Acute transcutaneous electrical stimulation (TES) augments esophageal contractility in patients with weak peristalsis.

BACKGROUND: Lung transplantation (LTx) remains controversial in patients with absent peristalsis (AP) given the increased risk for gastroesophageal reflux (GER), and chronic lung allograft dysfunction. Furthermore, specific treatments to facilitate LTx in those with AP have not been widely described. Transcutaneous Electrical Stimulation (TES) has been reported to improve foregut contractility in LTx patients and therefore we hypothesize that TES may augment the esophageal motility of patients with ineffective esophageal motility (IEM). METHODS: We included 49 patients, 14 with IEM, 5 with AP, and 30 with normal motility. All subjects underwent standard high-resolution manometry and intraluminal impedance (HRIM) with additional swallows as TES was delivered. RESULTS: TES induced a universal impedance change observable in real-time by a characteristic spike activity. TES significantly augmented the contractile vigor of the esophagus measured by the distal contractile integral (DCI) in patients with IEM [median DCI (IQR) 0 (238) mmHg-cm-s off TES vs. 333 (858) mmHg-cm-s on TES; p = .01] and normal peristalsis [median DCI (IQR) 1545 (1840) mmHg-cm-s off TES vs. 2109 (2082) mmHg-cm-s on TES; p = .01]. Interestingly, TES induced measurable contractile activity (DCI > 100 mmHg-cm-s) in three out of five patients with AP [median DCI (IQR) 0 (0) mmHg-cm-s off TES vs. 0 (182) mmHg-cm-s on TES; p < .001]. CONCLUSION: TES acutely augmented contractile vigor in patients with normal and weak/ AP. The use of TES may positively impact LTx candidacy, and outcomes for patients with IEM/AP. Nevertheless, further studies are needed to determine the long-term effects of TES in this patient population.

A prospective examination of swallow and cough dysfunction after lung transplantation.

OBJECTIVES: Swallow and cough dysfunction are possible surgical complications of lung transplantation (LT). We examined voluntary cough strength, sensorimotor reflexive cough integrity, and swallow-related respiratory rate (RR) across swallowing safety and aspiration response groups in recovering LT recipients. METHODS: Forty-five LT recipients underwent flexible endoscopic evaluation of swallowing indexed by the validated Penetration Aspiration Scale. RR before and after a 3-ounce water drinking task was measured. Voluntary and reflexive cough screening were performed to index motor and sensory outcomes. T-tests, one-way ANOVAs, and chi-square (odds ratios) were used. RESULTS: 60% of patients exhibited laryngeal penetration (n = 27) and 40% demonstrated tracheal aspiration (n = 18); 72% (n = 13) demonstrated silent aspiration. Baseline RR was higher in aspirators versus non-aspirators (26.5 vs. 22.6, p = 0.04) and in silent aspirators compared to non-silent aspirators (27.9 vs. 20.7, p = 0.01). RR change post-swallowing did not differ between aspiration response groups; however, it was significantly higher in aspirators compared to non-aspirators (3 vs. -2, p = 0.02). Compared to non-silent aspirators, silent aspirators demonstrated reduced voluntary cough peak expiratory flow (PEF; 166 vs. 324 L/min, p = 0.01). PEF, motor and urge to cough reflex cough ratings did not differ between aspirators and non-aspirators. Silent aspirators demonstrated a 7.5 times higher odds of failing reflex cough screening compared to non-silent aspirators (p = 0.07). CONCLUSIONS: During the acute recovery period, all LT participants demonstrated some degree of unsafe swallowing and reduced voluntary cough strength. Silent aspirators exhibited elevated RR, reduced voluntary cough physiologic capacity to defend the airway, and a clinically distinguishable blunted motor response to reflex cough screening.

Corrigendum: Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series.

[This corrects the article DOI: 10.3389/ti.2022.10433.].

Incidence, risk factors, and sequelae of dysphagia mediated aspiration following lung transplantation.

