Change In Total Lung Volume Research Articles

Prolonged Time of Lung Collapse Associated With Decreased Recovery of Functional Lung Following Palliative Radiotherapy

<h3>Purpose/Objective(s)</h3> Bronchial obstruction leading to lung collapse from primary lung or metastatic tumors is a common urgent consult to radiation oncology. Palliative chest radiotherapy (RT) can reduce the risk of progression of endobronchial or extrabronchial disease can be utilized alone or in combination with bronchial stenting to re-open existing collapsed lung. The ability to re-open collapsed lung following RT is likely multi-factorial with time since lung collapse long thought as an important predictor of reversibility. In this study, we sought to quantify the time-dependency of recovery of functional lung volume in patients with partial or complete lung collapse using a CT-based imaging metric highly correlated with lung function. <h3>Materials/Methods</h3> Patients with primary lung or metastatic tumors who received palliative chest RT due to segmental, lobar or whole lung collapse who additionally had follow-up CT imaging of the chest were identified from the institutional electronic health record. Total lung volumes on simulation and follow-up chest CTs were manually segmented using a commercially available software. To evaluate functional lung volume, a subthreshold function was applied to the image sets to determine volume of lung with attenuation of -950 to -701 HU. An estimate of time since initiation of lung collapse was determined by review of clinical records and imaging. <h3>Results</h3> A total of 25 evaluable patients were identified with non-small cell lung cancer (NSCLC) being the predominant histology observed (19/25, 76%). The median time of collapse before initiation of RT was 11 days (range = 3-57). The median dose received was 20 Gy in 5 fractions (range = 8 Gy/1 fx to 30 Gy/10 fx). The mean change in total lung volume was 1090 cc with mean change in functional lung volume of 1006 cc. Overall, a 92% increase in functional lung volume was observed following chest RT in this cohort. A linear trend toward decreasing recovery of functional lung was observed with more prolonged lung collapse (<i>P</i> = 0.074). Patients with estimated time of lung collapse of ≤14 days had higher mean recovery of functional lung (113%) compared with those with lung collapse > 14 days (55%) (<i>P</i> = 0.040). <h3>Conclusion</h3> Early initiation of palliative RT following lung collapse may lead to greater recovery of functional lung volume, which may confer a survival benefit/decrease hospitalization rates/improve fitness for systemic therapy. Improvements in targeted therapies are leading to more durable systemic responses potentially increasing the importance of timely chest RT for patients with existing or pending lung collapse as a bridge during acute thoracic events.

Comparison of inspiratory and expiratory lung and lobe volumes among supine, standing, and sitting positions using conventional and upright CT

Currently, no clinical studies have compared the inspiratory and expiratory volumes of unilateral lung or of each lobe among supine, standing, and sitting positions. In this prospective study, 100 asymptomatic volunteers underwent both low-radiation-dose conventional (supine position, with arms raised) and upright computed tomography (CT) (standing and sitting positions, with arms down) during inspiration and expiration breath-holds and pulmonary function test (PFT) on the same day. We compared the inspiratory/expiratory lung/lobe volumes on CT in the three positions. The inspiratory and expiratory bilateral upper and lower lobe and lung volumes were significantly higher in the standing/sitting positions than in the supine position (5.3–14.7% increases, all P < 0.001). However, the inspiratory right middle lobe volume remained similar in the three positions (all P > 0.15); the expiratory right middle lobe volume was significantly lower in the standing/sitting positions (16.3/14.1% decrease) than in the supine position (both P < 0.0001). The Pearson’s correlation coefficients (r) used to compare the total lung volumes on inspiratory CT in the supine/standing/sitting positions and the total lung capacity on PFT were 0.83/0.93/0.95, respectively. The r values comparing the total lung volumes on expiratory CT in the supine/standing/sitting positions and the functional residual capacity on PFT were 0.83/0.85/0.82, respectively. The r values comparing the total lung volume changes from expiration to inspiration on CT in the supine/standing/sitting positions and the inspiratory capacity on PFT were 0.53/0.62/0.65, respectively. The study results could impact preoperative CT volumetry of the lung in lung cancer patients (before lobectomy) for the prediction of postoperative residual pulmonary function, and could be used as the basis for elucidating undetermined pathological mechanisms. Furthermore, in addition to morphological evaluation of the chest, inspiratory and expiratory upright CT may be used as an alternative tool to predict lung volumes such as total lung capacity, functional residual capacity, and inspiratory capacity in situation in which PFT cannot be performed such as during an infectious disease pandemic, with relatively more accurate predictability compared with conventional supine CT.

