Lung Disease Stage Research Articles

Clinical implication of electrocardiogram change in patients experiencing lung transplantation with end stage lung disease.

End-stage lung disease causes cardiac remodeling and induces electrocardiogram (ECG) changes. On the other way, whether lung transplantation (LTx) in end-stage lung disease patients are associated with ECG change is unknown. The object of this study was to investigate ECG changes before and after LTx in end-stage lung disease patients and whether these changes had clinical significance. This was a single-center retrospective cohort study of 280 end-stage lung disease patients who consecutively underwent LTx at a tertiary referral hospital. ECG findings before LTx and within 1 week and 1, 3, and 6 months after LTx were obtained and analyzed. To find clinical meaning, the ECG at 1 month after LTx was analyzed according to 1-year survival (survivor vs non-survivor groups). Survival data were estimated using the Kaplan-Meier method. Significant differences were observed in the PR interval, QRS duration, QT interval, QTc interval, and heart rate before LTx and 1 month after LTx; the PR interval, QRS duration, QTc interval, and heart rate were decreased. Particularly, the QTc interval was significantly decreased 1 month after LTx, whereas there was no significant change in the QTc interval from 1 to 6 months thereafter. The PR interval, QT interval, QTc interval, and heart rate were significantly different between the survivor and non-survivor groups. The serial changes in QTc interval before LTx and 1 and 3 months after LTx were also significantly different between the survivor and non-survivor groups (p = 0.040 after adjusting for age and body mass index). Upon dividing the patients based on the range of QTc interval change ≤ -8 ms, >-8-10 ms, >10-35 ms, >35 ms), the survival rate was significantly lower in the group whose QTc interval at 1 month after LTx decreased by > 35 m (p = 0.019). LTx in patients with end-stage lung disease may induce ECG changes. Patients whose QTc interval at 1 month after LTx decreased by > 35 ms have a significantly higher 1-year mortality rate. Hence, these ECG changes may have clinical and prognostic significance.

The foregut in cystic fibrosis.

The aerodigestive organs share a kindred embryologic origin that allows for a more complete explanation as to how the foregut can remain a barrier to normalcy in people with cystic fibrosis (pwCF). The structures of the aerodigestive tract include the nasopharynx, the oropharynx, the hypopharynx, the esophagus, the stomach, as well as the supraglottic, glottic, and subglottic tubular airways (including the trachea). Additional gastrointestinal (GI) luminal/alimentary organs of the foregut include the duodenum. Extraluminal foregut structures include the liver, the gall bladder, the biliary tree, and the pancreas. There are a variety of neurologic controls within these complicated anatomic compartments to separate the transit of food and liquid from air. These structures share the same origin from the primitive foregut/mesenchyme. The vagus nerve is a critical structure that unites respiratory and digestive functions. This article comments on the interconnected nature of cystic fibrosis and the GI tract. As it relates to the foregut, this has been typically treated as simple "reflux" as the cause of worsened lung function in pwCF. That terms like gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD), heartburn, and regurgitation are used interchangeably to reflect pathology further complicates matters; we offer a more physiologically accurate term called "GI-related aspiration" or "GRASP." Broadly, this term reflects that aspiration of foregut contents from the duodenum through the stomachto the esophagus, into the pharynx and the respiratory tree in pwCF. As a barrier to normalcy in pwCF, GRASP is fundamentally two disease processes-GERD and gastroparesis-that likely contribute most to the deterioration of lung disease in pwCF. In the modulator era, successful GRASP management will be critical, particularly in those post-lung transplantation (LTx), only through successful management of both GERD and gastroparesis. Standardization of clinical management algorithms for GRASP in CF-related GRASP is a key clinical and research gap preventing normalcy in pwCF; what exists nearly exclusively addresses surgical evaluations or offers guidance for the management of GI symptoms alone (with unclear parameters for respiratory disease considerations). We begin first by describing the result of GRASP damage to the lung in various stages of lung disease. This is followed by a discussion of the mechanisms by which the digestive tract can injure the lungs. We summarize what we anticipate future research directions will be to reduce the impact of GRASP as a barrier to normalcy in pwCF.

