Socioeconomic status, diet, and recurrent severe asthma exacerbations in Puerto Rican youth.

Background: Why Puerto Rican youths have higher rates of severe asthma exacerbations (SAEs) than their non-Hispanic White peers is unclear. Objective: We aimed to identify risk factors associated with recurrent SAEs in Puerto Rican youths with asthma. Methods: We performed cross-sectional and longitudinal analyses of recurrent SAEs in 209 Puerto Rican youths with asthma who participated in 2 cross-sectional studies approximately 5.2 years apart: the Puerto Rico Genetics of Asthma and Lifestyle study (visit 1, participants aged 6-14 years) and the Epigenetic Variation and Childhood Asthma in Puerto Ricans study (visit 2, participants aged 9-20 years). Recurrent SAEs were defined as at least 2 SAEs in the previous year. Results: Of the youths in our study, there were 80 (38.3%) and 47 (22.4%) with recurrent SAEs at visit 1 and visit 2, respectively, and 31 participants (14.8%) had persistent recurrent SAEs (ie, recurrent SAEs at both visits). In multivariable analyses, low household income was significantly associated with 2.4 to 12.3 times increased odds of recurrent SAEs in all analyses, with stronger longitudinal associations. Low parental education level, nonprivate or employer-based health insurance, overweight or obesity, residential proximity to a major road, and low or moderate level of outdoor activity were each significantly associated with recurrent SAEs in at least 1 analysis. Further, persistence of low parental numeracy level, low household income, and an unhealthy diet were each associated with persistent recurrent SAEs. Conclusion: In this study of Puerto Rican youths with asthma, persistence of low parental numeracy level, a low household income, and an unhealthy diet were associated with persistent recurrent SAEs. Our findings support policies promoting equity and healthy lifestyles for Puerto Rican children and their families.

Best clinical practice in the treatment of juvenile systemic sclerosis: expert panel guidance - the result of the International Hamburg Consensus Meeting December 2022.

INTRODUCTION: Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1,000,000 children. Currently there is only one consensus treatment guideline concerning skin, pulmonary and vascular involvement for jSSc, the jSSc SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) initiative, which was based on data procured up to 2014. Therefore, an update of these guidelines, with a more recent literature and expert experience, and extension of the guidance to more aspects of the disease is needed. AREAS COVERED: Treatment options were reviewed, and opinions were provided for most facets of jSSc including general management, some of which differs from adult systemic sclerosis, such as the use of corticosteroids, and specific organ involvement, such as skin, musculoskeletal, pulmonary, and gastroenterology. EXPERT OPINION: We are suggesting the treat to target strategy to treat early to prevent cumulative disease damage in jSSc. Conclusions are derived from both expert opinion and available literature, which is mostly based on adult systemic sclerosis (aSSc), given shared pathophysiology, extrapolation of results from aSSc studies was judged reasonable.

Odds of COVID-19-associated asthma exacerbations in children higher during Omicron wave.

BACKGROUND: We aimed to determine the association of COVID-19 variant wave with asthma exacerbations in children with asthma. METHODS: We conducted a retrospective cross-sectional study of children in the Western Pennsylvania COVID-19 Registry (WPACR). We extracted data for all children in the WPACR with asthma and compared their acute clinical presentation and outcomes during the Pre-Delta (7/1/20-6/30/21), Delta (8/1/21-12/14/21), and Omicron (12/15/21-8/30/22) waves. We conducted multivariable logistic regression analyses of SARS-CoV-2-associated asthma exacerbations, adjusting for characteristics that have been associated with COVID-19 outcomes in prior studies. RESULTS: Among 573 children with asthma in the WPACR during the study period, the proportion of children with COVID-19 who had an asthma exacerbation was higher during the Omicron wave than during the prior two variant waves (40.2% vs. 22.6% vs. 26.2%, p = 0.002; unadjusted OR = 2.12 [95% confidence interval (CI) = 1.39-3.22], p < 0.001). In our multivariable regression models, the odds of an asthma exacerbation were 2.8 times higher during the Omicron wave than during prior waves (adjusted OR = 2.80 [95% CI = 1.70-4.61]). Results were similar after additionally adjusting for asthma severity but were no longer significant after additionally adjusting for poor asthma control. CONCLUSION: The proportion of children with asthma experiencing an asthma exacerbation during SARS-CoV-2 infection was higher during Omicron than prior variant waves, adding to the body of evidence that COVID-19-associated respiratory symptoms vary by variant. These findings provide additional support for vaccination and prevention.

