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Background: Oral immunotherapy (OIT) is a promising approach to cow’s milk and egg allergies, but reactions are frequent and some patients cannot be desensitized. Objective: To evaluate long-term OIT outcomes with omalizumab (OMZ) in paediatric patients with severe egg and/or milk allergies. Methods: This retrospective real-life study analysed findings in children with Immunoglobulin E-mediated allergy to cow’s milk and/or hen eggs refractory to conventional OIT, who underwent OIT with OMZ in our department between 1 January 2010 and 31 December 2015. Results: In all, 41 patients were included (median age: 7 years; interquartile range [IQR]: 5.5–9.5); 26/41 (63.4%) underwent OIT for milk, 8/41 (19.5%) for egg and 7/41 (17.1%) for both. The median time between initiation of OMZ and OIT was 27 weeks (IQR: 22–33). Forty (97.56%) patients reached the maintenance phase (200 mL of cow’s milk and 30 mL of raw egg or 1 cooked egg) in a median time of 27 weeks (IQR: 18–37). The median total time with OMZ was 117 weeks (IQR: 88–144). During the OMZ period, 2.44% (1/41) of patients presented anaphylaxis. After discontinuation of OMZ, 29.3% (12/41) presented anaphylaxis, 50% of them had a poor adherence to daily ingestion. One patient (2.44%) was diagnosed with eosinophilic esophagitis after 2 years of discontinuation of OMZ. Currently, after a median time of 9 years (IQR: 7–10) since the initiation of OMZ, 75.6% (31/41) are desensitized (27/31 without OMZ). Conclusions: Omalizumab allows desensitisation of children with severe allergies to cow’s milk and/or egg without developing severe reactions while receiving this treatment. However, discontinuation of OMZ leads to severe allergic reactions, and hence must be monitored carefully.

Background: In most cases, severe asthma in children has an allergic etiology, but allergen-specific immunotherapy (AIT) is contraindicated. Objective: This study aimed at analyzing the safety and efficacy of AIT in patients with severe asthma treated with omalizumab (OM). Methods: A descriptive real-life study was carried out by reviewing medical records. Effectiveness was measured by the degree of control (CAN questionnaire), number of hospitalizations per year, number of exacerbations per year, and maintenance treatment and lung function (FEV1). Some adverse reactions occurred (AAI-EAACI-WAO guidelines). Results: The retrospective study included 29 patients up to 18 years of age with severe asthma with OM plus AIT treatment. AIT treatment was started in a cluster schedule when patients treated with OM achieved disease control. Before starting AIT, patients were treated with OM for 1 year for achieving asthmatic control. AIT to mites (51%), Alternaria (37.9%), or pollens (10.3%) was administered. After one year with OM plus AIT,statistically significant differences in CAN scores and FEV1 measures were observed (P < 0.001). No patients under treatment with OM plus AIT required hospital admission. During the clustering schedule, only 3/64 doses showed systemic adverse reactions. During the AIT maintenance treatment, 348 doses were administered, with no significant adverse reactions. Conclusion: In this population-based study in children with severe asthma, the combined treatment with OM plus AIT was safe and effective. This strategy allows these pediatric patients to be safely treated with AIT.

There has been exciting progress in diagnosis and in the treatment of allergic patients. The objective of this review is to summarize the most relevant contributions in the past 10 years with a special focus on the pediatric population allergic to aeroallergens and provide the most relevant references and practical issues for the decision-making. Current guidelines on allergy diagnosis recommend a thorough clinical history as the first step, followed by allergen extract testing using an in vivo prick test and/or an in vitro specific IgE test. Molecular diagnosis is recommended when previous tests are inconclusive. In practice, the most important factors to decide the AIT treatment are the actual intensity and duration of the patient's symptoms and the availability of appropriate AIT products for the patient's sensitization profile at high allergen concentrations and with confirmed efficacy and safety from clinical trials. This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. The experts concluded that AIT is efficacious and safe for the treatment of allergic patients that is available for the most frequent aeroallergens.What is Known:• The prevalence of allergic asthma and rhinitis in children has increased in recent decades.• The efficacy and safety of allergen immunotherapy has been shown in multiple studies and systematic reviews.What is New:• This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. Recommendations of expert authors for the decision of the patients more suitable for allergen immunotherapy are included.

Background There is little evidence of the effects of early treatment with growth hormone (GH) in infants with Prader-Willi syndrome (PWS). A prospective study was conducted to assess the safety of GH therapy in infants younger than 2 years of age with PWS. Methods A total of 14 patients with PWS started treatment with GH under the age of 2 years and were followed over a 2-year period. A deletion of chromosome 15 was present in nine infants (64.3%) and maternal uniparental disomy 15 in five infants (35.7%). The median age at start of GH treatment was 9.6 months (interquartile range [IQR] 9.0–18.3 months). Changes in height standard deviation score (SDS), body mass index (BMI) SDS and subcapsular and tricipital skinfolds in the follow-up period were evaluated with a mixed-model regression analysis using the Package R. Results There were no fatal adverse events. A significant decrease (p Conclusions GH treatment in infants with PWS less than 2 years of age is safe and improved body composition. Infants who received GH before the age of 15 months started to walk earlier.

