Despite significant improvements in lung transplantation procedures, the incidence of airway complications (ACs) remains high (2%-18%); these complications are associated with high costs, great ...morbidities, and a decreased quality of life. There is general disagreement over potential risk factors determining ACs, including graft cold ischemic time (CIT). The aim of this study was to evaluate the association between CIT and ACs.
All patients undergoing lung transplantation between January 2011 and December 2017 were evaluated. We excluded retransplantations and patients with 90-day mortality. Demographic and clinical data regarding donors, recipients, and surgical procedures were analyzed using propensity score weighted marginal Cox regression model.
Out of the 161 lung transplantations performed in the study timeframe, 147 fulfilled the inclusion criteria and supplied complete data to be analyzed. Median follow-up was 25.5 months (interquartile range = 35.2). Ten patients (6.8%) had late ACs; out of the 260 anastomoses considered, 14 proved to be complicated (5.4%). Median time to event was 5.5 months (range, 3-15). ACs were classified as bronchial stenosis (12) and malacia (2). Mean CIT was 446.6 minutes (range, 117-1200). Without considering time-to-event data, CIT was significantly higher in complicated anastomoses (P = .002). The unweighted marginal univariate Cox model showed a significant association between ACs and CIT (P < .001). The propensity score weighted marginal univariable Cox model confirmed this significant association (P < .001).
The prolonged CIT time seems to be a risk factor for the development of late ACs; we endorse any measure that could limit CIT within 600 minutes.
•Airway complications are still regarded as a major problem in lung transplantation.•Prolonged cold ischemic time seems to be a risk factor for late airway complications after lung transplantations.•Cold ischemic time should be limited to 600 minutes to prevent airway complications.
•Anti-SARS-CoV-2 antibodies were measured in a vaccine-naïve population of pwCF.•Analysis was performed in 434 pwCF between march and june 2021.•64 patients had detectable anti-SARS-CoV-2 antibodies, ...indicating a 14.7% seroprevalence.•Seroprevalence among 49 transplant recipients was 6.1%.
The prevalence of anti-SARS-CoV-2 antibodies in people with cystic fibrosis (CF) is largely unknown. We carried out a cross-sectional study between March and June 2021 with the aim of estimating the seroprevalence of anti-SARS-CoV-2 antibodies in two CF centres in Northern Italy. Total serum anti-SARS-CoV-2 (spike) antibodies levels were measured and values ≥0.8 U/mL were considered positive. Among 434 patients aged >12 years, 64 patients had a positive result (14.7%, 95% CI: 11.5–18.4), 36 (56.3%) without experiencing any COVID-19-related symptoms. Three out of 49 transplanted patients tested positive with an odds ratio for a positive result among transplanted as compared to non-transplanted patients of 0.35 (95% CI: 0.07–1.14). No significant differences were observed between sexes, age groups, socioeconomic status and lung disease severity. In conclusion, SARS-CoV-2 has infected a relatively high proportion of our patients but in most cases the infection was asymptomatic.
Abstract
Aims
Primary graft dysfunction (PGD) is a form of acute lung injury, that occurs after lung transplantation (LTx), characterized by pulmonary oedema and diffuse alveolar damage. Pulmonary ...hypertension is a well-known risk factor for PGD and some invasive and non-invasive studies showed an association between PGD and altered left heart filling pressure. Despite the cardiopulmonary haemodynamic seems to be mainly involved in the pathogenesis of PGD, no reliable predictive parameter has been demonstrated. The aim of our study is to test whether pulmonary arterial pressure and left diastolic function may be considered in the risk PGD stratification.
Methods and results
we retrospectively analyzed the results of right heart catheterization (RHC) performed in occasion of the assessment for the LTx eligibility. All patients have been assessed at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico of Milan (Italy) from 2006 to 2018. We included all form of respiratory diseases except for cystic fibrosis. PGD was defined as PaO2/FIO2 < 300, with infiltrates at 72 h after reperfusion. We grouped patients in two groups according to the PGD development or absence (PGD+ and PGD−). Ninety patients were analyzed (mean age 55 ± 10; 53 male). Bilateral LTx was performed in 57 cases (63%). The most frequent indications for LTx were Interstitial Lung Disease (38%), Idiopathic Pulmonary Fibrosis (32%) an COPD (16%). Mean pulmonary arterial pressure (mPAP 29.4 ± 11.5 mmHg vs. 24.2 ± 9.7 mmHg, P = 0.016) and PAWP (12.9 ± 4.3 mmHg vs. 10.4 ±.,8 mmHg, P = 0.012) values were significantly higher in the PGD+ than in the PGD− group as well as PAWP values. At the multivariate analysis, both mPAP and PAWP were independent risk factors for PGD development even adjusted for BMI, age, or indication for LTx (mPAP non-adjusted OR: 1.05, 95% CI: 1.01–1.10, P = 0.027; mPAP adjusted OR: 1.06, 95% CI: 1.00–1.12, P = 0.046; PAWP non-adjusted OR: 1.13, 95% CI: 1.02–1.25, P = 0.016; PAWP adjusted OR: 1.14, 95% CI: 1.01–1.29, P = 0.036). No difference was observed between pulmonary vascular resistance (PVR) values. After a sub analysis of the patients with PAWP ≥15 mmHg, we observed that the ratio between PVR and PAWP was significantly higher in the PGD + group (0.18 ± 0.11 vs. 0.09 ± 0.05, P = 0.036).
