Publications by authors named "Erick Forno"

165 Publications

Urinary caffeine and caffeine metabolites, asthma, and lung function in a nationwide study of U.S. adults.

J Asthma 2021 Oct 13:1-13. Epub 2021 Oct 13.

Pediatrics, University of Pittsburgh, Pittsburgh, United States.

Coffee intake has been inversely associated with asthma in adults. We examined the relation between urinary levels of caffeine or caffeine metabolites and asthma, lung function, and fractional exhaled nitric oxide (FeNO) in adults. Cross-sectional study of 2,832 adults aged 18-79 years in the US National Health and Nutrition Examination Survey (NHANES). Multivariable logistic or linear regression was used for the analysis of urinary levels of caffeine or each of its three major metabolites (paraxanthine, theobromine, and theophylline) and current asthma, lung function, and FeNO. Subjects with urinary paraxanthine levels in the fourth quartile (Q4) had 53% lower odds of current asthma than those whose urinary paraxanthine levels were in the first quartile (Q1; 95% confidence =0.22 to 1.00). Among never and former smokers, subjects with urinary theophylline levels above Q1 had 41% lower odds of current asthma than those whose urinary theophylline level was in Q1 (95% CI =0.38 to 0.91). Among subjects without current asthma, each log-unit increment in paraxanthine level was associated with a 0.83% increment in percent predicted (%pred) FEV and a 1.27% increment in %pred FVC, while each log-unit in theophylline was associated with a 1.24% increment in %pred FVC. Neither urinary caffeine nor any urinary caffeine metabolite was associated with bronchodilator response or FeNO. Our findings suggest that two caffeine metabolites (theophylline and paraxanthine) may contribute to the previously reported inverse association between coffee intake and asthma in adults.
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http://dx.doi.org/10.1080/02770903.2021.1993250DOI Listing
October 2021

Violence-related distress and lung function in two longitudinal studies of youth.

Eur Respir J 2021 Sep 29. Epub 2021 Sep 29.

Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA

Increasing violence-related distress over time was associated with worse lung function and worse asthma-related quality of life in youth with asthma despite treatment with low-dose inhaled corticosteroids.Exposure to violence has been associated with lower lung function in cross-sectional studies. We examined whether increasing violence-related distress over time is associated with worse lung function and worse asthma control or quality of life in a secondary analysis of a 48-week randomized clinical trial in 98 youth with asthma (ages 9-16 years) treated with low-dose inhaled corticosteroids (the Vitamin D Kids Asthma Study [VDKA]). We then replicated our findings for lung function in a prospective study of 232 Puerto Rican youth followed for an average of 5·4 years. Violence-related distress was assessed using the Checklist of Children's Distress Symptoms (CCDS) scale. Our outcomes of interest were percent predicted (%pred) lung function measures and (in VDKA only) asthma control (assessed using the Asthma Control Test) and asthma-related quality of life (assessed using the Pediatric Asthma Quality of Life questionnaire). In a multivariable analysis in VDKA, each 1-point increment in the CCDS score was associated with decrements of 3.27% in %predFEV (95% confidence interval [CI]=-6.44% to -0.22%, p=0.04) and a 2.65% decrement in percent predicted FVC (95% CI=-4.86% to -0.45%, p=0.02), and 0.30 points in the overall PAQLQ score (95% CI=-0.50 to -0.10, p<0.01). Similar findings for FEV and FVC were obtained in the prospective study of Puerto Rican youth. Our findings suggest that violence-related distress may worsen lung function and quality of life in youth with asthma (even those treated with low-dose inhaled corticosteroids) and further support policies to reduce exposure to violence among children in the U.S. and Puerto Rico.
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http://dx.doi.org/10.1183/13993003.02329-2021DOI Listing
September 2021

The Dietary Inflammatory Index and asthma burden in children: A latent class analysis.

Pediatr Allergy Immunol 2021 Sep 16. Epub 2021 Sep 16.

Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.

Introduction: Unbalanced dietary intake has been increasingly recognized as an important modifiable risk factor for asthma. In this study, we assessed whether a pro-inflammatory diet is associated with higher asthma burden in three steps: (1) identification of asthma latent classes (LC) based on symptoms, indoor exposures, and pulmonary function; (2) identification of risk factors associated with LC membership; and (3) estimation of the probabilities of LC membership with variation in DII.

Methods: A cross-sectional study on 415 children aged 5-14 years (266 with persistent asthma and 149 controls). LC analysis was performed in asthmatic children. The DII was calculated based on a semiquantitative food frequency questionnaire. Elastic net logistic regression was used to investigate whether increasing DII was associated with worse asthma burden.

Results: Two LCs were identified. Children in Class 1, "high burden," had higher symptom burden and worse lung function. Children in Class 2, "low burden," had lower symptom burden and less impaired lung function but were more subject to indoor exposures. DII was the only risk factor significantly associated with Class 1 membership. As the DII increased (from -4.0 to +4.0), the probability of Class 1 membership increased from 32% to 65% when compared with control group, whereas it increased from 41% to 72% when compared with Class 2.

Conclusions: We identified two phenotypes of persistent asthma associated with different disease burden linked to indoor exposures. An increasing DII was associated with high-burden asthma, providing further evidence about the role of a pro-inflammatory diet in asthma morbidity.
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http://dx.doi.org/10.1111/pai.13667DOI Listing
September 2021

Circulating humanin is lower in coronary artery disease and is a prognostic biomarker for major cardiac events in humans.