Lung quantitative ultrasound to stage and monitor interstitial lung diseases

Chronic interstitial lung diseases (ILDs) require frequent point-of-care monitoring. X-ray-based methods lack resolution and are ionizing. Chest computerized tomographic (CT) scans are expensive and provide more radiation. Conventional ultrasound can detect severe lung damage via vertical artifacts (B-lines). However, this information is not quantitative, and the appearance of B-lines is operator- and system-dependent. Here we demonstrate novel ultrasound-based biomarkers to assess severity of ILDs. Lung alveoli scatter ultrasound waves, leading to a complex acoustic signature, which is affected by changes in alveolar density due to ILDs. We exploit ultrasound scattering in the lung and combine quantitative ultrasound (QUS) parameters, to develop ultrasound-based biomarkers that significantly correlate (p = 1e−4 for edema and p = 3e−7 for fibrosis) to the severity of pulmonary fibrosis and edema in rodent lungs. These innovative QUS biomarkers will be very significant for monitoring severity of chronic ILDs and response to treatment, especially in this new era of miniaturized and highly portable ultrasound devices.

Acute Rejection of the Lung Allograft: Phenotypes and Management

Treatment options for end stage lung diseases are limited to stabilizing lung failure, decreasing disease progression, and symptom management, but significant reversal of lost lung function is often not possible. For well selected patients, lung transplantation may be a viable option to improve both longevity and quality of life. Though outcomes for lung transplant recipients have improved over several decades, long term survival still lags behind that of other solid organ transplant recipients. Longevity after lung transplantation is limited by chronic lung allograft dysfunction. Numerous insults to the allograft contribute to chronic rejection, alloimmune injuries including acute T-cell mediated and antibody mediated rejection are chief among them. Therefore, monitoring for and management of acute cellular and antibody mediated rejection are of paramount importance to those caring for lung transplant recipients. We provide an up to date and comprehensive review of acute rejection affecting lung allografts and attempt to highlight pathophysiology, risk factors, clinical presentation, rejection phenotypes, management strategies, as well as related from of acute allograft injury.

Lung Transplantation: Selection of Candidates

Lung transplantation is a last-resort treatment option for patients with end stage lung disease. The procedure is being performed more frequently and scientific advances continue to be made, but the median post-transplant survival is far shorter than other solid organ transplant recipients. Candidate selection is a resource intensive process that attempts to balance risks of the procedure with the benefits of much higher quality of life. Transplant centers must weigh disease specific considerations, medical comorbidities, and psychosocial factors with the likelihood of a successful transplantation. While the candidate selection process is exceptionally challenging, it leads to many patients undergoing successful lung transplantation.

Early and sustained improvements of lung clearance index from two to sixteen weeks of elexacaftor/tezacaftor/ivacaftor therapy in patients with cystic fibrosis-a real world study.

Since the introduction of CFTR modulator therapies, longitudinal real-life data of lung clearance index (LCI) during treatment is scarce. In this single-centre, post-approval setting, we report data of 51 patients with different stages of lung disease, age 2-52years with repeated measurements of forced expiratory volume as a percentage of the predicted value (ppFEV₁) and LCI after 2, 4, and 16weeks of CFTR modulator treatment and at baseline. In 25 patients during elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) treatment, significant improvements of LCI (median -1.4) and ppFEV₁ (median +8.3%) were observed after only 2weeks, and were maintained after 4 and 16weeks of treatment (LCI: -2.0, -2.2; ppFEV₁: +7.2%, +11.8%). We observed a significant correlation between LCI improvement at week 16 and lower baseline LCI. In 26 younger and healthier patients receiving lumacaftor/ivacaftor (LUM/IVA) treatment, no significant changes of LCI and ppFEV₁ occured. With ELX/TEZ/IVA, our data shows rapid, significant improvements of LCI and ppFEV₁ already after 2weeks. Early LCI measurements can help to assess the patient's response to this high-cost therapy.

Functional comorbidities and brain tissue changes before and after lung transplant in adults.

