Alergológica 2015: A National Survey on Allergic Diseases in the Adult Spanish Population.

BACKGROUND AND OBJETIVE: The frequency of allergic diseases is increasing worldwide, particularly in industrialized countries. From a clinical, management, and public heath perspective, it is important to determine the reasons for consulting an allergist, the distribution by frequency of allergic diseases, and how health care is provided. Objective: Alergológica 2015 was carried out to obtain information on clinical practice in allergy departments in Spain, and compare it with the previous study editions. METHODS: The data cover the year 2014 and the first quarter of 2015. The target sample was 6000 patients seen at public and private centers throughout Spain. A total of 500 allergists were invited to participate. Data were collected on an electronic case report form. Data were compared with the Alergológica surveys for 1992 and 2005 to identify differences. RESULTS: The final study population comprised 2914 patients (mean age 33.6 [18.9] years, 58% women, 17% children), of whom 6.1% were foreign-born. The frequency distribution was as follows: rhinitis, 62%; asthma, 23.4%; drug allergy, 17.7%; urticaria/angioedema, 11.5%; food allergy, 10.4%; contact dermatitis, 4%; atopic dermatitis, 3%; insect venom allergy, 2%. A statistically significant increase was observed between data from 2005 and from 2015 with respect to the prevalence for allergic rhinitis, food allergy and drug hypersensitivity. An increase in the prevalence of a personal history of asthma, rhinitis, conjunctivitis, and eczema/atopic dermatitis were also observed. Besides, the number of relevant allergens in the same patient also increased. Most patients were referred from primary care, although a considerable percentage were referred by ENT specialists and dermatologists. CONCLUSIONS: Increasing trends were observed for allergic rhinitis, drug allergy, and food allergy, and a decreasing trend was observed for asthma. Findings for other diseases remained practically unchanged. Allergic patients are increasingly complex and present with a myriad of atopic manifestations.

Alergológica 2015: A National Survey on Allergic Diseases in the Spanish Pediatric Population.

BACKGROUND: Allergic diseases are highly prevalent in industrialized populations. In Spain, children suspected of having an allergic disease are usually referred by their primary care pediatrician to an allergy unit at a general hospital or a children's hospital. We report data from a subanalysis of the pediatric population in Alergológica 2015. METHODS: Data were collected from pediatric patients (age, ≤14 years) consulting an allergist for the first time in 2014 and the first quarter of 2015 in order to determine variations compared with data reported in Alergológica 2005. RESULTS: Alergológica 2015 included fewer pediatric patients than Alergológica 2005. The study population comprised 481 patients aged ≤14 years from more than 200 centers throughout Spain. Males accounted for 56.5%. Rhinoconjunctivitis was the main reason for consulting an allergist (53.8% vs 46.3% in 2005), followed by asthma (30.2% vs 34.6%), and food allergy (20.0% vs 14.5%). CONCLUSIONS: The findings of Alergológica 2015 show a notable increased frequency of allergic rhinitis, drug allergy, and food allergy. The frequency of other allergic conditions remained unchanged, except for asthma, whose frequency decreased, as in adult patients.

Evaluation of an Online Educational Program for Parents and Caregivers of Children With Food Allergies.

BACKGROUND AND OBJECTIVE: The increasing prevalence of food allergy affects both patients and their families. Objective: The aim of this study was to evaluate the impact of an online educational program designed for parents and caregivers of children with food allergies. The program was developed by a multidisciplinary group comprising health care professionals, researchers, and expert patients under the participatory medicine model. MATERIAL AND METHODS: Participants took a 2-week online educational program covering major topics in food allergy management. General knowledge about the disease, symptoms, treatment, and topics relevant to families' daily lives were evaluated. The contents included educational videos, online forums, and live video chats. A pretest/posttest questionnaire survey was used to evaluate the impact of the program. RESULTS: A total of 207 participants enrolled in the educational program, which was completed by 130 (62.8%). Knowledge acquisition improved significantly following participation in the program in 15 out of 30 items (50%), reaching P<.001 for 8 items (26.7%). Of the 207 participants who started the program, 139 (67.1%) visited online forums, and 27.5% attended video chats. Average overall satisfaction with the educational program was 8.78 (on a scale of 0 to 10). CONCLUSIONS: The results obtained show that parents improved their knowledge in all areas of food allergy. The high level of satisfaction among participants suggests that digital learning tools are effective and motivational, enabling patients to acquire appropriate knowledge and thus increasing their quality of life.

