Background Increasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii ( P. jirovecii ) is an opportunistic fungal pathogen that frequently causes lethal pneumonia in LTRs. However, the lung microbiota in LTRs with P. jirovecii pneumonia (PJP) remains unknow. Methods In this prospective observational study, we performed metagenomic next-generation sequencing (mNGS) on 72 bronchoalveolar lavage fluid (BALF) samples from 61 LTRs (20 with PJP, 22 with PJC, 19 time-matched stable LTRs, and 11 from LTRs after PJP recovery). We compared the lung microbiota composition of LTRs with and without P. jirovecii , and analyzed the related clinical variables. Results BALFs collected at the episode of PJP showed a more discrete distribution with a lower species diversity, and microbiota composition differed significantly compared to P. jirovecii colonization (PJC) and control group. Human gammaherpesvirus 4, Phreatobacter oligotrophus , and Pseudomonas balearica were the differential microbiota species between the PJP and the other two groups. The network analysis revealed that most species had a positive correlation, while P. jirovecii was correlated negatively with 10 species including Acinetobacter venetianus , Pseudomonas guariconensis , Paracandidimonas soli , Acinetobacter colistiniresistens , and Castellaniella defragrans , which were enriched in the control group. The microbiota composition and diversity of BALF after PJP recovery were also different from the PJP and control groups, while the main components of the PJP recovery similar to control group. Clinical variables including age, creatinine, total protein, albumin, IgG, neutrophil, lymphocyte, CD3 + CD45 + , CD3 + CD4 + and CD3 + CD8 + T cells were deeply implicated in the alterations of lung microbiota in LTRs. Conclusions This study suggests that LTRs with PJP had altered lung microbiota compared to PJC, control, and after recovery groups. Furthermore, lung microbiota is related to age, renal function, nutritional and immune status in LTRs.

Progressive multifocal leukoencephalopathy (PML) is a rare and yet serious central nervous system disorder due to JC viral infection.PML occurs predominantly in immunocompromised individuals, including solid organ transplant (SOT) recipients.Clinically, SOT-related PML commonly presents as cognitive and behavioral impairments. Pathologically, PML is characterized by multifocal demyelinating lesions, with neuroimaging technique typically revealing white matter damage in the temporoparietal regions. Clinical diagnosis usually involves integrating clinical manifestations, cranial magnetic resonance imaging, and detection of JC virus in cerebrospinal fluid. Currently, specific medications for PML are lacking, and the treatment mainly relies on supportive care and immunomodulatory strategies. The prognosis of PML remains unfavorable, early diagnosis and enhanced adaptive immune responses are crucial for PML management in SOT recipients.

Background:Nebulized amphotericin B (NAB) is recommended for preventing invasive fungal diseases (IFDs) after lung transplantation. However, the optimal duration of NAB treatment is still unknown. This study aimed to compare the effectiveness of three different durations of antifungal prophylaxis with NAB after lung transplantation: a prolonged course beyond post-transplant 3 months, a medium course of 2 weeks to 3 months, and a short course of less than 2 weeks. Methods:This a single-center retrospective cohort study analyzed 333 patients who underwent lung or heart-lung transplantation between January 2015 and November 2021. Results:A prolonged course of NAB treatment was associated with a significantly lower incidence of IFDs (12.6%) at 1 year post-transplant compared with a short (50.9%) or a medium course (28.0%) (P<0.001). There was no significant difference in the rates of adverse effects among the three durations of NAB treatment (P>0.05). A prolonged course of NAB treatment was associated with a significantly higher 1-year survival rate (94.7%) compared with a short (36.8%) or a medium course (72.0%) (P<0.001). Conclusions:A prolonged course of NAB treatment provided better protection against IFDs than a short or medium course after lung transplantation. Prolonged use of NAB did not significantly increase the incidence of adverse effects.

