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BACKGROUND:Childhood asthma is characterized by altered lung function and airway inflammation that is thought to result from complex gene-environment interactions, especially with allergens. However, previous studies have shown 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 (Canadian Healthy Infant Longitudinal Development) study with analyzed dust samples (including Canis familiaris 1 [dog], Felinus domesticus 1 [cat], and endotoxin) and physician-diagnosed asthma or spirometry data were used to examine the relationships between allergen levels in dust analytes at age 3 months and asthma and, separately, spirometry data at age 5 years, including potential effect modification by genetic factors obtained by using lung function polygenic scores (PGSs). RESULTS:Of 1050 children with dust samples, 6.6% developed asthma by age 5 years. In an adjusted multivariable model, higher Can f 1 level significantly decreased the risk of asthma (odds ratio = 0.52 [95% CI = 0.25-0.98]). Independently, children exposed to high levels of Can f 1 had significantly higher FEV1z scores (β = 0.23 [95% CI = 0.06-0.40]), regardless of asthma status. In the gene-environment analyses, there were significant effects of gene-environment interactions in the relationship between Can f 1 and PGS on lung function, independent of asthma status. CONCLUSIONS:In a general population birth cohort, early-life exposure to high levels of Can f 1 was associated with improved lung function and protection against asthma at age 5 years. Furthermore, exposure to high levels of Can f 1 may modulate lung function in individuals with low PGSs.

Freshwater harmful algal blooms (HABs) pose significant health risks to communities through drinking water sources and contact recreation. Cyanobacteria that drive HABs produce a complex array of secondary metabolites, notably cyanotoxins. The spatiotemporal variability of cyanometabolite mixtures during HAB events remains poorly understood, particularly in agroecosystems, where heavy nutrient loading can alter normal lake dynamics. Therefore, we applied high-resolution mass spectrometry-based suspect screening to characterize cyanometabolite mixture dynamics during active HAB events in two Eastern Iowa lakes as test sites, using time controlled sampling at one lake and locationally controlled sampling at the other. Using the CyanoMetDB to enable complex mixture comparisons alongside ELISA-based microcystin (MC) quantification, we tentatively identified 38 unique cyanometabolites, revealing substantial chemical diversity beyond traditional monitoring targets. Spatial analysis at one of the lakes exhibited dramatic variability across a 104-meter beach, where MC concentrations ranged from 0.65 µg L-1 (below advisory limits) to 36.86 µg L-1 (4.6-fold greater than the USEPA health advisory threshold), with metabolite mixtures exhibiting low similarity (cos(θ) = 0.38) for those same sites. Temporal monitoring at the other test lake demonstrated rapid temporal changes, with MC concentrations dropping from 19.98 to 8.64 µg L-1 within one hour; however, the cyanometabolite mixtures over the same time were similar (cos(θ) = 0.97). Collectively, these findings demonstrate that HAB chemical composition and toxicity fluctuate substantially over short distances and time scales. This first HAB metabolite suspect screening in agroecosystem lakes thus provides a useful initial framework for characterizing overlooked cyanometabolite diversity and tracking chemical dynamics, advancing efforts to better understand, monitor, and mitigate HAB-related exposure.

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.

Importance: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. Objective:To determine whether hurricane exposure is associated with cardiovascular and respiratory events among US veterans. Design, Setting, and Participants: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. Exposure:Living in an area affected by Hurricane Sandy or Hurricane Harvey. Main Outcomes and Measures: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. Results: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. Conclusions and Relevance: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.

