Search

Background: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK)., Methods: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum., Results: Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda., Conclusions: This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Introduction: Asthma is a growing health problem in children in marginalised urban settings in low-income and middle-income countries. Asthma attacks are an important cause of emergency care attendance and long-term morbidity. We designed a prospective study, the Asthma Attacks study, to identify factors associated with recurrence of asthma attacks (or exacerbations) among children and adolescents attending emergency care in three Ecuadorian cities., Methods and Analysis: Prospective cohort study designed to identify risk factors associated with recurrence of asthma attacks in 450 children and adolescents aged 5-17 years attending emergency care in public hospitals in three Ecuadorian cities (Quito, Cuenca and Portoviejo). The primary outcome will be rate of asthma attack recurrence during up to 12 months of follow-up. Data are being collected at baseline and during follow-up by questionnaire: sociodemographic data, asthma history and management (baseline only); recurrence of asthma symptoms and attacks (monthly); economic costs of asthma to family; Asthma Control Test; Pediatric Asthma Quality of life Questionnaire; and Newcastle Asthma Knowledge Questionnaire (baseline only). In addition, the following are being measured at baseline and during follow-up: lung function and reversibility by spirometry before and after salbutamol; fractional exhaled nitric oxide (FeNO); and presence of IgG antibodies to SARS-CoV-2 in blood. Recruitment started in 2019 but because of severe disruption to emergency services caused by the COVID-19 pandemic, eligibility criteria were modified to include asthmatic children with uncontrolled symptoms and registered with collaborating hospitals. Data will be analysed using logistic regression and survival analyses., Ethics and Dissemination: Ethical approval was obtained from the Hospital General Docente de Calderon (CEISH-HGDC 2019-001) and Ecuadorian Ministry of Public Health (MSP-CGDES-2021-0041-O N° 096-2021). The study results will be disseminated through presentations at conferences and to key stakeholder groups including policy-makers, postgraduate theses, peer-review publications and a study website. Participants gave informed consent to participate in the study before taking part., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: There is a high burden of asthma morbidity and mortality in Latin America. It has been proposed that this relates to limited access to diagnostic tests, asthma medications and specialised doctors. However, little is known of what caregivers of asthmatic children and healthcare professionals (HCPs) perceive as barriers and facilitators to adequate care. We aimed to explore the barriers and facilitators to asthma care access from caregivers' and HCP's perspective in an Ecuadorian low-resource setting., Methods: In 2017, we conducted 5 focus group discussions (FGD) with 20 caregivers of asthmatic children and 12 in-depth interviews with 3 paediatricians, 6 general doctors and 3 respiratory therapists in Esmeraldas city, Ecuador. FGDs and interviews were digitally recorded, transcribed, open-coded in QDA Miner, categorised using an interpretative phenomenological approach and analysed thematically. Barriers and facilitators were classified into availability, accessibility, acceptability and contact of healthcare services, based on Tanahashi model of health service access., Results: Limited resources, use of alternative medicines, fear of medication side-effects and lack of specific training for doctors and knowledge in families were common barriers for both caregivers and HCPs. Caregivers and HCPs proposed the implementation of public health asthma-focused programmes that would include close community-based follow-up of people with asthma, educational sessions for their families and public engagement activities. HCPs also suggested implementing training programmes on asthma management for general doctors., Conclusion: Multiple barriers identified by caregivers and HCPs referred to economic and health service organisational issues, fear of side effects of medication or ineffective self-management. Increasing caregivers and HCPs' asthma knowledge, as well as HCPs' communication skills to establish a patient-centred approach with a shared decision-making process could improve asthma care in this setting., Competing Interests: Competing interests: CA-G received a fellowship from the Wellcome Trust for this manuscript. JDB received grants or contracts from AZ, Novartis and GSK; consulting fees from GSK, Chiesi and Boehringer Ingelheim; payments or honoraria from AZ, Chiesi and GSK; support for meetings or travel from GSK, Boehringer Ingelheim and AZ; received equipment or materials from GSK and Teva; leadership or fiduciary roles for TSANZ, Asthma Australia and Asthma WA; other financial or non-financial interests from Optimum Patient Care Australia. PJC and NR-S have nothing to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Asthma is a common long-term disorder and strategies to improve asthma control are still a challenge. Integrated delivery of health systems is critical for effective asthma care: there is limited information on experiences of care coordination for asthma from Latin America, especially on perspectives of health personnel and in the context of the COVID-19 pandemic., Methods and Analysis: This protocol details a qualitative approach to analyse health workers' perspectives of healthcare coordination for asthma control during COVID-19 pandemic in Ecuador and Brazil, at primary and specialised levels, through in-depth semistructured interviews using a video communications platform. The analysis will identify knowledge and perspectives based on coordination of clinical information, clinical management and administrative coordination. Theoretical sampling will be used to obtain approximately equal numbers of women and men within each level of healthcare; data saturation will be used to determine sample size. Transcripts will be analysed using content-coding procedures to mark quotations related to major topics and subthemes included in the interview guide, and narrative analysis will be based on a theoretical framework for healthcare coordination to identify new themes and subthemes., Ethics and Dissemination: Ethical approval was obtained from the ethics committees of Hospital General Docente Calderón, Quito, Ecuador; and Universidade Federal da Bahia, Salvador, Brazil. The findings of this study will be disseminated through peer-reviewed articles, conference presentations and condensed summaries for key stakeholders and partners., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Early-life exposures to geohelminths may protect against development of wheeze/asthma and atopy., Objective: To study the effect of maternal geohelminths and infections in children during the first 5 years on atopy, wheeze/asthma and airways reactivity/inflammation at 8 years., Methods: Birth cohort of 2404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO) and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy., Results: 1933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and 45.5% of children to 5 years. Frequencies of outcomes at 8 years were as follows: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%) and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced SPT prevalence (OR 0.72). Childhood Trichuris trichiura infections during the first 5 years were associated with reduced wheeze (OR 0.57) but greater parasite burdens with Ascaris lumbricoides at 5 years were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite-specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non-atopic children., Conclusions: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086)., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Epidemiological studies have shown conflicting findings on the relationship between asthma, atopy, and intestinal helminth infections. There are no such studies from Angola; therefore, we aimed to evaluate the relationship between asthma, allergic diseases, atopy, and intestinal helminth infection in Angolan schoolchildren. We performed a cross-sectional study of schoolchildren between September and November 2017. Five schools (three urban, two rural) were randomly selected. Asthma, rhinoconjunctivitis, and eczema were defined by appropriate symptoms in the previous 12 months: atopy was defined by positive skin prick tests (SPT) or aeroallergen-specific IgE; intestinal helminths were detected by faecal sample microscopy. In total, 1023 children were evaluated (48.4% female; 57.6% aged 10-14 years; 60.5% urban). Asthma, rhinoconjunctivitis, or eczema were present in 9%, 6%, and 16% of the studies children, respectively. Only 8% of children had positive SPT, but 64% had positive sIgE. Additionally, 40% were infected with any intestinal helminth ( A. lumbricoides 25.9%, T. trichiura 7.6%, and H. nana 6.3%). There were no consistent associations between intestinal helminth infections and asthma, allergic diseases, or atopy, except for A. lumbricoides, which was inversely associated with rhinoconjuctivitis and directly associated with aeroallergen-specific IgE. We concluded that, overall, intestinal helminth infections were not consistently associated with allergic symptoms or atopy. Future, preferably longitudinal, studies should collect more detailed information on helminth infections as part of clusters of environmental determinants of allergies.

