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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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8 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

BRAVE_EBC-TMT.1.0

Exhaled breath condensate (EBC) represents a low-cost and non-invasive means of examining respiratory health. EBC has been used to discover and validate exhaled volatile and non-volatile biomarkers of disease related to the respiratory system distress such as asthma, COPD, lung cancer, and secondary infections. One newly emerging utilization of EBC, is proteomics analysis, which can provide an unbiased snapshot into ongoing biological processes in the airway. Fully characterizing the biological landscape of EBC collections is challenging though, due to sample variability, and low detection sensitivity. EBC is primarily composed of condensed water, causing technical challenges with detecting key macromolecules from the dilute sample matrix; therefore, high sensitivity techniques are required to unlock the full capability of EBC as a method for non-invasive biomarker detection. To overcome some of these technical challenges for proteomic analyses, we applied our recently developed microscale proteomic techniques and developed a novel TMT based approach which enabled reliable, relative quantification with significantly improved detection of low abundance peptides/proteins across multiple healthy volunteer EBC samples. Our EBC collection design includes longitudinal EBC collections from five individual healthy volunteers on three separate days of the week with triplicate, back-to-back donations each day. Here, we report a total of 235 quantifiable proteins corresponding to 1,877 non-redundant peptides for evaluating sample collection reproducibility and establishing a healthy (human host) baseline EBC biomarker proteome studies. This work will pave the way for further investigations of EBC protein expression profiles and showcase the value of using non-invasive collection method techniques for clinically relevant biomarker discovery. This research was supported by the LDRD Biomedical Resilience And Readiness in AdVerse Operating Environments (BRAVE) Project (73748), and was conducted at Pacific Northwest National Laboratory (PNNL) in Richland, WA. PNNL is a multiprogram national laboratory operated by Battelle for the Department of Energy (DOE) under Contract DE-AC05-76RLO 1830.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

A cross-sectional study of the nasal and fecal microbiota of sows from different health status within six commercial swine farms

Cull sows are a unique population on swine farms, often representing poor producing or compromised animals, and even though recent studies have reported that the microbiome is associated with susceptibility to diseases, the microbiome of the cull sow population has not been explored. The main objective of this study was to investigate whether there were differences in fecal and upper respiratory tract microbiota composition for groups of sows of different health status (healthy, cull, and compromised/ clinical sows) and from different farms (1 to 6). Six swine farms were visited once. Thirty individual fecal samples and nasal swabs were obtained at each farm and pooled by five across health status and farm. Samples underwent 16S rRNA gene amplicon sequencing and nasal and fecal microbiota were analyzed using QIIME2 v.2021.4. Overall, the diversity of the nasal microbiota was lower than the fecal microbiota (p < 0.01). No significant differences were found in fecal or nasal alpha diversity by sow’s health status or by farm. Furthermore, there were significant differences in nasal microbial composition by farm and health status (PERMANOVA, p < 0.05), and in fecal microbiota by farm (PERMANOVA, p < 0.05), but not by health status. Lastly, at the L7 level, there was one differentially abundant taxa across farms for each nasal and fecal pooled samples. This study provided baseline information for nasal and fecal microbiota of sows under field conditions, and results suggest that farm of origin can affect microbial diversity and composition. Furthermore, sow’s health status may have an impact on the nasal microbiota composition.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Exhaled breath biomarkers of influenza infection and influenza vaccination