Biochim Biophys Acta Gen Subj 2021 Sep 12:130010. Epub 2021 Sep 12.

The Cardiovascular Center, First Hospital of Jilin University, 71 Xinmin Road, Changchun, Jilin 130021, China. Electronic address:

Background: Humanin is an endogenous mitochondria-derived peptide that plays critical roles in oxidative stress, inflammation and CAD. In this study, we measured the levels of circulating humanin, markers of oxidative stress and inflammation in patients with unstable angina and MI and studied the relationship between these parameters and major adverse cardiac events (MACE).

Methods: A total of 327 subjects were recruited from the inpatient department at First Hospital of Jilin University and divided into 3 groups [control, angina and myocardial infarction (MI)] based on the clinical data and the results of the angiography. Serum humanin and thiobarbituric acid reactive substances (TBARS) were measured at the time of initial admission. The hospitalization data and MACE of all patients were collected.

Results: Circulating humanin levels were lower in the angina group compared to controls [124.22 ± 63.02 vs. 157.77 ± 99.93 pg/ml, p < 0.05] and even lower in MI patients [67.17 ± 24.35 pg/ml, p < 0.05 vs controls] and oxidative stress marker were higher in MI patients compared to the control and angina groups [12.94 ± 4.55 vs. 8.26 ± 1.66 vs. 9.06 ± 2.47 umol/ml, p < 0.05]. Lower circulating humanin levels was an independent risk factor of MI patients. Circulating humanin levels could be used to predict MACE in angina group.

Conclusions: Lower circulating humanin levels was an independent risk factor for CAD, and a potential prognostic marker for mild CAD.

General Significance: Humanin may become a new index for the diagnosis and treatment of CAD.
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http://dx.doi.org/10.1016/j.bbagen.2021.130010DOI Listing
September 2021

Vitamin D supplementation, lung function, and asthma control in children with asthma and low vitamin D levels.

Eur Respir J 2021 Jul 29. Epub 2021 Jul 29.

Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA

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http://dx.doi.org/10.1183/13993003.00989-2021DOI Listing
July 2021

CHIT: an allele-specific method for testing the association between molecular quantitative traits and phenotype-genotype interaction.

Bioinformatics 2021 Jul 29. Epub 2021 Jul 29.

Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.

Motivation: Allele specific differences in molecular traits can be obtained from next generation sequencing data and could potentially improve testing power, but such information is usually overlooked in association studies. Furthermore, the variation of molecular quantitative traits (e.g., gene expression) could result from the interaction effect of genotypes and phenotypes, but it is challenging to identify such interaction signals in complex disease studies in humans due to small genetic effect sizes and/or small sample sizes.

Results: We develop a novel statistical method, the combined haplotype interaction test (CHIT), which tests for association between molecular quantitative traits and phenotype-genotype interactions by modeling the total read counts and allele-specific reads in a target region. CHIT can be used as a supplementary analysis to the regular linear interaction regression. In our simulations, CHIT obtains non-inflated type I error rates, and it has higher power than a standard interaction quantitative trait locus approach based on linear regression models. Finally, we illustrate CHIT by testing associations between gene expression obtained by RNA-seq and the interaction of SNPs and atopy status from a study of childhood asthma in Puerto Ricans, and results demonstrate that CHIT could be more powerful than a standard linear interaction expression quantitative trait loci (eQTL) approach.

Availability: The CHIT algorithm has been implemented in Python. The source code and documentation are available and can be downloaded from https://github.com/QiYanPitt/CHIT.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab554DOI Listing
July 2021

The asthma predictive index as a surrogate diagnostic tool in preschoolers: Analysis of a longitudinal birth cohort.

Pediatr Pulmonol 2021 Oct 28;56(10):3183-3188. Epub 2021 Jul 28.

Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.

Diagnosing asthma in preschool children remains an unsolved challenge, at a time when early identification would allow for better education and treatment to prevent morbidity and lung function deterioration.

Objective: To evaluate if the asthma predictive index (API) can be used as surrogate for asthma diagnosis in preschoolers.

Methods: Birth cohort of 339 pregnant women enrolled at delivery and their offspring, who were followed for atopy, wheezing, and other respiratory illnesses through 30 months of age. The API was determined at 30 months of age by the researchers; and examined its association with physician-diagnosed asthma during the first 30 months, made independently by the primary care physician not involved in the study.

Results: Among 307 offspring with complete follow-up, 44 (14.3%) were API+. Maternal body mass index, maternal education, past oral contraceptive use, birthweight, placenta weight, age of daycare at 12 m, gastroesophageal reflux disease at 12 m, acute otitis media at 18 m, bronchiolitis, croup and pneumonia, cord blood adiponectin were all associated with API+. In the multivariable analysis, API+ was associated with almost sixfold odds of asthma diagnosis (adjusted OR = 5.7, 95% CI [2.6-12.3]), after adjusting for the relevant covariates above including respiratory infections like bronchiolitis and pneumonia. The API sensitivity was 48%, specificity 92%, 61% PPV, 88% NPV, 6.4 LR+, 0.56 LR-, 0.84 diagnosis accuracy. The adjusted odds for asthma was 11.4.

Conclusions: This longitudinal birth cohort suggests, for first time, that API (a structured definition for asthma), could be used as a diagnostic tool, not only as a prognostic tool, in toddlers and preschoolers.
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http://dx.doi.org/10.1002/ppul.25592DOI Listing
October 2021

Predictors of Diffusing Capacity in Children With Sickle Cell Disease: A Longitudinal Study.

