Immunological parameters as biomarkers of response to MicroCrystalline Tyrosine-adjuvanted mite immunotherapy.

BACKGROUND: Despite the effectiveness of allergen immunotherapy (AIT), some patients are unresponsive for reasons still unknown; yet validated response biomarkers remain unavailable. OBJECTIVE: To analyze immunological parameters as biomarkers to monitor and predict clinical response to a MicroCrystalline Tyrosine-adjuvanted house dust mite (HDM) AIT in patients with allergic rhinitis (AR). METHODS: Observational, prospective, multicenter study including adult patients (aged 18-65 years) with AR, with and without asthma, sensitized to the HDM Dermatophagoides pteronyssinus (DP) and prescribed Acarovac Plus® DP 100% in the routine practice. Serum concentrations of total IgE, specific IgE, specific IgG4, IL-4, IL-5, IL-10, IL-13, and IFN-γ were compared between baseline and 12 months after AIT. The relationship between patients' baseline immunological profiles and classification as low, high, and non-responders and between their sensitization profile to DP allergens and effectiveness were analyzed. RESULTS: Of 141 patients recruited, 118 (mean [SD] age of 33.6 [9.5] years) were evaluable. One year after treatment, Der p 1-specific IgE, DP-specific IgG4, and IL-10 increased by a mean (SD) of 3.4 (13.6) kU/L (p = 0.016), 0.43 (0.55) mg/L (p < 0.0001), and 1.35 (7.56) pg/mL (p = 0.033), respectively. Non-responders showed increased baseline levels of IL-13 compared to high responders (p = 0.037). Changes in effectiveness variables between baseline and after AIT were similar regardless of the sensitization profile. CONCLUSION: Non-responsive patients to AIT showed increased baseline IL-13 concentrations, suggesting its value as prognostic biomarker. DP-specific AIT increased Der p 1-specific IgE, DP-specific IgG4, and IL-10 concentrations in patients with AR. All patients benefited from treatment regardless of their sensitization profile to major DP allergens.

Consensus on the Clinical Approach to Moderate-to-Severe Atopic Dermatitis in Spain: A Delphi Survey.

BACKGROUND: The purpose of this study was to gather information on the current assessment and management of patients with moderate-to-severe AD in routine daily practice. METHODS: A cross-sectional two-round Delphi survey with the participation of dermatologists and allergologists throughout Spain was conducted. They completed a 46-item questionnaire, and consensus was defined when responses of ≥80% of participants coincided in the categories of a 5-point Likert scale for that item. RESULTS: A total of 105 specialists (aged 40-59 years) completed the two rounds. Participants agreed regarding the consideration of AD as a multifaceted disease and the differences in clinical presentation of AD according to the patient's age. It is recommendable to perform a skin biopsy to exclude early stage T-cell cutaneous lymphoma, psoriasis, or dermatitis herpetiformis, among others (99.1%). Also, consensus was reached regarding the use of the SCORAD index to quantify the severity of the disease (86.7%), the use of wet wraps to increase the effect of topical corticosteroids (90.4%), the usefulness of proactive treatment during follow-up (85.6%) and tacrolimus ointment (91.2%) to reduce new flares, and the fact that crisaborole is not the treatment of choice for severe AD (92.4%). AD was not considered a contraindication for immunotherapy in patients with allergic respiratory diseases (92.4%). In patients with severe AD, the use of immune response modifier drugs (97.6%) or phototherapy (92.8%) does not sufficiently cover their treatment needs. Consensus was also obtained regarding the role of the new biologic drugs (93.6%) targeting cytokines involved in the Th2 inflammatory pathway (92.0%) and the potential role of dupilumab as first-line treatment (90.4%) in moderate-to-severe AD patients. CONCLUSION: This study contributes a reference framework to the care of AD patients. There is no diagnostic test or biomarkers to direct treatment or to assess the severity of the disease, and many therapeutic challenges remain.

Real-life effect of a microcrystalline tyrosine adjuvanted mite immunotherapy in patients with allergic rhinitis.

