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Background: Individuals are exposed to a variety of indoor residential toxins including volatile organic compounds and particulates. In adults with asthma, such exposures are associated with asthma symptoms, asthma exacerbations, and decreased lung function. However, data on these exposures and asthma-related outcomes are generally collected at different times and not in real time. The integration of multiple platforms to collect real-time data on environmental exposure, asthma symptoms, and lung function has rarely been explored., Objective: This paper describes how adults with asthma perceive the acceptability and usability of three integrated devices: (1) residential indoor air quality monitor, (2) ecological momentary assessment (EMA) surveys delivered via a smartphone app, and (3) home spirometry, over 14 days., Methods: Participants (N=40) with uncontrolled asthma were mailed the Awair Omni indoor air quality monitor, ZEPHYRx home spirometer, and detailed instructions required for the in-home monitoring. The air quality monitor, spirometer, and EMA app were set up and tested during a videoconference or phone orientation with a research team member. Midway through the 14-day data collection period, participants completed an interview about the acceptability of the study devices or apps, instructional materials provided, and the setup process. At the end of the 14-day data collection period, participants completed a modified System Usability Scale. A random sample of 20 participants also completed a phone interview regarding the acceptability of the study and the impact of the study on their asthma., Results: Participants ranged in age from 26 to 77 (mean 45, SD 13.5) years and were primarily female (n=36, 90%), White (n=26, 67%), college graduates (n=25, 66%), and residing in a single-family home (n=30, 75%). Most indicated that the air quality monitor (n=23, 58%), the EMA (n=20, 50%), and the spirometer (n=17, 43%) were easy to set up and use. Challenges with the EMA included repetitive surveys, surveys arriving during the night, and technical issues. While the home spirometer was identified as a plausible means to evaluate lung function in real time, the interpretation of the readings was unclear, and several participants reported side effects from home spirometer use. Overall, the acceptability of the study and the System Usability Scale scores were high., Conclusions: The study devices were highly acceptable and usable. Participant feedback was instrumental in identifying technical challenges that should be addressed in future studies., (©Barbara Polivka, Kathryn Krueger, Olivia Bimbi, Luz Huntington-Moskos, Sharmilee Nyenhuis, Emily Cramer, Kamal Eldeirawi. Originally published in JMIR Formative Research (https://formative.jmir.org), 10.10.2024.)

Insulin secretion depends on the Ca 2+ -regulated fusion of granules with the plasma membrane. A recent model of Ca 2+ -triggered exocytosis in secretory cells proposes that lipids in the plasma membrane couple the calcium sensor Syt1 to the membrane fusion machinery (Kiessling et al. , 2018). Specifically, Ca 2+ -mediated binding of Syt1's C2 domains to the cell membrane shifts the membrane-anchored SNARE syntaxin-1a to a more fusogenic conformation, straightening its juxtamembrane linker. To test this model in live cells and extend it to insulin secretion, we enriched INS1 cells with a panel of lipids with different acyl chain compositions. Fluorescence lifetime measurements demonstrate that cells with more disordered membranes show an increase in fusion efficiency, and vice versa. Experiments with granules purified from INS1 cells and recombinant SNARE proteins reconstituted in supported membranes confirmed that lipid acyl chain composition determines SNARE conformation and that lipid disordering correlates with increased fusion. Addition of Syt1's C2AB domains significantly decreased lipid order in target membranes and increased SNARE-mediated fusion probability. Strikingly, Syt's action on both fusion and lipid order could be partially bypassed by artificially increasing unsaturated phosphatidylserines in the target membrane. Thus, plasma membrane lipids actively participate in coupling Ca 2+ /synaptotagmin-sensing to the SNARE fusion machinery in cells.

