS production, and consequently presented with an XL-CGD phenotype. One mother and her daughter experienced recurrent neck lymphadenitis despite having sufficient ROS production. Significant autoimmunity/autoinflammation did not develop in any of the carriers. Studies with a longer follow-up period are needed to validate our findings.

Active learning of medical students in Taiwan: a realist evaluation.

BACKGROUND: Active learning is defined as any instructional method that engages students in the learning process. Cultural differences in learning patterns can play an important role in engagement with active learning. We aimed to examine process models of active learning to understand what works, for whom and why. METHODS: Forty-eight sixth- and seventh-year medical students with experience of active learning methods were purposively selected to participate in ten group interviews. Interactions around active learning were analysed using a realist evaluation framework to unpack the 'context-mechanism-outcome' (CMO) configurations. RESULTS: Three core CMO configurations, including cultural, training and individual domains, were identified. In the cultural context of a strong hierarchical culture, the mechanisms of fear prompted students to be silent (outcome) and dare not give their opinions. In the training context of teacher-student familiarity alongside teachers' guidance, the mechanisms of learning motivation, self-regulation and enthusiasm were triggered, prompting positive learning outcomes and competencies (outcome). In the individual context of learning how to learn actively at an early stage within the medical learning environment, the mechanisms of internalisation, professional identity and stress resulted in recognising active learning and advanced preparation (outcomes). CONCLUSIONS: We identified three CMO configurations of Taiwanese medical students' active learning. The connections among hierarchical culture, fear, teachers' guidance, motivation, the medical environment and professional identity have been shown to affect the complex interactions of learning outcomes. Fear derived from a hierarchical culture is a concern as it is a significant and specific contextual factor, often sparking fear with negative outcomes.

Fetal Phagocytes Take up Allergens to Initiate T-Helper Cell Type 2 Immunity and Facilitate Allergic Airway Responses.

RATIONALE: Actively acquired tolerance occurs when foreign antigens come into contact with the immature fetal immune system. OBJECTIVES: Armed with the knowledge of actively acquired tolerance, we attempted to prenatally abolish or diminish allergic responses. METHODS: In utero injection of adjuvant-free ovalbumin (OVA) was conducted in Gestational Day 14 FVB/N mouse fetuses. Postnatally, mice were evaluated for their resistance to intraperitoneal OVA sensitization and oral or aerosolized OVA challenge, and then they were examined for humoral and cellular immunological profiles, airway hyperresponsiveness to bronchospastic stimuli, and lung histology. Fluorescent conjugates of OVA were used for further studies of mechanisms. MEASUREMENTS AND MAIN RESULTS: This presumed tolerogenic action turned out to be a sensitization process with the development of anaphylaxis or heightened recall, T-helper cell type 2-skewed responses to postnatal encounter with OVA. Further postnatal aerosolized OVA stress triggered allergic lungs with functional and structural alterations of airways. The unintended consequence resulted from macrophage-like fetal phagocytes that took up OVA and differentiated toward dendritic cells. These fetal dendritic cell progenitors attenuated proteolysis of endocytosed OVA for delayed presentation in postnatal life. This specialty of fetal phagocytes effectively retains the memory of antigens internalized early before full development of the immune system, leading to an event of in utero sensitization. CONCLUSIONS: Our results have mechanical implications for prenatal imprinting of atopy and shed light on the importance of fetal phagocytes in shaping the developing immune system and initiating allergic airway diseases.

Cord Blood Soluble CD14 Predicts Wheeze and Prolonged Cough in Young Children: The PATCH Study.