Conclusion
s our data confirmed that pulmonary circulation plays a crucial role in the prediction of PGD and elevated mPAP is the one of the main risk factors. Of note, despite in both group PAWP in was within normal values (<15 mmHg), it was determinant in the risk stratification for PGD development. We suppose that the increased PVR due to pulmonary parenchymal diseases may “mask” and “underestimate” the role of the left ventricular diastolic dysfunction creating a sort of vascular barrage witch is overcome after lung transplantation hesitating in pulmonary oedema. This hypothesis is corroborated by the significative difference of PVR/PAWP ratio that can select patients at risk for PGD.
•> 50% of patients awaiting lung transplantation (LTx) have fragility fractures (Fx).•After LTx, BMD worsen in absence of bone-active therapy while improves in presence.•BMD changes are similar in ...patients with (CF) and without cystic fibrosis (nCF).•Fx incidence after LTx is higher in nCF patients than in CF ones.•After LTx TBS worsen in nCF patients, while it improves in CF patients.
the effect of bone-active drugs on the risk of fragility fractures (Fx), bone mineral density (BMD) and trabecular bone score (TBS) changes in patients receiving lung transplantation (LTx) is largely unknown. This study assessed the bone-active drugs effect in patients undergoing LTx both with (CF) and without (nCF) cystic-fibrosis.
We evaluated incident Fx, both clinical and morphometric vertebral Fx by spinal X-ray, BMD and trabecular bone score (TBS) in 117 patients (CF=50, nCF n = 67) before and 24-months after LTx. A bone-active therapy was proposed to all LTx candidates.
83.8% of patients started a bone-active drug. Lumbar-spine (LS) T-score improved significantly only in treated patients (-1.4 ± 1.0 vs -2.0±1.0, p = 0.0001), whereas femur BMD and TBS remained stable in treated and not treated subjects. The rate of incident Fx was 15.3%, with no difference between treated and not treated patients. After LTx, LS T-score improved significantly only in nCF group (-1.3 ± 1.0 vs -1.8 ± 1.1, p = 0.0001), while femur remained stable in both nCF and CF groups. Patients with CF showed a significant Z-TBS increase (-3.6 ± 1.7 vs -3.0 ± 1.7, p = 0.019) and a lower Fx incidence as compared with nCF patients (4.1% vs 24.2%, p =0.003). Incident Fx were associated with nCF diagnosis (OR 7.300, CI95% 1.385–38.461, p = 0.019) regardless of prevalent Fx, previous glucocorticoid therapy and bone-active therapy introduced at least 6 months before LTx.
A prompt medical intervention helps in preventing BMD loss after LTx. As compared with nCF patients, CF patients show a TBS increase and a lower Fx risk after LTx.
•Lung donation after cardiac death is a valuable option to fight organ shortage.•Grafts from an extended uncontrolled DCD donor were transplanted.•The recipient was a high-risk fragile patient with ...cystic fibrosis.•Ex-vivo lung perfusion has a pivotal role in graft function evaluation.•Good results were achieved despite several relative contraindications.
Lung donation after circulatory death (DCD) has proved to be an effective strategy for expanding the donor pool, but is still considered challenging. We report a successful case of lung procurement from an extended-criteria uncontrolled DCD.
We evaluated the lungs of an uncontrolled DCD from a hospital without extracorporeal membrane oxygenation (ECMO) program. The donor was a non-smoker 20-year old male with a history of cardiomyopathy, cardiocirculatory arrests, and Lennox-Gastaut syndrome. Cardiac arrest occurred in a swimming pool, and bronchoscopy showed signs of inhalation. We employed our usual normothermic in-situ open-ventilated lung approach. After retrieval, lungs were stored on ice, then evaluated with ex-vivo lung perfusion (EVLP) and judged suitable for transplantation. The recipient was a 26-year old female with cystic fibrosis on long-term oxygen therapy, on the waitlist for up to 21 months due to her anthropomorphic characteristics. She required central VA-ECMO support during bilateral lung transplantation. Primary graft dysfunction (PGD) within the first 72 h reached grade 3; post-operative peripheral VV-ECMO support was discontinued two days after surgery. The patient was discharged 28 days after surgery; she is alive two years after transplantation with no signs of rejection nor anastomotic complications.
