Publications by authors named "Michael Eberlein"

121 Publications

The U-shaped association of post-lung transplant mortality with pretransplant eGFR underscores possible limitations of creatinine-based estimation equations for risk stratification.

J Heart Lung Transplant 2022 Jun 4. Epub 2022 Jun 4.

Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Veterans Affairs Medical Center, Iowa City, Iowa.

Background: Pre-existing chronic kidney disease (CKD) may have an impact on post-lung transplant survival and the development of end stage kidney disease (ESKD).

Methods: We analyzed the US transplant database from 2006 to 2020. Adult patients who received their first lung transplant and were not on dialysis were included. Multivariable Cox regression was used to assess the effect of pretransplant eGFR on mortality and cumulative incidence competing risk was used to explore the effect on ESKD.

Results: The adjusted hazard ratio (aHR) for mortality showed a "U" shaped association with eGFR with a rising mortality at <60 and >100 ml/min/1.73m. The increase in mortality with higher eGFR was only seen in those <30 year and were primarily in whites with a lower body mass index and in patients with cystic fibrosis (CF). The aHR for ESKD increased below an eGFR of 100 rising to 1.74 at an eGFR of 60. Any decrease in eGFR between listing and transplant >10% was associated with higher risk of ESKD.

Conclusions: The U-shaped association of pretransplant eGFR with post-transplant mortality correlated with younger age, lower BMI and a diagnosis of CF. The aHR for ESKD following lung transplantation increased exponentially with worsening eGFR pretransplant.
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http://dx.doi.org/10.1016/j.healun.2022.05.018DOI Listing
June 2022

A New Look at an Old Problem: Is Single Lung Transplantation an Option in Candidates With Significant Secondary Pulmonary Hypertension?

Transplantation 2022 Jun 6. Epub 2022 Jun 6.

Division of Pulmonary and Critical Care Medicine, University of Maryland, Baltimore, MD.

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http://dx.doi.org/10.1097/TP.0000000000004192DOI Listing
June 2022

Multimodality treatment of malignant pleural mesothelioma: evolving patient selection criteria using scores.

Eur J Cardiothorac Surg 2022 Jul;62(2)

Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

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http://dx.doi.org/10.1093/ejcts/ezac153DOI Listing
July 2022

Donor to recipient matching for lung transplant candidates with interstitial lung disease - A sizeable problem.

J Heart Lung Transplant 2021 11 2;40(11):1431-1432. Epub 2021 Aug 2.

Qld Lung Transplant Program, The Prince Charles Hospital, Brisbane, Australia; The University of Queensland, Brisbane, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.healun.2021.07.023DOI Listing
November 2021

Multimodal and palliative treatment of patients with pulmonary metastases.

J Thorac Dis 2021 Apr;13(4):2686-2691

Department of Thoracic Surgery, Evang. Kliniken Essen-Mitte, Essen, Germany.

Pulmonary metastasectomy has become an important part of the multimodality treatment. Surgical practice is based on observational studies published during the last decades, since no randomized clinical trials exist on the topic. However, the overall survival can be improved after pulmonary metastasectomy in carefully selected patients. The objective of resection of pulmonary metastases is to remove all tumor while preserving as much normal pulmonary parenchyma as possible and reduce invasiveness. Contrary, nonsurgical local treatment options for pulmonary metastases include thermal ablation techniques and stereotactic ablative body radiation. Thermal ablation techniques include microwave, cryotherapy and radiofrequency ablation. The present review article gives an overview on the topic and should help thoracic surgeons to make the right decisions in their daily practice.
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http://dx.doi.org/10.21037/jtd-2019-pm-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107530PMC
April 2021

Case Studies in Physiology: Untangling the cause of hypoxemia in a patient with obesity with acute leukemia.

J Appl Physiol (1985) 2021 08 6;131(2):788-793. Epub 2021 May 6.

Department of Internal Medicine, Division of Hematology, Oncology, and Bone Marrow Transplant, University of Iowa, Iowa City, Iowa.

