Impact of 1-Year Supplementation with High-Rich Docosahexaenoic Acid (DHA) on Clinical Variables and Inflammatory Biomarkers in Pediatric Cystic Fibrosis: A Randomized Double-Blind Controlled Trial.

A randomized, double-blind, and placebo-controlled study was conducted to assess the effect of dietary supplementation with high-rich docosahexaenoic acid (DHA) (Tridocosahexanoin-AOX® 70%) at 50 mg/kg/day in pediatric patients with cystic fibrosis (CF) as compared with placebo. The duration of supplementation was 12 months. A total of 22 patients were included, with 11 in the DHA group and 11 in the placebo group. The mean age was 11.7 years. The outcome variables were pulmonary function, exacerbations, sputum cellularity, inflammatory biomarkers in sputum and peripheral blood, and anthropometric variables. In the DHA group, there was a significant increase in FVC (p = 0.004) and FVE1 expressed in liters (p = 0.044) as compared with placebo, and a lower median number of exacerbations (1 vs. 2). Differences in sputum cellularity (predominantly neutrophilic), neutrophilic elastase, and sputum and serum concentrations of resolvin D1 (RvD1), interleukin (IL)-8 (IL-8), and tumor necrosis factor alpha (TNF-α) between the study groups were not found. Significant increases in weight and height were also observed among DHA-supplemented patients. The administration of the study product was safe and well tolerated. In summary, the use of a highly concentrated DHA supplement for 1 year as compared with placebo improved pulmonary function and reduced exacerbations in pediatric CF.

Airway surface liquid pH in paediatric patients with cystic fibrosis / PH del líquido de la vía aérea en pacientes pediátricos con fibrosis quística

Background: Cystic fibrosis (CF) patients have more acidic airway surface liquid (ASL), which can denature antimicrobial defensins. Induced sputum is non-invasive and is as representative as bronchoalveolar lavage. Objectives: The objectives of this study were to analyse the ASL pH obtained by induced sputum and assess the relationship between clinical features in paediatric CF patients. Methods: This is a prospective observational study in CF paediatric patients. Sputum was induced in a patient by inhaling 4.5% hypertonic saline, the sputum was collected into a sterile container for pathological analysis, and the pH was measured from the liquid part (ASL) in a gas machine. Results: A total of 27 patients were included in the study: mean age (11.96 ± 3.9) years, mean sweat test (99.38 ± 17.76) ng/L, common mutation Del508F (N24, 88.8%), mean FEV1% 91.94% ± –12.6%, Staphylococcus colonization 14 (51.9%), normal chest CT 8 (29.6%), air trapping 12 (44.4%), bronchiectasis 6 (22.2%), and mean ASL pH 6.72 ± 0.06 (n = 15). A significant correlation was found between a higher sweat test and lower ASL pH (R = 0.683, p = 0.005). There were no differences between altered chest CT (p = 0.199) and positive Staphylococcus aureus (p = 0.17). Conclusion: This is the first publication that use induced sputum to obtain the ASL pH in CF patients. The ASL pH in CF patients is usually acidic and correlated with altered transmembrane function conductance. (AU)