Adults undergoing lung transplant, as a lifesaving treatment for end stage lung disease, exhibit high levels of peri-operative neurocognitive dysfunction in multiple domains, including delirium, cognition, and autonomic deficits. These complications impact healthcare costs, quality of life, and patient outcomes. Post-operative symptoms likely result from loss of brain tissue integrity in sites mediating such regulatory functions. Our aim in this study was to examine peri-operative neurocognitive dysfunction and brain tissue changes after lung transplant in adults. We retrospectively examined the UCLA lung transplant database to identify 114 lung transplant patients with pre-operative clinical and neurocognitive data. Of 114 patients, 9 lung transplant patients had pre- and post-transplant brain magnetic resonance imaging. Clinical and neurocognitive data were summarized for all subjects, and brain tissue volume changes, using T1-weighted images, before and after transplant were examined. T1-weighted images were partitioned into gray matter (GM)-tissue type, normalized to a common space, smoothed, and the smoothed GM-volume maps were compared between pre- and post-transplant (paired t-tests; covariate, age; SPM12, p < 0.005). Increased comorbidities, including the diabetes mellitus (DM), hypertension, kidney disease, and sleep disordered breathing, as well as higher rates of neurocognitive dysfunction were observed in the lung transplant patients, with 41% experiencing post-operative delirium, 49% diagnosed with a mood disorder, and 25% of patients diagnosed with cognitive deficits, despite incomplete documentation. Similarly, high levels of delirium, cognitive dysfunction, and mood disorder were noted in a subset of patients used for brain MRI evaluation. Significantly decreased GM volumes emerged in multiple brain regions, including the frontal and prefrontal, parietal, temporal, bilateral anterior cingulate and insula, putamen, and cerebellar cortices. Adults undergoing lung transplant often show significant pre-operative comorbidities, including diabetes mellitus, hypertension, and chronic kidney disease, as well as neurocognitive dysfunction. In addition, patients with lung transplant show significant brain tissue changes in regions that mediate cognition, autonomic, and mood functions. The findings indicate a brain structural basis for many enhanced post-operative symptoms and suggest a need for brain tissue protection in adults undergoing lung transplant to improve health outcomes.

P090: Staging of Lung Lesions Survey Demonstrates Continued Need for Harmonization

Figure 1: Case vignettes and survey responses. Background: Staging of lung disease in Hodgkin lymphoma (HL) has been a longstanding and controversial challenge. In 1984, a survey of 14 experts was published in the Journal of Clinical Oncology. Four case vignettes were distributed, and experts designated each vignette as either Stage IIE or Stage IV disease. Results were very divided for 2 of the 4 case vignettes, and the conclusion was a call for clear guidance and group consensus for staging of lung lesions. Despite updates to the HL staging systems at both the Cotswold (1989) and Lugano (2014) meetings, there remains today, nearly 30 years later, a perceived lack of uniformity in the approach to the staging of lung lesions even among experts in the field. The approach to each of these issues not only varies across consortium groups but among individuals within the same consortium groups. When reviewing the most recent frontline HL trials from St. Jude-Stanford-Dana Farber, EuroNet PHL, and the Children’s Oncology Group, lung lesions were defined differently for each. This creates difficulty in comparing outcomes across trials and highlights the need for consensus and uniformity. Methods: The SEARCH for CAYAHL (Staging, Evaluation and Response Criteria Harmonization for Childhood, Adolescent, and Young Adult HL) group recreated a similar survey using 7 case vignettes and distributed it to 26 internationally recognized experts in pediatric HL to establish how current world experts are staging lung lesions (see Figure 1). Of the 21 survey respondents (81% response rate), 7 were radiologists or nuclear medicine radiologists, and 14 were pediatric oncologists. While there was near consensus for some of the cases, several remained very divided, namely around the role of PET avidity in lung lesions, the number and location of lung lesions, and the concept of contiguous disease. Conclusions: After reviewing the results of our survey, the SEARCH group acknowledges the controversy and inconsistency with which we are currently staging lung disease around the globe. We are now actively working to establish clear criteria, based on available data, and expert consensus through Delphi survey methods, and plan to have this completed in the fall of 2022.

Lymphocytic Airway Inflammation in Lung Allografts.

Lung transplant remains a key therapeutic option for patients with end stage lung disease but short- and long-term survival lag other solid organ transplants. Early ischemia-reperfusion injury in the form of primary graft dysfunction (PGD) and acute cellular rejection are risk factors for chronic lung allograft dysfunction (CLAD), a syndrome of airway and parenchymal fibrosis that is the major barrier to long term survival. An increasing body of research suggests lymphocytic airway inflammation plays a significant role in these important clinical syndromes. Cytotoxic T cells are observed in airway rejection, and transcriptional analysis of airways reveal common cytotoxic gene patterns across solid organ transplant rejection. Natural killer (NK) cells have also been implicated in the early allograft damage response to PGD, acute rejection, cytomegalovirus, and CLAD. This review will examine the roles of lymphocytic airway inflammation across the lifespan of the allograft, including: 1) The contribution of innate lymphocytes to PGD and the impact of PGD on the adaptive immune response. 2) Acute cellular rejection pathologies and the limitations in identifying airway inflammation by transbronchial biopsy. 3) Potentiators of airway inflammation and heterologous immunity, such as respiratory infections, aspiration, and the airway microbiome. 4) Airway contributions to CLAD pathogenesis, including epithelial to mesenchymal transition (EMT), club cell loss, and the evolution from constrictive bronchiolitis to parenchymal fibrosis. 5) Protective mechanisms of fibrosis involving regulatory T cells. In summary, this review will examine our current understanding of the complex interplay between the transplanted airway epithelium, lymphocytic airway infiltration, and rejection pathologies.

