Loss of resilience in Taiwan's pediatric care system after the COVID-19 pandemic.

During the COVID-19 pandemic, Taiwan's pediatric healthcare system faced its most severe shortage of pediatric residents in history. This review investigates the causes, consequences, and potential solutions to this shortage. Between 2020 and 2023, the recruitment rate of pediatric residents dropped by 27.3%, increasing workloads for attending pediatricians and may worsening health outcomes for pediatric patients. Compared to South Korea and Japan, Taiwan has the highest neonatal mortality rates and lowest life expectancy at birth. Additionally, Taiwan's National Health Insurance (NHI) pays pediatricians in hospitals half of what it pays those in local clinics, hindering the attraction of pediatric hospitalists. To sustain the pediatric healthcare system, the government could consider directly compensating pediatricians at clinic rates and transitioning to a capitation payment system. Systemic recommendations include increasing health expenditure as a percentage of gross domestic production (GDP) and amending the NHI Act to eliminate the global budget payment system. Managing the resulting increase in financial responsibility could involve raising tax revenue as a percentage of GDP. Implementing these measures could strengthen the pediatric healthcare system and prevent a collapse of pediatric inpatient care.

Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children.

BACKGROUND: Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. METHODS: We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM2.5, NO, and SO2 was estimated using land-use regression models data on children's school and home addresses. RESULTS: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM2.5 (P < 0.05). An increase of 1 µg/m3 PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO2. CONCLUSIONS: Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. IMPACT: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 µg/m3 annual PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children.

Small Airway Dysfunction Measured by Impulse Oscillometry and Fractional Exhaled Nitric Oxide Is Associated With Asthma Control in Children.

Background: Impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) are sensitive and non-invasive methods to measure airway resistance and inflammation, although there are limited population-based studies using IOS and FeNO to predict asthma control. Objective: This study aimed to investigate the utility of IOS and FeNO for assessing childhood asthma control in terms of small airway dysfunction and airway inflammation. Methods: This prospective observational cohort study enrolled 5,018 school children (aged 6-12 years), including 560 asthmatic children and 140 normal participants. FeNO, spirometry, IOS, bronchial dilation test, total IgE, and childhood asthma control test (C-ACT) were measured. FeNO, IOS, spirometry, and C-ACT results were correlated with childhood asthma with and without control. Results: Uncontrolled asthmatic children had abnormal FeNO, IOS, and spirometric values compared with control subjects (P < 0.05). IOS parameters with R5, R5-R20, X5, Ax, △R5, and FeNO can predict lower C-ACT scales by the areas under receiver operating characteristic curves (AUCs) (0.616, 0.625, 0.609, 0.622, 0.625, and 0.714). A combination of FeNO (>20 ppb) with IOS measure significantly increased the specificity for predicting uncontrolled asthma patients compared with FeNO alone (P < 0.01). A multiple regression model showed that small airway parameter (R5-R20) was the strongest risk factor [OR (95% CI): 87.26 (7.67-993.31)] for uncontrolled asthma patients. Poor control with lower C-ACT scales correlated with high FeNO (r = -0.394), R5 (r = -0.106), and R5-R20 (r = -0.129) in asthmatic children (P < 0.05). Conclusion: A combined use of FeNO and IOS measurements strongly predicts childhood asthma with or without control.

The association of hypertension and prehypertension with greenness and PM2.5 in urban environment.

