Peter S Thorne

Extracellular vesicles (EVs) are key mediators of intercellular communication and immune regulation; however, their proteomic composition in allergic asthma remains poorly understood. We performed tandem mass tag (TMT)-based quantitative proteomic analyses of bronchoalveolar lavage fluid (BALF) and BALF-derived EVs in a murine house dust mite (HDM) model of allergic airway inflammation. HDM challenge elicited significant upregulation of Th2-associated proteins (CLCA1, FCGBP, CHIL3, CHIL4, and RETNLA), which is consistent with hallmark features of asthma. EPX and CKM were detected exclusively in BALF-derived EVs, demonstrating that EVs can selectively carry disease-relevant proteins. Our results underscore EV's cargo-mediated mechanisms in asthma pathogenesis.

Global climate change is increasing the frequency and severity of hurricanes, which are associated with adverse health outcomes. Veterans may be more susceptible to the health impacts of hurricanes because of prior military exposures.
To determine whether hurricane exposure is associated with cardiovascular and respiratory events among US veterans.
This retrospective cohort study included US veterans enrolled in Veteran Health Administration (VHA) primary care who lived in areas affected by Hurricane Sandy (2011-2013) or Hurricane Harvey (2016-2018). Data were analyzed between June 2024 and February 2026. Study areas were defined by VHA Veterans Integrated Service Networks (VISNs): VISN 1, 2, 3, 4, and 6 for Hurricane Sandy, and VISNs 16 and 17 for Hurricane Harvey.
Living in an area affected by Hurricane Sandy or Hurricane Harvey.
Outcomes of interest were cardiovascular events (CVEs) and respiratory events (REs) that required urgent care and/or emergency department visits or in-patient admission. Associations between hurricane exposure and outcomes were estimated using Andersen-Gill Cox regression models.
Among veterans enrolled in VHA primary care, 1 468 774 lived in the study area during the quarter that Hurricane Sandy occurred, and 1 009 352 lived in the study area during the quarter that Hurricane Harvey occurred. After excluding veterans who were deceased at time of the hurricane or had incomplete data, the analytic cohort included 960 178 veterans exposed to Hurricane Sandy (mean [SD] age, 63 [16] years; 895 646 male [93.30%]) and 654 178 veterans exposed to Hurricane Harvey (mean [SD] age, 60 [16] years; 589 003 male [90.04%]). The analyses included 95 795 CVEs and 120 197 REs for the Hurricane Sandy cohort, and 91 774 CVEs and 98 660 REs for the Hurricane Harvey cohort. Higher levels of neighborhood disadvantage (for healthier veterans with highest levels of disadvantage, hazard ratios [HRs] for CVE were 1.75 [95% CI, 1.63-1.88] for Hurricane Sandy and 1.63 [95% CI, 1.48-1.80] for Hurricane Harvey; HRs for RE were 1.50 [95% CI, 1.43-1.58] for Hurricane Sandy and 1.67 [95% CI, 1.55-1.79] for Hurricane Harvey), age (among healthier veterans aged 60-70 years, HRs for CVE were 2.23 [95% CI, 2.11-2.35] for Hurricane Sandy and 4.12 [95% CI, 3.87-4.39] for those aged ≥70 years for Hurricane Harvey; HRs for RE among sicker veterans were 1.12 [95% CI, 1.08-1.16] for Hurricane Sandy and 1.31 [95% CI, 1.24-1.39] for Hurricane Harvey), and sex (among healthier female veterans, HRs for CVE were 0.52 [95% CI, 0.46-0.59] for Hurricane Sandy and 0.49 [95% CI, 0.44-0.53] for Hurricane Harvey; HRs for RE were 1.38 [95% CI, 1.32-1.43] for hurricane Sandy and 1.36 [95% CI, 1.31-1.41] for Hurricane Harvey) were associated with CVEs and REs in both cohorts. There were no associations between hurricane exposure and CVEs and REs after accounting for baseline differences between exposure regions.
This cohort study of 1 614 356 US veterans used an approach that addresses preexisting differences to isolate the association of hurricane exposure with CVEs and REs among veterans. Although changes in HRs specifically attributable to hurricane exposure were not significant, neighborhood disadvantage, advancing age, and sex remained independently associated with acute health events. These findings suggest that disaster preparedness policies should shift from a reactive model toward a longitudinal strategy that addresses baseline social determinants of health and regional environmental hazards.