Cell death in lung transplantation. The roles of apoptosis, necroptois, and pyroptosis

Abstract Objective For patients with end stage lung disease, lung transplantation (Ltx) is the unique treatment option. Nevertheless, a large number of lung allografts fail, because of acute or chronic rejection. Innate immune responses following Ltx play a critical role in the development of primary graft dysfunction, and ultimately promote the development of chronic lung allograft dysfunction, leading to increased mortality after lung transplantation. Here, we focus on the mechanisms responsible for disruption of the cells membranes integrity, resulting in the release of Damage Associated Molecular Patterns (DAMPs) and activation of cell death pathways triggering cell injury in lungs with different preservation status. Methods Rat lungs were exposed to cold ischemia (CI group, n=9) or warm ischemia (WI group, n=9). In CI group, after Perfadex flushing, and hypothermic preservation (4 h) left lung was transplanted. In WI group, after 1 h of in situ WI, flashing and 3 h cold preservation the left lung was transplanted. Lung mechanics were determined during reperfusion. Recipients were sacrificed at 30, 60 and 120 min after Ltx. Bronchoalveolar lavage (BAL) was performed on the grafts to measure markers of cellular injury, and cytokines. Cell death markers were determined in graft tissue. Biological samples were kept at -80°C for additional analysis. Results Compared to CI, WI group displayed significantly decreased graft function associated with increased activation of pyroptotic cell death (NLRP3, caspase1, IL-1β) pathway, whereas apoptotic (caspas3 and caspase7) and necroptotic (RIP1, RIP3, MLKL) cell death pathways activation were similar in both groups. WI group showed more important cellular damage with DAMPs release (LDH, sRAGE, HMGB) and inflammation (CXCL1, IL1-β, IL-33). Conclusion Our results suggest that pyroptosis could play a critical role in the development of early graft dysfunction in lungs subjected to warm ischemia. Inhibition of pyroptotic pathway could be a strategy to improve damaged donor lungs.

The Association between Medical Utilization and Chronic Obstructive Pulmonary Disease Severity: A Comparison of the 2007 and 2011 Guideline Staging Systems.

(1) Background: This study aimed to investigate the associations between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging systems, medical costs, and mortality among patients with chronic obstructive lung disease (COPD). Predictions of the effectiveness of the two versions of the staging systems were also compared. (2) Purpose: this study investigated the associations between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging systems, medical costs, and mortality among patients with COPD. Predicting effectiveness between the two versions of the staging systems was also compared. (3) Procedure: This study used a secondary clinical database of a medical center in central Taiwan to examine records between 2011 and 2017. A total of 613 patients with COPD were identified. The independent variables comprised the COPD GOLD Guideline staging of the 2007 and 2011 versions, demographic characteristics, health status, and physician seniority. The dependent variables included total medical cost, average length of hospital stay, and mortality. The statistical methods included binomial logistic regression and the general linear model (GLM). (4) Discussion: The total medical cost during the observation period for patients with COPD averaged TWD 292,455.6. The average length of hospital stay was 9.7 days. The mortality rate was 9.6%, compared with that of patients in Grade 1 of the 2007 version; patients in Grade 4 of the 2007 version had significantly higher odds of death (OR = 4.07, p = 0.02). The accuracy of mortality prediction for both the 2007 and 2011 versions of the staging was equal, at 90.4%. The adjusted GLM analysis revealed that patients in Group D of the 2011 version had a significantly longer length of hospital stay than those in Group A of the 2011 version (p = 0.04). No difference between the 2007 and 2011 versions was found regarding the total medical cost. Complications were significantly associated with the total medical cost and average length of hospital stay. (5) Conclusions: The COPD staging 2011 version was associated with an average length of hospital stay, whereas the COPD staging 2007 version was related to mortality risk. Therefore, the 2011 version can estimate the length of hospital stay. However, in predicting prognosis and mortality, the 2007 version is recommended.