Background: Although asthma has emerged as an important public health problem over recent decades in Latin America, there are limited published data on national hospital admission and mortality rates for asthma from countries in the region., Objective: To analyse trends in asthma hospitalisation and mortality rates in Ecuador over a 19-year period from 2000 to 2018., Methods: Hospital discharge and death certificates listing asthma, as defined in the International Classification of Diseases 10th Revision codes (J45 and J46), were used to analyse time trends in rates of hospital admissions and mortality for asthma. The data were obtained from the Ecuadorian National Institute of Statistics and Census. Crude and age-standardised rates were estimated for the entire population. Additionally, specific rates by sex, age and region were estimated. We used joinpoint analysis to identify national trends., Result: During 2000-2018, a total of 58 250 hospitalisations and 1328 deaths due to asthma were identified. The average annual rates for hospitalisation and mortality attributed to asthma were estimated to be 21 (95% CI 19.3 to 22.8) and 5.2 (95% CI 4.4 to 6.0) per 100 000 population, respectively, over this period. Asthma hospital admissions decreased from 28 to 13.7 per 100 000 population between 2000 and 2018, and asthma mortality decreased from 0.8 to 0.3 per 100 000 population over the same period. Based on jointpoint analysis, two temporal trends were identified for hospital admissions. Between 2000 and 2011, hospital admissions decreased 0.8% per year and between 2011 and 2018 decreased 6.6% per year (p<0.05). On average, hospitalisation rates decreased 3.1% per year (p<0.05) over the entire study period. Mortality rate decreased 5.6% per year (p<0.05) over the 19-year period. Hospitalisation rates were higher among females, those aged 5 to 19 years and those living in the Coast region., Conclusions: Our analysis shows a temporal trend of reduction in rates of hospitalisations and deaths attributed to asthma between 2000 and 2018 in Ecuador, consistent with similar trends elsewhere in the Latin American region. Health registration systems in Latin America need to be improved to provide reliable data for future between and within country comparisons of trends in asthma hospitalisations and deaths., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The urbanisation process has been associated with increases in asthma prevalence, an observation supported largely by studies comparing urban with rural populations. The nature of this association remains poorly understood, likely because of the limitations of the urban-rural approach to understand what a multidimensional process is., Objective: This study explored the relationship between the urbanisation process and asthma prevalence using a multidimensional and quantitative measure of urbanicity., Methods: A cross-sectional analysis was conducted in 1843 children living in areas with diverse levels of urbanisation in the district of Quinindé, Ecuador in 2013-2015. Categorical principal components analysis was used to generate an urbanicity score derived from 18 indicators measured at census ward level based on data from the national census in 2010. Indicators represent demographic, socioeconomic, built environment and geographical dimensions of the urbanisation process. Geographical information system analysis was used to allocate observations and urban characteristics to census wards. Logistic random effects regression models were used to identify associations between urbanicity score, urban indicators and three widely used definitions for asthma., Results: The prevalence of wheeze ever, current wheeze and doctor diagnosis of asthma was 33.3%, 13% and 6.9%, respectively. The urbanicity score ranged 0-10. Positive significant associations were observed between the urbanicity score and wheeze ever (adjusted OR=1.033, 95% CI 1.01 to 1.07, p=0.05) and doctor diagnosis (adjusted OR=1.06, 95% CI 1.02 to 1.1, p=0.001). For each point of increase in urbanicity score, the prevalence of wheeze ever and doctor diagnosis of asthma increased by 3.3% and 6%, respectively. Variables related to socioeconomic and geographical dimensions of the urbanisation process were associated with greater prevalence of wheeze/asthma outcomes., Conclusions: Even small increases in urbanicity are associated with a higher prevalence of asthma in an area undergoing the urban transition. The use of a multidimensional urbanicity indicator has greater explanatory power than the widely used urban-rural dichotomy to improve our understanding of how the process of urbanisation affects the risk of asthma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Limited data are available on prevalence and associated risk factors for atopy and allergic diseases from high-altitude urban settings in Latin America., Objective: To estimate the prevalence of atopy, asthma, rhinitis, and eczema, and associations with relevant risk factors in preschool children in the Andean city of Cuenca., Methods: A cross-sectional study was undertaken using a representative sample of 535 children aged 3-5 years attending 30 nursery schools in the city of Cuenca, Ecuador. Data on allergic diseases and risk factors were collected by parental questionnaire. Atopy was measured by skin prick test (SPT) reactivity to a panel of relevant aeroallergens. Associations between risk factors and the prevalence of atopy and allergic diseases were estimated using multivariable logistic regression., Results: Asthma symptoms were reported for 18% of children, rhinitis for 48%, and eczema for 28%, while SPT reactivity was present in 33%. Population fractions of asthma, rhinitis, and eczema attributable to SPT were 3.4%, 7.9%, and 2.9%, respectively. In multivariable models, an increased risk of asthma was observed among children with a maternal history of rhinitis (OR 1.85); rhinitis was significantly increased in children of high compared to low socioeconomic level (OR 2.09), among children with a maternal history of rhinitis (OR 2.29) or paternal history of eczema (OR 2.07), but reduced among children attending daycare (OR 0.64); eczema was associated with a paternal history of eczema (OR 3.73), and SPT was associated with having a dog inside the house (OR 1.67)., Conclusions: A high prevalence of asthma, rhinitis, and eczema symptoms were observed among preschool children in a high-altitude Andean setting. Despite a high prevalence of atopy, only a small fraction of symptoms was associated with atopy. Parental history of allergic diseases was the most consistent risk factor for symptoms in preschool children., Competing Interests: The authors have declared that no competing interests exists.