Background: In lung transplant recipients (LTRs), the primary causes of mortality are rejection and infection, which often present similar symptoms, making differentiation challenging. This study aimed to explore the diagnostic efficacy of plasma donor-derived cell-free DNA (dd-cfDNA) in conjunction with metagenomic next-generation sequencing (mNGS) for pathogen detection in differentiation between lung allograft rejection and infection in LTRs experiencing new-onset pulmonary complications. Methods: We conducted a retrospective study on 188 LTRs who underwent lung or heart-lung transplantation at our institution from 2015 to 2021. The LTRs were categorized into three groups: stable, rejection, and infection. We measured plasma dd-cfDNA levels and utilized both mNGS and culture methods to identify pathogens in the bronchoalveolar lavage fluid (BALF).Results: The rejection group exhibited the highest levels of plasma dd-cfDNA (median 1.34 %, interquartile range [IQR] 1.06-2.19 %) compared to the infection group (median 0.72 %, IQR 0.62-1.07 %) and the stable group (median 0.69 %, IQR 0.58-0.78 %) (both p < 0.001). Within the infection group, a significantly higher level of dd-cfDNA was observed in the cytomegalovirus infection subgroup (p < 0.001), but not in the fungal (p > 0.05) or bacterial infection subgroups (p > 0.05), when compared to the stable group. Elevated dd-cfDNA levels, in combination with negative mNGS results, strongly indicated lung allograft rejection, with a positive predictive value and negative predictive value of 88.7 % and 99.2 %, respectively.Conclusions: Plasma dd-cfDNA in combination with BALF pathogen detection by mNGS shows satisfactory accuracy in differentiating lung allograft rejection from infectious complications.

ObjectiveTo analyze the changes of postoperative pulmonary function in lung transplant recipients. MethodsClinical data of 81 recipients undergoing bilateral lung transplantation and combined heart-lung transplantation were collected, and postoperative status of the recipients was analyzed. Pulmonary ventilation and diffusion function indexes at 1 month, 3 months, every 3 months (3-18 months after lung transplantation) and every 6 months (18-36 months after lung transplantation) were analyzed in the recipients. The characteristics of the optimal pulmonary function in the recipients were assessed. ResultsPostoperative mechanical ventilation time was 4 (2, 9) d, and the length of postoperative ICU stay was 10 (7, 20) d. Among 81 recipients, 27 recipients developed primary graft dysfunction (PGD) after lung transplantation, with an incidence rate of 33%. Postoperative forced vital capacity to predicted value ratio (FVC%pred), forced expiratory volume in one second to predicted value ratio (FEV1%pred), forced vital capacity/forced expiratory volume in one second to predicted value ratio (FEV1/FVC%pred) and corrected diffusion lung capacity for CO to predicted value ratio (DLCOc%pred) were changed over time (all P<0.001). FVC%pred and FEV1%pred were gradually increased within postoperative 9 months, and DLCOc%pred was gradually elevated within postoperative 3 months (both P<0.05). Thirty-six recipients had FVC%pred≥80%, FEV1%pred≥80% in 41 cases, FEV1/FVC%pred≥92% in 76 cases, FVC%pred≤40% in 1 cases and FEV1%pred≤40% in 1 cases, respectively. Sixteen recipients had DLCOc%pred≥80%, corrected diffusion lung capacity for CO/alveolar volume to predicted value ratio (DLCOc/VA%pred) ≥80% in 63, DLCOc%pred≤40% in 4 cases and DLCOc/VA%pred≤40% in 1 cases, respectively. Postoperative FVC%pred, FEV1/FVC%pred and DLCOc%pred in patients with a primary disease of obstructive pulmonary disease were significantly higher than those in their counterparts with restrictive pulmonary disease (all P<0.05). Postoperative DLCOc%pred in recipients with PGD was significantly lower than that in those without PGD (P<0.05). ConclusionsPulmonary ventilation function in lung transplant recipients reaches the optimal state and maintains a steady state at postoperative 9 months, and pulmonary diffusion function reaches a steady state at postoperative 3 months. Primary diseases and the incidence of PGD may affect postoperative pulmonary function.

