Background: Radon is an omnipresent radioactive gas recently reported to be associated with increased asthma morbidity. Objectives: We aimed to identify biomarkers associated with radon exposure and hypothesized elevated radon exposure to be associated with increased inflammatory biomarker levels in an exploratory analysis. Methods: In 137 schoolchildren with asthma in the School Inner-City Asthma Study, we assessed estimated radon exposure (1-month averaged radon) by a spatiotemporal model and 46 inflammatory biomarker outcomes, adjusting for copollutants (particulate matter with diameter <_2.5 m, NO2, O3) and performed mixed-effect regression analysis. Causal mediation analysis was used to determine the association between radon exposure and absolute eosinophil count. Results: In a total of 137 observations, we found a positive association with radon exposure and IL-5, a TH2-cell cytokine known to recruit eosinophils to asthmatic airways. Higher radon was significantly associated with a greater increase in IL5 compared to low radon exposure (observations = 137; 1month moving radon average [% change = 13.4%; 95% CI: 0.4%-28.0%; P = .044]). Mediation analysis revealed an indirect effect of IL-5 ((3 = 0.006; 95% CI:0.001-0.012; P = .024) on the association between radon exposure and absolute eosinophil count. This suggests the effect of radon on eosinophil count is mediated through IL-5. Conclusions: Radon is a potential novel, modifiable risk factor for asthma recently reported to be associated with asthma morbidity. This work identifies important biological disease pathways via biomarkers that may be central to the exposure72.)

Objective To evaluate rates, risk factors and outcomes of delayed diagnosis of seven serious paediatric conditions. Methods This was a retrospective, cross-sectional study of children under 21 years old visiting 13 community and tertiary emergency departments (EDs) with appendicitis, bacterial meningitis, intussusception, mastoiditis, ovarian torsion, sepsis or testicular torsion. Delayed diagnosis was defined as having a previous ED encounter within 1week in which the condition was present per case review. Patients with delayed diagnosis were each matched to four control patients without delay by condition, facility and age. Conditional logistic regression models evaluated risk factors of delay. Complications were compared between by delayed diagnosis status. Results Among 14 972 children, delayed diagnosis occurred in 1.1% (range 0.3% for sepsis to 2.6% for ovarian torsion). Hispanic (matched OR 2.71, 95% CI 1.69 to 4.35) and non Hispanic black (OR 2.40, 95% CI 1.21 to 4.79) race/ethnicity were associated with delayed diagnosis, whereas Asian and other race/ethnicity were not. Public (OR 2.21, 95% CI 1.42 to 3.44) and other (OR 2.43, 95% CI 1.50 to 3.93) insurance were also associated with delay. Non-English language was associated with delay (OR 1.65, 95% CI 1.02 to 2.69). Abnormal vital signs were associated with a lower likelihood of delay (OR 0.15, 95% CI 0.09 to 0.25). In an adjusted model Hispanic race/ethnicity, other insurance, abnormal vital signs and complex chronic conditions (CCCs) were associated with delay. The odds of a complication were 2.5-fold (95% CI 1.6 to 3.8) higher among patients with a delay. Conclusion Delayed diagnosis was uncommon across 13 regional EDs but was more likely among children with Hispanic ethnicity, CCCs or normal vital signs. Delays were associated with a higher risk of complications.

Dynamic bursts of solar electromagnetic radiation modulate short-term geomagnetic disturbances when they interact with Earth's magnetic fields. Periods of intense solar and geomagnetic activity (SGMA) have been linked to a broad range of adverse health effects, including increased risk of cardiovascular and pulmonary disease and all-cause mortality,1,2 which may be due to oxidative stress or dysregulation of circadian rhythm-controlled melatonin release that can modify immune regulation.3,4