Obstructive sleep-disordered breathing includes a spectrum of clinical entities with variable severity ranging from primary snoring to obstructive sleep apnea syndrome (OSAS). The clinical suspicion for OSAS is most often raised by parental report of specific symptoms and/or abnormalities identified by the physical examination which predispose to upper airway obstruction (e.g., adenotonsillar hypertrophy, obesity, craniofacial abnormalities, neuromuscular disorders). Symptoms and signs of OSAS are classified into those directly related to the intermittent pharyngeal airway obstruction (e.g., parental report of snoring, apneic events) and into morbidity resulting from the upper airway obstruction (e.g., increased daytime sleepiness, hyperactivity, poor school performance, inadequate somatic growth rate or enuresis). History of premature birth and a family history of OSAS as well as obesity and African American ethnicity are associated with increased risk of sleep-disordered breathing in childhood. Polysomnography is the gold standard method for the diagnosis of OSAS but may not be always feasible, especially in low-income countries or non-tertiary hospitals. Nocturnal oximetry and/or sleep questionnaires may be used to identify the child at high risk of OSAS when polysomnography is not an option. Endoscopy and MRI of the upper airway may help to identify the level(s) of upper airway obstruction and to evaluate the dynamic mechanics of the upper airway, especially in children with combined abnormalities. Pediatr Pulmonol. 2017;52:260-271. © 2016 Wiley Periodicals, Inc.

This document summarises the conclusions of a European Respiratory Society Task Force on the diagnosis and management of obstructive sleep disordered breathing (SDB) in childhood and refers to children aged 2–18 years. Prospective cohort studies describing the natural history of SDB or randomised, double-blind, placebo-controlled trials regarding its management are scarce. Selected evidence (362 articles) can be consolidated into seven management steps. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are present (step 1). Central nervous or cardiovascular system morbidity, growth failure or enuresis and predictors of SDB persistence in the long-term are recognised (steps 2 and 3), and SDB severity is determined objectively preferably using polysomnography (step 4). Children with an apnoea–hypopnoea index (AHI) >5 episodes·h−1, those with an AHI of 1–5 episodes·h−1and the presence of morbidity or factors predicting SDB persistence, and children with complex conditions (e.g.Down syndrome and Prader–Willi syndrome) all appear to benefit from treatment (step 5). Treatment interventions are usually implemented in a stepwise fashion addressing all abnormalities that predispose to SDB (step 6) with re-evaluation after each intervention to detect residual disease and to determine the need for additional treatment (step 7).

STUDY OBJECTIVES Upper airway (UA) collapsibility is a major pathophysiologic feature of the obstructive sleep apnea syndrome (OSAS). In adolescents, it is measured by obtaining the slope of pressure-flow relationship (SPF) while applying negative nasal pressure during sleep. An easier technique to assess UA collapsibility, consisting of application of negative expiratory pressure (NEP) during wakefulness, has demonstrated differences between control and OSAS subjects. We hypothesized that the NEP technique would correlate with SPF as a measurement of UA collapsibility in adolescents. DESIGN During wakefulness, NEP of -5 cm H2O in the seated and supine position was applied during the first second of expiration. The area under the expiratory flow-volume curve during NEP was compared to tidal breathing (RatioNEP). In addition, adolescents underwent SPF measurements during sleep. Two SPF techniques were performed to measure the activated and relatively hypotonic UA. SETTING Pediatric sleep laboratory. PARTICIPANTS Seven adolescents with OSAS and 20 controls. RESULTS In the seated position, there was a correlation between RatioNEP and both hypotonic SPF (r = -0.39, P = 0.04) and activated SPF (r = -0.62, P = 0.001). In the supine position, there was a correlation between RatioNEP and activated SPF (r = -0.43, P = 0.03) and a trend for hypotonic SPF (r = -0.38, P = 0.06). CONCLUSIONS The negative expiratory pressure (NEP) technique correlates with the hypotonic and activated slope of pressure-flow relationship measurements. The seated position showed the strongest correlation. The NEP technique can be used as an alternative method to evaluate upper airway collapsibility in adolescents.

