Immunomodulation in pediatric asthma

Childhood asthma is actually defined as a heterogeneous disease, including different clinical variants and partially sharing similar immune mechanisms. Asthma management is mainly focused on maintaining the control of the disease and reducing the risk of adverse outcomes. Most children achieve good control with standard therapies, such as low doses of inhaled corticosteroids (ICS) and/or one or more controller. These medications are targeted to suppress bronchial inflammation and to restore airway responsiveness. However, they are not disease-modifying and do not specifically target inflammatory pathways of asthma; in addition, they are not significantly effective in patients with severe uncontrolled asthma. The aim of this review is to update knowledge on current and novel therapeutic options targeted to immunomodulate inflammatory pathways underlying pediatric asthma, with particular reference on biologic therapies

Food allergies: Current and future treatments

Food allergies are an increasingly public health problem, affecting up to 10% of children and causing a significant burden on affected patients, resulting in dietary restrictions, fear of accidental ingestion and related risk of severe reactions, as well as a reduced quality of life. Currently, there is no specific cure for a food allergy, so the only available management is limited to strict dietary avoidance, education on prompt recognition of symptoms, and emergency treatment of adverse reactions. Several allergen specific-and nonspecific-therapies, aiming to acquire a persistent food tolerance, are under investigation as potential treatments; however, to date, only immunotherapy has been identified as the most promising therapeutic approach for food allergy treatment. The aim of this review is to provide an updated overview on changes in the treatment landscape for food allergies

Allergen-specific immunotherapy: an update on immunological mechanisms of action

Specific immunotherapy (SIT) is the only treatment able to modify the natural history of the allergic subjects. Several aspects of the immunopathological response modified by SIT have been investigated; the first parameter historically studied was the production of allergen-specific antibodies. An increase of allergen-specific IgG4 and a decrease of IgE appear after SIT. A shift from Th2-polarized immune response toward Th1-oriented pattern has been reported after SIT. More recently, a crucial role for a subpopulation of T cells has been evidenced: T regulatory cells (Treg). Allergic patients have a defect of Tregs. SIT is able of inducing a specific Treg response. Sublingual immunotherapy is an alternative route of administration for SIT. Recent evidence shows that SLIT is also able of inducing a Treg response as detected by IL- 10 production

Measurement of transfer of colostral passive immunity in dairy calves

The administration of high quality colostrum reduces preweaning morbidity, mortality and, therefore, economic losses related to replacement animals. It also stimulates and improves calf growth, increasing milk production and longevity of the future dairy cows. The aim of the present study was to evaluate the influence of breed and parity of the dam on colostrum quality, and of breed and gender of the calf, and time from calf birth to the administration of the first colostrum meal on the transfer of passive immunity to the calf by the field test of the Failure of Passive Transfer (FPT) on calf serum. A further objective was to improve the diagnostic accuracy of the field FPT test through a second laboratory phase improving the turbidity evaluation. The amount of IgG fed to calves (IgG concentration multiplied by the volume of colostrum administered) was influenced by dam parity as significant differences (P < 0.05) were detected between first- and fourth-parity cows, and between second- and fourth-parity cows. The administration of good quality colostrum (IgG > 50 mg/ml) between 5 and 9 h of life was able to reduce the risk of FPT more effectively than the administration performed within the first 4 h of life. However, further studies on larger sample size is needed to confirm the present findings. The spectrophotometric measurements confirmed the results obtained by the field turbidity test at 14% sodium sulphite dilution. It would be interesting in future to expand the dataset and validate the spectrophometric method

Lo studio FAST: FAringotonsillite STreptococcica in età pediatrica Impatto farmacoeconomico delle Linee Guida dell'American Academy of Pediatrics sulla pratica clinica di 600 pediatri italiani

The American Academy of Pediatrics (AAP) has recently published its new guidelines for the treatment of pediatric tonsillopharyngitis; a diagnostic test for the detection of streptococci is recommended, followed by a treatment with penicillins (10 days) or cephalosporins (5 days) in case of positivity, and by no treatment otherwise. The success of a guideline, in general, depends on its diffusion in practice and on its adaptability to different local settings. The aim of the present study (FAST) was the evaluation of the clinical and economical impact of the application of the AAP guidelines in the Italian reality. The study was conducted with the cooperation of 600 pediatricians, uniformly distributed on the Italian territory, and involved 3072 patients. The pediatricians were left free to decide whether to follow the guidelines or not. The results of the analysis indicate that only some 20% of the pediatricians adhered to the suggested protocol; the total cost (calculated in the perspective of the National Health System, with a time horizon of about 3 months) per patient, nonetheless, resulted inferior in the group treated according to the proposed protocol (50,45 • vs. 53,30 •). Furthermore, a lower incidence of complications occurred in these patients. Among the "off-protocol" behaviors, two showed particularly evident misuse of health resources: inappropriate treatment after test positivity (59,15 •/patient), and treatment after test negativity (14% of the total population). Another interesting, although not surprising, result of this study was the evidence that penicillins are as effective as cephalosporins in the short-term, but significantly inferior in terms of complications, positivity for streptococci at the control test, and complications detected at follow-up

