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Acute cellular rejection (ACR) is a frequent and feared complication after lung transplantation, which occurs in ±30% of lung transplantation recipients (LTR) in the first year post-transplantation. LTR with ACR may be asymptomatic or present with non-specific pulmonary function alterations as well as non-specific symptoms such as cough, dyspnea, low-grade fever, and sputum production, making it hard to reliably discriminate ACR from infection. For the definite diagnosis of ACR bronchoscopy with transbronchial biopsies is required, which is an invasive procedure, with potential iatrogenic complications. As such, it is of interest to assess alternative non-invasive modalities as a diagnostic modality, such as exhaled breath analysis. We aimed to assess the ability of exhaled breath analysis using an electronic nose (eNose) to distinguish ACR from infection. LTR with either a FEV1 decline OR increased obstruction, OR new respiratory symptoms OR acute respiratory insufficiency, and subsequently proven (bacterial, viral, or fungal) infection or proven ACR were included. Exhaled breath analysis was performed using an eNose (SpiroNose). Partial least squares discriminant analysis was used to assess the discrimination of ACR from infection. In total, 44 LTR were included; 27% were female, median age was 61 (18 - 73) years, time after LTx was 1.5 (0.1 - 14.7) years. Of these LTR, 23 were diagnosed with ACR and 21 with infection. The eNose accurately discriminated ACR from infection with an AUC of 0.90 (CI 0.81 - 0.99, Figure 1), a sensitivity of 67%, specificity of 96%, and accuracy of 82%. Exhaled breath analysis using eNose technology has the potential to non-invasively discriminate ACR from infection in LTR and hence might limit the need of bronchoscopy and transbronchial biopsies in the future. [ABSTRACT FROM AUTHOR]

Lung transplantation (LTX) is the last life-extending option for selected patients with progressive fibrosing interstitial lung diseases (ILD). In around 30% (range 11 to 71%) of patients with severe ILD this concerns a hereditary form of pulmonary fibrosis (HPF) based on an underlying disease-associated genetic mutation (GM) and/or telomere shortening (TS) syndrome, and/or clustering in the family indicated as familial pulmonary fibrosis (FPF). HPF is associated with on average early onset, faster progression, and worse prognosis causing the HPF group to be referred to LTX relatively more often. Regarding outcomes of LTX in these patients there are contradictory reports on patient and graft survival, as well as numerous other outcomes. There is currently no consensus on whether HPF is associated with poorer outcomes after LTX and what considerations regarding candidacy are appropriate. We aimed to systematically review LTX outcomes of patients with HPF in comparison to those with non HPF-ILD. A systematic literature search was performed PubMed, Embase, MEDLINE, Web of Science, Cochrane Library, and Google Scholar for articles (01 June 2022). We included studies on LTX in ILD with and without underlying HPF and extracted separate outcome data on primary and secondary outcome parameters. Fourteen studies met the inclusion criteria (10 cohort studies and 4 case-series) including 1023 patients that underwent LTX, 297 for HPF and 726 for non HPF-ILD. There was large heterogeneity in methodological study quality and reported outcomes. Whereas a limited number of high quality studies report higher rate of ACR, CLAD and shorter survival in HPF, this could not be confirmed by an at least equal number of high quality studies. Specific secondary outcomes such as cytopenias, CMV reactivation and bronchial complications may be more prevalent in HPF, but there are insufficient studies for definitive conclusions. Due to large heterogeneity in methodological study quality and reported outcomes, no firm conclusions can be drawn. LTX in patients with HPF that are accepted for LTX does not unambiguously seem associated with poorer short and mid-term patient and graft outcomes, and thus this suggests that HPF in itself should not preclude from undergoing LTX. Nonetheless, differences may exist, especially regarding other transplant related outcomes. [ABSTRACT FROM AUTHOR]

Diabetes is very common in heart transplant recipients (HTR), with a 5-year post-transplant incidence of 34%. Post-transplant diabetes mellitus (PTDM) is associated with increased risk for severe renal dysfunction, retransplantation and death. As such, early recognition is warranted. An oral glucose tolerance test (OGTT) is the preferred test to screen for both prediabetes and PTDM. However, an OGTT is time-consuming and cumbersome which can discourage patients from screening procedures. As potential alternative and less burdensome test to distinguish between normal and impaired glucose tolerance, we assessed the diagnostic accuracy of exhaled breath analysis using an electronic nose (eNose) to distinguish between normal and impaired glucose tolerance. HTR, more than 1 year post-transplantation, who underwent OGTT screening were included. A control group consisted of known diabetic HTR who were fasting at time of measurement and did not undergo OGTT screening. Exhaled breath analysis was performed using an eNose (SpiroNose) pre-glucose loading. Partial least squares discriminant analysis was used to distinguish between normal and impaired glucose tolerance. In total, 40 HTR were included; 30% were female, median age was 59 (20 - 77) years, time after transplantation was 7.8 (1.5 - 26.5) years. Of these HTR, 6 had a normal test (HbA1c 38 mmol/mol, 35 - 39 mmol/mol) and 34 an impaired test (HbA1c 41 mmol/mol, 34 - 88 mmol/mol) indicating that 85% of patients had impaired glucose metabolism (pre-diabetes or PTDM). The eNose accurately discriminated between normal and impaired results with an AUC of 0.84 (CI 0.70 - 0.98, Figure 1), a sensitivity of 82%, specificity of 83%, and accuracy of 83%. Impaired glucose metabolism is a frequent finding in HTR. Exhaled breath analysis using eNose technology has the potential to non-invasively monitor HTR for PTDM. To possibly replace OGTT as a screening tool for impaired glucose metabolism, further confirmation in a larger cohort is warranted. [ABSTRACT FROM AUTHOR]