Clinico-Radiological-Pathologic Profile and Outcomes of Lung Transplant in Post–COVID-19 Phenotype: A Single Center Experience

BackgroundLung transplantation (LTx) has come as hope for select patients with post-COVID acute respiratory distress syndrome (ARDS). It has a different phenotype with unique challenges. We aimed to bring out our experience with and outcomes of LTx for post-COVID ARDS.MethodsThis study is retrospective case series from a single center in India. All the patients with post-COVID end stage lung disease (ESLD) who underwent bilateral LTx between 1st May 2020 and 30th August 2021 were included. LTx was performed following no improvement with optimal medical management with adequate time provided for recovery. Information relating to demographics, comorbidities, pretransplant status, perioperative parameters, gross and histopathological findings of explanted lungs, posttransplant morbidity, and mortality were analyzed.ResultsThis study included 23 patients. The median age of the patients in this study was 42 years and 20 participants were men (87%). The mean duration of intensive care unit stay was 15.83 ± 6.61 days. Mortality was observed among 8 participants (34.78%). Mean survival time was 34.54 weeks. Among the 8 patients who expired, the cause of death was sepsis for 6 patients (75.0%), neurologic cerebrovascular accident for 1 patient (12.5%), and cytomegalovirus for 1 patient (12.5%). All the deaths were reported in primary graft dysfunction grade 2 & 3 category. No rejections were observed on first and third month surveillance biopsies.ConclusionsLTx is the definitive option for survival in select patients with severe post–COVID-19–associated ESLD. This study brings out various challenges involved in such phenotypes and also observations in postoperative recovery.

Airway Complications After Lung Transplant for Post Coronaviral Disease (COVID-19) Acute Respiratory Distress Syndrome (ARDS) Related End Stage Lung Disease: Single Centre Experience

PurposeSevere COVID-19 ARDS related end stage lung fibrosis with irreversible changes is a newer indication for lung transplantation with acceptable survival rate. Airway complication post lung transplant is a major source of morbidity and mortality with incidence as high as 25 to 49 percent. Patients with end stage COVID-19 fibrosis are likely to be clinically deconditioned with long duration of extracorporeal oxygenator (ECMO) support, high burden of sepsis and prolonged respiratory support which may affect the airways post lung transplantation.MethodsThis is a retrospective observational study after obtaining institutional ethical clearance. We reviewed electronic medical data of patients who underwent lung transplantation for post COVID-19 ARDS related fibrosis. We evaluated the incidence and type of airway complications and the various therapeutic interventions applied for its management.ResultsBetween May 2020 and September 2021 our centre performed 23 bilateral lung transplants for end stage COVID-19 ARDS related fibrosis. 22 patients were on ECMO support with mean duration of 50.9 days before transplantation. All patients underwent lung transplantation with central Veno-Arterial ECMO support with mean organ ischaemia time of 360±154 minutes. The incidence of airway complication in our study group was 56%. We observed anastomotic narrowing in 3(13%), distal airway narrowing in 4(17%) and sloughing/coating of anastomotic site in 5(22%) patients. Nonspecific inflammatory polypi around the bronchial anastomotic site were noticed in 4(17%) and mild airway anastomotic dehiscence in 2 subjects. 8(34%) patients required serial bronchoscopy and balloon dilatation; 2 among them mandated additional cautery usage. 2 cases underwent polypectomy, further 4 subjects needed bronchial stent placement. 5 (21%) recipients were discharged with Tracheostomy while rest were successfully decannulated in the ward.ConclusionWe observed a high incidence of airway complications in post lung transplant for COVID-19 ARDS related fibrosis. Early detection, timely management and serial follow up is of paramount importance in this subset of patients.

Radiographic and Histopathologic Lessons from COVID-19 Explants

PurposeCOVID-19 acute respiratory distress syndrome (ARDS) can result in irreversible lung damage. Lung transplant is a viable option for such select patients. Our aim is to describe the radiologic features prior to lung transplant and post transplant explant pathology, in such patients.MethodsA single center retrospective chart review was performed of adults who underwent lung transplant for COVID-19 ARDS from 7/1/2020 until 7/31/2021. Demographic data, imaging reports at the time of listing and explant pathology were collected.Results25 patients were included and none of them had pre-existing lung disease. Chest CT reports obtained at the time of transplant listing and post transplant lung explant reports were reviewed. Most common radiographic and explant features were traction bronchiectasis and NSIP pattern interstitial fibrosis, respectively.ConclusionTo our knowledge, this is the largest descriptive report on COVID 19 explants. Though NSIP pattern is the most common finding on explants, only 48% of patients had fibrosis on CT scan prior to listing. Hence, other findings reflective of end stage lung disease such as traction bronchiectasis, GGO's should be considered along with respiratory mechanics while assessing the need for lung transplant for COVID-19 ARDS.

