Publications by authors named "Howard Huang"

Article Synopsis
  • A better understanding of chronic lung allograft dysfunction (CLAD) is needed, as it leads to high mortality rates after lung transplants.
  • The study focused on a genetic variation (C3R102G) that enhances complement activation, finding that lung transplant recipients with this variation tend to have poorer outcomes related to CLAD, especially if they develop donor-specific antibodies.
  • In experiments with mice, decreased regulation of the complement system resulted in worse airway damage and increased B cell activity, linking genetic predisposition to complement activation with worse survival outcomes after lung transplantation.
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Introduction: A history of lung transplantation is a risk factor for poor outcomes in patients undergoing laparoscopic fundoplication. We wanted to determine whether enhanced recovery after a robotic-assisted surgery program would mitigate these risks.

Methods: We performed a single-center retrospective analysis of the Society of Thoracic Surgery database for patients who underwent elective antireflux procedures from 1/2018 to 2/2021 under the enhanced recovery after surgery program using robotic assistance.

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A growing body of evidence supports the use of bivalirudin as an alternative to unfractionated heparin (UFH) for the prevention of thrombotic events in patients on venovenous (VV) extracorporeal membrane oxygenation (ECMO). However, data in patients bridged to lung transplantation are limited. In this case series, we describe the outcomes of six patients who were transitioned from UFH to bivalirudin during their course of VV ECMO support as a bridge to lung transplantation.

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Introduction: Tacrolimus forms the backbone of immunosuppression regimens in lung transplant recipients (LTRs). It is extensively metabolized by cytochrome P450 (CYP) 3A5 enzymes, of which polymorphisms can significantly affect tacrolimus dose requirements. It is unknown how coadministration of tacrolimus with voriconazole, a potent CYP3A5 inhibitor, affects rejection rates or empiric dose adjustments needed after voriconazole discontinuation.

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Background: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.

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Article Synopsis
  • CFTR modulator drugs improve lung function and body mass index in cystic fibrosis patients, but inflammation remains a challenge, indicating a need to target the underlying causes in the lungs of patients with established disease.* -
  • The study explores the presence of unique, potentially pathogenic stem cell variants in cystic fibrosis lungs, similar to those found in COPD, and aims to identify which of these variants contribute to ongoing inflammation.* -
  • Research utilized advanced stem cell cloning technology on end-stage CF lungs to identify five predominant stem cell variants, three of which are pro-inflammatory, highlighting the complexity of stem cell involvement in cystic fibrosis lung inflammation.*
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Article Synopsis
  • Idiopathic pulmonary fibrosis (IPF) is a severe lung disease characterized by the replacement of healthy lung tissue with dense fibrotic tissue, leading to progressive respiratory failure.
  • Research utilizing single-cell RNA sequencing has uncovered a specific type of stem cell in IPF patients that is capable of converting normal lung cells into harmful myofibroblasts, suggesting a critical role in disease progression.
  • Drug testing revealed that this profibrotic stem cell variant may be targeted with specific inhibitors, indicating potential new therapeutic approaches for treating IPF.
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Unlabelled: Combined liver-lung transplantation is an uncommon, although vital, procedure for patients with simultaneous end-stage lung and liver disease. The utility of lung-liver transplant has been questioned because of initial poor survival outcomes, particularly when compared with liver-alone transplant recipients.

Methods: A single-center, retrospective review of the medical records of 19 adult lung-liver transplant recipients was conducted, comparing early recipients (2009-2014) with a recent cohort (2015-2021).

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Background: Solid organ transplant (SOT) recipients are at increased risk for morbidity and mortality from COVID-19 due to their immunosuppressed state and reduced immunogenicity from COVID-19 mRNA vaccines. This investigation examined the association between COVID-19 mRNA vaccination status and mortality among SOT recipients diagnosed with COVID-19.

Methods & Findings: A retrospective, registry-based chart review was conducted investigating COVID-19 mortality among immunosuppressed solid organ transplant (SOT) recipients in a large metropolitan healthcare system in Houston, Texas, USA.

