Use of epigenetically modified bacteriophage and dual beta-lactams to treat a Mycobacterium abscessus sternal wound infection.

Nontuberculous mycobacterium (NTM) infections are challenging to manage and are frequently non-responsive to aggressive but poorly-tolerated antibiotic therapies. Immunosuppressed lung transplant patients are susceptible to NTM infections and poor patient outcomes are common. Bacteriophages present an alternative treatment option and are associated with favorable clinical outcomes.

Outcomes Following Lung Transplant for COVID-19-Related Complications in the US.

Importance: The COVID-19 pandemic led to the use of lung transplant as a lifesaving therapy for patients with irreversible lung injury. Limited information is currently available regarding the outcomes associated with this treatment modality.

Objective: To describe the outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis.

Effect of Antifibrotic Therapy on Survival in Patients With Idiopathic Pulmonary Fibrosis.

Purpose: Real-world studies have reported reduced mortality in patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotic therapy; however, the initiation or discontinuation of therapy during these studies may have introduced bias. This study investigated the effect of antifibrotic therapy on mortality and other outcomes in patients with IPF using causal inference methodology.

Methods: Data from a multicenter US registry of patients with IPF were used to assess the effect of antifibrotic therapy (nintedanib or pirfenidone) on death, death or lung transplant, respiratory-related hospitalization, and acute worsening of IPF (defined as any health care encounter deemed due to acute worsening of IPF).

Pharmacotherapy of chronic lung allograft dysfunction post lung transplantation.

Background: Chronic lung allograft dysfunction (CLAD) remains the primary cause of death in lung transplant recipients (LTRs) despite improvements in immunosuppression management. Despite advances in knowledge regarding the pathogenesis of CLAD, treatments that are currently available are usuallyineffective and delay progression of disease at best.There are currently no evidence-based guidelines and minimal publications regarding the optimal treatment ofCLAD.

Cell-mimicking nanodecoys neutralize SARS-CoV-2 and mitigate lung injury in a non-human primate model of COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has grown into a global pandemic, and only a few antiviral treatments have been approved to date. Angiotensin-converting enzyme 2 (ACE2) plays a fundamental role in SARS-CoV-2 pathogenesis because it allows viral entry into host cells. Here we show that ACE2 nanodecoys derived from human lung spheroid cells (LSCs) can bind and neutralize SARS-CoV-2 and protect the host lung cells from infection.

A pre-investigational new drug study of lung spheroid cell therapy for treating pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a lethal interstitial lung disease with unknown etiology, no cure, and few treatment options. Herein, a therapy option is presented that makes use of a heterogeneous population of lung cells, including progenitor cells and supporting cells lines, cultured in adherent and suspension conditions, the latter of which induces spontaneous spheroid formation. Within these spheroids, progenitor marker expression is augmented.

Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant.

Targeted repair of heart injury by stem cells fused with platelet nanovesicles.

Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites.

Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis.

Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies.

Background: Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality.

Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.

Unlabelled: Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies.

Pan-Resistant Achromobacter xylosoxidans and Stenotrophomonas maltophilia Infection in Cystic Fibrosis Does Not Reduce Survival After Lung Transplantation.

Background: The number of cystic fibrosis (CF) patients undergoing lung transplantation continues to grow, as does the prevalence of multidrug-resistant (MDR) gram-negative rods. However, the posttransplant survival of patients with MDR pathogens, specifically pan-resistant Achromobacter xylosoxidans and Stenotrophomonas maltophilia, is poorly characterized.

Methods: This was a retrospective review of CF patients (n = 186; all age, > 16 years) transplanted at the University of North Carolina from 1990 through 2013.

Respiratory infections in patients with cystic fibrosis undergoing lung transplantation.

Cystic fibrosis is an inherited disease characterised by chronic respiratory infections associated with bronchiectasis. Lung transplantation has helped to extend the lives of patients with cystic fibrosis who have advanced lung disease. However, persistent, recurrent, and newly acquired infections can be problematic.

Lung transplant outcomes in cystic fibrosis patients with pre-operative Mycobacterium abscessus respiratory infections.

Background: Mycobacterium abscessus in cystic fibrosis (CF) patients is considered a contraindication to lung transplantation. We examine the post-transplant outcomes of CF patients with M. abscessus pre-transplant.

Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation.

Background: Lung transplantation is limited by chronic lung allograft dysfunction. Acute cellular rejection (ACR) is a risk factor for allograft dysfunction; however, the role of antibody-mediated rejection (AMR) is not well characterized.

Methods: This was a retrospective review from 2007 to 2011 of lung transplant recipients with human leukocyte antigen (HLA) antibody testing using Luminex (Luminex Corp, Austin, TX) single-antigen beads.