Comparing Outcomes of COVID-19 vs NonCOVID-19 Lung Transplant Recipients on ECMO as a Bridge to Transplant

PurposeDespite advances in treatments for COVID-19, a subset of patients develop end stage lung disease, necessitating lung transplantation. However, COVID-19 ARDS often requires prolonged intubation with sedation and paralytics, resulting in profound deconditioning. As such, extracorporeal membranous oxygenation (ECMO) is a useful bridge to transplant to allow for a wakeful state and facilitate rehab. This study compares outcomes among patients with COVID-19 and nonCOVID-19 lung disease placed on ECMO as a bridge to transplant.MethodsAll patients on veno-venous ECMO prior to lung transplantation at a single center from Jan 2020 - Oct 2021 were identified. Patient characteristics and post-transplant outcomes were abstracted for comparison.ResultsA total of 7 patients were identified in the COVID-19 (C) cohort and 11 in the nonCOVID-19 (NC) cohort. Age and LAS at transplant were similar (Table 1). As expected, total duration on ECMO was longer for C cohort patients (85.4 vs 14.5 days). Patients in the C cohort had longer ischemia times and more returns to the OR within 72 hours of transplant (71% vs 45%). Rates of hemodialysis within 30 days of transplant were lower in the C cohort (14% vs 18%). Further, C cohort patients had higher rates of detectable donor specific antibodies by IgG (71% vs 55%), though all were negative by C1q and compatible cross matches. While total and ICU lengths of stay were longer in the C cohort, this group had a shorter post-transplant hospital length of stay. Median time post-transplant was 212 days for the C cohort and 154 days for the NC cohort; survival was 100% for both groups at follow up.ConclusionFor patients with COVID-19 ARDS, ECMO is a useful bridge to transplant to mitigate complications associated with prolonged mechanical ventilation. These preliminary data suggest prolonged periods of ECMO pre-transplant do not result in significant adverse events post-transplant. Additional analyses of graft function and survival at 6 and 12 months are ongoing.

The Mystery of Inappropriate Hypoxia After Single Lung Transplant

<h3>Introduction</h3> Single lung transplantation (SLT) is a treatment option for end stage lung disease in select patients, increasing utilization of a scarce resource. Increase in relative perfusion to the allograft from hypoxic vasoconstriction typically ameliorates hypoxia despite native lung disease. We present a SLT recipient with idiopathic pulmonary fibrosis (IPF) who developed hypoxia due to inappropriate shunting to the native lung after an IPF exacerbation. <h3>Case Report</h3> A 66 year old female with IPF had a left SLT eight months prior to presentation. Four months post transplant, she developed submassive bilateral extensive pulmonary embolism (PE) requiring suction thrombectomy, catheter-directed thrombolysis and anticoagulation without subsequent oxygen requirement. Three months later, she presented with two weeks of productive cough and hypoxia requiring high flow nasal cannula. CT chest showed worsening native lung fibrosis with ground glass opacities without PE or allograft infiltrate. Bronchoalveolar lavage was negative for infection, recent transbronchial biopsies were negative for rejection, and no donor specific antibodies were identified. Despite empiric antibiotics and pulse dose steroids for native lung exacerbation, she developed worsening hypoxia with progressive native lung infiltrates. A perfusion scan revealed 68% and 32% perfusion to the left and right lung, respectively. A right heart catheterization was performed, showing no intracardiac or pulmonary shunt, a mildly increased gradient across the left pulmonary artery (PA) anastomosis, and a marked improvement in left PA PaO2 during right PA balloon occlusion. On hospital day 16, repeat perfusion scan demonstrated an increase in relative perfusion to the allograft (83%). The patient was discharged on 3L oxygen and remains stable as an outpatient. <h3>Summary</h3> Severe hypoxia in the setting of a functioning SLT during a native lung exacerbation is rare. Literature on normal perfusion after SLT remains limited, with small studies suggesting ∼75% of fractional perfusion to the allograft without native lung exacerbation. Similar cases of inappropriate shunting after SLT had improvement in oxygenation after contralateral PA banding with other options including intravascular interventions or contralateral SLT. Further studies characterizing optimal perfusion after SLT and interventions for inappropriate shunting are needed.