BACKGROUND: The interplay of air pollution and urban greenness on hypertension (HTN) is not fully understood. METHODS: We conducted a cross-sectional study to explore the role of greenness and PM2.5 on HTN for 40,375 adult residents in the New Taipei City, Taiwan. Normalized Difference Vegetation Index (NDVI) defined greenness and land use regression derived exposures of PM2.5 were used to calculate odds ratios (ORs) of HTN in logistic regression models and common OR of normal to stage 3 HTN in ordinal logistic regression models. Linear regression model was used to evaluate the association between NDVI and blood pressures, including systolic (SBP), diastolic (DBP) and mean (MBP) pressures. The mediation and moderation analysis were used to assess the mediation and moderation effect of PM2.5 on the association between greenness and SBP. RESULTS: We found 37.3%, 21.4%, 8.2% and 2.7% of prehypertension and stage 1-3 hypertensions, respectively, for our study participants with annual PM2.5 exposures of 10.96-43.59 µg/m3 living in an urban environment with NDVI within 500 m buffer ranging from -0.22 to 0.26. The ORs of HTN were 0.744 (95% CI: 0.698-0.793) for NDVI (quartile 4 vs. quartile 1) and 1.048 (1.012-1.085) for each IQR (8.69 µg/m3) increase in PM2.5, respectively. The common OR of the higher level of 5 categories of BP was 1.1310 (1.241-1.383). With each IQR increase of NDVI (0.03), we found SBP, DBP and MBP were decreased by 0.78 mm Hg (-0.93-0.64), 0.52 mm Hg (-0.62-0.43) and 0.61 mm Hg (-0.71-0.51), respectively, in linear regression models. Stratified analysis found greenness effect was more prominent for people who are younger, female, never smoking, and without chronic diseases. PM2.5 is moderated rather than mediated the association between greenness and SBP. CONCLUSIONS: Greenness was associated with lower prevalence of prehypertension and all stages of HTN and this relationship was moderated by PM2.5.

Lupus nephritis with corticosteroid responsiveness: molecular changes of CD46-mediated type 1 regulatory T cells.

BACKGROUND: The engagement of the complement regulatory proteins CD46 and CD3 in human CD4+ T cells induces the type 1 regulatory T cells (Tr1) and interleukin-10 (IL-10) secretion. This study aimed to elucidate the molecular changes of Tr1 cells through CD46 cytoplasmic Cyt1 tail in lupus nephritis (LN) respond to intravenous methylprednisolone (ivMP) therapy. METHODS: We enrolled 40 pediatric patients with LN and 30 healthy controls. Clinical characteristics and peripheral blood mononuclear cells were collected before and 3 days after the administration of ivMP. Kidney specimens were taken from five LN and five minimal-change nephrotic syndrome patients. RESULTS: We found that defective CD46-mediated T-helper type 1 contraction (IL-10 switching) is present in active LN patients. The ivMP therapy enhanced LN remission, restored the production of IL-10, increased the CD46-Cyt1/Cyt2 ratio, AKT, and cAMP-responsive element-binding protein phosphorylation, and induced migration with the expression of chemokine receptor molecules CCR4, CCR6, and CCR7 of CD3/CD46-activated Tr1 cells. CONCLUSIONS: Pharmacologic interventions that alter the patterns of CD46-Cyt1/Cyt2 expression and the secretion of IL-10 by CD3/CD46-activated Tr1 cells can be used in patients with active LN. IMPACT: In patients with LN, ivMP was associated with increased IL-10 production and increased CD46-Cyt1/Cyt2 ratio and AKT phosphorylation by Tr1 cells, with enhanced potential to migration in response to CCL17. These results suggest that expression levels of CD46 isoforms Cyt1 and Cyt2 in CD4 + CD46 + Tr1 cells differ in patients with active LN but can be corrected by corticosteroid treatment. Enhancing the expression of functional CD4 + CD46 + Tr1 cells may be a useful therapeutic approach for LN.

Open space and adult's chronic kidney disease, overweight and diabetes in the metropolitan area of New Taipei City.