BACKGROUND: We aimed to determine dysphagia profiles before and after lung transplantation (prevalence, incidence) and to examine predictors and health-related outcomes of aspiration in individuals undergoing lung transplantation. METHODS: A retrospective single-center study of consecutive adults undergoing lung transplantation and completing a postoperative videofluoroscopic swallowing study between 2017 and 2020 was conducted. The validated penetration aspiration scale indexed swallowing safety and clinical outcomes were extracted from electronic medical records. T-tests, chi square with odds ratios, and multivariable logistic regression were conducted. RESULTS: Two hundred five participants were identified who underwent lung transplantation and a postoperative swallowing exam. Of those who underwent both a pre- and postoperative swallowing exam (n = 170), preoperatively 83% demonstrated safe swallowing and 17% unsafe swallowing. Following lung transplantation, 16% demonstrated safe swallowing and 84% demonstrated unsafe swallowing (39% penetration, 45% aspiration). Independent predictors of postoperative aspiration were venous-venous extracorporeal membrane oxygenation (odds ratio [OR]: 6.7, confidence interval [CI]: 2.0-81.5) and reintubation (OR: 4.5, CI: 1.0-60.3), p < .05. Compared to non-aspirators, aspirators demonstrated higher odds of being discharged to a dependent care setting (OR: 2.3, CI: 1.2-4.5), p < .05. Aspirators spent significantly longer NPO (median = 138.0 hours, 25th percentile, 75th percentile = 75.7, 348.3) compared to non-aspirators (median = 85.0 hours, 25th percentile, 75th percentile = 48.0, 131.6, p < .001). CONCLUSIONS: Pre-existing dysphagia was low in this cohort of patients undergoing lung transplantation, however increased approximately 5-fold following lung transplantation and was associated with increased morbidity.

Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series.

Background: Hyperammonemia after lung transplantation (HALT) is a rare but serious complication with high mortality. This systematic review delineates possible etiologies of HALT and highlights successful strategies used to manage this fatal complication. Methods: Seven biomedical databases and grey literature sources were searched using keywords relevant to hyperammonemia and lung transplantation for publications between 1995 and 2020. Additionally, we retrospectively analyzed HALT cases managed at our institution between January 2016 and August 2018. Results: The systematic review resulted in 18 studies with 40 individual cases. The mean peak ammonia level was 769 µmol/L at a mean of 14.1 days post-transplant. The mortality due to HALT was 57.5%. In our cohort of 120 lung transplants performed, four cases of HALT were identified. The mean peak ammonia level was 180.5 µmol/L at a mean of 11 days after transplantation. HALT in all four patients was successfully treated using a multimodal approach with an overall mortality of 25%. Conclusion: The incidence of HALT (3.3%) in our institution is comparable to prior reports. Nonetheless, ammonia levels in our cohort were not as high as previously reported and peaked earlier. We attributed these significant differences to early recognition and prompt institution of multimodal treatment approach.

Inpatient Management of the Acutely Decompensating Lung Transplant Candidate.

Lung allocation in the US changed nearly 15 years ago from time accrued on the waiting list to disease severity and likelihood of posttransplant survival, represented by the lung allocation score (LAS). Notably, the risk of death within a year plays a stronger role on the score calculation than posttransplant survival. While this change was associated with the intended decrease in waitlist mortality (most recently reported at 14.6%), it was predictable that transplant teams would have to care for increasingly older and complex candidates and recipients. This urgency-based allocation also led centers to routinely consider transplanting patients with higher acuity, often hospitalized and, not infrequently, in the intensive care unit (ICU). According to the Scientific Registry for Transplant Recipients, from 2009 to 2019, the proportion of lung recipients hospitalized and those admitted to the ICU at the time of transplant increased from 18.9% to 26.8% and from 9.2% to 16.5%, respectively..

Lung transplantation for acute exacerbation of interstitial lung disease.

BACKGROUND: Acute exacerbations of interstitial lung diseases (AE-ILD) have a high mortality rate with no effective medical therapies. Lung transplantation is a potentially life-saving option for patients with AE-ILD, but its role is not well established. The aim of this study is to determine if this therapy during AE-ILD significantly affects post-transplant outcomes in comparison to those transplanted with stable disease. METHODS: We conducted a retrospective study of consecutive patients with AE-ILD admitted to our institution from 2015 to 2018. The comparison group included patients with stable ILD listed for lung transplant during the same period. The primary end-points were in-hospital mortality for patients admitted with AE-ILD and 1-year survival for the transplanted patients. RESULTS: Of 53 patients admitted for AE-ILD, 28 were treated with medical therapy alone and 25 underwent transplantation. All patients with AE-ILD who underwent transplantation survived to hospital discharge, whereas only 43% of the AE-ILD medically treated did. During the same period, 67 patients with stable ILD underwent transplantation. Survival at 1 year for the transplanted patients was not different for the AE-ILD group versus stable ILD group (96% vs 92.5%). The rates of primary graft dysfunction, post-transplant hospital length-of-stay and acute cellular rejection were similar between the groups. CONCLUSION: Patients with ILD transplanted during AE-ILD had no meaningful difference in overall survival, rate of primary graft dysfunction or acute rejection compared with those transplanted with stable disease. Our results suggest that lung transplantation can be considered as a therapeutic option for selected patients with AE-ILD.

