Structural characterization of gas-phase cysteine and cysteine methyl ester complexes with zinc and cadmium dications by infrared multiple photon dissociation spectroscopy

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Chronic lung allograft dysfunction: Definition, diagnostic criteria, and approaches to treatment―A consensus report from the Pulmonary Council of the ISHLT

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Expectations and outcomes of prolonged mechanical ventilation*

Prolonged mechanical ventilation (PMV) provision is increasing markedly despite poor patient outcomes. Misunderstanding prognosis in the PMV decision making process could provide an explanation to this phenomenon. Therefore, we aimed to compare PMV decision makers' expectations for long-term patient outcomes with prospectively observed outcomes

Role of C-C Motif Ligand 2 and C-C Motif Receptor 2 in Murine Pulmonary Graft-versus-Host Disease after Lipopolysaccharide Inhalations

Environmental exposures are a potential trigger of chronic pulmonary graft-versus-host disease (pGVHD) after successful recovery from hematopoietic cell transplant (HCT). We hypothesized that inhalations of LPS, a prototypic environmental stimulus, trigger pGVHD via increased pulmonary recruitment of donor-derived antigen-presenting cells (APCs) through the C-C motif ligand 2 (CCL2)–C-C motif receptor 2 (CCR2) chemokine axis. B10.BR(H2k) and C57BL/6(H2b) mice underwent allogeneic (Allo) or syngeneic (Syn) HCT with wild-type (WT) C57BL/6, CCL2−/−, or CCR2−/− donors. After 4 weeks, recipient mice received daily inhaled LPS for 5 days and were killed at multiple time points. Allo mice exposed to repeated inhaled LPS developed prominent lymphocytic bronchiolitis, similar to human pGVHD. The increase in pulmonary T cells in Allo mice after LPS exposures was accompanied by increased CCL2, CCR2, and Type-1 T-helper cytokines as well as by monocytes and monocyte-derived dendritic cells (moDCs) compared with Syn and nontransplanted controls. Using CCL2−/− donors leads to a significant decrease in lung DCs but to only mildly reduced CD4 T cells. Using CCR2−/− donors significantly reduces lung DCs and moDCs but does not change T cells. CCL2 or CCR2 deficiency does not alter pGVHD pathology but increases airway hyperreactivity and IL-5 or IL-13 cytokines. Our results show that hematopoietic donor-derived CCL2 and CCR2 regulate recruitment of APCs to the Allo lung after LPS exposure. Although they do not alter pathologic pGVHD, their absence is associated with increased airway hyperreactivity and IL-5 and IL-13 cytokines. These results suggest that the APC changes that result from CCL2–CCR2 blockade may have unexpected effects on T cell differentiation and physiologic outcomes in HCT

Novel Role for Surfactant Protein A in Gastrointestinal Graft-versus-Host Disease

Graft-versus-host-disease (GVHD) is a severe and frequent complication of allogeneic bone marrow transplantation (BMT) that involves the gastrointestinal tract and lungs. The pathobiology of GVHD is complex and involves immune cell recognition of host antigens as foreign. We hypothesize a central role for the collectin surfactant protein A (SP-A) in regulating the development of GVHD after allogeneic BMT

Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model

Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recipient PTX3 in development of chronic rejection, we used a minor alloantigen-mismatched murine orthotopic single lung transplant model. Male C57BL/10 mice were used as donors. Male PTX3 knockout (KO) mice and their wild type (WT) littermates on 129/SvEv/C57BL6/J background were used as recipients. In KO recipients, 7/13 grafted lungs were consolidated without volume recovery on CT scan, while only 2/9 WT mice showed similar graft consolidation. For grafts where lung volume could be reliably analyzed by CT scan, the lung volume recovery was significantly reduced in KO mice compared to WT. Interstitial inflammation, parenchymal fibrosis and bronchiolitis obliterans scores were significantly higher in KO mice. Presence of myofibroblasts and lymphoid aggregation was significantly enhanced in the grafts of PTX3 KO recipients. Recipient PTX3 deficiency enhanced chronic rejection-like lesions by promoting a fibrotic process in the airways and lung parenchyma. The underlying mechanisms and potential protective role of exogenous PTX3 as a therapy should be further explored

Caregiver-assisted coping skills training for patients with COPD: background, design, and methodological issues for the INSPIRE-II study

Chronic Obstructive Pulmonary Disease (COPD) is a progressive illness characterized by airflow obstruction and dyspnea that afflicts over 12 million people and represents a leading cause of death in the United States. Not surprisingly, COPD is often associated with emotional distress and reduced psychosocial adjustment, which can negatively impact physical functioning and impair quality of life. However, the psychosocial consequences of COPD remain largely untreated. A previous randomized trial from our research team demonstrated that coping skills training (CST) can improve pulmonary-specific quality of life among pulmonary patients awaiting lung transplant (the INSPIRE study). To date, however, no studies have examined the effects of a caregiver-assisted CST intervention in patients with COPD with less severe disease

Neurobehavioral Functioning and Survival Following Lung Transplantation

Neurobehavioral functioning is widely recognized as being an important consideration in lung transplant candidates, but little is known about whether these factors are related to clinical outcomes. The present study examined the relationship of neurobehavioral functioning, including measures of executive function and memory, depression, and anxiety, to long-term survival among lung transplant recipients

The Effects of a Telehealth Coping Skills Intervention on Outcomes in Chronic Obstructive Pulmonary Disease: Primary Results From the INSPIRE-II Study

Chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality and reduced quality of life. Novel interventions are needed to improve outcomes in COPD patients. The present study assessed the effects of a telephone-based coping skills intervention on psychological and somatic quality of life and on the combined medical endpoint of COPD-related hospitalizations and all-cause mortality