Pediatric chronic urticaria: Clinical and laboratory characteristics and factors linked to remission.

BACKGROUND: Chronic urticaria (CU) is defined as the occurrence of wheals/angioedema for ≥6 consecutive weeks. Until now, guidelines and publications addressing CU have focused mainly on adults. As a result, evidence and guidance in the pediatric population are scarce. METHODS: This study aims to describe clinical and laboratory findings in pediatric CU and to determine factors associated with remission. RESULTS: 185 patients, 54% female, median age at onset of 8.8 years. Angioedema was present in almost half. The most common type of CU was chronic spontaneous urticaria (CSU) in 74%. At least one atopic comorbidity was found in almost a third (35%). In addition, 8% had an autoimmune disorder (exclusively in CSU) and 9% had a psychiatric condition. Basopenia was found in 67% and was more frequently associated with CSU. The basophil activation test (BAT) was positive in 40%. With regard to remission, being of male sex, angioedema absence, the absence of physical triggers, and eosinophil counts >0.51 × 109 /L were associated with shorter CU duration. CONCLUSION: Atopy is a common condition in pediatric CU. CSU is the most common type. Autoimmune comorbidities and basopenia were significantly more common in CSU. In addition, ours is one of the few studies, assessing BAT utility in the pediatric population, being positive in a relevant percentage (40%). BAT positivity was more frequent in CSU. Our results suggest that the absence of angioedema and physical triggers, male sex, and eosinophil counts >0.51 × 109 /L appear to be associated with a better prognosis in terms of remission.

Serum hepcidin levels, iron status, and HFE gene alterations during the first year of life in healthy Spanish infants.

The aims of this study were to describe hepcidin levels and to assess their associations with iron status and the main variants in the HFE gene in healthy and full-term newborns during the first year of life, as a longitudinal study conducted on 140 infants. Anthropometric and biochemical parameters, hepcidin, hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV), and C-reactive protein (CRP), were assessed in 6- and 12-month-olds. Infants were genotyped for the three main HFE variants: C282Y, H63D, and S65C. Hepcidin levels increased from 6 to 12 months of age (43.7 ± 1.5 to 52.0 ± 1.5 ng/mL; p < 0.001), showing higher levels in infants with better iron status compared to those with iron deficiency (ID) (44.8 ± 1.5 vs 37.9 ± 1.3 ng/mL, p < 0.018, and 54.3 ± 1.5 vs 44.0 ± 1.4 ng/mL, p < 0.038, in 6- and 12-month-olds, respectively). In multivariate linear regression models, iron status was found to be associated with hepcidin levels in infants with wild-type HFE gene (p = 0.046 and p = 0.048 in 6- and 12-month-olds, respectively). However, this association was not found in HFE-alteration-carrying infants. Hepcidin levels increased in healthy infants during the first year of life and were positively associated with iron levels only in infants with wild-type HFE gene, a situation that requires further investigation.

Nasal obstructive disorders induce medical treatment failure in paediatric persistent allergic rhinitis (The NODPAR Study).

BACKGROUND: Allergic rhinitis (AR) is the most common chronic disease among children. To characterize the disease, a modified classification of severity (m-ARIA) has recently been validated in AR children. When medical treatment fails, surgery for nasal obstructive disorders (NOD) may be a therapeutic option. Our objective was to assess the prevalence of NOD and their influence in medical treatment response among children with persistent AR (PER). METHODS: In a prospective, real-life study, 130 paediatric PER patients (13.1 ± 2.8 years, females 31.5%, severe rhinitis 49%) referred from Allergy to ENT department were assessed for their response (R, responders; NR, non-responders) to medical treatment (intranasal steroids and antihistamines or antileukotrienes) by direct questioning and nasal symptom visual analogue scale, the presence of NOD (septal deformity, turbinate enlargement and adenoidal hyperplasia), comorbidities, nasal symptoms, rhinitis severity (modified ARIA criterion) and asthma control (International Consensus On Pediatric Asthma criterion). RESULTS: After 2 months of treatment, the NR group presented a higher prevalence of obstructive septal deformity and severe inferior turbinate enlargement when compared with the R group. Higher septal deformity and turbinate enlargement scores were strongly associated with treatment refractoriness. The prevalence of severe PER was also higher for the NR group. Higher asthma control scores were associated with the probability of treatment-induced improvement. CONCLUSIONS: In paediatric PER patients, medical therapy refractoriness was associated with NOD, mainly septal deformity and turbinate enlargement. In those patients, ENT examination will facilitate an early NOD diagnosis in order to indicate potential corrective surgery.

Nasal obstructive disorders impair health-related quality of life in adolescents with persistent allergic rhinitis: A real-life study.

