The effect of sildenafil on pleural and peritoneal effusions after the TCPC operation

Background We evaluated whether the administration of sildenafil in children undergoing the TCPC operation shortened the interval from the operation to the removal of the pleural and peritoneal drains. Methods We retrospectively reviewed the data of 122 patients who had undergone the TCPC operation between 2004 and 2014. Patients were divided into two groups on the basis of their treatments. Sildenafil was orally administered pre-operatively in the morning of the procedure or within 24 hours after the TCPC operation to the sildenafil group (n = 48), which was compared to a control group (n = 60). Fourteen patients were excluded from the study. Results The primary outcome measure was the time from the operation to the removal of the drains. The study groups had similar demographics. The median [interquartile range] time for the removal of drains (sildenafil group 11 [8-19] vs control group 11 [7-16] d, P = .532) was comparable between the groups. The median [interquartile range] fluid balance on the first post-operative day was significantly higher (P = .001) in the sildenafil group compared with controls (47 [12-103] vs 7 [-6-67] mL kg(-1)). The first post-operative day fluid balance was a significant predictor for a prolonged need for drains in the multivariate analysis. Conclusions Sildenafil administration, pre-operatively or within 24 hours after the TCPC operation, did not reduce the required time for pleural and peritoneal drains but was associated with a significantly higher positive fluid balance.Peer reviewe

Pets, furry animal allergen components, and asthma in childhood

Abstract Background The use of component‐resolved allergy diagnostics has provided a clearer understanding of the species‐specific sensitization and severity of potential allergic reactions. This cross‐sectional study aimed to determine whether sensitization to allergen components in furry animals is indicative of blood eosinophilia, a positive fractional exhaled nitric oxide (FeNO) test, abnormal lung function, and asthma symptoms in children. Additionally, we investigated whether having pets during childhood affects the development of asthma or allergic sensitization to furry animals. Methods We recruited 203 children aged 4–17 years with asthma diagnosis based on abnormal lung function and 33 controls. IgE‐sensitization to allergen components for dogs, cats, and horses was analyzed using a multiplex microarray. Children were tested with FeNO, impulse oscillometry, spirometry, methacholine challenge, and skin prick test. A questionnaire was used to investigate pet ownership and symptom profile. Results FeNO results and blood eosinophilia revealed a correlation with sensitization to all furry animal allergens, particularly lipocalins (r = 0.203–0.560 and 0.206–0.560, respectively). Can f 3 was found to correlate with baseline R5 (r = 0.298). No association between methacholine challenge results and sensitization to furry animal allergens was found. Children with asthma who were sensitized to Can f 1, Can f 6, or both frequently reported asthma symptoms. Dog ownership was associated with a lower level of IgE‐sensitization to lipocalins, fewer asthma symptoms, and less blood eosinophilia. Conclusion Furry animal allergen component IgE‐sensitization is a risk factor for type 2‐inflammation and asthma symptoms

Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze

BACKGROUND: Prenatal vitamin D(3) supplementation has been linked to reduced risk of early life asthma/recurrent wheeze. This protective effect appears to be influenced by variations in the 17q21 functional SNP rs12936231 of the child, which regulates the expression of ORMDL3, and for which the high-risk CC-genotype is associated with early-onset asthma. However, this does not fully explain the differential effects of supplementation. We investigated the influence of maternal rs12936231 genotype variation on the protective effect of prenatal vitamin D(3) supplementation against offspring asthma/recurrent wheeze. METHODS: We determined the rs12936231 genotype of mother-child pairs from two randomized-controlled trials: the Vitamin D Antenatal Asthma Reduction Trial (VDAART, n=613) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC(2010), n=563) to examine the effect of maternal genotype variation on offspring asthma/recurrent wheeze at age 0–3 years between groups who received high-dose prenatal vitamin D(3) supplementation versus placebo. RESULTS: Offspring of mothers with low-risk GG-genotype or GC-genotype who received high-dose vitamin D(3) supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared to the placebo group (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.37–0.77; P<0.001 for VDAART and HR, 0.56; 95% CI, 0.35–0.92; P=0.021 for COPSAC(2010)), whereas no difference was observed among the offspring of mothers with high-risk CC-genotype (HR, 1.05; 95% CI, 0.61–1.84; P=0.853 for VDAART and HR, 1.11; 95% CI, 0.54–2.28; P=0.785 for COPSAC(2010)). CONCLUSION: Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D(3) supplementation against offspring asthma/recurrent wheeze

Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma.

