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Pro‐inflammatory fungal β‐d‐glucan (BDG) polysaccharides cause respiratory pathology. However, specific immunological effects of unique BDG structures on pulmonary inflammation are understudied. We characterized the effect of four unique fungal BDGs with unique branching patterns, solubility, and molecular weights in murine airways. Scleroglucan (1 → 3)(1 → 6)‐highly branched BDG, laminarin (1 → 3)(1 → 6)‐branched BDG, curdlan (1 → 3)‐linear BDG, and pustulan (1 → 6)‐linear BDG were assessed by nuclear magnetic resonance spectroscopy. Each BDG was tested by inhalation model with C3HeB/FeJ mice and compared to saline‐exposed control mice and unexposed sentinels (n = 3–19). Studies were performed ±heat‐inactivation (1 h autoclave) to increase BDG solubility. Outcomes included bronchoalveolar lavage (BAL) differential cell counts (macrophages, neutrophils, lymphocytes, eosinophils), cytokines, serum IgE, and IgG2a (multiplex and ELISA). Ex vivo primary cells removed from lungs and plated at monolayer were stimulated (BDG, lipopolysaccharide (LPS), anti‐CD3), and cytokines compared to unstimulated cells. Right lung histology was performed. Inhalation of BDGs with distinct branching patterns exhibited varying inflammatory potency and immunogenicity. Lichen‐derived (1 → 6)‐linear pustulan was the most pro‐inflammatory BDG, increasing inflammatory infiltrate (BAL), serum IgE and IgG2a, and cytokine production. Primed lung cells responded to secondary LPS stimulation with a T‐cell‐specific response to pustulan. Glucan source and solubility should be considered in exposure and toxicological studies. [ABSTRACT FROM AUTHOR]

The School Inner-City Asthma Intervention Study 2 (SICAS 2) tested interventions to reduce exposures in classrooms of students with asthma. The objective of this post-hoc analysis was limited to evaluating the effect of high-efficiency particulate (HEPA) filtration interventions on mold levels as quantified using the Environmental Relative Moldiness Index (ERMI) and the possible improvement in the students' asthma, as quantified by spirometry testing. Pre-intervention dust samples were collected at the beginning of the school year from classrooms and corresponding homes of students with asthma (n = 150). Follow-up dust samples were collected in the classrooms at the end of the HEPA or Sham intervention. For each dust sample, ERMI values and the Group 1 and Group 2 mold levels (components of the ERMI metric) were quantified. In addition, each student's lung function was evaluated by spirometry testing, specifically the percentage predicted forced expiratory volume at 1 sec (FEV1%), before and at the end of the intervention. For those students with a higher Group 1 mold level in their pre-intervention classroom than home (n = 94), the FEV1% results for those students was significantly (p < 0.05) inversely correlated with the Group 1 level in their classrooms. After the HEPA intervention, the average Group 1 and ERMI values were significantly lowered, and the average FEV1% test results significantly increased by an average of 4.22% for students in HEPA compared to Sham classrooms. HEPA intervention in classrooms reduced Group 1 and ERMI values, which corresponded to improvements in the students' FEV1% test results. [ABSTRACT FROM AUTHOR]

The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothesized that Rac1 induced pulmonary fibrosis via generation of ROS. Asbestos increased TNF-[alpha] and ROS in a Rac1-dependent manner. TNF-[alpha] was elevated only 1 day after exposure, whereas ROS generation progressively increased in bronchoalveolar lavage cells obtained from wild-type (WT) mice. To determine whether ROS generation contributed to pulmonary fibrosis, we overexpressed catalase in WT monocytes and observed a decrease in ROS generation in vitro. More importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo. For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos-induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease. macrophages doi: 10.1152/ajplung.90590.2008.

We conducted a randomized trial of portable HEPA air cleaners in the homes of children age 6–12 years with asthma in the Yakima Valley, Washington. All families received asthma education while intervention families also received two HEPA cleaners (child's bedroom, living room). We collected 14‐day integrated samples of endotoxin in settled dust and PM10 and PM10‐2.5 in the air of the children's bedrooms at baseline and one‐year follow‐up, and used linear regression to compare follow‐up levels, adjusting for baseline. Seventy‐one families (36 HEPA, 35 control) completed the study. Baseline geometric mean (GSD) endotoxin loadings were 1565 (6.3) EU/m2 and 2110 (4.9) EU/m2, respectively, in HEPA vs. control homes while PM10 and PM10‐2.5 were 22.5 (1.9) μg/m3 and 9.5 (2.9) μg/m3, respectively, in HEPA homes, and 19.8 (1.8) μg/m3 and 7.7 (2.0) μg/m3, respectively, in control homes. At follow‐up, HEPA families had 46% lower (95% CI, 31%–57%) PM10 on average than control families, consistent with prior studies. In the best‐fit heterogeneous slopes model, HEPA families had 49% (95% CI, 6%–110%) and 89% lower (95% CI, 28%–177%) PM10‐2.5 at follow‐up, respectively, at 50th and 75th percentile baseline concentrations. Endotoxin loadings did not differ significantly at follow‐up (4% lower, HEPA homes; 95% CI, −87% to 50%). [ABSTRACT FROM AUTHOR]

