Severe Asthma and Biological Therapies: Now and the Future.

Recognition of phenotypic variability in pediatric asthma allows for a more personalized therapeutic approach. Knowledge of the underlying pathophysiological and molecular mechanisms (endotypes) of corresponding biomarkers and new treatments enables this strategy to progress. Biologic therapies for children with severe asthma are becoming more relevant in this sense. The T2 phenotype is the most prevalent in childhood and adolescence, and non-T2 phenotypes are usually rare. This document aims to review the mechanism of action, efficacy, and potential predictive and monitoring biomarkers of biological drugs, focusing on the pediatric population. The drugs currently available are omalizumab, mepolizumab, benralizumab, dupilumab, and 1ezepelumab, with some differences in administrative approval prescription criteria between the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Previously, we described the characteristics of severe asthma in children and its diagnostic and therapeutic management.

Woodchip bioreactors for saline leachates denitrification can mitigate agricultural impacts in mediterranean areas: The Campo de Cartagena-Mar Menor environmental issue.

Leachates from intensive agriculture containing high nitrate have been identified as a major cause of the severe eutrophication crisis that impacts Mar Menor (SE Spain), the largest hypersaline coastal lagoon in the Mediterranean basin. A best management practice for removing NO3--N is denitrifying bioreactors. This is the first study to assess the efficiency of citrus woodchips bioreactors in treating agricultural leachates that flow to the Mar Menor via surface discharges. Denitrification capacity, woodchip degradation (by weight loss), formation of potentially harmful compounds, and greenhouse gas (GHG) emissions were assessed. Three bioreactors (6 m × 0.98 m x 1.2 m) filled with citrus woodchips (3 m3 d-1 per bioreactor) through which the untreated ditch water over 1.5 years. Bioreactors were operated at 8 h, 16 h, and 24 h hydraulic residence time respectively, in each bioreactor. The main characteristics of the ditch water were: pH ≈ 7.5-8.0, electrical conductivity ≈ 5-8 dS m-1, dissolved organic carbon ≈6-10 mg L-1, and NO3--N ≈ 22-45 mg L-1. Bioreactors were highly efficient in reducing NO3--N. The average RNO3 in effluents was for the complete experimental period 8 g N m-3 d-1, 10.9 g N m-3 d-1, and 12.6 g N m-3 d-1 for 8, 16 and 24 h residence time, respectively. Nitrate reduction efficiency was modulated by seasonal changes in temperature, with an increasing efficiency in warmer periods (maximum ≈ 85-90% for all hydraulic residence time) and decreasing in colder ones (minimum ≈ 12%, 23% and 41% for hydraulic residence time 8, 16 and 24 h respectively). Woodchips degradation was greatest during the first six months (average ≈ 29% weight loss) in the material above the water level, attributable to aerobic mineralization of the organic carbon, while weight loss was ≈11% in woodchip media continuously below the water level. Dissolved organic carbon, sulfide, ammonium, and soluble phosphorus concentrations in the effluents were mostly low, although some peaks in concentrations occurred. Design consideration must be taken to avoid environmental impacts due to the occasional presence of harmful compounds in the effluents.

Quality of life in children with diseases causing central airway obstruction: Reliability and validity of the TAPQOL questionnaire.

INTRODUCTION: The aim of this study was to analyse the psychometric performance (reliability and validity) of the TAPQOL questionnaire in measuring the global quality of life in children with central airway obstruction (CAO), which encompasses pathologies with a low prevalence that have a common anatomical or functional affectation. METHOD: The study population consisted of 109 patients with CAO attended in a national reference airway unitafter signing informed consent. The TAPQOL questionnaire was used to measure the global quality of life and its psychometric characteristics were analysed. The reliability was determined using Cronbach's α statistic and the validity was determined by means of a principal component analysis. RESULTS: The mean age was 4.8 years and there was no predominant sex. The most frequent diagnosis was laryngomalacia (24.5%), followed bysubglotticstenosis (20.2%). The lowest score in the TAPQOL questionnaire was obtained for the scales of anxiety (66.2 ± 23.7), respiratory (67.9 ± 29.6), and conduct 68.2 ± 21.4). The Cronbach's α was above 0.7 in the majority of the scales and the validity study by principal component analysis with a total variance of 76.7% fits the original 12-component model. CONCLUSIONS: TAPQOL is a valid tool to measure the health-related quality of life in patients with CAO. Measuring it in these patients indicates which fields are most affected, highlighting therapeutic needs that have not been resolved but which can be approached in normal clinical practice.

Woodchip bioreactors provide sustained denitrification of brine from groundwater desalination plants.

Woodchip bioreactors are widely known as a best management practice to reduce excess nitrate loads that are discharged with agricultural leachates. The aim of this study was to evaluate the performance of citrus woodchip bioreactors for denitrification of brine (electrical conductivity ≈ 17 mS cm-1) from groundwater desalination plants with high nitrate content (NO3--N ≈ 48 mg L-1) in the Campo de Cartagena agricultural watershed, one of the main providers of horticultural products in Europe. The performance was evaluated relative to seasonal changes in temperature, dissolved organic carbon (DOC) provided by woodchips, hydraulic residence time (HRT) and woodchip aging. Bioreactors (capacity 1 m3) operated for 2.5 years (121 weeks) in batch mode (24 h HRT) with three batches per week. Denitrification efficiency was modulated by DOC concentration, temperature, hydraulic residence time and the drying-rewetting cycles. High salinity of brine did not prevent nitrate removal from occurring. The high DOC availability (>25 mg C L-1) during the first ≈48 weeks resulted in high nitrate removal rate (>75%) and nitrate removal efficiency (until ≈ 25 g N m-3 d-1) regardless of temperature. Moreover, the high DOC contents in the effluents during this period may present environmental drawbacks. Denitrification was still high after 2.5 years (reaching ≈9.3 g N m-3 d-1 in week 121), but dependence on warm temperature became more apparent with woodchips aging from week ≈49 onwards. Nitrate removal efficiency was highest on the first weekly batch, immediately after woodchips had been unsaturated for four days. It was attributable to a flush of DOC produced by aerobic microbial metabolism during drying that stimulated denitrification following re-saturation. Hence, alternance of drying-rewetting cycles is an operation practice that increase bioreactors nitrate removal performance.

Bioreactors for brine denitrification produced during polluted groundwater desalination in fertigation areas of SE Spain: batch assays for substrate selection.

Increasing knowledge of nitrate removal using denitrifying bioreactors has illustrated the usefulness of this management practice for treating discharge water from agricultural land uses. The objective of this study was to assess the viability of almond shell, chopped carob, olive bone, and citrus woodchip as carbon media for denitrification of brine with high nitrate load (EC ≈ 20 dS m-1, NO3--N concentration ≈ 65-80 mg NO3--N L-1) in bioreactors. To the authors' knowledge, this is the first test of denitrifying brine using organic wastes as the carbon substrate, and the first use of these carbon media for that purpose. Nitrate removal efficiency and efficiency:cost ratio were considered. The results indicated that the best removal efficiency and cheapest cost were provided by citrus woodchip (3.02 ± 0.15 mg NO3--N m-3 d-1) at a cost of ≈ 6€ m-3, followed by almond shell (1.54 ± 0.20 mg NO3--N m-3 d-1) at a cost of ≈ 19€ m-3. Chopped carob and olive bone showed negligible nitrate removal in the brine; chopped carob generated acidic leachate with extremely high dissolved organic carbon, and olive bone resulted in a highly saline leachate. Of the four media tested, the results of this study indicated that citrus woodchip was the most suitable media for denitrification of the brine.