Plasma polyamines during pregnancy and their relationships with maternal allergies and the immune response of the neonates.

BACKGROUND: Some studies have reported that polyamine levels may influence immune system programming. The aim of this study was to evaluate the polyamine profile during gestation and its associations with maternal allergy and cytokine production in cord blood cells in response to different allergenic stimuli. METHODS: Polyamines were determined in plasma of pregnant women (24 weeks, N = 674) and in umbilical cord samples (N = 353 vein and N = 160 artery) from the Mediterranean NELA birth cohort. Immune cell populations were quantified, and the production of cytokines in response to different allergic and mitogenic stimuli was assessed in cord blood. RESULTS: Spermidine and spermine were the most prevalent polyamines in maternal, cord venous, and cord arterial plasma. Maternal allergies, especially allergic conjunctivitis, were associated with lower spermine in umbilical cord vein. Higher levels of polyamines were associated with higher lymphocyte number but lower Th2-related cells in cord venous blood. Those subjects with higher levels of circulating polyamines in cord showed lower production of inflammatory cytokines, especially IFN-α, and lower production of Th2-related cytokines, mainly IL-4 and IL-5. The effects of polyamines on Th1-related cytokines production were uncertain. CONCLUSIONS: Spermidine and spermine are the predominant polyamines in plasma of pregnant women at mid-pregnancy and also in umbilical cord. Maternal allergic diseases like allergic conjunctivitis are related to lower levels of polyamines in cord vein, which could influence the immune response of the newborn. Cord polyamine content is related to a decreased Th2 response and inflammatory cytokines production, which might be important to reduce an allergenic phenotype in the neonate.

Recommendations for asthma monitoring in children: A PeARL document endorsed by APAPARI, EAACI, INTERASMA, REG, and WAO.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

Urinary concentrations of non-essential and essential elements during weaning in infants from the NELA cohort in Spain.

Infancy is a period of continuous growth and development, where inadequate intake of essential elements and exposure to non-essential elements may have lifelong health consequences. Thus, the aim of this study is to evaluate the urine concentration of essential and non-essential elements as a proxy for internal exposure during the weaning period, from 3 to 18 months of age. The Nutrition in Early Life and Asthma (NELA) birth cohort generated the data for this study. Sociodemographic, dietary, and urine concentration of essential (Co, Cu, Mo, I, Fe, Mn, Se, Zn, and Ni) and non-essential elements (Al, V, As, Cd, Sb, Tl, and Pb) data were available for 490 participants at 3 months of age and 216 participants at 18 months of age. Paired urine samples at both time periods were available for 175 infants. At 3 months of age, exclusively breastfed infants had lower urine concentrations of Al, V, Fe, Co, Se, Sb, and Tl. Notably, the concentration of Mo had a median (IQR) of 0.60 (0.40-2.10) µg/L compared to a median (IQR) of 39.80 (25.00-56.40) µg/L observed in infants exclusively fed with formula. When we analyzed the change in urine elements concentrations between 3 and 18 months of age, we observed increased As (0.75 vs. 18.60 µg/L), Co (0.05 vs. 0.24 µg/L), Mo (1.98 vs. 50.0 µg/L), Pb (0.15 vs. 0.69 µg/L), Se (11.3 vs. 23.1 µg/L), Tl (0.02 vs. 0.11 µg/L), and V (0.05 vs. 0.11 µg/L). For Cu, lower urine concentrations were observed at 18 months of age in comparison with concentrations at 3 months (5.77 vs. 4.41 µg/L). Among the main food items identified as driving the changes in urine concentration between 3 and 18 months of age were white fish, rice and pasta, potato chips, custard, small blue fish, and legumes. Exclusively breastfed infants showed lower exposure to non-essential elements compared to those who were fed with a mixture or formula. With the introduction of solid foods, the exposure to some non-essential elements increased drastically, as in the case of As and Pb. In addition, exposure to the essential metal Mo also increased substantially with the introduction of solid food.

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.

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.

Prevalence and time trends of symptoms of allergic rhinitis and rhinoconjunctivitis in Spanish children: Global Asthma Network (GAN) study.

