Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

Validation of clinical exome sequencing in the diagnostic procedure of patients with intellectual disability in clinical practice.

Intellectual disability (ID) has a prevalence of 1-3% and aproximately 30-50% of ID cases have a genetic cause. Development of next-generation sequencing has shown a high diagnostic potential. The aim of this work was to evaluate the diagnostic yield of clinical exome sequencing in 188 ID patients and the economic impact of its introduction in clinical practice. An analysis of diagnostic yield according to the different clinical variables was performed in order to establish an efficient diagnostic protocol for ID patients. Diagnostic yield of clinical exome sequencing was significant (34%) supporting its utility in diagnosis of ID patients. Wide genetic heterogeneity and predominance of autosomal dominant de novo variants in ID patients were observed. Time to diagnosis was shortened and diagnostic study costs decreased by 62% after implementation of clinical exome sequencing. No association was found between any of the variables analyzed and a higher diagnostic yield; added to the fact that many of the diagnoses weren't clinically detectable, the reduction of time to diagnosis and the economic savings with respect to classical diagnostic studies, strengthen the clinical and economical convenience of early implementation of clinical exome sequencing in the diagnostic workup of ID patients in clinical practice.

Serum Vitamins A and E at Mid-Pregnancy and Their Relationships with Both Maternal and Cord Blood Antioxidant Status and Perinatal Conditions: The NELA Cohort.

INTRODUCTION: Most of the pregnant women do not achieve the recommended dietary intake of vitamins A and E. These vitamins may counteract oxidative stress involved in some adverse perinatal outcomes. We aimed to assess the associations between maternal vitamin A and E at mid-pregnancy with both maternal and fetal outcomes and to identify possible early biomarkers during pregnancy to predict and prevent oxidative stress in the offspring. METHODS: Data on dietary and serum levels of vitamins A and E were collected from 544 pregnant women from the Nutrition in Early Life and Asthma (NELA) study, a prospective mother-child cohort set up in Spain. RESULTS: There were large discrepancies between low dietary vitamin E intake (78% of the mothers) and low serum vitamin E levels (3%) at 24 weeks of gestation. Maternal serum vitamins A and E at mid-pregnancy were associated with higher antioxidant status not only in the mother at this time point (lower hydroperoxides and higher total antioxidant activity [TAA]) but also with the newborn at birth (higher TAA). Gestational diabetes mellitus (GDM) was negatively associated with maternal serum vitamin A (OR: 0.95 CI: 0.91-0.99, p = 0.009) at mid-pregnancy. Nevertheless, we could not detect any association between GDM and oxidative stress parameters. CONCLUSIONS: In conclusion, maternal vitamin A and E serum levels may be used as an early potential biomarker of antioxidant status of the neonate at birth. Control of these vitamins during pregnancy could help avoid morbid conditions in the newborn caused by oxidative stress in GDM pregnancies.

Cytokine production by newborns: influence of sex and season of birth.

BACKGROUND: Immune signatures at birth could be associated with clinical outcomes and will improve our understanding of immunity prenatal programming. METHODS: Data come from 235 newborns from the cohort study NELA. Production of cytokines was determined using Luminex technology. Associations between cytokine concentrations with sex and season of birth were examined by multivariate regression models. RESULTS: Umbilical cord blood cells produced high levels of inflammatory cytokines, moderate levels of Th1/Th2/Tr-related cytokines, and low levels of Th17 cytokines. Compared to females, male newborn cells secreted higher levels of Th2 (peptidoglycan-stimulated IL-13, odds ratio [OR] = 2.26; 95% CI 1.18, 4.31, p value = 0.013) and Th17 (polyinosinic:polycytidylic acid-stimulated IL-23, OR = 1.82, 95% CI 1.01, 3.27, p value = 0.046) and lower levels of Th1 (olive-stimulated IL-2, OR = 0.56, 95% CI 0.31, 0.99, p value = 0.047) cytokines. Also, children born during warm seasons showed decreased innate cytokine response to peptidoglycan (IL-6, OR = 0.28, 95% CI 0.15, 0.52, p value < 0.001) compared to those born in cold seasons; meanwhile, adaptive immunity cytokines were more frequently secreted by children born during warm seasons in response to allergen extracts (IL-10, OR = 2.11, 95% CI 1.12, 3.96, p value = 0.020; IL-17F, OR = 3.31, 95% CI 1.83, 5.99, p value < 0.001). CONCLUSION: Newborns showed specific cytokines signatures influenced by sex and season of birth. IMPACT: There is a limited number of population-based studies on the immune status at birth and the influence of prenatal and perinatal factors on it. Characterization of cytokine signatures at birth related to the prenatal environment could improve our understanding of immunity prenatal programming. Newborns exhibit specific unstimulated and stimulated cytokine signatures influenced by sex and season of birth. Unstimulated and stimulated cytokine signatures in newborns may be associated with the development of related clinical outcomes later in life.