Chronic lung allograft dysfunction (CLAD) increases risk of death of lung transplant recipients (LTR). Although the main CLAD phenotypes bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) differ in spirometric and radiological characteristics, establishing the final diagnosis can be challenging. Yet, differentiation between BOS and RAS is crucial, since prognosis of the phenotypes considerably differs. Timely diagnosis of CLAD and CLAD phenotypes remains problematic due to a lack of accurate markers of CLAD. Promising evidence suggests that electronic nose (eNose) technology has 86% accuracy for the detection of CLAD and may even identify CLAD phenotype. Therefore, we aimed to assess the diagnostic accuracy of exhaled breath analysis using an eNose to distinguish between CLAD phenotypes. In 'this cross-sectional study, exhaled breath of consecutive LTR with ISHLT criteria based CLAD was collected using an eNose (SpiroNose). Patients with mixed or undefined phenotype were excluded (n = 13). Statistical analyses were conducted using partial least square discriminant analysis and receiver operating characteristics (AUC) analysis to assess differences in breathprint between CLAD phenotypes. A total of 25 LTR with CLAD were included during outpatient follow-up. 56% were male, median age was 63 (range 32 - 77) years, time after LTx was 9.7 (2.5 - 18.8) years, and time till onset of CLAD was 5.8 (1.7 - 18.8) years. Based on ISHLT criteria, 20 LTR were diagnosed with BOS, and 5 with RAS. The eNose accurately discriminated between BOS and RAS with an AUC of 0.94 (CI 0.85-1.00, Figure 1), a sensitivity of 100%, specificity of 90%, and an accuracy of 92%. The BOS and RAS phenotype differ in breathprint. Exhaled breath analysis using an eNose is a promising tool to distinguish between CLAD phenotypes. Validation of results is needed in a larger dataset, as well as assessment whether this technique allows earlier diagnosis of CLAD and its phenotype. [ABSTRACT FROM AUTHOR]

Although the currently approved COVID-19 vaccines are highly effective, SARS-CoV-2-specific immune responses are diminished in lung transplant recipients (LTR), probably due to immunosuppression (IS). There is currently no marker of IS that can be used to predict vaccination responses. Here, we study if torque tenovirus (TTV) can be used as a predictive marker. The humoral response to the mRNA-1273 vaccine was assessed in 103 LTR, who were vaccinated 4 to 237 months after Lung transplantation. Spike (S)-specific IgG levels were measured at baseline, 28 days after first, and 28 days after the second vaccination. TTV loads were determined by RT-PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load. Humoral responses to the vaccine COVID-19 vaccination were found in 41/103 (40%) LTR at 28 days after the second vaccination. 62 /103 (60%) had no detectable antibodies. TTV loads at baseline correlated with S-specific antibodies and the percentage of responders (=<0.001) (Fig 1). TTV loads also strongly correlated with the time since transplantation, indicating that participants with lower TTV loads were longer after transplantation. This study shows an association between baseline TTV load and mRNA-1273-induced S-specific antibodies. If the TTV load is indeed a predictor of vaccination responses, this can be used in the future as a potential guidance for optimizing vaccination regimens. Therefore, we recommend that TTV load measurements are included in further vaccination efficacy studies in immunocompromised cohorts. [ABSTRACT FROM AUTHOR]

Concerns have been raised on the impact of the coronavirus disease (COVID-19) on lung transplant (LTx) patients. The aim of this study was to evaluate the effect on the clinical course and transplant function pre- and post-COVID-19 infection in LTx patients. Data were retrospectively collected from adult LTx patients with a proven COVID-19 infection from three Dutch transplant centres, between February 2020 and September 2021. Spirometry results were collected pre-COVID-19 infection and within 3 and 6 months post-COVID-19 infection. A total of 59 LTx patients had been tested positive for COVID-19. The median age was 58 years (IQR 49-66), 64% was male and median time since transplantation was 5 years (IQR 2-11). Thirty-three patients (56%) were hospitalized, 30 (51%) were in need for supplemental oxygen therapy, 17 (29%) were admitted to the intensive care unit (ICU) and 13 (22%) required invasive mechanical ventilation. Thirteen patients died (22%), 10 in ICU (77%), 3 (23%) on general wards. Post-COVID-19 spirometry results were available in 45 (76%) patients within three months post-infection and in 34 (58%) 6 months post-infection. Spirometry results and the prevalence of chronic lung allograft dysfunction (CLAD) are shown in Table 1. CLAD pre-COVID-19 was not associated with higher mortality (12% vs 10%, p = 0.162). In LTx patients COVID-19 infection results in high hospitalization and mortality rate. FVC and FEV1 was declined three months after infection and gradually improved at 6 months post-COVID-19 infection. However, FVC remained significantly lower after 6 months, demonstrating a more restrictive pattern. The prevalence of CLAD did not change after COVID-19 infection. Further follow-up is required to obtain more detailed information about CLAD. [ABSTRACT FROM AUTHOR]