Many children with type 1 diabetes do not meet nutritional guidelines. Little is known about how caregivers perceive the necessity of registered dietitian (RD) visits or how satisfied they are with nutrition care. This study aimed to evaluate nutrition experiences and perceptions of care among caregivers of children with type 1 diabetes at an academic medical center. We analyzed 159 survey responses. Using multivariable logistic regression, we assessed factors associated with the perception of need for annual nutrition visits, satisfaction with RD care, and encouragement from a nurse or doctor to meet with an RD. Covariates included age (<13 vs. ≥13 years), type 1 diabetes duration (≤3 vs. >3 years), sex, race/ethnicity, and insulin pump and continuous glucose monitoring use. More than half of caregivers (56%) considered annual visits necessary. Shorter type 1 diabetes duration (odds ratio [OR] 1.92, 95% CI 1.02–3.63) was associated with this finding. Less than half (46.5%) reported satisfaction with nutrition care; higher satisfaction was also correlated with shorter type 1 diabetes duration (OR 2.20, 95% CI 1.17–4.15). Although 42% reported meeting with an RD in the past year, less than two-thirds (62%) reported receiving a medical provider recommendation for nutrition care. Leading reasons for not meeting with an RD were “I am knowledgeable in nutrition and do not need to see an [RD]” (41%) and “I had a past visit with an [RD] that was not helpful” (40%). Our findings suggest that satisfaction with and perceived need for nutrition care may wane with longer type 1 diabetes duration. Improved strategies for therapeutic alliance between caregivers and RDs and engagement of families at later stages of type 1 diabetes are needed.

Introduction Exposure to particulate matter (PM) pollution has been associated with lower lung function in adults with chronic obstructive pulmonary disease (COPD). Patients with eosinophilic COPD have been found to have higher levels of airway inflammation, greater responsiveness to anti-inflammatory steroid inhalers and a greater lung function response to PM pollution exposure compared with those with lower eosinophil levels. This study will evaluate if reducing home PM exposure by high-efficiency particulate air (HEPA) air filtration improves respiratory health in eosinophilic COPD.Methods and analysis The Air Purification for Eosinophilic COPD Study (APECS) is a double-blinded randomised placebo-controlled trial that will enrol 160 participants with eosinophilic COPD living in the area of Boston, Massachusetts. Real and sham air purifiers will be placed in the bedroom and living rooms of the participants in the intervention and control group, respectively, for 12 months. The primary trial outcome will be the change in forced expiratory volume in 1 s (FEV1). Lung function will be assessed twice preintervention and three times during the intervention phase (at 7 days, 6 months and 12 months postrandomisation). Secondary trial outcomes include changes in (1) health status by St. George’s Respiratory Questionnaire; (2) respiratory symptoms by Breathlessness, Cough and Sputum Scale (BCSS); and (3) 6-Minute Walk Test (6MWT). Inflammatory mediators were measured in the nasal epithelial lining fluid (NELF). Indoor PM will be measured in the home for the week preceding each study visit. The data will be analysed to contrast changes in outcomes in the intervention and control groups using a repeated measures framework.Ethics and dissemination Ethical approval was obtained from the Institutional Review Board of Beth Israel Deaconess Medical Centre (protocol #2019P0001129). The results of the APECS trial will be presented at scientific conferences and published in peer-reviewed journals.Trial registration NCT04252235. Version: October 2023.

Radon is an omnipresent radioactive gas recently reported to be associated with increased asthma morbidity. We aimed to identify biomarkers associated with radon exposure and hypothesized elevated radon-derived particle radioactivity exposure would be associated with increased inflammatory biomarker levels.