Front Pediatr 2021 31;9:678174. Epub 2021 May 31.

Division of Pulmonary Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

Gas exchange abnormalities in Sickle Cell Disease (SCD) may represent cardiopulmonary deterioration. Identifying predictors of these abnormalities in children with SCD (C-SCD) may help us understand disease progression and develop informed management decisions. To identify pulmonary function tests (PFT) estimates and biomarkers of disease severity that are associated with and predict abnormal diffusing capacity (DLCO) in C-SCD. We obtained PFT data from 51 C-SCD (median age:12.4 years, male: female = 29:22) (115 observations) and 22 controls (median age:11.1 years, male: female = 8:14), formulated a rank list of DLCO predictors based on machine learning algorithms (XGBoost) or linear mixed-effect models, and compared estimated DLCO to the measured values. Finally, we evaluated the association between measured or estimated DLCO and clinical outcomes, including SCD crises, pulmonary hypertension, and nocturnal desaturation. Hemoglobin-adjusted DLCO (%) and several PFT indices were diminished in C-SCD compared to controls. Both statistical approaches ranked FVC (%), neutrophils (%), and FEF (%) as the top three predictors of DLCO. XGBoost had superior performance compared to the linear model. Both measured and estimated DLCO demonstrated a significant association with SCD severity: higher DLCO, estimated by XGBoost, was associated with fewer SCD crises [beta = -0.084 (95%CI: -0.13, -0.033)] and lower TRJV [beta = -0.009 (-0.017, -0.001)], but not with nocturnal desaturation ( = 0.12). In this cohort of C-CSD, DLCO was associated with PFT estimates representing restrictive lung disease (FVC, TLC), airflow obstruction (FEF, FEV1/FVC, R5), and inflammation (neutrophilia). We used these indices to estimate DLCO, and show association with disease outcomes, underscoring the prediction models' clinical relevance.
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http://dx.doi.org/10.3389/fped.2021.678174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200630PMC
May 2021

Update in Pediatrics 2020.

Am J Respir Crit Care Med 2021 08;204(3):274-284

Department of Respiratory Medicine, Children's Hospital at Westmead, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1164/rccm.202103-0605UPDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513597PMC
August 2021

Effect of vitamin D supplementation on total and allergen-specific IgE in children with asthma and low vitamin D levels.

J Allergy Clin Immunol 2021 Jun 9. Epub 2021 Jun 9.

Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pa. Electronic address:

Background: Observational studies have yielded inconsistent findings for the relation between vitamin D level and total IgE or allergic sensitization.

Objective: To determine whether vitamin D supplementation reduces levels of total IgE and IgE to each of 2 common indoor allergens in children with asthma and low vitamin D levels.

Methods: Total IgE, IgE to Dermatophagoides pteronyssinus, and IgE to Blattella germanica were measured at the randomization and exit visits for 174 participants in the Vitamin D Kids Asthma Study, a multicenter, double-blind, randomized placebo-controlled trial of vitamin D supplementation (4000 IU/d) to prevent severe exacerbations in children with persistent asthma and vitamin D levels less than 30 ng/mL. Multivariable linear regression was used for the analysis of the effect of vitamin D supplementation on change in each IgE measure.

Results: Participants were followed for an average of 316 days. At the exit visit, more subjects in the vitamin D arm achieved a vitamin D level equal to or more than 30 ng/mL compared with those in the placebo arm (87% vs 30%; P < .001). In a multivariable analysis, vitamin D supplementation had no significant effect on change in total IgE, IgE to Dermatophagoides pteronyssinus, or IgE to Blattella germanica between the exit and randomization visits (eg, for log total IgE, β = 0.007; 95% CI, -0.061 to 0.074; P = .85).

Conclusions: Vitamin D supplementation, compared with placebo, has no significant effect on serum levels of total IgE, IgE to dust mite, or IgE to cockroach in children with asthma and low vitamin D levels.
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http://dx.doi.org/10.1016/j.jaci.2021.05.037DOI Listing
June 2021

Sleep in children with cystic fibrosis: More under the covers.

Pediatr Pulmonol 2021 May 11. Epub 2021 May 11.

Pediatric Pulmonology, Sleep and Cystic Fibrosis Center, Department of Pediatrics, Hadassah Medical Center, Jerusalem, Israel.

Cystic fibrosis (CF) is a chronic multisystem disease with manifestations from birth. It involves the entire respiratory system, with increased cough, and recurrent pulmonary infections, and it also leads to intestinal malabsorption, all of which can have an impact on sleep. In this review, we summarize the available literature on the various sleep disturbances in children with CF. Sleep quality and sleep efficiency are often impaired in children with CF. They may be accompanied by symptoms associated with sleep-disordered breathing (SDB), and objective findings, such as nocturnal hypoxemia. Importantly, a strong association has been shown between SDB and the severity of lung disease, and some studies have reported a similar association for sleep quality. Further research is needed to better characterize the association of sleep disturbances with respiratory outcomes and the impact of treatment of sleep disorders on pulmonary status in children with CF.
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http://dx.doi.org/10.1002/ppul.25462DOI Listing
May 2021

Testosterone-to-estradiol ratio and lung function in a prospective study of Puerto Rican youth.

Ann Allergy Asthma Immunol 2021 08 20;127(2):236-242.e1. Epub 2021 Apr 20.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

Background: Age- and sex-related differences in asthma may be due to changes in sex hormone levels.

