Jose G Venegas

Harvard Medical School | HMS · Department of Anesthesia

Background Asthma exacerbations cause lung hyperinflation, elevation in load to inspiratory muscles, and decreased breathing capacity that, in severe cases, may lead to inspiratory muscle fatigue and respiratory failure. Hyperinflation has been attributed to a passive mechanical origin; a respiratory system time-constant too long for full exhalatio...

Introduction: Manual analysis of two-dimensional (2D) scintigraphy to evaluate aerosol deposition is usually subjective and has reduced sensitivity to quantify regional differences between central and distal airways. Aims: (1) To present a method to analyze 2D scans based on three-dimensional (3D)-linked anatomically consistent regions of intere...

Computational models of gas transport and aerosol deposition frequently utilize idealized models of bronchial tree structure, where airways are considered a network of bifurcating cylinders. However, changes in the shape of the lung during respiration affect the geometry of the airways, especially in disease conditions. In this study, the internal...

Distensibility data distribution. This is a histogram of the distribution of the distensibility data of the right and left lung for the airways of generation 3 and 4. The best-fit normal density function is also shown as a red line. (TIF)

Distensibility probability plot. The probability plot comparing the distensibility data to the normal distribution (reference line—-), created for the right and left lung generation 3 and 4 data. It can be observed that the fit of the data to the reference line deteriorates when distensibility values exceed one. (TIF)

Normalized hydraulic diameter data. The hydraulic diameter data are normalized to the hydraulic diameter calculated for the trachea and are collected for the same airway tree bronchial regions as the ones considered by Choi et al. [38] (where available). The data are give as average values ± standard deviation values. (DOCX)

Distensibility box and whisker plot. A box-plot of the distensibility for all the available airways of generations 3 and 4. Outliers are observed at above and under 1.5 Inter-Quartile range. (TIF)

Data processing file. This is the excel file used to gather and statistically analyze the bronchial tree morphometric information that are investigated in this study. The file contains the average inner diameter, average lumen area, average inner perimeter, calculated hydraulic diameter and several definitions for airway distensibility. The data ar...

Rationale: Regional hypoventilation in bronchoconstricted asthmatics is spatially associated with reduced perfusion, which is proposed to result from Hypoxic Pulmonary Vasoconstriction (HPV). Our study aimed to determine the role of HPV in the regional perfusion redistribution in bronchoconstricted asthmatics. Methods: Eight asthmatics completed...

In this article, we address a fundamental question regarding computational fluid dynamics (CFD) modeling within lung airways: does the inhaled volume during imaging have a significant effect on CFD computations of aerosol deposition? High resolution computed tomography (HRCT) images taken at mean lung volume (MLV) and at total lung capacity (TLC) o...

Background: Bariatric surgery (BS) in severely obese subjects causes a significant reduction of body weight with lung function improvement. We have shown that abnormalities in pulmonary gas exchange in morbidly obese subjects are substantially improved with BS. These abnormalities were thought to be related to reduced lung volumes as well as to ab...

Background: Acute respiratory distress syndrome (ARDS) is an inflammatory condition comprising diffuse lung edema and alveolar damage. ARDS frequently results from regional injury mechanisms. However, it is unknown whether detectable inflammation precedes lung edema and opacification and whether topographically differential gene expression consist...

Rationale: Along with reduced gas lung volumes, pulmonary gas exchange in severe obesity could be altered by inflammation and direct effects of perivascular adipose tissue (PVAT) in the pulmonary vasculature. Since both effects could be reflected by elevatedlung tissue volume( Vtiss ), we asked whether Vtiss was reduced by bariatric surgery (BS)....

Parenchymal strain is a key determinant of lung injury produced by mechanical ventilation. However, imaging estimates of volumetric tidal strain (e = regional tidal volume/reference volume) present substantial conceptual differences in reference volume computation and consideration of tidally recruited lung. We compared current and new methods to e...

Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participat...

Background: Theoretical models suggest that He-O2 as carrier gas may lead to more homogeneous ventilation and aerosol deposition than air. However, these effects have not been clinically consistent and it is unclear why subjects may or may not respond to the therapy. Here we present 3D-imaging data of aerosol deposition and ventilation distributio...

Background: Allergic non-asthmatic (ANA) adults experience upper airway symptoms of allergic disease such as rhinorrhea, congestion and sneezing without symptoms of asthma. The aim of this study was to utilize PET-CT functional imaging to determine whether allergen challenge elicits a pulmonary response in ANA subjects or whether their allergic di...