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Background: Solid organ transplant (SOT) recipients are predicted to have worse COVID-19 outcomes due to their compromised immunity. However, this association remains uncertain because published studies have had small sample sizes and variability in chronic comorbidity adjustment.

Methods: In this retrospective cohort study conducted at a multihospital health system, we compared COVID-19 outcomes and survival up to 60 days following hospital admission in SOT recipients taking baseline immunosuppressants versus hospitalized control patients.

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Background: Despite causing increased morbidity and mortality, pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) patients (COPD-PH) lacks treatment, due to incomplete understanding of its pathogenesis. Hypertrophy of pulmonary arterial walls and pruning of the microvasculature with loss of capillary beds are known features of pulmonary vascular remodeling in COPD. The remodeling features of pulmonary medium- and smaller vessels in COPD-PH lungs are less well described and may be linked to maladaptation of endothelial cells to chronic cigarette smoking (CS).

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Article Synopsis
  • COVID-19 can cause serious lung problems, and in some cases, patients may need a lung transplant to survive.
  • Researchers studied lung samples from patients with severe COVID-19 to understand how lung damage happens quickly.
  • They found that certain genes that help create scar tissue in the lungs are expressed at high levels in COVID-19 patients, which could help explain why some people's lungs get worse so fast.
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Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients, but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-β bioavailability without altering its expression.

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A recent study concluded that SARS-CoV-2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression- and machine learning-based analyses to compare antibody responses by immunosuppressive agents in a national cohort (n = 1037).

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Background: Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations.

Methods: Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines.

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Pulmonary hypertension (PH) comprises a diverse group of disorders that share a common pathway of pulmonary vascular remodeling leading to right ventricular failure. Development of anti-remodeling strategies is an emerging frontier in PH therapeutics that requires a greater understanding of the interactions between vascular wall cells and their extracellular matrices. The ubiquitous matrix glycan, hyaluronan (HA), is markedly elevated in lungs from patients and experimental models with PH.

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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally and cause significant morbidity and mortality. Antispike protein monoclonal antibody (mAb) therapy has been shown to prevent progression to severe coronavirus disease 2019 (COVID-19). The objective of this study was to report the outcomes of high-risk, SARS-CoV-2-positive patients infused with 1 of the 3 mAb therapies available through Food and Drug Administration Emergency Use Authorization (EUA).

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Purpose: Bronchiolitis obliterans syndrome (BOS) is a major cause of morbidity and mortality in lung transplantation and allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Clinical guidelines recommend lung function monitoring to aid early identification of BOS, but real-world rates of pulmonary function testing (PFT) have not been studied. The purpose of this study was to quantify PFT rates in lung transplantation and allo-HSCT recipients.

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Aims: Chronic lung allograft dysfunction (CLAD), a common complication of lung transplantation, is the leading cause of death for lung transplant recipients. While data on lung transplant costs are available, the impact of CLAD on healthcare resource use (HRU) and cost is not well understood. The primary objective was to quantify the HRU and costs of CLAD in the US using real-world data.

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Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. The role of the developmental transcription factor Sine oculis homeobox homolog 1 (SIX1) in the pathophysiology of lung fibrosis is not known. IPF lung tissue samples and IPF-derived alveolar type II cells (AT2) showed a significant increase in SIX1 mRNA and protein levels, and the SIX1 transcriptional coactivators EYA1 and EYA2 were elevated.

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The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a two-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial.

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Response to two doses of a nucleoside-modified messenger ribonucleic acid (mRNA) vaccine was evaluated in a large solid-organ transplant program. mRNA COVID-19 vaccine was administered to transplant candidates and recipients who met study inclusion criteria. Qualitative anti-SARS-CoV-2 Spike Total Immunoglobulin (Ig) and IgG-specific assays, and a semi-quantitative test for anti-SARS-CoV-2 Spike protein IgG were measured in 241 (17.

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Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease with a variable clinical course. Biomarkers that predict patient outcomes are needed. We leveraged data from 300 patients in the multicenter IPF-PRO Registry to determine associations between circulating proteins and the composite outcome of respiratory death or lung transplant.

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