Diagnosing the cause of hypoxemia and dyspnea can be complicated in complex patients with multiple comorbidities. This "Case Study in Physiology" describes an man with obesity admitted to the hospital for relapse of acute lymphoblastic leukemia, who experienced progressive hypoxemia, shortness of breath, and dyspnea on exertion during his hospitalization. After initial empirical treatment with diuresis and antibiotics failed to improve his symptoms and because an arterial blood gas measurement was not readily available, we applied a novel, recently described physiological method to estimate the arterial partial pressure of oxygen from the peripheral saturation measurement and calculate the alveolar-arterial oxygen difference to discern the source of his hypoxemia and dyspnea. Using basic physiological principles, we describe how hypoventilation, anemia, and the use of a β blocker and furosemide, collaborated to create a "perfect storm" in this patient that impaired oxygen delivery and limited utilization. This case illustrates the application of innovative physiology methodology in medicine and provides a strong rationale for continuing to integrate physiology education in medical education. Discerning the cause of dyspnea and hypoxemia in complex patients can be difficult. We describe the "real world" application of an innovative methodology to untangle the underlying physiology in a patient with multiple comorbidities. This case further demonstrates the importance of applying physiology to interrogate the underlying cause of a patient's symptoms when treatment based on probability fails.
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http://dx.doi.org/10.1152/japplphysiol.00867.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409924PMC
August 2021

Standard and extended sleeve resections of the tracheobronchial tree.

J Thorac Dis 2020 Oct;12(10):6163-6172

Department of Thoracic Surgery, Kerckhoff-Klinik, Bad Nauheim, Germany.

Anatomic resections with bronchial and/or vascular resections and reconstruction, so called sleeve resections were originally performed in patients with impaired cardio-pulmonary reserves. Nowadays, sleeve resections are established surgical procedures of first choice for tracheobronchial pathologies, whenever anatomically and oncologically feasible. Experienced thoracic surgeons have a broad surgical armentarium to avoid a pneumonectomy and the morbidity and mortality associated with it. Sleeve resections are associated with better outcomes in all aspects. Thus, sleeve resection is not an alternative for pneumonectomy and vice versa. In this review article we set out to provide a contemporary overview on this topic.
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http://dx.doi.org/10.21037/jtd.2020.02.65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656394PMC
October 2020

Survival of Pregnant Coronavirus Patient on Extracorporeal Membrane Oxygenation.

Ann Thorac Surg 2021 03 9;111(3):e151-e152. Epub 2020 Oct 9.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

A 27-year-old woman presented at 23 weeks' 6 days' gestation who tested positive for the coronavirus disease 2019 (COVID-19). Despite mechanical ventilation and paralysis, she remained hypoxic and was emergently cannulated for veno-venous extracorporeal membrane oxygenation (VV-ECMO). The patient ambulated while intubated and on VV-ECMO. She was decannulated and extubated. An ultrasound demonstrated an appropriately grown fetus without abnormalities. She was discharged to home and gave birth to a healthy baby girl at 39 weeks' gestation. Using VV-ECMO, this patient and her fetus survived acute hypoxemic respiratory failure due to COVID-19.
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http://dx.doi.org/10.1016/j.athoracsur.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544695PMC
March 2021

Preserved Ratio Impaired Spirometry in a Spirometry Database.

Respir Care 2021 Jan 1;66(1):58-65. Epub 2020 Sep 1.

Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospital and Clinics, Iowa City, Iowa.

Background: Spirometry results can yield a diagnosis of normal air flow, air flow obstruction, or preserved ratio impaired spirometry (PRISm), defined as a reduced FEV or FVC in the setting of preserved FEV/FVC. Previous studies have estimated the prevalence of PRISm to be 7-12%. Our objective was to examine the prevalence of PRISm in a spirometry database and to identify factors associated with PRISm.

Methods: We performed a retrospective analysis of 21,870 spirometries; 1,616 were excluded because of missing data or extremes of age, height, or weight. We calculated the prevalence of PRISm in prebronchodilator and postbronchodilator pulmonary function tests. Subsequently, we calculated the prevalence of PRISm by various age, race, body mass index, and diagnosis categories, as well as by gender and smokers versus nonsmokers. Finally, in the subset of the cohort with FEV < lower limit of normal, we performed a multivariable logistic regression analysis to identify factors associated with PRISm.