Objective: To evaluate whether a change in free testosterone or free testosterone-to-estradiol ratio is associated with changes in lung function and eosinophils in the Puerto Rican youth.

Methods: We tested for the association between the change in sex hormone levels and change in lung function or change in eosinophils in a prospective study of 317 children (with and without asthma) followed up from ages 6 to 14 years to ages 10 to 20 years (146 females, 171 males) in San Juan, Puerto Rico. Serum levels of testosterone, estradiol, sex hormone-binding globulin, and progesterone were measured at 2 study visits, approximately 4.9 years apart. Using testosterone and sex hormone-binding globulin levels, we derived free testosterone and the free testosterone-to-estradiol ratio. Multivariable linear regression was used for the analysis of change in lung function and eosinophils, conducted separately by sex.

Results: In girls, each quartile increment in the free testosterone-to-estradiol ratio was associated with a 2.03% increment in percent predicted forced expiratory volume in 1 second (FEV)/forced vital capacity (FVC) between study visits. In males, each quartile increment in the free testosterone-to-estradiol ratio was associated with a 3.27% increment in percent predicted FEV and a 1.81% increment in percent predicted FEV/FVC between study visits. In girls with asthma, an increased free testosterone-to-estradiol ratio was significantly associated with decreased eosinophils between visits (P=0.03).

Conclusion: In Puerto Rican youth, increased free testosterone-to-estradiol ratio over time was associated with an increased FEV/FVC in both sexes, and with an increased FEV in males.
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http://dx.doi.org/10.1016/j.anai.2021.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349830PMC
August 2021

A region-based method for causal mediation analysis of DNA methylation data.

Epigenetics 2021 03 23:1-11. Epub 2021 Mar 23.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Exposure to environmental factors can affect DNA methylation at a 5'-cytosine-phosphate-guanine-3' (CpG) site or a genomic region, which can then affect an outcome. In other words, environmental effects on an outcome could be mediated by DNA methylation. To date, single CpG-site-based mediation analysis has been employed extensively. More recently, however, there has been considerable interest in studying differentially methylated regions (DMRs), both because DMRs are more likely to have functional effects than single CpG sites and because testing DMRs reduces multiple testing. In this report, we propose a novel causal mediation approach under the counterfactual framework to test the significance of total (TE), direct (DE), and indirect effects (IE) of predictors on response variable with a methylated region (MR) as the mediator (denoted as MR-Mediation). Functional linear transformation is used to reduce the possible high dimension of the CpG sites in a predefined MR and to account for their location information. In our simulation studies, MR-Mediation retained the desired Type I error rates for TE, DE, and IE tests. Furthermore, MR-Mediation had better power performance than testing mean methylation level as the mediator in most considered scenarios, especially for IE (i.e., mediated effect) test, which could be more interesting than the other two effect tests. We further illustrate our proposed method by analysing the methylation mediated effect of exposure to gun violence on total immunoglobulin E or atopic asthma among participants in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study.
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http://dx.doi.org/10.1080/15592294.2021.1900026DOI Listing
March 2021

Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children.

Pediatr Pulmonol 2021 07 22;56(7):1896-1905. Epub 2021 Mar 22.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: Exposure to violence (ETV) or chronic stress may influence asthma through unclear mechanisms.

Methods: Epigenome-wide association study (EWAS) of ETV or chronic stress measures and DNA methylation in nasal epithelium from 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed four measures of ETV and chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by p value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).

Results: Three CpGs (in SNN, PTPRN2, and LINC01164) were associated with maternal perceived stress or gun violence (p = 1.28-3.36 × 10 ), but not with atopic asthma, in EVA-PR. In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA-PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4, and ANAPC13) were associated with atopic asthma at FDR-p < .05.

Conclusions: Pending confirmation in longitudinal studies, our findings suggest that nasal epithelial methylation markers associated with measures of ETV and chronic stress may be linked to atopic asthma in children and adolescents.
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http://dx.doi.org/10.1002/ppul.25372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217314PMC
July 2021

Sleep disorders in children with asthma.

Pediatr Pulmonol 2021 Mar 1. Epub 2021 Mar 1.

Division of Pulmonary Medicine, Department of Pediatrics, Children's Hospital of Pittsburgh and University of Pittsburgh, Pennsylvania, USA.

Asthma and sleep disorders are both common in childhood, and often co-exist in the same child. Moreover, studies have shown that in many children the rate of one is influenced by the other. Sleep disorders can be classified into six different groups-insomnia, hypersomnia, parasomnia, movement disorders, circadian disorders, and sleep-related breathing disorders. Children with asthma often present with complaints of insomnia with poor sleep quality, difficulty falling asleep and sleep disruptions. These complains are often associated with asthma control. They may also complain of daytime sleepiness and have higher rates of parasomnias, such as night terrors and nocturnal enuresis when compared with their healthy peers. Whether movement and circadian disorders are also more prevalent in children with asthma is less clear. Finally, there is a complex bidirectional interaction between sleep-related breathing disorders and asthma: poor sleep and sleep disorders may worsen asthma, and asthma, particularly when it is poorly controlled, may impair sleep. In the current review we examine the association of each of the sleep disorders with asthma and review the common pathophysiological pathways. We hope to convince the reader that appropriate management of asthma must include inquiries into the patient's sleep, and vice versa.
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http://dx.doi.org/10.1002/ppul.25264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408281PMC
March 2021

The association of trimethoprim-sulfamethoxazole with improved lung function in pediatric asthma.

Ann Allergy Asthma Immunol 2021 04 17;126(4):440-442. Epub 2021 Jan 17.

Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania; R.K. Mellon Institute for Pediatric Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

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http://dx.doi.org/10.1016/j.anai.2021.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009834PMC
April 2021

A Comprehensive Clinical Description of Pediatric SARS-CoV-2 Infection in Western Pennsylvania.

medRxiv 2020 Dec 16. Epub 2020 Dec 16.

Objective: We sought to characterize clinical presentation and healthcare utilization for pediatric COVID-19 in Western Pennsylvania (PA).

Methods: We established and analyzed a registry of pediatric COVID-19 in Western PA that includes cases in patients <22 years of age cared for by the pediatric quaternary medical center in the area and its associated pediatric primary care network from March 11 through August 20, 2020.

Results: Our cohort included 424 pediatric COVID-19 cases (mean age 12.5 years, 47.4% female); 65% reported exposure and 79% presented with symptoms. The most common initial healthcare contact was through telehealth (45%). Most cases were followed as outpatients, but twenty-two patients (4.5%) were hospitalized: 19 with acute COVID-19 disease, and three for multisystem inflammatory syndrome of children (MIS-C). Admitted patients were younger (p<0.001) and more likely to have pre-existing conditions (p<0.001). Black/Hispanic patients were 5.8 times more likely to be hospitalized than white patients (p=0.012). Five patients (1.2%) were admitted to the PICU, including all three MIS-C cases; two required BiPAP and one mechanical ventilation. All patients survived.

Conclusions: We provide a comprehensive snapshot of pediatric COVID-19 disease in an area with low to moderate incidence. In this cohort, COVID-19 was generally a mild disease; however, ~5% of children were hospitalized. Pediatric patients can be critically ill with this infection, including those presenting with MIS-C.
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http://dx.doi.org/10.1101/2020.12.14.20248192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755149PMC
December 2020

Serum insulin-like growth factor-1, asthma, and lung function among British adults.

Ann Allergy Asthma Immunol 2021 03 11;126(3):284-291.e2. Epub 2020 Dec 11.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

Background: Insulin-like growth factor-1 (IGF-1) plays a key role in the pathogenesis of metabolic syndrome, which is in turn associated with asthma. Whether IGF-1 contributes to asthma causation or asthma severity is largely unknown.

Objective: To evaluate the relation between serum IGF-1 and asthma, asthma outcomes, and lung function in adults.

Methods: Cross-sectional study of 297,590 adults (aged 40-69 years) who participated in the United Kingdom Biobank, had no diagnosis of diabetes, and were not on insulin. Multivariable logistic or linear regression was used to analyze serum IGF-1 and physician-diagnosed asthma, current wheezing, asthma hospitalizations, and lung function measures (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and FEV1 to FVC ratio).

Results: Serum IGF-1 levels above the lowest quartile (Q1) were significantly associated with lower odds of asthma (adjusted odds ratio for fourth quartile [Q4] vs Q1 = 0.88; 95% confidence interval [CI], 0.85-0.91). Among the participants with asthma, IGF-1 levels above Q1 were significantly associated with lower odds of current wheezing (adjusted odds ratio for Q4 vs Q1 = 0.89; 95% CI, 0.83-0.96), but not with asthma hospitalizations. Serum IGF-1 was significantly and positively associated with FEV1 (b = 20.9 mL; 95% CI, 19.1-22.7) and FVC (b = 25.6 mL; 95% CI, 23.4-27.7), regardless of an asthma diagnosis; these associations were significant in men and women, with larger estimated effects in men.

Conclusion: In a large study of British adults, higher serum IGF-1 levels were associated with lower odds of asthma and current wheezing and higher FEV1 and FVC. Our findings suggest potential beneficial effects of circulating IGF-1 on asthma and asthma outcomes in adults.
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http://dx.doi.org/10.1016/j.anai.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897263PMC
March 2021

A Potential New Treatment Option for Asthma in the Setting of Obesity or Insulin Resistance?

Authors:
Erick Forno

Am J Respir Crit Care Med 2021 04;203(7):788-789

Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania and.

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http://dx.doi.org/10.1164/rccm.202010-4017EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017569PMC
April 2021

Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children.

medRxiv 2020 Nov 4. Epub 2020 Nov 4.

Background: Exposure to violence (ETV) or stress may cause asthma through unclear mechanisms.

Methods: Epigenome-wide association study (EWAS) of DNA methylation in nasal epithelium and four ETV or chronic stress measures in 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed measures of ETV or chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by P-value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).

Results: In the EWAS of stress/violence in EVA-PR, gun violence was associated with methylation of cg18961589 in (β=0.03, =1.28×10 ), and maternal stress was associated with methylation of cg03402351 in (β=0.04, =1.69×10 ) and cg19064846 in (β=0.03, =3.36×10 ). In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence in EVA-PR, CpGs in and were associated with atopic asthma at FDR- < 0.05.

Conclusions: ETV and chronic stress may increase the risk of atopic asthma through DNA methylation in airway epithelium, though this needs confirmation in future longitudinal studies.
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http://dx.doi.org/10.1101/2020.11.03.20225250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654924PMC
November 2020

Maternal Depressive Symptoms, Lung Function, and Severe Asthma Exacerbations in Puerto Rican Children.

J Allergy Clin Immunol Pract 2021 03 28;9(3):1319-1326.e3. Epub 2020 Oct 28.

Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pa. Electronic address:

Background: Maternal depression has been linked to health care use for asthma in cross-sectional or short-term follow-up studies of school-aged children.

