Vitamin D and Omega-3 (Fatty Acid) Supplementation in Pregnancy for the Primary Prevention of Food Allergy in Children-Literature Review.

During the last decades the prevalence of food allergy (FA), an adverse immune response to a specific food antigen, has risen, with negative effects on the quality of life (QoL) of many children and their families. The pathogenesis of FA is complex, involving both genetic and environmental factors. SPINK5, STAT6, HLA and FOXP3 are some of the genes that are reported to be implicated in FA development. Regarding environmental factors, particular interest has been focused on modification of the dietary habits of pregnant women for the primary prevention of FA. Specifically, Vitamin D and omega-3 (Ω-3) fatty acid supplementation during pregnancy may influence the development of FA in the offspring. Vitamin D is a hormone with various actions, including mediation of the immune system, reducing the production of inflammatory cytokines and promoting tolerance. Vitamin D deficiency in pregnancy suppresses T-regulatory cells in the fetus, and Vitamin D supplementation might protect against FA development. Dietary Ω-3 fatty acids are found mainly in fish and vegetable oils. They are beneficial for human health, playing a role in the immune system as anti-inflammatory agents, and providing cell membrane stabilization with inhibition of antigen presentation. It is documented that maternal supplementation with Ω-3 during pregnancy may protect from allergic sensitization in the children. The aim of this literature review was to explore the potential preventive role of maternal supplementation during pregnancy with Vitamin D and Ω-3 in the development of FA in the offspring. With the prevalence of FA rising, all the possible protective mechanisms and measures for FA prevention need to be explored, starting with those that can be modified.

An Actual Perspective on I1-Imidazoline Agonists in Blood Pressure Control. Results of a Multicentric Observational Prospective Study.

Background: Despite the disadvantaged position of central adrenergic drugs (CAD) in the current therapeutic regimens of hypertensive patients, we hypothesized that the addition of the most recent representatives of this class - I1-imidazoline agonists (CAD-I1A) - to the usually recommended drugs might contribute to better blood pressure (BP) control. Method: This multicentric observational prospective study included patients with BP . 140/90 mm Hg who were using at least two antihypertensive drugs and were reassessed at three months apart in 44 urban medical centers. Patients with modifications in therapy were subsequently divided into two subgroups: one study group, with CAD-I1A added to the initial therapeutic regimen, and one control group characterized by the addition of a drug from any other class of antihypertensives. Results: The rate of BP normalization was 43% (144/333) after CAD-I1A addition vs 26% (15/58) following any other changes in treatment (p<0.01). The binomial logistic regression has validated the presence of CAD-I1A in the therapeutic regimen (p<0.001) and the stage of hypertension at baseline (p<0.01) as statistically significant predictors of a better BP control, while demographic, socio-economic, lifestyle factors and comorbidities were similarly distributed between the two groups. No differences in the rate of side effects were identified. Conclusions: The results of our study indicate a high probability of BP normalization when a CAD-I1A is added to the therapeutic regimen of patients with uncontrolled hypertension under at least two drugs.

Esophageal Pressure Measurement in Acute Hypercapnic Respiratory Failure Due to Severe COPD Exacerbation Requiring NIV-A Pilot Safety Study.

Esophageal pressure (Pes) measurements could optimise ventilator parameters in acute respiratory failure (ARF) patients requiring noninvasive ventilation (NIV). Consequently, the objectives of our study were to evaluate the safety and accuracy of applying a Pes measuring protocol in ARF patients with AECOPD under NIV in our respiratory intermediate care unit (RICU). An observational cohort study was undertaken. The negative inspiratory swing of Pes (ΔPes) was measured: in an upright/supine position in the presence/absence of NIV at D1 (day of admission), D3 (3rd day of NIV), and DoD (day of discharge). A digital filter for artefact removal was developed. We included 15 patients. The maximum values for ∆Pes were recorded at admission (mean ∆Pes 23.2 cm H2O) in the supine position. ∆Pes decreased from D1 to D3 (p < 0.05), the change being BMI-dependent (p < 0.01). The addition of NIV decreased ∆Pes at D1 and D3 (p < 0.01). The reduction of ∆Pes was more significant in the supine position at D1 (8.8 cm H2O, p < 0.01). Under NIV, ∆Pes values remained higher in the supine versus upright position. Therefore, the measurement of Pes in AECOPD patients requiring NIV can be safely done in an RICU. Under NIV, ∆Pes reduction is most significant within the first 24 h of admission.

