Plasma Redox Balance in Advanced-Maternal-Age Pregnant Women and Effects of Plasma on Umbilical Cord Mesenchymal Stem Cells.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timings of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that, throughout pregnancy until after delivery in patients, the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients. They could have clinical relevance for the prevention of complications related to AMA pregnancy.

Peanut allergy in Italy: A unique Italian perspective.

Background: Peanut allergy has not been well characterized in Italy. Objective: Our aim was to better define the clinical features of peanut allergy in Italy and to detect the peanut proteins involved in allergic reactions. Methods: A total of 22 centers participated in a prospective survey of peanut allergy over a 6-month period. Clinical histories were confirmed by in vivo and/or in vitro diagnostic means in all cases. Potential risk factors for peanut allergy occurrence were considered. Levels of IgE to Arachis hypogea (Ara h) 1, 2, 3, 6, 8, and 9 and profilin were measured. Results: A total of 395 patients (aged 2-80 years) were enrolled. Of the participants, 35% reported local reactions, 38.2% reported systemic reactions, and 26.6% experienced anaphylaxis. The sensitization profile was dominated by Ara h 9 (77% of patients were sensitized to it), whereas 35% were sensitized to pathogenesis-related protein 10 (PR-10) and 26% were sensitized to seed storage proteins (SSPs). Sensitization to 2S albumins (Ara h 2 and Ara h 6) or lipid transfer protein (LTP) was associated with the occurrence of more severe symptoms, whereas profilin and PR-10 sensitization were associated with milder symptoms. Cosensitization to profilin reduced the risk of severe reactions in both Ara h 2- and LTP-sensitized patients. SSP sensitization prevailed in younger patients whereas LTP prevailed in older patients (P < .01). SSP sensitization occurred mainly in northern Italy, whereas LTP sensitization prevailed in Italy's center and south. Atopic dermatitis, frequency of peanut ingestion, peanut consumption by other family members, or use of peanut butter did not seem to be risk factors for peanut allergy onset. Conclusions: In Italy, peanut allergy is rare and dominated by LTP in the country's center and south and by SSP in the north. These 2 sensitizations seem mutually exclusive. The picture differs from that in Anglo-Saxon countries.

Levocetirizine in persistent allergic rhinitis: continuous or on-demand use? A pilot study.

BACKGROUND: Allergic rhinitis is a high-prevalence disease that affects quality of life (QOL), sleep quality and productivity of patients. According to the ARIA initiative, it is classified as intermittent and persistent, the latter being the most troublesome. METHODS: The aim of this randomized, open-label, 6-month, pilot study was to determine whether levocetirizine 5 mg administered continuously once daily in the morning was better than levocetirizine 5 mg on-demand in symptomatic subjects with persistent allergic rhinitis. Total and individual symptom scores were recorded in a diary card throughout the study. QOL, quality of sleep, nasal cytology, rate of drug intake, and safety were also assessed at pre-defined time-points. RESULTS: In all, adult patients (31 in each group) were enrolled, of whom 22 dropped out. Both treatment regimens considerably decreased the total and individual symptoms scores from baseline and achieved similar levels up to week 14. Continuous treatment was generally better than on-demand from week 15 onwards, reaching statistical significance from weeks 17 to 21 (from week 19 to 21 for nasal pruritus). Both regimens substantially improved QOL and sleep quality. Both treatments were well tolerated, although the on-demand group reported more adverse events. CONCLUSION: The present open label study in 62 patients indicates that levocetirizine 5 mg reliably controls persistent rhinitis over a period of 6 months, and shows a trend to be more effective in controlling the symptoms of rhinitis, improving QOL and decreasing nasal inflammation, when administered as long-term continuous therapy rather than as on-demand therapy.

Targeted therapy for allergic asthma: predicting and evaluating response to omalizumab.

Evaluation of: Bousquet J, Rabe K, Humbert M et al. Predicting and evaluating response to omalizumab in patients with severe allergic asthma. Respir. Med. 101(7), 1483-1492 (2007). Among new asthma therapies, omalizumab is the only monoclonal antibody that has been proven to be effective and safe in treating severe, inadequately controlled asthma. Nevertheless, it has been pointed out that not all patients respond to it. This paper analyzes the results of a recent study that was aimed at achieving a more accurate evaluation of the response to omalizumab in patients with severe allergic asthma, by identifying possible pretreatment characteristics that can be predictive of a better and superior response to omalizumab. The results established that it is difficult to predict which patients will gain most benefit from treatment, according to pretreatment baseline characteristics.