Rural older adults, particularly those with Chronic Obstructive Pulmonary Disease (COPD), face significant risks to medical care during power outages caused by natural disasters. This cross-sectional study surveyed 222 Iowan adults aged 45-80 between March and May 2024 to assess disaster preparedness for power outages. Nearly nine in 10 participants experienced recent outages, yet 42% maintained a specific medical care plan for such events. Those with COPD exhibited moderately greater levels of preparedness, including higher rates of saving extra medication and establishing emergency communication plans. They were also twice as likely to have a care plan or emergency medication. Despite these gains, comprehensive preparedness remained low. The study highlights that recurrent disasters, such as windstorms and wildfire smoke, expose critical gaps in medical and emergency planning in rural communities. These results underscore the urgent need for tailored, disease-specific strategies and educational interventions to strengthen disaster resilience among rural populations.

Background
Childhood asthma is characterized by altered lung function and airway inflammation, thought to result from complex gene-environment interactions, especially with allergens. However, previous studies show inconsistent associations between allergen exposure and asthma.
Objectives
We aimed to examine the longitudinal relationship between indoor allergen exposure during infancy with subsequent asthma and spirometry and the potential effect modification by genetic factors.
Methods
Data from a subcohort of the CHILD study with analyzed dust samples (including Can f1 (dog), Fel d1 (cat), and endotoxin) and physician diagnosed asthma or spirometry were used to examine the relationships between allergen levels in dust analytes at 3 months and asthma and, separately, spirometry at 5 years, including potential effect modification by genetic factors using lung function polygenic scores (PGSs).
Results
Among 1050 children with dust samples, 6.6% developed asthma by age 5 years. In an adjusted multivariable model, higher Can f1 significantly decreased the risk of asthma (OR 0.52, 95% CI 0.25, 0.98). Independently, children exposed to high Can f1 had significantly higher FEV1 z-scores (β=0.23, 95% CI 0.06, 0.40), regardless of asthma status. In the gene environment analyses, there were significant gene-environment interactions in the relationship between Can f1 and PGSs on lung function, independent of asthma status.
Conclusions
In a general population birth cohort, early-life exposure to high levels of Can f1 was associated with improved lung function and protection against asthma at age 5. Furthermore, exposure to high Can f1 may modulate lung function in individuals with low PGSs.

Exposure to allergens may trigger inflammatory pathways contributing to poor sleep. We investigated the associations between indoor allergen concentrations with multiple sleep dimensions in children.
Bedroom dust aeroallergens were collected in participants' homes. The outcomes were caregiver-reported sleep-related daytime impairment and sleep disturbance (pediatric PROMIS instruments), sleep-disordered breathing (SDB; apnea-hypopnea index or oxygen desaturation index >5), and actigraphy-based short sleep (<8 hours) duration and poor sleep continuity (sleep fragmentation index > 75th percentile). Logistic regression was used to examine associations between aeroallergens (>50% detectable levels) and sleep outcomes, adjusting for potential confounders (i.e., sociodemographic, environmental, and health-related).
The sample included an urban cohort of 256 children (41% Hispanic, 29% Black; 43% female) aged 6-12 years. Mouse (Mus m 1), cat (Fel d 1), and dog (Can f 1) allergens were detected in 81%, 72%, and 53% of households, respectively. Elevated mouse allergen exposure (>0.55 μg/g-75th percentile) was associated with a 2.6-fold (95% CI: 1.34, 5.03) increased odds for sleep-related daytime impairment (PROMIS T-score > 55) after adjusting for demographic factors. This association persisted after further adjusting for inflammatory-related health factors (asthma, allergic rhinitis, obesity, and environmental tobacco smoke), neighborhood disadvantage, and SDB. There was attenuation of this association with poor sleep consolidation. Associations were not observed for other allergens or other sleep outcomes.
Exposure to elevated mouse dust was associated with increased sleep-related daytime impairment symptoms. The role of household pest exposure as a potentially modifiable target for improving sleep health should be further studied.

