Lung Transplantation

Fu-Zheng-Tong-Luo (FZTL) formula is a Chinese herbal prescription which is used to treat idiopathic pulmonary fibrosis (IPF). We previously reported that the FZTL formula could improve IPF injury in rats; however, the mechanism remains unelucidated.

To elucidate the effects and mechanisms of the FZTL formula on IPF.

The bleomycin-induced pulmonary fibrosis rat model and transforming growth factor-β-induced lung fibroblast model were used. Histological changes and fibrosis formation were detected in the rat model after treatment with the FZTL formula. Furthermore, the effects of the FZTL formula on autophagy and lung fibroblast activation were determined. Moreover, the mechanism of FZTL was explored using transcriptomics analysis.

We observed that FZTL alleviated IPF injury in rats and inhibited inflammatory responses and fibrosis formation in rats. Moreover, it promoted autophagy and inhibited lung fibroblast activation in vitro. Transcriptomics analysis revealed that FZTL regulates the Janus kinase 2 (JAK)/signal transducer and activator of the transcription 3 (STAT) signaling pathway. The JAK2/STAT3 signaling activator interleukin 6 inhibited the anti-fibroblast activation effect of the FZTL formula. Combined treatment with the JAK2 inhibitor (AZD1480) and autophagy inhibitor (3-methyladenine) did not enhance the antifibrotic effect of FZTL.

The FZTL formula can inhibit IPF injury and lung fibroblast activation. Its effects are mediated via the JAK2/STAT3 signaling pathway. The FZTL formula may be a potential complementary therapy for pulmonary fibrosis.

The overall survival in patients undergoing lung transplantation is poor. Although postsurgical atrial arrhythmias seem to play a major role in the morbidity and mortality of this population, data regarding the clinical and interventional management of this complication are still controversial. Through a review of the literature in the field, we observed that not only the surgical technique is clearly arrhythmogenic, but the new administration of peri-procedure beta-blockers and amiodarone for arrhythmia prevention and treatment, respectively, seems harmful in these postsurgical patients. However, low-dose beta-blockers administered after surgery seem feasible in arrhythmia prevention in specific patient subgroups, and, aside from amiodarone, alternative antiarrhythmic agents can be safely and effectively used to treat symptomatic patients on top of adequate rate control. Finally, as to complex atrial arrhythmias occurring late after lung transplant surgery, radiofrequency catheter ablation seems a feasible treatment option. In light of this evidence and considering the absence of clear recommendations in the field, we suggest a practical approach that may help the clinician in the management of this postsurgical complication. However, as most of these considerations are drawn from small-sized and retrospective studies, more evidence is needed in the future to clarify which medical and interventional strategies may best treat these postsurgical arrhythmias and thus potentially improve the outcome of these frail patients.

Little is known about the importance of changes in body composition of patients before and after heart or lung transplantation. Reduced muscle mass may be a poor prognostic factor for death and morbidity in patients after orthotopic heart transplantation. Only a few studies have shown data on changes in the amount of adipose tissue and muscle tissue and their impact on patient prognosis. Therefore, more data is needed concerning this issue.

The aim of this study was to assess the body composition of patients before and after heart or lung transplantation using bioimpedance.

Forty-two patients have been recruited to the study, including 20 patients before organ transplant, 11 patients after heart transplant, and 11 patients after lung transplant (up to 24 months after organ transplantation). The mean age of patients enrolled in the study before and after organ transplantation was 52.05 ± 16.24 years and 50.77 ± 13.38 years, respectively. Body composition measurements were performed by bioimpedance using the SECA mBCA 515 - medical Body Composition Analyzer.

In summary, we have shown that body composition was significantly changed after heart and lung transplantation, such as in muscle mass value and fat-free mass value. Adequate intervention at these points might reduce the risk of short and long-term mortality and morbidity.

Granulomatous infections are common in patients with chronic lung disease. We aim to study the incidence and clinicopathological features of granulomatous infections in a cohort of patients undergoing lung transplantation for end-stage chronic lung disease.