New insights in sublingual immunotherapy.

Sublingual immunotherapy (SLIT) is accepted in the official documents and is currently used in many European countries. In recent years, new clinical data on efficacy and safety have been published, including meta-analyses in adults and children and surveys of safety in children younger than age 5 years. Moreover, it has been shown that, similar to the injection route, SLIT can prevent the onset of new sensitizations and the onset of asthma. Additionally, the mechanisms of action are beginning to be systematically studied. Some points need further investigation, such as the effect in asthma, the mechanisms of action, and the optimal dose to be administered.

Safety profile of sublingual immunotherapy.

Sublingual immunotherapy (SLIT) was proposed for clinical practice about 20 years ago with the main aim of improving the safety and avoiding the adverse effects of traditional treatment for allergic airways disease. To date, 32 randomized controlled trials and 6 postmarketing surveys have been published that provide a robust documentation of the safety profile of the treatment.Looking at the randomized trials it emerges that the more frequent adverse event of SLIT is oral itching or swelling, followed by gastrointestinal complaints. These adverse events are invariably described as mild and easily managed by adjusting the dose. Relevant systemic adverse events (asthma, urticaria, angioedema) occur sporadically and, with the exception of oral/gastrointestinal adverse events, the incidence of adverse events seems not to differ between the placebo and active groups. The safety profile of SLIT does not differ between adults and children.The postmarketing surveys consistently show that the incidence of adverse events associated with SLIT is less than 10%, corresponding to less than 1 adverse event per 1000 doses, and is thus quite superior to the safety profile of subcutaneous immunotherapy. Of note, the most recent data show that the rate of adverse events with SLIT is not increased in children below the age of 5 years.

Antiallergic drugs and quality of life.

Allergic diseases represent a global health problem with a substantial impact on medical costs and socioeconomic outcomes. Furthermore, as well documented in the recent literature, these pathologies also have negative consequences on the functional, emotional and psychosocial aspects of daily life. Using validated and standardized tools, it is possible to evaluate individual outcomes. At present, the health-related quality of life parameter is used in clinical trials, population studies and public health, providing a comprehensive picture of both the disease and its treatment on the quality of life. While many studies have addressed this topic in respiratory allergy, further studies are needed to explore the use of health-related quality of life both before and after treatment in other allergic conditions such as dermatitis, eczema, urticaria and food allergy.

Sublingual and oral immunotherapy.

Sublingual immunotherapy (SLIT) is a viable alternative to the subcutaneous route for the treatment of respiratory allergy, whereas the pure oral route has been abandoned because of its lack of efficacy. The main distinctive feature of SLIT is its optimal safety profile, which has been demonstrated in adults and children. The indications for SLIT are similar to those for the subcutaneous route. A long-lasting effect has been demonstrated for the sublingual route, but data are needed to determine the optimal dose and the preventive effect in asthma.

Safety of allergen-specific sublingual immunotherapy and nasal immunotherapy.

Allergen-specific immunotherapy is a well-established treatment for respiratory allergy. It is usually administered subcutaneously, and with this route several severe adverse events and fatalities have been described. Therefore, in the last 15 years, novel routes of administration (local routes) were developed. Sublingual and local nasal immunotherapy are now considered as viable alternatives to the injection route, mainly due to their optimal safety. The use of nasal immunotherapy is at present declining. On the other hand, sublingual immunotherapy was investigated in twenty-two randomized controlled trials and two postmarketing surveys: its safety profile turned out to be satisfactory in both adults and children, gastrointestinal complaints being the most frequently reported side effects. These side effects were always mild and could be treated with proper dose adjusting. At variance with injection immunotherapy, no severe systemic adverse event has ever been described. Its safety is also supported by pharmacokinetics and immunological data. Experimental data on the safety of sublingual and nasal immunotherapy will be reviewed.

Sublingual immunotherapy.

Allergen-specific immunotherapy, together with drug therapy and allergen avoidance, is a cornerstone in the management of respiratory allergy in both adults and children. Since the introduction of sublingual administration of immunotherapy (SLIT), it was regarded as the most promising approach, especially because of its optimal safety profile. After 15 years of clinical trials, the WHO officially accepted SLIT as a routine clinical option in both adults and children. This paper reviews the up-to-date aspects about clinical efficacy, safety and pharmacokinetics of sublingual immunotherapy.