Antecedentes: Los pacientes con fibrosis quística (FQ) tienen el líquido de la vía aérea (ASL) ácido, provocando desnaturalización de defensinas antimicrobianas. El esputo inducido es reproducible, no invasivo y la muestra es equiparable al lavado broncoalveolar. Objetivo: Evaluar el pH ASL obtenido por esputo inducido y analizar sus implicaciones clínicas, en niños FQ. Métodos: Estudio observacional prospectivo desarrollado en niños FQ. El esputo se indujo mediante inhalación de solución salina hipertónica 4,5%. Se recolectó el esputo y posterior al análisis patológico el ASL se colocó en una jeringa y se midió pH con una máquina de gases. Resultados: Se incluyeron 27 pacientes: edad (11,96 ± 3,9) años, test del sudor (99,38 ± 17,76) ng/L, variante común Del508F (N24, 88,8%), FEV1% 91,94% ± 12,6%, Staphylococcus 14 (51,9%), TAC pulmonar normal 8 (29,6%), atrapamiento 12 (44,4%), bronquiectasias 6 (22,2%), pH ASL 6,72 ± 0,06 (n = 15). Se observó correlación significativa entre niveles elevados del test del sudor y pH ASL ácido (R = 0,683, p = 0,005). No hubo correlación entre pH ASL y TAC pulmonar alterado (p = 0,199) o S. aureus positivo (p = 0,17). Conclusiones: Esta es la primera publicación que utiliza esputo inducido para medir pH del ASL en FQ. El pH ASL se correlacionó con la alteración del gen de conductancia transmembranal. (AU)

Changes of Erythrocyte Fatty Acids after Supplementation with Highly Concentrated Docosahexaenoic Acid (DHA) in Pediatric Cystic Fibrosis: A Randomized Double-Blind Controlled Trial.

We characterized the fatty acid profiles in the erythrocyte membrane of pediatric patients with cystic fibrosis (CF) receiving highly concentrated docosahexaenoic acid (DHA) supplementation (Tridocosahexanoin-AOX® 70%) at 50 mg/kg/day (n = 11) or matching placebo (n = 11) for 12 months. The mean age was 11.7 years. The DHA group showed a statistically significant improvement in n-3 polyunsaturated fatty acids (PUFAs), which was observed as early as 6 months and further increased at 12 months. Among the n-3 PUFAs, there was a significant increase in DHA and eicosapentaenoic acid (EPA). Additionally, a statistically significant decrease in n-6 PUFAs was found, primarily due to a decrease in arachidonic acid (AA) levels and elongase 5 activity. However, we did not observe any changes in linoleic acid levels. The long-term administration of DHA over one year was safe and well tolerated. In summary, the administration of a high-rich DHA supplement at a dose of 50 mg/kg/day for one year can correct erythrocyte AA/DHA imbalance and reduce fatty acid inflammatory markers. However, it is important to note that essential fatty acid alterations cannot be fully normalized with this treatment. These data provide timely information of essential fatty acid profile for future comparative research.

Long-term outcome of omalizumab-assisted desensitisation to cow's milk and eggs in patients refractory to conventional oral immunotherapy: real-life study.

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.

Combination therapy of specific aeroallergens immunotherapy and omalizumab, in children with severe asthma

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 (AU)

Long-term outcome of omalizumab-assisted desensitisation to cow’s milk and eggs in patients refractory to conventional oral immunotherapy: real-life study

Background: Oral immunotherapy (OIT) is a promising approach to cow’s milk and egg aller-gies, 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 under-went 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 anaphy-laxis. 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 esoph-agitis 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, dis-continuation of OMZ leads to severe allergic reactions, and hence must be monitored carefully.© 2022 Codon Publications. Published by Codon Publications (AU)