This paper presents a novel approach to visualizing regional lung function, through quantitative three-dimensional maps of O2 and CO2 transfer rates. These maps describe the contribution of anatomical regions to overall gas exchange and demonstrate how transfer rates of the two gas species' differ regionally. An algorithm for generating such maps i...

A previous PET-CT imaging study of 14 bronchoconstricted asthmatic subjects showed that peripheral aerosol deposition was highly variable among subjects and lobes. The aim of this work was to identify and quantify factors responsible for this variability. A theoretical framework was formulated to integrate four factors affecting aerosol deposition:...

Variance is a statistical parameter used to characterize heterogeneity or variability in data sets. However, measurements commonly include noise, as random errors superimposed to the actual value, which may substantially increase the variance compared to a noise-free data set. Our aim was to develop and validate a method to estimate noise-free spat...

Cystic fibrosis (CF) is a common inherited condition caused by mutations in the gene encoding the CF transmembrane regulator protein. With increased understanding of the molecular mechanisms underlying CF and the development of new therapies there comes the need to develop new outcome measures to assess the disease, its progression and response to...

Deep inspirations (DIs) have a dilatory effect on airway smooth muscle (ASM) that helps to prevent or reduce more severe bronchoconstriction in healthy individuals. However, this bronchodilation appears to fail in some asthmatic patients or under certain conditions, and the reason is unclear. Additionally, quantitative effects of the frequency and...

Unlabelled: PET with (18)F-FDG allows for noninvasive assessment of regional lung metabolism reflective of neutrophilic inflammation. This study aimed at determining during early acute lung injury whether local (18)F-FDG phosphorylation rate and volume of distribution were sensitive to the initial regional inflammatory response and whether they de...

Lung parenchyma surrounding an atelectatic region is thought to be subjected to increased stress compared with the rest of the lung. Using 37 hexagonal cells made of linear springs, Mead et al. (J Appl Physiol 28: 596-608, 1970) measured a stress concentration greater than 30% in the springs surrounding a stiffer central cell. We re-examine the pro...

Inhomogeneous inflation or deflation of the lungs can cause dynamic pressure differences between regions and lead to interregional airflows known as pendelluft. This work first uses analytical tools to clarify the theoretical limits of pendelluft at a single bifurcation. It then explores the global and regional pendelluft that may occur throughout...

Background: This article presents a novel methodological approach to evaluate images of aerosol deposition taken with PET-CT cameras. Traditionally, Black-or-White (BW) Regions of Interest (ROIs) are created to cover Anatomical Regions (ARs) segmented from the high-resolution CT. Such ROIs do not usually consider blurring effects due to limited sp...

Regional tidal lung strain may trigger local inflammation during mechanical ventilation, particularly when additional inflammatory stimuli are present. However, it is unclear whether inflammation develops proportionally to tidal strain or only above a threshold. We aimed to 1) assess the relationship between regional tidal strain and local inflamma...

Airway narrowing by smooth muscle constriction is a hallmark of asthma attacks that may cause severe difficulties of breathing. However, the causes of asthma and the underlying mechanisms are not fully understood. Bronchoconstriction within a bronchial tree involves complex interactions among the airways that lead to the emergence of regions of poo...

In most diseases of the lung, both function and structure are spatially heterogeneous. As a result, global measures of lung function obtained from measurements at the mouth may be insensitive to localized pathological changes in the lungs and usually fail to detect the true extent of the functional impairment. With the development of imaging method...

Background: Helium-oxygen has been used for decades as a respiratory therapy conjointly with aerosols. It has also been shown under some conditions to be a means to provide more peripheral, deeper, particle deposition for inhalation therapies. Furthermore, we can also consider deposition along parallel paths that are quite different, especially in...

Acute lung injury occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48-72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced acute lung injury. Furthermore, noninvasive...

An input function indicative of a time-activity curve in pulmonary arterial plasma is produced from a series of PET image frames in lieu of manual blood sampling. Two manually acquired blood samples are input along with pixel values of a blood pool region of interest (ROI) in the PET image frames into a two-parameter model of the ROI's time-activit...

Rationale: The mechanisms underlying not well-controlled asthma (NWC) remain poorly understood but accumulating evidence points to peripheral airway dysfunction as a key contributor. The current study tests whether our recently-described respiratory system reactance (Xrs) assessment of peripheral airway dysfunction reveals insight into poor asthma...