Aim: Evaluate the effectiveness and safety of immunotherapy with Acarovac Plus® in a 1-year prospective multicentered real-life study. Methods: A total of 118 adults with allergic rhinitis sensitized to Dermatophagoides received subcutaneous immunotherapy with Acarovac Plus. Treatment outcomes were evaluated at baseline, 6 months and 1 year after treatment initiation. Primary end point was the evolution of the combined symptom and medication score. Secondary end points included other effectiveness outcomes and measurement of product tolerability. Results: Acarovac Plus induced significant improvements in primary and secondary end points after 6 months compared with baseline. These differences persisted after 1 year of treatment (p < 0.001; baseline vs 1 year): combined symptom and medication score (1.60 vs 0.79). No serious adverse events were recorded. Conclusion: Acarovac Plus for 1 year was effective and well tolerated in a real-life setting.

[Executive Summary of ARIA 2019: Integrated care pathways for allergic rhinitis in Argentina, Spain and Mexico]. / Resumen ejecutivo de ARIA 2019: Vías integradas de atención para la rinitis alérgica en Argentina, España y México.

The health and economic impact of allergic diseases are increasing rapidly, and changes in management strategies are required. Its influence reduces the capacity of work and school performance by at least a third. The ICPs of the airways (integrated care pathways for respiratory diseases) are structured multidisciplinary healthcare plans, promoting the recommendations of the guidelines in local protocols and their application to clinical practice. This document presents an executive summary for Argentina, Mexico, and Spain. Next-generation ARIA guidelines are being developed for the pharmacological treatment of allergic rhinitis (AR), using the GRADE-based guidelines for AR, tested with real-life evidence provided by mobile technology with visual analogue scales. It is concluded that in the AR treatment, H1-antihistamines are less effective than intranasal corticosteroids (INCS), in severe AR the INCS represent the first line of treatment, and intranasal combination INCS + anti-H1 is more effective than monotherapy. However, according to the MASK real-life observational study, patients have poor adherence to treatment and often self-medicate, according to their needs.

El impacto sanitario y económico de las enfermedades alérgicas está aumentando rápidamente y se necesitan cambios en las estrategias para su manejo. Su influencia reduce al menos en un tercio la capacidad de desempeño laboral y escolar. Los ICP (Vías Integradas de Atención) de las enfermedades de las vías respiratorias son planes de atención estructurados y multidisciplinarios, que promueven las recomendaciones de las guías en protocolos locales y su aplicación a la práctica clínica. En este documento se presenta un resumen ejecutivo para Argentina, México y España. Se desarrollan las guías ARIA de próxima generación para el tratamiento farmacológico de la rinitis alérgica (RA) utilizando las pautas basadas en GRADE para RA, probadas con evidencia de la vida real proporcionada por tecnología móvil basada en escalas visuales analógicas. Se concluye que en el tratamiento de la RA, los antihistamínicos anti-H1 son menos efectivos que los corticoides intranasales (CINS), que en la rinitis gravelos CINS representan la primera línea de tratamiento, y que la combinación intranasal de CINS + anti-H1 es más eficaz que la monoterapia. Sin embargo, según el estudio MASK observacional en vida real, los pacientes tienen pobre adherencia al tratamiento y frecuentemente se automedican de acuerdo con sus necesidades.

Analysis of comorbidities and therapeutic approach for allergic rhinitis in a pediatric population in Spain.