Despite the spreading use of lungs from controlled DCD, perplexities remain on uncontrolled DCD, namely: severe PDG, postoperative mortality, airway complications.
Our case report suggests that good results can be achieved with uncontrolled DCD despite the presence of relative contraindications: inhalation of water, prolonged ischemic times and recipient in poor conditions.
•An atypical clinical presentation of early antibody-mediated rejection in COVID era.•The radiological features mimicked SARS-CoV2 pneumonia, but tests were negative.•This is the first report of lung ...transplantation in the COVID era in Europe.•Decide whether to keep lung transplantation programmes open in a COVID Hospital.
In addition to morbidity and mortality rate per se, COVID-19 outbreak leads to potential ‘side effects’, which are difficult to evaluate and predict. Lung transplantation is a consolidated treatment for end-stage chronic lung disease requiring significantly demanding management. Deciding whether to keep transplant programmes open during an epidemic of this size is not easy, as immunosuppressed subjects face the risk of infection and related mortality. Additionally, there is a chance for the patient’s standard care process to be compromised.
We report the case of a patient undergoing bilateral lung transplantation during the explosion of COVID-19 epidemic in Lombardy; he died from definite early acute antibody-mediated rejection, clinically (persistent high fever, unresponsive to treatment) and radiologically mimicking viral pneumonia but persistently negative for SARS-CoV-2.
The diagnosis was difficult given this atypical presentation, confounded by global scenario. Grafts were procured from a donation after circulatory death donor in an uncontrolled setting and a donor-recipient transmission was possible. Our institute became a COVID-Hospital right during the first post-transplantation days. Radiological imaging had the same features of SARS-CoV-2 pneumonia.
This is the first report of lung transplantation of the COVID-19 era in Europe. Our extremely fragile patient was COVID-19 free up to the end. Donor-recipient transmission is conceivable, but the risk should be assessed with respect to waiting list mortality. Ultimately, treating COVID-19 patients can be a resource-consuming activity but we decided to keep our centre open.
Regional analysis by computed tomography (CT) is an attractive technique to interpret lung patterns after transplantation (LTx). We evaluated the application of CT functional mask derived parameters ...to determine whether development of primary graft dysfunction (PGD) is associated with short and/or long-term postoperative evidences of pulmonary function alterations.
A total of 38 patients who underwent bilateral LTx were evaluated at 24, 48 and 72 hours after the end of surgery to establish PGD occurrence and grading. CT scans at 3 and 12 months after LTx were analyzed to measure specific gas volume (SV
) changes normalized on expiratory SVgEXP of the whole lung (ΔSV
/SV
) and to obtain functional masks of density variation, namely maps of low ventilation (LV), consolidation (C), air trapping (AT) and healthy parenchyma (H).
Our main result was the evidence of a marked decrease in ΔSV
/SV
in all subjects, irrespectively on PGD, at each time point after LTx, indicating a high degree of ventilation defects versus healthy. High percentages of LV were found in all subjects while percentages of AT and C were negligible.
We demonstrate that quantification of ventilation defects by CT functional mask offers insights into the correlation between PGD and pulmonary function after LTx at short and mid-term.
INTRODUCTIONLung donation after circulatory death (DCD) has proved to be an effective strategy for expanding the donor pool, but is still considered challenging. We report a successful case of lung ...procurement from an extended-criteria uncontrolled DCD.PRESENTATION OF CASEWe evaluated the lungs of an uncontrolled DCD from a hospital without extracorporeal membrane oxygenation (ECMO) program. The donor was a non-smoker 20-year old male with a history of cardiomyopathy, cardiocirculatory arrests, and Lennox-Gastaut syndrome. Cardiac arrest occurred in a swimming pool, and bronchoscopy showed signs of inhalation. We employed our usual normothermic in-situ open-ventilated lung approach. After retrieval, lungs were stored on ice, then evaluated with ex-vivo lung perfusion (EVLP) and judged suitable for transplantation. The recipient was a 26-year old female with cystic fibrosis on long-term oxygen therapy, on the waitlist for up to 21 months due to her anthropomorphic characteristics. She required central VA-ECMO support during bilateral lung transplantation. Primary graft dysfunction (PGD) within the first 72 h reached grade 3; post-operative peripheral VV-ECMO support was discontinued two days after surgery. The patient was discharged 28 days after surgery; she is alive two years after transplantation with no signs of rejection nor anastomotic complications.DISCUSSIONDespite the spreading use of lungs from controlled DCD, perplexities remain on uncontrolled DCD, namely: severe PDG, postoperative mortality, airway complications.CONCLUSIONOur case report suggests that good results can be achieved with uncontrolled DCD despite the presence of relative contraindications: inhalation of water, prolonged ischemic times and recipient in poor conditions.
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