BACKGROUND: Soluble cluster of differentiation 14 (sCD14) plays a role in the development and manifestation of atopic symptoms, although the results of previous studies have been inconclusive. The aim of this study is to evaluate the practical use of sCD14 as a predictive biomarker of allergy in young children. METHODS: Children aged 0-1 year from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Cord blood sCD14 concentrations were measured. Pediatrician evaluation and questionnaire interviews were performed periodically until 1 year of age to determine the children's allergic and respiratory symptoms. RESULTS: Two hundred and six 1-year-old subjects were enrolled. Wheeze was positively associated with cord blood sCD14, a family member with asthma and parental smoking. Prolonged cough was associated with cord blood sCD14, older maternal age and more siblings. In the multivariate logistic regression analysis, cord blood sCD14 was the only independent predictive biomarker for wheeze and prolonged cough by 1 year of age. Every 100-ng/ml increase in cord blood sCD14 resulted in a 1.56-fold higher risk of developing wheeze and a 1.62-fold higher risk of prolonged cough in children by 1 year of age. CONCLUSIONS: Cord blood sCD14 may be a useful biomarker for predicting infant wheeze and prolonged cough by 1 year of age.

Cost-effectiveness study of pediatric atopic dermatitis in Asia: atopiclair vs. regular emollient (AD-ATOP).

BACKGROUND: Atopic dermatitis (AD) is a highly prevalent, chronic relapsing condition in childhood with significant financial burden and impact on the quality of life of patients and caregivers. Proactive maintenance treatment with moisturizing agents is the mainstay AD therapy. OBJECTIVES: The aim of this study was to assess the cost-effectiveness of a non-steroidal barrier cream (Atopiclair), compared to regular emollient in pediatric patients with mild-to-moderate AD. METHODS: A Markov decision model was developed to evaluate the cost-effectiveness of Atopiclair versus regular emollient in 12 Asia-Pacific countries, grouped by income categories based on gross domestic product (GDP) per capita. Data was obtained from structured literature review, expert opinion, fee schedules, and findings from a 2012 survey of 12 Asia-Pacific countries. Analysis was performed a societal perspective. RESULTS: In the base case analysis, Atopiclair was cost-effective against regular emollient, with USD786, USD499, and USD289 in cost savings per year for high, middle, and low-income countries, respectively. Sensitivity analyses showed that Atopiclair remained cost-effective versus regular emollient. CONCLUSIONS: Modelling analysis showed that Atopiclair is a cost-effective treatment compared to regular emollient for mild-to-moderate pediatric AD in the countries included in the study.

An Exploration of Pediatricians' Professional Identities: A Q-Methodology Study.

Professional identities may influence a wide range of attitudes, ethical standards, professional commitments and patient safety. This study aimed to explore the important elements that comprise pediatricians' professional identities. A Q-methodology was used to identify the similarities and differences in professional identity. Forty pediatricians were recruited from two tertiary referral hospitals in Taiwan. A list of statements was developed by five attending physicians and three residents. R software was used to analyze the Q-sorts to load the viewpoints and formulate the viewpoint arrays. Additional qualitative data-one-to-one personal interviews-were analyzed. Twenty-eight of forty pediatricians, 11 males and 17 females, with an average age of 39.9 (27-62) years, were associated with four viewpoints. We labeled the four viewpoints identified for professional identity as (1) professional recognition, (2) patient communication, (3) empathy and (4) insight. The professional recognition viewpoint comprised of youngest participants-28-36 years-with the majority as residents (77.8%), while the empathy viewpoint comprised the oldest participants-38-62 years-with all as attending physicians. All participants in the empathy and insight viewpoints were married. This study found professional identity to be a multifaceted concept for pediatricians, especially in the areas of professional recognition, patient communication, empathy and insight into patient care.

Autoantigen Exposure in Murine Fetuses Elicited Nonpathogenic Autoimmunity.