Introduction: Childhood infections, particularly those caused by helminths are considered to be important environmental exposures influencing the development of allergic diseases. However, epidemiological studies focusing on the relationship between helminth infections and risk of allergic diseases, performed worldwide, show inconsistent findings. Previous systematic reviews of observational studies published 10 or more years ago showed conflicting findings for effects of helminths on allergic diseases. Over the past 10 years there has been growing literature addressing this research area and these need to be considered in order to appreciate the most contemporary evidence. The objective of the current systematic review will be to provide an up-to-date synthesis of findings of observational studies investigating the influence of helminth infections on atopy, and allergic diseases., Methods and Analysis: This systematic review protocol was registered at PROSPERO. We will search Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED, ISI Web of Science, WHO Global Health Library, Scielo, IndMed, PakMediNet, KoreaMed, Ichushi for published studies from 1970 to January 2020. Bibliographies of all eligible studies will be reviewed to identify additional studies. Unpublished and ongoing research will also be searched in key databases. There will be no language or geographical restrictions regarding publications. Critical Appraisal Skills Programme quality assessment tool will be used to appraise methodological quality of included studies. A descriptive summary with data tables will be constructed, and if adequate, meta-analysis using random-effects will be performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist will be followed for reporting of the systematic review., Ethics and Dissemination: Since this systematic review will be only based on published and retrievable literature, no ethics approval will be sought. The multidisciplinary team performing this systematic review will participate in relevant dissemination activities. Findings will be presented at scientific meetings and publish the systematic review in international, peer-reviewed, open-access journals., Prospero Registration Number: CRD42020167249., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Asthma is a common cause of emergency care attendance in low- and middle-income countries (LMICs). While few prospective studies of predictors for emergency care attendance have been undertaken in high-income countries, none have been performed in a LMIC.We followed a cohort of 5-15-year-old children treated for asthma attacks in emergency rooms of public health facilities in Esmeraldas City, Ecuador. We collected blood and nasal wash samples, and performed spirometry and exhaled nitric oxide fraction measurements. We explored potential predictors for recurrence of severe asthma attacks requiring emergency care over 6 months' follow-up.We recruited 283 children of whom 264 (93%) were followed-up for ≥6 months or until their next asthma attack. Almost half (46%) had a subsequent severe asthma attack requiring emergency care. Predictors of recurrence in adjusted analyses were (adjusted OR, 95% CI) younger age (0.87, 0.79-0.96 per year), previous asthma diagnosis (2.2, 1.2-3.9), number of parenteral corticosteroid courses in previous year (1.3, 1.1-1.5), food triggers (2.0, 1.1-3.6) and eczema diagnosis (4.2, 1.02-17.6). A parsimonious Cox regression model included the first three predictors plus urban residence as a protective factor (adjusted hazard ratio 0.69, 95% CI 0.50-0.95). Laboratory and lung function tests did not predict recurrence.Factors independently associated with recurrent emergency attendance for asthma attacks were identified in a low-resource LMIC setting. This study suggests that a simple risk-assessment tool could potentially be created for emergency rooms in similar settings to identify higher-risk children on whom limited resources might be better focused., Competing Interests: Conflict of interest: C. Ardura-Garcia has nothing to disclose. Conflict of interest: E. Arias has nothing to disclose. Conflict of interest: P. Hurtado has nothing to disclose. Conflict of interest: L.J. Bonnett has nothing to disclose. Conflict of interest: C. Sandoval has nothing to disclose. Conflict of interest: A. Maldonado has nothing to disclose. Conflict of interest: L.J. Workman has nothing to disclose. Conflict of interest: T.A.E. Platts-Mills has nothing to disclose. Conflict of interest: P.J. Cooper reports grants from PATH Vaccines and National Institutes of Health Research, outside the submitted work. Conflict of interest: J.D. Blakey reports personal fees and non-financial support from Astra Zeneca, Boehringer Ingelheim and Napp, personal fees from Teva and non-financial support from Novartis, outside the submitted work., (Copyright ©ERS 2019.)

Background: Urbanisation has been associated with temporal and geographical differences in asthma prevalence in low-income and middle-income countries (LMICs). However, little is known of the mechanisms by which urbanisation and asthma are associated, perhaps explained by the methodological approaches used to assess the urbanisation-asthma relationship., Objective: This review evaluated how epidemiological studies have assessed the relationship between asthma and urbanisation in LMICs, and explored urban/rural differences in asthma prevalence., Methods: Asthma studies comparing urban/rural areas, comparing cities and examining intraurban variation were assessed for eligibility. Included publications were evaluated for methodological quality and pooled OR were calculated to indicate the risk of asthma in urban over rural areas., Results: Seventy articles were included in our analysis. Sixty-three compared asthma prevalence between urban and rural areas, five compared asthma prevalence between cities and two examined intraurban variation in asthma prevalence. Urban residence was associated with a higher prevalence of asthma, regardless of asthma definition: current-wheeze OR:1.46 (95% CI:1.22 to 1.74), doctor diagnosis OR:1.89 (95% CI:1.47 to 2.41), wheeze-ever OR:1.44 (95% CI:1.15 to 1.81), self-reported asthma OR:1.77 (95% CI:1.33 to 2.35), asthma questionnaire OR:1.52 (95% CI:1.06 to 2.16) and exercise challenge OR:1.96 (95% CI:1.32 to 2.91)., Conclusions: Most evidence for the relationship between urbanisation and asthma in LMICs comes from studies comparing urban and rural areas. These studies tend to show a greater prevalence of asthma in urban compared to rural populations. However, these studies have been unable to identify which specific characteristics of the urbanisation process may be responsible. An approach to understand how different dimensions of urbanisation, using contextual household and individual indicators, is needed for a better understanding of how urbanisation affects asthma., Prospero Registration Number: CRD42017064470., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Asthma attacks are common and have significant physical, psychological, and financial consequences. Improving the assessment of a child's risk of subsequent asthma attacks could support front-line clinicians' decisions on augmenting chronic treatment or specialist referral. We aimed to identify predictors for emergency department (ED) or hospital readmission for asthma from the published literature., Methods: We searched MEDLINE, EMBASE, AMED, PsycINFO, and CINAHL with no language, location, or time restrictions. We retrieved observational studies and randomized controlled trials (RCT) assessing factors (personal and family history, and biomarkers) associated with the risk of ED re-attendance or hospital readmission for acute childhood asthma., Results: Three RCTs and 33 observational studies were included, 31 from Anglophone countries and none from Asia or Africa. There was an unclear or high risk of bias in 14 of the studies, including 2 of the RCTs. Previous history of emergency or hospital admissions for asthma, younger age, African-American ethnicity, and low socioeconomic status increased risk of subsequent ED and hospital readmissions for acute asthma. Female sex and concomitant allergic diseases also predicted hospital readmission., Conclusion: Despite the global importance of this issue, there are relatively few high quality studies or studies from outside North America. Factors other than symptoms are associated with the risk of emergency re-attendance for acute asthma among children. Further research is required to better quantify the risk of future attacks and to assess the role of commonly used biomarkers., (© 2018 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.)

Rationale: Exposures to geohelminths during gestation or early childhood may reduce risk of wheezing illness/asthma and atopy during childhood in tropical regions., Objectives: To investigate the effect of maternal and early childhood geohelminths on development of wheeze/asthma and atopy during the first 5 years of life., Methods: A cohort of 2,404 neonates was followed to 5 years of age in a rural district in coastal Ecuador. Data on wheeze were collected by questionnaire and atopy was measured by allergen skin prick test reactivity to 10 allergens at 5 years. Stool samples from mothers and children were examined for geohelminths by microscopy., Measurements and Main Results: A total of 2,090 (86.9%) children were evaluated at 5 years. Geohelminths were observed in 45.5% of mothers and in 34.1% of children by 3 years. Wheeze and asthma were reported for 12.6% and 5.7% of children, respectively, whereas 14.0% had skin test reactivity at 5 years. Maternal geohelminths were associated with an increased risk of wheeze (adjusted odds ratio, 1.41; 95% confidence interval, 1.06-1.88), whereas childhood geohelminths over the first 3 years of life were associated with reduced risk of wheeze (adjusted odds ratio, 0.70; 95% confidence interval, 0.52-0.96) and asthma (adjusted odds ratio, 0.60; 95% confidence interval, 0.38-0.94) but not skin prick test reactivity. The effects on wheeze/asthma were greatest with later age of first infection, were observed only in skin test-negative children, but were not associated with parasite burden or specific geohelminths., Conclusions: Although maternal exposures to geohelminths may increase childhood wheeze, childhood geohelminths during the first 3 years may provide protection through a nonallergic mechanism. Registered as an observational study (ISRCTN41239086).

