Asthma Exacerbation in Children: A Practical Review

Asthma is the most common chronic lower respiratory tract disease in childhood throughout the world. Despite advances in asthma management, acute exacerbations continue to be a major problem in patients and they result in a considerable burden on direct/indirect health care providers. A severe exacerbation occurring within 1 year is an independent risk factor. Respiratory tract viruses have emerged as the most frequent triggers of exacerbations in children. It is becoming increasingly clear that interactions may exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this study, we provide an overview of current knowledge about asthma exacerbations, including its definition, impact on health care providers, and associated factors. Prevention management in intermittent asthma as well as intermittent wheeze in pre-school children and those with persistent asthma are discussed. Our review findings support the importance of controlling persistent asthma, as indicated in current guidelines. In addition, we found that early episodic intervention appeared to be crucial in preventing severe attacks and future exacerbations. Besides the use of medication, timely education after an exacerbation along with a comprehensive plan in follow up is also vitally important

Use of electroporation and reverse iontophoresis for extraction of transdermal multibiomarkers

Congo Tak-Shing Ching1,2, Lin-Shien Fu3-5, Tai-Ping Sun1, Tzu-Hsiang Hsu1, Kang-Ming Chang21Department of Electrical Engineering, National Chi Nan University, Puli, Nantou County, 2Department of Photonics and Communication Engineering, Asia University, Wufeng, Taichung, 3Department of Pediatrics, National Yang Ming University, Taipei, 4Institute of Technology, National Chi Nan University, Puli, 5Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, TaiwanBackground: Monitoring of biomarkers, like urea, prostate-specific antigen (PSA), and osteopontin, is very important because they are related to kidney disease, prostate cancer, and ovarian cancer, respectively. It is well known that reverse iontophoresis can enhance transdermal extraction of small molecules, and even large molecules if reverse iontophoresis is used together with electroporation. Electroporation is the use of a high-voltage electrical pulse to create nanochannels within the stratum corneum, temporarily and reversibly. Reverse iontophoresis is the use of a small current to facilitate both charged and uncharged molecule transportation across the skin. The objectives of this in vitro study were to determine whether PSA and osteopontin are extractable transdermally and noninvasively and whether urea, PSA, and osteopontin can be extracted simultaneously by electroporation and reverse iontophoresis.Methods: All in vitro experiments were conducted using a diffusion cell assembled with the stratum corneum of porcine skin. Three different symmetrical biphasic direct currents (SBdc), five various electroporations, and a combination of the two techniques were applied to the diffusion cell via Ag/AgCl electrodes. The three different SBdc had the same current density of 0.3 mA/cm2, but different phase durations of 0 (ie, no current, control group), 30, and 180 seconds. The five different electroporations had the same pulse width of 1 msec and number of pulses per second of 10, but different electric field strengths of 0 (ie, no voltage, control group), 74, 148, 296, and 592 V/cm. Before and after each extraction experiment, skin impedance was measured at 20 Hz.Results: It was found that urea could be extracted transdermally using reverse iontophoresis alone, and further enhancement of extraction could be achieved by combined use of electroporation and reverse iontophoresis. Conversely, PSA and osteopontin were found to be extracted transdermally only by use of reverse iontophoresis and electroporation with a high electrical field strength (>296 V/cm). After application of reverse iontophoresis, electroporation, or a combination of the two techniques, a reduction in skin impedance was observed.Conclusion: Simultaneous transdermal extraction of urea, PSA, and osteopontin is possible only for the condition of applying reverse iontophoresis in conjunction with high electroporation.Keywords: electroporation, reverse iontophoresis, nanochannels, noninvasive, urea, prostate-specific antigen, osteoponti

Risk of acute exacerbation between acetaminophen and ibuprofen in children with asthma

