Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotype

Aims: Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obeseallergen sensitized mice. Main methods: Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1+) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression. Key findings: Obesity and allergen-sensitization together increased the number of LYVE-1+ lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues. Significance: The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.

Formaldehyde: exposure and genotoxicity assessments and potential health effects

Worldwide formaldehyde is manipulated with diverse usage properties, since industrial purposes to health laboratory objectives, representing the economic importance of this chemical agent. Therefore, many people are exposed to formaldehyde environmentally and/or occupationally. Considering the latter, there was recommended occupational exposure limits based on threshold mechanisms, limit values and indoor guidelines. Formaldehyde is classified by the International Agency for Cancer Research (IARC) as carcinogenic to humans (group 1), since a wide range of epidemiological studies in occupational exposure settings have suggested possible links between the concentration and duration of exposure and elevated risks of nasopharyngeal cancer, and others cancers, and more recently, with leukemia. Although there are different classifications, such as U.S. EPA that classified formaldehyde as a B1 compound, probable human carcinogen under the conditions of unusually high or prolonged exposure, on basis of limited evidence in humans but with sufficient evidence in animals. Formaldehyde genotoxicity is well-known, being a direct-acting genotoxic compound positively associated for almost all genetic endpoints evaluated in bacteria, yeast, fungi, plants, insects, nematodes, and cultured mammalian cells. There are many human biomonitoring studies that associate formaldehyde occupational exposure to genomic instability, and consequently possible health effects. Besides the link with cancer, also other pathologies and symptoms are associated with formaldehyde exposure, namely respiratory disorders such as asthma, and allergic contact dermatitis. Nowadays, there are efforts to reduce formaldehyde exposure, namely indoor. Europe and United States developed more strict regulation regarding formaldehyde emissions from materials containing this agent. Despite the regulations and restrictions, formaldehyde still continues to be difficult to eliminate or substitute, being biomonitoring an important tool to control possible future health effects.

Temporal trends in the prevalence of asthma and rhinoconjunctivitis in adolescents

ABSTRACT OBJECTIVE To analyze the temporal trend of asthma and rhinoconjunctivitis prevalences as well as their symptoms in adolescents. METHODS Two cross-sectional studies were conducted using the same methodology and questionnaire as was used for adolescents aged 12 to 14 years in the Brazilian city of Florianopolis, SC, Southern Brazil. Based on the international protocol of the International Study of Asthma and Allergies in Childhood (ISAAC) study, adolescents were evaluated in 2001 and 3,150 in 2012. The schools included in this study were the same as in the 2001 study. These schools were randomly selected after stratification by network (public and private) and geographic location. The total average percentage variation was estimated for the prevalence of asthma and rhinoconjunctivitis and their symptoms. RESULTS The prevalence of reported asthma was 10.9% in 2001 and 14.8% in 2012, with an average variation of 2.8% in the period. The highest average variation in the period was observed among female adolescents (4.1%). In parallel a significant increase occurred in reported physician-diagnosed asthma, 7.3% in 2001 and 11,1% in 2012, with an annual variation of 4.5%. The largest increases in reported physician-diagnosed asthma were seen in female (5.9%) and male (4.5%) public school pupils. In addition, a significant increase in reported rhinoconjunctivitis occurred, with the average variation in the period being 5.2%. Reports of severe asthma symptoms remained unchanged during the period, while the annual variation for reported current wheezing (-1.3%) and wheezing during exercise (-1.2%) decreased. CONCLUSIONS The results showed a significant increase in the annual average variation for asthma and rhinoconjunctivitis prevalence during the 2001 to 2012 period.