Toxocara canis, Toxocara cati, are roundworms that live in the intestines of dogs and cats, respectively, and are predominantly agents of human toxocariasis. Studies have suggested that Toxocara spp. seroprevalence increases levels of total and aeroallergen-specific IgE (sIgE), asthma prevalence and asthma morbidity. Nevertheless, other work reported a negative association between Toxocara spp. seropositivity with skin hypersensititity and a positive association with sIgE. The objective of the present study was to evaluate risk factors for acquiring Toxocara spp. infection and to investigate possible significant association between its seroprevalence with atopy and asthma. Students from elementary schools, residents in a small town and its surroundings of Northeast Brazil, underwent blood sampling to measure levels of anti-Toxocara spp. IgG, peripheral blood eosinophils, and specific IgE to aeroallergens. We used univariable and multivariable logistic regression analyses to assess possible risk factors for Toxocara spp. seropositivity and its association with atopy, wheeze/asthma with asthma phenotypes, in a sample of 791 elementary school children aged 6-13 years. Toxocara spp. seroprevalence reached 63.6%; 49.9% had sIgE; 7.2% and 3.3% had atopic wheeze/asthma and non-atopic wheeze/asthma respectively. Risk factors associated with Toxocara spp. seropositivity were: contact with dogs (adj. OR 2.33; 95% CI=1.70-3.19) and cats (adj. OR 3.09; 95% CI=2.10-4.55), and male sex (adj. OR 2.21; 95% CI=1.62-3.02). The presence of anti-Toxocara IgG was statistically associated with blood eosinophils >4% and >10% (adj. OR 1.84; 95% CI=1.33-2.55 and adj. OR 2.07; 95% CI=1.45-2.97, respectively), and atopy (adj. OR 2.00; 95% CI=1.49-2.68), but it was not associated with wheeze/asthma. Concluding, the results obtained in this study showing the association of Toxocara spp. seroprevalence with sIgE may suggest a possible immunological cross-reactivity between IgE epitopes from Toxocara spp. and aeroallergens., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists' hypotheses about the underlying biological mechanisms to be integrated., Results: We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach., Conclusion: The proposed analytical approach may be especially useful to quantify complex immune responses in immuno-epidemiological studies, where investigators examine the relationship among epidemiological patterns, immune response, and disease outcomes.

Consistent with the diversity of Latin America, there is profound variability in asthma burden among and within countries in this region. Regional variation in asthma prevalence is likely multifactorial and due to genetics, perinatal exposures, diet, obesity, tobacco use, indoor and outdoor pollutants, psychosocial stress and microbial or parasitic infections. Similarly, non-uniform progress in asthma management leads to regional variability in disease morbidity. Future studies of distinct asthma phenotypes should follow-up well-characterised Latin American subgroups and examine risk factors that are unique or common in Latin America (eg, stress and violence, parasitic infections and use of biomass fuels for cooking). Because most Latin American countries share the same barriers to asthma management, concerted and multifaceted public health and research efforts are needed, including approaches to curtail tobacco use, campaigns to improve asthma treatment, broadening access to care and clinical trials of non-pharmacological interventions (eg, replacing biomass fuels with gas or electric stoves)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Despite the high asthma rates described in Latin America, asthma risk factors in poor urban settings are not well established. We investigated risk factors for acute asthma among Ecuadorian children., Methods: A matched case-control study was carried out in a public hospital serving a coastal city. Children with acute asthma were age- and sex-matched to non-asthmatics. A questionnaire was administered, and blood, as well as stool, and nasopharyngeal swabs were collected., Results: Sixty cases and 119 controls aged 5-15 were evaluated. High proportions of cases were atopic with population-attributable fractions for atopy of 68.5% for sIgE and 57.2% for SPT. Acute asthma risk increased with greater titers of mite IgE (3.51-50 kU/l vs. <0.70kU/l - OR 4.56, 95% CI 1.48-14.06, p = 0.008; >50kU/l vs. <0.70kU/l - OR 41.98, 95% CI: 8.97-196.39, p < 0.001). Asthma risk was significantly independently associated with bronchiolitis (adj. OR: 38.9, 95% CI 3.26-465), parental educational level (adj. OR 1.26, 95% CI: 1.08-1.46), and presence of sIgE (adj. OR: 36.7, 95% CI: 4.00-337), while a reduced risk was associated with current contact with pets (adj. OR: 0.07, 95% CI: 0.01-0.56). Rhinovirus infection was more frequent in cases (cases 35.6% vs. controls 7.8%, p = 0.002). None of the cases were on maintenance therapy with inhaled corticosteroids and most relied on emergency department for control., Conclusions: A high proportion of children presenting to a public hospital with acute asthma were allergic to mite, particularly at high IgE titer. Poor asthma control resulted in overuse of emergency care., (© 2015 The Authors. Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.)

Background: The acquisition of a modern lifestyle may explain variations in asthma prevalence between urban and rural areas in developing countries. However, the effects of lifestyle on asthma have been investigated as individual factors with little consideration given to the effects of lifestyle as a set of attributes. The aim of the present study was to identify modern lifestyle domains and assess how these domains might explain wheeze prevalence in urban and rural areas., Methods: We analysed data from cross-sectional studies of urban and rural schoolchildren in Esmeraldas Province, Ecuador. Variables were grouped as indicators of socioeconomic factors, sedentarism, agricultural activities and household characteristics to represent the main lifestyle features of the study population. We used multiple correspondence analyses to identify common lifestyle domains and cluster analysis to allocate children to each domain. We evaluated associations between domains and recent wheeze by logistic regression., Results: We identified 2-3 lifestyle domains for each variable group. Although wheeze prevalence was similar in urban (9.4%) and rural (10.3%) schoolchildren, lifestyle domains presented clear associations with wheeze prevalence. Domains relating to home infrastructure (termed transitional, rudimentary, and basic urban) had the strongest overall effect on wheeze prevalence in both urban (rudimentary vs. basic urban, OR = 2.38, 95% CI 1.12-5.05, p = 0.024) and rural areas (transitional vs. basic urban, OR = 2.02, 95% CI 1.1-3.73, p = 0.024; rudimentary vs. basic urban, OR = 1.88, 95% CI 1.02-3.47, p = 0.043). A high level of sedentarism was associated with wheeze in the rural areas only (OR = 1.64, 95% CI 1.23-2.18, p = 0.001)., Conclusions: We identified lifestyle domains associated with wheeze prevalence, particularly living in substandard housing and a high level of sedentarism. Such factors could be modified through programmes of improved housing and education. The use of lifestyle domains provides an alternative methodology for the evaluation of variations in wheeze prevalence in populations with different levels of development.