ImportanceHurricanes are associated with a wide range of adverse health effects in the general population and are increasing in frequency and severity due to global climate change. Due to prior military exposures and distinct sociodemographic characteristics, US veterans may be more vulnerable than the general population to negative health effects of hurricanes.ObjectiveTo evaluate whether acute care mental health visits among US veterans were associated with exposure to hurricanes.Design, Setting, and ParticipantsThis retrospective cohort study consisted of US veterans enrolled in Veteran Health Administration (VHA) primary care and whose home addresses were in regions that were affected by Hurricanes Sandy or Harvey. The Hurricane Sandy cohort included data from 960 394 veterans between October 29, 2011, and October 28, 2016, and the Hurricane Harvey cohort included data from 795 746 veterans between August 25, 2016, and August 24, 2021. Affected regions were determined from Federal Emergency Management Agency designations; patient-level clinical data were obtained through VHA electronic health records. Statistical analysis was conducted from October 2022 to November 2023.Main Outcomes and MeasuresThe outcome of interest was acute care mental health visits, which included urgent care or emergency department visits or having an inpatient admission. The association between the outcome and exposure to hurricanes was estimated using Cox proportional hazards regression models with adjustments for multiple demographic and neighborhood characteristics, including neighborhood disadvantage, assessed using the Area Deprivation Index, and prior health status, assessed using the Care Assessments Need (CAN) score.ResultsOf the 960 394 veterans in the Hurricane Sandy cohort, the mean (SD) age was 63 (16) years, and 895 726 (93.3%) were men; of the 795 746 veterans in the Hurricane Harvey cohort, the mean (SD) age was 59 (16) years, and 715 460 (89.9%) were men. For both hurricane cohorts, increasing neighborhood disadvantage was associated with an increased hazard of having a subsequent acute care mental health visit; this association was more pronounced among healthier veterans (Sandy cohort: 1-year hazard ratio [HR], 1.62 [95% CI, 1.53-1.71]; Harvey cohort: 1-year HR, 1.64 [95% CI, 1.54-1.74]) compared with veterans who had severe illness (Sandy cohort: HR, 1.22 [95% CI, 1.17-1.26]; Harvey cohort: HR, 1.21 [95% CI, 1.13-1.30]). After adjusting for baseline data, the association between hurricane exposure and our outcomes of interest was largely null. For the Hurricane Sandy cohort, those who were flooded and received individual assistance demonstrated a 1-year HR of 1.31 (95% CI, 0.81-2.12) if their CAN score was 80 or above and 0.86 (95% CI, 0.60-1.22) for a CAN score below 80. Similarly, those affected by Hurricane Harvey who were flooded and received individual assistance had a 1-year HR of 1.06 (95% CI, 0.99-1.14) for a CAN score of 80 or above and a 1-year HR of 0.98 (95% CI, 0.91-1.05) for a CAN score less than 80.Conclusions and RelevanceThis study used a novel and highly granular approach to examine the associations of hurricanes with mental health outcomes. These findings are the first to show that hurricane exposure was not associated with adverse mental health outcomes among US veterans and illustrate the importance of considering preexisting regional differences when assessing the associations of hurricanes with mental health outcomes. The results suggest that neighborhood characteristics, rather than exposure to a hurricane, are the dominant determinants of mental health outcomes.

Long-term exposure to hexavalent chromium [Cr(VI)] has been linked to lung cancer, and cyclooxygenase-2 (COX-2) is a well-known inflammatory factor. However, the role and mechanism of COX-2 in Cr(VI)-induced carcinogenesis are not clear yet. To address this question, we employed a mouse model exposed to Cr(VI) through intranasal instillation of particulate zinc chromate (ZnCrO4) for 12 weeks. Metabolomics and RNA-seq assays revealed enhanced activity of the arachidonic acid (AA)/eicosanoid metabolism pathway in lung tissues from mice exposed to Cr(VI). COX-2, the key enzyme of the AA/eicosanoid pathway, was significantly upregulated in Cr(VI)-exposed lung tissues, as well as in the Cr(VI)-induced transformed (Cr-T) cells compared to parental BEAS-2B (B2B) cells. We then employed multidisciplinary in vitro and in vivo functional assays to characterize the role of COX-2 in Cr(VI)-induced lung cancer. The results indicated that COX-2 functioned as an oncogene to promote the malignant transformation of B2B cells and enhance the proliferation, migration, tumor growth, and angiogenesis of Cr-T cells. Nuclear factor E2-related factor-2 (Nrf2) was identified as a transcription factor for COX-2. Nrf2 was upregulated in response to Cr(VI) exposure and contributed to Cr(VI)-induced lung cancers, in part by upregulating COX-2 expression. Moreover, microRNA-379 (miR-379) was found to target COX-2 to inhibit its expression posttranscriptionally. MiR-379 was downregulated in Cr(VI)-exposed lung tissues and Cr-T cells, and ectopic miR-379 expression reduced Cr-T cell viability and migration, with partial reversal upon COX-2 restoration. In summary, our study revealed the oncogenic role of COX-2 and identified two novel regulatory mechanisms for COX-2 overexpression in Cr(VI)-induced carcinogenesis.