Results: We identified 18,059 prebronchodilator spirometries, and 22.3% of these yielded a PRISm diagnosis. This prevalence remained stable in postbronchodilator spirometries (17.7%), after excluding earlier pulmonary function tests for subjects with multiple pulmonary function tests (20.7% in prebronchodilator and 24.3% in postbronchodilator), and when we limited the analysis to prebronchodilator spirometries that met American Thoracic Society criteria (20.6%). The PRISm prevalence was higher in subjects 45-60 y old (24.4%) and in males (23.7%) versus females (17.9%). The prevalence rose with body mass index and was higher for those with a referral diagnosis of restrictive lung disease (50%). PRISm prevalence was similar between races and smokers versus nonsmokers. In a multivariable analysis, higher % of predicted FEV (odds ratio 1.51, 95% CI 1.42-1.60), body mass index (odds ratio 1.52, 95% CI 1.39-1.68), and restrictive lung disease (odds ratio 4.32, 95% CI 2.54-7.57) were associated with a diagnosis of PRISm. Smoking was inversely associated (odds ratio 0.55, 95% CI 0.46-0.65) with PRISm.

Conclusions: In a spirometry database at an academic medical center, the PRISm prevalence was 17-24%, which is higher than previously reported.
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http://dx.doi.org/10.4187/respcare.07712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856524PMC
January 2021

Surveillance and screening in lung cancer survivors.

Eur J Cardiothorac Surg 2020 04;57(4):779-780

Division of Pulmonary, Department of Internal Medicine, Critical Care and Occupational Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

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http://dx.doi.org/10.1093/ejcts/ezz344DOI Listing
April 2020

Minimally invasive bronchial and bronchovascular sleeve resections.

J Thorac Dis 2019 May;11(Suppl 9):S1177-S1179

Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

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http://dx.doi.org/10.21037/jtd.2019.03.94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560580PMC
May 2019

A novel air leak test using surfactant: a step forward or a bubble that will burst?

J Thorac Dis 2019 May;11(Suppl 9):S1119-S1122

Department of Thoracic Surgery, Evangelische Kliniken Essen-Mitte, Essen, Germany.

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http://dx.doi.org/10.21037/jtd.2019.05.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560585PMC
May 2019

Rabbit Antithymocyte Globulin Causes and Antigenemia.

Open Forum Infect Dis 2019 May 28;6(5):ofz165. Epub 2019 Mar 28.

Division of Infectious Diseases, Carver College of Medicine, University of Iowa, Iowa City, Iowa.

Rabbit antithymocyte globulin (rATG) is known to yield false-positive antigenemia. The fourth generation MiraVista antigen assay was modified to block this effect (MiraVista Diagnostics, Indianapolis, Indiana). We report a case of rATG-induced false-positive and antigenemia in a lung transplant recipient despite modifications of these antigen assays.
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http://dx.doi.org/10.1093/ofid/ofz165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499897PMC
May 2019

The Peak Index: Spirometry Metric for Airflow Obstruction Severity and Heterogeneity.

Ann Am Thorac Soc 2019 08;16(8):982-989

10Department of Electrical and Computer Engineering, University of Alabama at Birmingham, Birmingham, Alabama.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation. Spirometry loops are not smooth curves and have undulations and peaks that likely reflect heterogeneity of airflow. To assess whether the Peak Index, the number of peaks adjusted for lung size, is associated with clinical outcomes. We analyzed spirometry data of 9,584 participants enrolled in the COPDGene study and counted the number of peaks in the descending part of the expiratory flow-volume curve from the peak expiratory flow to end-expiration. We adjusted the peaks count for the volume of the lungs from peak expiratory flow to end-expiration to derive the Peak Index. Multivariable regression analyses were performed to test associations between the Peak Index and lung function, respiratory morbidity, structural lung disease on computed tomography (CT), forced expiratory volume in 1 second (FEV) decline, and mortality. The Peak Index progressively increased from Global Initiative for Chronic Obstructive Lung Disease stage 0 through 4 ( < 0.001). On multivariable analysis, the Peak Index was significantly associated with CT emphysema (adjusted β = 0.906; 95% confidence interval [CI], 0.789 to 1.023;  < 0.001) and small airways disease (adjusted β = 1.367; 95% CI, 1.188 to 1.545;  < 0.001), St. George's Respiratory Questionnaire score (adjusted β = 1.075; 95% CI, 0.807 to 1.342;  < 0.001), 6-minute-walk distance (adjusted β = -1.993; 95% CI, -3.481 to -0.506;  < 0.001), and FEV change over time (adjusted β = -1.604; 95% CI, -2.691 to -0.516;  = 0.004), after adjustment for age, sex, race, body mass index, current smoking status, pack-years of smoking, and FEV The Peak Index was also associated with the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index and mortality ( < 0.001). The Peak Index is a spirometry metric that is associated with CT measures of lung disease, respiratory morbidity, lung function decline, and mortality.Clinical trial registered with www.clinicaltrials.gov (NCT00608764).
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http://dx.doi.org/10.1513/AnnalsATS.201811-812OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774744PMC
August 2019

