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.

Intravenous magnesium sulfate for asthma exacerbations in children: Systematic review with meta-analysis.

BACKGROUND: Asthma is the most prevalent chronic disease in children and constitutes a significant healthcare burden. First-line therapy for acute asthma exacerbations is well established. However, secondary treatments, including intravenous magnesium sulfate (IV-MgSO4), remain variable due to scarcity of data on its efficacy and safety. OBJECTIVE: To assess the effectiveness and safety of IV-MgSO4 as a second line of treatment in managing children with asthma exacerbations. METHODS: We searched five databases from inception until April 2023 on randomized clinical trials of IV-MgSO4 in children with acute asthma exacerbations. The primary outcomes were hospitalization rate and length, and change in the severity score. Secondary outcomes included percentage increase in peak expiratory flow rate (PEFR), hospital re-admission rate, need and length for pediatric intensive care unit (PICU) treatment, and adverse effects. Meta-analysis was performed for three outcomes with estimated odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs). RESULTS: Eleven studies met the final criteria. In comparison to control, administration of IV-MgSO4 was associated with a reduced hospitalization risk (OR 0.15; 95%CI: 0.03, 0.73) in four studies, and improvement of lung function (MD 26.77% PEFR; 95%CI: 18.41, 54.79) in two studies. There were no significant differences in the length of stay between groups. Due to heterogeneity, a narrative synthesis of other outcomes was performed. CONCLUSION: The use of IV-MgSO4 demonstrated a reduction in the hospitalization rate and PEFR improvement in children with asthma exacerbations. Adverse effects were rare. Further well-designed studies are needed to better determine the efficacy and safety profile of IV-MgSO4.

Association of respiratory virus types with clinical features in bronchiolitis: Implications for virus testing strategies. A systematic review and meta-analysis.

BACKGROUND: Bronchiolitis is a leading cause of infant hospitalization, linked to respiratory syncytial virus (RSV) and rhinovirus (RV). Guidelines lack specific viral testing for bronchiolitis management. To establish effective management strategies, it is crucial to assess whether specific respiratory virus types are correlated with distinct examination features. METHODS: Through a systematic search of three databases, 21 studies were qualitatively analyzed, with 18 used for meta-analysis. Various outcomes like wheezing on auscultation, fever, atopic traits, and infection severity were evaluated. RESULTS: RSV-positive bronchiolitis was associated with a higher need for oxygen supplementation (OR 1.78, 95% CI 1.04-3.02) in 5 studies, while RV-positive bronchiolitis was more frequently linked to personal history of eczema (OR 0.60, 95% CI 0.41-0.88) in 6 studies. No significant differences were observed in the other outcomes examined. CONCLUSIONS: Bronchiolitis caused by RSV or RV presents with similar clinical features. Despite the associations between RSV-positive bronchiolitis and need for oxygen supplementation, and RV-positive bronchiolitis and a history of eczema, our study shows that viral etiology of bronchiolitis cannot be determined solely based on clinical presentation. Tailored management strategies, informed by accurate viral testing, seem crucial in clinical practice for enhancing patient outcomes in severe bronchiolitis.

Reactance inversion in moderate to severe persistent asthma: low birth weight, prematurity effect, and bronchodilator response.

INTRODUCTION: Reactance inversion (RI) has been associated with impaired peripheral airway function in persistent asthma. However, there is little to no data about the difference between asthmatic children with and without RI. This study aimed to detect clinical and lung function differences in moderate-severe asthmatic children with and without RI. METHODS: This study was conducted between 2021 and 2022 in asthmatic school-age children. Impulse oscillometry (IOS) and spirometry were performed according to ATS/ERS standards. RESULTS: A total of 62 patients, with a mean age of 8.4 years, 54.8% were males and were divided into three groups: group 1 (32.3%) with no RI, group 2 (27.4%) with RI but disappearing after bronchodilator test and group 3 (40.3%) with persistent RI after bronchodilator test. Children in groups 2 and 3 had significantly lower birth weights than in group 1. Group 2 had lower gestational age compared to group 1. FEV1 and FEF25-75 of forced vital capacity were significantly lower in groups 2 and 3. In group 3, R5, AX, R5-20, and R5-R20/R5 ratios were significantly higher. Bronchodilator responses (BDR) in X5c, AX, and R5-R20 were significantly different between groups and lower in group 3. CONCLUSION: RI is frequently found in children with moderate-severe persistent asthma, particularly in those with a history of prematurity or low birth weight. In some patients, RI disappears after the bronchodilator test; however, it, persists in those with the worst pulmonary function. RI could be a small airway dysfunction marker.