Background Patients with work-related lung disease (WRLD) are at increased risk of death caused by severe lung tissue damage and fibrosis. This study aimed to assess the clinical outcomes of lung transplantation (LTx) for WRLD and compare the results of LTx between WRLD and idiopathic pulmonary fibrosis (IPF). Methods This single-center retrospective cohort study reviewed the clinical data of patients who underwent LTx for WRLD or IPF at our hospital between January 2015 and December 2021. Cumulative survival rates after LTx were estimated using the Kaplan-Meier method. Results The final analysis included 33 cases of WRLD and 91 cases of IPF. The 33 WRLD patients consisted of 19 (57.6%) cases of silicosis, 8 (24.2%) cases of coal workers’ pneumoconiosis, 3 (9.09%) cases of asbestosis, and 3 (9.09%) cases of other WRLD. Pneumothorax as an indication for LTx was significantly more common in the WRLD group than in the IPF group (51.5% vs. 2.2%, P < 0.001). There was no significant difference in the 5-year cumulative survival rate between the WRLD patients and the IPF patients (66.6% vs. 56.7%, P = 0.67). There was no significant difference in the best performance of exercise capacity and lung function between the two groups at 1 year post-transplant. Conclusions LTx had similar survival outcomes and lung function for WRLD and IPF patients. Pneumothorax was the primary indication for lung transplantation in WRLD.

BACKGROUND:Reported data on the disease spectrum of interstitial lung diseases (ILDs) of China are sparse and varied. We aimed to investigate the spectrum of ILDs and the distribution of diagnostic methods under a uniform diagnosis.METHODS:This retrospective study enrolled ILDs cases from Guangzhou Institute of Respiratory Health (GIRH). All cases were classified into specific subgroups of ILDs according to updated guidelines.RESULTS:A total of 1,945 subjects were enrolled from January 2012 to December 2017. The mean age was 57.9 years, and 1,080 (55.5%) patients were male. The most common subtype of ILDs was idiopathic pulmonary fibrosis (IPF, 20.3%), followed by interstitial pneumonia with autoimmune features (IPAF, 17.9%), connective tissue disease associated ILD (CTD-ILD, 18.3%) and unclassifiable idiopathic interstitial pneumonia (UIIP, 14.7%). A total of 818 (42.1%) patients underwent lung biopsy in order to obtain a histological diagnose. TBLB was performed in 565 (29.0%) patients, eleven of whom underwent SLB because TBLB failed to obtain lung samples. SLB was performed in 213 (11.0%) patients and TBCB was performed in 51 (2.6%) patients. Among them, histological results were considered clinically helpful in 722 (88.3%) cases, and provided definitive histopathological diagnoses in 368 cases. Surgical lung biopsy (SLB) was performed in 213 (10.9%) subjects, while 115 (54.0%) cases were performed among the idiopathic interstitial pneumonia (IIP). Among SLB cases in IIP, the highest rate of SLB was desquamative interstitial pneumonia/respiratory bronchiolitis-interstitial lung disease (DIP/RB-ILD, 10/10), lymphoid interstitial pneumonia (LIP, 9/9), followed by cryptogenic organizing (COP, 18/26), nonspecific interstitial pneumonia (NSIP, 22/53), IPF (43/395), UIIP (13/285).CONCLUSIONS:IPF was the most common ILDs in our ILD center, followed by IPAF, CTD-ILD and UIIP. Histological information may help to establish diagnostic algorithm in ILD.

We aimed to evaluate the alteration of diagnosis of individual expert and multidisciplinary discussion (MDD) team in the longitudinal diagnostic assessment of idiopathic interstitial pneumonia (IIP). The retrospective analysis included 56 patients diagnosed as IIP by The First Affiliated Hospital of Guangzhou Medical University with follow-up visits during Jan 1st to Aug 31st 2014. Each expert was provided information in a sequential manner and was asked to assign an individual diagnosis and an MDD diagnosis after group discussion. The level of agreement among individual experts and between different visits was calculated by kappa and the agreement between individual specialist and MDD team with different consensus levels was measured by weighted-kappa coefficients. Follow-up data changed the original clinical diagnosis and MDD diagnosis in 24.1% and 10.7% of all cases, respectively, and clinician and MDD consensus level in 55.4% and 25.0%, respectively. The diagnostic performance of individual clinicians or radiologist was closer to that of the MDD compared with the pathologist, and follow-up further increased the agreement. The longitudinal evaluation of patients with IIP improved the inter-observer agreement in a multidisciplinary team. The performance of individual clinicians or radiologist was approaching the accuracy of multidisciplinary team when provided with follow-up data.