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 [14C]-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 [14C]-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.

Polychlorinated biphenyls (PCBs) are linked to cancer, learning disabilities, liver and cardiovascular disease, and diabetes. Older schools often contain high levels of PCBs, and inhalation is a major source of exposure. Technical PCB mixtures, called Aroclors, and individual dioxin-like PCBs impair adipocyte function, which can lead to type II diabetes. To determine how PCB52, a non-dioxin like PCB congener found in school air, affects adipose, adolescent male and female rats were exposed to PCB52 by nose-only inhibition for 4 h per day for 28 consecutive days. Transcriptomic analysis of white adipose revealed sex-specific differences in gene expression between PCB52- and sham-exposed males and females. Exposed females showed mitochondrial gene changes, including downregulation of the thermogenic uncoupling gene, Ucp1. Human preadipocytes/adipocytes exposed to PCB52 or its main metabolite, 4-OH-PCB52, also showed reduced norepinephrine-induced UCP1 expression. These findings suggest that PCB52 inhalation disrupts thermogenesis in adipose tissue, potentially contributing to metabolic syndrome.

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.

Rationale: Allergic sensitization and exposure to indoor allergens and endotoxin are important risk factors for asthma; however, few national studies have examined how different IgE-mediated sensitization and exposure patterns relate to asthma. Methods: Data for this cross-sectional analysis were collected as part of the National Health and Nutrition Examination Survey 2005-2006, the largest study assessing serum levels of IgE specific to a wide variety of allergens (sIgEs) and indoor allergen and endotoxin exposures. The study population consisted of children and adults; our analyses included participants with complete co-variate data (sIgEs, N=6,772; allergens, N=5,970). We performed separate latent class analyses to identify sensitization and exposure patterns and investigated how these data-driven classes were associated with asthma and wheeze related outcomes. Results: We identified 8 latent sensitization classes: 4 classes with a low likelihood for polysensitization and 4 classes with a high likelihood for polysensitization. Each class showed distinct sensitization patterns with respect to types and levels of sIgEs (median best-class probability 99.5%) and differed in their associations with the outcomes. Dust mite dominant polysensitization and sensitization to multiple allergens showed the strongest associations; the odds of asthma outcomes were up to 7- to 8-fold higher compared to the reference class with no/few sIgEs. Sensitization to only pet allergens was also consistently associated with 3- to 5-fold higher odds of asthma and wheeze. In contrast, the median best-class probability across participants was lower among the latent exposure classes (84.4%). When we evaluated the associations between the exposure class memberships and the outcomes, the effect of membership in the 6 identified latent exposure classes on asthma and wheeze was likewise less consistent and much weaker than for the 8 sensitization classes. Conclusions: Our nationally representative findings highlight the importance of allergic sensitization in asthma and demonstrate that subtypes of atopy are differently associated with asthma and wheeze.