BACKGROUND: Allergic rhinitis (AR) is the most common chronic disease in children. The main objective of this study was to analyze the comorbidities and therapeutic approaches for AR in a Spanish pediatric population. METHODS: Children aged 6 to 12 years with AR were included in an observational, cross-sectional, multicenter study. RESULTS: 1,275 children were recruited from 271 centers. AR was intermittent in 59.5% of cases, persistent in 40.5%, seasonal in 60.7%, and perennial in 39.3% of patients. The most frequent comorbidities were conjunctivitis (53.6%), asthma (49.5%), atopic dermatitis (40%), rhinosinusitis(26.1%), otitis media (23.8%), and adenoid hypertrophy (17.3%). Overall, patients with persistent, moderate or severe, AR were more likely to present comobidities, except for food allergy and urticaria. The most common drugs used for treatment of AR were oral antihistamines(76%), nasal corticosteroids(49%) and a combination of both (45%). Antihistamines and nasal corticosteroids were used on demand (<18 days) in 38 and 41% of patients, respectively; for 18-30 days in 22 and 27%; for 1-3 months in 31 and 29%; and for more than 3 months in 8 and 3%, respectively. Eye drops were used in 32% and specific immunotherapy in 21% of patients. CONCLUSION: Comorbidities are frequent in children with AR, supporting the notion of allergy as a systemic disease. Severity and duration of AR were significantly associated with presence of most of comorbidities. The most common drugs used for AR treatment were oral antihistamines, followed by nasal corticosteroids and a combination of both used on demand.

Platelet-activating factor nasal challenge induces nasal congestion and reduces nasal volume in both healthy volunteers and allergic rhinitis patients.

BACKGROUND: Platelet-activating factor (PAF) is a lipid mediator produced by most inflammatory cells. Clinical and experimental findings suggest that PAF participates in allergic rhinitis (AR) pathogenesis. The aim was to assess the PAF ability to induce clinical response in nasal airway after local stimulation. METHOD: Ten nonatopic healthy volunteers (HVs) and 10 AR patients out of pollen season were enrolled. PAF increasing concentrations (100, 200, and 400 nM) were instilled into both nasal cavities (0, 30, and 60 minutes, respectively). Nasal symptoms (congestion, rhinorrhea, sneezing, itching, and total 4 symptom score and nasal volume between the 2nd and 5th cm (Vol(2-5)) using acoustic rhinometry (AcR), were assessed at -30, 0, 30, 60, 90, 120, and 240 minutes. RESULT: PAF increased individual and total nasal symptom score in both HVs and seasonal AR (SAR) patients from 30 to 120 minutes (maximum score at 120', p < 0.05). Nasal obstruction was the most relevant and lasting nasal symptom. PAF also induced a significant reduction of Vol(2-5) at 90' (27%), 120' (38.7%), and 240' (36.4%). No differences in the response to PAF nasal challenge were observed between HVs and SAR subjects in either clinical symptoms or AcR. CONCLUSION: This is the first description of PAF effects on human nasal mucosa using a cumulative dose schedule and evaluated by both nasal symptoms and AcR. Nasal provocation with PAF showed long-lasting effects on nasal symptoms and nasal obstruction in HVs and in patients with SAR. Nasal challenge may be a useful tool to investigate the role of PAF in AR and the potential role of anti-PAF drugs.

Human milk probiotic Lactobacillus fermentum CECT5716 reduces the incidence of gastrointestinal and upper respiratory tract infections in infants.

OBJECTIVES: The aim of the study was to examine the effects of a follow-on formula containing Lactobacillus fermentum CECT5716 (L. fermentum) on the incidence of infections in infants between the ages of 6 and 12 months. PATIENTS AND METHODS: A randomized double-blinded controlled study including infants at the age of 6 months was conducted. Infants were assigned randomly to either follow-on formula supplemented with L. fermentum plus galactooligosaccharide (experimental group, EG), or the same formula supplemented with only galactooligosaccharide (control group, CG). The main outcome was the incidence of infections for the 6-month duration of the study. RESULTS: The EG showed a significant 46% reduction in the incidence rate (IR) of gastrointestinal infections (EG: 0.196 ±â€Š0.51, CG: 0.363 ±â€Š0.53, IR ratio 0.54, 95% confidence interval [CI] 0.307-0.950, P = 0.032), 27% reduction in the incidence of upper respiratory tract infections (EG: 0.969 ±â€Š0.96, CG: 1.330 ±â€Š1.23, IR ratio 0.729, 95% CI 0.46-1.38, P = 0.026), and 30% reduction in the total number of infections (EG: 1.464 ±â€Š1.15, CG: 2.077 ±â€Š1.59, IR ratio 0.70, 95% CI 0.46-1.38, P = 0.003), at the end of the study period compared with CG. CONCLUSIONS: Administration of a follow-on formula with L. fermentum CECT5716 may be useful for the prevention of community-acquired gastrointestinal and upper respiratory infections.