Background: India is facing overlapping opioid injection and HIV epidemics among people who inject drugs (PWID) in several cities. Integrated Care Centers (ICCs) provide single-venue HIV and substance use services to PWID. We evaluated PWID engagement in daily observed buprenorphine treatment at 7 ICCs to inform interventions.Methods: We analyzed 1-year follow-up data for PWID initiating buprenorphine between 1 January - 31 December 2018, evaluating receipt frequency, treatment interruptions (no buprenorphine receipt for 60 consecutive days with subsequent re-engagement), and drop-out (no buprenorphine receipt for 60 consecutive days without re-engagement). Using descriptive statistics, we explored differences between ICCs in the opioidendemic Northeast region and ICCs in the emerging opioid epidemic North/Central region. We used a multivariable logistic regression model to determine predictors of treatment drop-out by 6 months.Results: 1312 PWID initiated buprenorphine (76% North/Central ICCs vs. 24% Northeast ICCs). 31% of PWID in North/Central, and 25% in Northeast ICCs experienced >= 1 treatment interruption in 1 year. Over 6 months, 48% of PWID in North/Central vs. 60% in Northeast ICCs received buprenorphine <= 2 times/week (p < 0.0001). A third of PWID in North/Central vs. half in Northeast ICCs experienced treatment drop-out by 6 months (p < 0.001). In the multivariable model, living in Northeast cities was associated with increased odds of drop-out while counseling receipt was associated with decreased odds.Conclusions: Retention among PWID initiating buprenorphine at ICCs was comparable to global reports. However, regional heterogeneity in retention, and low daily buprenorphine receipt suggest patient-centered interventions adapted to regional contexts are urgently needed.

Background: Few data on the relationships between environmental exposures, asthma morbidity, and systemic IL-6 inflammation exist.Objective: We sought to determine whether baseline plasma IL-6 level is associated with increased asthma morbidity in children exposed to mouse allergen in inner-city classrooms.Methods: Data from the longitudinal School Inner-City Asthma Studies of 215 children with asthma, aged 4 to 14 years and recruited from urban elementary schools, were analyzed. Given the unknown threshold of IL-6 risk levels and skewness of the distribution, the children were stratified into tertiles as follows: low baseline IL-6 level (<0.013 pg/mL), moderate baseline IL-6 level (0.013-0.302 pg/mL), and high baseline IL-6 level (>0.302 pg/mL). Relationships between plasma IL-6 level and body mass index (BMI) percentile, inflammatory markers, lung function, mouse allergen exposure, and asthma outcomes were assessed.Results: Cross-sectional analysis demonstrated that increasing IL-6 level was associated with higher BMI percentile (P < .0001), C-reactive protein level (P = .0006), and blood neutrophil count (P = .0024). IL-6 was not associated with type 2 inflammatory markers, including blood eosinophil count, allergic sensitization, or fractional exhaled nitric oxide level. Longitudinal analysis showed that children with high IL-6 levels had a higher number of days with asthma symptoms than did those children with moderate (incidence rate ratio = 1.74 [95% CI = 1.10-2.77]; P = .0187) or low (incidence rate ratio =1.83 [95% CI = 1.21-2.77]; P = .0043) IL-6 levels. Children with high IL-6 levels who were exposed to increasing levels of mouse allergen exhibited lower ratios of FEV1 value to forced vital capacity than did children with moderate IL-6 levels (beta = -0.0044 [95% CI = -0.0073 to -0.0015]; pairwise interaction P = .0028) or low IL-6 levels (beta = -0.0042 [95% CI = - 0.0070 to -0.0013]; pairwise interaction P = .0039).Conclusions: Inner-city children with asthma and high plasma IL-6 levels are more likely to have an increased BMI, elevated C-reactive protein level, elevated blood neutrophil count, and greater asthma symptoms. High IL-6 level appears to increase susceptibility to the effects of classroom exposure to mouse allergen on lung function in urban children.

Background: Radon may have a role in obstructive lung disease outside its known carcinogenicity. Little is known about radon’s effects on asthma morbidity. Objective: To determine the effect of radon on fractional exhaled nitric oxide (F NO), asthma symptom-days, and lung function in inner-city asthmatic school-children. Methods: Two hundred ninety-nine school-aged asthmatic children enrolled in the School Inner-City Asthma Study (SICAS-1) were followed. One and two-month averaged radon was assessed using a spatiotemporal model predicting zip code-specific monthly exposures. F NO and spirometry were measured twice during the academic year. Asthma symptoms were assessed four times during the academic year. The interaction between indoor radon exposure (Bq/m ) and seasonality predicting log-transformed F NO, FEV % predicted, FVC% predicted, FEV /FVC, and asthma symptom-days was evaluated. Results: Participants with high radon exposure had greater change in F NO from warm to cold periods compared to low radon exposure (interaction p=0.0013). Participants with >50 percentile radon exposure experience significant F NO increase from warm to cold weather ( β =0.29 [95% CI: 0.04,0.54], p=0.0240). We report a positive association between radon 1-month moving average (IRR=1.01, p=0.0273) and 2-month moving average (IRR=1.01, p=0.0286) with maximum asthma symptom-days (n=299, obs=1,167). Conclusions: In asthmatic children, radon may be associated with increased asthma morbidity, suggesting radon may be a modifiable environmental risk factor for airway inflammation.