Pulmonary Nodules in Juvenile Systemic Sclerosis: A Case-Series from the National Registry for Childhood Onset Scleroderma (NRCOS).

BACKGROUND: Juvenile systemic sclerosis (jSSc) is a systemic inflammatory and fibrotic autoimmune disease. Adult guidelines recommend obtaining a screening high-resolution computed tomography scan (CT) at diagnosis. As these recommendations are adopted as standard of care for jSSc, increased screening with CT may lead to increased detection of nodules. The implications of nodules identified in jSSc are unclear and unreported. METHODS: A retrospective chart review was performed on the prospectively enrolled National Registry for Childhood-Onset Scleroderma (NRCOS) cohort over an enrollment period of 20 years. Clinical associations with presence of nodules and nodule characteristics were investigated. RESULTS: In this jSSc cohort, the prevalence of pulmonary nodules was 31% (n = 17 of 54). Nodule characteristics were heterogeneous, and most displayed stability over time. More participants with nodules had structural esophageal abnormalities, restriction, and reduced diffusing capacity on lung function tests, and follow-up imaging. Most participants had multiple nodules, and although most nodules were <5 mm, most participants had at least one nodule >5 mm. CONCLUSIONS: Pulmonary nodules are seen in children with jSSc and may be related to more severe disease and/or esophageal dysfunction. More work is needed to provide guidance on radiologic follow-up and clinical management of pulmonary nodules in jSSc.

Exposure to violence and asthma in Puerto Rican youth with high Th2 immunity.

BACKGROUND: Little is known about the determinants of asthma among youth with high T helper 2 (Th2) immunity. We hypothesized that exposure to violence (ETV) and violence-related distress are associated with asthma in children and adolescents with high Th2 immunity. METHODS: We analyzed data from Puerto Ricans with high Th2 immunity aged 9-20 years in the Puerto Rico Genetics of Asthma and Lifestyle (PR-GOAL) and the Epigenetic Variation of Childhood Asthma in Puerto Ricans (EVA-PR) studies, and in a prospective study (PROPRA). High Th2-immunity was defined as ≥1 positive allergen-specific IgE and/or a total IgE ≥ 100 IU/mL and/or an eosinophil count ≥ 150 cells/µL. Asthma was defined as physician-diagnosed asthma and current wheeze. ETV and violence-related distress were assessed with the validated ETV Scale and Checklist of Children's Distress Symptoms (CCDS) questionnaires, respectively. RESULTS: In multivariable analyses, each 1-point increment in ETV score was significantly associated with 1.13-1.17 times increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.01), and each 1-point increment in CCDS score was significantly associated with 1.53-1.54 increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.03). Further, a persistently high ETV score was significantly associated with asthma in PROPRA (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.10-7.29). Similar results were obtained in a sensitivity analysis using an eosinophil count ≥ 300 cells/µL instead of ≥150 cells/µL to define high Th2 immunity. CONCLUSIONS: ETV during childhood is associated with increased risk of persistent or new-onset asthma in youth with high Th2 immunity.

Ozone and childhood respiratory health: A primer for US pediatric providers and a call for a more protective standard.