Objective: To examine whether increased or persistent maternal depressive symptoms over approximately 5 years are associated with severe asthma exacerbations or worse lung function in youth.

Methods: A prospective study of 386 youth living in Puerto Rico, aged 6 to 14 years at a baseline visit and 9 to 20 years at a second visit, was performed. Our exposure of interest was change in persistence of maternal depressive symptoms, assessed at both visits using the Center for Epidemiologic Studies Depression Scale (CESD). Our outcomes of interest were change in percent predicted forced expiratory volume in 1 second (FEV) and FEV/forced vital capacity (FVC) between the first and second visits in all subjects, and ≥1 severe asthma exacerbation in the year before the second visit in subjects with asthma.

Results: In a multivariable analysis, each 1-point increment in the CESD score was associated with decrements of 0.15% in percent predicted FEV (95% confidence interval [CI] = -0.28% to -0.01%; P = .03) and 0.10% in percent predicted FEV/FVC (95% CI = -0.20% to 0.001%; P = .05) between visits, as well as with 1.03 times increased odds of ≥1 severe asthma exacerbation at the second visit (95% CI for odds ratio = 0.99 to 1.06, P = .09). In a multivariable analysis, the presence of maternal depressive symptoms (a CESD score ≥21 points) at the second visit or at both visits was significantly associated with 3.17 to 3.52 times increased odds of ≥1 severe asthma exacerbation in the year before the second visit.

Conclusions: Increasing or persistent maternal depressive symptoms over approximately 5 years are associated with worse lung function measures and severe asthma exacerbations among Puerto Rican youth, a high-risk population.
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http://dx.doi.org/10.1016/j.jaip.2020.10.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946650PMC
March 2021

A genome-wide association study of severe asthma exacerbations in Latino children and adolescents.

Eur Respir J 2021 04 1;57(4). Epub 2021 Apr 1.

Division of Pediatric Pulmonary Medicine, University of Pittsburgh Medical Centre, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA

Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups.To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus, expression quantitative trait locus and expression quantitative trait methylation analyses to assess whether the top single nucleotide polymorphism (SNP) in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents.In the meta-analysis of GWAS, an SNP in (rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbation (95% CI 1.34-1.79, p=6.3×10). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the locus, which was in turn associated with increased expression of in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, p=2.18×10).SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents ().
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http://dx.doi.org/10.1183/13993003.02693-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026735PMC
April 2021

Indoor endotoxin, proximity to a major roadway, and severe asthma exacerbations among children in Puerto Rico.

Ann Allergy Asthma Immunol 2020 12 8;125(6):658-664.e2. Epub 2020 Sep 8.

Division of Pediatric Pulmonary Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

Background: Few studies have examined concurrent exposure to household endotoxin and traffic-related air pollution in relation to childhood asthma, yet both factors are associated with asthma outcomes.

Objective: To examine whether proximity to a major roadway (a traffic-related air pollution proxy) modifies the estimated effects of indoor endotoxin on asthma outcomes in children.

Methods: Cross-sectional study of 200 children with asthma (ages, 6-14 years) living in Puerto Rico. Residential distance to a major roadway was calculated as the distance from the participant's residential US census block centroid to the nearest major road. The outcomes of interest were severe asthma exacerbations, missed school days for asthma, atopy, lung function, and bronchodilator response (BDR). Logistic, linear, or negative binomial regression was used for the multivariable analysis.

Results: In the multivariable analysis, there was an interaction between indoor endotoxin and residential distance to a roadway on severe asthma exacerbations (P = .02) and BDR (P = .07). In an analysis stratified by distance to a roadway, each log-unit increase in endotoxin was associated with 4.21 times increased odds of severe asthma exacerbations among children living within 499 m (the lower 3 quartiles of residential distance) to a road (95% confidence interval, 1.5-12.0). Among subjects living further than 499 m away from a roadway, each log-unit increase in endotoxin was associated with reduced odds of severe asthma exacerbations (odds ratio, 0.03; 95% confidence interval, 0.001-0.67). Similar but less substantial findings were observed for BDR.

Conclusion: Our findings suggest that residential proximity to a major road modifies the estimated effect of endotoxin on severe asthma exacerbations in children.
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http://dx.doi.org/10.1016/j.anai.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680389PMC
December 2020

A genome-wide association study of asthma hospitalizations in adults.

J Allergy Clin Immunol 2021 03 2;147(3):933-940. Epub 2020 Sep 2.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pa. Electronic address:

Background: Little is known about the genetic determinants of severe asthma exacerbations.

Objectives: We aimed to identify genetic variants associated with asthma hospitalizations.

Methods: We conducted a genome-wide association study of asthma hospitalizations in 34,167 white British adults with asthma, 1,658 of whom had at least 1 asthma-related hospitalization. This analysis was conducted by using logistic regression under an additive genetic model with adjustment for age, sex, body mass index, smoking status, and the first 5 principal components derived from genotypic data. We then analyzed data from 2 cohorts of Latino children and adolescents for replication and conducted quantitative trait locus and functional annotation analyses.

Results: At the chromosome 6p21.3 locus, the single-nucleotide polymorphism (SNP) rs56151658 (8 kb from the promoter of HLA-DQB1) was most significantly associated with asthma hospitalizations (for test allele A, odds ratio = 1.36 [95% CI = 1.22-1.52]; P = 3.11 × 10); 21 additional SNPs in this locus were associated with asthma hospitalizations at a P value less than 1 × 10. In the replication cohorts, multiple SNPs in strong linkage disequilibrium with rs56151658 were associated with severe asthma exacerbations at a P value of .01 or less in the same direction of association as in the discovery cohort. Three HLA genes (HLA-DQA2, HLA-DRB6, and HLA-DOB) were also shown to mediate the estimated effects of the SNPs associated with asthma hospitalizations through effects on gene expression in lung tissue.