INTRODUCTION: The time trends of the prevalence of rhinitis, rhinoconjunctivitis and nasal allergy previously described in the ISAAC (International Study of Asthma and Allergies in Childhood) in 2002 are unknown; or if the geographical or age differences in Spain persist. OBJECTIVE: To describe the prevalence of rhinitis, rhinoconjunctivitis and nasal allergy in different Spanish geographical areas and compare them with those of the ISAAC. METHODS: Cross-sectional study of the prevalence of rhinitis, rhinoconjunctivitis and nasal allergy, carried out in 2016-2019 on 19943 adolescents aged 13-14 years and 17215 schoolchildren aged 6-7 years from six Spanish areas (Cartagena, Bilbao, Cantabria, La Coruña, Pamplona, and Salamanca), through a questionnaire based on the Global Asthma Network (GAN) protocol. RESULTS: The prevalences of recent rhinitis and rhinoconjunctivitis (last 12 months), and nasal allergy/hay fever were 35.1%, 17.6%, and 14.6% in the adolescents and 20%, 8.5%, and 8.9% in the schoolchildren, respectively, with rhinoconjunctivitis in adolescents varying from 20.9% in Bilbao to 13.4% in Cartagena; and in schoolchildren, from 9.8% in La Coruña to 6.4% in Pamplona. These prevalences of rhinoconjunctivitis and nasal allergy in adolescents were higher than those described in the ISAAC (16.3% and 13%) and similar in schoolchildren to the ISAAC (9% and 9.4%). CONCLUSIONS: There has been a stabilisation of rhinitis, rhinoconjunctivitis and nasal allergy in schoolchildren that slows the previous upward trend of ISAAC; and a slight non-significant increase in rhinoconjunctivitis and nasal allergy in adolescents. The variability found in adolescents would require local research to be better understood.

The role of Human Development Index in the epidemiology of asthma in adolescents in Kosovo: A cross-sectional multicentre Global Asthma Network (GAN) study.

BACKGROUND: Very limited information is available on the prevalence and risk factors of asthma in adolescents in Kosovo, and no study has previously addressed the role of Human Development Index (HDI) on asthma in the region. The present study addresses these two issues. METHODS: Following the Global Asthma Network (GAN) methodology, a cross-sectional survey, through standardised self-completed questionnaires, was conducted in the following six centres of Kosovo: Ferizaj, Gjakova, Gjilan, Peja, Prishtina and Prizren. Current asthma symptoms (CAS) and severe current asthma symptoms (sCAS) were defined according to the GAN standards. Environmental questionnaire inquired about gender, exercise, screening time, siblings, truck traffic, use of paracetamol, pet ownership, and smoking habits. Height and weight were also measured. Multivariate logistic regression analyses were performed in each centre along with meta-analyses to summarise the overall effects of each factor in the centres as a whole. Meta-regression of the prevalence rates was calculated using HDI as a moderator. RESULTS: Participation rate was high (80.0-99.9%). Prevalence of CAS ranged from 4.6% to 11.3%, and sCAS from 1.7% to 4.5%. Factors associated with CAS were exercise, computer time, paracetamol use and dog ownership. sCAS was associated with paracetamol use and physical exercise. HDI explained 46% and 80% of prevalence variability of CAS and sCAS between centres, respectively. CONCLUSIONS: Prevalence of CAS and sCAS in Kosovo varies highly between centres. This variability is explained partly by HDI. Individual risk factors are common, with some determined in other studies conducted in other regions.

Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study.

BACKGROUND: Asthma is the most common chronic disease in children globally. The Global Asthma Network (GAN) Phase I study aimed to determine if the worldwide burden of asthma symptoms is changing. METHODS: This updated cross-sectional study used the same methods as the International study of Asthma and Allergies in Childhood (ISAAC) Phase III. Asthma symptoms were assessed from centres that completed GAN Phase I and ISAAC Phase I (1993-95), ISAAC Phase III (2001-03), or both. We included individuals from two age groups (children aged 6-7 years and adolescents aged 13-14 years) who self-completed written questionnaires at school. We estimated the 10-year rate of change in prevalence of current wheeze, severe asthma symptoms, ever having asthma, exercise wheeze, and night cough (defined by core questions in the questionnaire) for each centre, and we estimated trends across world regions and income levels using mixed-effects linear regression models with region and country income level as confounders. FINDINGS: Overall, 119 795 participants from 27 centres in 14 countries were included: 74 361 adolescents (response rate 90%) and 45 434 children (response rate 79%). About one in ten individuals of both age groups had wheeze in the preceding year, of whom almost half had severe symptoms. Most centres showed a change in prevalence of 2 SE or more between ISAAC Phase III to GAN Phase I. Over the 27-year period (1993-2020), adolescents showed a significant decrease in percentage point prevalence per decade in severe asthma symptoms (-0·37, 95% CI -0·69 to -0·04) and an increase in ever having asthma (1·25, 0·67 to 1·83) and night cough (4·25, 3·06 to 5·44), which was also found in children (3·21, 1·80 to 4·62). The prevalence of current wheeze decreased in low-income countries (-1·37, -2·47 to -0·27], in children and -1·67, -2·70 to -0·64, in adolescents) and increased in lower-middle-income countries (1·99, 0·33 to 3·66, in children and 1·69, 0·13 to 3·25, in adolescents), but it was stable in upper-middle-income and high-income countries. INTERPRETATION: Trends in prevalence and severity of asthma symptoms over the past three decades varied by age group, country income, region, and centre. The high worldwide burden of severe asthma symptoms would be mitigated by enabling access to effective therapies for asthma. FUNDING: International Union Against Tuberculosis and Lung Disease, Boehringer Ingelheim New Zealand, AstraZeneca Educational Grant, National Institute for Health Research, UK Medical Research Council, European Research Council, and Instituto de Salud Carlos III.