Background: Helminths are modulators of the host immune system, and infections with these parasites have been associated with protection against allergies and autoimmune diseases. The human host is often infected with multiple helminth parasites and most studies to date have investigated the effects of helminths in the context of infections with single parasite or types of parasites (e.g. geohelminths). In this study, we investigated how co-infections with three nematodes affect markers of allergic inflammation and asthma in children. We selected Ascaris lumbricoides and Trichuris trichiura, two parasites that inhabit the human intestine and Toxocara spp (Toxocara canis and/or T. cati), intestinal roundworms of dogs and cats that cause systemic larval infection in humans. These parasites were selected as the most prevalent helminth parasites in our study population., Results: 36.4% of children were infected with one parasite; 12.7% with 2 and 5.2% with 3. Eosinophilia>4% and >10% was present in 74.3% and 25.5% of the children, respectively. Total IgE>200 IU/mL, sIgE≥0.70 kU/L and SPT positivity were present in 59.7%, 37.1% and 30% of the children, respectively. 22.7% had recent asthma (12.0% non-atopic and 10.7% atopic). Helminth infections were associated in a dose-dependent way to decrease in the prevalence of SPT and increase in eosinophilia, total IgE, and the production of the regulatory cytokine IL-10 by unstimulated peripheral blood leukocytes. No association with asthma was observed., Conclusions: Helminth co-infections in this population were associated with increased markers of the Th2 immune response, and with a host immune regulatory phenotype that may suppress allergic effector responses such as immediate hypersensitivity reactions in the skin.

This review provides an update on asthma in Hispanics, a diverse group tracing their ancestry to countries previously under Spanish rule. A marked variability in the prevalence and morbidity from asthma remains among Hispanic subgroups in the United States and Hispanic America. In the United States, Puerto Ricans and Mexican Americans have high and low burdens of asthma, respectively (the "Hispanic Paradox"). This wide divergence in asthma morbidity among Hispanic subgroups is multifactorial, likely reflecting the effects of known (secondhand tobacco smoke, air pollution, psychosocial stress, obesity, inadequate treatment) and potential (genetic variants, urbanization, vitamin D insufficiency, and eradication of parasitic infections) risk factors. Barriers to adequate asthma management in Hispanics include economic and educational disadvantages, lack of health insurance, and no access to or poor adherence with controller medications such as inhaled corticosteroids. Although considerable progress has been made in our understanding of asthma in Hispanic subgroups, many questions remain. Studies of asthma in Hispanic America should focus on environmental or lifestyle factors that are more relevant to asthma in this region (e.g., urbanization, air pollution, parasitism, and stress). In the United States, research studies should focus on risk factors that are known to or may diverge among Hispanic subgroups, including but not limited to epigenetic variation, prematurity, vitamin D level, diet, and stress. Clinical trials of culturally appropriate interventions that address multiple aspects of asthma management in Hispanic subgroups should be prioritized for funding. Ensuring high-quality healthcare for all remains a pillar of eliminating asthma disparities.

Background: Helminth infections are associated with protection against allergies. It is postulated that IL-10 production after helminth infection suppresses skin hypersensitivity and increases IgG₄ production, protecting against allergies., Objective: We aimed to determine whether IL10 polymorphisms are associated with helminth infection and the risk of wheeze and allergy., Methods: Twelve IL10 single nucleotide polymorphisms were genotyped in 1353 children aged 4 to 11 years living in a poor urban area in Salvador, Brazil. Wheezing status, Ascaris lumbricoides and Trichuris trichiura infection, IL-10 production by peripheral blood leukocytes stimulated with A lumbricoides extract, serum total IgE levels, specific IgE levels, skin prick test responses to common aeroallergens, and IgG4 and IgE anti-A lumbricoides antibody levels were measured in all children. Association tests were performed by using logistic or linear regression when appropriate, including sex, age, helminth infection, and principal components for ancestry informative markers as covariates by using PLINK., Results: Allele G of marker rs3024496 was associated with the decreased production of IL-10 by peripheral blood leukocytes in response to A lumbricoides stimulation. Allele C of marker rs3024498 was negatively associated with helminth infection or its markers. Marker rs3024492 was positively associated with the risk of atopic wheeze, total IgE levels, and skin prick test responses to cockroach., Conclusions: Our findings suggest that IL10 polymorphisms might play a role in the production of IL-10, helminth infection, and allergy. We hypothesize that polymorphisms related to protection against helminths, which would offer an evolutionary advantage to subjects in the past, might be associated with increased risk of allergic diseases., Competing Interests: of potential conflict of interest: M. L. Barreto has received grants from the Wellcome Trust and the National Research Council–Brazil and is employed by the Federal University of Bahia. P. J. Cooper has received grants from the Wellcome Trust and is employed by the Liverpool School of Tropical Medicine. A. A. Cruz serves on boards for Merck Sharp & Dohme and Roche; has consultant arrangements with Mantecorp; receives grants from GlaxoSmithKline; receives payment for lectures from Merck Sharp & Dohme; has received travel/accommodations/meeting expenses from Merck Sharp & Dohme and Novartis; and has conducted clinical trials for AstraZeneca, Novartis, TAKEDA, Eurofarma, GlaxoSmithKline, and Genentech. L. C. Pontes-de-Carvalho is employed by the Ministry of Health, Brazil. C. Vergara, C. Foster, M. Campbell, and R. A. Mathias are employed by Johns Hopkins University and have received grants from the National Institutes of Health. K. C. Barnes serves on boards for Genentech; has consultant arrangements with Sanofi-Aventis and Sirius Genomics; is employed by Johns Hopkins University; has received grants from the National Institutes of Health/National Heart, Lung, and Blood Institute; has received payment for lectures from the “Evolution and Diseases of Modern Environments” Symposium, the Cincinnati Children’s Hospital Medical Center Allergy Conference, the 50th Annual Swineford Allergy Conference, and the American Academy of Allergy, Asthma & Immunology; and receives royalties from Up-To-Date. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: It has been proposed that improved hygiene and reduced experience of infections in childhood influences the development of allergic diseases. The mechanisms by which the hygiene operates are not well established but are underpinned by two apparently incompatible immunologic paradigms, the balance of TH1 versus TH2 cytokines and IL-10-mediated regulation of TH2 cytokines., Objective: This study defined immunologic phenotypes with the use of latent class analysis and investigated their associations with environmental factors, markers of allergy and asthma, in a Latin American population., Methods: We studied 1127 children living in urban Brazil. Data on wheeze and environmental exposures were collected with standardized questionnaires. Atopy was measured by specific IgE in serum and skin prick test reactivity to aeroallergens. Cytokines were measured in culture after the stimulation of peripheral blood leukocytes with mitogen. Infections with pathogens were assessed by serology and stool examinations. Children were classified as having high or low burden of infection. Latent class analysis was used to identify immune phenotypes on the basis of cytokine production. Logistic regression was used to evaluate the adjusted effects of environment and burden of infection on the immunologic phenotypes and the effect of the phenotypes on atopy and asthma., Results: Three phenotypes were identified, labeled underresponsive, intermediate, and responsive. Children of more educated mothers, living in improved environmental conditions, and with a low burden of infection were significantly more likely to have the responsive phenotype. The responsive phenotype was significantly associated with an increased prevalence of atopy but not asthma., Conclusion: Our findings contribute to a better understanding of the immune mechanisms by which the hygiene hypothesis operates in urban Latin America., Competing Interests: of potential conflict of interest: P. J. Cooper has received grants from the Wellcome Trust. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Severe asthma is associated with fixed airway obstruction attributable to inflammation, copious luminal mucus, and increased airway smooth muscle (ASM) mass. Paradoxically, studies demonstrated that the hypertrophic and hyperplastic ASM characteristic of severe asthma has reduced contractile capacity. We compared the G-protein-coupled receptor (GPCR)-induced Ca(2+) mobilization and expression of GPCRs and signaling proteins related to procontractile signaling in ASM derived postmortem from subjects who died of nonrespiratory causes, with cells from subjects who died of asthma. Despite the increased or comparable expression of contraction-promoting GPCRs (bradykinin B2 or histamine H1 and protease-activated receptor 1, respectively) in asthmatic ASM cells relative to cells from healthy donors, asthmatic ASM cells exhibited reduced histamine-induced Ca(2+) mobilization and comparable responses to bradykinin and thrombin, suggesting a postreceptor signaling defect. Accordingly, the expression of regulator of G-protein signaling-5 (RGS5), an inhibitor of ASM contraction, was increased in cultured, asthmatic ASM cells and in bronchial smooth muscle bundles of both human subjects with asthma and allergen-challenged mice, relative to those of healthy human subjects or naive mice. The overexpression of RGS5 impaired the release of Ca(2+) to thrombin, histamine, and carbachol, and reduced the contraction of precision-cut lung slices to carbachol. These results suggest that increased RGS5 expression contributes to decreased myocyte shortening in severe and fatal asthma.