BACKGROUND AND AIM: Autoimmunity refers to the presence of autoantibodies and autoreactive lymphocytes against the structural molecules of an individual's cells or tissues, known as self-antigens or autoantigens. It might exist in the absence of autoimmune disease. However, how autoimmunity develops remains a mystery, despite the discovery of autoantibodies in human cord blood. METHODS: Murine fetuses on day 14 of gestation were subjected to intraperitoneal injection of murine thyroid peroxidase (TPO) peptides or collagen type II (CII) at graded doses via transuterine approach. Postnatally, the recipients were examined for autoantibodies by ELISA and autoreactive lymphocytes by in vitro incorporation of tritium and for the development of autoimmune thyroiditis or arthritis. RESULTS: At one month of age, the recipients did not secrete significant levels of anti-TPO or CII IgG2a in sera until a dose of 0.5 µg TPO or 5.0 µg CII was injected in utero. Serum anti-TPO or CII IgG2a persisted for at least two to four months postnatally. In recipients with elevated autoantibodies, their lymphocytes also showed proliferative responses specifically to TPO or CII. However, the development of autoantibodies and autoreactive lymphocytes was not associated with inflammatory cell infiltration of thyroid glands or paw joints even though anti-TPO or CII IgG2a was enhanced by postnatal TPO or CII challenge. CONCLUSION: Fetal exposure to free autoantigens could be immunogenic, shedding new light on the in utero origin of autoantibodies and autoreactive lymphocytes. The development of autoimmunity requires a threshold intensity of autoantigen exposure in the fetus.

Allogeneic lymphocytes exerted graft-versus-host rather than tolerogenic effects on preimmune fetuses.

BACKGROUND: Among cell suspensions from different origins, lymphocytes were reported to have the superiority of tolerance-conferring capacity in preimmune hosts. However, this belief was derived directly from murine combinations with fewer major histocompatibility complex (MHC) barriers that are exceptional in the clinical arena. Because of the potential for prenatal tolerance induction to facilitate postnatal therapies, it is important to examine the relative merits and hazards of fully MHC-mismatched naïve lymphocytes as the prenatal tolerogenic agent in the preimmune fetus to cross MHC barriers. MATERIALS AND METHODS: In utero injection of C57BL/6 splenic lymphocytes was conducted in gestational day 14 FVB/N fetuses. Then, FVB/N recipients were subjected to the evaluation of hematopoietic chimerism, donor-specific tolerance, and graft-versus-host disease (GVHD). RESULTS: With a dose of ≥ 5 × 10(5) C57BL/6 lymphocytes, the recipients born alive either died unexpectedly by maternal cannibalization or succumbed to GVHD within postnatal 1 mo. GVHD mice showed significant hematopoietic chimerism that was dominated by donor CD3 T cells. It was found that allogeneic lymphocytes could rapidly damage the fetal liver within 5 d after injection. Fetal recipients could survive a dose of ≤ 2 × 10(5) allogeneic lymphocytes beyond 1 mo of age, but at best showed microchimerism that was insufficient to confer donor-specific skin tolerance. CONCLUSIONS: Fully MHC-mismatched lymphocytes injected in utero had lethal graft-versus-host effects, which might rapidly develop within 1 wk after injection in preimmune fetuses. They were incapable of conferring significant hematopoietic chimerism and graft tolerance even at bearable doses.

C1-C2 subluxation in enthesitis-related arthritis: two case reports and literature review of ten cases.

BACKGROUND: C1-C2 subluxation is a rare complication of enthesitis-related arthritis (ERA). If left untreated, it may lead to functional impairment or cervical spinal cord compression. This study aims to highlight key points regarding the management of C1-C2 subluxation in ERA. CASE PRESENTATION: We present two cases of C1-C2 subluxation: an 8-year-old boy with ERA and 16-year-old boy with ERA with bilateral sacroiliitis. Ten cases of ERA in the literature were reviewed. The diagnosis of C1-C2 subluxation is mostly based on radiographs and cervical spine computed tomography. All patients were treated with non-steroidal anti-inflammatory drugs. Six ERA patients were treated surgically for cervical fusion. Most ERA patients with sacroiliitis had cervical collar protection. Neurologic abnormalities after treatment were not reported. Despite the use of cervical collar, cervical fusion and persisting ankylosis were found in two ERA patients with sacroiliitis without surgical treatment. CONCLUSIONS: Cervical spine protection and ruling out spinal cord compression should be prioritized, in addition to controlling the underlying inflammation in ERA. Cervical halter traction may be applied after severe cervical inflammation is excluded. To reduce the risk of complications, early recognition and appropriate treatments of C1-C2 subluxation in ERA are essential.