Obesity and Infection: What Have We Learned From the COVID-19 Pandemic.

Objective: The critical role played by the nutritional status in the complications, duration of hospitalization and mortality in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) has emerged from several research studies in diverse populations. Obesity has been associated with an increased risk of serious complications, as the adipose tissue appears to have significant effects on the immune response. The aim of this narrative review was to investigate the relationship between COVID-19 and obesity. Methods: We performed a review of papers in the English language derived from PubMed, Science Direct, and Web of Science. The primary outcomes investigated were the severity of the disease, admission to the intensive care unit (ICU), need for intubation, and mortality. Results and Conclusion: Review of 44 eligible studies from 18 countries around the world revealed evidence that obesity increases the risk of severe COVID-19 complications, ICU admission, intubation and mortality. Patients with a higher body mass index (BMI) appear to be more vulnerable to SARS-CoV-2 infection, with more severe illness requiring admission to ICU and intubation, and to have higher mortality. A healthy body weight should be targeted as a long-term prevention measure against acute complications of infection, and in the event of COVID-19, overweight and obese patients should be monitored closely.

Successful Dabrafenib Desensitization Protocols in a Patient with Metastatic Melanoma.

Dabrafenib and trametinib are two available molecules that have been approved for the treatment of metastatic melanoma with BRAF-V600E or V600K mutations. Their combined therapy has led to long-lasting survival benefits and substantially improved outcomes. Until now, only a few cases of severe hypersensitivity reactions to dabrafenib and vemurafenib have been reported, and even fewer desensitization protocols to these molecules have been documented. We report the case of a 71-year-old female patient with metastatic melanoma harboring a BRAF-V600E mutation undergoing targeted therapy with dabrafenib and trametinib. Two weeks after the initiation of the combined treatment, she developed a hypersensitivity reaction. The cause-effect relationship between dabrafenib and the hypersensitivity reaction was demonstrated twice, when symptoms recurred upon dabrafenib reintroduction. We started a rapid 3-day dabrafenib desensitization protocol, which was well tolerated. When the patient discontinued the drug administration, we decided on a longer protocol that included more steps and more days in order to prevent the occurrence of other hypersensitivity reactions. Our patient tolerated both rapid and slow-going schedules, the first one reaching the final dose within 3 days and the second one reaching the total daily dose within 14 days. Depending on the patient's needs, the severity of the hypersensitivity reaction and the hospital's availability, the doctor may choose either the rapid or slow-going desensitization protocol.

Mechanisms of allergen immunotherapy supporting its disease-modifying effect.

Allergen immunotherapy (AIT) is considered the only disease-modifying treatment available at present for allergic disorders. Its main benefits include improvement of symptoms, decreased need for pharmacotherapy, prevention of new sensitizations and sustained effect after AIT completion. The key pillars of AIT-induced tolerance include a shift from Th2 to Th1 response, an increase of regulatory T and B cells, pro-inflammatory effector cell downregulation and IgE suppression, in addition to IgG4, IgA and IgD induction. AIT may also induce trained immunity, characterized by a durable decrease in group 2 of innate lymphoid cells (ILCs) and increased ILC1 and ILC3s. Understanding the immune mechanisms of AIT is essential for validating biomarkers for the prediction of AIT response and for achieving AIT success.

