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.
•Symptoms of TEF include cough with oral intake, respiratory infections or no symptoms.•The best initial test is esophogram with contrast performed by a skilled provider.•Repeat esophogram if clinical suspicion remains high despite negative studies.•Additional testing include CT and bronchoscopy, which is preferred over esohoscopy.
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.
Close to half of all patients with sickle cell disease (SCD) will have at least one episode of acute chest syndrome (ACS) during their lifetime. Multiple cells and molecules involved with the ...inflammatory cascade play a role in the development of ACS. We found that patients with SCD who developed ACS as a complication of a vaso-occlusive crisis (VOC) had a significant increase in leukocytes and decrease in platelets from their steady state when compared with a separate admission for VOC without ACS development. No significant change from steady state hemoglobin or reticulocyte count was noted between the two admissions. These results indicate that trending laboratory markers may be useful to predict patients at risk for ACS development.
In newborns, developmental disorders such as congenital diaphragmatic hernia (CDH) and specific types of congenital heart disease (CHD) can lead to defective alveolarization, pulmonary hypoplasia, ...and pulmonary arterial hypertension (PAH). Therapeutic options for these patients are limited, emphasizing the need for new animal models representative of disease conditions. In most adult mammals, compensatory lung growth (CLG) occurs after pneumonectomy; however, the underlying relationship between CLG and flow-induced pulmonary hypertension (PH) is not fully understood. We propose a murine model that involves the simultaneous removal of the left lung and right caval lobe (extended pneumonectomy), which results in reduced CLG and exacerbated reproducible PH. Extended pneumonectomy in mice is a promising animal model to study the cellular response and molecular mechanisms contributing to flow-induced PH, with the potential to identify new treatments for patients with CDH or PAH-CHD.
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•A murine pneumonectomy model involving removal of the left lung and right caval lobe•Reduced compensatory lung growth and alveolarization•Reproducible induction of pulmonary hypertension•Potential for studying molecular mechanisms and targeted therapeutics
Unilateral pneumonectomy in rodents is a widely used animal model for investigating compensatory lung growth (CLG) and flow-induced pulmonary hypertension (PH). However, an important limitation lies in the rapid and complete restoration of lung volumes following the removal of a single lobe, which does not mimic the persistence observed in human pulmonary diseases. Given the high prevalence of developmental lung disease and the limited therapeutic options available for such patients, there is an urgent need to develop and characterize an animal model of CLG and PH that more accurately recapitulates disease reproducibility and persistence. In this study, we propose a simple and effective approach to enhance the traditional left pneumonectomy mouse model by employing a single-incision extended pneumonectomy technique that effectively addresses these gaps. This method exhibits robustness, reproducibility, and a broad adaptability for translational and mechanistic studies.
Tsikis et al. describe an extended pneumonectomy mouse model that involves the simultaneous removal of the left lung and right caval lobe. The model is characterized by reduced compensatory lung growth and exacerbated pulmonary hypertension. Using this approach, future studies could explore molecular mechanisms and identify new therapeutics.
Lung disease (LD) is an increasingly recognized complication of systemic juvenile idiopathic arthritis (sJIA). As there are no currently available guidelines for pulmonary screening in sJIA, we ...sought to develop such an algorithm at our institution.
A multidisciplinary workgroup was convened, including members representing rheumatology, pulmonary, stem cell transplantation, and patient families. The workgroup leaders drafted an initial algorithm based on published literature and experience at our center. A modified Delphi approach was used to achieve agreement through three rounds of anonymous, asynchronous voting and a consensus meeting. Statements approved by the workgroup were rated as appropriate with moderate or high levels of consensus. These statements were organized into the final approved screening algorithm for LD in sJIA.
The workgroup ultimately rated 20 statements as appropriate with a moderate or high level of consensus. The approved algorithm recommends pulmonary screening for newly diagnosed patients with sJIA with clinical features that the workgroup agreed may confer increased risk for LD. These "red flag features" include baseline characteristics (young age of sJIA onset, human leukocyte antigen type, trisomy 21), high disease activity (macrophage activation syndrome MAS, sJIA-related ICU admission, elevated MAS biomarkers), respiratory symptoms or abnormal pulmonary examination findings, and features of drug hypersensitivity-like reactions (eosinophilia, atypical rash, anaphylaxis). The workgroup achieved consensus on the recommended pulmonary work-up and monitoring guidelines.
We developed a pulmonary screening algorithm for sJIA-LD through a multidisciplinary consensus-building process, which will be revised as our understanding of sJIA-LD continues to evolve.
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.
