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Background: Ventilation-perfusion (VQ) scintigraphy and lung function testing are often used to assess allograft function after single lung transplantation (SLTX). However, it is unknown whether allograft defects on VQ scintigraphy presage all-cause mortality after SLTX., Objective: To investigate whether allograft defects on VQ scintigraphy portend poorer lung function and increased mortality after SLTX., Methods: We retrospectively identified 45 consecutive patients in which a VQ scintigraphy was performed as part of the routine workup 12 weeks after SLTX. VQ scintigraphies were scored for matched and mismatched perfusion defects in the allograft. Lung function testing was performed according to established guidelines six months after SLTX. Time to all-cause mortality was the endpoint., Results: 19 (42%) patients had matched VQ defects. After a median follow-up of 4.1 (IQR 1.5-7.9) years since SLTX, 35 (78%) had died. Those with matched defects in the allograft had lower diffusing capacity (mean 42 [SD 14] versus mean 54 [SD 18] % of predicted, p < .05) and increased mortality (univariable HR 2.06, 95% CI: 1.05-4.06, p = .04). However, in multivariate analysis, only lower post-transplantation diffusing capacity remained associated with mortality (HR 1.08, 95% CI: 1.02-1.30 per % lower diffusing capacity of predicted, p = .003)., Conclusion: In SLTX patients, a lower diffusing capacity appeared to explain the increased mortality among those with matched VQ defects in the allograft., (© 2020 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Background: Establishment of baseline values for forced expiratory volume in the first second (FEV 1 ), forced vital capacity (FVC), or total lung capacity (TLC) is required when diagnosing and phenotyping chronic lung allograft dysfunction after lung transplant. It is generally accepted that the baseline (peak) values of these parameters occur simultaneously, but this assumption has not been substantiated for TLC., Methods: All lung function measurements in all double lung transplant recipients from a single center in the period from 1992-2014 were included. Time to baseline FEV 1 was assessed according to standards from the International Society for Heart and Lung Transplantation, and time to peak FVC, TLC, and diffusion capacity for carbon monoxide were evaluated., Results: A total of 288 double lung transplants surviving more than 3 months after transplant were included. Baseline FEV 1 occurred at a median of 0.77 years post transplant and was statistically different from median times to the peak FVC (1.02 years), to peak TLC (1.37 years), and to peak diffusion capacity for carbon monoxide 1.04 years post transplant (all log-rank P < .001). At the time of baseline FEV1, FVC, and TLC were at a mean of 96% and 95% of their peak values, respectively., Conclusion: The peak lung function is reached at different time points for different parameters post transplant with FEV 1 baseline occurring first. For most patients values of FVC and TLC obtained at time for baseline FEV 1 is a good estimate of peak values, but in a small percentage of patients this procedure may jeopardize phenotyping of chronic lung allograft dysfunction based solely on lung function parameters., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Post-transplantation mortality after lung transplantation (LTX) is higher than for other solid organ transplantations. Thoracic surgery is associated with increased risk of thromboembolic complications, and as LTX recipients lack the collateral bronchial circulation, pulmonary thromboembolism (PTE) may represent a pertinent yet largely underdiagnosed cause of post-transplantation respiratory failure. In this systematic review, we sought to elucidate the occurrence and predilection site of PTE after LTX, and its potential impact on LTX-associated mortality. Based on twelve original articles identified by a systematic search strategy in PubMed, we found that PTE was reported in 4% of LTX recipients, and 38% of these events occurred within the first 30 days after the LTX procedure. In single-lung transplantation (SLTX) recipients, 12% were diagnosed with PTE, with 92% of these affecting the allograft. Of LTX patients diagnosed with PTE, 11% died within 1 year after LTX and 75% of these deaths occurred within the first 30 days. Our findings suggest that PTE is a potentially underdiagnosed cause of early post-LTX respiratory failure. This should be confirmed in larger studies with systematic follow-up diagnostic imaging., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation, and to investigate whether scintigraphic findings at 3 months were predictive for the outcome at 12 months in relation to primary graft dysfunction (PGD) and lung function. A retrospective study was carried out on all patients who prospectively and consecutively were referred for a routine lung scintigraphy procedure 3 months after single lung transplantation (SLTX). A total of 41 patients were included in the study: 20 women and 21 men with the age span of patients at transplantation being 38-66 years (mean ± SD: 54.2 ± 6.0). Patient records also included lung function tests and chest X-ray images. We found no significant correlation between lung function distribution at 3 months and PGD at 72 h. There was also no significant correlation between PGD scores at 72 h and lung function at 6 and 12 months. The same applied to scintigraphic scores for heterogeneity at 3 months compared with lung function at 6 and 12 months. Fifty-five percent of all patients had decreased ventilation function measured in the period from 6 to 12 months. Forty-nine percent of the patients had normal perfusion evaluations, and 51% had abnormal perfusion evaluations at 3 months. For ventilation evaluations, 72% were normal and 28% were abnormal. There was a significant difference in the normal versus abnormal perfusion and ventilation scintigraphic images evaluated from the same patients. Ventilation was distributed more homogenously in the transplanted lung than perfusion in the same lung. The relative distribution of perfusion and ventilation to the transplanted lung of patients with and without a primary diagnosis of fibrosis did not differ significantly from each other. We conclude that PGD defined at 72 h does not lead to recognizable changes in ventilation-perfusion scintigrapy at 3 months, and scintigraphic findings do not correlate with development in lung function in the first 12 months.

