Wen-I Lee

Associations of Age, Gender, and BMI with Prevalence of Allergic Diseases in Children: PATCH Study

Background. Little is known about the prevalence of allergic diseases in children of different ages. This study aimed to investigate the prevalence of allergic diseases and allergic sensitization in children over a wide age range, with emphasis on the influence of age, gender, and body mass index (BMI). Methods. In a cross-sectional study, we assessed 5351 Taiwanese children aged 4–18 years using an International Study of Asthma and Allergies in Childhood questionnaire, BMI, and total and specific serum immunoglobulin E. Results. Forty-eight percent were currently symptomatic for at least one of three allergic diseases. Prevalence of wheeze ever, current wheeze, and diagnosed asthma were 17.0%, 7.5%, and 9.8%, respectively; analogous features for rhinitis were 47.8%, 44.2%, and 39.8%. Allergic sensitization was very common (57.3%). Half of the children (50.6%) with current wheeze had not been diagnosed with asthma by physicians, whereas undiagnosed rates were 32.3% for rhinitis and 25.3% for eczema. The male-to-female prevalence ratios of current wheeze increased with age from <1 at 4–5 years, peaked at 10–11 years (2.24), then reversed to 0.57 at 16–18 years. Childhood wheezing tended to remit with age, but rhinitis and eczema were more persistent. Total immunoglobulin E levels increased with age until 14–15 years, and declined thereafter. Elevated BMI was associated with greater prevalence of wheezing and eczema, with no evidence of significant effect modification by either gender or age. Multivariate analyses revealed that younger age, boys, and obesity were significantly and independently associated with current wheezing in children (all p < .01). Conclusions. The burden and co-morbidity of childhood allergies are substantial. There are striking age-dependent gender differences in asthma prevalence, exhibiting an inverted U-shaped curve for male-to-female prevalence ratios by age. Obesity is associated with a greater prevalence of asthma in children with no evidence of a significant modulation by either gender or age.

PFAPA SYNDROME (PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS, ADENITIS)

Abstract: This paper aims to remind paediatric clinicians to suspect and confirm ‘PFAPA’ syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis syndrome). We report two cases of PFAPA syndrome: a 3-year-old healthy boy with atopic rhinitis and a boy aged 8 years 5 months who simultaneously had lymphocytic vasculitis syndrome treated with immunosuppressive drugs. Both met Marshall’s criteria. The literature regarding PFAPA syndrome was complied using a Medline search for articles published between 1963 and 1998 and we then reviewed the reference lists of the articles. The Medline search revealed 28 cases with available clinical manifestations, management and prognosis. Our study describes two additional cases. We divided the cases into typical (28 cases) and atypical (two cases) PFAPA syndrome. In typical PFAPA, the age of onset was less than 5 years in most cases and the patients presented 4.9 ± 1.4 days of fever (100%), pharyngitis (89.3%), cervical adenitis (72.1%), stomatitis (71.4%), malaise (64.3%), headache (60.7%), abdominal pain (53.6%) and nausea/vomiting (17.9%). Afebrile intervals were 3.2 ± 2.4 months and increased with age. The time from initial onset to final episode was 3 years 7 months ± 3 years 6 months. The total number of episodes was 8.3 ± 2.5 (range 6–14). Effective treatment included steroids, tonsillectomy/adenoidectomy and cimetidine. The general outcome was good. In atypical PFAPF, the clinical manifestations were similar to those of typical PFAPA except that the age of onset was more than 5 years, and life-threatening intestinal perforation happened once in a patient with underlying Fanconi’s anaemia. It was concluded that typical PFAPA syndrome is benign and can be diagnosed by detailed history-taking and from physical findings during repeated febrile episodes with tests to rule out other periodic fever syndromes. A review of the literatures since the first report in 1987 has shown that typical PFAPA syndrome is not associated with significant long-term sequelae and has a good response to steroids. One patient with atypical PFAPA, who received low-dose steroids for over 1 year, developed intestinal perforation after an increment of the 7-day steroid dose. If an underlying problem requires long-term immunosuppressive medication, it is wiser to choose cimetidine rather than increasing the steroid dosage to resolve atypical PFAPA.

