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BackgroundLung transplantation outcomes remain complicated by bronchiolitis obliterans syndrome (BOS), a major cause of mortality and retransplantation for patients. A variety of factors linking inflammation and BOS have emerged, meriting further exploration of the microbiome as a source of inflammation. In this analysis, we determined features of the pulmonary microbiome associated with BOS susceptibility.MethodsBronchoalveolar lavage (BAL) samples were collected from 25 patients during standard of care bronchoscopies before BOS onset. Microbial DNA was isolated from BAL fluid and prepared for metagenomics shotgun sequencing. Patient microbiomes were phenotyped using k-means clustering and compared to determine effects on BOS-free survival.ResultsClustering identified 3 microbiome phenotypes: Actinobacteria dominant (AD), mixed, and Proteobacteria dominant. AD microbiomes, distinguished by enrichment with Gram-positive organisms, conferred reduced odds and risks for patients to develop acute rejection and BOS compared with non-AD microbiomes. These findings were independent of treatment models. Microbiome findings were correlated with BAL cell counts and polymorphonuclear cell percentages.ConclusionsIn some populations, features of the microbiome may be used to assess BOS susceptibility. Namely, a Gram-positive enriched pulmonary microbiome may predict resilience to BOS.

The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has disproportionately affected persons living in congregate settings, including homeless shelters (2,2). People experiencing homelessness are [...]

Health disparities are prevalent across diseases of the respiratory system, and are major sources of morbidity and mortality among disadvantaged populations in the United States. The American Thoracic Society (ATS) aims to reduce disparities that are both avoidable and unjust. In meeting this goal, the ATS is committed to creating the Lung Corps, a diverse group of senior, mid-level, and junior clinicians, trainees, researchers, and public health practitioners to help achieve health equality. This will be achieved through the following mechanisms: (1) increase awareness of health disparities; (2) empower health professionals with the knowledge and tools to address disparities; (3) shape research agendas to focus on the root causes, to identify modifiable targets, and to promote innovative approaches to reduce disparities; and (4) develop and advocate for health-related policies and regulations that improve the respiratory health of the population. To ensure success, the Lung Corps will interact with other societies, agencies, and organizations to effect elimination of disparities in respiratory health. The ATS is committed to identifying and addressing health disparities to improve the overall health of individuals affected by respiratory diseases.

The prevalence of atopic diseases is increasing globally, particularly in children. Heritable genetics can partially explain risk of disease. Evidence also points to acquired genetic material, in the form of the microbiome, as an important factor in disease pathogenesis. The acquisition of the microbiome dynamically changes in response to differences in lifestyle and environmental factors. Also, in utero, maternal and environmental factors influence atopic risk for allergic rhinitis, eczema, asthma, and food allergy. Combining the analytical power of omics, we focus on how the microbiota mediates effects between mother, environment, immunity, and risk of atopic disease. In parallel, we stress that health care disparities impact asthma morbidity and mortality. Efforts to improve asthma outcomes must include multidisciplinary strategies. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs), which express CD4 and FOXP3, are critical for modulating the immune response and promoting immune tolerance. Consequently, methods to expand Tregs for therapeutic use are of great interest. While transfer of Tregs after massive ex vivo expansion can be achieved, in vivo expansion of Tregs would be more practical. Here, we demonstrate that targeting the CD45 tyrosine phosphatase with a tolerogenic anti-CD45RB mAb acutely increases Treg numbers in WT mice, even in absence of exogenous antigen. Treg expansion occurred through substantial augmentation of homeostatic proliferation in the preexisting Treg population. Moreover, anti-CD45RB specifically increased Treg proliferation in response to cognate antigen. Compared with conventional T cells, Tregs differentially regulate their conjugation with DCs. Therefore, we determined whether CD45 ligation could alter interactions between Tregs and DCs. Live imaging showed that CD45 ligation specifically reduced Treg motility in an integrin-dependent manner, resulting in enhanced interactions between Tregs and DCs in vivo. Increased conjugate formation, in turn, augmented nuclear translocation of nuclear factor of activated T cells (NFAT) and Treg proliferation. Together, these results demonstrate that Treg peripheral homeostasis can be specifically modulated in vivo to promote Treg expansion and tolerance by increasing conjugation between Tregs and DCs., Introduction Regulatory [CD4.sup.+] T cells expressing FOXP3 (Tregs) play a critical role in tolerance by modulating immune responses to both endogenous and exogenous antigens (1, 2). FOXP3 is required for [...]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential for rapid transmission in congregate settings. We describe the multidisciplinary response to an outbreak of coronavirus disease (COVID-19) in a large homeless shelter in Chicago, Illinois, USA. The response to the outbreak included 4 rounds of mass PCR testing of all staff and residents and subsequent isolation of persons who tested positive for SARS-CoV-2. We further describe the dynamics of the shelter outbreak by fitting a modified susceptible-exposed-infectious-recovered compartmental model incorporating the widespread SARS-CoV-2 testing and isolation measures implemented in this shelter. Our model demonstrates that rapid transmission of COVID-19 in the shelter occurred before the outbreak was detected; rates of transmission declined after widespread testing and isolation measures were put in place. Overall, we demonstrate the feasibility of mass PCR testing and isolation in congregate settings and suggest the necessity of prompt response to suspected COVID-19 outbreaks in homeless shelters. [ABSTRACT FROM AUTHOR]