Diagnosis and treatment of grass pollen-induced allergic rhinitis in specialized current clinical practice in Spain.

Allergic rhinitis (AR) is the leading cause of consultation at the allergy specialist's office, but detailed, reliable, and validated clinical data on this condition are limited. This study was designed to define the clinical features, diagnostic methods, and therapeutic approaches of patients with AR induced by grass pollen in Spain. Two hundred twelve specialists participated in a multicenter, observational, epidemiologic, questionnaire-based study. Each investigator had to recruit at least two patients consulting for the first time and with a diagnosis of AR induced by grass pollen. Five hundred twenty-four patients (52% men; mean age, 29.3 years) with grass pollen-induced rhinitis (mean disease duration, 8.7 years) were recruited. Just 18.4% of patients reported that their symptom status had improved since the beginning of the condition, 89.4% had moderate-severe rhinitis (Allergic Rhinitis and Its Impact on Asthma classification) and 35.1% had concomitant bronchial asthma. For 52.1% of patients, control of symptoms with previous drug treatment was poor. Most of the patients were polysensitized to other pollens (sensitization to olive tree pollen, 57.1%). Oral antihistamines (97.3%) and nasal corticosteroids (82.3%) were the most frequently prescribed drugs and 43.1% of patients received specific immunotherapy. The clinical profile for the majority of Spanish patients consulting an allergy specialist for AR induced by grass pollen corresponds to a young adult with a lengthy moderate-severe rhinitis, often accompanied by bronchial asthma. Their symptoms progressively worsen and rhinitis is poorly controlled by symptomatic treatment. Oral antihistamines and nasal corticosteroids are the most frequently used therapeutic approaches and less than one-half receive specific immunotherapy.

Epidemiology of allergic rhinitis caused by grass pollen or house-dust mites in Spain.

BACKGROUND: Although the prevalence of allergic rhinitis (AR) is increasing, relatively little is known about patient characteristics in Spain. The aim of this study was to investigate the clinical profile and therapeutic strategies in patients attending Spanish specialists for AR caused by grass pollen or house-dust mites (HDMs). METHODS: This was a multicenter cross-sectional epidemiological study of consecutive patients aged ≥5 years with confirmed diagnosis of AR caused by grass pollen or HDMs attending allergy specialists throughout Spain. Demographic and clinical data and information on treatment were collected. RESULTS: Data from 1043 patients were analyzed (524 with grass pollen allergy and 519 with HDM allergy; mean age, 27.1 years). Three-quarters had persistent AR as per the Allergic Rhinitis and Its Impact on Asthma (ARIA) definition, with disease duration of >2 years in 94.3% of those with pollen allergy and 85.5% of those with HDM allergy. Approximately 38% had concurrent asthma. Over one-half of the patients were considered to have gotten worse since the first onset of symptoms. In total, 51.5% did not achieve good disease control with pharmacotherapy and 47.7% were treated with immunotherapy (52.2% of HDM allergic patients and 43.2% of grass pollen-allergic patients). CONCLUSION: The duration of AR in patients attended for the first time by specialists is long and, in general, the disease does not improve over time and is often not well controlled with pharmacologic interventions. Less than one-half of patients receive allergen-specific immunotherapy that is more often prescribed in HDM allergy.

Validation of ARIA (Allergic Rhinitis and its Impact on Asthma) classification in a pediatric population: the PEDRIAL study.

