With an improved median survival of 6.2 years, lung transplantation has become an increasingly acceptable treatment option for end-stage lung disease. Besides survival benefit, improvement of quality ...of life is achieved in the vast majority of patients. Many developments have taken place in the field of lung transplantation over the past decade. Broadened indication criteria and bridging techniques for patients awaiting lung transplantation have led to increased waiting lists and changes in allocation schemes worldwide. Moreover, the use of previously unacceptable donor lungs for lung transplantation has increased, with donations from donors after cardiac death, donors with increasing age and donors with positive smoking status extending the donor pool substantially. Use of
ex vivo
lung perfusion further increased the number of lungs suitable for lung transplantation. Nonetheless, the use of these previously unacceptable lungs did not have detrimental effects on survival and long-term graft outcomes, and has decreased waiting list mortality. To further improve long-term outcomes, strategies have been proposed to modify chronic lung allograft dysfunction progression and minimise toxic immunosuppressive effects. This review summarises the developments in clinical lung transplantation over the past decade.
Idiopathic Pulmonary Fibrosis (IPF) is thought to be triggered by repeated alveolar epithelial cell injury. Current evidence suggests that aberrant immune activation may contribute. However, the role ...of B-cell activation remains unclear. We determined the phenotype and activation status of B-cell subsets and evaluated the contribution of activated B-cells to the development of lung fibrosis both in humans and in mice.
B-cells in blood, mediastinal lymph node, and lung single-cell suspensions of IPF patients and healthy controls (HC) were characterized using 14-color flow cytometry. Mice were exposed to bleomycin to provoke pulmonary fibrosis.
More IgA
memory B-cells and plasmablasts were found in blood (n = 27) and lungs (n = 11) of IPF patients compared to HC (n = 21) and control lungs (n = 9). IPF patients had higher levels of autoreactive IgA in plasma, which correlated with an enhanced decline of forced vital capacity (p = 0.002, r = - 0.50). Bruton's tyrosine kinase expression was higher in circulating IPF B-cells compared to HC, indicating enhanced B-cell activation. Bleomycin-exposed mice had increased pulmonary IgA
germinal center and plasma cell proportions compared to control mice. The degree of lung fibrosis correlated with pulmonary germinal center B-cell proportions (p = 0.010, r = 0.88).
Our study demonstrates that IPF patients have more circulating activated B-cells and autoreactive IgA, which correlate with disease progression. These B-cell alterations were also observed in the widely used mouse model of experimental pulmonary fibrosis. Autoreactive IgA could be useful as a biomarker for disease progression in IPF.
Illness after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is less severe compared with previous variants. Data on the disease burden in ...immunocompromised patients are lacking. We investigated the clinical characteristics and outcomes of immunocompromised patients with coronavirus disease 2019 (COVID-19) caused by Omicron.
Organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients infected with the Omicron variant were included. Characteristics of consenting patients were collected and patients were contacted regularly until symptom resolution. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed.
114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received 3 mRNA vaccinations. While only 1 patient died, 23 (20%) were hospitalized for a median of 11 days. A low SARS-CoV-2 immunoglobulin G (IgG) antibody response (<300 BAU binding antibody units/mL) at diagnosis, being older, being a lung transplant recipient, having more comorbidities, and having a higher frailty score were associated with hospital admission (all P < .01). At the end of follow-up, 25% had still not fully recovered. Of the 23 hospitalized patients, 70% had a negative and 92% had a low IgG (<300 BAU/mL) antibody response at admission. Sotrovimab was administered to 17 of these patients, and 1 died.
While the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. In addition to vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients.
Solid organ transplant recipients (SOTRs) are at high risk of human herpesvirus (HHV)-related morbidity and mortality due to the use of immunosuppressive therapy. We aim to increase awareness and ...understanding of HHV disease burden in SOTRs by providing an overview of current prevention and management strategies as described in the literature and guidelines. We discuss challenges in both prevention and treatment as well as future perspectives.
Abstract
Lower respiratory tract (LRT) disease induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can deteriorate to acute respiratory distress syndrome (ARDS). Because the ...release of neutrophil extracellular traps (NETs) is implicated in ARDS pathogenesis, we investigated the presence of NETs and correlates of pathogenesis in blood and LRT samples of critically ill patients with COVID-19. Plasma NET levels peaked early after intensive care unit admission and were correlated with the SARS-CoV-2 RNA load in sputum and levels of neutrophil-recruiting chemokines and inflammatory markers in plasma samples. The baseline plasma NET quantity was correlated with disease severity but was not associated with soluble markers of thrombosis or with development of thrombosis. High NET levels were present in LRT samples and persisted during the course of COVID-19, consistent with the detection of NETs in bronchi and alveolar spaces in lung tissue from deceased patient with COVID-19. Thus, NETs are produced and retained in the LRT of critically ill patients with COVID-19 and could contribute to SARS-CoV-2–induced ARDS disease.