Youth with complex regional pain syndrome (CRPS) commonly experience mechani-cal allodynia and disability. Assessment of mechanical allodynia is typically binary (present or absent), making it difficult to assess the quality and degree of mechanical allodynia before and after treatment. This study developed and validated the Pediatric Tactile Sensitivity Test of Allo-dynia (Pedi-Sense) to provide an easy way for rehabilitation clinicians to evaluate mechanical allodynia before and after intensive interdisciplinary pain treatment. The 6 Pedi-Sense items demonstrated adequate internal consistency reliability (CR) at admission (CR = .956) and dis-charge (CR = .973), reasonably fit the hypothesized linear model of stimulus intensity (P < .0001), and significantly loaded onto a single latent factor, mechanical allodynia (P < .0001), at admission and discharge. Pedi-Sense scores significantly correlated with disability (rs = .40; P = .004) and pain catastrophizing (rs = .33; P = .017) at admission. The Pedi-Sense appeared responsive to intervention as participants' total scores improved by 1.44 points (95% CI: .72, 2.15) after IIPT interventions that included daily tactile desensitization. However, test-retest and interrater reliability and the specific contribution of desensitization treatment to the overall suc-cess of multi-modal pain rehabilitation still needs to be evaluated. Perspective: This article presents the development and preliminary validation of a novel clinical assessment of static and dynamic mechanical allodynia. The Pediatric Tactile Sensitivity Test of Allo-dynia (Pedi-Sense) allows rehabilitation clinicians to easily evaluate mechanical allodynia at the bed-side with minimal training and simple equipment to guide desensitization treatment in clinical settings. (c) 2022 by United States Association for the Study of Pain, Inc.

Neutrophil extracellular traps (NETs) not only counteract bacterial and fungal pathogens but can also promote thrombosis, autoimmunity, and sterile inflammation. The presence of citrullinated histones, generated by the peptidylarginine deiminase 4 (PAD4), is synonymous with NETosis and is considered independent of apoptosis. Mitochondrial- and death receptor-mediated apoptosis promote gasdermin E (GSDME)-dependent calcium mobilization and membrane permeabilization leading to histone H3 citrullination (H3Cit), nuclear DNA extrusion, and cytoplast formation. H3Cit is concentrated at the promoter in bone marrow neutrophils and redistributes in a coordinated process from promoter to intergenic and intronic regions during apoptosis. Loss of GSDME prevents nuclear and plasma membrane disruption of apoptotic neutrophils but prolongs early apoptosis-induced cellular changes to the chromatin and cytoplasmic granules. Apoptotic signaling engages PAD4 in neutrophils, establishing a cellular state that is primed for NETosis, but that occurs only upon membrane disruption by GSDME, thereby redefining the end of life for neutrophils.