Imaging Biomarkers and Pathobiological Profiling in a Rat Model of Drug-Induced Interstitial Lung Disease Induced by Bleomycin.

A large number of systemically administered drugs have the potential to cause drug-induced interstitial lung disease (DIILD). We aim to characterize a model of DIILD in the rat and develop imaging biomarkers (IBs) for detection and quantification of DIILD. In this study, Sprague–Dawley rats received one single dose of intratracheal (i.t.) bleomycin and were longitudinally imaged at day 0, 3, 7, 14, 21, and 28 post dosing, applying the imaging techniques magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT). Bronchoalveolar lavage fluid (BALF) was analyzed for total protein and inflammatory cells. Lungs were saved for further evaluation by gene analysis using quantitative-PCR and by histology. Lung sections were stained with Masson’s-Trichrome staining and evaluated by modified Ashcroft score. Gene expression profiling of inflammatory and fibrotic markers was performed on lung tissue homogenates. Bleomycin induced significant increase in total protein concentration and total cell count in bronchoalveolar lavage (BAL), peaking at day 3 (p > 0.001) and day 7 (p > 0.001) compared to control, respectively. Lesions measured by MRI and PET signal in the lungs of bleomycin challenged rats were significantly increased during days 3–14, peaking at day 7. Two subgroups of animals were identified as low- and high-responders by their different change in total lung volume. Both groups showed signs of inflammation initially, while at later time points, the low-responder group recovered toward control, and the high-responder group showed sustained lung volume increase, and significant increase of lesion volume (p < 0.001) compared to control. Lastly, important inflammatory and pro-fibrotic markers were assessed from lung tissue, linking observed imaging pathological changes to gene expression patterns. In conclusion, bleomycin-induced lung injury is an adequate animal model for DIILD studies and for translational lung injury assessment by MRI and PET imaging. The scenario comprised disease responses, with different fractions of inflammation and fibrosis. Thereby, this study improved the understanding of imaging and biological biomarkers in DIILD and lung injury.

Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume.

ABSTRACTIn vivo lung micro-computed tomography (micro-CT) is being increasingly embraced in pulmonary research because it provides longitudinal information on dynamic disease processes in a field in which ex vivo assessment of experimental disease models is still the gold standard. To optimize the quantitative monitoring of progression and therapy of lung diseases, we evaluated longitudinal changes in four different micro-CT-derived biomarkers [aerated lung volume, lung tissue (including lesions) volume, total lung volume and mean lung density], describing normal development, lung infections, inflammation, fibrosis and therapy. Free-breathing mice underwent micro-CT before and repeatedly after induction of lung disease (bleomycin-induced fibrosis, invasive pulmonary aspergillosis, pulmonary cryptococcosis) and therapy (imatinib). The four lung biomarkers were quantified. After the last time point, we performed pulmonary function tests and isolated the lungs for histology. None of the biomarkers remained stable during longitudinal follow-up of adult healthy mouse lungs, implying that biomarkers should be compared with age-matched controls upon intervention. Early inflammation and progressive fibrosis led to a substantial increase in total lung volume, which affects the interpretation of aerated lung volume, tissue volume and mean lung density measures. Upon treatment of fibrotic lung disease, the improvement in aerated lung volume and function was not accompanied by a normalization of the increased total lung volume. Significantly enlarged lungs were also present in models of rapidly and slowly progressing lung infections. The data suggest that total lung volume changes could partly reflect a compensatory mechanism that occurs during disease progression in mice. Our findings underscore the importance of quantifying total lung volume in addition to aerated lung or lesion volumes to accurately document growth and potential compensatory mechanisms in mouse models of lung disease, in order to fully describe and understand dynamic processes during lung disease onset, progression and therapy. This is highly relevant for the translation of therapy evaluation results from preclinical studies to human patients.