The role of respiratory syncytial virus- and rhinovirus-induced bronchiolitis in recurrent wheeze and asthma-A systematic review and meta-analysis.

INTRODUCTION: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis. RSV-induced bronchiolitis has been associated with preschool wheeze and asthma in cohort studies where the comparison groups consist of healthy infants. However, recent studies identify rhinovirus (RV)-induced bronchiolitis as a potentially stronger risk factor for recurrent wheeze and asthma. AIM: This systematic review and meta-analysis aimed to compare the associations of RSV- and RV-induced bronchiolitis with the development of preschool wheeze and childhood asthma. METHODS: We performed a systematic search of the published literature in five databases by using a MeSH term-based algorithm. Cohort studies that enrolled infants with bronchiolitis were included. The primary outcomes were recurrent wheeze and asthma diagnosis. Wald risk ratios and odds ratios (ORs) were estimated, along with their 95% confidence intervals (CIs). Individual and summary ORs were visualized with forest plots. RESULTS: There were 38 studies included in the meta-analysis. Meta-analysis of eight studies that had data on the association between infant bronchiolitis and recurrent wheeze showed that the RV-bronchiolitis group were more likely to develop recurrent wheeze than the RSV-bronchiolitis group (OR 4.11; 95% CI 2.24-7.56). Similarly, meta-analysis of the nine studies that had data on asthma development showed that the RV-bronchiolitis group were more likely to develop asthma (OR 2.72; 95% CI 1.48-4.99). CONCLUSION: This is the first meta-analysis that directly compares between-virus differences in the magnitude of virus-recurrent wheeze and virus-childhood asthma outcomes. RV-induced bronchiolitis was more strongly associated with the risk of developing wheeze and childhood asthma.

The wheezy infant: A viewpoint from low-middle income countries.

OBJECTIVE: To review the recent evidence in the literature of various aspects of recurrent/severe wheezing in children under 3 in low-middle income countries [LMICS]. SOURCES: A non-systematic review including articles in English. We mainly selected publications from the last 5 years. Studies on epidemiology, aetiology, diagnosis, treatment, and prevention were included in the search. We reviewed differential diagnoses of wheezing that focused on LMICS. We also reviewed aspects of prevention. SUMMARY OF THE FINDINGS: Many epidemiological studies have shown a variable but significant number of wheezy infants [WI] cases in LMICS when compared to other countries. The differential diagnosis of causes of wheezing in this age group is mandatory, taking into account local facilities. Few treatment options have been well studied for this age group. In LMICS, a pragmatic approach could be considered, as described in the article. It is difficult to study primary prevention for WI and secondary prevention (mainly environmental) may have some impact. A schematic approach for recurrent wheezers is presented, which takes into account settings with limited resources. CONCLUSION: Severely or recurrently wheezy children under 3 is a common clinical issue in LMICS. Studies on this age group are needed to reduce the significant morbidity. It may be possible to lower the high burden of wheezing in this age group by selecting the phenotype which may respond to inhaled steroids.

"Reactance inversion" at low frequencies during lung function measurement by impulse oscillometry in children with persistent asthma.