Combining Volumetric Capnography And Barometric Plethysmography To Measure The Lung Structure-function Relationship.

J Vis Exp 2019 01 8(143). Epub 2019 Jan 8.

Department of Health and Human Physiology, Department of Internal Medicine, University of Iowa; Institute for Clinical and Translational Science and Stead Family Department of Pediatrics, University of Iowa;

Tools to measure lung and airways volume are critical for pulmonary researchers interested in evaluating the impact of disease or novel therapies on the lung. Barometric plethysmography is a classic technique to evaluate the lung volume with a long history of clinical use. Volumetric capnography utilizes the profile of exhaled carbon dioxide to determine the volume of the conducting airways, or dead space, and provides an index of airways homogeneity. These techniques may be used independently, or in combination to evaluate the dependence of airways volume and homogeneity on lung volume. This paper provides detailed technical instructions to replicate these techniques and our representative data demonstrates that the airways volume and homogeneity are highly correlated to lung volume. We also provide a macro for the analysis of capnographic data, which can be modified or adapted to fit different experimental designs. The advantage of these measures is that their advantages and limitations are supported by decades of experimental data, and they can be made repeatedly in the same subject without expensive imaging equipment or technically advanced analysis algorithms. These methods may be particularly useful for investigators interested in perturbations that change both the functional residual capacity of the lung and airways volume.
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http://dx.doi.org/10.3791/58238DOI Listing
January 2019

New Spirometry Indices for Detecting Mild Airflow Obstruction.

Sci Rep 2018 11 30;8(1):17484. Epub 2018 Nov 30.

Department of Electrical and Computer Engineering, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.

The diagnosis of chronic obstructive pulmonary disease (COPD) relies on demonstration of airflow obstruction. Traditional spirometric indices miss a number of subjects with respiratory symptoms or structural lung disease on imaging. We hypothesized that utilizing all data points on the expiratory spirometry curves to assess their shape will improve detection of mild airflow obstruction and structural lung disease. We analyzed spirometry data of 8307 participants enrolled in the COPDGene study, and derived metrics of airflow obstruction based on the shape on the volume-time (Parameter D), and flow-volume curves (Transition Point and Transition Distance). We tested associations of these parameters with CT measures of lung disease, respiratory morbidity, and mortality using regression analyses. There were significant correlations between FEV/FVC with Parameter D (r = -0.83; p < 0.001), Transition Point (r = 0.69; p < 0.001), and Transition Distance (r = 0.50; p < 0.001). All metrics had significant associations with emphysema, small airway disease, dyspnea, and respiratory-quality of life (p < 0.001). The highest quartile for Parameter D was independently associated with all-cause mortality (adjusted HR 3.22,95% CI 2.42-4.27; p < 0.001) but a substantial number of participants in the highest quartile were categorized as GOLD 0 and 1 by traditional criteria (1.8% and 33.7%). Parameter D identified an additional 9.5% of participants with mild or non-recognized disease as abnormal with greater burden of structural lung disease compared with controls. The data points on the flow-volume and volume-time curves can be used to derive indices of airflow obstruction that identify additional subjects with disease who are deemed to be normal by traditional criteria.
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http://dx.doi.org/10.1038/s41598-018-35930-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269456PMC
November 2018

Diode-pumped neodymium:yttrium aluminum garnet laser effects on the visceral pleura in an ex vivo porcine lung model†.

Interact Cardiovasc Thorac Surg 2019 03;28(3):339-343

Division of Thoracic Surgery and Lung Transplantation, Department of Cardiothoracic Surgery, University Hospital of Münster, Münster, Germany.