Acute Right Ventricular Dysfunction Secondary to Hereditary Angioedema Exacerbation.

This is a case report of a 31-year-old woman with past medical history of hereditary angioedema (HAE) who developed acute right ventricular dysfunction. The patient presented to the emergency department with complaints of acute abdominal pain and swelling. Her electrocardiogram demonstrated sinus tachycardia and T wave inversion in leads V1-V3, otherwise without findings suggestive of ischemia. Troponin was elevated at 1.83 ng/mL. A transthoracic echocardiogram showed normal left ventricular function with ejection fraction of 65-70%, but the right ventricle (RV) was dilated and severely hypokinetic and there was moderate tricuspid regurgitation. Patient was managed symptomatically for her HAE exacerbation. Her abdominal swelling resolved, troponins continued to trend down, and she was discharged home after three days. A follow up echocardiogram done six months later demonstrated normal RV function.

Early outcomes after lung transplantation for severe COVID-19: a series of the first consecutive cases from four countries.

BACKGROUND: Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications. METHODS: We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed. FINDINGS: Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19. INTERPRETATION: The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients. FUNDING: National Institutes of Health. VIDEO ABSTRACT.

Successful bridge to lung transplantation with transcatheter aortic valve replacement.

End-stage lung disease and advanced cardiac conditions are frequently seen together and represent a clinical dilemma. Even though both issues may be amenable to surgical management, combining lung transplant with surgical valve repair is rarely done and theoretically associated with increased morbidity and mortality risks, especially in elderly patients. Here, we describe 2 patients presenting with end-stage lung disease and significant aortic stenosis who were successfully bridged to lung transplant via transcatheter aortic valve replacement. Patient 1 was a 66-year-old man who underwent a double lung transplant 56 days after transcatheter aortic valve replacement. Patient 2 was a 70-year-old man who underwent a single right lung transplant 103 days after transcatheter aortic valve replacement. Both patients had uneventful postoperative courses and are alive at the 1-year time point with excellent performance status. This report suggests that transcatheter aortic valve replacement may favorably impact lung transplant candidacy for patients with end-stage lung disease in the setting of severe aortic stenosis, likely representing a better alternative to concomitant aortic valve replacement and lung transplant in elderly patients.

Intravenous Alpha-1 Antitrypsin Therapy for Alpha-1 Antitrypsin Deficiency: The Current State of the Evidence.

Alpha-1 antitrypsin deficiency (AATD) is a largely monogenetic disorder associated with a high risk for the development of chronic obstructive pulmonary disease (COPD) and cirrhosis. Intravenous alpha-1 antitrypsin (AAT) therapy has been available for the treatment of individuals with AATD and COPD since the late 1980s. Initial Food and Drug Administration (FDA) approval was granted based on biochemical efficacy. Following its approval, the FDA, scientific community and third-party payers encouraged manufacturers of AAT therapy to determine its clinical efficacy. This task has proved challenging because AATD is a rare, orphan disorder comprised of individuals who are geographically dispersed and infrequently identified. In addition, robust clinical trial outcomes have been lacking until recently. This review provides an update on the evidence for the clinical efficacy of intravenous AAT therapy for patients with AATD-related emphysema.

Do patients with submassive pulmonary embolism benefit from thrombolytic therapy?

Despite growing interest in thrombolytic agents to treat submassive pulmonary embolism, their role in this scenario remains controversial. Needed is a way to identify patients with this condition who are at risk of clinical deterioration and who would benefit from thrombolytic therapy. Here, we review the use of thrombolytic agents in submassive pulmonary embolism to help distinguish the risk and benefits of this therapy.