In the last decades, allergic diseases have become a public health concern worldwide. Currently, their treatment is mainly based on medications that control the symptoms or decrease future disease risk. The only disease-modifying treatment available for allergic diseases is allergen immunotherapy (AIT). Its main benefits include improvement of symptoms, prevention of new sensitizations and sustained effect after therapy completion. The allergen tolerance induced by AIT is explained by an increase in the number of regulatory immune cells, which reduce inflammation, and a progressive decrease in pro-inflammatory immune cells and IgE synthesis. Better understanding of the mechanisms of AIT is essential for improving efficacy and safety.

Precision medicine in the allergy clinic: the application of component resolved diagnosis.

INTRODUCTION: A precise diagnosis is key for the optimal management of allergic diseases and asthma. In vivo or in vitro diagnostic methods that use allergen extracts often fail to identify the molecules eliciting the allergic reactions. AREAS COVERED: Component-resolved diagnosis (CRD) has solved most of the limitations of extract-based diagnostic procedures and is currently valuable tool for the precision diagnosis in the allergy clinic, for venom and food allergy, asthma, allergic rhinitis, and atopic dermatitis. Its implementation in daily practice facilitates: a) the distinction between genuine multiple sensitizations and cross-reactive sensitization in polysensitized patients; b) the prediction of a severe, systemic reaction in food or insect venom allergy; c) the optimal selection of allergen immunotherapy based on the patient sensitization profile. This paper describes its main advantages and disadvantages, cost-effectiveness and future perspectives. EXPERT OPINION: The diagnostic strategy based on CRD is part of the new concept of precision immunology, which aims to improve the management of allergic diseases.

Omalizumab for successful chemotherapy desensitisation: What we know so far.

BACKGROUND: Hypersensitivity reactions induced by chemotherapeutic drugs may influence the course of the oncologic disease by preventing doctors from prescribing first-line therapy. In order to prevent another hypersensitivity reaction to the culprit chemotherapeutic agent, the physician can decide between two possibilities: premedication or desensitisation protocols. Rapid drug desensitisation showed successful results for most patients, but some of them may develop symptoms. Although omalizumab is not licensed as premedication or adjuvant therapy in chemotherapy desensitisation protocols, there have been published some case reports and small sample size studies that indicated promising results. METHODS: We reviewed all the published literature regarding the use of omalizumab during chemotherapy desensitisation protocols. RESULTS AND CONCLUSIONS: We found a great heterogeneity between the doses and the interval between omalizumab injections and chemotherapy - rapid drug desensitisation, but most of the studies showed promising results. As a corollary, we propose a dose regimen of omalizumab administered before the first desensitisation protocol. Then, omalizumab should be administered one day before every chemotherapy regimen. Omalizumab might be used as an adjuvant therapy and might be a solution for a hopeless situation.

Clinical Experience with Anti-IgE Monoclonal Antibody (Omalizumab) in Pediatric Severe Allergic Asthma-A Romanian Perspective.

BACKGROUND: Asthma is the most common chronic disease affecting children, with a negative impact on their quality of life. Asthma is often associated with comorbid allergic diseases, and its severity may be modulated by immunoglobulin E (IgE)-mediated allergen sensitization. Omalizumab is a humanized monoclonal anti-IgE antibody, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omalizumab in Romanian children with severe allergic asthma. METHODS: In this observational real-life study, 12 children and adolescents aged 6 to 18 years (mean 12.4 years) with severe allergic asthma received Omalizumab as an add-on treatment. Asthma control, exacerbations, lung function, and adverse events were evaluated at baseline and after the first year of treatment. RESULTS: We observed general improvement in total asthma symptom scores and reduction in the rate of exacerbation of severe asthma. Omalizumab treatment was associated with improvement in the measures of lung function, and no serious adverse reactions were reported. FEV1 improved significantly after one year of treatment with Omalizumab [ΔFEV1 (% pred.) = 18.3], and [similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rate of asthma decreased from 4.1 ± 2.8 to 1.15 ± 0.78 (p < 0.0001) during the year of treatment with Omalizumab. CONCLUSIONS: This study showed that Omalizumab can be an effective and safe therapeutic option for Romanian children and adolescents with severe allergic asthma, providing clinically relevant information on asthma control and exacerbation rate in children and adolescents. The results demonstrated the positive effect of Omalizumab in young patients with asthma, starting from the first year of treatment.