Leukocyte infiltration is central to the development of acute lung injury, but it is not known how mechanical ventilation strategy alters the distribution or activation of inflammatory cells. We explored how protective (vs. injurious) ventilation alters the magnitude and distribution of lung leukocyte activation following systemic endotoxin adminis...

Omalizumab promotes clinical improvement in patients with allergic asthma, but its effect on pulmonary function is unclear. One possibility is that omalizumab improves asthma symptoms through effects on the regional distributions of ventilation, perfusion, and ventilation/perfusion matching, metrics which can be assessed with Nitrogen-13-saline Pos...

Differences in the volume median diameter (VMD) and geometric standard deviation (GSD) between various breathing patterns studied were small. Further, mean VMDs and GSDs were not different between He/O 2 and air. Accordingly, the aerosol delivery system can be used to directly study the effects of helium/oxygen on regional deposition patterns. Abov...

Background: A previous PET-CT imaging study of 14 bronchoconstricted asthmatic subjects showed that peripheral aerosol deposition was highly variable among subjects and lobes. The aim of this work was to identify and quantify factors responsible for this variability. Methods: A theoretical framework was formulated to integrate four factors affectin...

Background: Lung derecruitment is common during general anesthesia. Mechanical ventilation with physiological tidal volumes could magnify derecruitment, and produce lung dysfunction and inflammation. The authors used positron emission tomography to study the process of derecruitment in normal lungs ventilated for 16 h and the corresponding changes...

Imaging studies have demonstrated that ventilation during bronchoconstriction in subjects with asthma is patchy with large ventilation defective areas (Vdefs). Based on a theoretical model, we postulated that during bronchoconstriction, as smooth muscle force activation increases, a patchy distribution of ventilation should emerge, even in the pres...

Airflow obstruction and heterogeneities in airway constriction and ventilation distribution are well-described prominent features of asthma. However, the mechanistic link between these global and regional features has not been well defined. We speculate that peripheral airway resistance (R(p)) may provide such a link. Structural and functional para...

Abstract Physiological conditions and pathophysiological changes in the lungs may affect many applications in aerosol medicine and pulmonary drug delivery. In the diseased lung, spatial heterogeneity in function and structure may cause substantial changes in aerosol transport and local deposition among different lung regions. Non-uniform aerosol de...

Heterogeneous, small-airway diameters and alveolar derecruitment in poorly aerated regions of normal lungs could produce ventilation heterogeneity at those anatomic levels. We modeled the washout kinetics of (13)NN with positron emission tomography to examine how specific ventilation (sV) heterogeneity at different length scales is influenced by lu...

Invited editorial.

In asthma, the relationship among airway inflammation, airway hyperresponsiveness, and lung function is poorly understood. Methods to noninvasively assess these relationships in human subjects are needed. We sought to determine whether (18)F-FDG uptake rate (K(i), min(-1)) could serve as a biomarker of eosinophilic inflammation and local lung funct...

Heterogeneity in narrowing among individual airways is an important contributor to airway hyperresponsiveness. This paper investigates the contribution of longitudinal heterogeneity (the variability along the airway in cross-sectional area and shape) to airway resistance (R(aw)). We analyzed chest high-resolution computed tomography scans of 8 asth...

Inflammation during mechanical ventilation is thought to depend on regional mechanical stress. This can be produced by concentration of stresses and cyclic recruitment in low-aeration dependent lung. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) allows for noninvasive assessment of regional metabolic activity, an inde...

The behavior of respiratory diseases such as asthma and COPD may involve complicated interactions among multiple factors. Theoretical and experimental data suggest that interdependence among the airways of the bronchial tree leads to the emergence of self-organized patterns of airway narrowing, ventilation defects, and other phenomena when a tippin...

Dynamic positron emission tomography (PET) imaging of the lung using the radiotracer 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ((18)F-FDG) is an emerging method to assess noninvasively the metabolic activity of pulmonary inflammatory cells. Nevertheless, because of the distinct functional and structural characteristics of inflamed lung tissue standa...

The difference in effectiveness between volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) on mechanically ventilated patients during bronchoconstriction is not totally clear. PCV is thought to deliver a more uniform distribution of ventilation than VCV, but the delivered tidal volume could be unstable and affected by cha...