Bridge Using the Hemolung System for Re-Do Double Lung Transplant In Situs Inversus Patient

IntroductionExtracorporeal life support (ECLS) use in redo-lung transplant is limited due to poor outcomes. Extracorporeal circulation with a single cannula provides the advantage of mobility and effective rehabilitationn in patients with an expected long run. The Hemolung veno-venous extracorporeal carbon dioxide removal (ECCO2R) system allows for adequate removal of carbon dioxide with a small French double lumen catheter.Case ReportA 29-year-old female with Kartagener syndrome and complete situs inversus underwent a double lung transplant for end stage lung disease. Her postoperative course was uneventful. After an aspiration event, she experienced a severe and persistent decline in her lung function within her first year. She ultimately was hospitalized requiring mechanical ventilation and a tracheostomy. The patient had primarily hypercapnic respiratory failure with radiographic signs of CLAD. The need for a high respiratory rate led to increased calory consumption with a significant impact on her BMI. To optimize her nutritional status and muscle strength before re-do lung transplantation, we decided to bridge her with ECLS. The use of an Avalon cannula was limited by her anatomy as the outflow jet will point against the atrial wall. Dual site cannulation was deemed suboptimal to preserve mobility. We decided to proceed with a Hemolung after emergency FDA authorization. A dual-lumen 15.5Fr catheter was placed via the left IJ into the superior vena cava. As we normalized her CO2 by active ECCO2R removal, we were able to reduce her ventilatory needs, improve her nutritional status and mobility. She was listed and underwent an uneventful redo-double lung transplant with cardiopulmonary support. The patient is 200 days out and doing well.SummaryThis experience demonstrates that ECCO2R technologies can be safely and effectively used to bridge lung transplant patients with hypercapnic respiratory failure in which anatomical challenges limit cannulation options. Extracorporeal life support (ECLS) use in redo-lung transplant is limited due to poor outcomes. Extracorporeal circulation with a single cannula provides the advantage of mobility and effective rehabilitationn in patients with an expected long run. The Hemolung veno-venous extracorporeal carbon dioxide removal (ECCO2R) system allows for adequate removal of carbon dioxide with a small French double lumen catheter. A 29-year-old female with Kartagener syndrome and complete situs inversus underwent a double lung transplant for end stage lung disease. Her postoperative course was uneventful. After an aspiration event, she experienced a severe and persistent decline in her lung function within her first year. She ultimately was hospitalized requiring mechanical ventilation and a tracheostomy. The patient had primarily hypercapnic respiratory failure with radiographic signs of CLAD. The need for a high respiratory rate led to increased calory consumption with a significant impact on her BMI. To optimize her nutritional status and muscle strength before re-do lung transplantation, we decided to bridge her with ECLS. The use of an Avalon cannula was limited by her anatomy as the outflow jet will point against the atrial wall. Dual site cannulation was deemed suboptimal to preserve mobility. We decided to proceed with a Hemolung after emergency FDA authorization. A dual-lumen 15.5Fr catheter was placed via the left IJ into the superior vena cava. As we normalized her CO2 by active ECCO2R removal, we were able to reduce her ventilatory needs, improve her nutritional status and mobility. She was listed and underwent an uneventful redo-double lung transplant with cardiopulmonary support. The patient is 200 days out and doing well. This experience demonstrates that ECCO2R technologies can be safely and effectively used to bridge lung transplant patients with hypercapnic respiratory failure in which anatomical challenges limit cannulation options.