Importance: School and classroom allergens and particles are associated with asthma morbidity, but the benefit of environmental remediation is not known.Objective: To determine whether use of a school-wide integrated pest management (IPM) program or high-efficiency particulate air (HEPA) filter purifiers in the classrooms improve asthma symptoms in students with active asthma.Design, Setting, and Participants: Factorial randomized clinical trial of a school-wide IPM program and HEPA filter purifiers in the classrooms was conducted from 2015 to 2020 (School Inner-City Asthma Intervention Study). There were 236 students with active asthma attending 41 participating urban elementary schools located in the Northeastern US who were randomized to IPM by school and HEPA filter purifiers by classroom. The date of final follow-up was June 20, 2020.Interventions: The school-wide IPM program consisted of application of rodenticide, sealing entry points, trap placement, targeted cleaning, and brief educational handouts for school staff. Infestation was assessed every 3 months, with additional treatments as needed. Control schools received no IPM, cleaning, or education. Classroom portable HEPA filter purifiers were deployed and the filters were changed every 3 months. Control classrooms received sham HEPA filters that looked and sounded like active HEPA filter purifiers. Randomization was done independently (split-plot design), with matching by the number of enrolled students to ensure a nearly exact 1:1 student ratio for each intervention with 118 students randomized to each group. Participants, investigators, and those assessing outcomes were blinded to the interventions.Main Outcomes and Measures: The primary outcome was the number of symptom-days with asthma during a 2-week period. Symptom-days were assessed every 2 months during the 10 months after randomization.Results: Among the 236 students who were randomized (mean age, 8.1 [SD, 2.0] years; 113 [48%] female), all completed the trial. At baseline, the 2-week mean was 2.2 (SD, 3.9) symptom-days with asthma and 98% of the classrooms had detectable levels of mouse allergen. The results were pooled because there was no statistically significant difference between the 2 interventions (P = .18 for interaction). During a 2-week period, the mean was 1.5 symptom-days with asthma after use of the school-wide IPM program vs 1.9 symptom-days after no IPM across the school year (incidence rate ratio, 0.71 [95% CI, 0.38-1.33]), which was not statistically significantly different. During a 2-week period, the mean was 1.6 symptom-days with asthma after use of HEPA filter purifiers in the classrooms vs 1.8 symptom-days after use of sham HEPA filter purifiers across the school year (incidence rate ratio, 1.47 [95% CI, 0.79-2.75]), which was not statistically significantly different. There were no intervention-related adverse events.Conclusions and Relevance: Among children with active asthma, use of a school-wide IPM program or classroom HEPA filter purifiers did not significantly reduce symptom-days with asthma. However, interpretation of the study findings may need to consider allergen levels, particle exposures, and asthma symptoms at baseline.Trial Registration: ClinicalTrials.gov Identifier: NCT02291302. [ABSTRACT FROM AUTHOR]

Adverse respiratory health effects in the agricultural industry have been linked to particulate endotoxin exposure. However, whether the endotoxin concentration is significantly correlated to the size of the particle remains an open question. To date, limited research has been conducted to assess particulate endotoxin exposures in the agricultural industry in general or the equine industry in particular. A task-based exposure assessment was conducted to characterize the endotoxin levels of inhalable and respirable particles on four Kentucky farms during the summer season. We conducted personal sampling of respirable and inhalable particles (n = 75) across all four farms and particulate endotoxin (n = 58) on two of them. Simultaneously, we collected real-time area samples across all four farms by task – horse care, filing hooves, cleaning stalls, cleaning barns, cleaning dry lots, and cleaning trucks. The endotoxin concentration of inhalable particles (geometric mean: 50.2–1,024 EU/m3) was ~50 times higher than that of respirable particles (geometric mean: 1.72–19.0 EU/m3). Horse care generated the lowest endotoxin concentrations for both particle sizes, while cleaning tasks tended to produce higher concentrations. There was no significant correlation between the endotoxin and particle concentrations for each size fraction based on tasks by farm (R2 = 0.069 for inhalable; 0.214 for respirable). The equine workers in this study were exposed to higher endotoxin concentrations than workers in other industries, such as the swine industry. Providing exposure control guidelines and recommendations to the equine industry is necessary to reduce long-term endotoxin exposure and to prevent adverse respiratory symptoms. [ABSTRACT FROM AUTHOR]

The kinetic Limulus amebocyte lysate (LAL) assay and the recombinant factor C (rFC) assay are used for comparing airborne endotoxin concentrations in laboratory- and field-collected parallel air samples. Mixed-model analysis of variance (ANOVA) for the field studies has showed major interactions of facility-sampler and facility-assay and the studies have shown that the LAL assay and rFC assay have returned similar estimates of exposure in livestock facilities.