ERICA: prevalence of asthma in Brazilian adolescents

ABSTRACT OBJECTIVE To describe the prevalence of asthma and physician-diagnosed asthma in Brazilian adolescents. METHODS Cross-sectional, national, school-based study with adolescents from 12 to 17 years old, participants in the Study of Cardiovascular Risks in Adolescents (ERICA). The study stratified the sample by region and grouped according to schools and classes with representativeness to the set of cities with more than 100,000 inhabitants of the Country, macro-regions, capitals, and Federal District. A questionnaire collected data through a self-filled in method. We calculated the prevalences and their confidence intervals of 95% (95%CI) according to sex, age group, type of school and skin color. RESULTS Between 2013 and 2014, 74,589 adolescents were evaluated, 55.3% of the female sex. The total prevalence of active asthma was of 13.1% (95%CI 12.1-13.9), being higher in girls (14.8%; 95%CI 13.7-16.0) when compared to boys (11.2%; 95%CI 10.3-12.2) in all geographical strata examined. It was also higher between students of private schools (15.9%; 95%CI 14.2-17.7) when compared to public ones (12.4%; 95%CI 11.4-13.4). It was higher in the Southeast region (14.5%; 95%CI 12.9-16.1), and in the city of Sao Paulo (16.7%; 95%CI 14.7-18.7). The lowest prevalence was observed in North region (9.7%; 95%CI 9.7-10.5), and in Teresina (6.3%; 95%CI 4.9-7.7). The prevalence of physician-diagnosed asthma was of 8.7% (95%CI 8.2-9.1); higher in the North region (13.5%; 95%CI 12.7-14.2), and in Porto Alegre (19.8%; 95%CI 17.5-22.3). It was lower in the Midwest (6.9%; 95%CI 6.0-7.8), and in Cuiaba (4.8%; 95%CI 3.8-5.9). We found no significant difference in the expression of this rate between the sexes, as well as in other variables evaluated by the study. CONCLUSIONS The prevalence of asthma in Brazilian adolescents is high. Rates of active asthma and physician-diagnosed asthma vary widely in different regions and capitals evaluated by the ERICA. These results may assist in the preparation of preventive programs and policies on health and a better understanding of the factors associated with asthma in this age group.

Evaluation of lung function abnormalities prevalence in poultry workers

Introduction - Poultry workers can be at an increased risk of occupational respiratory diseases, like asthma, chronic obstructive pulmonary disease and extrinsic allergic alveolitis. Spirometry screening is fundamental to early diagnosis trough the identification of related ventilatory defects. Purpose - We aimed to assess the prevalence of lung function abnormalities in poultry workers.

Evaluation of the allergenicity of spore and mycelia extracts of Pisolithus tinctorius

The antigenic and allergenic chemical analysis of spore and mycelia extracts of Pisolithus tinctorius was carried out. The spores were collected from basidiocarps in plantations of Eucalyptus spp and the mycelia from culture in MNM medium. With basis on the fungus growth curve, the mycelia masses were obtained after 10, 20, 30, and 40 days of incubation, which correspond, respectively, to the beginning, middle and end of the log phase, and beginning of the decline phase. The mycelia masses, together with the spores, were submitted to the action of three extractors (Coca, Tris-HCl, and ammonium bicarbonate). The contents of carbohydrates and proteins were determined. The SDS-PAGE electrophoretical analysis revealed separate fractions in these extracts, besides common fractions, in function of cultivation time and extraction methods. The selected extracts for the allergic tests were the ones with the highest number of fractions. The prick-tests were conducted in 374 patients – rural workers, eucalyptus plantation works and college students. The positivity to the "prick test" with the antigenic extract of P. tinctorius was, respectively, 3.78%, 28.20% and 6.40%. Most prick-test positive patients (82.75%) also presented symptoms of respiratory allergy (asthma and rhinitis). There was no reactivity difference when the spore and mycelia extracts were employed. The analysis of the positive patients’ sera revealed the presence of IgE specific to the P. tinctorius antigens. Since Pisolithus tinctorius is found as mycorrhyza of Eucalyptus spp, and this plant is used in reforestation in most countries, the importance of that fungus should be regarded as a possible cause of respiratory allergies, especially in occupationally exposed workers

Intranasal sensitization with Blomia Tropicalis antigens induces allergic responses in mice characterized by elevated antigen-specific and non-specific serum ige and peripheral blood eosinophil counts