Physician's experience on managing asthma in adolescents: results of the International AMADO (Asthma Management in ADOlescents) survey.

BACKGROUND: Worldwide prevalence of asthma seems to be increasing in adolescents, but limited data is available regarding the management of asthma in this age group. OBJECTIVE: Therefore, we conducted an international survey focused on physicians who manage asthma in order to understand how Asthma Management in ADOlescents (AMADO) is currently performed. METHODS: The AMADO survey is a web-based global survey of physician's attitudes towards the management of asthma in adolescents, circulated for 17 weeks. The survey had an anonymous and voluntary standard. The questionnaire consisted in 27 questions covering the training background of respondents, difficulties in diagnosis, and in management of asthma in adolescents. RESULTS: Two hundred forty-four responses were received from 46 countries, from all continents. Most (65%) of participants indicated allergy as being their main specialty. The majority of participants (62%) had more than 5 years of clinical practice, but 62% have no formal training in management of adolescents with asthma. Most of participants (96%) indicated having at least one case of asthma in adolescents per month. 60% of respondents mentioned that the asthmatic adolescents only had the consultation due to the family imposition. All respondents mentioned having difficulties in the management of asthma in adolescents due to patient poor adherence. Overall, 44% of participants have no specific health care resources for adolescents in their departments. Main suggestions from the participants were: optimization of time and personalized communication to these cohort, and standardization of multidisciplinary actions to improve adherence to asthma control treatment. CONCLUSION: Management of asthma in adolescents is still a challenge in clinical practice. The results from this survey helped us to identify the key issues to improve clinical outcomes in the future. This survey is the first step of the international AMADO initiative, which intends to optimize diagnosis and control of asthma and prevent avoidable deaths.

Contact Allergy Induced by Mango (Mangifera indica): A Relevant Topic?

INTRODUCTION: The most common clinical manifestation of mango allergy is contact dermatitis, which can be localized or systemic. The sensitising substances that have long been suspected are alk(en)yl catechols and/or alk(en)yl resorcinols. METHODS: We reviewed the original articles published on Pubmed, Embase and Cochrane Library before 15 September 2021, on the topic of contact allergy induced by mango and we synthesized the key data. RESULTS: We found 12 case reports and four case series, with a total of 37 patients. Only seven of these cases were reported in patients from mango-cultivating countries, the other 30 were from countries where mango cultivation does not occur, and 26 were also from countries where poison ivy/oak are commonly found. We found that contact dermatitis may occur on the first exposure to mango due to previous sensitisation to urushiol-containing plants. The diagnosis was confirmed by patch testing in some of the cases. There was great heterogeneity between the reagents used. CONCLUSION: Mango fruit is frequently consumed, but mango induced contact dermatitis, the main hypersensitivity reaction induced by mango, is rare. Further data is necessary for a better understanding of sensitising substances and, consecutively, standardization of patch test reagents.

Drug Provocation Testing in the Diagnosis of Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE) Induced by Clarithromycin.

Introduction: Hypersensitivity reactions to macrolides are rarely described in the literature wherefore they are considered one of the safest choices for antibiotic treatment. Out of the reported reactions, cutaneous manifestations have the highest frequency, particularly non-immediate ones. Materials and methods: We report a case of a 71-year-old female who was referred to us for the drug allergy work-up of a rash unaccompanied by systemic signs, compatible with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by clarithromycin. Results: The diagnosis was confirmed by a drug provocation test, which reproduced the index reaction. Discussion: As SDRIFE is quite infrequent, it can easily be misdiagnosed if the patient cannot present a clear history of the index reaction or the causal connection with the incriminated drug is not clear. Despite the fact that macrolides rarely induce hypersensitivity reactions, they must not be overlooked in the assessment of a drug induced reaction, as they are a potential etiological factor.