BACKGROUND: Small airway dysfunction (SAD) in asthma can be measured by impulse oscillometry (IOS). Usually, the reactance should decrease with decreases in frequency oscillation. Sometimes an upward shift of the curve at low frequencies can be observed together with lower than expected reactance values. The actual value of the reactance at 5 Hz (X5) is calculated by the Sentry Suite application of the Jaeger Master screen iOS system™, providing the corrected X5 parameter (CX5). Our hypothesis is that correction of X5 is common in persistent asthma and it correlates better than X5 with the IOS parameters for evaluating SAD. METHODS: In this transversal study, we evaluated 507 children (3-18 years old) using IOS-spirometry (Sentry Suite, Vyntus®). Resistance of all airways (R5), reactance area (AX), resonant frequency (Fres), X5, CX5, difference between R5 and R20 (D5-20), and spirometry parameters were analyzed. Reactance inversion and CX5 prevalence by age range was determined. The mean IOS-Spyrometry values in children with and without CX5 were compared, and correlations with each IOS-spirometry parameter in the age groups were performed. RESULTS: CX5 was found in 83.5% of preschool children, 66.2% of schoolchildren, and 43.3% of adolescents (p < 0.001). The means of R5, AX, and D5-20 were significantly higher and FEV1 was significantly lower in children with CX5 (p < 0.05). In all ages, CX5 correlated better than X5 with IOS-spirometry parameters. CONCLUSION: Reactance inversion and CX5 are frequent in asthmatic children, decrease with age, and correlate more closely than X5 with other IOS-spirometry parameters for evaluating SAD.

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.

A cluster randomized trial of interferon ß-1a for the reduction of transmission of SARS-Cov-2: protocol for the Containing Coronavirus Disease 19 trial (ConCorD-19).

BACKGROUND: SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19). Herein we provide a protocol for a cluster randomized trial that will examine the effectiveness of treatment with interferon (IFN) ß-1a compared to standard of care in limiting the transmission of SARS-CoV-2. Co-primary objectives are to determine whether IFN therapy reduces (a) the proportion of infected cases shedding SARS-CoV-2 at day 11 post randomization and (b) the incidence of transmission of SARS-CoV-2 infection from index cases to treatment-eligible household post-exposure contacts at day 11 after randomization. Secondary objectives include assessing the impact of IFN treatment on duration of viral clearance, hospitalizations and fatalities, and evaluating the safety of IFN treatment. METHODS: Three hundred and ten households, each including an index case with a recent COVID-19 diagnosis and at least one asymptomatic treatment-eligible household contact, will be randomized to receive 3 doses of 125 µg IFN ß-1a by subcutaneous administration (days 1, 6, and 11), or standard of care. All participants will be followed until day 29. DISCUSSION: The results from this trial will identify whether IFN ß treatment of mild or moderate COVID-19 cases accelerates viral clearance and prevents disease progression and whether IFN ß treatment of post-exposure contacts of COVID-19 cases reduces transmission of infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov NCT04552379; date of registration September 17, 2020.

Maternal Obesity Is Associated With Higher Cord Blood Adipokines in Offspring Most Notably in Females.

BACKGROUND: Deleterious long-term effects in the offspring from women with pregravid obesity have been described; however, the evidence supporting early metabolic and inflammatory markers in the offspring at birth and gender differences are conflicting. OBJECTIVE: The present study aimed to compare cord blood adipokines and cytokines concentrations and anthropometric characteristics of the offspring of women with maternal obesity (MO) and normal-weight mothers (NWM). Also, maternal and neonatal variables on the association of maternal body mass index (BMI) with cord blood adipokines were evaluated. METHODS: A cross-sectional analysis of a subsample of mother-child dyads participating in a cohort study (n = 221) was assessed. Anthropometrics, cord blood adipokines (leptin and adiponectin) and cytokines (interleukin [IL]-1ß, IL-4, IL-10, IL-12 p40, IL-12p70, IL-13, and tumor necrosis factor α) concentrations in the offspring of normal-weight women (BMI >18.5 and <24.9 kg/m2) and women with pregravid obesity (BMI > 30 kg/m2) without comorbidities was performed. RESULTS: Offspring from mothers with obesity had higher birth weight, a higher proportion of large for gestational age, higher ponderal index, and heavier placentae than offspring from normal-weight mothers (P < 0.05). Within the offspring from women with obesity, males had significantly higher weight, length, the proportion of large-for-gestational-age newborns, higher weight for length ratio. Males had more efficient placentas than females (P < 0.05). Higher adiponectin and leptin in both sexes and higher leptin in female offspring of mothers with obesity after adjusting for birth size (P < 0.05) were found. Higher IL-12p40 in the offspring of women with MO with no other differences in other cytokines among groups were evidenced. CONCLUSIONS: Maternal obesity associates with a higher concentration of adiponectin and leptin in their offspring at birth. There is a relevant effect on anthropometrics in male offspring and on leptin in female newborn. Further studies need to evaluate the extension of these effects in postnatal life. TRAIL IDENTIFICATION NUMBER: NCT02903134.