In order to evaluate the potential allergenicity of Blomia tropicalis (Bt) antigen, IgE production of both specific and non-specific for Bt antigen was monitored in BALB/c mice after exposure to the antigen by nasal route. It was evidenced that B. tropicalis contains a functional allergen in its components. The allergenic components, however, when administered intranasally without any adjuvant, did not function to induce IgE response within a short period. On the other hand, intranasal inoculation of Bt antigens augmented serum IgE responses in mice pretreated by a subcutaneous priming injection of the same antigens. Inoculation of Bt antigen without subcutaneous priming injections induced IgE antibody production only when the antigen was continuously administered for a long period of over 24 weeks. Even when the priming injection was absent, the Bt antigen inoculated with cholera toxin (CT) as a mucosal adjuvant also significantly augmented the Bt antigen-specific IgE responses depending on the dose of CT co-administered. The present study also demonstrated that Bt antigen/CT-inoculated mice showed increased non-specific serum IgE level and peripheral blood eosinophil rates without noticeable elevations of the total leukocyte counts. The immunoblot analysis demonstrated 5 main antigenic components reactive to IgE antibodies induced. These components at about 44-64 kDa position were considered to be an important candidate antigen for diagnosis of the mite-related allergy.

Adolescents and School Asthma Knowledge and Attitudes

Introduction: bronchial asthma is a chronic disease that affects a high percentage of adolescents, with a significant restriction of daily activities, and is a cause of school absenteeism. The relationships between adolescents and asthma disease in school were assessed, with a view to improving knowledge about the asthmatic adolescent. Methods: a survey was conducted in the Lisbon metropolitan area, covering urban (Lisbon) and rural (Lourinh˜a ) zones and including 1879 students and 81 teachers from the 7th to 9th high school years. The study groups were asthmatic students, their peers, and teachers. A self-administered questionnaire was applied to collect information. The results were compared with a reference group of 91 asthmatic students attending our Department of Immunoallergy-Hospital Dona Estefânia. Cotinine urinary measurements were made in a sample of asthmatics and a control group. Results: the prevalence of current asthma among students was 10%. Estimates of asthma annual burden among 7th to 9th year students from Lisbon and Lourinh˜a high schools included 4,307 days missed from school, 4,148 medical consultations and a minimum of 351 hospital emergency care and 80 hospital admissions. Exposure to passive smoking was not significantly different between asthmatic students and theirs peers. Cotinine urinary measurements did not discriminate between exposed and non-exposed individuals. Cigarette smoking was almost as common among adolescent asthmatics (5.4%) as it was in non-asthmatic subjects (6.7%). However, 55% of asthmatics mentioned active and passive smoking as an asthma exacerbating factor. Asthmatic students, theirs peers and teachers showed a deficient knowledge about asthma (mean group scores: 17.6; 14.2 and 17.7 of a possible 30), particularly in the areas related to asthma recognition and its management. Asthmatics attending our Allergy Department had the highest scores. All groups showed tolerance in the sense of a positive and understanding attitude toward a person with asthma. However, traditional beliefs about asthma disease (dependence, inferiority...) were confirmed. A positive correlation between knowledge levels and tolerance attitudes was found. Conclusion: in view of the dimension of the asthma problem in adolescence and its social and economic impact, it is justifiable to assess the need for the implementation of asthma education programs in schools in order to improve asthma management by the adolescents and their schools.

Prevalence of Asthma in a Portuguese Countryside Town:Repercussions on Absenteeism and Self-Concept

Background: Childhood asthma represents an increasing health problem and is the leading cause of hospital admission and absenteeism in children with chronic disease. It also compromises quality of life, eventually contributing to disturbances in self-concept. Self-concept is a recent and global perspective of “the self” and relates to skills, self-image and self-esteem. Little information is available on this topic and there are no data from Portuguese countryside towns. Objective: The aim of this study was to determine the prevalence of asthma among all school children in the 5th and 6th grades in a Portuguese countryside town and to establish its possible correlation with absenteeism and self-concept. Methods: In April 2002, two questionnaires were administered in the presence of the researcher to a group of 950 children attending different schools. The children completed the internationally renowned questionnaires: ISAAC and the Self-Concept Scale by Susan Harter. Results: Our sample (n = 818) had a mean age of 11 years (10-15 years) and a male-to-female ratio of 1/1. The cumulative prevalence of asthma was11.9% and that of active asthma was 8.8 %; 63.9% of asthmatics were male and 36.1 % were female. The mean age of asthmatics was 11.34 years and 74 % had active symptoms. Comparison of this group of 97 asthmatic children with the remaining children revealed a statistically significant correlation between the presence of asthma and school absenteeism (global: p = 0.04; gymnastics: 0.05). Regarding the Self-Concept Scale a statistically significant association was found between the presence of asthma and school achievement (p = 0.027), physical appearance (p = 0.015), behavior (p < 0.000) and self-esteem (p < 0.000). No statistically significant correlations were found in social acceptance (p = 0.289) or athletic competence (p = 0.085). Asthmatic boys had higher self-concept scores than girls, except in the domain of behavior. Conclusions: Twelve percent of the population studied was asthmatic. In asthmatic children, absenteeism was higher and self-concept was lower for almost all domains, except social acceptance and athletic achievement, probably due to overprotection.