The present statement was produced by a European Respiratory Society Task Force to summarise the evidence and current practice on the diagnosis and management of obstructive sleep disordered breathing (SDB) in children aged 1–23 months. A systematic literature search was completed and 159 articles were summarised to answer clinically relevant questions. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are identified. Morbidity (pulmonary hypertension, growth delay, behavioural problems) and coexisting conditions (feeding difficulties, recurrent otitis media) may be present. SDB severity is measured objectively, preferably by polysomnography, or alternatively polygraphy or nocturnal oximetry. Children with apparent upper airway obstruction during wakefulness, those with abnormal sleep study in combination with SDB symptoms (e.g.snoring) and/or conditions predisposing to SDB (e.g.mandibular hypoplasia) as well as children with SDB and complex conditions (e.g.Down syndrome, Prader–Willi syndrome) will benefit from treatment. Adenotonsillectomy and continuous positive airway pressure are the most frequently used treatment measures along with interventions targeting specific conditions (e.g.supraglottoplasty for laryngomalacia or nasopharyngeal airway for mandibular hypoplasia). Hence, obstructive SDB in children aged 1–23 months is a multifactorial disorder that requires objective assessment and treatment of all underlying abnormalities that contribute to upper airway obstruction during sleep.

Obstructive sleep-disordered breathing includes a spectrum of clinical entities with variable severity ranging from primary snoring to obstructive sleep apnea syndrome (OSAS). The clinical suspicion for OSAS is most often raised by parental report of specific symptoms and/or abnormalities identified by the physical examination which predispose to upper airway obstruction (e.g., adenotonsillar hypertrophy, obesity, craniofacial abnormalities, neuromuscular disorders). Symptoms and signs of OSAS are classified into those directly related to the intermittent pharyngeal airway obstruction (e.g., parental report of snoring, apneic events) and into morbidity resulting from the upper airway obstruction (e.g., increased daytime sleepiness, hyperactivity, poor school performance, inadequate somatic growth rate or enuresis). History of premature birth and a family history of OSAS as well as obesity and African American ethnicity are associated with increased risk of sleep-disordered breathing in childhood. Polysomnography is the gold standard method for the diagnosis of OSAS but may not be always feasible, especially in low-income countries or non-tertiary hospitals. Nocturnal oximetry and/or sleep questionnaires may be used to identify the child at high risk of OSAS when polysomnography is not an option. Endoscopy and MRI of the upper airway may help to identify the level(s) of upper airway obstruction and to evaluate the dynamic mechanics of the upper airway, especially in children with combined abnormalities. Pediatr Pulmonol. 2017;52:260-271. © 2016 Wiley Periodicals, Inc.

Resumen Introduccion La hiperreactividad bronquial (HRB)es caracteristica del asma bronquial. Se ha observado que pacientes afectos de rinitis alergica que no refieren clinica de asma bronquial al realizar una espirometria presentan HRB. Esto podria indicar la presencia de inflamacion subclinica de la via respiratoria inferior. Hemos revisados los pacientes diagnosticados de rinitis alergica sin clinica de asma bronquial en relacion a la hiperreactividad bronquial con el objetivo de determinar si los pacientes diagnosticados, en nuestra unidad, de rinitis alergica sin clinica de asma bronquial presentan hiperreactividad bronquial y observar que alergenos son los causantes de esta clinica en nuestros pacientes Metodos y resultados Estudio retrospectivo, observacional. Poblacion, pacientes diagnosticados de rinitis alergica en nuestra Unidad de Alergologia entre agosto 2000 y diciembre 2001. Se ha procedido a la revision de las historias clinicas recogiendo los datos siguientes: demograficos, edad, sexo, clinica de rinitis (perenne o estacional), conjuntivitis, dermatitis atopica, bronquitis, sensibilizacion (IgE especifica, pruebas cutaneas, pruebas de provocacion nasal), valor de IgE total, espirometria realizada mediante prueba de esfuerzo (positiva con un descenso del FEV1 > 15 % con el esfuerzo o un ascenso del FEV1 del 12 % tras broncodilatacion) y la presencia de antecedentes familiar de patologia alergica. Se han revisado un total de 135 historias clinicas de pacientes afectos de rinitis alergica. Hemos hallado 68/135 que no referian sintomas de asma bronquial (35 hombres y 33 mujeres) con edades comprendidas entre 4-18 anos. La mayoria de nuestros pacientes refieren rinitis perenne(50/68) y estan sensibilizados a acaros (44/68). No se habia realizado espirometria en el momento del diagnostico en 14/68. Presentaron prueba de esfuerzo positiva 13/54 (24%).Todos los pacientes que mostraron hiperreactividad bronquial estaban sensibilizados a acaros y solo uno de ellos referia rinitis estacional Conclusiones Segun los ultimos consensos en el tratamiento y control de la rinitis alergica –The Allergic Rhinitis and its Impact on Asthma Workshop Report– asma bronquial y rinitis alergica son distintas manifestaciones de una sola via aerea y de la misma patologia. Con los resultados que hemos obtenido sugerimos la valoracion sistematica de la hiperreactividad bronquial en el protocolo de estudio de la rinitis alergica en pacientes que no refieren clinica de asma bronquial