Improving lung health in low-income and middle-income countries: from challenges to solutions.

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.

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.

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.

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.

Infection with SARS-CoV-2 among children with asthma: evidence from Global Asthma Network.

BACKGROUND: Clinical presentations of coronavirus disease 2019 (COVID-19) among children with asthma have rarely been investigated. This study aimed to assess clinical manifestations and outcome of COVID-19 among children with asthma, and whether the use of asthma medications was associated with outcomes of interest. METHODS: The Global Asthma Network (GAN) conducted a global survey among GAN centers. Data collection was between November 2020 and April 2021. RESULTS: Fourteen GAN centers from 10 countries provided data on 169 children with asthma infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was asymptomatic in 58 (34.3%), mild in 93 (55.0%), moderate in 14 (8.3%), and severe/critical in 4 (2.4%). Thirty-eight (22.5%) patients had exacerbation of asthma and 21 (12.4%) were hospitalized for a median of 7 days (interquartile range 3-16). Those who had moderate or more severe COVID-19 were significantly more likely to have exacerbation of asthma as compared to those who were asymptomatic or had mild COVID-19 (adjusted odds ratio (adjOR) 3.97, 95% CI 1.23-12.84). Those who used inhaled bronchodilators were significantly more likely to have a change of asthma medications (adjOR 2.39, 95% CI 1.02-5.63) compared to those who did not. Children who used inhaled corticosteroids (ICS) did not differ from those who did not use ICS with regard to being symptomatic, severity of COVID-19, asthma exacerbation, and hospitalization. CONCLUSIONS: Over dependence on inhaled bronchodilator may be inappropriate. Use of ICS may be safe and should be continued in children with asthma during the pandemic of COVID-19.

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.

Use of inhaled corticosteroids on an intermittent or as-needed basis in pediatric asthma: a systematic review of the literature.

OBJECTIVE: To summarize the principal findings of all available studies that have evaluated the use of inhaled corticosteroids (ICS) on an intermittent or as-needed basis as an add-on therapy to short-acting ß2-agonists (SABAs) or fast-acting ß2-agonists (FABAs) in pediatric asthmatic patients. Studies could either include or omit the use of ICS during stable periods of the disease. DATA SOURCES: Electronic databases MEDLINE, EMBASE, CINAHL, SCOPUS, and the Cochrane Database of Systematic Reviews from inception to February 2021. STUDY SELECTIONS: Relevant articles in the literature published by February 2021. RESULTS: Of 294 references identified, 14 studies were included. The use of ICS on an intermittent or as-needed basis (as an add-on therapy to SABAs) has been shown to be more effective than treatment with SABA alone and to be similarly or less effective compared to regular daily ICS administration. Furthermore, strategies involving increasing the dose of ICS only when needed (as an add-on therapy to formoterol, a FABA) and keeping it low during stable stages of the disease (i.e. single maintenance and reliever therapy, SMART) have been shown to be similarly or more effective than comparators. CONCLUSION: The use of ICS on an intermittent or as-needed basis as an add-on therapy to SABAs or FABAs, with or without ICS use during stable periods of the disease in pediatric asthmatic patients, encompasses several effective treatment strategies.

Parental education moderates the association between indoor moisture environment and asthma in adolescents: the Greek Global Asthma Network (GAN) cross-sectional study.