Background/objective: Non-clinical aspects of life, such as social, environmental, behavioral, psychological, and economic factors, what we call the sociome, play significant roles in shaping patient health and health outcomes. This paper introduces the Sociome Data Commons (SDC), a new research platform that enables large-scale data analysis for investigating such factors., Methods: This platform focuses on "hyper-local" data, i.e., at the neighborhood or point level, a geospatial scale of data not adequately considered in existing tools and projects. We enumerate key insights gained regarding data quality standards, data governance, and organizational structure for long-term project sustainability. A pilot use case investigating sociome factors associated with asthma exacerbations in children residing on the South Side of Chicago used machine learning and six SDC datasets., Results: The pilot use case reveals one dominant spatial cluster for asthma exacerbations and important roles of housing conditions and cost, proximity to Superfund pollution sites, urban flooding, violent crime, lack of insurance, and a poverty index., Conclusion: The SDC has been purposefully designed to support and encourage extension of the platform into new data sets as well as the continued development, refinement, and adoption of standards for dataset quality, dataset inclusion, metadata annotation, and data access/governance. The asthma pilot has served as the first driver use case and demonstrates promise for future investigation into the sociome and clinical outcomes. Additional projects will be selected, in part for their ability to exercise and grow the capacity of the SDC to meet its ambitious goals., Competing Interests: S.N. served on an advisory board for Avillion/Astra Zeneca, receives royalties from Wolters-Kluwer and Springer, and research funding from NIH and Asthma Allergy Foundation of America. C.S. served on advisory boards for Gilead and Merck, receives royalties from Wolters-Kluwer, and research funding from CDC. A.S. Holds voluntary positions in the American Medical Informatics Association and is an equity investor in healthcare companies and other industries. J.S. reports a potential financial interest in PulmOne Advanced Medical Devices, Ltd, Israel, and research grant funding from NIH, NSF, and Respiratory Health Association of Metropolitan Chicago. S.V. is co-founder and Chief Medical Officer for Litmus Health, Inc., and receives consulting royalties from CVS Accordant., (© The Author(s) 2023.)

Background: It is estimated that over 60% of adults with asthma have uncontrolled symptoms, representing a substantial health and economic impact. The effects of the home environment and exposure to volatile organic compounds (VOCs) and fine particulate matter (PM 2.5 ) on adults with asthma remain unknown. In addition, methods currently used to assess the home environment do not capture real-time data on potentially modifiable environmental exposures or their effect on asthma symptoms., Objective: The aims of this study are to (1) determine the feasibility and usability of ecological momentary assessment (EMA) to assess self-report residential environmental exposures and asthma symptoms, home monitoring of objective environmental exposures (total VOCs and PM 2.5 ), and lung function in terms of forced expiratory volume in 1 second (FEV 1 %); (2) assess the frequency and level of residential environmental exposures (eg, disinfectants/cleaners, secondhand smoke) via self-reported data and home monitoring objective measures; (3) assess the level of asthma control as indicated by self-reported asthma symptoms and lung function; and (4) explore associations of self-reported and objective measures of residential environmental exposures with self-reported and objective measures of asthma control., Methods: We will recruit 50 adults with asthma who have completed our online Global COVID-19 Asthma Study, indicated willingness to be contacted for future studies, reported high use of disinfectant/cleaning products, and have asthma that is not well controlled. Participants will receive an indoor air quality monitor and a home spirometer to measure VOCs, PM 2.5 , and FEV 1 %, respectively. EMA data will be collected using a personal smartphone and EMA software platform. Participants will be sent scheduled and random EMA notifications to assess asthma symptoms, environmental exposures, lung function, and mitigation strategies. After the 14-day data collection period, participants will respond to survey items related to acceptability, appropriateness, and feasibility., Results: This study was funded in March 2021. We pilot tested our procedures and began recruitment in April 2022. The anticipated completion of the study is 2023., Conclusions: Findings from this feasibility study will support a powered study to address the impact of home environmental exposures on asthma symptoms and develop tailored, home-based asthma interventions that are responsive to the changing home environment and home routines., Trial Registration: ClinicalTrials.gov NCT05224076; https://clinicaltrials.gov/ct2/show/NCT05224076., International Registered Report Identifier (irrid): DERR1-10.2196/39887., (©Sharmilee Nyenhuis, Emily Cramer, Matthew Grande, Luz Huntington-Moskos, Kathryn Krueger, Olivia Bimbi, Barbara Polivka, Kamal Eldeirawi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 02.08.2022.)

Schistosomes control inflammation in their hosts via highly effective mechanisms such as induction of Tregs, Bregs, and alternatively activated macrophages (AAMs). Notably, IPSE/alpha-1, the major secretory product from Schistosoma mansoni eggs, triggers basophils to release interleukin (IL)-4 and IL-13. Both cytokines are essential for AAM induction, suggesting an important role for IPSE/alpha-1 in inflammation control. Here, we show by in vitro co-culture experiments that IPSE/alpha-1-induced basophil IL-4/IL-13 inhibited pro-inflammatory cytokine release from human LPS-activated monocytes. This effect was cell/cell contact-independent but dependent on IL-4, since it was abrogated in the presence of anti-IL-4 antibodies. Importantly, the IPSE/alpha-1-induced IL-4/IL-13 release from basophils was amplified in the presence of LPS. Moreover, monocytes co-cultured in the presence of LPS with IPSE/alpha-1-stimulated basophils adopted an AAM-like phenotype as assessed by elevated expression of CD206 and CD209. The putative in vivo relevance of these findings was supported by immunohistological staining of S. mansoni -infected murine tissue revealing close physical contact between IPSE/alpha-1 and basophils in schistosome egg granulomas. Taken together, we found that IPSE/alpha-1 dampens inflammatory cytokine responses by triggering basophil IL-4/IL-13, in particular in the context of TLR activation, thereby turning inflammatory monocytes into anti-inflammatory AAMs. This might represent a mechanism used by schistosomes to control inflammation in the host.