For which infants with viral bronchiolitis could it be deemed appropriate to use albuterol, at least on a therapeutic trial basis?

Although there is increasing evidence showing that infants with viral bronchiolitis exhibit a high degree of heterogeneity, a core uncertainty shared by many clinicians is with regard to understanding which patients are most likely to benefit from bronchodilators such as albuterol. Based on our review, we concluded that older infants with rhinovirus (RV) bronchiolitis, especially those with a nasopharyngeal microbiome dominated by Haemophilus influenzae; those affected during nonpeak months or during non-respiratory syncytial virus (RSV) predominant months; those with wheezing at presentation; those with clinical characteristics such as atopic dermatitis or a family history of asthma in a first-degree relative; and those infants infected with RSV genotypes ON1 and BA, have the greatest likelihood of benefiting from albuterol. Presently, this patient profile could serve as the basis for rational albuterol administration in patients with viral bronchiolitis, at least on a therapeutic trial basis, and it could also be the starting point for future targeted randomized clinical trials (RCTs) on the use of albuterol among a subset of infants with bronchiolitis.

Challenges of COVID-19 in children in low- and middle-income countries.

As the coronavirus pandemic extends to low and middle income countries (LMICs), there are growing concerns about the risk of coronavirus disease (COVID-19) in populations with high prevalence of comorbidities, the impact on health and economies more broadly and the capacity of existing health systems to manage the additional burden of COVID-19. The direct effects of COVID are less of a concern in children, who seem to be largely asymptomatic or to develop mild illness as occurs in high income countries; however children in LMICs constitute a high proportion of the population and may have a high prevalence of risk factors for severe lower respiratory infection such as HIV or malnutrition. Further diversion of resources from child health to address the pandemic among adults may further impact on care for children. Poor living conditions in LMICs including lack of sanitation, running water and overcrowding may facilitate transmission of SARS-CoV-2. The indirect effects of the pandemic on child health are of considerable concern, including increasing poverty levels, disrupted schooling, lack of access to school feeding schemes, reduced access to health facilities and interruptions in vaccination and other child health programs. Further challenges in LMICs include the inability to implement effective public health measures such as social distancing, hand hygiene, timely identification of infected people with self-isolation and universal use of masks. Lack of adequate personal protective equipment, especially N95 masks is a key concern for health care worker protection. While continued schooling is crucial for children in LMICs, provision of safe environments is especially challenging in overcrowded resource constrained schools. The current crisis is a harsh reminder of the global inequity in health in LMICs. The pandemic highlights key challenges to the provision of health in LMICs, but also provides opportunities to strengthen child health broadly in such settings.

The impact of viral bronchiolitis phenotyping: Is it time to consider phenotype-specific responses to individualize pharmacological management?

Although recent guidelines recommend a minimalist approach to bronchiolitis, there are several issues with this posture. First, there are concerns about the definition of the disease, the quality of the guidelines, the method of administration of bronchodilators, and the availability of tools to evaluate the response to therapies. Second, for decades it has been assumed that all cases of viral bronchiolitis are the same, but recent evidence has shown that this is not the case. Distinct bronchiolitis phenotypes have been described, with heterogeneity in clinical presentation, molecular immune signatures and clinically relevant outcomes such as respiratory failure and recurrent wheezing. New research is critically needed to refine viral bronchiolitis phenotyping at the molecular and clinical levels as well as to define phenotype-specific responses to different therapeutic options.