Evaluation of postoperative change in lung volume in adolescent idiopathic scoliosis: Measured by computed tomography.

Background:Change in total lung volume after surgical correction in adolescent idiopathic scoliosis (AIS), measured by computed tomography (CT), has not been studied previously. The primary objective of this study was to measure the change in lung volume between pre and postoperative AIS using low-dose CT and secondary objective was to investigate its relationship to postoperative pulmonary complications.Materials and Methods:55 AIS patients underwent surgery for correction and fusion using a posterior only approach and pedicle screws. Pre and postoperative lung volumes were measured using a 3-dimensional (3D) whole spine CT (low dose protocol: Tube current, 60 mA; tube voltage 120 kV). Postoperative low dose CT was undertaken at 4 weeks after operation to evaluate the acute changes of postoperative lung volumes and pulmonary complications. The software that was used recognizes the “air density shade” of the lung and the volume of every section of the lung. The software then automatically calculates total lung volume by summation of all section volumes. The relationships between postoperative pulmonary complications and changes in lung volume on low dose CT as well as preoperative forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were calculated using logistic regression analysis.Results:There was a decrease of 12% ± 23.2% in total lung volume postoperatively on 3D low dose CT (P < 0.001). Thirteen patients had increased lung volume while 42 had decreased lung volume postoperatively. Pulmonary complications were treated without severe sequale. Lung volume increased by 19.65% ± 19.84% in 13 patients and decreased by 21.85% ± 13.32% in 42 patients (P = 0.647). Lung volume was increased in patients whose preoperative lung volume, FEV1 and FVC were lower than in patients whose values were higher (r = −0.273, −0.291 and − 0.348; P = 0.044, 0.045 and 0.015, respectively). Postoperative lung volume was also increased when intraoperative fluid administration was larger and operative time was longer (r = 0.354, 0.417 and P = 0.008, 0.002, respectively). There was a statistically significant negative correlation in the change of lung volume in female patients when compared with male patients (r = −0.294, P = 0.03).Conclusion:Patients with AIS who have preoperative reduced lung volumes or lung functions can achieve further increased lung volume after surgical correction. Pulmonary complications during perioperative period were mostly treated with proper management without severe sequale. Therefore, although surgery for AIS is considered to be a high risk procedure, we can recommend to correct spine deformity in patients with severe AIS in order to improve lung function and long term prognosis.

SU-E-T-516: Evaluation of the Effects of Total Lung Volume, Age, and Body Mass Index on Breath-Hold Level for Left Breast Cancer Patients

Purpose: To determine if abdominal height displacement between free- breathing and breath-hold correlates with change in total lung volume (TLV). Correlation between abdominal height during breath-hold versus patient age and body mass index (BMI) was also investigated. Methods: The study involved 35 patients, each with free-breathing and breath-hold CT scans. The RPM System (Varian Oncology Systems, Palo Alto, Ca) was used to measure abdominal height. Abdominal height displacement was defined as the distance from end of normal inspiration to the average breath- hold level during simulation. Breathing data for each patient was exported from the RPM system and analyzed. Free-breathing and breath-hold scans were fused by matching the field borders, scar, excision cavity, and left breast skin. One physician performed all contouring and image fusions. TLV was calculated by the planning system. Box displacement was plotted against change in TLV, patient age, and BMI. Correlation coefficients (r) were calculated for each comparison. Results: An r-value of 0.59 was calculated for TLV versus breath-hold level. The relationship showed larger TLV changes with greater abdominal height displacement. Comparing box displacement against all ages the r-value was 0.48. Separating by age, patients 70 years and older had an r-value of 0.91 with box displacement decreasing with age. For the remaining age groups (30–49, 50–59, and 60– 69), r-values were 0.30, 0.33, and 0.07, respectively. For BMI, the r-value was 0.35. Conclusions: The data in this investigation was plotted between patients, therefore only inter-patient trends can be described. Younger patients generally achieve deeper breath-holds as measured by abdominal motion than older patients. It can be concluded that abdominal height carries a moderate predictive value for change in TLV for patients under age 70, regardless of BMI. However, a strong correlation exists for patients over age 70.