Respiratory viral infections are considered a major public health threat, and breath metabolomics can provide new ways to detect and understand how specific viruses affect the human pulmonary system. In this pilot study, we characterized the metabolic composition of human breath for an early diagnosis and differentiation of influenza viral infection, as well as other types of upper respiratory viral infections. We first studied the non-specific effects of planned seasonal influenza vaccines on breath metabolites in healthy subjects after receiving the immunization. We then investigated changes in breath content from hospitalized patients with flu-like symptoms and confirmed upper respiratory viral infection. The exhaled breath was sampled using a custom-made breath condenser, and exhaled breath condensate (EBC) samples were analysed using liquid chromatography coupled to quadruplole-time-of-flight mass spectrometer (LC-qTOF). All metabolomic data was analysed using both targeted and untargeted approaches to detect specific known biomarkers from inflammatory and oxidative stress biomarkers, as well as new molecules associated with specific infections. We were able to find clear differences between breath samples collected before and after flu vaccine administration, together with potential biomarkers that are related to inflammatory processes and oxidative stress. Moreover, we were also able to discriminate samples from patients with flu-related symptoms that were diagnosed with confirmatory respiratory viral panels (RVPs). RVP positive and negative differences were identified, as well as differences between specific viruses defined. These results provide very promising information for the further study of the effect of influenza A and other viruses in human systems by using a simple and non-invasive specimen like breath.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Differential transcriptomic alterations in nasal versus lung tissue of acrolein-exposed rats

Introduction: Acrolein is a significant component of anthropogenic and wildfire emissions, as well as cigarette smoke. Although acrolein primarily deposits in the upper respiratory tract upon inhalation, patterns of site-specific injury in nasal versus pulmonary tissues are not well characterized. This assessment is critical in the design of in vitro and in vivo studies performed for assessing health risk of irritant air pollutants. Methods: In this study, male and female Wistar-Kyoto rats were exposed nose-only to air or acrolein. Rats in the acrolein exposure group were exposed to incremental concentrations of acrolein (0, 0.1, 0.316, 1 ppm) for the first 30 min, followed by a 3.5 h exposure at 3.16 ppm. In the first cohort of male and female rats, nasal and bronchoalveolar lavage fluids were analyzed for markers of inflammation, and in a second cohort of males, nasal airway and left lung tissues were used for mRNA sequencing. Results: Protein leakage in nasal airways of acrolein-exposed rats was similar in both sexes; however, inflammatory cells and cytokine increases were more pronounced in males when compared to females. No consistent changes were noted in bronchoalveolar lavage fluid of males or females except for increases in total cells and IL-6. Acrolein-exposed male rats had 452 differentially expressed genes (DEGs) in nasal tissue versus only 95 in the lung. Pathway analysis of DEGs in the nose indicated acute phase response signaling, Nrf2-mediated oxidative stress, unfolded protein response, and other inflammatory pathways, whereas in the lung, xenobiotic metabolism pathways were changed. Genes associated with glucocorticoid and GPCR signaling were also changed in the nose but not in the lung. Discussion: These data provide insights into inhaled acrolein-mediated sex-specific injury/inflammation in the nasal and pulmonary airways. The transcriptional response in the nose reflects acrolein-induced acute oxidative and cytokine signaling changes, which might have implications for upper airway inflammatory disease susceptibility.

Alewel, Devin I.↗
DOE OSTI2023

Wildfire smoke exposure and early childhood respiratory health: a study of prescription claims data

Abstract Wildfire smoke is associated with short-term respiratory outcomes including asthma exacerbation in children. As investigations into developmental wildfire smoke exposure on children’s longer-term respiratory health are sparse, we investigated associations between developmental wildfire smoke exposure and first use of respiratory medications. Prescription claims from IBM MarketScan Commercial Claims and Encounters database were linked with wildfire smoke plume data from NASA satellites based on Metropolitan Statistical Area (MSA). A retrospective cohort of live infants (2010–2016) born into MSAs in six western states (U.S.A.), having prescription insurance, and whose birthdate was estimable from claims data was constructed ( N = 184,703); of these, gestational age was estimated for 113,154 infants. The residential MSA, gestational age, and birthdate were used to estimate average weekly smoke exposure days ( smoke-day ) for each developmental period: three trimesters, and two sequential 12-week periods post-birth. Medications treating respiratory tract inflammation were classified using active ingredient and mode of administration into three categories:: 'upper respiratory', 'lower respiratory', 'systemic anti-inflammatory'. To evaluate associations between wildfire smoke exposure and medication usage, Cox models associating smoke-days with first observed prescription of each medication category were adjusted for infant sex, birth-season, and birthyear with a random intercept for MSA. Smoke exposure during postnatal periods was associated with earlier first use of upper respiratory medications (1–12 weeks: hazard ratio (HR) = 1.094 per 1-day increase in average weekly smoke-day, 95%CI: (1.005,1.191); 13–24 weeks: HR = 1.108, 95%CI: (1.016,1.209)). Protective associations were observed during gestational windows for both lower respiratory and systemic anti-inflammatory medications; it is possible that these associations may be a consequence of live-birth bias. These findings suggest wildfire smoke exposure during early postnatal developmental periods impact subsequent early life respiratory health.