Advantage of inhaled corticosteroids as additional therapy to systemic corticosteroids for pediatric acute asthma exacerbations: a cost-effectiveness analysis.

Objective: Although the efficacy of systemic corticosteroids (SCs) in acute asthma exacerbations is well established, the fact that many children still require admission to hospital and that SCs have a slow onset of action are cause of concern. For this reason, the use of inhaled corticosteroids (ICS) as a therapy added to SCs has been explored, with no clarity about its cost-effectiveness. The aim of the present study was to evaluate the cost-effectiveness of ICS in addition to SCs (ICS + SCs) compared to standard therapy with SCs for treating pediatric asthma exacerbations.Methods: A decision-analysis model was developed to estimate the cost-effectiveness of SCs compared to ICS + SCs for treating pediatric patients with acute asthma exacerbations. Effectiveness parameters were obtained from a systematic review of the literature. Cost data obtained from hospital bills and from the national manual of drug prices. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome of the model was avoidance of hospital admission.Results: For the base-case analysis, the model showed that compared to SCs, therapy with ICS + SCs was associated with lower total costs (US$88.76 vs.US$97.71 average cost per patient) and a lower probability of hospital admission (0.9060 vs. 0.9000), thus showing dominance.Conclusions: This study shows that compared with standard therapy with SCs, ICS + SCs for treating pediatric patients with acute asthma exacerbations is the preferred strategy because it was associated with a lower probability of hospital admission, at lower total treatment costs.

Preschoolers with recurrent wheezing have a high prevalence of sleep disordered breathing.

Objective: Sleep-disordered breathing (SDB) is highly prevalent in school children with poorly-controlled asthma. However, this association has not been assessed in preschoolers with recurrent wheeze, nor in those at risk for asthma. We hypothesized that preschoolers with asthma risk (positive asthma predictive index [API]) have a higher prevalence of SDB and higher inflammatory biomarkers (blood-hsCRP and urinary-LTE4) levels than those with negative API.Method: Children 2 to 5 years of age with recurrent wheezing were classified as positive or negative API. SDB was determined by the pediatric sleep questionnaire (PSQ) and its subscale (PSQSub6). Demographic characteristics, spirometry, blood hsCRP and urinary LTE4 were assessed.Results: We enrolled 101 preschoolers: 70 completed all measurements, 55.4% were males, mean age 4.07 ± 0.87 years, 45% overweight or obese, 70% had positive API, 87.5% had rhinitis. The prevalence of SDB measured by PSQ was 40.8% and by PSQSub6 was 29.6%. However, the proportion of SDB was similar between positive and negative API groups. The hsCRP (mean ± SD) was higher in the positive than in negative API (3.58 ± 0.58 and 1.32 ± 0.36 mg/L, p = 0.69, respectively); moreover, no differences in urinary LTE4 were found between groups. No correlation of PSQ (+) or PSQSub6 (+) with hsCRP and uLTE4 was found. However, preschoolers with positive API had significantly more post-bronchodilator percentage change in FEF25-75 than negative API (24.14 ± 28.1 vs. 4.13 ± 21.8, respectively, p = 0.01).Conclusions: In preschoolers with recurrent wheezing, we should be investigating for the coexistence of SDB, using early screening methods for detecting those conditions.

Early origins of allergy and asthma (ARIES): study protocol for a prospective prenatal birth cohort in Chile.

