precision-cut-lung-slices-as-an-efficient-tool-for-ex-vivo-pulmonary

Precision Cut Lung Slices as an Efficient Tool for <em>Ex vivo</em> Pulmonary Vessel Structure and Contractility Studies

The visualization of murine lung tissue provides valuable structural and cellular information regarding the underlying airway and vasculature. However, ...

Boston Children's Hospital

Congenital TEFs without esophageal atresia are rare but may occur more frequently than previously documented in literature. Careful history is required to suspect the diagnoses, as most patients will present with coughing associated with solid or liquids, recurrent unexplained pulmonary infections and complaints with eating. Some patients may show signs of chronic airway changes from recurrent aspiration pneumonia at the time of presentation. Diagnosis is challenging, with multiple imaging modalities including x ray, CT scan and esophogram able to identify a fistula. Surgery is required to improve quality of life and prevent chronic airway changes, and most cases repaired have no complications.

Presentation of an H-type tracheoesophageal fistula in an adolescent male with cystic fibrosis: A case report and review of literature.

Pediatric Lung Transplant: Influences of Viral and Fungal Infections on Outcomes and Viral Markers as a Predictor of Outcome.

The delicate structure of murine lungs poses many challenges for acquiring high-quality images that truly represent the living lung. Here, we describe several optimized procedures for obtaining and imaging murine lung tissue. Compared to traditional paraffin cross-section and optimal cutting temperature (OCT), agarose-inflated vibratome sections (aka precision-cut lung slices), combines comparable structural preservation with experimental flexibility. In particular, we discuss an optimized procedure to precision-cut lung slices that can be used to visualize three-dimensional cell-cell interactions beyond the limitations of two-dimensional imaging. Super-resolution microscopy can then be used to reveal the fine structure of lung tissue's cellular bodies and processes that regular confocal cannot. Lastly, we evaluate the entire lung vasculature with clearing technology that allows imaging of the entire volume of the lung without sectioning. In this manuscript, we combine the above procedures to create a novel and evolutionary method to study cell behavior , trace and reconstruct pulmonary vasculature, address fundamental questions relevant to a wide variety of vascular disorders, and perceive implications to better imaging clinical tissue.

From 2D to 3D: Promising Advances in Imaging Lung Structure.

Alveolar rhabdomyosarcoma presenting as a pleural effusion: An atypical presentation of a malignancy.

Despite recent advances over the past decade in lung transplantation including improved surgical technique and immunotherapy, the diagnosis and treatment of chronic lung allograft dysfunction remains a significant barrier to recipient survival. Aside from bronchiolitis obliterans syndrome, a restrictive phenotype called restrictive allograft syndrome has recently been recognized and affects up to 35% of all patients with CLAD. The main characteristics of RAS include a persistent and unexplained decline in lung function compared to baseline and persistent parenchymal infiltrates on imaging. The median survival after diagnosis of RAS is 6 to 18 months, significantly shorter than other forms of CLAD. Treatment options are limited, as therapies used for BOS are typically ineffective at halting disease progression. Specific medications such as fibrinolytics are lacking large, multicenter prospective studies. In this manuscript, we discuss the definition, mechanism, and characteristics of RAS while highlighting the similarities and differences between other forms of CLAD. We also review the diagnoses along with current and potential treatment options that are available for patients. Finally, we discuss the existing knowledge gaps and areas for future research to improve patient outcomes and understanding of RAS.

Restrictive allograft syndrome after lung transplantation.

Pulmonary artery hypertension (PAH) is a devastating cardiopulmonary disease characterized by vascular remodeling and obliteration of the precapillary pulmonary arterioles. Alterations in the structure and function of pulmonary vessels result in the resistance of blood flow and can progress to right-sided heart failure, causing significant morbidity and mortality. There are several types of PAH, and the disease can be familial or secondary to an underlying medical condition such as a connective tissue disorder or infection. Regardless of the cause, the exact pathophysiology and cellular interactions responsible for disease development and progression are largely unknown.There is significant evidence to suggest altered immune and vascular cells directly participate in disease progression. Inflammation has long been hypothesized to play a vital role in the development of PAH, as an altered or skewed immune response favoring a proinflammatory environment that can lead to the infiltration of cells such as lymphocytes, macrophages, and neutrophils. Current treatment strategies focus on the dilation of partially occluded vessels; however, such techniques have not resulted in an effective strategy to reverse or prevent vascular remodeling. Therefore, current studies in human and animal models have attempted to understand the underlying pathophysiology of pulmonary hypertension (PH), specifically focusing on the inflammatory cascade predisposing patients to disease so that better therapeutic targets can be developed to potentially reverse or prevent disease progression.The purpose of this chapter is to provide a comprehensive review of the expanding literature on the inflammatory process that participates in PH development while highlighting important and current studies in both animal and human models. While our primary focus will be on cells found in the adaptive and innate immune system, we will review all potential causes of PAH, including cells of the endothelium, pulmonary lymphatics, and genetic mutations predisposing patients. In addition, we will discuss current therapeutic options while highlighting potential future treatments and the questions that still remain unanswered.

Article	Year
Presentation of an H-type tracheoesophageal fistula in an adolescent male with cystic fibrosis: A case report and review of literature. Clinical imaging\| PubMed ID: 31864198	2020
Pediatric Lung Transplant: Influences of Viral and Fungal Infections on Outcomes and Viral Markers as a Predictor of Outcome. American journal of respiratory and critical care medicine\| PubMed ID: 32223550	2020
From 2D to 3D: Promising Advances in Imaging Lung Structure. Frontiers in medicine\| PubMed ID: 32766264	2020
Alveolar rhabdomyosarcoma presenting as a pleural effusion: An atypical presentation of a malignancy. Pediatric pulmonology\| PubMed ID: 33085831	2020
Restrictive allograft syndrome after lung transplantation. Pediatric transplantation\| PubMed ID: 33728767	2021
Inflammation in Pulmonary Arterial Hypertension. Advances in experimental medicine and biology\| PubMed ID: 33788202	2021

Timothy Klouda

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