Allergic asthma: an overview of metabolomic strategies leading to the identification of biomarkers in the field.

Allergic asthma is a prominent disease especially during childhood. Indoor allergens, in general, and particularly house dust mites (HDM) are the most prevalent sensitizers associated with allergic asthma. Available data show that 65-130 million people are mite-sensitized world-wide and as many as 50% of these are asthmatic. In fact, sensitization to HDM in the first years of life can produce devastating effects on pulmonary function leading to asthmatic syndromes that can be fatal. To date, there has been considerable research into the pathological pathways and structural changes associated with allergic asthma. However, limitations related to the disease heterogeneity and a lack of knowledge into its pathophysiology have impeded the generation of valuable data needed to appropriately phenotype patients and, subsequently, treat this disease. Here, we report a systematic and integral analysis of the disease, from airway remodelling to the immune response taking place throughout the disease stages. We present an overview of metabolomics, the management of complex multifactorial diseases through the analysis of all possible metabolites in a biological sample, obtaining a global interpretation of biological systems. Special interest is placed on the challenges to obtain biological samples and the methodological aspects to acquire relevant information, focusing on the identification of novel biomarkers associated with specific phenotypes of allergic asthma. We also present an overview of the metabolites cited in the literature, which have been related to inflammation and immune response in asthma and other allergy-related diseases.

Profile of patients treated with omalizumab in routine clinical practice in Spain.

BACKGROUND: Omalizumab is indicated in patients with severe allergic asthma not controlled by high-dose inhaled glucocorticoids and long-acting beta-agonists. Few data are available on the profile of patients treated with this drug in routine clinical practice in Spain. OBJECTIVE: To describe the profile of patients with severe allergic asthma treated with omalizumab and the course of the disease after a period of treatment. METHODS: Retrospective, multicentre study, recording the data on patients of either sex and ≥12 years with uncontrolled severe allergic asthma, previously treated with omalizumab. Data were evaluated in relation to pulmonary function, symptoms, quality of life, and concomitant anti-asthma treatment before the prescription of omalizumab and at the time of the study visit. RESULTS: 214 patients were evaluable (mean age=48.2±17.7 years; mean age at the time of diagnosis=26.6±16.5 years). 90.7% had experienced exacerbations the year before receiving omalizumab, and the mean total IgE level was 273±205.4IU/ml. The mean monthly dose was 380.5±185.4mg. Compared with the baseline situation, differences were observed after treatment with omalizumab in mean FEV1 (62.7±15.9% vs. 70.8±18.7%), in the proportion of patients requiring oral corticosteroids (47.7% vs. 14.0%), and in the ACQ and AQLQ scores. 32.7% of the patients received doses not recommended by the Summary of Product Characteristics (SPC). CONCLUSIONS: Profile of asthmatic patients treated with omalizumab predominantly corresponds to uncontrolled severe asthma cases, in accordance with SPC's indications. The results of the study suggest a favourable clinical course similar to that observed in other studies.

Allergy, living and learning: diagnosis and treatment of allergic respiratory diseases in Europe.

