Emphysema is one of the pathological hallmarks of chronic obstructive pulmonary disease. We have recently reported that radiofrequency therapy improves lung function in rodent models of emphysema. However, preclinical data using large animals is necessary for clinical translation.
View Article and Find Full Text PDFEmerging data demonstrate that the smallest conducting airways, terminal bronchioles, are the early site of tissue destruction in chronic obstructive pulmonary disease (COPD) and are reduced by as much as 41% by the time someone is diagnosed with mild (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1) COPD. To develop a single-cell atlas that describes the structural, cellular, and extracellular matrix alterations underlying terminal bronchiole loss in COPD. This cross-sectional study of 262 lung samples derived from 34 ex-smokers with normal lung function ( = 10) or GOLD stage 1 ( = 10), stage 2 ( = 8), or stage 4 ( = 6) COPD was performed to assess the morphology, extracellular matrix, single-cell atlas, and genes associated with terminal bronchiole reduction using stereology, micro-computed tomography, nonlinear optical microscopy, imaging mass spectrometry, and transcriptomics.
View Article and Find Full Text PDFMechanical forces affect the alveolar shape, depending on location and tissue composition, and vary during the respiratory cycle. This study performs alveolar morphomics in different lobes of human lungs using models generated from three-dimensional (3-D) micro-computed tomography (microCT) images. Cylindrical tissue samples (1.
View Article and Find Full Text PDFPeople with pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19). Still, an interrogation of the immune response to COVID-19 infection, spatially throughout the lung structure, is lacking in patients with COPD. For this study, we characterized the immune microenvironment of the lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, all of whom died of COVID-19, using spatial transcriptomic and proteomic profiling.
View Article and Find Full Text PDFLung resistance () is determined by airway and parenchymal tissue resistance, as well as the degree of heterogeneity in airway constriction. Deep inspirations (DIs) are known to reverse experimentally induced increase in , but the mechanism is not entirely clear. The first step toward understanding the effect of DI is to determine how each of the resistance components is affected by DI.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
May 2022
Lung resistance () and elastance () can be measured during positive or negative pressure ventilation. Whether the different modes of ventilation produce different and is still being debated. Although negative pressure ventilation (NPV) is more physiological, positive pressure ventilation (PPV) is more commonly used for treating respiratory failure.
View Article and Find Full Text PDFRationale: Peripheral airway obstruction is a key feature of chronic obstructive pulmonary disease (COPD), but the mechanisms of airway loss are unknown. This study aims to identify the molecular and cellular mechanisms associated with peripheral airway obstruction in COPD.
Methods: Ten explanted lung specimens donated by patients with very severe COPD treated by lung transplantation and five unused donor control lungs were sampled using systematic uniform random sampling (SURS), resulting in 240 samples.
To improve disease outcomes in idiopathic pulmonary fibrosis (IPF), it is essential to understand its early pathophysiology so that it can be targeted therapeutically. Perform three-dimensional assessment of the IPF lung microstructure using stereology and multiresolution computed tomography (CT) imaging. Explanted lungs from patients with IPF ( = 8) and donor control subjects ( = 8) were inflated with air and frozen.
View Article and Find Full Text PDFBackground: The transition from normal lung anatomy to minimal and established fibrosis is an important feature of the pathology of idiopathic pulmonary fibrosis (IPF). The purpose of this report is to examine the molecular and cellular mechanisms associated with this transition.
Methods: Pre-operative thoracic Multidetector Computed Tomography (MDCT) scans of patients with severe IPF (n = 9) were used to identify regions of minimal(n = 27) and established fibrosis(n = 27).
The alveolar ducts are connected to peripheral septal fibers which extend from the visceral pleura into interlobular septa, and are anchored to axial fibers in the small airways. Together these axial and septal fibers constitute a fiber continuum that provides tension and integrity throughout the lung. Building on the observations that alveolar ducts associated with sub-pleural alveoli are orientated perpendicular to the visceral pleura, and in parallel to each other, the goal of the present study was to investigate the nature of the collagen fiber organization within sub-pleural alveolar ducts in healthy control and elastase-induced emphysema murine lungs.