Ground level ozone is a potent respiratory toxicant with decades of accumulated data demonstrating respiratory harms to children. Despite the ubiquity of ozone in the United States, impacting both urban and rural communities, the associated harms of exposure to this important air pollutant are often infrequently or inadequately covered during medical training including pulmonary specialization. Thus, many providers caring for children's respiratory health may have limited knowledge of the harms which may result in reduced discussion of ozone pollution during clinical encounters. Further, the current US air quality standard for ozone does not adequately protect children. In this nonsystematic review, we present basic background information for healthcare providers caring for children's respiratory health, review the US process for setting air quality standards, discuss the respiratory harms of ozone for healthy children and those with underlying respiratory disease, highlight the urgent need for a more protective ozone standard to adequately protect children's respiratory health, review impacts of climate change on ozone levels, and provide information for discussion in clinical encounters.

Air Quality Index and Childhood Asthma: A Pilot Randomized Clinical Trial Intervention.

INTRODUCTION: To reduce air pollution exposure, the U.S. asthma guidelines recommend that children check the Air Quality Index before outdoor activity. Whether adding the Air Quality Index and recommendations to asthma action plans reduces exacerbations and improves control and quality of life in children with asthma is unknown. METHODS: A pilot, unblinded, randomized clinical trial of 40 children with persistent asthma, stratified by age and randomized 1:1, recruited from the University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (Pittsburgh, PA) was conducted. All participants received asthma action plans and Air Quality Index education. The intervention group received printed Air Quality Index information and showed the ability to use AirNow. Asthma exacerbations were assessed through a questionnaire, asthma control was assessed with the Asthma Control Test and Childhood Asthma Control Test, and quality of life was assessed with the Pediatric Asthma Quality of Life Questionnaire. After randomization (July-October 2020), participants were followed monthly for 6 months (exit January-March 2021). Outcome differences between groups were evaluated at the exit visit and over time (analysis was in 2021). RESULTS: At randomization, there were no significant differences in age, sex, race, or asthma severity. At exit, more intervention participants checked the Air Quality Index (63% vs 15%) with no differences in the proportion of asthma exacerbations or mean Childhood Asthma Control Test or Pediatric Asthma Quality of Life Questionnaire scores. The mean change in Asthma Control Test score was higher in the intervention group (change in Asthma Control Test=2.00 vs 0.15 for the control), which was modified by time (ß=1.85, CI=0.09, 3.61). Physical activity was decreased overall and showed modification by treatment and time. CONCLUSIONS: Addition of the Air Quality Index to asthma action plans led to improved asthma control by Asthma Control Test scores but may decrease outdoor activity.

Parental knowledge and usage of air quality in childhood asthma management.

Background: The current United States asthma management guidelines recommend usage of the Air Quality Index (AQI) for outdoor activity modification when air pollution is high. Little is known about parental knowledge and usage of air quality including the AQI in managing childhood asthma. Methods: Forty parents (or legal guardians) of children with persistent asthma completed a questionnaire designed to assess 4 areas related to outdoor air pollution: awareness, perception, behavioral modification, and prior healthcare provider discussion. Descriptive statistics were obtained and Fisher's exact test was used for analysis of behavioral change by selected variables. Results: Almost all parents reported awareness of air quality alerts or AQI, however, only 20% checked the AQI on the AirNow app or website. Most parents reported air pollution as a trigger (65%), yet few parents reported behavioral modification of their child's outdoor activity based on the perception of poor air quality (43%) or based on AQI or alerts (40%). Over half of parents reported a healthcare provider had ever discussed air pollution as a trigger, with few parents (23%) reporting recommendations for behavior change. Perception of air pollution as a trigger, healthcare provider discussion and recommendations, and usage of AirNow were associated with increased reported activity change. Conclusion: Healthcare providers should discuss outdoor air pollution during asthma management in children and should discuss AirNow as a source for AQI information and behavioral recommendations.

Differential gene expression in nasal airway epithelium from overweight or obese youth with asthma.