Analysis of response of severe eosinophilic asthmatic patients to benralizumab.

INTRODUCTION: Clinical trials and real-life studies have been published showing effectiveness of benralizumab in severe eosinophilic asthmatic patients. The aim of the present study is to describe super-responders to benralizumab in a series of 79 patients who completed at least 1 year of treatment, and to compare super-responders with non super-responders. METHODS: This is a multicenter study of the Register of Severe Asthma of the Region of Murcia (RE-ASGRAMUR) Group performed in eight hospitals under the conditions of routine clinical practice. Patients with zero exacerbations and no oral corticosteroid therapy for asthma were considered super-responders. We analyzed clinical, functional, and inflammatory parameters of selected patients. RESULTS: In all, 50 of the 79 patients (63%) met the super-responder criteria. In addition, 36% of the patients (26/71) were considered as complete responders to treatment (super--responder + Asthma Control Test [ACT] ≥ 20 + forced expiratory volume in 1 s [FEV1] ≥ 80%). The super--responders were significantly older in age (P = 0.0029), had higher eosinophils count (P = 0.0423), higher proportion of nasal polyps (P = 0.036), and they had less severe disease at baseline. After 1 year of treatment, the super-responders had higher levels of ACT questionnaire (23 vs 19, P = 0.0007) and better percentage of FEV1 (83 vs 75, P = 0.0359). CONCLUSION: Almost two of the three patients treated with benralizumab were super--responders after 1 year of treatment and 36% had a complete response. Super-responders were associated with older age, higher eosinophils count, had nasal polyposis as comorbidity, and had less severe disease at baseline. This data illustrated the good real-life response of patients with severe eosinophilic asthma to the treatment with benralizumab.

The Influence of the Thickness of the Materials for the Provisionalization in Minimally Invasive Restorations.

This in vitro study aimed to determine the flexural strength and modulus of elasticity of two bisacrylic resins for temporary crowns at different thicknesses, i.e., Structur 3 and Structur Premium, and to compare them with each other. Sixty samples were prepared, thirty of each material, which were made at different thicknesses (1 mm, 1.5 mm, and 2 mm). The dimensions followed the UNE-EN ISO 178:2019 standard, with a length of 24 mm, a width of 10 mm, and the thicknesses described. Materials were subjected to a three-point bending test. For the modulus of elasticity, statistically significant differences were observed between the 1.5 mm and 2 mm thicknesses of Structur 3 material. For Structur Premium, statistically significant differences were observed between the thicknesses 1 mm and 1.5 mm as well as between 1 mm and 2 mm thickness. With respect to flexural strength, no statistically significant differences were observed for either material at the different thicknesses. Significant differences were observed between the materials for both flexural strength and modulus of elasticity, being higher for Structur Premium: Structur Premium has a higher flexural strength and modulus of elasticity than Structur 3. There are significant differences for the modulus of elasticity but not for the flexural strength between thicknesses.

Multi-approach LC-MS methods for the characterization of species-specific attributes of monoclonal antibodies from plants.

In this work, an analytical platform based on the use of chromatography and mass spectrometry (MS), has been applied to the characterization of Rituximab (RTX) obtained from two plant expression systems (rice and tobacco) in comparison to the mammalian cell-derived reference monoclonal antibody (mAb). Different chromatographic approaches, hyphenated to high resolution MS (HRMS), were applied to RTX structural investigation both at middle- and peptide level. In particular, cation exchange chromatography (CEX), size exclusion chromatography (SEC), reversed phase (RPLC) and hydrophilic interaction liquid chromatographic (HILIC) methods were developed and applied on intact mAbs, IdeS-, and trypsin digests in order to address critical attributes such as primary structure, glycan composition, species-related heterogeneity, glycosylation degree, charge variants, aggregation tendency and enzymatic stability. All the collected data highlight the features and criticalities of each production approach. Production in rice results in a heterogeneous but stable product over time, suggesting the absence of proteases in seeds; while tobacco expression system leads to more homogeneous glycosylation, but protein stability seems to be a critical issue probably due to the presence of proteases. This analytical strategy represents a robust support to scientists in the selection and optimization of the best plant expression system to produce recombinant humanized mAbs.