Objectives: Resection of tumour spread on a very thin visceral pleura might be challenging, and collateral damage to the lung parenchyma might occur. We aimed to develop an operative technique, which might facilitate the parenchyma-sparing destruction of the visceral pleura. This experimental work investigated the effects of a neodymium:yttrium aluminum garnet (Nd:YAG) laser on the visceral pleura in an ex vivo porcine lung model.

Methods: We used a diode-pumped Nd:YAG laser (Limax® 120, KLS Martin, Tuttlingen, Germany) to investigate the effects on the visceral pleural in 20 porcine lungs. The laser was applied on a standardized length in 4 different settings: Group I (80 W, 6 s), Group II (80 W, 12 s), Group III (120 W, 6 s) and Group IV (120 W, 12 s). All specimens were analysed histologically.

Results: The mean thickness of the visceral pleura was 81 ± 10 μm. Increasing power levels and longer application duration resulted in significantly enhanced laser destruction effects. The mean depths of the carbonization zone were 142 ± 42 µm, 378 ± 137 µm, 607 ± 155 µm and 1371 ± 271 μm for Groups I-IV, respectively (P < 0.001). The ratio of carbonization zone to pleural thickness was measured for each section (C/P ratio) to quantify the thermal effects. The corresponding C/P ratio for Groups I-IV were 1.72 ± 0.55, 4.98 ± 1.96, 7.11 ± 1.61 and 17.35 ± 4.35, respectively (P < 0.001).

Conclusions: Our study showed that increasing power levels and application duration of the laser lead to a significantly increased carbonization and destruction zones. Further in vivo human studies should evaluate the feasibility of laser application for a potential translational relevance for human use.
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http://dx.doi.org/10.1093/icvts/ivy254DOI Listing
March 2019

Can the Plateau Be Higher Than the Peak Pressure?

Ann Am Thorac Soc 2018 06;15(6):754-759

1 Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa; and.

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http://dx.doi.org/10.1513/AnnalsATS.201707-553CCDOI Listing
June 2018

Treatment of malignant pleural mesothelioma: lessons learned and quo vadis?

J Thorac Dis 2018 Mar;10(3):1183-1185

Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

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http://dx.doi.org/10.21037/jtd.2018.01.171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906295PMC
March 2018

Secondary Lingular Sleeve Resection to Avoid Pneumonectomy Following Bronchial Anastomotic Dehiscence after Left Lower Lobe Sleeve Resection for Destroyed Lung Syndrome.

Surg J (N Y) 2018 Jan 27;4(1):e14-e17. Epub 2018 Feb 27.

Division of Thoracic Surgery, and Lung Transplantation, University Hospital Münster, Münster, Germany.

Bronchial sleeve resections are technically demanding procedures compared with lobectomies. In case of bronchial anastomotic dehiscence, secondary pneumonectomy is the treatment of choice. However, a secondary pneumonectomy is usually associated with high morbidity and mortality. Here, we first report, to the best of our knowledge, a secondary lingular sleeve resection following bronchial anastomotic dehiscence after left lower lobe sleeve resection in a patient with a destroyed lobe syndrome due to a pseudotumor. This approach enabled the avoidance of secondary pneumonectomy, hence reducing the possible pneumonectomy-associated complications.
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http://dx.doi.org/10.1055/s-0038-1635124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828922PMC
January 2018

Pulmonary lobe separation in expiration chest CT scans based on subject-specific priors derived from inspiration scans.

J Med Imaging (Bellingham) 2018 Jan 9;5(1):014003. Epub 2018 Feb 9.

University of Iowa, Department of Electrical and Computer Engineering, Iowa City, Iowa, United States.

Segmentation of pulmonary lobes in inspiration and expiration chest CT scan pairs is an important prerequisite for lobe-based quantitative disease assessment. Conventional methods process each CT scan independently, resulting typically in lower segmentation performance at expiration compared to inspiration. To address this issue, we present an approach, which utilizes CT scans at both respiratory states. It consists of two main parts: a base method that processes a single CT scan and an extended method that utilizes the segmentation result obtained on the inspiration scan as a subject-specific prior for segmentation of the expiration scan. We evaluated the methods on a diverse set of 40 CT scan pairs. In addition, we compare the performance of our method to a registration-based approach. On inspiration scans, the base method achieved an average distance error of 0.59, 0.64, and 0.91 mm for the left oblique, right oblique, and right horizontal fissures, respectively, when compared with expert-based reference tracings. On expiration scans, the base method's errors were 1.54, 3.24, and 3.34 mm, respectively. In comparison, utilizing proposed subject-specific priors for segmentation of expiration scans allowed decreasing average distance errors to 0.82, 0.79, and 1.04 mm, which represents a significant improvement ([Formula: see text]) compared with all other methods investigated.
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http://dx.doi.org/10.1117/1.JMI.5.1.014003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806033PMC
January 2018

Predictive value of prebronchodilator and postbronchodilator spirometry for COPD features and outcomes.