Highly sensitive enzyme immunoassays are developed for measuring airborne [beta]-(1,3)-glucans in low-exposure environments, like homes. The combination of the newly developed [beta]-(1,3)-glucan sandwich enzyme immunoassay (EIA) with electrostatic dust fall collector (EDC) sampling has allowed the assessment in large-scale populations studies of exposure to airborne [beta]-(1,3)-glucans in homes or other low-exposure environments.

Endotoxin exacerbates asthma. We designed the Louisa Environmental Intervention Project (LEIP) and assessed its effectiveness in reducing household endotoxin and improving asthma symptoms in rural Iowa children. Asthmatic school children (N = 104 from 89 homes) of Louisa and Keokuk counties in Iowa (aged 5‐14 years) were recruited and block‐randomized to receive extensive (education + professional cleaning) or educational interventions. Environmental sampling collection and respiratory survey administration were done at baseline and during three follow‐up visits. Mixed‐model analyses were used to assess the effect of the intervention on endotoxin levels and asthma symptoms in the main analysis and of endotoxin reduction on asthma symptoms in exploratory analysis. In the extensive intervention group, dust endotoxin load was significantly reduced in post‐intervention visits. The extensive compared with the educational intervention was associated with significantly decreased dust endotoxin load in farm homes and less frequent nighttime asthma symptoms. In exploratory analysis, dust endotoxin load reduction from baseline was associated with lower total asthma symptoms score (Odds ratio: 0.52, 95% confidence interval: 0.29‐0.92). In conclusion, the LEIP intervention reduced household dust endotoxin and improved asthma symptoms. However, endotoxin reductions were not sustained post‐intervention by residents. [ABSTRACT FROM AUTHOR]

Assessing the environmental, health and climate impacts of bioaerosols requires knowledge of their size and abundance. These two properties were assessed through daily measurements of chemical tracers for pollens (sucrose, fructose, and glucose), fungal spores (mannitol and glucans) and Gram-negative bacterial endotoxins in fine particulate matter (PM2.5), coarse PM (PM10-2.5) and PM10 (as the combination of PM2.5 and PM10-2.5) during the spring tree pollen season (mid-April to early-May) and late summer ragweed season (late-August to early-September) in the Midwestern US in 2013. Under dry conditions, pollen and fungal spore tracers were primarily in coarse PM (˃ 75%), as expected for particles greater than 2.5 µm. Rainfall on May 2 corresponded to maximum atmospheric pollen tracer levels and a redistribution of pollen tracers to the fine PM fraction (˃ 80%). Both changes were attributed to the osmotic rupture of pollen grains that led to the suspension of fine-sized pollen fragments. Fungal spore tracers peaked in concentration following spring rain events and decreased in particle size, but to a lesser extent than pollens. A short, heavy thunderstorm in late summer corresponded to an increase in endotoxin and glucose levels, with a simultaneous shift to smaller particle sizes. Simultaneous increases in bioaerosol levels and decrease in their size has significant implications for population exposures to bioaerosols, particularly during rain events. Chemical mass balance (CMB) source apportionment modelling and regionally-specific pollen profiles were used to apportion PM mass to pollens and fungal spores. Springtime pollen contributions to PM10 mass ranged from 0.04-0.8 µg m-3 (0.2-38%, averaging 4%), with maxima occurring on rainy days. Fungal spore contributions to PM10 mass ranged from 0.1-1.5 µg m-3 (0.8-17%, averaging 5%), with maxima occurring after rain. Overall, this study defines changes to size distributions and concentrations of pollens, fungal spores, and endotoxins in response to rain in the Midwestern United States and advances the ability to apportion PM mass to pollens. [ABSTRACT FROM AUTHOR]

Electrostatic Dust Collectors (EDCs) are in use for passive sampling of bioaerosols, but particular aspects of their performance have not yet been evaluated. This study investigated the effect of mailing EDCs on endotoxin loading and the effect of EDC deployment in front of, and away from, heated ventilation on endotoxin sampling. Endotoxin sampling efficiency of heated and unheated EDC cloths was also evaluated. Cross-country express mailing of dust-spiked EDCs yielded no significant changes in endotoxin concentrations compared to dust-only samples for both high-spiked EDCs (p = 0.30) and low-spiked EDCs (p = 0.36). EDCs were also deployed in 20 identical apartments with one EDC placed in front of the univent heater in each apartment and contemporaneous EDC placed on the built-in bookshelf in each apartment. The endotoxin concentrations were significantly different (p = 0.049) indicating that the placement of EDC does impact endotoxin sampling. Heated and unheated EDCs were deployed for 7 days in pairs in farm homes. There was a significant difference between endotoxin concentrations (p = 0.027) indicating that heating EDCs may diminish their electrostatic capabilities and impact endotoxin sampling. The last study investigated the electrostatic charge of 12 heated and 12 unheated EDC cloths. There was a significant difference in charge (p = 0.009) which suggests that heating EDC cloths may make them less effective for sampling. In conclusion, EDCs can be mailed to and from deployment sites, EDC placement in relationship to ventilation is crucial, and heating EDCs reduces their electrostatic charge which may diminish their endotoxin sampling capabilities. [ABSTRACT FROM AUTHOR]