Valores de corte de FEV1/FVC para el diagnóstico de obstrucción al flujo aéreo en población pediátrica: estudio PAO (Pediatric Airflow Obstruction) / FEV1/FVC Cut-off Values for the Diagnosis of Airflow Obstruction in Pediatric Patients: The Pediatric Airflow Obstruction (PAO) Study

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[Translated article] FEV1/FVC Cut-off Values for the Diagnosis of Airflow Obstruction in Pediatric Patients: The Pediatric Airflow Obstruction (PAO) Study / Valores de corte de FEV1/FVC para el diagnóstico de obstrucción al flujo aéreo en población pediátrica: estudio PAO (Pediatric Airflow Obstruction)

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Development of Lung Function in Preterm Infants During the First Two Years of Life.

INTRODUCTION: It remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size. AIM: To assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period. METHODS: This observational longitudinal study assessed lung function in 74 preterm (30+0 to 35+6 weeks' gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V'maxFRC and FEF25-75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age. RESULTS: Lung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V'maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV0.5 and forced expiratory flows was seen in preterm infants. CONCLUSION: When compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function.

Development of Lung Function in Preterm Infants During the First Two Years of Life / Desarrollo de la función pulmonar en lactantes pretérmino durante los 2 primeros años de vida

Introduction: It remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size.AimTo assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period.MethodsThis observational longitudinal study assessed lung function in 74 preterm (30+0 to 35+6 weeks’ gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V’maxFRC and FEF25–75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age.ResultsLung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V’maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV0.5 and forced expiratory flows was seen in preterm infants.ConclusionWhen compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function. (AU)

Introducción: Todavía no está claro si la prematuridad por sí sola puede tener influencia en el desarrollo pulmonar tras el parto y, en particular, en el tamaño bronquial.ObjetivoValorar la función pulmonar durante los 2 primeros años de vida en lactantes pretérmino sanos y comparar las medidas con las obtenidas en lactantes nacidos a término sanos durante el mismo periodo de tiempo.MétodosEste ensayo longitudinal observacional valoró la función pulmonar en 74 lactantes pretérmino (30+0 a 35+6 semanas de edad gestacional) y 76 lactantes nacidos a término sanos como controles, que se seleccionaron entre 2011 y 2013. Se llevaron a cabo las mediciones de la respiración corriente, la mecánica respiratoria pasiva, los flujos espiratorios forzados a volumen corriente y con insuflación previa (V’maxFRC y FEF25-75, respectivamente) tras la sedación con hidrato de cloral siguiendo las recomendaciones de las ATS/ERS a la edad corregida de 6 y 18 meses.ResultadosInicialmente se obtuvieron las medidas de función pulmonar de los lactantes pretérmino y los controles a término a los 6 meses de edad. Los lactantes pretérmino presentaron unos valores absolutos y ajustados (a la edad gestacional, la edad posnatal, el sexo, el tamaño corporal y los factores de confusión) menores para la distensibilidad pulmonar y la V’maxFRC. A los 18 meses de edad posnatal corregida, se repitieron las mismas mediciones en 57 lactantes pretérmino y 61 controles a término. Se observó una recuperación del volumen corriente, los parámetros de mecánica respiratoria, el FEV0,5 y los flujos espiratorios forzados en los lactantes pretérmino.ConclusiónEn comparación con los controles a término, los flujos espiratorios forzados más bajos observados en el grupo de pretérminos sanos a los 6 meses no se observaron a los 18 meses de edad corregida, lo que evidencia un crecimiento de recuperación de la función de la vía respiratoria. (AU)

The burden of asthma, hay fever and eczema in children in 25 countries: GAN Phase I study.