BACKGROUND: The beneficial effects of urban open green space on residential health had few investigations in Taiwan. METHODS: A total of 40,375 participants older than 30-year-old attended the health screening program during 2007-2009 in the Metropolitan area in the New Taipei City. We defined urban open green spaces (UOGS) if land use belongs to parks, green, plaza, public schools and sport venues. Small public urban open space (SPUOS) is defined as UOGS with area less than 1 hector and with at least three of the followings: vegetations, sport facilities and benches. Greenness is defined as the mean Normalized Difference Vegetation Index (NDVI). Air quality was accessed by land use regression model. Logistic regression model was used to calculate odds ratios of diseases for proximity to UOGS or greenness. RESULTS: We found that CKD was significantly associated with proximity to SPUOS. No relationship was found between proximity to UOGS or NDVI and overweight or diabetes. The adjusted odds ratio of CKD comparing distance to SPUOS >200 m and ≤200 m was 1.144 (95% CI, 1.059-1.237). The effect of open space on CKD was similar if we incorporated public schools to SPUOS. Greenness was not associated with CKD. Subgroups analyses revealed the effect of SPUOS on CKD was more prominent in health residents, including in those who never smoke, no hypertension, no diabetes and no hypertriglyceridemia. CONCLUSION: Proximity to SPUOS or schools is associated with lower risk of CKD for adults living in the Metropolitan area in New Taipei City.

Comparison of the PCB serum levels among mother-child pairs in areas of Eastern Japan and Central Taiwan.

Polychlorinated biphenyls (PCBs) have been prohibited for two decades in Japan and Taiwan. The aim of this study was to compare the PCB congeners in maternal and cord serum between two countries. Our study subjects were 248 and 100 mother-child pairs in Japan and Taiwan. The measured levels of 23 serum PCB congeners between two countries were analyzed using gas chromatography-electron capture negative ionization quadrupole mass spectrometry (GC-NICI-qMS). The statistical comparisons were conducted by Student's t-test and principal component analysis with further stratification by maternal age and parity. The maternal total PCBs levels in Japan (426 ± 244 pg/g wet wt) were significantly higher than those in Taiwan (254 ± 155 pg/g wet wt), and the similar results were found in cord total PCBs levels (97 ± 76 and 58 ± 87 pg/g wet wt). It showed different distributions of PCB congeners between two countries. Whether in maternal or cord serum, the CB138, CB153 and CB180 were the highest detectable congeners whether in Japan or Taiwan. And, the CB66, CB99, CB206 and CB209 were only detected in maternal serum of Taiwan. The women of advanced maternal age had higher levels of PCB congeners, especially in Taiwan, and the primiparous women had higher levels of PCB congeners in two countries. In summary, the PCB congeners in Japan's mother-child pairs were with higher levels and different distributions when compared to those in Taiwan, and the maternal age and parity were important factors associated with the PCB levels.

Cardiac Autonomic Modulation during on-Call Duty under Working Hours Restriction.

Background: Medical residency is a time of high stress and long working hours, which increase the risk of cardiovascular disease. This study aimed to investigate the autonomic modulation of resident physicians throughout the on-call duty cycle. Methods: Spectral analysis of heart rate variability (HRV) was used to compute cardiac parasympathetic modulation (high-frequency power, HF) and cardiac sympathetic modulation (normalized low-frequency power, LF%, and the ratio of LF and HF, LF/HF) of 18 residents for a consecutive 4-day cycle. Results: Male residents show reduced cardiac sympathetic modulation (i.e., higher LF/HF and LF%) than the female interns. Medical residents' cardiac parasympathetic modulation (i.e., HF) significantly increased on the first and the second post-call day compared with the pre-call day. In contrast, LF% was significantly decreased on the first and the second post-call day compared with the pre-call day. Similarly, LF/HF was significantly decreased on the second post-call day compared with the pre-call day. LF/HF significantly decreased on the first post-call day and on the second post-call day from on-call duty. Conclusion: The guideline that limits workweeks to 80 h and shifts to 28 h resulted in reduced sympathetic modulation and increased parasympathetic modulation during the two days following on-call duty.

A Pilot Survey of Potentially Hazardous Trace Elements in the Aquatic Environment Near a Coastal Coal-Fired Power Plant in Taiwan.