BACKGROUND: We previously reported a higher prevalence of nasal obstructive disorders (NOD) in pediatric patients with persistent allergic rhinitis (PER) not responding to medical treatment. The aim of this study was to determine the impact of NOD on quality of life (QoL) in this population. METHODS: Real-life prospective study including 142 patients (41 children, 6-11 years old and 101 adolescents, 12-17 years old) with moderate and severe PER. After 2 months of medical treatment (intranasal steroids and antihistamines), patients were asked whether their symptoms had improved (yes/no) and classified accordingly in R, responders and NR, non-responders. Nasal symptoms (visual analog scale, VAS), NOD (nasal endoscopy), and QoL (PRQLQ, AdolQRLQ) were also assessed. RESULTS: Sixty-nine adolescents and 24 children were included in the NR group. NR presented worse QoL overall scores in adolescents (3.16±1.1 vs 1.63±0.99; P=.00001) and children (2.19±0.82 vs 1.51±0.77, P=.02). Medical treatment failure was associated with worse outcomes in QoL (adolescents OR: 1.6, P<.0001; children OR: 1.04, P=.036). Female adolescents presented worse QoL scores than males (3.19 vs 2.36, P=.001). The presence of obstructive septal deviation (OR: 1.02, P=.005), obstructive turbinate hyperplasia (OR: 1.03, P=.0006), and coexistence of both (OR=2.06, P=.001) was associated with worse QoL in adolescents. A strong and highly significant correlation was found between nasal symptoms VAS and QoL. CONCLUSION: The presence of NOD, particularly in adolescents, is associated with poor QoL outcomes. Assessment of NOD in pediatric PER should be considered an essential approach to determine the response to treatment and its impact on patient's QoL.

Onset of Effect, Changes in Airflow Obstruction and Lung Volume, and Health-Related Quality of Life Improvements with Benralizumab for Patients with Severe Eosinophilic Asthma: Phase IIIb Randomized, Controlled Trial (SOLANA).

OBJECTIVE: In the SOLANA trial, we sought to physiologically characterize benralizumab's onset of effect and maintenance of that effect for patients with severe eosinophilic asthma. METHODS: SOLANA (NCT02869438) was a multicenter, randomized, double-blind, parallel-group, placebo-controlled, Phase IIIb study conducted at 49 centers in six countries (Chile, Germany, Hungary, the Philippines, South Korea, and the United States). Eligible patients with baseline blood eosinophil counts ≥300 cells/µL were randomized to subcutaneous benralizumab (30 mg) or placebo administered at Days 0, 28, and 56. The primary endpoint was the average change from baseline in prebronchodilator forced expiratory volume in 1 s (pre-BD FEV1) during the Day 28‒Day 84 period for benralizumab vs placebo. Secondary endpoints included patient-reported outcomes (PROs). A subset of patients participated in a whole-body plethysmography substudy. Safety was also assessed. RESULTS: In total, 233 patients were randomized to benralizumab (n=118) or placebo (n=115). Improvement from baseline in pre-BD FEV1 with benralizumab 30 mg was not statistically significant compared with placebo (least-squares mean change difference [95% confidence interval] 57 mL [-22 to 135]; p=0.16). Compared with placebo, benralizumab demonstrated early (Day 7) nonstatistically significant improvements in whole-body plethysmography assessments of hyperinflation and clinically meaningful improvements in PRO measures (Asthma Control Questionnaire 6 at Day 14 and St. George's Respiratory Questionnaire at Day 28), which were maintained over the treatment period. Benralizumab's safety profile was commensurate with previously reported studies. CONCLUSION: The observed early changes in lung volume despite relatively small improvements in airflow obstruction suggest that the anti-inflammatory effect of benralizumab may be manifested as deflation over time for patients with hyperinflation, who potentially have a greater degree of airway remodeling. This early effect could partially explain the rapid PRO improvements observed for certain patients.

Are there early inflammatory biomarkers that affect neurodevelopment in infancy?

Few studies have investigated the relationship between post-natal inflammatory biomarkers at early age and child neurodevelopment outcomes. The main aim of this study was to examine the relationship between IL-6, IL-1ß, IL-4 cytokines, as well as cortisol at 6 and 12months of age, and neurodevelopment and psychological problems at 30months of age. The study was conducted on a sample of 51 full-term newborns who were followed up at 6, 12, and 30months of age. Infant neurodevelopment was assessed using the Bayley Scales of Infant Development-II, psychological problems were assessed with the Child Behavior Checklist 1.5-5 (CBCL 1.5-5) and the mother's emotional symptoms were assessed with the General Health Questionnaire-28. When the infants were 6 and 12months old, IL-6, IL-1ß, IL-4 cytokines, and cortisol were measured in blood samples. The results showed that higher IL-6 at 12months predicted higher scores in internalizing (emotionally reactive, anxious/depressed, withdrawn and attention problems) and externalizing problems (aggressive behavior) at 30months. By contrast, high levels of IL-1ß at 6months were related to worse motor skills. Inflammatory biomarkers were not related to mental performance. IL-6 and IL-1ß could be early markers of later psychological problems and psychomotor disabilities.