Incidence of severe combined immunodeficiency through newborn screening in a Chinese population.

BACKGROUND/PURPOSE In order to know the true incidence of severe combined immunodeficiency (SCID) in a Chinese population, we conducted and implemented SCID newborn screening in Taiwan. METHODS Between May 1, 2010 and December 31, 2011, the National Taiwan University Hospital Newborn Screening Center screened all newborns for T-cell lymphopenia by measuring the copy number of T-cell receptor excision circles (TRECs) and RNase P. Newborns with low TREC values were subjected to complete blood cell counts and flow cytometry. RESULTS A total of 106,391 newborns were screened using the TREC assay over a period of 19 months. Five newborns were immediately referred for confirmatory tests, including two SCID patients and two patients with persistent T-cell lymphopenia; a third SCID patient was found 2 months after the study period. All three SCID cases received stem cell transplantation at the age of 2-5 months. We also identified five cases of 22q11.2 microdeletion syndrome. During this period, two SCID patients from among the unscreened newborns were reported, and they died at ages 3 months and 4 months, respectively. CONCLUSION Newborn screening to measure the number of TREC copies successfully identifies newborns with T-cell lymphopenia, 22q11.2 microdeletion syndrome, and other high-risk conditions. Taken together, the incidence of T-cell lymphopenia in apparently healthy newborns is more than 1 in 11,821, and further attention to their immune functions is warranted.

Stroke Volume Variation Derived by Arterial Pulse Contour Analysis Is a Good Indicator for Preload Estimation During Liver Transplantation

BACKGROUND Accurate determination of preload during liver transplantation is essential. Continuous right ventricular end diastolic volume index (RVEDVI) has been shown to be a better preload indicator during liver transplantation than the filling pressures. However, recent evidence has shown that dynamic variables, in this case stroke volume variation (SVV), are also good indicators of preload responsiveness. In this study, we evaluated the correlation between SVV, which we derived from arterial pulse contour analysis and RVEDVI. METHODS In this study, we looked for possible relationships between SVV obtained through FloTrac/Vigileo monitor, central venous pressure (CVP), pulmonary arterial occlusion pressure (PAOP), and RVEDVI in 30 patients undergoing liver transplantation. Measurements were taken at 11 defined points during different phases across liver transplantation. Each set of measurement was taken during a steady state, which means at least 15 minutes elpased after any changes occured in either the infusion rate of catecholamines or ventilator settings. Pearsons test was used for correlation estimation. RESULTS There was a statistically significant (P<.01) relationship between SVV and RVEDVI with a correlation coefficient of -0.87. The correlations between CVP (r=0.42), PAOA (r=0.46), and RVEDVI were less strong. CONCLUSION We conclude that SVV is a good indicator for preload estimation during liver transplantation. A higher SVV value is associated with a more hypovolemic fluid status.

Distribution, Infections, Treatments and Molecular Analysis in a Large Cohort of Patients with Primary Immunodeficiency Diseases (PIDs) in Taiwan

One hundred and twenty-four patients (from 120 families) diagnosed as primary immunodeficiency diseases were enrolled from five tertiary medical centers. The distribution by an update eight categories showed 45 patients (13 females/32 males; 36.3%) with “predominant antibody deficiencies,” 27 patients (6/21; 21.8%) with “T- and B-cell immunodeficiency,” 25 patients (9/16; 20.2%) with “congenital defects of phagocyte,” 25 patients (4/21; 20.2%) with “other well-defined immunodeficiency syndromes,” one boy (0.8%) with “disease in immune deregulation” (Chediak-Higashi syndrome) and another with “complement 3 deficiency.” None had “defects in innate immunity” or “auto inflammatory disorders.” Pseudomonas and Salmonella spp. were the two most identified microorganisms in septicemia (39.7%; 27/68 episodes). Twenty-three patients (18.5%) had mortality. Stem cell transplantation succeeded in 7 of 12 patients. In addition to nine patients with DiGerge syndrome recognized by FISH, direct sequencing identified 12 unique mutations from 20 families, reflecting distinct Taiwan geography, although a selection bias may exist.