BACKGROUND: A limited number of potentially hazardous trace elements were quantified in the aquatic environment near the world's second largest coal-fired power plant (CFPP) and the coal combustion residual (CCR) disposition sites in Central Taiwan. We postulated that contamination from specific trace elements would be present in the abovementioned aquatic environments. METHODS: Cross-sectional sampling of trace elements was first performed between September 24, 2017 and October 3, 2017 outside the CFPP, in the effluent sampled from Changhua, a county south of metropolitan Taichung, and at the historical CCR disposal sites, using the intertidal zone surface seawater and the seawater in an oyster farm as controls. Aqueous samples were collected from 12 locations for analysis of 13 trace elements (Al, As, B, Cd, total Cr, Co, Fe, Pb, Mn, Se, Sr, Tl, and V). We used inductively coupled plasma (ICP) optical emission spectrometry to determine B and Fe levels, and ICP mass spectrometry for all other trace elements. The Spearman rank correlation coefficient (Rho) was calculated to examine the pairwise relation among the trace elements. RESULTS: Al (50% of all samples), B (66.7%), Fe (25%), Mn (50%), Sr (8.3%), and V (25%) were identified as being above the Environmental Protection Agency (EPA) regulation limit. The oyster farm seawater had no concerns. Mn (96.4 µg/L) in the CFPP drainage effluent was 1.9-fold above the regulation limit. Fe, Mn, and V were detected from the cooling channel at 4379, 625, and 11.3 µg/L, respectively. The effluent and water from the areas surrounding the 2 CCR dump sites revealed similar magnitudes of trace element contamination. B is highly correlated with Sr (Rho = 0.94, 95% confidence interval [CI], 0.80-0.98). Meanwhile, Fe is highly correlated with Al (Rho = 0.77), Pb (Rho = 0.71), Co (Rho = 0.75), and V (Rho = 0.84). CONCLUSIONS: The EPA must set an explicit regulation limit for aluminum, boron, iron, and strontium in the aquatic environment. This exploratory research will inform policymaking regarding certain trace elements that could potentially have an adverse impact on public health and wildlife.

Urban Open Space Is Associated with Better Renal Function of Adult Residents in New Taipei City.

The purpose of this study is to explore the association between proximity to open space and adult renal function. This was a cross-sectional study. Adult residents of Taipei metropolis were recruited in the analysis. The proximity of each subject to open space was measured using the Geographic Information System. Residents were divided into two groups: with and without chronic kidney disease (CKD). We made univariable comparisons between the two groups. The logistic regression models were used to estimate the odds ratio of CKD. Forest plot was used to examine the effect of interaction between distance to open space and subgroup variable on CKD. A total number of 21,656 subjects with mean age 53.6 years were enrolled in the study. Of the subjects, 2226 (10.28%) had CKD. The mean and standard deviation of distance to open space were 117.23 m and 80.19 m, respectively. Every 100 m distance to open space was associated with an odds ratio of 1.071 for CKD. Subgroup analysis revealed that residents of female, without hypertension, or without impaired fasting glucose (IFG) living more than 200 m from open spaces have greater odds of CKD than those living less than 200 m. Conclusions: Proximity to open space was associated with a lower prevalence of CKD among adults in Taiwan. Such association was enhanced among females and healthy adults without hypertension or impaired fasting glucose (IFG).

Allergen-specific immunotherapy enhances CD8+ CD25+ CD137+ regulatory T cells and decreases nasal nitric oxide.