Lysophosphatidic acid (LPA), a lipid mediator in biological fluids and tissues, is generated mainly by autotaxin that hydrolyzes lysophosphatidylcholine to LPA and choline. Total LPA levels are increased in bronchoalveolar lavage fluid from asthmatic lung, and are strongly induced following subsegmental bronchoprovocation with allergen in subjects with allergic asthma. Polyunsaturated molecular species of LPA (C22:5 and C22:6) are selectively synthesized in the airways of asthma subjects following allergen challenge and in mouse models of allergic airway inflammation, having been identified and quantified by LC/MS/MS lipidomics. This review discusses current knowledge of LPA production in asthmatic lung and the potential utility of polyunsaturated LPA molecular species as novel biomarkers in bronchoalveolar lavage fluid and exhaled breath condensate of asthma subjects.

Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different from those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal of this study was to define the mechanisms that control AM phenotypic and functional transformation in response to acute allergic airway inflammation. The phenotype and functional characteristics of AMs obtained from human subjects with asthma after subsegmental bronchoprovocation with allergen was studied. Using macrophage-depleted mice, the role and trafficking of AM populations was determined using an acute allergic lung inflammation model. We observed that depletion of AMs in a mouse allergic asthma model attenuates Th2-type allergic lung inflammation and its consequent airway remodeling. In both human and mouse, endobronchial challenge with allergen induced a marked increase in monocyte chemotactic proteins (MCPs) in bronchoalveolar fluid, concomitant with the rapid appearance of a monocyte-derived population of AMs. Furthermore, airway allergen challenge of allergic subjects with mild asthma skewed the pattern of AM gene expression toward high levels of the receptor for MCP1 (CCR2/MCP1R) and expression of M2 phenotypic proteins, whereas most proinflammatory genes were highly suppressed. CCL2/MCP-1 gene expression was prominent in bronchial epithelial cells in a mouse allergic asthma model, and in vitro studies indicate that bronchial epithelial cells produced abundant MCP-1 in response to house dust mite allergen. Thus, our study indicates that bronchial allergen challenge induces the recruitment of blood monocytes along a chemotactic gradient generated by allergen-exposed bronchial epithelial cells.

Rationale: Bioactive lipid mediators, derived from membrane lipid precursors, are released into the airway and airspace where they bind high-affinity cognate receptors and may mediate asthma pathogenesis. Lysophosphatidic acid (LPA), a bioactive lipid mediator generated by the enzymatic activity of extracellular autotaxin (ATX), binds LPA receptors, resulting in an array of biological actions on cell proliferation, migration, survival, differentiation, and motility, and therefore could mediate asthma pathogenesis., Objectives: To define a role for the ATX-LPA pathway in human asthma pathogenesis and a murine model of allergic lung inflammation., Methods: We investigated the profiles of LPA molecular species and the level of ATX exoenzyme in bronchoalveolar lavage fluids of human patients with asthma subjected to subsegmental bronchoprovocation with allergen. We interrogated the role of the ATX-LPA pathway in allergic lung inflammation using a murine allergic asthma model in ATX-LPA pathway-specific genetically modified mice., Measurements and Main Results: Subsegmental bronchoprovocation with allergen in patients with mild asthma resulted in a remarkable increase in bronchoalveolar lavage fluid levels of LPA enriched in polyunsaturated 22:5 and 22:6 fatty acids in association with increased concentrations of ATX protein. Using a triple-allergen mouse asthma model, we showed that ATX-overexpressing transgenic mice had a more severe asthmatic phenotype, whereas blocking ATX activity and knockdown of the LPA2 receptor in mice produced a marked attenuation of Th2 cytokines and allergic lung inflammation., Conclusions: The ATX-LPA pathway plays a critical role in the pathogenesis of asthma. These preclinical data indicate that targeting the ATX-LPA pathway could be an effective antiasthma treatment strategy.