Rationale: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract., Objectives: To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens., Methods: Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131)., Measurements and Main Results: Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001)., Conclusions: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.

Purpose of Review: Asthma in Latin America is a growing public health problem and seems to be most prevalent and cause most morbidity among poor urban populations. This article will review the findings of recent human studies of the associations of asthma prevalence in Latin America with factors associated with poverty and inequality including childhood infections, stress, environment, nutrition and diet., Recent Findings: Most asthma in childhood in Latin America is nonatopic and has been associated with exposures related to environmental dirt, diet and psychosocial distress. These factors are strongly linked to poverty and inequality. Interestingly, infections with bacterial, viral and parasitic pathogens in childhood appear to attenuate atopy in childhood but have no effect on asthma symptoms. There are biologically plausible mechanisms by which dirt exposures (e.g. endotoxin and other microbial products and nonmicrobial irritants), diet and obesity and psychosocial stress may cause airways inflammation., Summary: Most childhood asthma in Latin America is nonatopic for which important risk factors are those of poverty including poor hygiene (i.e. dirt), poor diet and obesity and psychosocial stress. There is evidence that exposures to infections in early childhood reduce atopy but not asthma. Research is needed to identify causes of nonatopic asthma that may be suitable for primary prevention or other public health intervention strategies for asthma in Latin America.

In severe asthma, bronchodilator- and steroid-insensitive airflow obstruction develops through unknown mechanisms characterized by increased lung airway smooth muscle (ASM) mass and stiffness. We explored the role of a Regulator of G-protein Signaling protein (RGS4) in the ASM hyperplasia and reduced contractile capacity characteristic of advanced asthma. Using immunocytochemical staining, ASM expression of RGS4 was determined in endobronchial biopsies from healthy subjects and those from subjects with mild, moderate and severe asthma. Cell proliferation assays, agonist-induced calcium mobilization and bronchoconstriction were determined in cultured human ASM cells and in human precision cut lung slices. Using gain- and loss-of-function approaches, the precise role of RGS proteins was determined in stimulating human ASM proliferation and inhibiting bronchoconstriction. RGS4 expression was restricted to a subpopulation of ASM and was specifically upregulated by mitogens, which induced a hyperproliferative and hypocontractile ASM phenotype similar to that observed in recalcitrant asthma. RGS4 expression was markedly increased in bronchial smooth muscle of patients with severe asthma, and expression correlated significantly with reduced pulmonary function. Whereas RGS4 inhibited G protein-coupled receptor (GPCR)-mediated bronchoconstriction, unexpectedly RGS4 was required for PDGF-induced proliferation and sustained activation of PI3K, a mitogenic signaling molecule that regulates ASM proliferation. These studies indicate that increased RGS4 expression promotes a phenotypic switch of ASM, evoking irreversible airway obstruction in subjects with severe asthma.

Background: Studies conducted in transitional communities from Africa and Asia have pointed to the process of urbanisation as being responsible for the increase in asthma prevalence in developing regions. In Latin America, there are few published data available on the potential impact of urbanisation on asthma prevalence. The aim of the present study was to explore how the process of urbanisation may explain differences in asthma prevalence in transitional communities in north-eastern Ecuador., Methodology/principal Findings: An ecological study was conducted in 59 communities in Esmeraldas Province, Ecuador. Indicators of urbanisation were grouped into three indices representing the processes associated with urbanisation: socioeconomic, lifestyle and urban infrastructure. Categorical principal components analysis was used to generate scores for each index and a fourth index--a summary urbanisation index--was derived from the most representative variables in each of the three indices. The authors analysed the associations between community asthma prevalence and the indices, as well as with each indicator variable of every group. The overall prevalence of asthma was 10.1% (range 0-31.4% between communities). Three of the four indices presented significant associations with community asthma prevalence: socioeconomic (r = 0.295, p = 0.023), lifestyle (r = 0.342, p = 0.008) and summary urbanisation index (r = 0.355, p = 0.006). Variables reflecting better socioeconomic status and a more urban lifestyle were associated with greater asthma prevalence., Conclusions: These data provide evidence that the prevalence of asthma increases with increasing levels of urbanisation in transitional communities, and factors associated with greater socioeconomic level and changes towards a more urban lifestyle may be particularly important.

Background: Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease., Methods/design: A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also., Discussion: The study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and the first 2 years of life) on the development of vaccine immunity and allergy. The data will inform an ongoing debate of potential effects of geohelminths on child health and will contribute to policy decisions on new interventions designed to improve vaccine immunogenicity and protect against the development of allergic diseases., Trial Registration: Current Controlled Trials ISRCTN41239086.

