Pediatric asthma: An unmet need for more effective, focused treatments.

BACKGROUND: Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. METHODS: A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. RESULTS: These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. CONCLUSIONS: There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real-world evidence studies assessing anti-immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti-IgE and non-steroid-based alternative therapies may delay disease progression, leading to improved clinical outcomes.

Efficacy and effectiveness of omalizumab in the treatment of childhood asthma.

INTRODUCTION: Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E, a mediator involved in the clinical manifestations of allergic asthma. Evidence for its efficacy and safety in the treatment of moderate-to-severe allergic asthma is based primarily on studies in adolescents and adults. However, there is increasing evidence of its utility in children with allergic asthma aged 6-12 years. Areas covered: This article reviews efficacy, safety, and effectiveness of omalizumab in the treatment of moderate-to-severe allergic asthma in children aged 6-12 years in clinical trials and in studies in clinical practice. Pharmacoeconomic aspects of its use among this population and the positioning of omalizumab in pediatric asthma management guidelines are also discussed. Additionally, an algorithm for the management of poorly controlled severe pediatric asthma in children older than 6 years is proposed. Electronic databases, such as PubMed, were searched for terms Asthma and Omalizumab and for asthma management guidelines. Expert commentary: Add-on omalizumab is an effective maintenance therapy in children aged 6-12 years with poorly controlled moderate-to-severe allergic asthma treated with medium-high inhaled corticosteroids doses and inhaled long-acting ß2-agonists. Omalizumab appears safe in children in both clinical trials and real-life setting and may be cost-effective.

Efficacy of MP-AzeFlu in children with seasonal allergic rhinitis: Importance of paediatric symptom assessment.

BACKGROUND: This study aimed to assess the efficacy of MP-AzeFlu (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single spray) in children with seasonal allergic rhinitis (SAR) and explore the importance of child symptom severity assessment in paediatric allergic rhinitis (AR) trials. METHODS: A total of 348 children (4-11 years) with moderate/severe SAR were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Efficacy was assessed by changes from baseline in reflective total nasal symptom score (rTNSS), reflective total ocular symptom score (rTOSS) and individual symptom scores over 14 days (children 6-11 years; n = 304), recorded by either children or caregivers. To determine whether a by-proxy effect existed, efficacy outcomes were assessed according to degree of child/caregiver rating. Moreover, total Paediatric Rhinitis Quality of Life Questionnaire (PRQLQ) score was compared between the groups. RESULTS: A statistically superior, clinically relevant efficacy signal of MP-AzeFlu versus placebo was apparent for PRQLQ overall score (diff: -0.29, 95% CI -0.55, -0.03; p = 0.027), but not for rTNSS (diff: -0.80; 95% CI: -1.75; 0.15; p = 0.099). However, as the extent of children's self-rating increased, so too did the treatment difference between MP-AzeFlu and placebo; MP-AzeFlu provided significantly better relief than placebo for rTNSS (p = 0.002), rTOSS (p = 0.009) and each individual nasal and ocular symptom assessed (except rhinorrhoea; p = 0.064) when children mostly rated their own symptoms. CONCLUSIONS: MP-AzeFlu is an effective treatment for AR in childhood. Caregivers are less able than children to accurately assess response to treatment with available tools. A simple paediatric-specific tool to assess efficacy in AR trials in children is needed.

Association of FcgR2a, but not FcgR3a, with inflammatory bowel diseases across three Caucasian populations.

BACKGROUND: The Fc receptors II and III (FcgR2a, and FcgR3a) play a crucial role in the regulation of the immune response. The FcgR2a*519GG and FcgR3a*559CC genotypes have been associated with several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, nephritis, and possibly to type I diabetes, and celiac disease. In a large multicenter, two-stage study of 6570 people, we tested whether the FcgR2a and FcgR3a genes were also involved in inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We genotyped the FcgR2a*A519G and FcgR3a*A559C functional variants in 4205 IBD patients in six well-phenotyped Caucasian IBD cohorts and 2365 ethnically matched controls recruited from the Netherlands, Spain, and New Zealand. RESULTS: In the initial Dutch study we found a significant association of FcgR2a genotypes with IBD (P-genotype = 0.02); while the FcgR2a*519GG was more common in controls (23%) than in IBD patients (18%; odds ratio [OR] = 0.75; 95% confidence interval [CI] 0.61-0.92; P = 0.004). This association was corroborated by a combined analysis across all the study populations (Mantel-Haenszel [MH] OR = 0.84; 0.74-0.95; P = 0.005) in the next stage. The Fcgr2a*GG genotype was associated with both UC (MH-OR = 0.84; 0.72-0.97; P = 0.01) and CD (MH-OR = 0.84; 0.73-0.97; P = 0.01), suggesting that this genotype confers a protective effect against IBD. There was no association of FcgR3a*A559C genotypes with IBD, CD, or UC in any of the three studied populations. CONCLUSIONS: The FcgR2a*519G functional variant was associated with IBD and reduced susceptibility to UC and to CD in Caucasians. There was no association between FcgR3a*5A559C and IBD, CD or UC.

Adverse effects of inhaled corticosteroids in funded and nonfunded studies.

BACKGROUND: Evidence regarding the safety profile of drugs may vary depending on study sponsorship. We aimed to evaluate differences between studies funded by the pharmaceutical manufacturer of the drug (PF) and those with no pharmaceutical funding (NoPF) regarding the finding and interpretation of adverse effects of inhaled corticosteroids. METHODS: We assessed the safety reporting of inhaled corticosteroids in 275 PF and 229 NoPF studies identified by a MEDLINE search using prespecified criteria. RESULTS: Overall, the finding of statistically significant differences for adverse effects was significantly less frequent in PF (34.5%) than in NoPF (65.1%) studies (prevalence ratio, 0.53; 95% confidence interval, 0.44-0.64). This association became nonsignificant (prevalence ratio, 0.94; 95% confidence interval, 0.77-1.15) after controlling for design features (such as dose or use of parallel groups) that tended to be associated with less frequent finding of adverse effects and were more common in PF studies. Among studies finding a statistically significant increase in adverse effects associated with the study drug, the authors of PF articles concluded that the drug was "safe" more frequently than the authors of NoPF studies (prevalence ratio, 3.68; 95% confidence interval, 2.14-6.33). CONCLUSIONS: The type of funding may have determinant effects on the design of studies and on the interpretation of findings: funding by the industry is associated with design features less likely to lead to finding statistically significant adverse effects and with a more favorable clinical interpretation of such findings. Disclosure of conflicts of interest should be strengthened for a more balanced opinion on the safety of drugs.

Portadores faringeos de streptococcus pyogenes en escolares de diferente nivel socio-económico / Pharyngeal carries of streptococcus pyogenes in school children of different socioeconomic levels

Se estudiaron 196 niños, 103 varones y 93 hembras, en edades comprendidas entre 7 y 14 años, de dos niveles socieconómicos; el nivel alto, representado por 100 niños de un grupo educativo ubicado en la urbanización Prados del Este y el bajo, representado por 96 niños de una unidad escolar ubicada en la urbanización Prado de María. Se demostró la presencia de Streptococcus pyogenes en 11(11,0%) niños del nivel socieconomico alto. La mayor incidencia del Streptococcus pyogenes en la faringe de niños con bajo nivel socieconómico podría explicarse por razones epidemiológicas relacionadas con el hacinamiento del grupo familiar al cual pertenecen estos niños esto determinaria un mayor contacto interpersonal y, por lo tanto, estarían repetida y frecuentemente, expuestos a la adquisición del microorganismo