IL-12-independent Th1 polarization in human mononuclear cells infected with varicella-zoster virus.

T helper type 1 (Th1) cells perform a critical role in fighting intracellular organisms, and interleukin‐12 (IL‐12) is known to promote a Thl response. This study was conducted to identify whether an IL‐12‐independent Th1 reaction is induced by the varicella‐zoster virus (VZV) in human beings. It was found that different intracellular microorganisms could induce IFNγ but not IL‐12 production. Induction of IFNγ production by VZV was associated with IFNα production and phosphorylation of both the signal transducer and activator of transcription‐1 (STAT‐1) and STAT‐4 in lymphocytes. In contrast, Bacillus Calmette‐Guerin (BCG) induced IL‐12 production in association with STAT‐4 but not STAT‐1 activation. Anti‐IFNα but not anti‐IL‐12 antibodies blocked the VZV‐induced Th1 polarization. A patient with an IL‐12 receptor β1 chain deficiency showed a normal VZV‐ but not a normal BCG‐induced Th1 reaction, further supporting the concept of an IFNα‐mediated, IL‐12‐independent Th1 reaction in response to certain intracellular infections. Identification of the early Th1 polarization induced by IFNα versus IL‐12 in response to specific viruses may enable the development of better therapeutic strategies tailored to different infections.

Total Serum IgE in a Population-Based Study of Asian Children in Taiwan: Reference Value and Significance in the Diagnosis of Allergy

Background Total serum immunoglobulin (IgE) test is usually performed to aid in the diagnosis of allergic diseases, but its reference values may vary among people of different ethnic backgrounds. Objectives To establish reference values of total IgE in Asian children and to assess their significance in the diagnosis of atopy and allergic diseases. Study design 1321 Asian children aged 5-18 years in the Prediction of Allergies in Taiwanese CHildren (PATCH) study, a population-based cohort, were evaluated for total and specific IgE by ImmunoCAP and Phadiatop Infant, respectively. Results Male, atopy, allergic diseases, recent symptoms of upper respiratory infection, and lower FEV1/FVC, were associated with higher total IgE levels in univariate analyses. Multivariate analysis revealed that atopy was the single most important determinant explaining 66.1% of the variability of total IgE levels in this population. The area under the receiver-operator characteristic (ROC) curve of total IgE for diagnosing atopy, asthma, rhinitis, and eczema were 0.92, 0.72, 0.70, and 0.70, respectively. The sensitivity, specificity, and positive and negative predictive values of total IgE at the optimal cutoff of 77.7 kU/L on the ROC curve for diagnosing atopy were 82.3%, 87.1%, 89.5%, and 78.6%, respectively. The corresponding values using the upper 95% CI of total IgE (164.3 kU/L) in non-atopic children were 61.2%, 95.0%, 94.3%, and 64.6%, respectively; whereas a customary cutoff (100 kU/L) provided accuracy between that of the aforementioned two cutoffs. Total IgE at the cutoff of 77.7 kU/L provided modest sensitivity and specificity (49.0%-78.3%) for diagnosing allergic diseases, but had high negative predictive values (84.2%-97.9%). Conclusions Total serum IgE discriminates Asian children with and without atopy independent of allergic symptoms, with an optimal cutoff of 77.7 kU/L. The study confirms the insufficient diagnostic accuracy of total IgE alone to detect allergic diseases, but low total IgE levels may help exclude allergic diseases.

Maturation of Toll-like receptor 1-4 responsiveness during early life.