Objective: This study aimed to explore the association between asthma and atopy in a cohort of children living in a large urban center in Brazil. Atopy was defined by the presence of allergen-specific IgE in serum or by a positive skin prick test., Methods: In a sample of 1 445 Brazilian children, the association between the prevalence of asthma, skin prick test positivity, and allergen-specific IgE in serum was investigated., Results: The prevalence of asthma was 22.6%. The presence of serum allergen-specific IgE was frequent in asthmatics and nonasthmatics, and the prevalence of asthma increased only with levels of allergen-specific IgE > 3.5 kilounits/L. The proportion of asthma attributable to atopy was estimated to be 24.5% when atopy was defined by the presence of allergen-specific IgE. With a given level of specific IgE, no association between skin test reactivity and asthma was observed. Skin prick tests were less sensitive than specific IgE for detection of atopy., Conclusions: Most asthma cases in an urban underprivileged setting in Brazil were not attributable to atopy. This observation has important implications for understanding the risk factors for the asthma epidemic in Latin America.

Background: The causation of asthma is poorly understood. Risk factors for atopic and non-atopic asthma may be different. This study aimed to analyze the associations between markers of poverty, dirt and infections and wheezing in atopic and non-atopic children., Methods: 1445 children were recruited from a population-based cohort in Salvador, Brazil. Wheezing was assessed using the ISAAC questionnaire and atopy defined as allergen-specific IgE ≥ 0.70 kU/L. Relevant social factors, environmental exposures and serological markers for childhood infections were investigated as risk factors using multivariate multinomial logistic regression., Results: Common risk factors for wheezing in atopic and non-atopic children, respectively, were parental asthma and respiratory infection in early childhood. No other factor was associated with wheezing in atopic children. Factors associated with wheezing in non-atopics were low maternal educational level (OR 1.49, 95% CI 0.98-2.38), low frequency of room cleaning (OR 2.49, 95% CI 1.27-4.90), presence of rodents in the house (OR 1.48, 95% CI 1.06-2.09), and day care attendance (OR 1.52, 95% CI 1.01-2.29)., Conclusions: Non-atopic wheezing was associated with risk factors indicative of poverty, dirt and infections. Further research is required to more precisely define the mediating exposures and the mechanisms by which they may cause non-atopic wheeze.

Background: During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs) function in the presence and absence of IL-13 and TNFalpha, cytokines known to be important in asthma., Method: Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS) were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma., Results: PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFalpha) stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFalpha had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as well as from those with asthma., Conclusion: Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a potential role for inflammation-induced changes in oxytocin receptor signaling in the regulation of airway hyper-responsiveness in asthma.

BACKGROUND Asthma has emerged as an important public health problem of urban populations in Latin America. Epidemiological data suggest that a minority of asthma cases in Latin America may be associated with allergic sensitisation and that other mechanisms causing asthma have been overlooked. The aim of the present study was to investigate risk factors for atopic and non-atopic asthma in school-age children. METHODS A cross-sectional study was conducted among 3960 children aged 6-16 years living in Afro-Ecuadorian rural communities in Esmeraldas province in Ecuador. Allergic diseases and risk factors were assessed by questionnaire and allergic sensitisation by allergen skin prick reactivity. RESULTS A total of 390 (10.5%) children had wheeze within the previous 12 months, of whom 14.4% had at least one positive skin test. The population-attributable fraction for recent wheeze associated with atopy was 2.4%. Heavy Trichuris trichiura infections were strongly inversely associated with atopic wheeze. Non-atopic wheeze was positively associated with maternal allergic symptoms and sedentarism (watching television (>3 h/day)) but inversely associated with age and birth order. CONCLUSIONS The present study showed a predominance of non-atopic compared with atopic wheeze among schoolchildren living in a poor rural region of tropical Latin America. Distinct risk factors were associated with the two wheeze phenotypes and may indicate different causal mechanisms. Future preventive strategies in such populations may need to be targeted at the causes of non-atopic wheeze.

Background: Evidence suggests that chronic stimulation of beta(2)-adrenergic receptors (beta(2)-ARs) induces receptor tolerance that limits the efficacy of beta-agonists in the treatment of asthma. The precise mechanisms that induce beta(2)-AR tolerance remain unclear., Objective: We sought to determine whether steroids modulate albuterol-induced beta(2)-AR tolerance in human small airways., Methods: beta(2)-AR responsiveness to isoproterenol was characterized in human precision-cut lung slices (PCLSs) precontracted to carbachol after pretreatment with albuterol., Results: Incubation of PCLSs with albuterol for 3, 6, or 12 hours attenuated subsequent isoproterenol-induced relaxation in a dose- and time-dependent manner. A 40% decrease (P < .0001) in maximum relaxation and a 45% decrease (P = .0011) in airway sensitivity from control values occurred after the maximum time and concentration of albuterol incubation. Desensitization was not evident when airways were relaxed to forskolin. Dexamethasone pretreatment of PCLSs (1 hour) prevented albuterol-induced beta(2)-AR desensitization by increasing the maximum drug effect (P = .0023) and decreasing the log half-maximum effective concentration values (P < .0001) from that of albuterol alone. Albuterol (12-hour incubation) decreased the beta(2)-AR cell-surface number (P = .013), which was not significantly reversed by 1 hour of preincubation with dexamethasone., Conclusion: These data suggest that beta(2)-AR desensitization occurs with prolonged treatment of human small airways with albuterol through mechanisms upstream of protein kinase A and that steroids prevent or reverse this desensitization. Clarifying the precise molecular mechanisms by which beta(2)-AR tolerance occurs might offer new therapeutic approaches to improve the efficacy of bronchodilators in asthma and chronic obstructive pulmonary disease.

Background: Asthma and allergic diseases are becoming increasingly frequent in children in urban centres of Latin America although the prevalence of allergic disease is still low in rural areas. Understanding better why the prevalence of asthma is greater in urban migrant populations and the role of risk factors such as life style and environmental exposures, may be key to understand what is behind this trend., Methods/design: The Esmeraldas-SCAALA (Social Changes, Asthma and Allergy in Latin America) study consists of cross-sectional and nested case-control studies of school children in rural and urban areas of Esmeraldas Province in Ecuador. The cross-sectional study will investigate risk factors for atopy and allergic disease in rural and migrant urban Afro-Ecuadorian school children and the nested case-control study will examine environmental, biologic and social risk factors for asthma among asthma cases and non-asthmatic controls from the cross-sectional study. Data will be collected through standardised questionnaires, skin prick testing to relevant aeroallergen extracts, stool examinations for parasites, blood sampling (for measurement of IgE, interleukins and other immunological parameters), anthropometric measurements for assessment of nutritional status, exercise testing for assessment of exercise-induced bronchospasm and dust sampling for measurement of household endotoxin and allergen levels., Discussion: The information will be used to identify the factors associated with an increased risk of asthma and allergies in migrant and urbanizing populations, to improve the understanding of the causes of the increase in asthma prevalence and to identify potentially modifiable factors to inform the design of prevention programmes to reduce the risk of allergy in urban populations in Latin America.

