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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.

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]

Background and Purpose: Asthma presents as a heterogeneous syndrome characterized by airway obstruction, inflammation and hyper-reactivity (AHR). Spleen tyrosine kinase (Syk) mediates allergen-induced mast cell degranulation, a central component of allergen-induced inflammation and AHR. However, the role of Syk in IgE-mediated constriction of human small airways remains unknown. In this study, we addressed whether selective inhibition of Syk attenuates IgE-mediated constriction and mast cell mediator release in human small airways.Experimental Approach: Human precision cut lung slices (hPCLS) ex vivo derived from non-asthmatic donors were incubated overnight with human IgE, dexamethasone, montelukast, antihistamines or a selective Syk inhibitor (SYKi). High-affinity IgE receptor (FcεRI) activation by anti-IgE cross-linking was performed, and constriction and mediator release measured. Airway constriction was normalized to that induced by maximal carbachol stimulation. Syk expression (determined by qPCR and immunoblot) was also evaluated in human primary airway smooth muscle (HASM) cells to determine whether Syk directly modulates HASM function.Key Results: While dexamethasone had little effect on FcεR-mediated contraction, montelukast or antihistamines partially attenuated the response. SYKi abolished anti-IgE-mediated contraction and suppressed the release of mast cell or basophil mediators from the IgE-treated hPCLS. In contrast, SYKi had little effect on the non-allergic contraction induced by carbachol. Syk mRNA and protein were undetectable in HASM cells.Conclusions and Implications: A selective Syk inhibitor, but not corticosteroids, abolished FcεR-mediated contraction in human small airways ex vivo. The mechanism involved FcεRI receptor activation on mast cells or basophils that degranulate causing airway constriction, rather than direct actions on HASM. [ABSTRACT FROM AUTHOR]

Background We tested whether objectively measured indices of obstructive sleep apnoea (OSA) and sleep quality are associated with coronary artery calcification (CAC) prevalence independent of obesity, a classic confounder. Methods 1465 Multi-Ethnic Study of Atherosclerosis participants (mean age 68 years), who were free of clinical cardiovascular disease, had both coronary CT and in-home polysomnography and actigraphy performed. OSA categories were defined by the Apnea-Hypopnea Index (AHI). Prevalence ratios (PRs) for CAC >0 and >400 (high burden) were calculated. Results Participants with severe OSA (AHI ≥30; 14.6%) were more likely to have prevalent CAC, relative to those with no evidence of OSA, after adjustment for demographics and smoking status (PR 1.16; 95% CI 1.06 to 1.26), body mass index (1.11; 1.02 to 1.21) and traditional cardiovascular risk factors (1.10; 1.01 to 1.19). Other markers of hypoxaemia tended to be associated with a higher prevalence of CAC >0. For CAC >400, a higher prevalence was observed with both a higher arousal index and less slow-wave sleep. Overall, associations were somewhat stronger among younger participants, but did not vary by sex or race/ethnicity. Conclusions In this population-based multi-ethnic sample, severe OSA was associated with subclinical coronary artery disease (CAC >0), independent of obesity and traditional cardiovascular risk factors. Furthermore, the associations of the arousal index and slow-wave sleep with high CAC burden suggest that higher nightly sympathetic nervous system activation is also a risk factor. These findings highlight the potential importance of measuring disturbances in OSA as well as sleep fragmentation as possible risk factors for coronary artery disease. [ABSTRACT FROM AUTHOR]

Summary: Brazil is a middle‐income country undergoing the epidemiological transition. Effects of changes in daily life habits and access to clean water, sanitation and urban services on a growing urban population have contributed to a double burden of both infectious and noncommunicable chronic diseases. Studies have indicated that parasite infections may modulate the human immune system and influence the development of allergic conditions such as asthma. However, there is no consensus in the published literature on the effects of parasitic infections on allergy, perhaps as a consequence of factors determining the epidemiology of these infections that vary between populations such as age of first infection, duration and chronicity of infections, parasite burden and species, and host genetic susceptibility. In this review, we discuss the observations from Brazil concerning the relationship between parasite infections and allergy. [ABSTRACT FROM AUTHOR]

Background Asthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment. Objective We sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting. Methods We conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography. Results As previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze. Conclusions Our findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy. [ABSTRACT FROM AUTHOR]