BACKGROUND Toll-like receptors (TLRs) are part of the highly conserved components of the innate immune system, and have been investigated extensively; however, little is known about TLR function during early postnatal life, a critical period for immune maturation. AIMS In order to achieve a more complete understanding of the ontogeny of immune system during the first years of life, our study investigated age-matched TLR1-4 responsiveness at several time points up to the age of two years. STUDY DESIGN Mononuclear cells were isolated from cord blood (n=150) and peripheral blood from infants at 6 (n=68), 12 (n=75), and 24 (n=74)months of age, and from 50 adults. Cells were stimulated with Toll-like receptor ligands (TLR1-4) and phytohemagglutinin (PHA). Stimulated cells were assessed for their production of the cytokines tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and for TLR4 gene expression. RESULTS Our results suggested that cord response of IL-6 and TNF-α was not affected by allergic background. In addition, neonatal mononuclear cell had enhanced IL-6 production upon TLR1, 2, and 4 stimulations as compared to those of young children and adults. Nevertheless, after 6 months of age, the level remained comparable throughout the first two years of life. While TNF-α response to all TLR stimulations remained fairly similar during early life. This cytokine pattern closely paralleled our findings for TLR4 mRNA expression, and longitudinal cytokine changes within the same individual. CONCLUSIONS Our findings provided additional information to the understanding of immune development during early life, and offered stronger evidence of neonatal innate immunity being capable of responding adequately to TLR stimulation.

Cardiac Output Derived From Arterial Pressure Waveform Analysis: Validation of the Third-Generation Software in Patients Undergoing Orthotopic Liver Transplantation

BACKGROUND The upgraded third-generation software (version 3.02) for the FloTrac/Vigileo system has been developed to particularly improve the accuracy of cardiac output (CO) measurements in hyperdynamic conditions. The aim of our study was to compare the CO values obtained using the FloTrac/Vigileo system during orthotopic liver transplantation (OLT) with those obtained in the same circumstances using a Swan-Ganz catheter (bolus thermodilution method). METHODS Twenty consecutive recipients scheduled for OLT were studied. Simultaneous CO values measured by both devices were obtained at 10 predefined time points throughout the surgery. A percentage error of not more than 30% was established as the criterion for device interchangeability. RESULTS A total of 200 paired measurements were obtained. The CO values derived from the FloTrac/Viligeo ranged from 2.8 to 10.9 L/min, with a mean of 5.91±1.81 L/min. The values from bolus thermodilution ranged from 2.2 to 13.2 L/min, with a mean of 6.12±2.07 L/min. The bias was 0.22, and the limits of agreement were -3.13 to 3.56 L/min. The percentage error between the FloTrac/Viligeo and bolus thermodilution measurements was 54.93%. The percentage errors of paired measurements in three surgical phases by subgroup analysis were 43.50% (dissecting phase), 62.9% (anhepatic phase), and 56.05% (reperfusion phase), respectively. CONCLUSION CO measurements obtained using the less invasive arterial waveform FloTrac/Vigileo system upgraded with the third-generation software had poor intraoperative agreement with pulmonary artery thermodilution CO measurements in patients undergoing OLT.

Cardiac output derived from arterial pressure waveform analysis in patients undergoing liver transplantation: validity of a third-generation device.

BACKGROUND Hemodynamic monitoring is essential to a successful liver transplantation procedure. FloTrac, a hemodynamic monitor that uses arterial-waveform-based pulse contour analysis for cardiac output (CO) measurement, has proven useful in many clinical settings. One of the primary foci of FloTracs recent third-generation software upgrade was improving its accuracy in low systemic vascular resistance status. We evaluated the accuracy of the upgraded FloTrac monitor during liver transplantation. MATERIALS AND METHODS Twenty-eight patients undergoing liver transplantation were enrolled in the study. Two sets of CO were measured with a radial arterial line connected to a FloTrac monitor (COFT) and a pulmonary artery catheter connected to a continuous cardiac output Vigilence monitor (COPAC). Simultaneous CO measurement was performed and recorded every 5 minutes throughout the surgery. Bland-Altman analysis was used to estimate the accuracy. The comparative method and reference method were considered interchangeable if the limits of agreement did not exceed a threshold set a priori at the greater of ±1 L/min, or a percentage error of lesser than 30%. RESULTS In all, 3234 paired data were collected. The bias was -0.8 L/min and the limits of agreements were -5.6 to 4.0 L/min. Percentage error was 75%. Regression analysis of the systemic vascular resistance index (SVRI) and the bias between COPAC and COFT showed that the bias was inversely related to the SVRI [r2=0.49; P<.001, y=-32.1983+9.9978 Log(x)]. CONCLUSIONS Despite a software upgrade, the effectiveness of the FloTrac artery-derived cardiac output monitor for CO measurement during liver transplantation remains limited.