Management of two circulations in a COVID-19 patient with secondary superinfection.

Optimal oxygenation in the intensive care unit requires adequate pulmonary gas exchange, oxygen-carrying capacity in the form of hemoglobin, sufficient delivery of oxygenated hemoglobin to the tissue, and an appropriate tissue oxygen demand. In this Case Study in Physiology, we describe a patient with COVID-19 whose pulmonary gas exchange and oxygen delivery were severely compromised by COVID-19 pneumonia requiring extracorporeal membrane oxygenation (ECMO) support. His clinical course was complicated by a secondary superinfection with staphylococcus aureus and sepsis. This case study is provided with two goals in mind (1) We outline how basic physiology was used to address life-threatening consequences of a novel infection-COVID-19. (2) We describe a strategy of whole-body cooling to lower the cardiac output and oxygen consumption, use of the shunt equation to optimize flow to the ECMO circuit, and transfusion to improve oxygen-carrying capacity when ECMO alone failed to provide sufficient oxygenation.

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

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/1.73m2. 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.

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

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 ß 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.NEW & NOTEWORTHY 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.

Multimodal and palliative treatment of patients with pulmonary metastases.

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.

Survival of Pregnant Coronavirus Patient on Extracorporeal Membrane Oxygenation.

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.

Preserved Ratio Impaired Spirometry in a Spirometry Database.

BACKGROUND: Spirometry results can yield a diagnosis of normal air flow, air flow obstruction, or preserved ratio impaired spirometry (PRISm), defined as a reduced FEV1 or FVC in the setting of preserved FEV1/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 FEV1 < 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 FEV1 (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.

Standard and extended sleeve resections of the tracheobronchial tree.

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.

Rabbit Antithymocyte Globulin Causes Blastomyces and Histoplasma Antigenemia.

Rabbit antithymocyte globulin (rATG) is known to yield false-positive Histoplasma antigenemia. The fourth generation MiraVista Histoplasma antigen assay was modified to block this effect (MiraVista Diagnostics, Indianapolis, Indiana). We report a case of rATG-induced false-positive Blastomyces and Histoplasma antigenemia in a lung transplant recipient despite modifications of these antigen assays.

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

Rationale: 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.Objectives: To assess whether the Peak Index, the number of peaks adjusted for lung size, is associated with clinical outcomes.Methods: 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 (FEV1) decline, and mortality.Results: The Peak Index progressively increased from Global Initiative for Chronic Obstructive Lung Disease stage 0 through 4 (P < 0.001). On multivariable analysis, the Peak Index was significantly associated with CT emphysema (adjusted ß = 0.906; 95% confidence interval [CI], 0.789 to 1.023; P < 0.001) and small airways disease (adjusted ß = 1.367; 95% CI, 1.188 to 1.545; P < 0.001), St. George's Respiratory Questionnaire score (adjusted ß = 1.075; 95% CI, 0.807 to 1.342; P < 0.001), 6-minute-walk distance (adjusted ß = -1.993; 95% CI, -3.481 to -0.506; P < 0.001), and FEV1 change over time (adjusted ß = -1.604; 95% CI, -2.691 to -0.516; P = 0.004), after adjustment for age, sex, race, body mass index, current smoking status, pack-years of smoking, and FEV1. The Peak Index was also associated with the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index and mortality (P < 0.001).Conclusions: 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).

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

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.

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

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.

New Spirometry Indices for Detecting Mild Airflow Obstruction.

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 FEV1/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.