Aberrant neutrophil extracellular trap (NET) formation is implicated in acute respiratory distress syndrome (ARDS) pathogenesis. We demonstrate that NETs are present in blood and persist at high levels in the lower respiratory tract of critically ill patients with coronavirus disease 2019 and ARDS.
Summary
Solid organ transplant (SOT) recipients may be at risk for severe COVID‐19. Data on the clinical course of COVID‐19 in immunosuppressed patients are limited, and the effective treatment ...strategy for these patients is unknown. We describe our institutional experience with COVID‐19 in SOT. Demographic, clinical, and treatment data were extracted from the electronic patient files. A total of 23 SOT transplant recipients suffering from COVID‐19 were identified (n = 3 heart; n = 15 kidney; n = 1 kidney‐after‐heart; n = 3 lung, and n = 1 liver transplant recipient). The presenting symptoms were similar to nonimmunocompromised patients. Eighty‐three percent (19/23) of the patients required hospitalization, but only two of these were transferred to the intensive care unit. Five patients died from COVID‐19; all had high Clinical Frailty Scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only three patients were treated with chloroquine. Most patients recovered without experimental antiviral therapy. Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID‐19. Pre‐existent frailty is associated with death from COVID‐19.
Concerns have been raised on the impact of coronavirus disease (COVID-19) on lung transplant (LTx) patients. The aim of this study was to evaluate the transplant function pre- and post-COVID-19 in ...LTx patients.
Data were retrospectively collected from LTx patients with confirmed COVID-19 from all 3 Dutch transplant centers, between February 2020 and September 2021. Spirometry results were collected pre-COVID-19, 3- and 6-months post-infection.
Seventy-four LTx patients were included. Forty-two (57%) patients were admitted, 19 (26%) to the intensive care unit. The in-hospital mortality was 20%. Twelve out of 19 ICU patients died (63%), a further 3 died on general wards. Patients with available spirometry (78% at 3 months, 65% at 6 months) showed a significant decline in mean FEV1 (ΔFEV1 138 ±39 ml, p = 0.001), and FVC (ΔFVC 233 ±74 ml, p = 0.000) 3 months post-infection. Lung function improved slightly from 3 to 6 months after COVID-19 (ΔFEV1 24 ±38 ml; ΔFVC 100 ±46 ml), but remained significantly lower than pre-COVID-19 values (ΔFEV1 86 ml ±36 ml, p = 0.021; ΔFVC 117 ±35 ml, p= 0.012). FEV1/FVC was > 0.70.
In LTx patients COVID-19 results in high mortality in hospitalized patients. Lung function declined 3 months after infection and gradually improved at 6 months, but remained significantly lower compared to pre-COVID-19 values. The more significant decline in FVC than in FEV1 and FEV1/FVC > 70%, suggested a more restrictive pattern.
Studies on herpes zoster (HZ) incidence in solid organ transplant (SOT) recipients report widely varying numbers. We investigated HZ incidence, severity, and risk factors in recipients of four ...different SOTs, with a follow-up time of 6-14 years.
Records of 1,033 transplant recipients after first heart (HTx: n = 211), lung (LuTx: n = 121), liver (LiTx: n = 258) and kidney (KTx: n = 443) transplantation between 2000 and 2014 were analyzed for VZV-PCR, clinical signs of HZ, and complications.
HZ was diagnosed in 108 of 1,033 patients (10.5%): 36 HTx, 17 LuTx, 15 LiTx, and 40 KTx recipients. Overall HZ incidence rate after HTx (30.7 cases/1,000 person-years (PY)), LuTx (38.8 cases/1,000 PY), LiTx (22.7 cases/1,000 PY) and KTx (14.5 cases/1,000 PY) was significantly higher than in the general 50-70 year population. Multivariable analysis demonstrated age ≥50 years at transplantation (p = 0.038, RR 1.536), type of organ transplant (overall p = 0.002; LuTx p = 0.393; RR 1.314; LiTx p = 0.011, RR 0.444; KTx p = 0.034, RR 0.575), CMV prophylaxis (p = 0.043, RR 0.631) and type of anti-rejection therapy (overall p = 0.020; methylprednisolone p = 0.008, RR 0.475; r-ATG p = 0.64, RR1.194) as significant risk factors. Complications occurred in 33 of 108 (31%) patients (39% of HTx, 47% of LuTx, 20% of LiTx, 20% of KTx): post-herpetic neuralgia, disseminated disease, and cranial nerve involvement.
HZ incidence and severity in SOT recipients are most pronounced after heart and lung transplantation, in older patients, and when CMV prophylaxis is lacking.
PDF