BMJ Open Respir Res 2017 18;4(1):e000213. Epub 2017 Dec 18.

Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.

Introduction: We compared the predictive value of prebronchodilator and postbronchodilator spirometry for chronic obstructive pulmonary disease (COPD) features and outcomes.

Methods: We analysed COPDGene data of 10 192 subjects with smoking history. We created regressions models with the following dependent variables: clinical, functional and radiographic features, and the following independent variables: prebronchodilator airflow obstruction (PREO) and postbronchodilator airflow obstruction (POSTO), prebronchodilator and postbronchodilator FEV% predicted. We compared the model performance using the Akaike information criterion (AIC).

Results: The COPD prevalence was higher using PREO. About 8.5% had PREO but no airflow obstruction in postbronchodilator spirometry (POSTN) (PREO-POSTN) and 3% of all subjects had no aiflow obstruction in prebronchodilator spirometry (PREN) but POSTO (PREN-POSTO). We found no difference in COPD features and outcomes between PREO-POSTN and PREN-POSTO subjects. Although, both prebronchodilator and postbronchodilator spirometries are both associated with chronic bronchitis, dyspnoea, exercise capacity and COPD radiographic findings, models that included postbronchodilator spirometric measures performed better than models with prebronchodilator measures to predict these COPD features. The predictive value of prebronchodilator and postbronchodilator spirometries for respiratory exacerbations, change in forced expiratory volume in 1 s, dyspnoea and exercise capacity during a 5-year period is relatively similar, but postbronchodilator spirometric measures are better predictors of mortality based on AIC.

Conclusions: Postbronchodilator spirometry may be a more accurate predictor of COPD features and outcomes.
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http://dx.doi.org/10.1136/bmjresp-2017-000213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759707PMC
December 2017

Chest wall strapping increases expiratory airflow and detectable airway segments in computer tomographic scans of normal and obstructed lungs.

J Appl Physiol (1985) 2018 05 4;124(5):1186-1193. Epub 2018 Jan 4.

Department and Internal Medicine, University of Iowa , Iowa City, Iowa.

Chest wall strapping (CWS) induces breathing at low lung volumes but also increases parenchymal elastic recoil. In this study, we tested the hypothesis that CWS dilates airways via airway-parenchymal interdependence. In 11 subjects (6 healthy and 5 with mild to moderate COPD), pulmonary function tests and lung volumes were obtained in control (baseline) and the CWS state. Control and CWS-CT scans were obtained at 50% of control (baseline) total lung-capacity (TLC). CT lung volumes were analyzed by CT volumetry. If control and CWS-CT volumetry did not differ by more than 25%, airway dimensions were analyzed via automated airway segmentation. CWS-TLC was reduced on average to 71% of control-TLC in normal subjects and 79% of control-TLC in subjects with COPD. CWS increased expiratory airflow at 50% of control-TLC by 41% (3.50 ± 1.6 vs. 4.93 ± 1.9 l/s, P = 0.04) in normals and 316% in COPD(0.25 ± 0.05 vs 0.79 ± 0.39 l/s, P = 0.04). In 10 subjects (5 normals and 5 COPD), control and CWS-CT scans at 50% control-TLC did not differ more than 25% on CT volumetry and were included in the airway structure analysis. CWS increased the mean number of detectable airways with a diameter of ≤2 mm by 32.5% (65 ± 10 vs. 86 ± 124, P = 0.01) in normal subjects and by 79% (59 ± 19 vs. 104 ± 16, P = 0.01) in subjects with COPD. There was no difference in the number of detectable airways with diameters 2-4 mm and >4 mm in normal or in COPD subjects. In conclusion, CWS enhances the detection of small airways via automated CT airway segmentation and increases expiratory airflow in normal subjects as well as in subjects with mild to moderate COPD. NEW & NOTEWORTHY In normal and COPD subjects, chest wall strapping(CWS) increased the number of detectable small airways using automated CT airway segmentation. The concept of dysanapsis expresses the physiological variation in the geometry of the tracheobronchial tree and lung parenchyma based on development. We propose a dynamic concept to dysanapsis in which CWS leads to breathing at lower lung volumes with a corresponding increase in the size of small airways, a potentially novel, nonpharmacological treatment for COPD.
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http://dx.doi.org/10.1152/japplphysiol.00184.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008079PMC
May 2018

