Advances in Pediatric Lung Function Testing Techniques.

For decades spirometry has been the benchmark test for capturing lung function in children but its recognized limitations required the development of other techniques. This article introduces novel techniques in lung function assessment for pediatric patients, including multiple breath washout, impulse oscillometry, structured light plethysmography, and electrical impedance tomography, and common themes in interpreting the results. Challenges include standardization, reference data, and clinical integration of these innovative tools. Further research is ongoing to optimize these tests for clinical use, especially in diverse populations and pediatric settings.

Nasal Epithelium Transcriptomics Predict Clinical Response to Elexacaftor/Tezacaftor/Ivacaftor.

Elexacaftor/tezacaftor/ivacaftor (ETI) has made a substantial positive impact for people living with CF (pwCF). However, there can be substantial variability in efficacy, and we lack adequate biomarkers to predict individual response. We thus aimed to identify transcriptomic profiles in nasal respiratory epithelium that predict clinical response to ETI treatment. We obtained nasal epithelial samples from pwCF prior to ETI initiation and performed a transcriptome-wide analysis of baseline gene expression to predict changes in FEV1 (∆FEV1), year's best FEV1 (∆ybFEV1), and body mass index (∆BMI). Using the top differentially expressed genes (DEGs), we generated transcriptomic risk scores (TRS) and evaluated their predictive performance. The study included 40 pwCF aged ≥6 years (mean 27.7 [SD=15.1] years; 40% female). After ETI initiation, FEV1 improved ≥5% in 22 (61.1%) participants and ybFEV1 improved ≥5% in 19 (50%). TRS were constructed using top over-expressed and under-expressed genes for each. Adding the ∆FEV1 TRS for to a model with age, sex, and baseline FEV1 increased the AUC from 0.41 to 0.88; the ∆ybFEV1 TRS increased the AUC from 0.51 to 0.88; and the ∆BMI TRS increased the AUC from 0.46 to 0.92. Average accuracy was thus ~85% in predicting the response to the three outcomes. Results were similar in models further adjusted for F508del zygosity and previous CFTR modulator use. In conclusion, we identified nasal epithelial transcriptomic profiles that help accurately predict changes in FEV1 and BMI with ETI treatment. These novel TRS could serve as predictive biomarkers for clinical response to modulator treatment in pwCF.

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.

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.

The Impact of SARS-CoV-2 Infection on Symptom Control and Lung Function in Children with Asthma.

Rationale: Little is known about the long-term impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on children with asthma. Objectives: To determine whether SARS-CoV-2 infection affects symptom control and lung function in children with asthma. Methods: Using data from clinical registries and the electronic health record, we conducted a prospective case-control study of children with asthma aged 6-21 years who had (cases) or did not have (control subjects) SARS-CoV-2 infection, comparing baseline and follow-up asthma symptom control and spirometry within an ∼18-month time frame and, for cases, within 18 months of acute coronavirus disease (COVID-19). Results: A total of 171 cases had baseline and follow-up asthma symptom data, and 114 cases had baseline and follow-up spirometry measurements. There were no significant differences in asthma symptom control (P = 0.50), forced expiratory volume in 1 second (P = 0.47), forced vital capacity (P = 0.43), forced expiratory volume in 1 second/forced vital capacity (P = 0.43), or forced expiratory flow, midexpiratory phase (P = 0.62), after SARS-CoV-2 infection. Compared with control subjects (113 with symptom data and 237 with spirometry data), there were no significant differences in follow-up asthma symptom control or lung function. A similar proportion of cases and control subjects had poorer asthma symptom control (17.5% vs. 9.7%; P = 0.07) or worse lung function (29.0% vs. 32.5%; P = 0.50) at follow-up. Patients whose asthma control worsened after COVID-19 had a shorter time to follow-up (3.5 [1.5-7.5] vs. 6.1 [3.1-9.8] mo; P = 0.007) and were more likely to have presented with an asthma exacerbation during COVID-19 (46% vs. 26%; P = 0.04) than those without worse control. Conclusions: We found no significant differences in asthma symptom control or lung function in youth with asthma up to 18 months after acute COVID-19, suggesting that COVID-19 does not affect long-term asthma severity or control in the pediatric population.

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.

Child maltreatment and asthma.