Conclusions: We identified strong candidate genes for asthma hospitalizations in adults in the region for class II HLA genes through genomic, quantitative trait locus, and summary data-based mendelian randomization analyses.
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http://dx.doi.org/10.1016/j.jaci.2020.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921212PMC
March 2021

Serum free testosterone and asthma, asthma hospitalisations and lung function in British adults.

Thorax 2020 10 31;75(10):849-854. Epub 2020 Aug 31.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Objective: We examined the relation between serum-free testosterone and asthma, wheeze, asthma hospitalisations and lung function in older adults.

Design: Cross-sectional study.

Setting: UK.

Participants: 256 419 adults aged 40 to 69 years, recruited from 2006 to 2010.

Main Outcome Measures: Multivariable logistic or linear regression was used for the analysis of free testosterone and physician-diagnosed asthma, current wheeze, asthma hospitalisations and lung function measures, which was adjusted for serum estradiol, smoking status and other covariates.

Results: Free testosterone levels above the lowest quartile (Q1) were significantly associated with lower odds of asthma in both women (adjusted OR (aOR) for Q4 (the highest quartile) versus Q1=0.67, 95% CI=0.64 to 0.71) and men (aOR for Q4 versus Q1=0.87, 95% CI=0.82 to 0.91). Among subjects with asthma, free testosterone levels above Q1 were significantly associated with lower odds of current wheeze in women (aOR range=0.78 to 0.87), and free testosterone levels in Q4 were associated with lower odds of current wheeze in men (aOR for Q4 versus Q1=0.86, 95% CI=0.77 to 0.95). Among women with asthma, free testosterone levels in Q4 were also associated with lower odds of ≥1 asthma hospitalisation. Among men, free testosterone was positively associated with FEV and FVC. Among women, free testosterone was negatively and weakly associated with FVC.

Conclusion: In a large study of British adults, elevated free testosterone levels are associated with lower odds of asthma and current wheeze in women and men, lower odds of asthma hospitalisations in women, and higher FEV and FVC in men. DISSEMINATION TO PARTICIPANTS, AND RELATED PATIENT AND PUBLIC COMMUNITIES: The results of the study will be linked to the UK Biobank website.
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http://dx.doi.org/10.1136/thoraxjnl-2020-214875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938359PMC
October 2020

Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D Levels: The VDKA Randomized Clinical Trial.

JAMA 2020 08;324(8):752-760

Division of Pulmonary Medicine, Department of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania.

Importance: Severe asthma exacerbations cause significant morbidity and costs. Whether vitamin D3 supplementation reduces severe childhood asthma exacerbations is unclear.

Objective: To determine whether vitamin D3 supplementation improves the time to a severe exacerbation in children with asthma and low vitamin D levels.

Design, Setting, And Participants: The Vitamin D to Prevent Severe Asthma Exacerbations (VDKA) Study was a randomized, double-blind, placebo-controlled clinical trial of vitamin D3 supplementation to improve the time to severe exacerbations in high-risk children with asthma aged 6 to 16 years taking low-dose inhaled corticosteroids and with serum 25-hydroxyvitamin D levels less than 30 ng/mL. Participants were recruited from 7 US centers. Enrollment started in February 2016, with a goal of 400 participants; the trial was terminated early (March 2019) due to futility, and follow-up ended in September 2019.

Interventions: Participants were randomized to vitamin D3, 4000 IU/d (n = 96), or placebo (n = 96) for 48 weeks and maintained with fluticasone propionate, 176 μg/d (6-11 years old), or 220 μg/d (12-16 years old).

Main Outcomes And Measures: The primary outcome was the time to a severe asthma exacerbation. Secondary outcomes included the time to a viral-induced severe exacerbation, the proportion of participants in whom the dose of inhaled corticosteroid was reduced halfway through the trial, and the cumulative fluticasone dose during the trial.

Results: Among 192 randomized participants (mean age, 9.8 years; 77 girls [40%]), 180 (93.8%) completed the trial. A total of 36 participants (37.5%) in the vitamin D3 group and 33 (34.4%) in the placebo group had 1 or more severe exacerbations. Compared with placebo, vitamin D3 supplementation did not significantly improve the time to a severe exacerbation: the mean time to exacerbation was 240 days in the vitamin D3 group vs 253 days in the placebo group (mean group difference, -13.1 days [95% CI, -42.6 to 16.4]; adjusted hazard ratio, 1.13 [95% CI, 0.69 to 1.85]; P = .63). Vitamin D3 supplementation, compared with placebo, likewise did not significantly improve the time to a viral-induced severe exacerbation, the proportion of participants whose dose of inhaled corticosteroid was reduced, or the cumulative fluticasone dose during the trial. Serious adverse events were similar in both groups (vitamin D3 group, n = 11; placebo group, n = 9).

Conclusions And Relevance: Among children with persistent asthma and low vitamin D levels, vitamin D3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in this group of patients.

Trial Registration: ClinicalTrials.gov Identifier: NCT02687815.
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http://dx.doi.org/10.1001/jama.2020.12384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448830PMC
August 2020

A genome-wide study of DNA methylation in white blood cells and asthma in Latino children and youth.