AIMS: There have been no worldwide standardised surveys of prevalence and severity of asthma, rhinoconjunctivitis and eczema in school children for 15 years. The present study aims to provide this information. METHODS: Following the exact International Study of Asthma and Allergies in Childhood (ISAAC) methodology (cross-sectional questionnaire-based survey), Global Asthma Network (GAN) Phase I was carried out between 2015 and 2020 in many centres worldwide. RESULTS: The study included 157 784 adolescents (13-14 years of age) in 63 centres in 25 countries and 101 777 children (6-7 years of age) in 44 centres in 16 countries. The current prevalence of symptoms, respectively, was 11.0% and 9.1% for asthma, 13.3% and 7.7% for rhinoconjunctivitis and 6.4% and 5.9% for eczema. The prevalence of asthma ever was 10.5% and 7.6%, hay fever ever was 15.2% and 11.1% and eczema ever was 10.6% and 13.4%, respectively. Centres in low or lower middle gross national income countries (LICs or LMICs) had significantly lower prevalence of the three disease symptoms and diagnoses (except for hay fever). In children, the prevalence of asthma and rhinoconjunctivitis symptoms was higher in boys, while the reverse occurred among adolescents. For eczema, while the prevalence among female adolescents was double that of males, there was no sex difference among children. Centre accounted for non-negligible variability in all disease symptoms (10-20%). CONCLUSION: The burdens of asthma, rhinoconjunctivitis and eczema vary widely among the limited number of countries studied. Although symptom prevalence is lower in LICs and LMICs, it represents a considerable burden everywhere studied.

The burden of asthma, hay fever and eczema in adults in 17 countries: GAN Phase I study.

AIMS: Asthma, hay fever and eczema are three common chronic conditions. There have been no recent multi-country data on the burden of these three conditions in adults; the aims of this study are to fill this evidence gap. METHODS: The Global Asthma Network Phase I is a multi-country cross-sectional population-based study using the same core methodology as the International Study of Asthma and Allergies in Childhood Phase III. It provides data on the burden of asthma, hay fever and eczema in children and adolescents, and, for the first time, in their parents/guardians. RESULTS: Data were available from 193 912 adults (104 061 female; mean±sd age 38±7.5 years) in 43 centres in 17 countries. The overall prevalence (range) of symptoms was 6.6% (0.9-32.7%) for current wheeze, 4.4% (0.9-29.0%) for asthma ever, 14.4% (2.8-45.7%) for hay fever ever and 9.9% (1.6-29.5%) for eczema ever. Centre prevalence varied considerably both between countries and within countries. There was a moderate correlation between hay fever ever and asthma ever, and between eczema ever and hay fever ever at the centre level. There were moderate to strong correlations between indicators of the burden of disease reported in adults and the two younger age groups. CONCLUSION: We found evidence for a substantial burden of asthma, hay fever ever and eczema ever in the countries examined, highlighting the major public health importance of these diseases. Prevention strategies and equitable access to effective and affordable treatments for these three conditions would help mitigate the avoidable morbidity they cause.

Cytokine profiles in cord blood in relation to prenatal traffic-related air pollution: The NELA cohort.

BACKGROUND: Outdoor air pollution may disturb immune system development. We investigated whether gestational exposure to traffic-related air pollutants (TRAP) is associated with unstimulated cytokine profiles in newborns. METHODS: Data come from 235 newborns of the NELA cohort. Innate response-related cytokines (IL-6, IFN-α, IL1-ß, and TNF-α), Th1-related (IFN-γ and IL-2), Th2-related (IL-4, IL-5, and IL-13), Th17-related (IL-17 and IL-23), and immunomodulatory cytokine IL-10 were quantified in the supernatant of unstimulated whole umbilical cord blood cells after 7 days of culture using the Luminex technology. Dispersion/chemical transport modeling was used to estimate long-term (whole pregnancy and trimesters) and short-term (15 days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2 ), particulate matter (PM2.5 and PM10 ), and ozone (O3 ). We fitted multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models. RESULTS: NO2 during the whole pregnancy increased the odds of detection of IL-1ß (OR per 10 µg/m3 increase = 1.37; 95% CI, 1.02, 1.85) and IL-6 (OR per 10 µg/m3 increase = 1.32; 95% CI 1.00, 1.75). Increased odds of detected concentrations of IL-10 was found in newborns exposed during whole pregnancy to higher levels of NO2 (OR per 10 µg/m3 increase = 1.30; 95% CI 0.99, 1.69), PM10 (OR per 10 µg/m3 increase = 1.49; 95% CI 0.95, 2.33), and PM2.5 (OR per 5 µg/m3 increase = 1.56; 95% CI 0.97, 2.51). Exposure to O3 during the whole pregnancy increased the odds of detected IL-13 (OR per 10 µg/m3 increase = 1.22; 95% CI 1.01, 1.49). WQS model revealed first and third trimesters of gestation as windows of higher susceptibility. CONCLUSIONS: Gestational exposure to TRAP may increase detection of pro-inflammatory, Th2-related, and T regulatory cytokines in newborns. These changes might influence immune system responses later in life.