BACKGROUND: Allergy Living and Learning (ALL) is a European initiative designed to increase knowledge and understanding of people living with allergies in order to improve respiratory allergy care. OBJECTIVES: To investigate diagnostic and treatment patterns associated with respiratory allergies, patients' perception of their treatment, and restrictions on daily activities. METHODS: Using a telephone-based randomized screening method, we recruited and analyzed 7004 patients (aged 16-60 years) with self-reported respiratory allergic disease from 10 European countries. Patients answered questions assessing their knowledge, experience, and perception of their condition and its treatment. Data analyses were descriptive. RESULTS: The most prevalent conditions were allergic rhinitis (66%) and asthma (26%), and the average duration of the symptoms of respiratory allergy was 14.5 years. Over 30% of patients had never had a specific diagnostic test. About 80% of patients used medication for their respiratory allergy, and 10% of those not receiving treatment had severe symptoms. One-third of patients were not satisfied with their treatment, and two-thirds experienced restrictions in daily activities. Medication was most commonlytaken in the form of tablets and nasal spray. Allergy-specific immunotherapy was received by 16% of patients. Knowledge of specific immunotherapy was low overall and varied widely by country: 30% of patients (country range, 10%-52%) had never heard of this treatment option. CONCLUSIONS: A notable proportion of individuals with respiratory allergy in Europe are underdiagnosed, undertreated, and dissatisfied with their treatment. Addressing these shortcomings may help to optimize respiratory allergy care and, ultimately, quality of life.

Allergic Rhinitis and its Impact on Asthma update (ARIA 2008). The perspective from Spain.

Allergic rhinitis is a global health problem. Over 600 million patients suffer from this disease worldwide. ARIA (Allergic Rhinitis and its Impact on Asthma), an evidence-based document, was produced and published in 2001 using an extensive review of the available literature. The ARIA 2008 update was recently published and covers tertiary prevention of allergy, pharmacologic treatments, and immunotherapy. Nonallergic rhinitis is still a controversial area and may pose some treatment problems. Another important aspect of the ARIA update is the comorbidity of allergic rhinitis, in particular, asthma. The recommendations of the 2008 ARIA Update, as in 2001, are that patients with allergic rhinitis, particularly if persistent, should be evaluated for asthma, patients with asthma should be evaluated for rhinitis, and an effective and safe combination strategy should be used to treat diseases of the upper and lower airways. Over the last few years, severa studies performed in Spain report new data on the prevalence of allergic rhinitis sensitivity to common aeroallergens, comorbidity of allergic rhinitis and asthma, and impact on quality of life. The studies reviewed in this manuscript confirm--as do those from other developed countries--the enormous impact of the disease on society and health care in Spain.

Cross-reactivity between Anisakis simplex sensitization and visceral larva migrans by Toxocara canis.

The aim of this work was to study cross-reactivity in the diagnosis of two related ascaridosis. Nineteen patients diagnosed with recidivous acute urticaria (RAU) caused by Anisakis simplex and 26 patients diagnosed with visceral larva migrans (VLM) caused by Toxocara canis were studied employing commercial diagnostic kits and "in house" assay kits. Cross-reactivity observed was greater when using "in house" assay kits, suggesting that T. canis excretory-secretory antigens were not only recognized by antibodies from patients with RAU but with greater intensity compared to the A. simplex excretory-secretory antigens.

National prevalence of respiratory allergic disorders.

BACKGROUND: Many epidemiological studies have assessed the prevalence of respiratory allergic disorders in confined geographical locations. However, no study has yet established nationally prevalence data in a uniform manner representing whole countries and, thus, enabling cross-national comparisons. METHODS: In 10 European countries, screening of random, representative samples of telephone numbers identified the target population aged 16-60. The inclusion criteria were a positive reporting of respiratory allergy to named allergens and, concomitantly, an unassisted description of appropriate symptoms. To obtain a truly representative, national prevalence of each country, the data were weighted against the actual sex and age composition. RESULTS: 31,065 screening interviews were performed. The nationally balanced prevalence varied significantly among the 10 countries (P<0.001) from 11.7% in Spain to 33.6% in Italy. The overall weighted prevalence for Europe was 24.4%. Comparing males and females, overall, the odds-ratio was 0.874 (P<0.001). For age intervals of 16-29, 30-49, and 50-60 years, the odds-ratios for males were 1.104 (P<0.088), 0.827 (P<0.001), and 0.658 (P<0.001), respectively. The prevalence correlated inversely with age. CONCLUSIONS: Respiratory allergic disorders constitute a huge health problem in Europe, and the impact may be increasing as the prevalence is highest among young people.