Epigenetics 2021 May 31;16(5):577-585. Epub 2020 Aug 31.

Division of Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Latinos are heavily affected with childhood asthma. Little is known about epigenetic mechanisms of asthma in Latino youth. We conducted a meta-analysis of two epigenome-wide association studies (EWAS) of asthma, using DNA from white blood cells (WBCs) from 1,136 Latino children and youth aged 6 to 20 years. Genes near the top CpG sites in this EWAS were examined in a pathway enrichment analysis, and we then assessed whether our results replicated those from publicly available data from three independent EWAS conducted in non-Latino populations. We found that DNA methylation profiles differed between subjects with and without asthma. After adjustment for covariates and multiple testing, two CpGs were differentially methylated at a false discovery rate (FDR)-adjusted P < 0.1, and 193 CpG sites were differentially methylated at FDR-adjusted P < 0.2. The two top CpGs are near genes relevant to inflammatory signalling, including (Calcium/Calmodulin Dependent Protein Kinase ID) and (T Cell Immunoreceptor With Ig And ITIM Domains). Moreover, 25 genomic regions were differentially methylated between subjects with and without asthma, at Šidák-corrected P < 0.10. An enrichment analysis then identified the TGF-beta pathway as most relevant to asthma in our analysis, and we replicated some of the top signals from publicly available EWAS datasets in non-Hispanic populations. In conclusion, we have identified novel epigenetic markers of asthma in WBCs from Latino children and youth, while also replicating previous results from studies conducted in non-Latinos.
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http://dx.doi.org/10.1080/15592294.2020.1809872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078676PMC
May 2021

Leptin in Cord Blood Associates with Asthma Risk at Age 3 in the Offspring of Women with Gestational Obesity.

Ann Am Thorac Soc 2020 12;17(12):1583-1589

Division of Pediatrics, School of Medicine.

Maternal obesity is associated with asthma in the offspring. Whether cord blood leptin is associated with risk of asthma in offspring is unclear. To assess whether cord blood leptin from women with pregestational obesity predict preschool asthma. In this birth cohort study, we divided pregnant women into three weight categories during the first obstetric visit: normal (NL), overweight (OW), and obese (OB). We followed the offspring recording atopy, wheezing, and other respiratory illnesses through 30 months of age. Cord blood and peripheral blood at 30 months of age were taken to measure cytokines, adipokines, metabolic biomarkers, and specific immunoglobulin E. Adjusted regression models were used to evaluate the association between maternal obesity and offspring asthma risk, defined by a positive Asthma Predictive Index. Three hundred thirty-nine mothers were recruited; 140 offspring were born from NL, 80 from OW, and 119 from OB mothers. OB women were older and less educated and had higher parity and higher C-section frequency. Offspring from OB women had higher birthweight, head circumference, and placental weight compared with other groups. The proportion of Asthma Predictive Index positive at 30 months of age was 12.2% in the NL, 14.7% in the OW, and 16.8% in the OB group ( = 0.18). Offspring from OB women had higher leptin, leptin/adiponectin ratio, interleukin-10, and insulin than the OW group and higher leptin than the NL group. In the adjusted analysis, offspring from OB mothers with high cord blood leptin had increased risk of asthma (adjusted odds ratio, 1.30; 95% confidence interval, 1.1-1.55;  = 0.003). Offspring from obese mothers with high cord blood leptin have 30% higher asthma risk at age 3.Clinical trial registered with ClinicalTrials.gov (NCT02903134).
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http://dx.doi.org/10.1513/AnnalsATS.202001-080OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706596PMC
December 2020

Risk factors for atopic and nonatopic asthma in Puerto Rican children.

Pediatr Pulmonol 2020 09 7;55(9):2246-2253. Epub 2020 Jul 7.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: Little is known about the risk factors for atopic and nonatopic asthma among children in Puerto Rico. We aimed to identify modifiable risk factors for atopic and nonatopic asthma in this vulnerable population.

Methods: Case-control study of children with (n = 305) and without (n = 327) asthma in San Juan (Puerto Rico). Asthma was defined as physician-diagnosed asthma and wheeze in the previous year. Atopic asthma (n = 210) was defined as asthma and greater than or equal to one positive IgE to aero-allergens. Nonatopic asthma (n = 95) was defined as asthma and no positive IgE to the allergens tested. Logistic regression was used for the multivariable analysis of atopic and nonatopic asthma.

Results: In a multivariable analysis, body mass index (BMI) z score, prematurity, parental asthma, lifetime exposure to gun violence, and having a bird in the child's home were associated with increased odds of atopic asthma, while each one-point increment in a dietary score (range: -2 [least healthy diet] to +2 [healthiest diet]) was associated with 37% reduced odds of atopic asthma (95% confidence interval [CI] = 0.48-0.81; P < .01). In a separate multivariable analysis, parental asthma, early-life second-hand smoke (SHS) exposure, and daycare attendance in the first year of life were significantly associated with increased odds of nonatopic asthma, while each one-point increment in the dietary score was associated with 42% reduced odds of nonatopic asthma (95% CI = 0.45-0.76; P < .01).

Conclusions: We have identified potentially modifiable risk factors for atopic asthma (eg, BMI and gun violence), nonatopic asthma (eg, early-life SHS and daycare attendance), or both (eg, an unhealthy diet) in Puerto Rican children.
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http://dx.doi.org/10.1002/ppul.24930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686279PMC
September 2020
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