Background: The prevalence of asthma and allergic diseases has increased in industrialised countries, and it is known that rates vary according whether the area is urban or rural and to socio-economic status. Surveys conducted in some urban settings in Latin America found high prevalence rates, only exceeded by the rates observed in industrialised English-speaking countries. It is likely that the marked changes in the environment, life style and living conditions in Latin America are responsible for these observations. The understanding of the epidemiological and immunological changes that underlie the increase in asthma and allergic diseases in Latin America aimed by SCAALA studies in Brazil and Ecuador will be crucial for the identification of novel preventive interventions., Methods/design: The Salvador-SCAALA project described here is a longitudinal study involving children aged 4-11 years living in the city of Salvador, Northeastern Brazil. Data on asthma and allergic diseases (rhinitis and eczema) and potential risk factors will be collected in successive surveys using standardised questionnaire. This will be completed with data on dust collection (to dust mite and endotoxin), skin test to most common allergens, stool examinations to helminth and parasites, blood samples (to infection, total and specific IgE, and immunological makers), formaldehyde, physical inspection to diagnoses of eczema, and anthropometric measures. Data on earlier exposures when these children were 0-3 years old are available from a different project., Discussion: It is expected that knowledge generated may help identify public health interventions that may enable countries in LA to enjoy the benefits of a "modern" lifestyle while avoiding--or minimising--increases in morbidity caused by asthma and allergies.

Background: There are limited data from non‐industrialized settings on the effects of early life viral respiratory disease on childhood respiratory illness. We followed a birth cohort in tropical Ecuador to understand how early viral respiratory disease, in the context of exposures affecting airway inflammation including ascariasis, affect wheezing illness, asthma, and rhinoconjunctivitis in later childhood. Methods: A surveillance cohort nested within a birth cohort was monitored for respiratory infections during the first 2 years in rural Ecuador and followed for 8 years for the development of wheeze and rhinoconjunctivitis. Nasal swabs were examined for viruses by polymerase chain reaction and respiratory symptom data on recent wheeze and rhinoconjunctivitis were collected by periodic questionnaires at 3, 5, and 8 years. Stools from pregnant mothers and periodically from children aged 2 years were examined microscopically for soil‐transmitted helminths. Atopy was measured by allergen skin prick testing at 2 years. Spirometry, fractional exhaled nitric oxide measurement, and nasal washes were performed at 8 years. Associations between clinically significant respiratory disease (CSRD) and wheezing or rhinoconjunctivitis at 3, 5, and 8 years were estimated using multivariable logistic regression. Results: Four hundred and twenty six children were followed of which 67.7% had at least one CSRD episode; 12% had respiratory syncytial virus (RSV)+CSRD and 36% had rhinovirus (RHV)+CSRD. All‐cause CSRD was associated with increased wheeze at 3 (OR 2.33 [95% confidence intervals (CI) 1.23–4.40]) and 5 (OR: 2.12 [95% CI 1.12–4.01]) years. RHV+CSRD was more strongly associated with wheeze at 3 years in STH‐infected (STH‐infected [OR 13.41, 95% CI 1.56–115.64] vs. uninfected [OR 1.68, 95% CI 0.73–3.84]) and SPT+ (SPT+ [OR 9.42, 95% CI 1.88–47.15] versus SPT‐ [OR 1.92, 95% CI 0.84–4.38]) children. No associations were observed between CSRD and rhinoconjunctivitis. Discussion: CSRD was significantly associated with childhood wheeze with stronger associations observed for RHV+CSRD in SPT+ and STH‐infected children. [ABSTRACT FROM AUTHOR]

Asthma is an important health concern in Latin America (LA) where it is associated with variable prevalence and disease burden between countries. High prevalence and morbidity have been observed in some regions, particularly marginalized urban populations. Research over the past 10 years from LA has shown that childhood disease is primarily non‐atopic. The attenuation of atopy may be explained by enhanced immune regulation induced by intense exposures to environmental factors such as childhood infections and poor environmental conditions of the urban poor. Non‐atopic symptoms are associated with environmental and lifestyle factors including poor living conditions, respiratory infections, psychosocial stress, obesity, and a diet of highly processed foods. Ancestry (particularly African) and genetic factors increase asthma risk, and some of these factors may be specific to LA settings. Asthma in LA tends to be poorly controlled and depends on access to health care and medications. There is a need to improve management and access to medication through primary health care. Future research should consider the heterogeneity of asthma to identify relevant endotypes and underlying causes. The outcome of such research will need to focus on implementable strategies relevant to populations living in resource‐poor settings where the disease burden is greatest. [ABSTRACT FROM AUTHOR]

There is considerable research interest in the role of helminth infections in the development of allergic diseases. However, findings from previous studies are mixed. Existing systematic reviews of these studies are outdated. We performed a systematic review of the global literature on the association between helminth infections and development and clinical outcomes of allergic diseases. We searched Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, PubMed, Global Index Medicus, Scielo, KoreaMed, Google Scholar, and Lilacs for studies published up to January 2020. We included observational epidemiological studies (cohort, case-control, and cross-sectional studies) of children and adults reporting associations between helminth infections and asthma, allergic rhinitis, eczema, and atopy. We performed random-effects meta-analysis to summarize the effect estimates. We included 80 studies with 99,967 participants. In the meta-analyses, we did not observe an overall association between helminth infections and allergic diseases. There was, however, evidence that Ascaris lumbricoides infections were associated with an increased risk of bronchial hyperreactivity in children (risk ratio, 1.41; 95% CI, 1.17-1.70; I 2 = 50; P for I 2 =.09), and were associated with an increased risk of atopy among helminth-infected adults (risk ratio, 1.37; 95% CI, 1.18-1.61; I 2 = 52; P for I 2 =.02). We found no study that addressed the association between helminth infection and clinical outcomes of allergic diseases. The overall strength of the underlying evidence was low to moderate. Helminth infections may increase the risk of bronchial hyperreactivity in children and atopy in adults. Well-designed longitudinal cohorts may help clarify potential causal associations between chronic helminth infections and allergic diseases. [ABSTRACT FROM AUTHOR]

Allergic diseases are on the increase globally in parallel with a decrease in parasitic infection. The inverse association between parasitic infections and allergy at an ecological level suggests a causal association. Studies in human subjects have generated a large knowledge base on the complexity of the interrelationship between parasitic infection and allergy. There is evidence for causal links, but the data from animal models are the most compelling: despite the strong type 2 immune responses they induce, helminth infections can suppress allergy through regulatory pathways. Conversely, many helminths can cause allergic-type inflammation, including symptoms of “classical” allergic disease. From an evolutionary perspective, subjects with an effective immune response against helminths can be more susceptible to allergy. This narrative review aims to inform readers of the most relevant up-to-date evidence on the relationship between parasites and allergy. Experiments in animal models have demonstrated the potential benefits of helminth infection or administration of helminth-derived molecules on chronic inflammatory diseases, but thus far, clinical trials in human subjects have not demonstrated unequivocal clinical benefits. Nevertheless, there is sufficiently strong evidence to support continued investigation of the potential benefits of helminth-derived therapies for the prevention or treatment of allergic and other inflammatory diseases. [ABSTRACT FROM AUTHOR]