Lung Transplantation in COVID-19 Induced End Stage Lung Disease

IntroductionIn a subset of patients COVID-19 induced lung injury progresses to irreversible lung damage and pulmonary fibrosis. Bilateral orthotopic lung transplant (BOLT) has been used as a rescue therapy in these patients. We describe four patients who were bridged to BOLT using venovenous extracorporeal membrane oxygenation (VV-ECMO).Case ReportBetween October 13, 2020 and February 14, 2021, four patients with SARS-CoV-2 infection underwent BOLT for end-stage pulmonary fibrosis demonstrated on computed tomography. Median age was 42 years and three were male. One patient had a prior history of undifferentiated interstitial lung disease managed with chronic steroids. Pre-transplant hospital course was complicated by right ventricular failure due to pulmonary hypertension in two patients and ventilator-associated pneumonia in one. One patient developed heparin-induced thrombocytopenia requiring anticoagulation with bivalirudin perioperatively. Three patients were non-ambulatory and bedridden for a median of 54 days prior to surgery. Timing of transplantation ranged from hospital day 26 - 68 with a median of 48 days. At the time of transplant, three patients were mechanically ventilated via tracheostomy, while all were on VV-ECMO a median of 27 (IQR 11 - 42) days. All patients underwent BOLT via clamshell exposure utilizing cardiopulmonary bypass (CPB) with aortic and right atrial cannulation. VV-ECMO was discontinued intraoperatively in all cases after initiating CPB. All patients required intraoperative blood transfusion with a median of 3 units. The three patients with tracheostomy prior to transplant were liberated from the ventilator a median of 9 days postoperatively and decannulated from their tracheostomy a median of 11 days postoperatively. Aside from one patient requiring short courses of hemodialysis, there were no significant postoperative complications. Patients were discharged a median of 17 (14 - 20) days following surgery. After a median follow-up of 226.5 (223 - 257.75) days, all four patients were alive with no supplemental oxygen requirement.SummaryPulmonary fibrosis secondary to COVID-19 pneumonia can be successfully treated with VV-ECMO and subsequent lung transplantation in select patients. Special consideration should be given to this patient population as they may not meet traditional listing requirements. We report a 100% oxygen-free survival rate at six months.

Metabolic Syndrome in Post-Pulmonary Tuberculosis-Associated Obstructive Airway Disease: A Cross-Sectional Analytical Study

BackgroundThe aim of this study is to assess the prevalence of metabolic syndrome in tuberculosis-associated obstructive airway disease (TOPD) patients, as well as the association of its components with the severity of airflow obstruction.MethodologyIn this cross-sectional analytical study, we evaluated the clinical profile, spirometry, waist circumference, blood pressure, lipid profile, fasting plasma glucose, and the association of each component with the severity of airflow obstruction.ResultsThe prevalence of metabolic syndrome in TOPD was found to be was 25.77% (95% confidence interval = 18.11-35.28) among study participants. Reduced high-density lipoprotein was the deranged component and was associated with increased severity in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II compared to GOLD stage IV.ConclusionsThe prevalence of metabolic syndrome in TOPD has a severe impact on patients’ treatment, outcomes, and complications. However, in our study, tuberculosis-associated metabolic syndrome was the same as the general population. Low high-density lipoprotein levels were associated with the severity of the airflow obstruction.

Quantitative assessment the longitudinal changes of pulmonary vascular counts in chronic obstructive pulmonary disease

BackgroundChest computed tomography (CT) is a widely used method to assess morphological and dynamic abnormalities in chronic obstructive pulmonary disease (COPD). The small pulmonary vascular cross-section (CSA), quantitatively extracted from volumetric CT, is a reliable indicator for predicting pulmonary vascular changes. CSA is associated with the severity of symptoms, pulmonary function tests (PFT) and emphysema and in COPD patients the severity increases over time. We analyzed the correlation longitudinal changes in pulmonary vascular parameters with clinical parameters in COPD patients.Materials and methodsA total of 288 subjects with COPD were investigated during follow up period up to 6 years. CT images were classified into five subtypes from normal to severe emphysema according to percentage of low-attenuation areas less than -950 and -856 Hounsfield units (HU) on inspiratory and expiratory CT (LAA-950, LAA-856exp). Total number of vessels (Ntotal) and total number of vessels with area less than 5 mm2 (N<5 mm) per 1 cm2 of lung surface area (LSA) were measured at 6 mm from the pleural surface.ResultsNtotal/LSA and N<5 mm/LSA changed from 1.16 ± 0.27 to 0.87 ± 0.2 and from 1.02 ± 0.22 to 0.78 ± 0.22, respectively, during Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage progression. Both parameters changed from normal to severe emphysema according to CT subtype from 1.39 ± 0.21 to 0.74 ± 0.17 and from 1.18 ± 0.19 to 0.67 ± 0.15, respectively. LAA-950 and LAA-856exp were negatively correlated with Ntotal/LSA (r = − 0.738, − 0.529) and N<5 mm /LSA (r = − 0.729, -− .497). On the other hand, pulmonary function test (PFT) results showed a weak correlation with Ntotal/LSA and N<5 mm/LSA (r = 0.205, 0.210). The depth in CT subtypes for longitudinal change both Ntotal/LSA and N<5 mm/LSA was (− 0.032, − 0.023) and (− 0.027) in normal and SAD, respectively.ConclusionsQuantitative computed tomography features faithfully reflected pulmonary vessel alterations, showing in particular that pulmonary vascular alteration started.