Patient and Physician Perspectives on Asthma and Its Therapy in Romania: Results of a Multicenter Survey.

Background and Objectives: Patient's behaviours, attitudes and beliefs related to asthma and its treatment were shown to influence the adherence to therapy and the level of asthma control. This survey aimed to assess the level of asthma control and patient-reported behaviours, attitudes and expectations related to their disease in Romanian patients. Materials and Methods: This cross-sectional quantitative survey was performed in February-March 2019 and enrolled 70 specialist physicians experienced in asthma management and 433 asthma patients under their care. Results: Of the 433 patients enrolled, 19.4% had mild asthma, 60.5% moderate asthma and 20.1% severe asthma. For the previous 12 months, asthma symptoms, exacerbations and emergency room visits were common in the sample analysed, with significantly higher figures in severe asthma patients (p < 0.001). The most important treatment goal for asthma patients was participation in all activities of daily living, while for physicians this was preventing asthma exacerbations. The valuation of the treatment goals was different between patients with severe asthma and those with mild and moderate forms. Based on the patients' responses, 3 attitude clusters were identified: empowered savvy (36.5% of the patients), pessimistic non-compliers (43.2%), and anxious strugglers (20.3%). "Empowered savvy" had the lowest frequency of severe asthma, the highest adherence to maintenance therapy and the highest level of confidence in the effectiveness of asthma medication. The opposite of this attitude cluster is the "anxious strugglers", containing more patients with severe asthma, a higher score for worries about asthma therapy and better self-reported knowledge of their treatment, contrasting with a proportion of 25% taking maintenance therapy only when having breathing difficulties. Conclusion: Asthma control in Romania remains poor, with frequent exacerbations and hospitalizations. The differences in treatment goals found between patients and physicians and between different asthma severity groups suggest the need for more patient-centred approaches.

Probiotics and prebiotics in atopic dermatitis: Pros and cons (Review).

Atopic dermatitis (AD) represents a chronic inflammatory skin condition in which the skin barrier is impaired; thus, the permeability is increased. Hence, there is a greater risk of allergic sensitization, as well as a higher pH and lower protection against resident microbes. Since this condition is currently increasing among children, it requires further study, as little is known regarding the pathogenesis that makes the skin prone to chronic relapsing inflammation. Trying to standardize the data regarding the use of prebiotics and probiotics in AD, we encountered tremendous variability in the literature data. Literature abounds in conflicting data: studies regarding prophylactic and therapeutic applications, different types of strains and dosages, applications in young children up to 5 years of age and above, usage of probiotics alone, prebiotics alone or synbiotics combined. There are also conflicting data regarding the outcome of these studies; some confirming a positive effect of prebiotics, probiotics or synbiotics and some showing no efficacy at all. The articles were divided into those assessing probiotics or prebiotics alone and a combination of the two, with studies showing a positive effect and studies proving no efficacy at all. We tried to critically analyze those articles showing weak and strong points. In summary, the most studied probiotics were the strains of Lactobacilli and Bifidobacteria. The Severity Scoring of Atopic Dermatitis (SCORAD) index was used to measure the efficacy of the treatment. Most studies compared their results with a placebo group and the efficacy when seen in moderate to severe forms of AD in patients with other allergic diseases present. However, the results are difficult to interpret, as in many studies the authors suggest that the disease may have a tendency to improve in time in some groups of patients.

Mite allergy and atopic dermatitis: Is there a clear link? (Review).