Counterpoint: Chronic Hypoxia-induced Pulmonary Hypertension does not Lead to Loss of Pulmonary Vasculature

Exposure of native sea level dwellers to chronic hypoxia due to migration to high altitude leads to the development of increased pulmonary vascular resistance causing pulmonary hypertension. In some susceptible individuals this progressively worsens causing right ventricular failure and ultimately

Preoperative Severity of Emphysema Predictive of Improvement After Lung Volume Reduction Surgery: Use of CT Morphometry

To determine how the volume and severity of emphysema measured by CT morphometry (CTM) before and after lung volume reduction surgery (LVRS) relates to the functional status of patients after LVRS. A histologically validated CT algorithm was used to quantify the volume and severity of emphysema in 35 patients before and after LVRS: total lung volume (TLV), normal lung volume (< 6.0 mL gas per gram of tissue), volume of mild/moderate emphysema (ME; 6.0 to 10.2 mL gas per gram of tissue), volume of severe emphysema (> 10.2 mL gas per gram of tissue), surface area/volume (SA/V; meters squared per milliliter), and surface area (SA; meters squared). Outcome parameters included maximal cardiopulmonary exercise (CPX) performance in 21 patients and routine pulmonary function in all patients. We hypothesized that baseline CTM parameters predict response to LVRS and that the change in these parameters may offer insight into mechanisms of improvement. Thirty-five patients with severe emphysema who had successful LVRS. The significant decrease in TLV following LVRS was entirely accounted for by a decrease in severe emphysema. The SA/V and the SA both increased significantly following LVRS. The change in maximal CPX in watts following surgery correlated significantly with baseline values of severe emphysema (r = 0.60), which was collinear with TLV, and SA/V. The change in diffusing capacity of the lung for carbon monoxide revealed a significant positive linear relationship with preoperative severe emphysema (r = 0.37) and a negative relationship with ME (r = -0.37). Change in watts revealed a strong relationship with changes in severe emphysema (r = -0.75) and weaker but significant relationships with change in TLV, ME, SA/V, and SA. Other measures of pulmonary function revealed significant albeit less dominant relationships with baseline CTM and change in these indexes. Using CTM, we have identified a close relationship between baseline severe emphysema, or change in severe emphysema, and the improvement in CPX after LVRS. These observations support a potential role of CTM in future clinical trials for predicting responders to LVRS and identifying mechanisms of improvement.

Time course of and stimuli to compensatory growth of the lung after pneumonectomy.

Left pneumonectomy in the mature rat led to an increase of [3Ha1 thymidine incorporation into DNA of the remaining lung in the first 3 postoperative days, and resulted in a subsequent 38% increase of lung weight and 41% increase of lung tissue volume measured 1 wk after surgery. Despite these early changes, total lung volume (TLV) did not increase until the 2nd postoperative wk, reaching values 33% greater than in controls. Analysis of lung pressure-volume curves revealed that lung recoil was increased at low lung volumes 1 wk after surgery, but returned to normal by the 2nd postoperative wk, suggesting that synthesis of both lung elastin and collagen had occurred by this time. Increased inspired oxygen concentration (28% or 35%) during the 1st but not the 2nd postoperative wk abolished the change in TLV without influencing the increase in lung weight, while diminished inspired oxygen (17% or 14%) accentuated the postoperative increase in TLV. Lung pressure-volume curves demonstrated changes in distensibility at low lung volumes, suggesting that oxygen may have influenced synthesis or cross-linking of lung elastin. Alterations of minute ventilation in the postoperative period produced by 3% CO2 did not influence the compensatory growth process, nor did administration of cyclophosphamide. These studies suggest that postpneumonectomy lung growth is a two-phase process, beginning with cell proliferation and increased tissue volume, followed by increasing lung volume associated with formation of lung structural proteins. The latter process is profoundly influenced by inspired oxygen concentration in the early postoperative period.