BACKGROUND: 4-1BB (CD137), a member of the inducible tumor necrosis factor receptor (TNFR) family, is expressed on regulatory T (Treg) cells and regulates Treg cells to control allergic inflammation. Pam3CSK4, a synthetic TLR2 ligand that can expand CD8+ Treg function, is a promising adjuvant for allergen immunotherapy (IT). We examined whether Dermatophagoides pteronyssinus (Der p) IT and Pam3CSK4 could enhance CD8+  CD25+  CD137+ Treg suppressive function to decrease nasal nitric oxide (nNO) levels. METHODS: Nasal symptom scores, nNO levels, PBMCs, and inferior turbinate biopsies were obtained from 40 mite-sensitive perennial allergic rhinitis (PAR) patients before and after one year of Der p IT and 30 non-allergic control subjects. CD137 expression on CD8+  CD25+ T cells and suppressive function of CD8+  CD25+  CD137+ Tregs was measured using flow cytometry. Cytokine levels were analyzed by ELISA. Inducible nitric oxide synthase production by nasal epithelial cells after co-culturing with CD8+  CD25+  CD137+ T cells was analyzed by Western blotting. RESULTS: Der p IT improved nasal symptom scores, decreased nNO levels, and increased CD137 expression on CD8+ T cells in PBMCs and nasal mucosa. Pam3CSK4 expanded the CD8+  CD25+  CD137+ population in PBMCs. Pam3CSK4-stimulated CD8+  CD25+  CD137+ Tregs induced IL-10 and TGF-ß and suppressed CD4+  CD25- T-cell proliferation mainly by cell contact inhibition. CD8+  CD25+  CD137+ Tregs cultured with nasal epithelial cells suppressed Der p 2-induced iNOS production. Silencing CD137 in sorted CD8+  CD25+ T cells decreased Pam3CSK4-activated Foxp3 expression. CONCLUSION: Der p IT expanded CD8+  CD25+  CD137+ Tregs and decreased nNO levels. Induced CD137 expression on CD8+  CD25+ Tregs by Pam3CSK4 stimulation may help suppress allergic inflammation during IT.

Wheezing as a sign of cor triatriatum sinister culminating in multiple organ failure.

Cardiac asthma or cardiac wheezing (CW) refers to a syndrome of dyspnea and wheezing that mimicks asthma clinically. Reported herein is the case of a 2-month-old boy who presented with refractory wheezing as a sign of cor triatriatum sinister (CTS) that culminated in overwhelming multiple organ failure in a short time. On the day of admission, oxygen saturation (SpO2 ) was <80%. Heart rate was 198 beats/min and respiratory rate 58 breaths/min. Chest radiogram showed pulmonary edema. Electrocardiogram showed right atrial enlargement and right ventricular hypertrophy. N-terminal pro-brain natriuretic peptide (NTproBNP) was very high at >20,000 pg/mL. Two-dimensional echocardiography with Doppler showed CTS, which was complicated with severe pulmonary arterial hypertension due to flagrant pulmonary venous obstruction. Cardiac surgery was undertaken, after which pulmonary edema subsided, SpO2 increased to ≥96%, and NTproBNP dropped to normal. He was discharged 11 days later, and was free of cardiac, pulmonary, renal, and neurological sequelae at 24 month follow up.

Urinary 8-hydroxy-2'-deoxyguanosine (8-oxodG) level can predict acute renal damage in young children with urinary tract infection.

BACKGROUND: There are no good biomarkers to predict renal parenchymal involvement in children with urinary tract infection (UTI). METHODS: Children (N = 73) younger than 5 years with UTI were enrolled. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8-oxodG) and total antioxidant capacity (TAC) were checked as markers of oxidative stress and antioxidant capacity, respectively. Tc99m-dimercaptosuccinic acid (DMSA) renal scintigraphy was used to find evidence of renal involvement. RESULTS: Patients with positive DMSA findings had higher levels of urinary 8-oxodG (p = 0.003) and higher urinary TAC (p = 0.001) than patients with normal DMSA findings. CONCLUSIONS: High level of urinary 8-oxodG may be a risk factor of severe renal damage.

Long-acting beta 2 agonists suppress IP-10 expression in human bronchial epithelial cells.