Living & learning with allergy: a European perception study on respiratory allergic disorders.

BACKGROUND: Knowledge of allergy patients' perception of own disease is inadequate, and understanding of the impact of local environment, including family and health-care system, on patients' management of disease is insufficient. We examined the potential of telephone-based survey techniques for establishing this knowledge in 10 European countries. METHODS: A two-phased questionnaire developed by use of focus groups in seven countries was translated into 10 languages. To ensure that the true values of the populations were restored in randomly selected populations, 75,343 telephone numbers selected for screening represented balanced national distributions of households. RESULTS: Eight thousand two hundred and sixty-eight respiratory allergy sufferers were identified by the telephone screening process. 85.4% accepted to participate in the survey and 89.6% completed both phases comprising 34 questions and rating of 49 statements. Data for each country were weighted in terms of age, sex and the recorded allergy prevalence within age intervals. CONCLUSIONS: The telephone survey technique allowed for establishment of random representative samples, and application of mathematical weighting procedures assured that the true national values were restored in the data set. As all interviews were performed in a standardised manner we conclude that the telephone-based survey methodology enables national representative data set to be established and compared.

Anaphylaxis induced by ingestion of a pollen compound.

We report on the case of a 32-year-old atopic patient who showed a severe anaphylactic reaction due to the ingestion of a pollen compound prepared in an herbalist's. A few minutes after ingestion, generalized pruritus, difuse erythema, facial edema, cough, hoarseness and dysphonia appeared, and the emergency administration of subcutaneous epinephrine and intravenous methylprednisolone was necessary. Skin tests with a battery of inhalants and food allergens were performed. The patient only showed sensitization to Artemisia vulgaris, Taraxacum officinalis and Salix alba. Specific IgE levels were evaluated by FEIA-CAP giving a seric level of CAP class 3 to Artemisia vulgaris and class 2 to Taraxacum officinalis and Salix alba. Samples of the pollen compound were shown in the microscopical analysis to be 93% pollens and 6% fungi. In the qualitative study Taraxacum officinalis (15%), Artemisia vulgaris (5%) and Salix alba (15%) were the main elements identified. In summary, this case study describes a food-induced systemic reaction due to a pollen compound in an atopic patient with a history of allergic rhinitis. Pollinic patients must be informed on the risks that the consumption of these compounds might cause.

[Allergology in the public health service of the Community of Madrid: current situation and opportunities in the XXI century public health system]. / La alergología en el sistema sanitario público de la Comunidad de Madrid: situación actual y oportunidades en el sis. sanitario público del siglo XXI.

The high prevalence of allergic diseases and the use of more complex diagnostic techniques and therapeutic options require allergists to be highly trained professionals and health-care organizations to be knowledgeable about available structural and human resources. Updated information is lacking in Spain, and current activity indicators do not reflect complexity. The present article analyzes the situation of allergology in Madrid and proposes improvements where necessary. The heads of the allergy departments of public hospitals in Madrid voluntarily completed a purpose-designed survey. Data on care activity (2010) and on teaching and research activity (2009-2010) were provided. A SWOT analysis was performed, and strategic lines and proposals for improvement were designed. One hundred and seventeen allergists (41% with a PhD) worked in 24 hospitals with an allergology department (4.6 physicians/center; ≤3 in 10 hospitals). All the institutions had an outpatient clinic (4,000 first consultations/hospital/year, 36% high-resolution rate; 6200 successive visits/hospital/year) performing complex diagnostic and therapeutic procedures, most of which were not taken into account by activity indicators. Two hospitals had their own hospitalization facilities and 10 were accredited teaching hospitals (2.78 medical residents/year). The survey revealed that, twice yearly, a typical allergology service participated in 4 research projects, 2 clinical trials, 16 publications and 17 communications at scientific meetings, with notable differences between hospitals. Allergists in Madrid are well prepared. The allergology care structure is adequate, although possibly insufficient. Quality and efficiency can be improved with new tools for recording activity and by increasing coordination and taking advantage of new technologies and geographical proximity.