OBJECTIVE: Asthma is a major contributor to childhood morbidity. Several environmental and socioeconomic status (SES) factors have been implicated in its etiopathogeneses such as indoor moisture and parental education level. Our study examined the association between exposure to indoor dampness and/or mould (IDM) with adolescent asthma and how parental education could modify or mediate this relationship. METHOD: A total of 1934 adolescents (boys: 47.5%, mean age (standard variation): 12.7(0.6) years) and their parents were voluntarily enrolled and completed a validated questionnaire on adolescents' asthma status, parental educational level, and adolescents' indoor exposure to IDM during three different lifetime periods, i.e., pregnancy, the first year of life and the current time. RESULTS: There was a significant modification effect of parental education only for the current exposure; higher parental education lowered almost 50% the odds of IDM and asthma (adjusted odds ratio (aOR): 1.96, 95% Confidence Intervals (CI): (1.05-3.68) and aOR:1.55, 95% CI (1.04-2.32), for primary/secondary and tertiary parental education, respectively). CONCLUSION: Adolescents whose parents had a higher education level had lesser odds to have asthma, even if they were exposed to a moisture home environment. This could be attributed to the increased knowledge about asthma risk factors and the improved measures for the amelioration of moisture-home environment that highly educated parents are more likely to take. Further research is needed in order to elucidate the interweaved role of family SES in the aforementioned relation.

Hierarchical analysis of Mediterranean Dietary pattern on atopic diseases' prevalence in adolescence: The Greek Global Asthma Network study.

INTRODUCTION: The contribution of dietary patterns in the occurrence of atopic diseases, mainly asthma, allergic rhinits, and eczema is ambiguous. Our study examined the association between the level of adherence to the Mediterranean diet (MedDiet) and the prevalence of atopic diseases in adolescence. METHODS: A total of 1934 adolescents (boys: 47.5%, mean age [standard variation]: 12.7[0.6] years) enrolled voluntarily. Participants completed a validated questionnaire on atopic disease status, dietary habits, and other sociodemographic and lifestyle characteristics. KIDMED score was used for the evaluation of adherence to the MedDiet. Discriminant analysis was applied to the hierarchy of foods and beverages consumed in relation to the presence of atopic diseases. RESULTS: Logistic regression analyses revealed that adolescents with moderate and good adherence to the MedDiet had 34 and 60% lower odds of having any asthma symptoms, respectively, and 20 and 41% lower odds of having any allergic rhinitis symptoms, respectively, adjusted for several confounders. The food group with the most important contribution to the MedDiet was cooked and raw vegetables, followed by fruits (Wilk's λ = 0.881 and λ = 0.957, respectively). CONCLUSION: Our study provided evidence for a strong and inverse association between the level of adherence to the MedDiet and the occurrence of asthma and allergic rhinitis symptoms and signified the importance of contribution of fruits and vegetable consumption in this association. Thus, the promotion of MedDiet could be an efficient lifestyle intervention that can contribute to the reduction of the burden of these atopic diseases in adolescents.

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort.

BACKGROUND: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. METHODS: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. RESULTS: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. CONCLUSION: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.

Air pollution from traffic during pregnancy impairs newborn's cord blood immune cells: The NELA cohort.

BACKGROUND: Hazards of traffic-related air pollution (TRAP) on the developing immune system are poorly understood. We sought to investigate the effects of prenatal exposure to TRAP on cord blood immune cell distributions; and to identify gestational windows of susceptibility. METHODS: In-depth immunophenotyping of cord blood leukocyte and lymphocyte subsets was performed by flow cytometry in 190 newborns embedded in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). 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) were estimated using dispersion/chemical transport modelling. Associations between TRAP concentrations and cord blood immune cell counts were assessed using multivariate Poisson regression models. RESULTS: Mean number of natural killer (NK) cells decreased 15% in relation to higher NO2 concentrations (≥36.4 µg/m3) during whole pregnancy (incidence relative risk (IRR), 0.85; 95% CI, 0.72, 0.99), with stronger associations in the first trimester. Higher PM2.5 concentrations (≥13.3 µg/m3) during whole pregnancy associated with a reduced mean number of cytotoxic T cells (IRR, 0.88; 95% CI, 0.78, 0.99). Newborns exposed to higher PM10 (≥23.6 µg/m3) and PM2.5 concentrations during the first and third trimester showed greater mean number of helper T type 1 (Th1) cells (P < 0.05). Decreased number of regulatory T (Treg) cells was associated with greater short-term NO2 (IRR, 0.90; 95% CI, 0.80, 1.01) and PM10 (IRR, 0.88; 95% CI, 0.77, 0.99) concentrations. CONCLUSIONS: Prenatal exposure to TRAP, particularly in early and late gestation, impairs fetal immune system development through disturbances in cord blood leukocyte and lymphocyte distributions.