BACKGROUND: The mechanisms underlying the known link between overweight/obesity and childhood asthma are unclear. We aimed to identify differentially expressed genes and pathways associated with obesity-related asthma through a transcriptomic analysis of nasal airway epithelium. METHODS: We compared the whole transcriptome in nasal airway epithelium of youth with overweight or obesity and asthma with that of youth of normal weight and asthma, using RNA sequencing data from a cohort of 235 Puerto Ricans aged 9-20 years (EVA-PR) and an independent cohort of 66 children aged 6-16 years in Pittsburgh (VDKA). Differential expression analysis adjusting for age, sex, sequencing plate number, and sample sorting protocol, and the first five principal components were performed independently in each cohort. Results from the two cohorts were combined in a transcriptome-wide meta-analysis. Gene enrichment and network analyses were performed on top genes. RESULTS: In the meta-analysis, 29 genes were associated with obesity-related asthma at an FDR-adjusted p <.05, including pro-inflammatory genes known to be differentially expressed in adipose tissue of obese subjects (e.g., CXCL11, CXCL10, and CXCL9) and several novel genes. Functional enrichment analyses showed that pathways for interferon signaling, and innate and adaptive immune responses were down-regulated in overweight/obese youth with asthma, while pathways related to ciliary structure or function were up-regulated. Upstream regulatory analysis predicted significant inhibition of the IRF7 pathway. Network analyses identified "hub" genes like GBP5 and SOCS1. CONCLUSION: Our transcriptome-wide analysis of nasal airway epithelium identified biologically plausible genes and pathways for obesity-related asthma in youth.

Air Quality Index and Emergency Department Visits and Hospitalizations for Childhood Asthma.

Rationale: Outdoor air pollution causes emergency department visits and hospitalizations for childhood asthma. In the United States, the Air Quality Index (AQI) alerts the public to air quality and provides behavioral recommendations to reduce exposure and harm, yet little is known about the relationship between the AQI and childhood asthma exacerbations. Objectives: To test for association between the AQI and childhood asthma exacerbations resulting in emergency department visits and hospitalizations. Methods: This was a retrospective time-stratified case-crossover study, conducted using medical records data from 2010 through 2018 for children aged 6-17 years with a primary diagnosis of an asthma exacerbation (defined as an emergency department visit or hospitalization for asthma) at UPMC Children's Hospital of Pittsburgh. Daily AQI data was obtained for Allegheny County, Pennsylvania from the Environmental Protection Agency. Conditional logistic regression was used for analyses of the AQI (as both a continuous and categorical variable) and asthma exacerbations. Stratified analyses were conducted to explore modification of the AQI effects on asthma exacerbations by race and other covariates. Results: There were 6,573 events. Particulate matter <2.5 µm (PM2.5) was the primary pollutant responsible for the AQI, followed by ozone (62% and 29% of days with events, respectively). The overall AQI was associated with asthma exacerbations (e.g., as continuous, per 10-unit increase, Lag Day 2: odds ratio [OR], 1.014; 95% confidence interval [CI], 1.003-1.025; Lag Day 3: OR, 1.012; 95% CI, 1.001-1.023). By pollutant-specific AQI, the association was strongest for PM2.5. In stratified analyses, the AQI was associated with exacerbations in Black and younger children (6-11 yr) on Lag Day 4. Conclusions: The AQI is associated with asthma exacerbations among children in Allegheny County. This is driven primarily by PM2.5, with Black and younger children particularly affected. Healthcare providers should discuss the AQI in asthma management.

Diet, Asthma, and Severe Asthma Exacerbations in a Prospective Study of Puerto Rican Youth.