BACKGROUND: Growing evidence shows that atopic dermatitis (AD), food allergy (FA), allergic rhinitis, and asthma are largely determined during the first 1000 days (time elapsed from conception to the 2nd birthday). The ARIES birth cohort aims to determine prenatal and perinatal conditions, as well as genetic and epigenetic factors, that participate in the early setting of immune responses, and the role of these in the later determination of the risk of allergic diseases and asthma in the offspring. METHODS: We have designed a birth cohort of 250 families with prenatal recruitment (~ 14 weeks). We will genotype relevant allergy/asthma-associated variants in trios and will perform immunophenotyping and evaluation of allergy biomarkers in cord blood. At 1 and 2 years of age we will assess if infants have developed allergic sensitization, AD, FA, as well as biomarkers of asthma including the asthma predictive index. We will also evaluate how maternal conditions modify immune programming through epigenetic modifications and will then depict newborn epigenetic cues of allergy/asthma risk. Next, we will assess composition/diversity of maternal gut, placenta, breastmilk and infant gut microbiome and their association with immunophenotype and biomarkers at birth, and clinical outcomes at age 1 and 2. Finally, we plan to assess how environmental exposures (perinatal outdoor and indoor pollution, allergens and endotoxin) affect the incidence of allergic sensitization, AD, FA, and risk of asthma. DISCUSSION: The in-depth study of the ARIES birth cohort shall provide crucial information to understand the rising incidence of allergies and asthma in developing countries, and hopefully provide cues on how to prevent and treat these diseases. TRIAL REGISTRATION: clinicaltrials.gov NCT04186949, retrospectively registered on December 5, 2019.

A cost-effectiveness threshold analysis of a multidisciplinary structured educational intervention in pediatric asthma.

OBJECTIVE: Asthma educational interventions have been shown to improve several clinically and economically important outcomes. However, these interventions are costly in themselves and could lead to even higher disease costs. A cost-effectiveness threshold analysis would be helpful in determining the threshold value of the cost of educational interventions, leading to these interventions being cost-effective. The aim of the present study was to perform a cost-effectiveness threshold analysis to determine the level at which the cost of a pediatric asthma educational intervention would be cost-effective and cost-saving. METHODS: A Markov-type model was developed in order to estimate costs and health outcomes of a simulated cohort of pediatric patients with persistent asthma treated over a 12-month period. Effectiveness parameters were obtained from a single uncontrolled before-and-after study performed with Colombian asthmatic children. Cost data were obtained from official databases provided by the Colombian Ministry of Health. The main outcome was the variable "quality-adjusted life-years" (QALYs). RESULTS: A deterministic threshold sensitivity analysis showed that the asthma educational intervention will be cost-saving to the health system if its cost is under US$513.20. Additionally, the analysis showed that the cost of the intervention would have to be below US$967.40 in order to be cost-effective. CONCLUSIONS: This study identified the level at which the cost of a pediatric asthma educational intervention will be cost-effective and cost-saving for the health system in Colombia. Our findings could be a useful aid for decision makers in efficiently allocating limited resources when planning asthma educational interventions for pediatric patients.

Differences between preschoolers with asthma and allergies in urban and rural environments.

OBJECTIVE: Previous studies have provided conflicting results about how living in a rural or urban environment influences schoolchildren with asthma and allergic diseases in different ways. The aim of the present study was to evaluate if recurrent wheezing preschoolers from rural or urban areas differ in asthma, allergic diseases, and atopy. METHODS: A cross-sectional-study in Rafaela, Argentina, on 143 preschoolers with recurrent wheezing from rural and urban settings was performed (2010-2012). Diagnosis of asthma (by positive asthma predictive index [API]), allergic diseases (rhinitis, dermatitis), and atopy (by skin prick test [SPT], peripheral blood eosinophils, and serum total IgE) were assessed. RESULTS: Preschoolers from rural settings had significantly higher prevalence of vaginal delivery, longer breastfeeding, earlier onset of wheezing, more parental smoking, siblings, shared a bedroom, and more exposure to chemicals used in plant fumigation or farm animals, and unpasteurized milk consumption, in comparison to preschoolers living in urban setting. In contrast, preschoolers from urban areas had significantly higher prevalence of parental history of allergy, positive skin prick test, and positive API. After multivariate analysis adjusting for covariates, maternal smoking [odds ratio (OR) = 3.44] and positive SPT (OR = 5.57) significantly increase the risk of asthma diagnosis (positive API); in contrast, living in rural setting (OR = 0.04), and having more siblings (OR = 0.51) decrease their risk. CONCLUSIONS: Recurrent wheezing preschoolers from rural areas had a significant inverse odds of being diagnosed with asthma (type-2 inflammation) when compared to those from urban areas. Exposure to farm animals and consumption of unpasteurized milk might have a role.