A growing body of evidence suggests a potential link between child maltreatment and asthma. Determining whether and how child maltreatment causes or worsens asthma would have major implications for disease prevention and treatment, as well as public health policy. In this article, we examine epidemiologic studies of child maltreatment and asthma and asthma-related outcomes, review the evidence for potential mechanisms underlying the child maltreatment-asthma association, and discuss future directions. To date, a child maltreatment-asthma link has been reported in most studies of children and adults, though the type of maltreatment associated with asthma has differed across studies. Such discrepant findings are likely explained by differences in study design and quality. All studies have been limited by potential under-reporting of child maltreatment and selection bias, and nonthorough assessment of asthma. Despite these limitations, the aggregate evidence from epidemiologic studies suggests a possible causal link between child maltreatment and asthma, though the relative contributions of various types of maltreatment (physical, sexual, emotional, or neglect) are unclear. To date, there is insufficient evidence of an association between child maltreatment and lung function in children or adults. Limited evidence further suggests that child maltreatment could influence the development or severity of asthma through direct effects on stress responses and anxiety- or depressive-related disorders, immunity, and airway inflammation, as well as indirect effects such as increased obesity risk. Future prospective studies should aim to adequately characterize both child maltreatment and asthma, while also assessing relevant covariates and biomarkers of stress, immune, and therapeutic responses.

Asthma as a risk factor for hospitalization in children with COVID-19: A nested case-control study.

BACKGROUND: Most pediatric studies of asthma and COVID-19 to date have been ecological, which offer limited insight. We evaluated the association between asthma and COVID-19 at an individual level. METHODS: Using data from prospective clinical registries, we conducted a nested case-control study comparing three groups: children with COVID-19 and underlying asthma ("A+C" cases); children with COVID-19 without underlying disease ("C+" controls); and children with asthma without COVID-19 ("A+" controls). RESULTS: The cohort included 142 A+C cases, 1110 C+ controls, and 140 A+ controls. A+C cases were more likely than C+ controls to present with dyspnea and wheezing, to receive pharmacologic treatment including systemic steroids (all p < .01), and to be hospitalized (4.9% vs. 1.7%, p = .01). In the adjusted analysis, A+C cases were nearly 4 times more likely to be hospitalized than C+ controls (adjusted OR = 3.95 [95%CI = 1.4-10.9]); however, length of stay and respiratory support level did not differ between groups. Among A+C cases, 8.5% presented with an asthma exacerbation and another 6.3% developed acute exacerbation symptoms shortly after testing positive for SARS-CoV-2. Compared to historic A+ controls, A+C cases had less severe asthma, were less likely to be on controller medications, and had better asthma symptom control (all p < .01). CONCLUSIONS: In our cohort, asthma was a risk factor for hospitalization in children with COVID-19, but not for worse COVID-19 outcomes. SARS-CoV-2 does not seem to be a strong trigger for pediatric asthma exacerbations. Asthma severity was not associated with higher risk of COVID-19.

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.

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

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.

Brief Report: Diminished Gaze Preference for Dynamic Social Interaction Scenes in Youth with Autism Spectrum Disorders.

In this study, we present an eye-tracking paradigm, adapted from previous work with toddlers, for assessing social-interaction looking preferences in youth ages 5-17 with ASD and typically-developing controls (TDC). Videos of children playing together (Social Scenes, SS) were presented side-by-side with animated geometric shapes (GS). Participants with ASD demonstrated reduced SS preferences compared to TDC, results also represented continuously by associations between higher SS preferences and fewer social difficulties across the combined sample. Exploratory analyses identified associations between increased SS preferences and higher Vineland Daily Living Skills in ASD and suggested SS preferences in TDC females might drive ASD versus TDC between-group differences. These findings describe potentially sex-linked couplings between preferences for social information and social functioning in school-aged children.

Effects of pesticide exposure and the amphibian chytrid fungus on gray treefrog (Hyla chrysoscelis) metamorphosis.

Pesticides are detectable in most aquatic habitats and have the potential to alter host-pathogen interactions. The amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), has been associated with amphibian declines around the world. However, Bd-associated declines are more prominent in some areas, despite nearly global distribution of Bd, suggesting other factors contribute to disease outbreaks. In a laboratory study, the authors examined the effects of 6 different isolates of Bd in the presence or absence of a pesticide (the insecticide carbaryl or the fungicide copper sulfate) to recently hatched Cope's gray treefrog (Hyla chrysoscelis) tadpoles reared through metamorphosis. The authors found the presence or absence of pesticides differentially altered the mass at metamorphosis of tadpoles exposed to different Bd isolates, suggesting that isolate could influence metamorphosis but not in ways expected based on origin of the isolate. Pesticide exposure had the strongest impact on metamorphosis of all treatment combinations. Whereas copper sulfate exposure reduced the length of the larval period, carbaryl exposure had apparent positive effects by increasing mass at metamorphosis and lengthening larval period, which adds to evidence that carbaryl can stimulate development in counterintuitive ways. The present study provides limited support to the hypothesis that pesticides can alter the response of tadpoles to isolates of Bd and that the insecticide carbaryl can alter developmental decisions.