Prevalence, associated factors, and impact of adolescent asthma in Taiwan: Global Asthma Network phase I survey.

Background: The prevalence of asthma in Taiwan was increasing in the past 30 years, causing a great impact on adolescent health. This study aimed to investigate the current prevalence, impact, and associated factors of asthma in Taiwanese adolescents. Material and methods: Parents or guardians provided passive consent at home prior to the survey. Adolescents aged 13-14 years completed a questionnaire survey in 2017 in Taipei, Taiwan. The prevalence, impact, and associated factors of asthma were analyzed. We also compared the asthma prevalence with the prevalence in 1995 and 2001. Results: We analyzed 3474 validated questionnaires. The prevalence of physician-diagnosed asthma was 12.4%. The prevalence of current wheezing was 9.2% in 2017, which was 5.2% in 1995 and 7.0% in 2001. 3.3% of 13-14-year-old adolescents had severe asthma symptoms. Asthma significantly impacted the lives of adolescents. Of the students with asthma, 10.9% had school absenteeism, 16.5% urgently needed to see a doctor, 9.5% went to the emergency department, and 3.5% were admitted to hospitals within the preceding 12 months. The associated factors for physician-diagnosed asthma in Taiwanese adolescents were male (prevalence ratio [PR], 1.38; 95% confidence interval [CI], 1.05-1.83; p = 0.02), maternal history of asthma (PR, 2.61; 95% CI, 1.69-4.02; p < 0.01), and recent paracetamol use at least once per month (PR, 2.60; 95% CI, 1.24-5.42; p = 0.01). The associated factors for school absenteeism were nocturnal cough (PR, 1.99; 95% CI, 1.16-3.41; p = 0.01), current wheezing (PR, 7.52; 95% CI, 4.39-12.9; p < 0.01), and recent paracetamol use (at least once per month, PR, 3.16; 95% CI, 1.10-9.06; p = 0.03; at least once per year, PR, 2.19; 95% CI, 1.25-3.83; p < 0.01). Conclusions: The prevalence of physician-diagnosed asthma was 12.4%. Asthma substantially impacted the lives of adolescents. Reducing nocturnal cough, wheezing frequency, and paracetamol usage might help decrease school absenteeism.

Rising prevalence of food allergies in Taiwan: An epidemiological study.

BACKGROUND: Food allergies are becoming more prevalent globally. The purpose of this study was to investigate the epidemiology of food allergies in Taiwan. METHODS: In 2017, a food allergy questionnaire was administered to 6-7-year-old children, 13-14-year-old adolescents, and their parents in Taipei. The results were compared to those from a previous survey conducted in 2004. RESULTS: A total of 16,200 questionnaires were completed, revealing a rise in the prevalence of food allergies from 7.7% to 10.4% in the pediatric group and from 6.4% to 12.5% in the adult group. Peanut allergies also increased to 1.1%. Shrimp and crabs were the most common allergens, with urticaria being the most common symptom. Shortness of breath or wheezing occurred in 10% of individuals, while 2.1% experienced syncope or shock, and 0.1% were admitted to an intensive care unit. Personal history of allergic rhinitis and atopic dermatitis, as well as family histories of food allergies, were risk factors for food allergy in 6-7-year-old children. In the 13-14-year-old group, personal history of asthma, allergic rhinitis, or atopic dermatitis, recent use of acetaminophen, and living with dogs were risk factors. Females, personal histories of asthma, allergic rhinitis, atopic dermatitis, and moist and damp at home were risk factors in adults. Breastfeeding was a protective factor in 6-7-year-old children. CONCLUSION: The increasing prevalence of food allergies, including peanut allergies, in Taiwan warrants attention from physicians to provide appropriate care and education to patients with food allergies. The protective effect of breastfeeding against food allergies shall be emphasized.