Resumen Antecedentes La inmunoterapia especifica con alergenos es el unico tratamiento capaz de modificar el curso natural de las enfermedades alergicas, siendo mas eficaz cuanto mas precozmente se inicie. Sin embargo, las recomendaciones de la OMS continuan considerando la edad inferior a 5 anos como una contraindicacion relativa. Por este motivo se ha revisado un grupo de 22 ninos que han iniciado inmunoterapia antes de los 5 anos de edad en la unidad de alergia pediatrica hospitalaria Metodos y resultados El grupo esta formado por22 ninos diagnosticados de asma bronquial conhipersensibilidad a acaros domesticos que iniciaronlainmunoterapia antes de los 5 anos de edad. Entodos ellos se utilizaron extractos estandarizados biologicamente siguiendo pauta convencional subcutanea y control hospitalario. La tolerancia y eficacia de inmunoterapia se evaluaron mediante criterios clinicos. La duracion media del tratamiento fue de 16,95 (± 10,12) meses. Se observaron reacciones adversas locales en 5 ninos y sistemicas moderadas en 7 ninos. En los ninos que llevaban mas de 1 ano de tratamiento (15 ninos) se observo una reduccion del numero de crisis anuales (de 5,13 a 2,57) y de los ingresos hospitalarios (5 ninos antes y 2 ninos despues). Los requerimientos de tratamiento farmacologico de alivio disminuyeron en 10 ninos Conclusion Los datos de este estudio sugieren que la inmunoterapia especifica con un extracto deacaros bajo control hospitalario puede ser iniciadaprecozmente con buena tolerancia y mejoriaclinica

STUDY OBJECTIVES Upper airway (UA) collapsibility is a major factor in the pathophysiology of sleep disordered breathing (SDB). We hypothesized that the negative expiratory pressure (NEP) technique could distinguish between normal children and children with SDB even during wakefulness. DESIGN During wakefulness, NEP of -5 and -10 cm H(2)O was applied during expiration in seated and supine positions. UA muscle activity (EMG) was measured using intra-oral electrodes. SETTING Sleep laboratory. PARTICIPANTS Twenty children with snoring, 20 with obstructive sleep apnea syndrome (OSAS), and 20 controls. MEASUREMENTS AND RESULTS The ratio of the area under the expiratory flow-volume curve during NEP compared to tidal breathing (RatioNEP) was calculated. Similarly, EMG area under the curve during NEP as a ratio of baseline was measured (RatioEMG). There were significant differences in RatioNEP between controls and snorers and controls and OSAS, at both pressures, in both the seated and supine positions; P < 0.0001 for all (e.g., RatioNEP at -5 cm H(2)O, seated: 1.8 ± 0.5, 2.1 ± 0.4, and 3.0 ± 0.6 for OSAS, snorers, and controls, respectively). However, no significant differences were found between snorers and OSAS. For RatioEMG, no significant differences were found between groups. CONCLUSIONS RatioNEP distinguishes between normal children and children with SDB, be it snoring or OSAS, indicating that these children have a more collapsible UA even during wakefulness. However, it does not differentiate between snorers and OSAS, highlighting the important role of UA muscle activity during sleep. NEP technique does not elicit a different UA muscle activity response between controls and children with SDB.

Our purpose is to determine the inflammatory changes in the airways of allergic paediatric asthma patients treated with omalizumab, measured by the percentage of

Rituximab (RTX) is a monoclonal antibody; recently it has been use as a new treatment strategy in patients with high-degree steroid-dependent nephrotic syndrome. It provokes a lymphocyte B depletion in some cases that interacts with Immunoglobulins creating decreased plasma IgG levels and hypogammaglobulinemia. We report the case of a 2.5 year old male diagnosed of idiopathic nephrotic syndrome. He presented resistance to systemic steroids as well as second line treatments (cyclophosphamide and mycophenolate). Patient started with intravenous infussion of rituximab at 375mg/m2. Baseline analysis before RTX treatment evidenced low IgG levels, although these values are not conclusive because they were taken during nephrotic state. Twenty days later, the patient presented severe hypogammaglobulinemia with IgG levels of 149 mg/dL, without nephrotic proteinuria. We decided to start intravenous gammaglobulin (IVIG) every 4-6 weeks. Analysis showed low levels of lymphocytes (predominantly B type) four days after initiated the treatment. Follow up demonstrated complete recovery of lymphocyte count two years later. After 3 years of RTX administration the patient continues to have hypogammaglobulimenia, requiring IVIG until now.