Title: Hematological Changes from Baseline in Children with Sickle Cell Disease Admitted for Acute Chest Syndrome Compared to Acute Pain Crisis
Authors: Timothy Klouda1, Deepti. Raybagkar2, Bruce ...Bernstein1, Nataly Apollonsky2,
Institutes:1Pediatrics, St Christopher's Hospital for Children, Philadelphia, PA, United States, 2Hematology, St Christopher's Hospital for Children, Philadelphia, PA, United States,
Introduction: Children with Sickle Cell Disease suffer from multiple complications including acute pain crisis (VOC) and acute chest syndrome (ACS). Nearly 30% of children with SCD have had one episode of ACS, with the incidence higher in early childhood. The proposed pathophysiology of ACS is thought to be multi-factorial, with pulmonary fat embolism or infectious etiology being identified in a large number of patients. Increased sickling due to hypoxemia or pain has been shown to place patients at risk for ACS development., Studies have shown an increase in inflammatory markers including leukocytes and neutrophils, along with a decreased hemoglobin in SCD children who developed ACS, but no studies to date have compared laboratory changes during the acute illness to their baseline values. We hypothesized that children with SCD who are admitted for ACS will have a larger decrease in hemoglobin from baseline and a higher increase in white blood cell count from baseline when compared to those admitted for an acute pain crisis.
Methods: Through retrospective chart review of patients with SCD admitted to St.Christopher's Hospital for Children we identified 45 patients with ACS. Laboratory data collected on admission from chart review included SCD genotype, age, BMI, hemoglobin, white blood cell count, absolute neutrophil count, absolute eosinophil count, platelets, reticulocyte count, hemoglobin F, vital signs and medication history. All 45 children had laboratory data collected from an acute pain crisis that occurred during a different admission for comparison. Collected data was compared to baseline laboratory data, collected during routine visit at sickle cell clinic within 1 year of admission. Changes in laboratory data from baseline during admission for ACS were compared to changes during admission for uncomplicated VOC.
Results: Children with SCD who were admitted or developed ACS during admission had a larger increase in leukocyte count (6.99 vs 4.18, p=0.027) and neutrophil count (6.3 vs 3.74, p=0.04) from baseline compared to those admitted for VOC alone. Patients with ACS development also had a larger decrease in platelets (-124.74 vs -56.21, p=.047) from baseline when compared to VOC admissions. There was no statistically significant change from baseline labs when comparing hemoglobin (p=0.10), eosinophil count (p=.382), reticulocyte count (p=0.754), AST (p=0.061) and ALT (p=0.082) in the ACS and VOC groups. Children with a history of 2 or more lifetime ACS were more likely to have OSA (p=0.021), 3 or more VOCs in the past year (p=0.002), and a history of splenectomy, but it was not found to be statistically significant (p=0.155)
Conclusion: Children with SCD who developed or were admitted with ACS had a significant increase in leukocyte and neutrophil count from baseline, and a decrease in platelets when compared to VOC admissions. There was no significant change from baseline in hemoglobin, reticulocyte and eosinophils detected. Future larger and multi-center prospective studies need to be performed to confirm the various changes identified in hematological markers seen in ACS vs VOC.
No relevant conflicts of interest to declare.
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.
A 12‐year‐old male was admitted to the Medical Intensive Care Unit for respiratory failure requiring temporary tracheostomy secondary to an extensive necrotizing methicillin‐resistant Staphylococcus ...aureus pneumonia. Imaging revealed destructive bronchiectasis and multifocal lung abscesses, more advanced in the right lung. He was discharged home after 42‐day hospital admission. 3.5 months after his discharge, he re‐presented to the Emergency Department with a large right pneumothorax and a pneumatocele measuring 10.2 × 6.2 cm2. He was admitted to the hospital and while his pneumothorax resolved in 2 days, the size of the pneumatocele was noted to fluctuate with different phases of respiration. A computed tomography scan of the chest demonstrated a fistula between the pneumatocele and right upper lobe bronchus. Following discussion between Pulmonary medicine and Interventional radiology, transbronchial closure of the air leak was planned. Intubation was done with a dual‐lumen endotracheal tube. Bronchography was performed using a diagnostic catheter. A large air leak was noted from the anterior segment of the right upper lobe bronchus. Embolization of the fistula was performed using n‐butyl cyanoacrylate (nBCA, glue) injected through a second catheter under fluoroscopic guidance. The residual pneumatocele slowly resolved over 2 months. Endobronchial embolization has been described in the literature as a treatment strategy for air leaks, largely in adult patients. Endobronchial embolization of large pneumatoceles and bronchopleural fistulas may offer an alternative treatment option with less morbidity than the classic surgical approach.
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