Toxicities of lower-chlorinated biphenyls (LC-PCBs) have drawn increasing attention due to growing evidence of their presence in school indoor air, with 2,4,4'-trichlorobiphenyl (PCB28) being a prevalent congener. The tissue levels and characteristics of individual PCB congeners determine the PCB toxicity. Yet, the tissue disposition time course of individual LC-PCBs following pulmonary exposure is largely unknown. To address this data gap, we investigated the whole-body disposition, metabolism, and elimination kinetics of PCB28 in rats following intratracheal lung dosing of radiolabeled [
C]-PCB28. Blood, 36 tissue types, 6 digestive matters, and excreta were sampled at specific intervals (12, 25, 50, 100, 200, 400, 720, and 1440 min) postexposure. The pulmonary uptake of PCB28 was nearly complete at 99.9 ± 3.5%. PCB28 rapidly distributed across multiple tissues, initially accumulating in lung and liver, followed by redistribution to the adipose and skin. PCB28 exhibited linear toxicokinetics (TK) in highly perfused tissues, resulting in dose-proportional increases in the area under the concentration-time curves. In contrast, adipose tissue, skin, and prostate displayed nonlinear TK. The elimination half-life of [
C]-PCB28 was 12 h, with elimination primarily via the fecal route. This study provides new data on the toxicokinetics of PCB28 following pulmonary exposure to support the development of TK models for evaluating the health risks posed by this persistent environmental pollutant.

Despite increased recognition of the adverse impacts of PCB exposure on human health, comprehensive risk assessments, particularly regarding inhalation exposure and effects on the developing fetus, are lacking. Out of all PCB congeners, lower-chlorinated PCBs have been more prevalent in indoor and outdoor atmospheres. Thus, we investigated
toxicokinetics and placental transfer of radiolabeled [
C]-PCB52 (0.157 mg/kg administered intratracheally) in Sprague-Dawley rats at gestational day 11 ± 1. Following dosing, 99.4 ± 0.5% of the administered dose was distributed to the systemic circulation. Radioactivity disappeared biexponentially following lung exposure, with 41.1% of the dose retained after 96 h. PCB52 was rapidly distributed to the maternal serum, lung, heart, and liver, with subsequent accumulation in the ovaries, brain, white and brown adipose, muscle, and mammary glands. The time to reach a maximum concentration in the maternal serum was 0.21 h, with an apparent terminal elimination half-life of 40.7 h. The peak concentration of [
C]-PCB52 and its metabolites in the placenta, fetus, and amniotic fluid was achieved 1.7 h after exposure, with a fetal half-life of 34.8 h. The maternal serum level was significantly correlated with levels in amniotic fluid, placenta, fetus, and the maternal brain. However, PCB52 exposure in the placenta, fetus, and amniotic fluid was limited with their respective maternal serum exposure ratio values of 0.5, 0.27, and 0.05. These results demonstrate for the first time a comprehensive whole-body disposition of PCB52 in dams and fetuses after lung exposure during gestation. PCB52 and its metabolites accumulate predominantly in the ovaries, brain, and mammary glands. The apparent half-life of PCB52 in developing fetuses and placenta is comparable to that of maternal serum. This study provides novel quantitative foundations for the development and evaluation of physiologically based toxicokinetic modeling to inform the exposure and risk assessment for public health decisions.

Sarcoidosis is a multi-system disease frequently affecting the lungs. It is thought to be mediated by gene-environment interaction; for example, epidemiological data show organic aerosol exposure increases risk of pulmonary sarcoidosis. The aim of this study was to assess whether exposure to bioaerosol associates with worse lung disease in patients with pulmonary sarcoidosis.
Using an observational, cohort study design, we measured residential exposure to fungal and bacterial cell wall material, β-(1,3)-D-glucan (BDG) and endotoxin, respectively, in healthy control subjects and those with pulmonary sarcoidosis. In the case cohort, we compared bioaerosol concentrations to pulmonary disease severity, assessed by pulmonary function testing, qualitative chest computed tomography (CT), and serum biomarkers. Log-transformed bioaerosol concentrations were compared to lung function and significance and correlation determined by Pearson correlation.
Homes of subjects with sarcoidosis had higher BDG and endotoxin concentrations than control subjects. Patients with significant pulmonary fibrosis had greater disease severity (Wasfi severity score, visual analogue scale) and reduced pulmonary function compared to those without fibrosis (all P<0.01). Residential fungal BDG correlated with declining FVC, only in patients with fibrosis on CT imaging (P=0.02). Survey data revealed higher BDG concentrations were found in homes of cat-owners, and the number of houseplants owned correlated with declines in FVC and FEV1 (P=0.05 and 0.02, respectively). In patients without fibrosis, eight inflammatory markers correlated with BDG (6CKine/CCL21, IL-9, IL-17F, IL-21, IL-28A, I-309, MIP-1β, TARC), while in those with pulmonary fibrosis, BDG correlated with two inflammatory markers (Eotaxin-3, M-CSF), suggesting immune anergy to inhaled antigens in patients with fibrosis.
In patients with pulmonary fibrosis, disease severity was correlated with residential exposure to fungal cell wall material, but not gram-negative bacterial cell wall material. These patients may experience immune anergy to inhaled antigens.