BACKGROUND: Interferon-γ-inducible protein (IP)-10 (CXCL10) is an important chemokine secreted by the airway epithelium that functions as a biomarker for virus-induced asthma. Long-acting beta 2 (ß2) agonists (LABAs) are frequently used as inhaled medication for asthma and chronic obstructive pulmonary disease. However, previous research failed to investigate the effects of LABAs on IP-10 in bronchial epithelial cells. OBJECTIVE: To study the effects and signaling pathways of formoterol and salmeterol on polyriboinosinic polyribocytidylic acid (poly I:C)-induced IP-10 expression in BEAS-2B cells. METHODS: BEAS-2B cells were pretreated with formoterol and salmeterol for 2 hours before poly I:C stimulation. ICI 118551 (ß2 adrenoreceptor antagonist) or mitogen-activated protein kinase (MAPK) inhibitors were added 30 minutes before LABAs were added. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction were used to measure IP-10 protein and messenger RNA levels. Mitogen-activated protein kinase inhibitors and Western blotting were used to identify MAPK pathways, whereas bioassay revealed the MAPK functions. RESULTS: Long-acting ß2 agonists significantly down-regulated the poly I:C-induced IP-10 protein and messenger RNA expression in BEAS-2B cells. ICI 118551 reversed this effect. Forskolin, a cyclic adenosine monophosphate activator, produced a similar inhibitory effect. Western blotting showed that formoterol suppressed poly I:C-induced IP-10 expression via the c-Jun N-terminal kinase-c-Jun pathway. CONCLUSION: Long-acting ß2 agonists down-regulate poly I:C-induced IP-10 expression in BEAS-2B cells via the ß2 adrenoreceptor-cyclic adenosine monophosphate and c-Jun N-terminal kinase/c-Jun pathways. Long-acting ß2 agonists also inhibit IP-10 production in bronchial epithelial cells and may prolong viral elimination.

TLR2 agonists enhance CD8+Foxp3+ regulatory T cells and suppress Th2 immune responses during allergen immunotherapy.

Pam3CSK4, a synthetic TLR2 ligand, has been shown to expand CD4+ regulatory T cells (Treg cells). Less is known about the function of CD8+ Treg cells than about the function of CD4+ Treg cells generated during allergen-specific immunotherapy (IT). This study investigated whether Dermatophagoides pteronyssinus-specific IT could expand the CD8+CD25+Foxp3+ Treg population and whether Pam3CSK4 could enhance the Treg population. PBMCs were isolated from healthy control subjects and from mite-sensitive asthmatic patients during IT at three specific times: before IT and 6 mo and 1 y after the maximum-tolerated dose. This study was performed without a placebo-controlled group. D. pteronyssinus-specific IT induced a significant increase in CD8+Foxp3+ Treg cells expressing intracellular IL-10 and granzyme B. Costimulation of PBMCs with Pam3CSK4 and D. pteronyssinus 2 expanded the CD8+CD25+Foxp3+ Treg population and inhibited D. pteronyssinus 2-induced IL-4 production. Pam3CSK4-treated CD8+CD25+ Treg cells directly suppressed CD4+ T cell proliferation by cell-contact inhibition. TUNEL revealed that CD8+CD25+ Treg cells, but not CD4+CD25+ Treg cells, directly induced CD4+CD45ROhi+ apoptosis. Our results provide direct evidence that Pam3CSK4 induces an immunomodulatory effect by inducing CD8+ Treg cells; therefore, it may be a good adjuvant for the treatment of mite allergies.

Induction of IL-10+ CD4+ CD25+ regulatory T cells with decreased NF-κB expression during immunotherapy.

MyD88 is a major toll-like receptor (TLR) adaptor to activate NF-κB, which acts as a mater switch for allergic inflammation disease. Sterile hust dust extracts have been reported with TLR-dependent immunostimulatory activities. The aim of this study was to evaluate whether Dermatophagoides pteronyssinus (Der p) immunotherapy may increase IL-10+ CD4+ CD25+ T cells with modulating MyD88 signaling proteins, to decrease NF-κB expression. Peripheral blood mononuclear cells were isolated from patients before and after 1 yr of Der p immunotherapy, and also from matched control subjects. After 2 days of Der p-2 stimulation, intracellular IL-10 and Foxp3 expression of CD4(+) CD25(+) T cells were measured by flow-cytometry. The expression of IL-1 receptor-associated kinase (IRAK)-1 in cytoplasm and IFN-regulator factor-3 (IRF-3) with NF-κB/p65 in nuclei was determined by Western-blot analysis. Patients undergoing immunotherapy produced more soluble CD14, IL-10, and TGF-ß that correlated with FEV(1) improvement (p < 0.05). In the immunotherapy group, the number of Foxp3+ CD4+ Treg cells increased more than the baseline status (25.06 ± 4.19 vs. 16.08 ± 3.54, p < 0.05). Additionally, increased IL-10 production with decreased IRAK-1 and NF-κB/p65 nuclear translocation was observed in sorted-purified Treg cells. IL-10(+) CD4(+) CD25(+) Treg cells may respond to Der p-2 and down-regulate NF-κB/p65 expression to maintain immune tolerance during immunotherapy.