Barnacle Allergy: Allergen Characterization and Cross-Reactivity with Mites

Background: Barnacles are a type of seafood with worldwide distribution and abundant along the shores of temperate seas. They are particularly appreciated and regularly consumed in Portugal as well as in Spain, France and South America, but barnacle allergy is a rare condition of which there is only one reference in the indexed literature. The molecular allergens and possible cross-reactivity phenomena implicated (namely with mites) have not been established. Objective: To demonstrate the IgE-mediated allergy to barnacle and to identify the proteins implicated as well as possible cross-reactivity phenomena with mites. Methods: We report the clinical and laboratory data of five patients with documented IgE-mediated allergy to barnacle. The diagnosis was based on a suggestive clinical history combined with positive skin prick tests (SPT) to barnacle – prick to prick method. Two barnacle extracts were prepared (raw and cooked barnacle) and sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) and IgE-immunoblotting were performed. An immunoblotting inhibition assay with Dermatophagoides pteronyssinus was also done in order to evaluate cross-reactivity. Results: All patients had mite-related asthma and the allergic rhinoconjunctivitis; they all experienced mucocutaneous symptoms. All of them had positive SPT to barnacle, and the immunoblotting showed several allergenic fractions with a wide molecular weight range (19 – 94 kDa). The D. pteronyssinus extract inhibited several IgE-binding protein fractions in the barnacle extract. Conclusions: We describe five patients with IgE-mediated barnacle allergy. We also describe a group of IgEbinding+ proteins between 30 and 75 kDa as the allergenic fractions of this type of Crustacea. Cross-reactivity with D. pteronyssinus was demonstrated in two cases.

Drug Provocation Tests to Betalactam Antibiotics: Experience in a Paediatric Setting

Background: Few studies have been performed in children withs uspected betalactam allergy.We aimed to assess the role of the drug provocation test(DPT)with betalactams in a paediatric setting and to study the association between allergy to betalactam antibiotics and other allergic diseases. Methods:We included all the patients under 15 years old who were consecutively referred to the Immunoallergy Department, Dona Estefânia Hospital,Portugal(January 2002 to April 2008)for a compatible history of allergic reaction to betalactam. All were submitted to a DPT.Children were proposed to performs kintests(ST)to betalactam antibiotics followed by DPT. If they decline ST,a DPT with the culprit drug was performed. Results: We studied 161 children,60%were boys,with a median age of 5years old at the time of the DPT.Thirty-three patients(20.5%)had an immediate reaction and 33(20.5%)a non-immediate reaction. These verity of there porte dreactions was low in most cases. Skin tests to betalactams were performed in 47 children and were positive in 8.DPT was positive inonlyone(3.4%)of the patients skin tested and in 11(13.4%)of those not skin tested. These verity of the DPT reaction was low.Asthma and food allergy were associated with a positive DPT in the later group. Conclusions: DPT seems a safe procedure even in the absence of ST in non-severe cases. This could be a practical optionin infants and pre-school children,where ST are painful and difficult to perform.Additional caution should be taken in children with asthma and food allergy.

Fexofenadine is Efficacious and Safe in Children (Aged 6-11 Years) with Seasonal Allergic Rhinitis

Background: This is the first prospective, randomized, doubleblind, placebo-controlled study showing statistical improvement of an H1-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. Objective: This randomized, placebo-controlled, parallelgroup,double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. Methods: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (±1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point.