Background Antipyretics are widely prescribed in pediatric practice. Some reports have mentioned that acetaminophen and non-steroid anti-inflammatory drugs may negatively affect asthma control by causing asthma exacerbation (AE). However, many confounding factors can also influence the risks. We assessed the impact of using acetaminophen or ibuprofen on AE in asthmatic children, especially those with strong risk factors. Methods We used the 2010 Taiwan National Health Insurance Research Database and identified 983 children with persistent asthma aged 1–5 years old; among them, 591 used acetaminophen alone and 392 used ibuprofen alone in 2010. Then, we analyzed the risk of AE over 52 weeks in the patients with and without severe AE in the previous year. Results The ibuprofen group had a higher risk of an emergency room (ER) visit or hospitalization for AE (odds ratio (OR) = 2.10, 95% confidence interval (CI) [1.17–3.76], P = 0.01). Among asthmatic children who had severe AE in the previous year, the risk of AE was higher in the ibuprofen group than in the acetaminophen group (OR = 3.28, 95% CI [1.30–8.29], P = 0.01), where as among those who did not, the risks of AE were similar between the acetaminophen and ibuprofen groups (OR = 1.52, 95% CI [0.71–3.25], P = 0.28). Conclusions Among young asthmatic children, use of ibuprofen was associated with a higher risk of AE than acetaminophen, if they had severe AE with ER visit or hospitalization in the previous year. Pediatricians should use antipyretics among children with asthma after a full evaluation of the risk

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Concurrence of Incontinentia Pigmenti and Behçet's Disease

We report here a rare case of incontinentia pigmenti (IP) in a 10-year-old girl who developed Behçet's disease. IP was diagnosed in infancy and Behçet's disease was diagnosed at 10 years of age. The initial presentations of Behçet's disease were spiking fever and recurrent painful oral and genital ulcers that were refractory to antibiotics. After corticosteroid treatment, her fever subsided and ulcers subsequently healed. The patient's mother and sister were also diagnosed with IP. Her mother had suffered from Behçet's disease since her teenage years and it was complicated with colon perforation. Although there are several reports on the combination of IP and Behçet's disease, this is the first reported case of a family with such concurrence

Allergic children with extremely high total IgE but no allergen identified in the initial screening panel

Background: High serum IgE level in atopic children usually implies a highly sensitized condition. However, there is a subgroup of atopic children for whom a specific allergen cannot be identified. In this study, we analyzed follow-up data from these children. Methods: From March 2014 to July 2017, we recruited 14 atopic children with serum total IgE level higher than 500 Ku/L, but with no specific allergen identified by repeated MAST tests initially. Follow-up studies of specific IgE were conducted by the OPTIGEN MAST Allergy test and ImmunoCAP assays (Thermo Fisher Scientific/Phadia), while total IgE and specific IgG were measured by ImmunoCAP. Results: The patients were aged from 2 to 17 y/o. The follow-up MAST tests showed significantly positive results in 10 patients. There were no significant differences in any of the clinical characteristics between the MAST-positive and MAST-negative groups. In the MAST-negative group, five allergen-specific IgE antibodies, including those for cockroach, Euroglyphus maynei, Blomia tropicalis, shrimp, and crab, were strongly predictive of negative ImmunoCAP results, according to ROC (Receiver operating characteristic curve) analysis of the AUC (Area under the Curve of ROC) (0.70–0.95), with significance set at p < 0.05. Conclusion: In two thirds of atopic children with a high serum IgE whose specific allergen had yet to be identified, it was possible to identify the specific MAST allergen(s) after an average follow-up of 33.2 months. For patients who still had negative results in follow-up MAST, mite DP, DF, and DM may be suitable choices for further allergen identification by ImmunoCAP

Evaluation of the Effect of Lactobacillus paracasei (HF.A00232) in Children (6–13 years old) with Perennial Allergic Rhinitis: A 12-week, Double-blind, Randomized, Placebo-controlled Study