Influence of nasal septum deformity on nasal obstruction, disease severity, and medical treatment response among children and adolescents with persistent allergic rhinitis.

OBJECTIVE: To evaluate the impact of different types of nasal septum deformity (NSD) on nasal obstruction, rhinitis severity and response to medical treatment among pediatric persistent allergic rhinitis (PER) patients. METHODS: In a prospective, real-life study, 150 children and adolescents (mean age 13 ± 2.8 years, females 32.6%) diagnosed with PER according to ARIA guidelines were assessed by nasal endoscopy for NSD according to Mladina's classification, their response to medical treatment (intranasal steroids and antihistamines or antileucotriens), the presence of comorbidities, rhinitis severity (modified-ARIA criterion) and nasal obstruction visual analog scale score (VAS). RESULTS: Most patients (87%) had 1 of the 7 types of septal deformities. There was a high prevalence of bilateral (types 4 and 6; 46%) and anterior unilateral (types 1 and 2; 25%) NSD in patients not responding to medical treatment. Type 4 (OR = 6.4; p = 0.005) or type 6 (OR = 4.4; p = 0.03) NSD increased the risk of lack of improvement with medical treatment. Coexistence of anterior unilateral or bilateral NSD with severe turbinate enlargement increased >20-fold the risk of lack of improvement. Patients with bilateral NSD presented greater rhinitis severity. Non-responder adolescents displayed higher prevalence of bilateral NSD than children (53% vs. 23%; p = 0.02). Nasal obstruction VAS was higher for patients with anterior than posterior NSD, and greater for patients with bilateral NSD than any other type of septal morphology. CONCLUSION: Nasal endoscopy shows that bilateral and unilateral anterior nasal septum deformities are strongly associated with a poor response to medical treatment, greater rhinitis severity and higher nasal obstruction VAS. Consequently, nasal endoscopy is necessary in the PER patients to understand the disease severity as well as to plan a specific surgical treatment in order to improve nasal obstruction, disease severity, and patient's quality of life.

Platelet dysfunction-eosinophilia syndrome in parasitized Venezuelan children.

Platelet dysfunction was detected in six children with purpura and eosinophilia. We conducted clinical evaluations, hematologic and platelet function tests, clotting studies (bleeding time, prothrombin time, partial thromboplastin time, thrombin time, factor XIII, factor VIII, and von Willebrand factor), assays for IgG and IgM antibodies to platelets, and a search for stool parasites. Mild bleeding phenomena (ecchymoses, petechiae, epistaxis, and gingival) were transient. All children showed intestinal parasites and marked eosinophilia (mean count = 2,615.2 cells/muL, 95% confidence interval = 1,259.6-5,429.8). Main abnormalities included prolonged bleeding times (50%) and defective aggregation with collagen (100%) adrenaline (66%), or ADP (66%). Antibodies to platelets were not detected. Anti-parasite therapy reversed the hemorrhagic manifestations and normalized eosinophil counts and platelet alterations. No relationship could be established between excess eosinophils, intensity of bleeding, or type and degree of platelet abnormalities. Thrombocytopathic features mimicked the intrinsic defect of storage pool disease. The possible pathogenic roles of eosinophilia and parasitism are reviewed. This is the first report of this pathologic combination in Latin American children.

Quantitative analysis of the scientific literature on acetaminophen in medicine and biology: a 2003-2005 study.

This study quantifies the utilization of acetaminophen in life sciences and clinical medicine using bibliometric indicators. A total of 1626 documents involving acetaminophen published by 74 countries during 2003-2005 in the Thompson-Scientific Life sciences and Clinical Medicine collections were identified and analyzed. The USA leads in the number of publications followed by the UK, and industrialized countries, including France, Japan and Germany; the presence of countries such as China, India and Turkey among the top 15 countries deserves to be noticed. The European Union stands as a comparable contributor to the USA, both in terms of number of publications and in terms of profile of papers distributed among subcategories of Life Sciences and Clinical Medicine disciplines. All documents were published in 539 different journals. The most prolific journals were related to pharmacology and/or pharmaceutics. All aspects of acetaminophen (chemistry, pharmacokinetics, metabolism, etc.) were studied with primary interest for therapeutic use (42%) and adverse effects (28%) comprising a large part of publications focusing on acetaminophen hepatotoxicity. This quantitative overview provides as to the interest of the scientific community in this analgesic and completes the various review documents that regularly appear in the scientific literature.