Dhingra, Radhika↗
DOE OSTI2024

Subject-specific multi-scale modeling of the fate of inhaled aerosols

Determining the fate of inhaled aerosols in the respiratory system is essential in assessing the potential toxicity of inhaled airborne materials, responses to airborne pathogens, or in improving inhaled drug delivery. The availability of high-resolution clinical lung imaging and advances in the reconstruction of lung airways from CT images have led to the development of subject-specific in-silico 3D models of aerosol dosimetry, often referred to as computational fluid-particle-dynamics (CFPD) models. As CFPD models require extensive computing resources, they are typically confined to the upper and large airways. These models can be combined with lower-dimensional models to form multiscale models that predict the transport and deposition of inhaled aerosols in the entire respiratory tract. Understanding where aerosols deposit is only the first of potentially several key events necessary to predict an outcome, being a detrimental health effect or a therapeutic response. To that end, multiscale approaches that combine CFPD with physiologically-based pharmacokinetics (PBPK) models have been developed to evaluate the absorption, distribution, metabolism, and excretion (ADME) of toxic or medicinal chemicals in one or more compartments of the human body. CFPD models can also be combined with host cell dynamics (HCD) models to assess regional immune system responses. Here, this paper reviews the state of the art of these different multiscale approaches and discusses the potential role of personalized or subject-specific modeling in respiratory health.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Sex-specific respiratory and systemic endocrine effects of acute acrolein and trichloroethylene inhalation

Acrolein and trichloroethylene (TCE) are priority hazardous air pollutants due to environmental prevalence and adverse health effects; however, neuroendocrine stress-related systemic effects are not characterized. Comparing acrolein, an airway irritant, and TCE with low irritancy, we hypothesized that airway injury would be linked to neuroendocrine-mediated systemic alterations. Male and female Wistar-Kyoto rats were exposed nose-only to air, acrolein or TCE in incremental concentrations over 30 min, followed by 3.5-hr exposure to the highest concentration (acrolein - 0.0, 0.1, 0.316, 1, 3.16 ppm; TCE - 0.0, 3.16, 10, 31.6, 100 ppm). Real-time head-out plethysmography revealed acrolein decreased minute volume and increased inspiratory-time (males>females), while TCE reduced tidal-volume. Acrolein, but not TCE, inhalation increased nasal-lavage-fluid protein, lactate-dehydrogenase activity, and inflammatory cell influx (males>females). Neither acrolein nor TCE increased bronchoalveolar-lavage-fluid injury markers, although macrophages and neutrophils increased in acrolein-exposed males and females. Systemic neuroendocrine stress response assessment indicated acrolein, but not TCE, increased circulating adrenocorticotrophic hormone, and consequently corticosterone, and caused lymphopenia, but only in males. Acrolein also reduced circulating thyroid-stimulating hormone, prolactin, and testosterone in males. Furthermore, acute acrolein inhalation resulted in sex-specific upper respiratory irritation/inflammation and systemic neuroendocrine alterations linked to hypothalamic-pituitary-adrenal axes activation, which is critical in mediating extra-respiratory effects.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates

The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses.

60 APPLIED LIFE SCIENCES↗