Depletion of Airway Submucosal Glands and TP63KRT5 Basal Cells in Obliterative Bronchiolitis.

Am J Respir Crit Care Med 2018 04;197(8):1045-1057

1 Department of Surgery.

Rationale: Obliterative bronchiolitis (OB) is a major cause of mortality after lung transplantation. Depletion of airway stem cells (SCs) may lead to fibrosis in OB.

Objectives: Two major SC compartments in airways are submucosal glands (SMGs) and surface airway p63 (also known as TP63 [tumor protein 63])-positive/K5 (also known as KRT5 [keratin 5])-positive basal cells (BCs). We hypothesized that depletion of these SC compartments occurs in OB.

Methods: Ferret orthotopic left lung transplants were used as an experimental model of OB, and findings were corroborated in human lung allografts. Morphometric analysis was performed in ferret and human lungs to evaluate the abundance of SMGs and changes in the expression of phenotypic BC markers in control, lymphocytic bronchiolitis, and OB airways. The abundance and proliferative capacity of proximal and distal airway SCs was assessed using a clonogenic colony-forming efficiency assay.

Measurements And Main Results: Ferret allografts revealed significant loss of SMGs with development of OB. A progressive decline in p63/K5 and increase in K5/K14 and K14 BC phenotypes correlated with the severity of allograft rejection in large and small ferret airways. The abundance and proliferative capacity of basal SCs in large allograft airways declined with severity of OB, and there was complete ablation of basal SCs in distal OB airways. Human allografts mirrored phenotypic BC changes observed in the ferret model.

Conclusions: SMGs and basal SC compartments are depleted in large and/or small airways of lung allografts, and basal SC proliferative capacity declines with progression of disease and phenotypic changes. Global airway SC depletion may be a mechanism for pulmonary allograft failure.
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http://dx.doi.org/10.1164/rccm.201707-1368OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909161PMC
April 2018

Incomplete fissures are associated with increased alveolar ventilation via spiracles in severe emphysema.

Interact Cardiovasc Thorac Surg 2017 12;25(6):851-855

Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.

Objectives: In emphysema, air can flow preferentially via collateral pathways, which can connect an entire lung when incomplete fissures are present. Spiracles are openings through the chest wall into the lung parenchyma. We previously observed increased alveolar ventilation (VA) in subjects with severe emphysema, when spiracles occurred during lung transplant operations. In this study, we set out to identify a computed tomography (CT) imaging phenotype associated with improved VA via spiracles in severe emphysema.

Methods: We retrospectively reviewed 4 patients with severe emphysema who exhaled ≥75% of the inhaled tidal volume via transpleural spiracles during a lung transplant operation. We used quantitative image analysis via VIDA VISION CT software to describe emphysema severity and distribution and fissure integrity from pretransplant CT scans of the chest. We analysed partial pressure of carbon dioxide and calculated estimates of VA at baseline and during spiracle ventilation.

Results: All 4 subjects demonstrated severe hyperinflation (total lung capacity 148 ± 24%predicted, residual volume 296 ± 79% predicted). On CT imaging, severe emphysema was present, with an average 38.7 ± 9% (range 28-50%) of lung parenchyma showing low-attenuation areas of - 950 Hounsfield units or less. Lung fissure integrity analysis demonstrated evidence of incomplete fissures (average detectable fissure integrity 67 ± 19%, range 40 ± 11-90 ± 10%). During spiracle ventilation on unchanged ventilator settings, there was a significant reduction in partial pressure of carbon dioxide (61 ± 4-35 ± 4 mmHg, P < 0.001) and increase in estimated VA (2.1 ± 0.5-3.8 ± 0.8 l/min, P < 0.001).