Daily urinary interleukin-11 excretion correlated with proteinuria in IgA nephropathy and lupus nephritis.

Interleukin-11 (IL-11) is a multifunctional cytokine with both thrombopoietic and anti-inflammatory effects. In an animal study IL-11 was shown to reduce proteinuria in mice with necrotizing glomerulonephritis. The purpose of this current study is to explore the role of IL-11 in human glomerulonephritis. Subjects of this study were patients with proteinuria (daily urine protein excretion >40 mg/m2 per hour) and underlying pathology of IgA nephropathy (IgAN) (n=20), lupus nephritis (LN) (n=40), and idiopathic nephrotic syndrome (INS) (n=68). Daily urinary IL-11 level was measured by enzyme-linked immunosorbent assay (ELISA). Correlation between urinary IL-11 and urinary protein was determined by Pearson's correlation coefficient. Another five patients with serial data of urinary protein, IL-11 and IL-11 messenger RNA (mRNA) expression in urine sediment are presented. The correlation between urinary IL-11 and daily urinary protein was significant for patients with IgAN (r=0.596, P=0.006) and LN (r=0.630, P<0.001), but not for patients with INS (r=0.030, P=0.812). Serial data revealed the same correlation. Furthermore, the peak of urinary IL-11 mRNA preceded that of urinary IL-11. We conclude that daily urinary IL-11 excretion is correlated with urinary protein loss in nephritis having local T helper (Th)1 predominant immune response, such as IgAN and LN. Local IL-11 production may serve as a counter cytokine against Th1-mediated inflammation.

Induced apoptosis of TH2 lymphocytes in asthmatic children treated with Dermatophagoides pteronyssinus immunotherapy.

Allergen-specific immunotherapy (IT) has been effectively used for the treatment of asthma. Allergen specific IT induced immune tolerance with induction of TH2 cells anergy remain to be clarified. The aim of this study was to evaluate whether the mite allergen Dermatophagoides pteronyssinus (Dpt) specific IT serially decreased IL-4+/CD4+ (TH2) lymphocytes and induced apoptosis of TH2 lymphocytes in asthmatic children. Sixty Dpt-sensitive asthmatic children were randomly assigned to a received IT and an untreated group. Dermatophagoides pteronyssinus specific IT treated patients were examined at three time points: before IT, after 6 months of an increased dose phase and with maximum tolerated doses after 1 yr. Peripheral blood mononuclear cells (PBMC) were isolated and cultured for 48 h for cellular staining with CD4+, CD45RO cell phenotypes and interleukin (IL)-4 and interferon-gamma expression by fluorescence monoclonal antibodies. Apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method. A simultaneous flow cytometric study using the same permeabilized cell was examined to determine whether apoptosis occurred preferentially in TH2 lymphocytes. The data demonstrated that Dpt specific IT decreased Dpt-specific IgE levels (p < 0.01) after 1 yr of treatment. In addition, decreased CD4+IL-4+ TH2 cells with increased CD4+IFN-gamma+ TH(1) cells were observed at 6 months and 1 yr after IT treatment (p < 0.05). At the same time, apoptosis of CD4+IL-4+ TH2 lymphocytes in the IT group had increased after 1 yr of treatment when compared with the results before treatment (p < 0.001) and after 6 months of treatment (p = 0.046). In addition, CD45RO cells apoptosis mainly occurred after 6 months of IT treatment and after 1-year period of IT treatment (p < 0.05). All of the data suggested that Dpt specific IT decreased Dpt specific IgE and CD4+IL-4+ TH2 lymphocytes with induction apoptosis of CD4+IL-4+ TH2 lymphocytes subsets serially.