Pediatric PulmonologyVolume 57, Issue 12 p. 3165-3168 LETTER Environmental radon and childhood asthma Lana Mukharesh MD, Lana Mukharesh MD orcid.org/0000-0002-7062-2257 Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA Contribution: Writing - original draft, Methodology, Writing - review & editing, Conceptualization, Formal analysis, ​Investigation, Data curationSearch for more papers by this authorKimberly F. Greco MPH, Kimberly F. Greco MPH Institutional Centers for Clinical and Translational Research (ICCTR), Boston Children's Hospital, Boston, Massachusetts, USA Contribution: Formal analysis, Data curation, Methodology, Conceptualization, ​Investigation, Writing - review & editingSearch for more papers by this authorTina Banzon MD, Tina Banzon MD Harvard Medical School, Boston, Massachusetts, USA Division of Allergy and Immunology, Boston Children's Hospital, Boston, Massachusetts, USA Contribution: Writing - review & editing, ​InvestigationSearch for more papers by this authorPetros Koutrakis PhD, Petros Koutrakis PhD Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Contribution: Funding acquisition, Data curation, Methodology, ​Investigation, Conceptualization, Writing - review & editing, Formal analysisSearch for more papers by this authorLongxiang Li ScD, Longxiang Li ScD Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Contribution: Formal analysis, Data curationSearch for more papers by this authorMarissa Hauptman MD, MPH, Marissa Hauptman MD, MPH Harvard Medical School, Boston, Massachusetts, USA Department of General Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA Contribution: Writing - review & editing, ​Investigation, MethodologySearch for more papers by this authorWanda Phipatanakul MD, MS, Wanda Phipatanakul MD, MS Harvard Medical School, Boston, Massachusetts, USA Division of Allergy and Immunology, Boston Children's Hospital, Boston, Massachusetts, USA Contribution: Funding acquisition, Writing - review & editing, ​Investigation, Methodology, Data curation, Supervision, ConceptualizationSearch for more papers by this authorJonathan M. Gaffin MD, MMSc, Corresponding Author Jonathan M. Gaffin MD, MMSc [email protected] orcid.org/0000-0003-2213-4504 Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA Correspondence Jonathan M. Gaffin, MD, MMSc, Division of Pulmonary Medicine, Boston Children's Hospital, 300 Longwood Ave, Farley 4, Boston, MA 02215, USA. Email: [email protected] Contribution: Conceptualization, Writing - review & editing, Methodology, Supervision, Funding acquisition, ​Investigation, Data curation, Formal analysisSearch for more papers by this author Lana Mukharesh MD, Lana Mukharesh MD orcid.org/0000-0002-7062-2257 Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA Contribution: Writing - original draft, Methodology, Writing - review & editing, Conceptualization, Formal analysis, ​Investigation, Data curationSearch for more papers by this authorKimberly F. Greco MPH, Kimberly F. Greco MPH Institutional Centers for Clinical and Translational Research (ICCTR), Boston Children's Hospital, Boston, Massachusetts, USA Contribution: Formal analysis, Data curation, Methodology, Conceptualization, ​Investigation, Writing - review & editingSearch for more papers by this authorTina Banzon MD, Tina Banzon MD Harvard Medical School, Boston, Massachusetts, USA Division of Allergy and Immunology, Boston Children's Hospital, Boston, Massachusetts, USA Contribution: Writing - review & editing, ​InvestigationSearch for more papers by this authorPetros Koutrakis PhD, Petros Koutrakis PhD Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Contribution: Funding acquisition, Data curation, Methodology, ​Investigation, Conceptualization, Writing - review & editing, Formal analysisSearch for more papers by this authorLongxiang Li ScD, Longxiang Li ScD Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Contribution: Formal analysis, Data curationSearch for more papers by this authorMarissa Hauptman MD, MPH, Marissa Hauptman MD, MPH Harvard Medical School, Boston, Massachusetts, USA Department of General Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA Contribution: Writing - review & editing, ​Investigation, MethodologySearch for more papers by this authorWanda Phipatanakul MD, MS, Wanda Phipatanakul MD, MS Harvard Medical School, Boston, Massachusetts, USA Division of Allergy and Immunology, Boston Children's Hospital, Boston, Massachusetts, USA Contribution: Funding acquisition, Writing - review & editing, ​Investigation, Methodology, Data curation, Supervision, ConceptualizationSearch for more papers by this authorJonathan M. Gaffin MD, MMSc, Corresponding Author Jonathan M. Gaffin MD, MMSc [email protected] orcid.org/0000-0003-2213-4504 Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA Correspondence Jonathan M. Gaffin, MD, MMSc, Division of Pulmonary Medicine, Boston Children's Hospital, 300 Longwood Ave, Farley 4, Boston, MA 02215, USA. Email: [email protected] Contribution: Conceptualization, Writing - review & editing, Methodology, Supervision, Funding acquisition, ​Investigation, Data curation, Formal analysisSearch for more papers by this author First published: 13 September 2022 https://doi.org/10.1002/ppul.26143Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume57, Issue12December 2022Pages 3165-3168 RelatedInformation