The Nutrition in Early Life and Asthma (NELA) birth cohort study: Rationale, design, and methods.

BACKGROUND: Primary prevention strategies for asthma are lacking. Its inception probably starts in utero and/or during the early postnatal period as the developmental origins of health and disease (DOHaD) paradigm suggests. OBJECTIVES: The main objective of Nutrition in Early Life and Asthma (NELA) cohort study is to unravel whether the following factors contribute causally to the developmental origins of asthma: (1) maternal obesity/adiposity and foetal growth; (2) maternal and child nutrition; (3) outdoor air pollution; (4) endocrine disruptors; and (5) maternal psychological stress. Maternal and offspring biological samples are used to assess changes in offspring microbiome, immune system, epigenome and volatilome as potential mechanisms influencing disease susceptibility. POPULATION: Randomly selected pregnant women from three health areas of Murcia, a south-eastern Mediterranean region of Spain, who fulfilled the inclusion criteria were invited to participate at the time of the follow-up visit for routine foetal anatomy scan at 19-22 weeks of gestation, at the Maternal-Fetal Medicine Unit of the "Virgen de la Arrixaca" University Clinical Hospital over a 36-month period, from March 2015 to April 2018. DESIGN: Prospective, population-based, maternal-child, birth cohort study. METHODS: Questionnaires on exposures and outcome variables were administered to mothers at 20-24 gestation week; 32-36 gestation week; and delivery. Children were surveyed at birth, 3 and 18 months of age and currently at 5 years. Furthermore, physical examinations were performed; and different measurements and biological samples were obtained at these time points. PRELIMINARY RESULTS: Among the 1350 women invited to participate, 738 (54%) were finally enrolled in the study and 720 of their children were eligible at birth. The adherence was high with 612 children (83%) attending the 3 months' visit and 532 children (72%) attending the 18 months' visit. CONCLUSION: The NELA cohort will add original and unique knowledge to the developmental origins of asthma.

Worldwide time trends in prevalence of symptoms of rhinoconjunctivitis in children: Global Asthma Network Phase I.

BACKGROUND: The Global Asthma Network (GAN), by using the International Study of Asthma and Allergies in Childhood (ISAAC) methodology, has updated trends in prevalence of symptoms of childhood allergic diseases, including non-infective rhinitis and conjunctivitis ('rhinoconjunctivitis'), which is reported here. METHODS: Prevalence and severity of rhinoconjunctivitis were assessed by questionnaire among schoolchildren in GAN Phase I and ISAAC Phase I and III surveys 15-23 years apart. Absolute rates of change in prevalence were estimated for each centre and modelled by multi-level linear regression to compare trends by age group, time period and per capita national income. RESULTS: Twenty-seven GAN centres in 14 countries surveyed 74,361 13- to 14-year-olds ('adolescents') and 45,434 6- to 7-year-olds ('children'), with average response proportions of 90% and 79%, respectively. Many centres showed highly significant (p < .001) changes in prevalence of rhinoconjunctivitis in the past year ('current rhinoconjunctivitis') compared with ISAAC. The direction and magnitude of centre-level trends varied significantly (p < .001) both within and between countries. Overall, current rhinoconjunctivitis prevalence decreased slightly from ISAAC Phase III to GAN: -1.32% per 10 years, 95% CI [-2.93%, +0.30%] among adolescents; and -0.44% [-1.29%, +0.42%] among children. Together, these differed significantly (p < .001) from the upward trend within ISAAC. Among adolescents, centre-level trends in current rhinoconjunctivitis were highly correlated with those for eczema symptoms (rho = 0.72, p < .0001) but not with centre-level trends in asthma symptoms (rho = 0.15, p = .48). Among children, these correlations were positive but not significant. CONCLUSION: Symptoms of non-infective rhinoconjunctivitis among schoolchildren may no longer be on the increase globally, although trends vary substantially within and between countries.