Assessment of dd-cfDNA Levels in Clinically Stable Lung Allograft Recipients Beyond the Initial 2 y Posttransplant.

Donor-derived cell-free DNA (dd-cfDNA) is a useful biomarker for the diagnosis of acute allograft injury within the first 1 to 2 y after lung transplant, but its utility for diagnosing chronic lung allograft dysfunction (CLAD) has not yet been studied. Understanding baseline dd-cfDNA kinetics beyond the initial 2 y posttransplant is a necessary first step in determining the utility of dd-cfDNA as a CLAD biomarker. We seek to establish baseline dd-cfDNA% levels in clinically stable lung allograft recipients who are >2 y posttransplant. Methods: We performed a prospective, single-center, observational study to identify plasma dd-cfDNA levels in clinically stable lung allograft recipients >2 y posttransplant. Results: Fifty-one subjects were enrolled and ≥3 baseline dd-cfDNA measurements were acquired during a median of 252 d. The median baseline percent dd-cfDNA level in our cohort was 0.45% (interquartile range [IQR], 0.26-0.69). There were statistically significant differences in dd-cfDNA based on posttransplant duration (≤5 y posttransplant median 0.41% [IQR, 0.21-0.64] versus >5 y posttransplant median 0.50% [IQR, 0.33-0.76]; P < 0.02). However, the clinical significance of this small change in dd-cfDNA is uncertain because this magnitude of change is within the biologic test variation of 73%. Conclusions: This study is the first to define levels of dd-cfDNA in clinically stable patients who are >2 y post-lung transplant. These findings lay the groundwork for the study of dd-cfDNA as a possible biomarker for CLAD.

Clinical course of SARS-CoV-2 infection and recovery in lung transplant recipients.

BACKGROUND: Reports on outcomes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in lung transplant recipients remain limited. METHODS: We performed a single-center, observational study of outcomes in lung transplant recipients diagnosed with SARS-CoV-2 between 5/1/2020 and 3/15/2022 that were followed for a median of 123 days. We analyzed changes in spirometry, acute lung allograft dysfunction (ALAD) incidence, hospitalization, mechanical ventilation needs, secondary infection, and survival. RESULTS: In our cohort of 336 patients, 103 developed coronavirus disease (COVID) (27 pre-Delta, 20 Delta, and 56 Omicron-era). Twenty-five patients (24%) required hospitalization and 10 patients ultimately died (10%). Among 85 survivors who completed ambulatory spirometry, COVID-19 did not alter change in forced expiratory volume in 1 s (FEV1 ) or forced vital capacity (FVC) over time compared to the preceding 6 months. The pre-COVID FEV1 change was -0.05 ml/day (IQR -0.50 to 0.60) compared to -0.20 ml/day (IQR -1.40 to 0.70) post-COVID (p = .16). The pre-COVID change in FVC was 0.20 ml/day (IQR -0.60 to 0.70) compared to 0.05 ml/day (IQR -1.00 to 1.10) post-COVID (p = .76). Although the cohort overall had stable lung function, 33 patients (39%) developed ALAD or accelerated chronic lung allograft dysfunction (FEV1 decline >10% from pre-COVID baseline). Nine patients (35%) with ALAD recovered lung function. Within 3 months of acute COVID infection, 18 patients (17%) developed secondary infections, the majority being bacterial pneumonia. Finally, vaccination with at least two doses of mRNA vaccine was not associated with improved outcomes. CONCLUSIONS: This study describes the natural history of SARS-CoV-2 infection in a large cohort of lung transplant recipients. Although one third of patients develop ALAD requiring augmented immunosuppression, infection with SARS-CoV-2 is not associated with worsening lung function.

Lung transplantation and atrial septostomy in pulmonary arterial hypertension.

This article summarizes the current literature regarding surgical interventions in pulmonary hypertension, excluding chronic thromboembolic pulmonary hypertension. The article discusses the use of atrial septostomy in patients meeting criteria as well as single, double, and heart-lung transplantation.

Rescue therapy in adult and pediatric patients with pH1N1 influenza infection: a tertiary center intensive care unit experience from April to October 2009.

OBJECTIVE: Severe respiratory failure is a well-recognized complication of pH1N1 influenza infection. Limited data regarding the efficacy of rescue therapies, including high-frequency oscillatory ventilation and extracorporeal membrane oxygenation, have been previously reported in the setting of pH1N1 influenza infection in the United States. DESIGN: Retrospective, single-center cohort study. SETTING: Pediatric, cardiac, surgical, and medical intensive care units in a single tertiary care center in the United States. PATIENTS: One hundred twenty-seven consecutive patients with confirmed influenza A infection requiring hospitalization between April 1, 2009, and October 31, 2009. INTERVENTIONS: Electronic medical records were reviewed for demographic and clinical data. MEASUREMENTS AND MAIN RESULTS: The number of intensive care unit admissions appears inversely related to age with 39% of these admissions <20 yrs of age. Median duration of intensive care unit care was 10.0 days (4.0-24.0), and median duration of mechanical ventilation was 8.0 days (0.0-23.5). Rescue therapy (high-frequency oscillatory ventilation or extracorporeal membrane oxygenation) was used in 36% (12 of 33) of intensive care unit patients. The severity of respiratory impairment was determined by Pao²/Fio² ratio and oxygenation index. High-frequency oscillatory ventilation at 24 hrs resulted in improvements in median Pao²/Fio² ratio (71 [58-93] vs. 145 [126-185]; p < .001), oxygenation index (27 [20-30] vs. 18 [12-25]; p = .016), and Fio2 (100 [70-100] vs. 45 [40-55]; p < .001). Extracorporeal membrane oxygenation resulted in anticipated improvement in parameters of oxygenation at both 2 hrs and 24 hrs after initiation of therapy. Despite the severity of oxygenation impairment, overall survival for both rescue therapies was 75% (nine of 12), 80% (four of five) for high-frequency oscillatory ventilation alone, and 71% (five of seven) for high-frequency oscillatory ventilation + extracorporeal membrane oxygenation. CONCLUSION: In critically ill adult and pediatric patients with pH1N1 infection and severe lung injury, the use of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation can result in significant improvements in Pao²/Fio² ratio, oxygenation index, and Fio². However, the impact on mortality is less certain.

Reversible cardiac dysfunction associated with pandemic 2009 influenza A(H1N1).

Historical influenza A epidemics have carried elevated rates of cardiovascular disease, including transient cardiac dysfunction. Whether such an association holds for the novel influenza A strain, pandemic 2009 influenza A(H1N1) [A(H1N1)], remains unknown. We report an index case of transient cardiac dysfunction associated with A(H1N1) infection. Next, we reviewed 123 sequential cases of patients hospitalized with pandemic A(H1N1) at a single academic medical center in the United States from April 1, 2009, through October 31, 2009. We identified that 4.9% (6/123) of patients had either new or worsened left ventricular dysfunction. These cases ranged in age from 23 to 51 years, and all had preexisting medical conditions. ICU level care was required in 83% (5/6) of the cases. Sixty-seven percent (4/6) of the cases had follow-up echocardiograms, and left ventricular function improved in all four. We conclude that potentially reversible cardiac dysfunction is a relatively common complication associated with hospitalized pandemic A(H1N1) influenza.