Characterization of severe asthma in the pediatric population

Introduction and objectives Relationship between the causal mechanisms of pediatric severe asthma and severity of symptoms would be helpful for developing personalized strategies for treatment and prevention. Materials and methods For this study, 698 medical histories of asthmatics between 6 and 18 years of age were reviewed in a period of 2 years. Variables analyzed were: age, sex, ethnicity, perinatological history, allergy history, asthma predictive index (API), exposure to tobacco, heavy traffic or epithelium, lung function, age of onset of symptoms, hospitalization admissions/PICU, systemic corticosteroids, daily symptoms control, device prescribe for daily control, and adherence. Results A total of 86 children with severe asthma were included (12.3%). Mean age 13.3 +/− 1.86 years, sex ratio1:1, mean age of symptom onset 2.765 +/− 3.06 years, mean IgE 1076.18KU / L +/− 1136, mean eosinophils 604c / mcl +/− 511.9, mean of FEV1 93.15% +/− 16.3. Evidently, 70 children (81.4%) had positive API, 68 (79.1%) rhinitis, 34 (39.5%) atopic dermatitis. 73 (83.9%) sensitized to inhalants and 56 (65.1%) to dermatophagoides, 39 (45.3%) passive smokers, 19 (22.1%) exposure to heavy traffic; 55 (64%) showed symptoms with exercise, 35 (40.7%) had audible wheezing. The mean systemic corticosteroid cycles/year was 3.63 +/− 3.23, mean PICU admissions 0.36 +/− 0.83, mean hospital admissions 4.31 +/− 5.3, average emergency room visits/year 19.44 +/− 16.28. 38 (56.7%) had good adherence, 44 (51%) used an MDI device and 39 (45.3%) used dry powder. Conclusions Children with severe asthma meet the following criteria: premature, positive API, rhinitis, atopic dermatitis, high IgE, eosinophilia, passive smokers, exposure to heavy traffic, decreased lung function, and low adherence to controller medication (AU)

Omalizumab outcomes for up to 6 years in pediatric patients with severe persistent allergic asthma.

BACKGROUND: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. METHODS: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients < 18 years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared with the baseline period. RESULTS: Of the 484 patients included, 101 (20.9%) reached 6 years of treatment. The mean ± standard deviation number of exacerbations decreased during the first year of treatment (7.9 ± 6.6 to 1.1 ± 2.0, P < .001) and remained likewise for up to 6 years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. CONCLUSION: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

Characterization of severe asthma in the pediatric population.

INTRODUCTION AND OBJECTIVES: Relationship between the causal mechanisms of pediatric severe asthma and severity of symptoms would be helpful for developing personalized strategies for treatment and prevention. MATERIALS AND METHODS: For this study, 698 medical histories of asthmatics between 6 and 18 years of age were reviewed in a period of 2 years. Variables analyzed were: age, sex, ethnicity, perinatological history, allergy history, asthma predictive index (API), exposure to tobacco, heavy traffic or epithelium, lung function, age of onset of symptoms, hospitalization admissions/PICU, systemic corticosteroids, daily symptoms control, device prescribe for daily control, and adherence. RESULTS: A total of 86 children with severe asthma were included (12.3%). Mean age 13.3 +/- 1.86 years, sex ratio1:1, mean age of symptom onset 2.765 +/- 3.06 years, mean IgE 1076.18KU / L +/- 1136, mean eosinophils 604c / mcl +/- 511.9, mean of FEV1 93.15% +/- 16.3. Evidently, 70 children (81.4%) had positive API, 68 (79.1%) rhinitis, 34 (39.5%) atopic dermatitis. 73 (83.9%) sensitized to inhalants and 56 (65.1%) to dermatophagoides, 39 (45.3%) passive smokers, 19 (22.1%) exposure to heavy traffic; 55 (64%) showed symptoms with exercise, 35 (40.7%) had audible wheezing. The mean systemic corticosteroid cycles/year was 3.63 +/- 3.23, mean PICU admissions 0.36 +/- 0.83, mean hospital admissions 4.31 +/- 5.3, average emergency room visits/year 19.44 +/- 16.28. 38 (56.7%) had good adherence, 44 (51%) used an MDI device and 39 (45.3%) used dry powder. CONCLUSIONS: Children with severe asthma meet the following criteria: premature, positive API, rhinitis, atopic dermatitis, high IgE, eosinophilia, passive smokers, exposure to heavy traffic, decreased lung function, and low adherence to controller medication.

Infección bronquial por Pseudomonas aeruginosa en los pacientes con fibrosis quística diagnosticados por cribado neonatal / Bronchial Infection due to Pseudomonas Aeruginosa in Patients with Cystic Fibrosis Diagnosed in Neonatal Screening

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Polisomnografía: ¿Gold estándar? / No disponible

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