Evaluation of a common variant of the gene encoding clara cell 10 kd protein (CC10) as a candidate determinant for asthma severity and steroid responsiveness among Chinese children.

OBJECTIVE: The gene (SCGB1A1) encoding Clara cell 10-kDa protein (CC10), a steroid-inducible immune modulator, is a candidate gene for asthma, but the evidence is equivocal. The potential influence of a common variant on asthma severity and serum CC10 levels during acute exacerbation and after corticosteroid treatment in Chinese case-control children and its functional relevance was investigated. METHODS: Genotyping of a non-coding variant G+38A was performed in 489 children, of whom 277 had asthma with varying severity, and 212 healthy controls. Associations were tested for asthma, asthma severity, and responsiveness to steroid treatment. The transcriptional activity of this variant was examined in a Clara-like cell line (H358) using transient transfection assays. RESULTS: Significant association was observed for the combined GA and AA genotypes of the CC10 G+38A variant and an increased risk of asthma [odds ratio (OR), 2.62, p < .001]. This association was correlated with asthma severity (moderate: OR, 2.85, p < .001; near-fatal: OR, 4.81, p < .001). Also, patients with the GA and AA genotypes showed significantly lower serum CC10 (p < .01) and provocation concentration causing a 20% fall (PC(20)) in forced expiratory volume in 1 s (FEV(1)) (p < .0001) when compared with those with the GG. After glucocorticoid treatment, the CC10 levels were significantly increased in asthmatic patients with GG (p < .0001), but not those with the GA and AA genotypes. Moreover, a lower dexamethasone-induced reporter (luciferase) activity was observed for H358 cells transiently transfected with the G38A risk allele (A) compared with wild-type allele (G). CONCLUSIONS: These findings suggest that the CC10 G+38A variant may contribute to the severity of asthma and lower level of steroid responsiveness.

Rescue by hematopoietic progenitor cells derived from engrafted cord blood unit in a child with brain tumor after transplantation for T-cell acute lymphoblastic leukemia.

An 8-year-old boy with T-cell acute lymphoblastic leukemia received unrelated cord blood transplantation in April 2006. His course was uneventful until February 2007, when a hyperintense lesion was noted in the pons. A subsequent bone marrow examination confirmed that he was in remission with full donor chimerism. He was therefore diagnosed with an inoperable brain tumor after cord blood transplantation. Despite radiotherapy for the brain lesion, his neurological status worsened. High-dose chemotherapy with "autologous" progenitor cell rescue was adopted, although the fact that these cells were originally derived from engrafted umbilical cord unit. He was in apparent remission of his brain tumor for 3 years.

Taiwan guidelines for the diagnosis and management of pediatric atopic dermatitis: Consensus statement of the Taiwan Academy of Pediatric Allergy, Asthma and Immunology.

Atopic dermatitis (also known as atopic eczema) is a chronic relapsing inflammatory skin disease commonly seen in children, with increasing prevalence over the past few decades in many countries including Taiwan. The management of pediatric atopic dermatitis can be challenging, particularly as treatment options are expanding with the emergence of novel systemic and topical anti-inflammatory medications in recent years. The Taiwan Academy of Pediatric Allergy, Asthma and Immunology (TAPAAI) has developed the Taiwan guidelines for the diagnosis and management of pediatric atopic dermatitis, which provides a concise overview of its epidemiology, clinical characteristics and diagnosis, mechanisms, treatments, and education. The contents of this guideline integrate the principles of recent national and international guidelines for the diagnosis and management of atopic dermatitis, latest research findings, and expert opinions of experienced pediatric allergy specialists in Taiwan. For practical purposes, this guideline presents simplified and easy-to-use diagnostic criteria and severity grading for pediatric atopic dermatitis. A stepwise treatment algorithm is also proposed to expedite rational, cost-effective, and evidence-based management strategy. This guideline, developed based on current best evidence and real-world experience of pediatric allergy experts in Taiwan, is intended to facilitate practical, up-to-date management of pediatric atopic dermatitis among physicians.