Exposure to allergens has been shown to trigger inflammatory pathways contributing to sleep-disordered breathing (SBD) and fragmented sleep, specifically in children with atopic diseases. However, little is known about the relationship between indoor allergen exposure and sleep symptoms in children in the general population, or how several inflammatory-related health factors, such as asthma, allergic rhinitis, or obesity, contribute to this relationship. We investigated the associations between high indoor allergen concentrations, sleep quality dimensions, and SDB in children ages 6-12 years old living in predominantly low-income neighborhoods.
Methods

Bedroom dust aeroallergens were collected in participants’ bedrooms. Outcomes were caregiver-reported sleep-related daytime impairment and sleep disturbance (pediatric PROMIS instruments), symptoms of SDB (AHI/ODI), and actigraphy based short sleep (< 8 hours) duration and poor sleep continuity (sleep fragmentation > 75th percentile). Logistic regression was used to examine associations between aeroallergens and sleep disturbances, adjusting age, sex, race, ethnicity, maternal education.
Results

The sample included 256 children (age 9.5 years; 41% Hispanic, 29% Black, 22% White, 8% Other; 43% female) with 27% reported maternal education attainment of a high school or less. 38% lived in disadvantaged neighborhoods (neighborhood Child Opportunity Index < 40). Mouse (Musm1), cat (Feld1), and dog (Canf1) allergens were detected in 81%, 72%, and 53% of households, respectively. Elevated mouse allergen exposure (>0.55 μg/g-75th percentile) was associated with a 2.6-fold (95%CI:1.34, 5.03) increased adjusted odds for sleep-related daytime impairment (PROMIS T-score > 55). This association persisted after adjustment for health factors (asthma, allergic rhinitis, obesity, and environmental tobacco smoke exposure), neighborhood disadvantage, and SDB. There was attenuation of this association with poor sleep consolidation and frequent awakenings. There were no associations with the other sleep outcomes or exposures.
Conclusion

Our results reveal that elevated mouse exposure was associated with increased sleep-related daytime impairment symptoms in children living in predominantly low-income neighborhoods. The mechanisms that link this association are not clear, however poor sleep quality explained some of this relationship. Strategies to reduce household exposure and improve air quality should be tested as approaches for reducing health disparities.

Background: The cost-effectiveness of school environmental remediation in asthma is not known. The School Inner City Asthma Intervention Study (SICAS2) was a randomized controlled trial that assessed school integrated pest management (IPM) and classroom high efficiency particulate
air (HEPA) filtration on asthma morbidity in urban schools. Objective: The objective was to evaluate the cost-effectiveness of SICAS2. Methods: We conducted a cost-effectiveness analysis from a societal perspective that compared four interventions: IPM,
HEPA, IPM + HEPA, and no intervention. Quality-adjusted life years (QALY) were derived from the EuroQol-5 Dimension-Youth and EuroQol-5 Dimension-3 levels instruments. Total costs (2021 U.S. dollars) included intervention cost, cost of caregiver productivity impacted by child school absenteeism,
and health-care utilization costs (e.g., emergency department visits). The evaluation period was based on a mean follow-up time of 166 days. Sensitivity analyses were performed by using cost estimates 50% above and below initial cost benchmarks. Results: A total of 154
SICAS2 participants were included. Intervention costs per student were $12.21 (IPM + HEPA), $7.27 (IPM), and $4.94 (HEPA). Sequential analyses revealed that IPM + HEPA was the most cost-effective option, with an incremental cost-effectiveness ratio of $19,667 per
QALY. Sensitivity analyses demonstrated stability, with variability in probability estimates not exceeding 10%. Conclusion: IPM + HEPA demonstrated good value to society, which reflected the low cost and the economic impact of missed school days. This intervention may have
a pronounced benefit for historically minoritized and marginalized children in urban schools who are disproportionately exposed to air pollution and indoor allergens. The SICAS2 intervention may offer a cost-effective tool to target proximal causes of disparities even in the most resource-limited
schools.