The application of large-scale metabolomic profiling provides new opportunities for realizing the potential of omics-based precision medicine for asthma. By leveraging data from over 14,000 individuals in four distinct cohorts, this study identifies and independently replicates 17 steroid metabolites whose levels were significantly reduced in individuals with prevalent asthma. Although steroid levels were reduced among all asthma cases regardless of medication use, the largest reductions were associated with inhaled corticosteroid (ICS) treatment, as confirmed in a 4-year low-dose ICS clinical trial. Effects of ICS treatment on steroid levels were dose dependent; however, significant reductions also occurred with low-dose ICS treatment. Using information from electronic medical records, we found that cortisol levels were substantially reduced throughout the entire 24-hour daily period in patients with asthma who were treated with ICS compared to those who were untreated and to patients without asthma. Moreover, patients with asthma who were treated with ICS showed significant increases in fatigue and anemia as compared to those without ICS treatment. Adrenal suppression in patients with asthma treated with ICS might, therefore, represent a larger public health problem than previously recognized. Regular cortisol monitoring of patients with asthma treated with ICS is needed to provide the optimal balance between minimizing adverse effects of adrenal suppression while capitalizing on the established benefits of ICS treatment.Effort from PK, JALS and STW is supported by P01HL132825 from the National Heart, Lung and Blood Institute, National Institutes of Health (NIH/NHLBI), USA. IDS is funded by the Medical Research Council (MC_UU_00006/1 - Etiology and Mechanisms). Effort for RK, DIS, MC, KM, MS and JALS is supported by R01HL123915 from the NIH/NHLBI and W81XWH-17-1-0533 from the U.S.A Department of Defense. Effort for RSK is supported by K01HL146980 from the NIH/NHLBI. Effort for SHC is supported by K01HL153941 from the NIH/NHLBI. Effort for MH and JALS is supported by R01HL141826 from the NIH/NHLBI. Effort for AD is supported by K01HL130629 from the NIH/NHLBI. Effort for AD and JALS is supported by 1R01HL152244 from the NIH/NHLBI. Effort for MM and JALS is supported by R01HL155742 from the NIH/NHLBI. Effort for HK is supported by the Jane and Aatos Erkko Foundation, the Paulo Foundation, and the Pediatric Research Foundation. Effort for KLS is supported by K08HL148178 from the NIH/NHLBI. Effort for MM is supported by R01HL139634 from the NIH/NHLBI. Effort for AW is supported by K23HL151819 from the NIH/NHLBI and Thrasher Research Fund Award (15115). Effort for ACW is supported by 1R01HD085993 from the NICHD. Effort for YV is supported by K23AI130408 from the NIAID. Effort for JALS, STW, EWK is supported by the NIH U01HG008685. Effort for PZ and CEW was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant (JP19K21239), the Japanese Environment Research and Technology Development Fund (No. 5-1752), the Gunma University Initiative for Advanced Research (GIAR), the Japan-Sweden Research Cooperative Program between JSPS and STINT (grant no. JPJSBP-1201854), the Swedish Heart Lung Foundation (HLF 20180290, HLF 20200693), and the Swedish Research Council (2016-02798). The EPIC-Norfolk study (https://doi.org/10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 MC-UU_12015/1 and MC_UU_00006/1) and Cancer Research UK (C864/A14136). Metabolite measurements in the EPIC-Norfolk study were supported by the MRC Cambridge Initiative in Metabolic Science (MR/L00002/1) and the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372