Acute rejection post lung transplant.

PURPOSE OF REVIEW: To review what is currently known about the pathogenesis, diagnosis, treatment, and prevention of acute rejection (AR) in lung transplantation. RECENT FINDINGS: Epigenomic and transcriptomic methods are gaining traction as tools for earlier detection of AR, which still remains primarily a histopathologic diagnosis. SUMMARY: Acute rejection is a common cause of early posttransplant lung graft dysfunction and increases the risk of chronic rejection. Detection and diagnosis of AR is primarily based on histopathology, but noninvasive molecular methods are undergoing investigation. Two subtypes of AR exist: acute cellular rejection (ACR) and antibody-mediated rejection (AMR). Both can have varied clinical presentation, ranging from asymptomatic to fulminant ARDS, and can present simultaneously. Diagnosis of ACR requires transbronchial biopsy; AMR requires the additional measuring of circulating donor-specific antibody (DSA) levels. First-line treatment in ACR is increased immunosuppression (pulse-dose or tapered dose glucocorticoids); refractory cases may need antibody-based lymphodepletion therapy. First line treatment in AMR focuses on circulating DSA removal with B and plasma cell depletion; plasmapheresis, intravenous human immunoglobulin (IVIG), bortezomib, and rituximab are often employed.

Successful treatment of pulmonary mucormycosis (Lichtheimia spp.) in a post-partum patient with COVID-19 ARDS requiring extra-corporeal membrane oxygenation using salvage therapy.

Case Summary: A 31-year-old female presented to a regional hospital at 27 weeks pregnant and was found to have COVID-19 ARDS. She underwent intubation and caesarian section for worsening hypoxia and non-reassuring fetal heart tones. Hypoxemia was refractory to proning requiring ECMO and transfer to a tertiary care center. Admission chest radiography showed a new right lower lobe cavitating lesion with computed tomography scan revealing a large multi-loculated cavity in the right lung and extensive bilateral ground-glass opacities. The patient was started on amphotericin and posaconazole, with final respiratory cultures growing Lichtheimia spp. Source control was discussed via possible open thoracostomy, but medical management alone was continued. Total ECMO support was 3 weeks. At the time of discharge to acute rehab, 1 month of amphotericin and posaconazole had been completed, with continuation of posaconazole. At last update, she had been discharged from rehab and was back home with her infant. Conclusion: Pulmonary mucormycosis, even in the non-ECLS population, carries a high mortality. Treatment in pulmonary disease with surgery improves mortality but is not always feasible. Salvage therapy with extended course antifungal medications may be an option for those not amendable.

Duration of noninvasive ventilation is not a predictor of clinical outcomes in patients with acute exacerbation of COPD and respiratory failure.

PURPOSE: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity. Noninvasive ventilation (NIV) is proven to be effective in the majority of patients with acute exacerbation COPD (AECOPD) complicated with respiratory failure. NIV could be lifesaving but also can delay mechanical ventilation if its efficacy is not assessed in a timely manner. In this study, we analyzed potential predictors of NIV failure in AECOPD in a tertiary medical intensive care unit (MICU). In particular, we wondered whether duration of NIV among those who eventually failed was associated with poor outcomes. METHODS: A retrospective review of consecutive patients with a primary diagnosis of AECOPD requiring NIV admitted to the MICU was conducted for the period between 2012 and 2017. Baseline data included demographics, APACHE III score, albumin level, blood lactate, and blood gas elements. Additional chart review was performed to collect NIV setting parameters on presentation to the MICU. Clinical outcome variables collected included outcome and duration of NIV, duration of invasive mechanical ventilation, MICU length of stay, hospital length of stay, and in-hospital mortality. Multivariate regression analysis was performed to determine independent variables associated with clinical outcomes. RESULTS: There were 370 patients who met the inclusion criteria; 53.2% were male. Mean age was 64.7 ± 11.2 years old. Mean baseline FEV1 was 34 ±17% of predicted. Patients had mean pH of 7.20 ± 0.54 and PaCO2 of 70.3 ± 28.7 on presentation; 323 patients (87.3%) were successfully weaned off NIV; 47 patients (12.7%) failed NIV and required invasive mechanical ventilation. APACHE III score was higher among patients who failed NIV (68.3±18.9 versus 48.8± 15.2, P < 0.001). In the subset of 47 patients who failed NIV requiring intubation, duration of NIV was 25.0 ± 58.8 h. Multivariate regression analysis yielded a model consisting of APACHE III score and body mass index as predictive variables for NIV failure (C-statistic = 0.809). Duration of NIV was not associated with worse clinical outcomes among patients who failed NIV. CONCLUSIONS: NIV is successful in preventing invasive mechanical ventilation in majority of patients with acute respiratory failure due to COPD. Patients with worse clinical status at presentation are more likely to fail NIV and require mechanical ventilation. In the subgroup of patients who failed NIV, duration of NIV prior to intubation was not associated with poor clinical outcomes.

Radiation Exposure in Extracorporeal Life Support.

Extracorporeal membrane oxygenation (ECMO) exposes patients to multiple radiologic studies. We hypothesized ECMO patients endure radiation exposure in excess of the International Commission of Radiological Protection (ICRP) recommendations of cumulative effective dose (CED, >20 mSv and 5-year cumulative limit of CED >100 mSv). We conducted a retrospective observational study in an academic medical center between January 2016 and December 2018 involving adult admissions (N = 306) on ECMO. Ionizing radiation was calculated from reference values to determine CED. Approximately 9.4% (N = 29) patients accrued CED >50 mSv and 4.5% (N = 14) accrued CED >100 mSv during ECMO. Over the entire hospitalization, 28% (N = 85) accrued >50 mSv and 14.7% (N = 45) accrued CED >100 mSv. Median CED during ECMO was 2.3 mSv (IQR, -0.82 to 8.1 mSv), and the entire hospitalization was 17.4 mSv (IQR, -4.5 to 56.6 mSv). Thirteen percent of the median CED accrued during hospitalization could be attributed to ECMO. Longer hospitalization was associated with a higher CED (50 days [IQR, -25 to 76 days] in CED >50 vs. 19 days [IQR, -10 to 32 days] in CED <50). Computer tomography (CT) scans and interventional radiology (IR) procedures contributed to 43.8% and 44.86%, respectively, of CED accrued on ECMO and 52.2% and 37.1% of CED accumulated during the whole hospitalization. Guidelines aimed at mitigating radiation exposure are urgently needed.

On the horizon: Extracorporeal carbon dioxide removal.

Extracorporeal carbon dioxide removal (ECCO2R) uses mechanical systems to treat hypercapnic respiratory failure. Its utility has been investigated in acute respiratory distress syndrome (ARDS), acute exacerbations of chronic obstructive pulmonary disease (COPD), and status asthmaticus, and as a bridge to lung transplant. In this review, we discuss how it works, why it should help, and current evidence supporting its use.