Atopic dermatitis (AD) represents a widespread chronic skin disease associated with different atopic disorders and allergies. These associations, similar to overall AD pathophysiology, are entangled, multifactorial and they are yet to be clarified. IgE and non IgE mediated pathomechanisms appear to be implicated in AD. Allergens constitute key aspects in AD pathogenesis, as they may serve as trigger factors. This review emphasizes mainly house dust mites (HDM), as they are likely the most relevant airborne allergen for AD. Here we review in a concise form the mite allergens, the role of molecular diagnosis and the treatment strategies for HDM. Strategies of avoiding allergens, with a few exceptions, are not enough to control children's AD; recent studies show HDM avoidance procedures in diagnosed AD are insufficient. Regardless, some guidelines acknowledge the benefit of mattress and pillow covers in patients with dust mite sensitization that are unresponsive to optimal AD management. Most clinical trials investigating allergen-specific immunotherapy (AIT) as a potential treatment for AD were done with adult patients; a scarce number of studies looked into the efficacy of AIT as a treatment option in children suffering from AD, with conflicting data among them. One of the most feasible of these studies showed significant improvement of AD outcomes only in the mild/moderate group, but not in the severe group. Uncontrolled studies are hard to interpret, considering the natural history of remitting and relapsing of AD, in many of the patients, without clinical interventions. More AIT studies, especially pediatric studies, are required in order to either prove the reproducibility of positive results or to deny its effectiveness.

Toward personalization of asthma treatment according to trigger factors.

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.

A rapid desensitization protocol in a case of drotaverine-induced serum sickness-like reaction in a pregnant woman: A case report.

Drotaverine is an antispasmodic drug used to treat gastrointestinal and genitourinary smooth muscle spasms. There are very few hypersensitivity reactions reported. Serum sickness-like disease is an immune-complex-mediated hypersensitivity reaction that presents with some typical features that include rash, fever and articular impairment sometimes associated with liver and renal dysfunctions, beginning 1-2 weeks after exposure to a culprit drug. Diagnosis is a clinical one, made usually on the basis of knowledge obtained by medical history and physical examination. Desensitization usually is recommended for type I reaction, but may be a solution for this type of immunological reaction when other therapeutic alternatives are ineffective or do not exist. We report the case of a 29-year-old pregnant female who developed serum sickness-like reaction after 5 days of daily drotaverine oral administration. The patient required antispasmodic treatment, with this drug, having a pregnancy with an imminent risk of abortion and the other therapeutic alternatives being ineffective. She underwent a rapid 7-step oral drotaverine desensitization protocol without recurrence of serum sickness-like reaction. To our knowledge, this is the first case report of desensitization to drotaverine, previously involved in a serum sickness-like reaction.

Management problems in severe chronic inducible urticaria: Two case reports.

Chronic inducible urticaria (CIndU) is a subgroup of chronic urticaria which can cause severe quality of life impairment by their refractory forms. The recommended treatment approach in CindU is the same as that for chronic spontaneous urticaria (CSU). However, CIndU seem to be more resistant to standard doses of H1 antihistamines (AHs) and higher doses of AHs are required for symptom control. Omalizumab, a recombinant anti-IgE antibody, effectively treats CSU. Nevertheless, there is not enough evidence in patients with CIndU, especially in AHs resistant cases. This study analyzed 2 severe cases of CIndU (cold urticaria and symptomatic dermographism) with completely different response to omalizumab. We describe 2 patients with 2 subtypes of CIndU: one with severe cold urticaria (including anaphylaxis) and the other with severe extensive symptomatic dermographysm. In both cases, we performed complete positive and differential diagnostic work-up. Management strategies included first line and second line symptomatic therapy, but with no success in either case. Avoidance of eliciting triggers was difficult to achieve (occupational reasons). We decided to start omalizumab treatment, 300 mg every 4 weeks for 6 months. The cold urticaria patient gained complete symptom relief 10 days after the first dose of omalizumab; the quality of life improved substantially with no side effects of the treatment. The urticaria factitia patient showed no benefit of the add-on 5 months treatment with omalizumab. He refused the 6th dose of omalizumab due to the lack of response, and also cyclosporine, but he showed some benefits of oral corticosteroids. Although many clinical studies support the use of omalizumab in the treatment of patients with CIndU, we certainly need more data for prediction of a good clinical response.