Conclusions: Incomplete lung fissures on quantitative CT analysis seem to be a key image phenotype associated with substantial improvements in VA during transpleural ventilation via spiracles in severe emphysema.
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http://dx.doi.org/10.1093/icvts/ivx220DOI Listing
December 2017

Higher BMI is associated with higher expiratory airflow normalised for lung volume (FEF25-75/FVC) in COPD.

BMJ Open Respir Res 2017 13;4(1):e000231. Epub 2017 Oct 13.

Department of Medicine, University of Iowa, Iowa City, Iowa, USA.

Introduction: The obesity paradox in chronic obstructive pulmonary disease (COPD), whereby patients with higher body mass index (BMI) fare better, is poorly understood. Higher BMIs are associated with lower lung volumes and greater lung elastic recoil, a key determinant of expiratory airflow. The forced expiratory flow (25-75) (FEF)/forced vital capacity (FVC) ratio reflects effort-independent expiratory airflow in the context of lung volume and could be modulated by BMI.

Methods: We analysed data from the COPDGene study, an observational study of 10 192 subjects, with at least a 10 pack-year smoking history. Data were limited to subjects with BMI 20-40 kg/m (n=9222). Subjects were stratified according to forced expiratory volume in 1 s (FEV) (%predicted)-quintiles. In regression analyses and Cox proportional hazard models, we analysed the association between BMI, the FEF/FVC ratio, the imaging phenotype, COPD exacerbations, hospitalisations and death.

Results: There was no correlation between BMI and FEV(%predicted). However, a higher BMI is correlated with a higher FEF/FVC ratio. In CT scans, a higher BMI was associated with less emphysema and less air trapping. In risk-adjusted models, the quintile with the highest FEF/FVC ratio was associated with a 46% lower risk of COPD exacerbations (OR 0.54, p<0.001) and a 40% lower risk of death (HR 0.60, p=0.02), compared with the lowest quintile. BMI was not independently associated with these outcomes.

Conclusions: A higher BMI is associated with lower lung volumes and higher expiratory airflows when normalised for lung volume, as quantified by the FEF/FVC ratio. A higher FEF/FVC ratio is associated with a lower risk of COPD exacerbations and death and might quantify functional aspects of the paradoxical effect of higher BMIs on COPD.
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http://dx.doi.org/10.1136/bmjresp-2017-000231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652498PMC
October 2017

Survival of Lung Transplant Candidates With COPD: BODE Score Reconsidered.

Chest 2018 03 17;153(3):697-701. Epub 2017 Oct 17.

Department of Medicine, Brigham and Women's Hospital, Boston, MA.

Background: The BMI, obstruction, dyspnea, and exercise capacity (BODE) score is used to inform prognostic considerations for lung transplantation for COPD, but it has not been validated in this context. A large proportion of mortality in COPD is attributable to comorbidities that could preclude transplant candidacy. We hypothesized that patients with COPD who are selected as transplant candidates experience better survival than traditional interpretation of BODE scores might indicate.

Methods: We performed a retrospective analysis of survival according to the BODE score for patients with COPD in the United Network of Organ Sharing (UNOS) database of lung transplantation candidates (n = 4,377) compared with the cohort of patients with COPD in which the BODE score was validated (n = 625).

Results: Median survival in the fourth quartile of BODE score was 59 months (95% CI, 51-77 months) in the UNOS cohort and 37 months (95% CI, 29-42 months) in the BODE validation cohort. In models controlling for BODE score and incorporating lung transplantation as a competing end point, the risk of death was higher in the BODE validation cohort (subhazard ratio, 4.8; 95% CI, 4.0-5.7; P < .001). The risk difference was greatest in the fourth quartile of BODE scores (SHR, 6.1; 95% CI, 4.9-7.6; P < .001).

Conclusions: Extrapolation of prognosis based on the BODE score overestimates mortality risk in lung transplantation candidates with COPD. This is likely due to a lower prevalence of comorbid conditions attributable to the lung transplantation evaluation screening process.
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http://dx.doi.org/10.1016/j.chest.2017.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989634PMC
March 2018

Persistent Air Leaks.

Chest 2017 08;152(2):449-450

Department of Thoracic Surgery, University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, Germany.

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http://dx.doi.org/10.1016/j.chest.2017.03.060DOI Listing
August 2017
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