Allergic rhinitis (AR) is the commonest chronic disease in children. Allergic Rhinitis and its Impact on Asthma (ARIA) classification based on symptom duration (intermittent vs. persistent) and severity (mild vs. moderate/severe) has not been yet validated in children. Thus our objective was to validate ARIA classification in children, after determining the severity and duration of AR in a pediatric population, using ARIA definitions. Children aged 6-12 with a diagnosis of AR were included in an observational, cross-sectional, multicenter study. Patients were classified according to ARIA guidelines. AR symptoms were assessed using the Total Four Symptoms Score (T4SS). Severity was also evaluated by the patient using a visual analogue scale (VAS). Comparisons were made by means of a statistical analysis. One thousand two hundred and seventy-five children from 271 centers were included. Among them, 59.5% had intermittent and 40.5% persistent AR, while 60.7% seasonal and 39.3% perennial according to dated classification, with significant differences existing between one classification and another; 89.7% had moderate/severe rhinitis. Significantly higher T4SS and VAS scores were obtained in moderate/severe compared to mild AR. In our experience, the current ARIA classification can be considered a valid tool also in children from 6- to 12-yr old.

Anaphylaxis to wheat flour-derived foodstuffs and the lipid transfer protein syndrome: a potential role of wheat lipid transfer protein Tri a 14.

BACKGROUND: Food allergy to wheat-derived foodstuffs is on the rise. Tri a 14, a wheat flour lipid transfer protein (LTP) allergen, has been described as a major allergen associated with baker's asthma and wheat food allergy. Cross-reactivity among LTP allergens leads to the so-called 'LTP syndrome'. METHODS: Eight adult patients showing anaphylaxis after ingestion of wheat-derived foodstuffs were selected. A homemade wheat extract, purified natural (n) and recombinant (r) Tri a 14, and peach fruit and Artemisia pollen LTP allergens Pru p 3 and Art v 3 were subjected to skin prick test, specific IgE determination (ELISA) and IgE immunodetection assays. RESULTS: All tests were positive in the 8 selected patients with the homemade extract. Positive skin prick test responses to nTri a 14, Pru p 3 and Art v 3 were found in 5/8, 6/8 and 4/4 patients, respectively. Specific IgE determined by ELISA assays was detected in 6 to nTri a 14 and rTri a 14, in 4 to Pru p 3 and in 3 to Art v 3 out of 8 individual sera tested, whereas all these sera showed IgE binding to nTri a 14 and Pru p 3 in immunodetection after SDS-PAGE separation. CONCLUSIONS: Tri a 14 seems to be a relevant allergen in patients with anaphylaxis after ingestion of wheat flour foodstuffs, according to in vitro and in vivo results. Clinical history of the analyzed patients, together with sensitization to peach Pru p 3 and Artemisia pollen Art v 3, suggests that 6 of them suffer from LTP syndrome.

The administration of a multivitamin/mineral fortified dairy product improves folate status and reduces plasma homocysteine concentration in women of reproductive age.

BACKGROUND AND OBJECTIVES: Folate deficiency during the periconceptional period is related to the occurrence and recurrence of neural tube defects. The aim of the study was to assess whether the administration of folic acid and other vitamins and minerals as a fortified dairy product (400 microg per day of folic acid) improves the folate status in women of reproductive age. DESIGN AND METHODS: Plasma and red blood cell folate, plasma vitamin E, B12, total plasma homocysteine, plasma lipid profile, and serum ferritin and transferrin levels were investigated in 31 healthy nonpregnant women receiving 500 mL/day of the fortified dairy product for eight weeks. RESULTS: The women showed a significant increase in plasma levels of folate and vitamin B12 concentrations after four and eight weeks of supplementation. Moreover, we observed an increase in red blood cell folate concentration during the period of the study. Simultaneously, total plasma homocysteine levels decreased significantly during the intervention period. CONCLUSIONS: The regular consumption of a folic acid and other vitamins (mainly vitamins B6 and B12) and minerals in a fortified dairy product improves folate status and reduces total plasma homocysteine concentration in healthy women of childbearing age.