Pathology reports of 50 explanted native lungs of patients who underwent lung transplantation since 2015 at our institution were reviewed. Four cases with granulomatous lesions were identified. Correlation was made with clinical findings in the 4 cases.

The granulomatous infections include non-necrotizing cryptococcal pneumonitis (case 1), necrotizing pneumonia due to Scedosporium sp. and Mycobacterium avium Complex (MAC) (Cases 2 and 3), and invasive Aspergillus pneumonia (Case 4). One patient received pre-transplant fungal prophylaxis (Case 4). Post-transplant infectious complications included invasive (Cases 2 and 4) and non-invasive (Case 1) fungal infections and bacterial pneumonia (Cases 1 and 2). Two patients (Cases 3 and 4) developed acute cellular rejection (ACR) in the first 30 days. The third patient (Case 1) was identified with ACR in the 9 months post-transplant and chronic lung allograft dysfunction at 29 months. In terms of mortality, 1 patient (Case 1) died at 30 months post-transplant from pseudomonal sepsis and chronic graft failure. Two patients with invasive fungal infections (Cases 2 and 4) are on secondary prophylaxis and doing well. One patient (Case 3) remains infection-free and on MAC prophylaxis.

In our case series, patients with chronic lung diseases with superimposed granulomatous infestations frequently experienced post-transplant complications. These include invasive infections and repeat ACRs that predispose patients to chronic graft dysfunction. Pre- and post-transplant antifungal prophylaxis reduces fungal load and complication risk post-transplant.

Blood transfusion can have detrimental effects on the pulmonary system, leading to lung injury and respiratory decompensation with subsequent increased morbidity and mortality in surgical and critically ill patients. How much of this effect is carried from a lung donor to transplant recipient is not fully understood, raising questions regarding transplant suitability of lungs from transfused donors.

United Network for Organ Sharing data were reviewed. Lung transplants from adult donors and known donor transfusion status were included; multiorgan transplants and retransplants were excluded. Recipient mortality was evaluated based on donor and recipient characteristics using a Kaplan-Meier survival estimate, Cox proportional hazards, and logistic regression models. We further assessed whether recipient mortality risk modified the donor transfusion effect.

From March 1996 to June 2017, 20,294 transplants were identified. Outcome analysis based on transfusion status showed nonsignificant difference in 1-year mortality (P = .214). Ninety-day recipient mortality was significantly higher with transfusion of >10 units (U) vs 1-10 U or no transfusion (8.5%, 6.1%, and 6.0%, respectively, P = .005). Multivariable analysis showed increased 90-day mortality with transfusion of >10 U compared to no transfusion (odds ratio 1.62, P < .001), whereas 1-10 U showed no difference (odds ratio 1.07, P = .390). When stratified by recipient transplant risk, transfusion of >10 U was associated with increased mortality even with the lowest-risk recipients, while transfusion of 1-10 U showed no mortality increase even in the highest-risk recipients.

Donor transfusion of >10 U of blood was associated with increased 90-day recipient mortality even in low-risk transplants. This risk should be considered when evaluating donor lungs.

Culture-independent study of the lower respiratory tract after lung transplantation has enabled an understanding of the microbiome – that is, the collection of bacteria, fungi, and viruses, and their respective gene complement – in this niche. The lung has unique features as a microbial environment, with balanced entry from the upper respiratory tract, clearance, and local replication. There are many pressures impacting the microbiome after transplantation, including donor allograft factors, recipient host factors such as underlying disease and ongoing exposure to the microbe-rich upper respiratory tract, and transplantation-related immunosuppression, antimicrobials, and postsurgical changes. To date, we understand that the lung microbiome after transplant is dysbiotic; that is, it has higher biomass and altered composition compared to a healthy lung. Emerging data suggest that specific microbiome features may be linked to host responses, both immune and non-immune, and clinical outcomes such as chronic lung allograft dysfunction (CLAD), but many questions remain. The goal of this review is to put into context our burgeoning understanding of the lung microbiome in the postlung transplant patient, the interactions between microbiome and host, the role the microbiome may play in post-transplant complications, and critical outstanding research questions.