A bright nanowire single photon source based on SiV centers in diamond

The practical implementation of many quantum technologies relies on the development of robust and bright single photon sources that operate at room temperature. The negatively charged silicon-vacancy (SiV-) color center in diamond is a possible candidate for such a single photon source. However, due to the high refraction index mismatch to air, color centers in diamond typically exhibit low photon out-coupling. An additional shortcoming is due to the random localization of native defects in the diamond sample. Here we demonstrate deterministic implantation of Si ions with high conversion efficiency to single SiV- centers, targeted to fabricated nanowires. The co-localization of single SiV- centers with the nanostructures yields a ten times higher light coupling efficiency than for single SiV- centers in bulk diamond. This enhanced photon out-coupling, together with the intrinsic scalability of the SiV- creation method, enables a new class of devices for integrated photonics and quantum science.Comment: 15 pages, 5 figure

Strongly enhanced photon collection from diamond defect centres under micro-fabricated integrated solid immersion lenses

The efficiency of collecting photons from optically active defect centres in bulk diamond is greatly reduced by refraction and reflection at the diamond-air interface. We report on the fabrication and measurement of a geometrical solution to the problem; integrated solid immersion lenses (SILs) etched directly into the surface of diamond. An increase of a factor of 10 was observed in the saturated count-rate from a single negatively charged nitrogen-vacancy (NV-) within a 5um diameter SIL compared with NV-s under a planar surface in the same crystal. A factor of 3 reduction in background emission was also observed due to the reduced excitation volume with a SIL present. Such a system is potentially scalable and easily adaptable to other defect centres in bulk diamond.Comment: 5 Pages, 5 figures (4 subfigures) - corrected typ

Rhinosinusitis and asthma: a very long engagement

Upper and lower airways may be considered as a unique entity, interested by coexisting inflammatory processes that share common etiopathogenic mechanisms. Previous studies have strongly demonstrated a relationship between rhinosinusitis and asthma. This has led to the introduction of the concept of United Airways , which has also been included in the WHO document Allergic Rhinitis and its Impact on Asthma (ARIA); this concept has important consequences also on the treatment of these disorders. To better summarize the evident connection between upper and lower airway disease we decided to describe it as a multilayered construction, each level pointing out more deeply the relationship between these entities

Acute pain management in children: A survey of Italian pediatricians

Background: Current guidelines recommend assessing and relieving pain in all children and in all instances; yet, in clinical practice, management is frequently suboptimal. We investigated the attitude of Italian family pediatricians towards the evaluation and treatment of different types of acute pain in children aged 7-12 years. Methods: This is a cross-sectional study based on a 17-question survey accessible online from October 2017 to October 2018. Responders had to describe cases of children suffering from any type of acute pain among headache, sore throat, musculoskeletal/post-traumatic pain, and earache. Children's characteristics, pain assessment modalities and therapeutic approaches were queried. The following tests were used: Z-proportion to evaluate the distribution of categorical data; chi-squared and Kruskall-Wallis to explore data heterogeneity across groups; Mann-Whitney for head-to-head comparisons. Results: Overall, 929 pediatricians presented 6335 cases uniformly distributed across the types examined. Pain was more frequently of moderate intensity (42.2%, P < 0.001) and short duration (within some days: 98.4%, P < 0.001). Only 50.1% of responders used an algometric scale to measure pain and 60.5% always prescribed a treatment. In children with mild-moderate pain (N = 4438), the most commonly used first-line non-opioids were ibuprofen (53.3%) and acetaminophen (44.4%). Importantly, a non-recommended dosage was prescribed in only 5.3% of acetaminophen-treated cases (overdosing). Among the misconceptions emerged, there were the following: I) ibuprofen and acetaminophen have different efficacy and safety profiles (when choosing the non-opioid, effectiveness weighted more for ibuprofen [79.7% vs 74.3%, P < 0.001] and tolerability for acetaminophen [74.0% vs 55.4%, P < 0.001]); ii) ibuprofen must be taken after meals to prevent gastric toxicities (52.5%); ibuprofen and acetaminophen can be used combined/alternated for persisting mild-moderate pain (16.1%). In case of moderate-severe pain not completely controlled by opioids, ibuprofen and acetaminophen were the most used add-on medications, with ibuprofen being much more prescribed than acetaminophen (65.2% vs 23.7%, respectively) overall and in all pain types. Conclusions: Several gaps exist between the current practice of pain assessment and treatment and recommendations. Further efforts are needed to raise awareness and improve education on the possible exposure of the child to short- A nd long-term consequences in case of suboptimal pain management

Bronchial hyperreactivity and spirometric impairment in patients with allergic rhinitis.

Background: The Link between allergic rhinitis and asthma is well known. Bronchial hyperreactivity (BHR) may be present in rhinitics. The present study is aimed at evaluating a large group of subjects suffering from allergic rhinitis alone to investigate the presence of spirometric impairment and BHR both during and outside the pollen season. Methods: 360 rhinitics (subdivided in 3 groups: seasonal, SAR, perennial, PAR, and polysensitized, PolysR) were investigated by spirometry and methacholine challenge. Results: There was a significant seasonal difference concerning the number of rhinitics with impaired FEV1 (p<0.01 for SAR, p<0.02 for PAR, and p<0.03 for PolysR) and FEF25-75 (p<0.05 for SAR, p<0.03 for PAR, and p<0.05 for PolysR) as well as with BHR (p<0.05 for SAR and p<0.03 for PAR). Conclusions: This study evidences that an impairment of spirometric parameters and BHR may be observed in patients with allergic rhinitis alone. Thus, careful evaluation of lower airways should be performed in patients with allergic rhinitis alone