Diagnosing human anisakiasis: recombinant Ani s 1 and Ani s 7 allergens versus the UniCAP 100 fluorescence enzyme immunoassay.

Commercially available serological methods for serodiagnosis of human anisakiasis either are poorly specific or do not include some of the most relevant Anisakis allergens. The use of selected recombinant allergens may improve serodiagnosis. To compare the diagnostic and clinical values of enzyme-linked immunosorbent assay (ELISA) methods based on Ani s 1 and Ani s 7 recombinant allergens and of the UniCAP 100 fluorescence enzyme immunoassay (CAP FEIA) system, we tested sera from 495 allergic and 25 non-food-related allergic patients. The decay in specific IgE antibodies in serum was also investigated in 15 positive patients over a period of 6 to 38 months. Considering sera that tested positive by either Ani s 1 or Ani s 7 ELISA, the CAP FEIA classified 25% of sera as falsely positive, mainly in the group of patients with the lowest levels of anti-Anisakis IgE antibodies, and 1.28% of positive sera as falsely negative. Considering allergens individually, the overall sensitivities of Ani s 7 ELISA and Ani s 1 ELISA were 94% and 61%, respectively. The results also showed that anti-Anisakis IgE antibodies can be detected in serum for longer with Ani s 1 ELISA than with Ani s 7 ELISA and CAP FEIA (P < 0.01). Our findings suggest that ELISA methods with Ani s 7 and Ani s 1 allergens as targets of IgE antibodies are currently the best option for serodiagnosis of human anisakiasis, combining specificity and sensitivity. The different persistence of anti-Ani s 1 and anti-Ani s 7 antibodies in serum may help clinicians to distinguish between recent and old Anisakis infections.

Western blot antibody determination in sera from patients diagnosed with Anisakis sensitization with different antigenic fractions of Anisakis simplex purified by affinity chromatography.

Using Western blot techniques, the specificities of crude and purified (PAK and PAS) Anisakis simplex antigens were compared against 24 sera from patients diagnosed with Anisakis sensitization. All patients recognized a 60 kDa protein against the A. simplex crude extract, while 37.5% and 12.5% reacted with proteins of 40 and 25 kDa, respectively, when IgG was tested. In the case of IgE determination, 41.6% of sera were negative, while 12.5% and 20.8% appeared to cross-react against Toxocara canis and Ascaris suum, respectively. When the PAK antigen (A. simplex antigen purified by means of a column of IgG anti-A. simplex) was tested, immune recognition towards the 60, 40 and 25 kDa proteins increased in 83.3%, 16.7% and 4.2%, respectively, when the Ig antibodies were tested. In the case of the PAS antigen (PAK antigen purified by means of a column of IgG anti-A. suum), the reaction against the 40 and 25 kDa proteins increased to 45.8% and 25%, respectively, when Ig antibodies were used. Finally, when the EAS antigen (eluted from the anti-A. suum column after PAK purification) was tested, 83.3% of the assayed sera reacted against the 14 kDa protein, when the Ig antibodies, IgG and IgM immunoglobulins were measured. With the IgE determination, the reactions were observed in 41.7% of patients with proteins between 60 and 35 kDa against the PAS antigen. With the EAS antigen, reactive bands of 184, 84 and 14 kDa appeared. In conclusion, in the purification process of the A. simplex larval crude extract, the proteins implicated in cross-reactions with Ascaris and Toxocara were eliminated, with an important concentration of proteins responsible for the induction of specific responses.

Enzyme-linked immunosorbent assay and Western blot antibody determination in sera from patients diagnosed with different helminthic infections with Anisakis simplex antigen purified by affinity chromatography.