BACKGROUND: Poor diet quality may contribute to the disproportionate asthma burden in Puerto Rican youth. OBJECTIVE: To examine whether an unhealthy diet at one or two study visits conducted over about 5 years was associated with asthma, severe asthma exacerbations, and worse lung function in Puerto Rican youth. METHODS: This was a prospective study of 406 Puerto Rican youth aged 6 to 14 years at a baseline visit and 9 to 20 years at a follow-up visit. As in prior work, diet was assessed using a dietary score ranging from -2 to +2. The exposure of interest was an unhealthy diet, defined as a nonpositive dietary score (0 to -2) at one or both visits. Outcomes of interest were asthma (defined as physician-diagnosed asthma and one of more episode of wheeze in the year before the second visit), one or more severe asthma exacerbation in the year before the second visit, and change in percent predicted lung function measures (FEV1, FVC, and FEV1/FVC) between the first and second visits. RESULTS: In a multivariable analysis, an unhealthy diet at both visits was associated with increased odds of asthma (adjusted odds ratio = 3.38; 95% confidence interval, 1.74-6.57) and severe asthma exacerbations (adjusted odds ratio = 2.65; 95% confidence interval, 1.16-6.03), but not with change in lung function. CONCLUSIONS: An unhealthy diet at both visits was associated with increased odds of asthma and severe asthma exacerbations, compared with a healthy diet at both visits. Our findings support health policies promoting a healthy diet in Puerto Rican youth, a population at high risk for asthma.

Persistent overweight or obesity, lung function, and asthma exacerbations in Puerto Rican youth.

BACKGROUND: Whether persistent overweight or obesity affects lung function or asthma morbidity in youth is unclear. OBJECTIVE: To evaluate overweight or obesity that persists between school age and adolescence and change in lung function and total immunoglobulin (Ig)E and severe asthma exacerbations in Puerto Rican youth. METHODS: Prospective study of 340 Puerto Rican youth assessed at 2 visits, the first at ages 6 to 14 years and the second at ages 9 to 20 years. Persistent overweight or obesity was defined as a body mass index z-score greater than or equal to 85th percentile at both visits. Outcomes of interest were change in percent predicted (%pred) lung function measures and total IgE between study visits and severe asthma exacerbations in the year before visit 2. Logistic or linear regression was used for multivariable analysis. RESULTS: In multivariable analysis, persistently overweight or obese subjects had changes in %pred forced expiratory volume in 1 second (FEV1) (ß = -5.07%; 95% confidence interval, -1.51% to -8.62%; P < .01) and %pred FEV1 to forced vital capacity (FVC) ratio (ß = -2.85%; 95% confidence interval, -0.18% to -5.51%; P = .04) which were lower than those observed in subjects with normal weight at both study visits (control subjects). Compared with control subjects, those who were persistently overweight or obese and those who became overweight or obese at visit 2 had increased odds of more than or equal to 1 severe asthma exacerbation in the year before visit 2. There was no significant association between persistent overweight or obesity and change in %pred FVC or total IgE (P > .20 for both instances). CONCLUSION: In a prospective study of Puerto Rican youth, persistently overweight or obese subjects had lower changes in FEV1 or FEV1 to FVC ratio and higher odds of severe asthma exacerbations than subjects of normal weight.

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

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 D3 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 D3 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 log10 total IgE, ß = 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.

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

BACKGROUND: Exposure to violence has been associated with lower lung function in cross-sectional studies. METHODS: 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 randomised clinical trial in 98 youth with asthma (aged 9-16 years) treated with low-dose inhaled corticosteroids (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 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 (PAQLQ)). RESULTS: In a multivariable analysis in VDKA, each 1-point increment in CCDS score was associated with decrements of 3.27% in forced expiratory volume in 1 s (FEV1) % pred (95% CI -6.44- -0.22%; p=0.04), 2.65% in forced vital capacity (FVC) % pred (95% CI -4.86- -0.45%; p=0.02) and 0.30 points in the overall PAQLQ score (95% CI -0.50- -0.10 points; p<0.01). Similar findings for FEV1 and FVC were obtained in the prospective study of Puerto Rican youth. CONCLUSIONS: 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 USA and Puerto Rico.

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

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 (FEV1) and FEV1/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 FEV1 (95% confidence interval [CI] = -0.28% to -0.01%; P = .03) and 0.10% in percent predicted FEV1/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.