Dietary supplementation with probiotics alters intestinal microflora of children and may have immunomodulatory effects in prevention of allergic diseases. The aim of this study was to evaluate the effects of Lactobacillus paracasei (LP), strain HF.A00232, as a supplementary agent to levocetirizine in treating children with perennial allergic rhinitis (AR). Methods: This study was a 12-week, double-blind, randomized, placebo-controlled trial. Sixty children with AR aged 6–13 years with nasal total symptoms score (NTSS) ≥5 who fulfilled the inclusion criteria were enrolled. Patients were randomized into two groups with 28 participants receiving levocetirizine plus placebo and 32 participants receiving regular levocetirizine plus LP (HF.A00232) for the first 8 weeks, with a shift to levocetirizine as rescue treatment during the following 4 weeks. Parameters evaluated, including nasal, throat, and eye TSS (NTSS, TTSS, and ETSS, respectively), TSS and levocetirizine use, were recorded daily. Physical examinations and Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQs) were administered at each visit. In addition, blood samples were obtained for evaluation of cytokines including interleukin-4, interferon-γ, interleukin-10, and transforming growth factor-β at baseline, Week 8, and Week 12. Results: The LP (HF.A00232) group had significantly lower PRQLQ scores even after discontinuing regular levocetirizine from Week 9 to Week 12 (p < 0.01). There was more improvement in individual parameters in the PRQLQ, including sneezing (p = 0.005), itchy nose (p = 0.040), and swollen puffy eyes (p = 0.038), in the LP (HF.A00232) group. No significant differences in TSS, NTSS, TTSS, ETSS, or cytokine levels were found between the two groups. Conclusion: Dietary supplementation with LP (HF.A00232) provided no additional benefit when used with regular levocetirizine in treating AR in the initial 8 weeks of our study, but there was a continuing decrease in PRQLQ scores, as well as a significant improvement in individual symptoms of sneezing, itchy nose, and swollen eyes, after discontinuing regular levocetirizine treatment

The Role of New 3D Pathology and Lymphocyte Expression of Interstitial Inflammation in Pediatric-Onset Lupus Nephritis

Lupus nephritis (LN) is a common and severe manifestation of pediatric-onset systemic lupus erythematosus (pSLE). It is one of the major causes of long-term glucocorticoid/immune suppressants use in pSLE. It causes long-term glucocorticoid/immune suppressants use and even end-stage renal disease (ESRD) in pSLE. It is now well known that high chronicity, especially the tubulointerstitial components in the renal biopsy, predicts a poor renal outcome. Interstitial inflammation (II), a component of activity in LN pathology, can be an early predictor for the renal outcome. With the advent of 3D pathology and CD19-targeted CAR-T cell therapy in the 2020s, the present study focuses on detailed pathology and B cell expression in II. We recruited 48 pSLE patients with class III/IV LN to analyze the risk of ESRD based on different II scores. We also studied 3D renal pathology and immunofluorescence (IF) staining of CD3, 19, 20, and 138 in patients with a high II score but low chronicity. Those pSLE LN patients with II scores of 2 or 3 showed a higher risk for ESRD (p = 0.003) than those with II scores of 0 or 1. Excluding patients with chronicity >3, high II scores still carried a higher risk for ESRD (p = 0.005). Checking the average scores from the renal specimens from different depths, the II, and chronicity showed good consistency between 3D and 2D pathology (interclass correlation coefficient [ICC], II = 0.91, p = 0.0015; chronicity = 0.86, p = 0.024). However, the sum of tubular atrophy plus interstitial fibrosis showed no good consistency (ICC = 0.79, p = 0.071). The selected LN patients with negative CD19/20 IF stains showed scattered CD3 infiltration and a different IF pattern of Syndecan-1 expression. Our study provides unique data in LN, including 3D pathology and different in situ Syndecan-1 patterns in LN patients

Monte Carlo Noisy HMM Estimation and Segmental Differential Features on the Aurora2 Clean Training Evaluation

Abstract. In this paper, the compensation of mismatch between clean training hidden Markov models (HMMs) and noisy test speech is addressed. The purpose is to approach the performance of Aurora2 multi-condition training but use only clean training material. The idea is to integrate three methods including (1) mean subtraction, variance normalization and ARMA filtering (MVA) post-processing for Mel-scaled cepstral coefficients (MFCCs) normalization, (2) Monte Carlo noisy HMM estimation by adding artificial noises in the linear mel-scale filterbank parameter (MELSPEC) domain and (3) novel segmental differential features for increasing recognizer’s discriminative power. Experimental results on Aurora2 clean training corpus have shown that great performance improvement was achieved. Especially, although only clean training material was used, the performance did close to the level of Aurora2 multi-condition training