Asthma is one of the most common chronic diseases of childhood. Allergen sensitization and high frequencies of comorbid allergic diseases are characteristic of severe asthma in children. Omalizumab, ...an anti-IgE mAb, is the first targeted biologic therapeutic approved for the treatment of moderate-to-severe persistent allergic asthma (AA) that remains uncontrolled despite high-dose inhaled corticosteroids plus other controller medications. Since its initial licensing for use in adults and adolescents 12 years of age and older, the clinical efficacy, safety, and tolerability of omalizumab have been demonstrated in several published clinical trials in children aged 6 to less than 12 years with moderate-to-severe AA. These studies supported the approval of the pediatric indication (use in children aged ≥6 years) by the European Medicines Agency in 2009 and the US Food and Drug Administration in 2016. After this most recent change in licensing, we review the outcomes from clinical trials in children with persistent AA receiving omalizumab therapy and observational studies from the past 7 years of clinical experience in Europe. Data sources were identified by using PubMed in 2016. Guidelines and management recommendations and materials from the recent US Food and Drug Administration's Pediatric Advisory Committee meeting are also reviewed.
The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. An important step ...forward in the diagnosis of allergy to furry animals has been made with the introduction of molecular-based allergy diagnostics. A workshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components.
Background Isolated Ara h 8 sensitization is suggested to be associated with no or mild symptoms among peanut-sensitized subjects. Objective We sought to investigate the occurrence of systemic ...reactions in children with isolated sensitization to Ara h 8. Methods Participants were 144 children sensitized to Ara h 8 (≥0.35 kUA /L) but not to Ara h 1, Ara h 2, or Ara h 3 (<0.35 kUA /L). An open oral challenge with peanut was performed in those subjects who did not consume peanut regularly, and an extended IgE reactivity profile was obtained. If the child had a documented history of systemic reactions up to grade I anaphylaxis, double-blind, placebo-controlled food challenges were performed. Results One hundred twenty-nine (89.5%) children were either peanut consumers or did not react to peanut challenge. Another 14 (9.7%) children experienced oral cavity symptoms at the first 2 but not subsequent challenge doses. At the time of the double-blind, placebo-controlled food challenge, 1 boy with a previous mild systemic reaction to peanut experienced lip swelling, stomach cramping, and objective tiredness. Reanalysis of IgE levels showed an increase in peanut IgE levels from 1.5 to 8.8 kUA /L, but IgE levels to Ara h 8 remained stable and IgE levels to Ara h 1, Ara h 2, and Ara h 3 were all still less than 0.35 kUA /L. The IgE level to Ara h 6 was 0.45 kUA /L. Conclusion Isolated Ara h 8 sensitization indicates tolerance to peanuts in almost all cases. However, sensitization against thus far unidentified determinants in peanut might cause symptoms in rare cases.
Background Problematic severe childhood asthma includes a subgroup of patients who are resistant to therapy. The specific mechanisms involved are unknown, and novel biomarkers are required to ...facilitate treatment and diagnosis of therapy-resistant asthma. The chitinase-like protein YKL-40 has been related to asthma and airway remodeling. Objectives To compare serum YKL-40 levels in children with severe, therapy-resistant asthma (n = 34), children with controlled persistent asthma (n = 39), and healthy controls (n = 27), and to investigate correlations with biomarkers of inflammation and airway remodeling. Methods The study protocol included questionnaires, measurement of exhaled nitric oxide in exhaled air, blood sampling for inflammatory biomarkers, and high-resolution computed tomography of the lungs to identify bronchial wall thickening (therapy-resistant only). Serum YKL-40 levels were measured by ELISA, and all asthmatic children were genotyped for a CHI3L1 promoter single nucleotide polymorphism (rs4950928). Results Serum YKL-40 levels were significantly higher in children with therapy-resistant asthma than in healthy children (19.2 ng/mL vs 13.8 ng/mL, P = .03). Among children with severe, therapy-resistant asthma, YKL-40 levels correlated with fraction of exhaled nitric oxide in exhaled air ( r = 0.48, P = .004), blood neutrophils ( r = 0.63, P < .001), and bronchial wall thickening on high-resolution computed tomography ( r = 0.45, P = .01). Following adjustment for CHI3L1 genotype, significantly greater levels of YKL-40 were found in children with therapy-resistant asthma than in children with controlled asthma. Conclusions YKL-40 levels are increased in children with severe, therapy-resistant asthma compared to healthy children, and also compared to children with controlled asthma following correction for genotype.
Background Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration ...of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA). Objective We sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes. Methods Gene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs. Results Sample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA) , which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA. Conclusion Circulating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches.
Methods Thirty-one children diagnosed with wheat allergy by either a positive oral wheat challenge or a convincing recent history, and 72 grass-pollen allergic children currently eating wheat ...(controls) were recruited for the study.
Sensitisation at 4 years, vs. those non-sensitised, was associated with FHS in adolescence (OR 5.09; 95%CI 3.10-8.36). ...concomitant sensitisation to food and aeroallergens more strongly increased ...FHS risk in adolescence (OR 11.2; 95%CI 7.55-16.6), than either food (OR 2.65) or aeroallergens (OR 3.02) alone.
Results Severe asthmatic children had inferior asthma control (p<0.001) and increased bronchial hyperresponsiveness (p=0.01)in spite of high doses of inhaled steroids (> 800ug budesonide), compared ...to children with controlled asthma.
PDF