An evaluation of the sensitivity and the specificity of the Anisakis simplex antigens purified by affinity chromatography was performed using sera from patients diagnosed with Anisakis sensitisation and sera from patients previously diagnosed with different helminthic infections. Only the sera of the patients diagnosed with Schistosoma mansoni or Onchocerca volvulus parasitic infections were negative against the A. simplex antigen and its purified fractions (PAK antigen: A. simplex antigen purified using columns prepared with anti-A. simplex rabbit IgG and PAS antigen: PAK antigen purified using columns prepared with anti-Ascaris suum rabbit IgG). However all the sera were positive against the A. suum antigen. In all the sera from the patients diagnosed with Anisakis sensitisation, the antibody levels detected using the purified antigens (PAK and PAS antigens) were lower than the observed using the A. simplex crude extract with the highest diminution in the case of the IgG. When these same sera were tested against the A. simplex crude extract by Western blot, several bands of high molecular masses were observed as well as, intense bands at 60 and/or 40 kDa. A concentration of these last proteins was observed in the PAK and the PAS antigens. When the sensitivity and the specificity determinations were performed, only seven of the 38 patients diagnosed of Anisakis sensitisation were positive, as well as, the sera from the patients diagnosed with parasitisms by Echinococcus granulosus or Fasciola hepatica.

Recidivous acute urticaria caused by Anisakis simplex.

This study aimed to determine the cause of acute recidivous urticaria in patients who usually eat fish or other seafood. Twenty-five patients were studied. The skin prick test with larval Anisakis simplex extract was performed; total and specific IgE against A. simplex was measured with the CAP System; specific antibodies to A. simplex were determined by ELISA; and immunorecognition patterns of the sera were studied by Western blot. Nineteen patients showed specific IgE to A. simplex, but specific IgE to Ascaris was demonstrated in only two patients. No patients reacted to Toxocara canis or Echinoccocus granulosus antigens with the same test. The skin prick test was positive in 16 patients, in two of them persisting for 48 h. Five patients showed neither skin reaction nor specific IgE to A. simplex. Sera showed specific immunoglobulin levels against A. simplex larval crude extract, by both ELISA and Western blot. Likewise, specific immunoglobulin levels against excretory-secretory antigen were also measured by ELISA. Only one patient showed sensitization to fish. A. simplex was found to be the main cause of acute recidivous urticaria in patients who usually eat fish and are not sensitized to it.

Evaluation by the skin prick test of Anisakis simplex antigen purified by affinity chromatography in patients clinically diagnosed with Anisakis sensitization.

Anisakis simplex crude extracts (CE) (IPI, ASAC and ALK-ABELLO), A. simplex larval antigens purified using a column of IgG anti-A. simplex (PAK) or a column of IgG anti-Ascaris suum (PAS), antigen eluted from columns of IgG anti-A. suum (EAS) and an A. suum adult CE were assayed by the skin prick test. Thirty percent of assayed patients showed a negative reaction in the Anisakis skin prick test. Of 70% positives, two patients had a weal greater than that produced by histamine with the A. simplex extract from ABELLO and IPI. The A. suum skin prick test was positive in 35% of patients, with a lower reaction than that observed with the A. simplex extract from IPI in 57% of the sera and a higher reaction in 28% of the sera. All patients with positive reactions with the crude extract also showed positive weals with the two purified antigens, PAK and PAS. All patients, except three, with a reaction to A. suum antigen, were positive to the EAS antigen. In five patients the weal size produced by PAS was greater than that observed with PAK, whereas in another six patients the contrary was observed. Only one of these six patients did not react to EAS antigen, coincident with the patient showing only a slight increase (7%) in the weal size induced by PAK vs. PAS. When the EAS antigen was tested on patients positive to both PAK and PAS, six patients presented a weal size of >30% and only three patients who were positive to PAS did not react to the EAS antigen. These three patients were also negative against the A. suum CE. Purification by affinity chromatography eliminates from the PAS antigen the proteins responsible for producing cross-reactions with Ascaris (present in the EAS antigen).