Background: Common indoor allergens can accumulate within the sleep microenvironment (eg, bedding) and may contribute to poor sleep health. Objective: We sought to examine bedroom allergen exposure in relation to multiple sleep dimensions among US adults. Methods: Data for this study (N = 3399) were collected during the 2005 to 2006 National Health and Nutrition Examination Survey. Concentrations of 8 bedroom allergens were assessed and classified as elevated when levels exceeded 75th/90th percentile thresholds. Self-reported sleep measures included having trouble sleeping, any sleep disorder, snoring, and sleep medication use. Adjusting for confounders, we used Poisson regression to estimate associations between bedroom allergen exposures and sleep dimensions overall and by race/ethnicity, sex/gender, and socioeconomic status. Results: Among adults, elevated pet allergen exposure was the most prevalent (41.2%). Elevated pest allergen exposure was associated with a lower likelihood of a reported sleep disorder diagnosis (prevalence ratio [PRoverall], 0.68; 95% CI, 0.51-0.90). For Hispanic/Latino participants, elevated pet allergen exposure was associated with having trouble sleeping (PR, 1.74; 95% CI, 1.02-2.96) and frequent snoring (PR, 1.31; 95% CI, 1.01-1.70). Elevated fungal allergen exposure was associated with any sleep disorder diagnosis among participants with moderate socioeconomic status (PR, 3.31; 95% CI, 1.21-9.10) and a higher prevalence of sleep medication use for Hispanic/Latino participants (PR, 5.72; 95% CI, 2.53-12.90; P-interaction < .01). Elevated exposures to pet (PR, 1.93; 95% CI, 1.12-3.32) and fungal (PR, 1.71; 95% CI, 1.05-2.80) allergens were also associated with being diagnosed with any sleep disorder among women. Conclusions: In a nationally representative sample of US adults, exposure to elevated levels of bedroom allergens was associated with poor sleep health, and the magnitude of the associations was generally the strongest among minoritized racial/ethnic groups and women.

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. 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. 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. 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. National Institutes of Health (R01HL137192), (U01AI110397, K24AI106822 [to Phipatanakul]), (P30ES000002 [to Gold]), and (R35HL135818 [to Redline]).

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 in vivo toxicokinetics and placental transfer of radiolabeled [14C]-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 [14C]-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.

BACKGROUND AND AIM: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

Introduction Throughout the perinatal period children are exposed to complex mixtures, including indoor chemicals such as phthalates, and biological agents. However, few studies focus on interactions between early-life co-exposures to shed light on how co-exposures modify their individual effects. Therefore, our study aims to assess whether early-life exposure to pets and related biological agents, namely pet allergens and endotoxin, modifies the association between di-(2-ethylhexyl) phthalate (DEHP) and asthma and wheeze in preschoolers to gain insight into interactions. Methods Using data from a Canadian birth cohort study (CHILD), we conducted two complementary analyses on respiratory outcomes. First, we combined pet ownership with DEHP measurements from house dust (N=726). Second, we focused on a subgroup of children with exposure measurements of both DEHP and biological agents in dust (N=261). We used multivariable logistic regression models to assess whether pets and quantified biological agent levels modify associations between DEHP and asthma at 5 years and recurrent wheeze between 2 and 5 years. Interaction terms were included in the models and stratified analyses were further conducted. Results Associations between DEHP and asthma and wheeze were modified by pet ownership and related biological agents. For persistent/recurrent wheeze, the association with DEHP became larger among children with dogs at home and with higher dog allergens (p-interaction <0.1) and became smaller and insignificant when exposed to cats. Similarly, for asthma, the association with DEHP tended to be larger among children with dogs (also higher dog allergens) and among children without cats (also lower cat allergens) at home, respectively. Endotoxin levels modified the association between DEHP and persistent wheeze (p-interaction < 0.1). Conclusions Early-life exposure to pets and related biological agents may modify the associations between phthalates and asthma and wheeze in children. Heterogeneity in single exposure studies could be a result of differences in co-exposures among studies.