Automated chart review utilizing natural language processing algorithm for asthma predictive index.

BACKGROUND: Thus far, no algorithms have been developed to automatically extract patients who meet Asthma Predictive Index (API) criteria from the Electronic health records (EHR) yet. Our objective is to develop and validate a natural language processing (NLP) algorithm to identify patients that meet API criteria. METHODS: This is a cross-sectional study nested in a birth cohort study in Olmsted County, MN. Asthma status ascertained by manual chart review based on API criteria served as gold standard. NLP-API was developed on a training cohort (n = 87) and validated on a test cohort (n = 427). Criterion validity was measured by sensitivity, specificity, positive predictive value and negative predictive value of the NLP algorithm against manual chart review for asthma status. Construct validity was determined by associations of asthma status defined by NLP-API with known risk factors for asthma. RESULTS: Among the eligible 427 subjects of the test cohort, 48% were males and 74% were White. Median age was 5.3 years (interquartile range 3.6-6.8). 35 (8%) had a history of asthma by NLP-API vs. 36 (8%) by abstractor with 31 by both approaches. NLP-API predicted asthma status with sensitivity 86%, specificity 98%, positive predictive value 88%, negative predictive value 98%. Asthma status by both NLP and manual chart review were significantly associated with the known asthma risk factors, such as history of allergic rhinitis, eczema, family history of asthma, and maternal history of smoking during pregnancy (p value < 0.05). Maternal smoking [odds ratio: 4.4, 95% confidence interval 1.8-10.7] was associated with asthma status determined by NLP-API and abstractor, and the effect sizes were similar between the reviews with 4.4 vs 4.2 respectively. CONCLUSION: NLP-API was able to ascertain asthma status in children mining from EHR and has a potential to enhance asthma care and research through population management and large-scale studies when identifying children who meet API criteria.

IL-10 expression in macrophages from neonates born from obese mothers is suppressed by IL-4 and LPS/INFγ.

Obese women offspring have a higher risk of developing chronic diseases associated with an altered immune function. We aim to determine, in neonatal monocyte-derived macrophages, whether maternal obesity is associated with an altered expression and DNA methylation of pro- and anti-inflammatory genes, along with a higher pro-inflammatory response. Cord blood from newborns of obese (Ob) and lean (control) women were obtained at delivery. Monocytes were isolated and differentiated into macrophages, in which M1 (LPS/IFNγ) and M2 (IL-4) polarization were assayed. The mRNA levels for TNFα, IL-1ß, IL-12A, IL-12B, IL-10, and IL-4R were quantified by qPCR and the DNA methylation of candidate genes determined by pyrosequencing. RESULTS: Ob-monocytes had decreased levels of mRNA for pro-inflammatory cytokines IL-1ß, IL-10, and IL-12B compared with controls. Conversely, Ob-macrophages showed increased levels of mRNA for TNFα, IL-4R, and IL-10 compared with controls. M1 response was comparable between both groups, characterized by an important induction of TNFα and IL-1ß. In response to an M2 stimulus, control macrophages showed a decreased expression of inflammatory mediators while Ob-macrophages had an additional suppression of the anti-inflammatory mediator IL-10. Changes in IL-1ß (monocytes) and IL-10 (macrophages) in Ob-monocytes were paralleled by changes in their promoter DNA methylation in fetal monocytes. These results suggest that monocyte-derived macrophages from obese newborns show a basal anti-inflammatory phenotype with an unbalanced response to M1 and M2 polarization stimuli. The presence of changes in DNA methylation of key inflammatory genes in neonatal monocytes suggests an intrauterine programing of immune function by maternal obesity.