The misuse of opioids is increasingly a global epidemic. India has experienced burgeoning HIV epidemics in several regions that are primarily driven by an alarming rise in injection of opioids. Among the ∼850,000 people who inject drugs (PWID) in India, at least a quarter are adolescents and young adults (YPWID: 15-24 years) who have the highest HIV incidence. There is limited data on substance use treatment and HIV testing gaps in this population. We established Integrated Care Centers (ICCs) across 8 Indian cities, which provide single-window free HIV services and daily observed buprenorphine treatment in a stigma-free environment. We evaluated engagement of YPWID in substance use treatment and HIV testing at ICCs to inform interventions. We performed a retrospective analysis of ICC service utilization data, utilizing 1-year follow-up data for YPWID who initiated buprenorphine between 1 January 2018 to 31 December 2018 across the 8 ICCs. We used summary statistics to describe HIV testing uptake and buprenorphine receipt, including receipt frequency, treatment interruptions (i.e., no buprenorphine receipt for >= 60 days with subsequent re-initiation within 1 year) and treatment drop-out (i.e., no buprenorphine receipt for >= 60 days without re-initiation during study period). To evaluate regional differences in buprenorphine uptake, we used chi-squared analysis to compare regions representing historical opioid epidemics (i.e., Northeast cities (NEC)) and those with emerging opioid epidemics (i.e., North/Central cities (NCC)). We used a multivariable logistic regression model to determine predictors of treatment drop within 6 months of initiation. 444 YPWID initiated buprenorphine (83% vs. 17%; NCC vs. NEC) in 2018. The median number of days of buprenorphine receipt in 1 year was 74 days in NCC (IQR: 14, 237) and 25 days in NEC (IQR: 8, 98). 37% of YPWID in NCC, and 27% in NEC experienced >= 1 treatment interruption. About a third (33%) of YPWID in NCC vs. 59% in NEC dropped out within 6 months of initiation (p<0.0001). Over a 6-month period, 47% of YPWID in NCC vs. 60% in NEC received buprenorphine <= 2 times per week on average (p=0.0345). In multivariable models, being unemployed, HIV uninfected, and living in NEC were significant predictors of treatment drop-out by 6 months. Regular HIV testing every 6 months was significantly lower in HIV uninfected YPWID who received buprenorphine <= 2 times per week (34% vs. 69%, p<0.0001). YPWID at ICCs in India have significant substance use treatment gaps including low buprenorphine receipt frequency and retention. YPWID who are under-engaged in substance use treatment also have decreased uptake of regular HIV testing. Our findings suggest that co-located services alone may be insufficient to engage YPWID. There is an urgent need to develop youth-responsive interventions adapted to regional contexts to ameliorate these gaps.

BACKGROUND: Atopic dermatitis (AD) and food allergy (FA) may share genetic risk factors. It is unknown whether genetic factors directly cause FA or are mediated through AD, as the dual-allergen hypothesis suggests. OBJECTIVE: To test the hypothesis that AD mediates the relationship between an IL-4 receptor alpha chain gene (IL4RA) variant, the human IL-4 receptor alpha chain protein-R576 polymorphism, and FA. METHODS: A total of 433 children with asthma enrolled in the School Inner-City Asthma Study underwent genotyping for the IL4RA(576) allele. Surveys were administered to determine FA, AD, and associated allergic responses. Mediation analysis was performed adjusting for race and ethnicity, age, sex, and household income. Multivariate models were used to determine the association between genotype and FA severity. RESULTS: AD was reported in 193 (45%) and FA in 80 children (19%). Each risk allele increased odds of AD 1.39-fold ([1.03-1.87], P=.03), and AD increased odds of FA 3.67-fold ([2.05-6.57], P<.01). There was an indirect effect of genotype, mediated by AD, predicting FA; each risk allele increased the odds of FA by 1.13 (odds ratio [95% CI], Q/R = 1.13 [1.02-1.24], R/R = 1.28 [1.04-1.51]; P<.01). Each risk allele increased the odds of severe FA symptoms 2.68-fold ([1.26-5.71], P=.01). CONCLUSIONS: In a cohort of children with asthma, AD is part of the causal pathway between an IL4RA variant and FA. This variant is associated with increased risk of severe FA reactions. Addressing AD in children with an IL4RA polymorphism may modulate the risk of FA. (C) 2022 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology

Fractional exhaled nitric oxide (FeNO) measures airway inflammation, with higher levels associated with asthma exacerbations and lung function decline. Radon, an omnipresent radioactive gas, may have a role in obstructive lung disease outside its known carcinogenicity. We hypothesized that radon exposure would be associated with increased FeNO levels in inner-city children with asthma. 184 elementary school-aged children with asthma enrolled in the School Inner-City Asthma Study (SICAS-1) were included. Repeated measures linear mixed effects models were used to assess the interaction between ground radon exposure and seasonality predicting log-transformed FeNO. Predictors were: 1) ground radon exposure (dichotomous: 25th percentile of radon exposure) over a 2-month moving average, and 2) weather (dichotomous: warm [April – September] or cold [October – March]). All models were adjusted for age, BMI, and height. Participants with high radon exposure had significantly greater change in FeNO from warm to cold periods compared to low exposure (interaction p=0.0013). Subjects with >25th percentile radon exposure experience significant FeNO increase from warm to cold weather (ß=0.27 [95% CI: 0.12, 0.41], p=0.0003). Subjects with <25th percentile radon exposure do not experience a change in FeNO across weather patterns (ß=-0.14 [95% CI: -0.34, 0.06], p=0.1779). We report a positive association of FeNO with colder seasons compared to warm for participants with higher ground radon exposure, suggesting radon exposure may be an important indoor environmental risk factor for airway inflammation.

Abstract Introduction Sleep-disordered breathing (SDB) and asthma have a bidirectional relationship. Almost half of former premature school age children with bronchopulmonary dysplasia (BPD) have asthma or asthma-like symptoms. Prematurity is a known risk factor for sleep-disordered breathing. However, little is known about the association of SDB and asthma symptoms in former premature school age children with BPD. Methods Study sample comprised of participants in an ongoing cohort study, the AERO-BPD study. Participants were 6-12 years old, were born < 32 weeks gestational age and had been diagnosed with BPD. We administered the Pediatric Sleep Questionnaire (PSQ) and asthma symptom questionnaires. The prevalence of SDB was determined based on a PSQ > 0.33. The relationship between SDB and daytime asthma symptoms was assessed by multivariate logistic regression, adjusting for sex, race, BMI, rhinitis, asthma controller medication and days on respiratory support in the NICU. Results There were 33 subjects with a mean age of 8.8 years, roughly half were male and one third were overweight/obese. About half (48.5%) had daytime asthma symptoms and 39.4% had SDB. About half were on controller medication (inhaled corticosteroid or leukotriene receptor antagonist) and 39.4% had rhinitis. Among the 13 subjects with SDB, 11 reported daytime asthma symptoms and 5 of the 20 subjects without SDB reported daytime asthma symptoms. Subjects with SDB had over 17 times the odds of daytime asthma symptoms (OR 17.61, 95% CI [1.23, 251.76], p=0.035) compared to subjects without SDB, while adjusting for sex, race, BMI, rhinitis, controller medications and days on respiratory support in the NICU. Conclusion Our findings suggest that SDB is highly prevalent among former premature school age children with BPD. The findings suggest a relationship between SDB and daytime respiratory symptom burden among these patients rather than mere co-existence. Support (If Any)