View Article and Find Full Text PDFIdiopathic pulmonary fibrosis (IPF) is a fibrotic disease with the histology of usual interstitial pneumonia (UIP). Although the pathologist's visual inspection is central in histologic assessments, three-dimensional microcomputed tomography (microCT) assessment may complement the pathologist's scoring. We examined associations between the histopathologic features of UIP and IPF in explanted lungs and quantitative microCT measurements, including alveolar surface density, total lung volume taken up by tissue (%), and terminal bronchiolar number.
View Article and Find Full Text PDFAm J Respir Crit Care Med
September 2020
Although centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are commonly identified on multidetector computed tomography (MDCT), little is known about the pathology associated with PSE compared with that of CLE. To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD). Air-inflated frozen lung specimens ( = 6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT.
View Article and Find Full Text PDFThe application of stereology to lung casts and two-dimensional microscopy images is the gold standard for quantification of the human lung anatomy. However, these techniques are labor intensive, involving fixation, embedding, and histological sectioning of samples and thus have prevented comprehensive studies. Our objective was to demonstrate the application of stereology to volumetric multiresolution computed tomography (CT) to efficiently and extensively quantify the human lung anatomy.
View Article and Find Full Text PDFBackground: The observation that patients with idiopathic pulmonary fibrosis (IPF) can have higher than normal expiratory flow rates at low lung volumes led to the conclusion that the airways are spared in IPF. This study aimed to re-examine the hypothesis that airways are spared in IPF using a multiresolution imaging protocol that combines multidetector CT (MDCT), with micro-CT and histology.
Methods: This was a retrospective cohort study comparing explanted lungs from patients with severe IPF treated by lung transplantation with a cohort of unused donor (control) lungs.
Donor organ shortage results in significant waiting list mortality. Donor lung assessment is currently based on donors' history, gas exchange, chest X-ray, bronchoscopy findings, and ultimately in situ inspection but remains subjective. We correlated histopathology and radiology in nontransplanted donor lungs with the clinical indications to decline the offered organ.
View Article and Find Full Text PDFBackground Total kidney volume (TKV) assessment is valuable in autosomal dominant polycystic kidney disease (ADPKD) but the reference standard method of MRI planimetry requires access to MRI and time-consuming interpretation. Purpose To determine whether accurate TKV measurements comparable to the resource-intensive reference standard of MRI planimetry can be obtained by using alternate methods including dose-reducing CT protocols and time-saving measurement equations. Materials and Methods In this prospective study conducted September 2016 to June 2017, adult participants with ADPKD underwent one MRI and two CT examinations.
View Article and Find Full Text PDFEvidence suggests damage to small airways is a key pathologic lesion in chronic obstructive pulmonary disease (COPD). Computed tomography densitometry has been demonstrated to identify emphysema, but no such studies have been performed linking an imaging metric to small airway abnormality. To correlate parametric response mapping (PRM) analysis to lung tissue measurements of patients with severe COPD treated by lung transplantation and control subjects.
View Article and Find Full Text PDFBackground: The concept that small conducting airways less than 2 mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the scientific literature, and the last generation of small conducting airways, terminal bronchioles, are known to be destroyed in patients with very severe COPD. We aimed to determine whether destruction of the terminal and transitional bronchioles (the first generation of respiratory airways) occurs before, or in parallel with, emphysematous tissue destruction.
Methods: In this cross-sectional analysis, we applied a novel multiresolution CT imaging protocol to tissue samples obtained using a systematic uniform sampling method to obtain representative unbiased samples of the whole lung or lobe of smokers with normal lung function (controls) and patients with mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1), moderate COPD (GOLD 2), or very severe COPD (GOLD 4).