We evaluated the diagnostic value of high-resolution computed tomography (HRCT) images generated from 64 detector multi-slice CT scanners (HRCT(64-MSCT) imaging) in relation to primary graft dysfunction (PGD) after lung-transplantation (LUTX) in a pilot study. PGD has mortality rates ranging from 17 to 50% over a 90-day period. Detailed HRCT lung images, reconstructed using 64-MSCT, may aid diagnostic and therapeutic efforts in PGD. Thirty-two patients were scanned four times within a year post-LUTX, in a single-centre prospective study. HRCT lung images were reviewed, evaluated and scored by two observers, for ground-glass (GG) opacities, consolidation, septal thickening (ST) and pulmonary embolism. Image and PGD scores were compared in each patient. GG and consolidation changes were largely present up until 2 weeks post-LUTX, and markedly reduced by the 12th week. ST was predominantly found in patients with PGD. There were no vascular changes found at CT angiographies. The most severe cases of GG opacities and consolidation were found in patients with PGD. ST seems to be an important indicator of PGD. HRCT(64-MSCT) imaging may be a useful tool for the identification of pathological features of PGD not detected by classical evaluation in patients undergoing LUTX.

Background: The prevalence, prognostic importance, and factors that predict the presence and degree of pulmonary hypertension (PH) diagnosed with right heart catheterization (RHC) in patients with end-stage chronic obstructive pulmonary disease (COPD) remain unclear., Methods: This retrospective study included 409 patients (61% women) with COPD/emphysema or α-1-antitrypsin deficiency who underwent lung transplant evaluation during 1991 to 2010. We analyzed the occurrence and degree of PH and compared demographics, oxygenation, lung function, hemodynamics, functional capacity, and survival in patients with and without PH. Prediction of PH was assessed using univariate and multivariate regression analysis., Results: The mean age at evaluation was 54 ± 7 years. All patients were in New York Heart Association functional class III-IV, with forced expiratory volume in 1 second of 23% ± 7% and total lung capacity of 126% ± 21% of predicted. PH was present in 146 (36%). The analysis excluded 53 (13%) with pulmonary venous hypertension (PVH). The distribution of the mean pulmonary artery pressure (mPAP) in patients with or without PH showed a unimodal normally distributed population, with a mean of 23.8 ± 6.0 mm Hg. Predictors of PH were partial pressures of oxygen and carbon dioxide. The 5-year survival rate was 37% in COPD patients with PH vs 63% in patients without PH (p = 0.016). Survival after lung transplantation did not differ (p = 0.37)., Conclusions: RHC verified PH in 36% of COPD patients. Hypoxemia and hypercapnia were associated with mPAP. PH is associated with worse survival in COPD, but PH does not influence the prognosis after lung transplantation., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Post-transplant baseline forced expiratory volume in 1 second (FEV(1)) constitutes a systematic bias in analyses of bronchiolitis obliterans syndrome (BOS). This retrospective study evaluates risk factors for BOS adjusting for the confounding of post-transplant baseline FEV(1)., Methods: A multivariate survival and competing risk analysis of a large consecutive series of patients (n = 389) from a national center 1992 to 2004. Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and no available lung function measurements (n = 4)., Results: The first maximum FEV(1) occurred at a median 183 days post-transplant. Freedom from BOS was 81%, 53%, 38% and 15%, and cumulative incidence of BOS was 18%, 43%, 57% and 77% at 1, 3, 5 and 10 years post-transplantation, respectively. Acute cellular rejection was independently associated with an increased cause-specific hazard of BOS (hazard ratio 1.4, confidence interval 1.1 to 1.8, p = 0.009). The absolute value of baseline FEV(1) was a significant confounder in all survival and competing risk analyses of BOS (p < 0.05)., Conclusion: Despite early diagnosis and prompt treatment, acute cellular rejection remains an independent risk factor for the development of BOS after adjusting for the confounding of post-transplant baseline FEV(1).

Background: Because bronchiolitis obliterans syndrome (BOS) is defined and graded according to the decline in forced expiratory volume in 1 second (FEV(1)) relative to a maximal baseline value obtained post-transplantation, the criteria discriminates against recipients with lower maximal baseline values (i.e., constitutes a statistical bias). This study describes the effect of transplant procedure on the development of BOS, adjusting for the absolute value of post-transplant baseline FEV(1)., Methods: All patients receiving a cadaveric lung transplant from 1992 to 2004 were included in the study (n = 389). Exclusion criteria were patients surviving <3 months (n = 39) and missing spirometry measurements (n = 4)., Results: Baseline FEV(1) was strongly associated with the freedom from BOS Grade 1, and longer-duration BOS-free survival in univariate and multivariate survival analyses. After adjusting for baseline FEV(1), and recipient-donor gender, bilateral lung transplantation (BLT) was associated with an increase in the cause-specific risk of BOS Grade 1 (hazard ratio [HR] 2.0, confidence interval [CI] 1.2 to 3.1, p = 0.004), and an increase in the cause-specific risk of death/re-transplantation or BOS Grade 1 as a combined end-point (HR 2.3, CI 1.5 to 3.4, p < 0.0001) compared with single-lung transplantation (SLT). In the competing risk regression model adjusting for recipient-donor gender and transplant procedure, only baseline FEV(1) remained independently associated with the cumulative incidence of BOS Grade 1 (p < 0.05); however, BLT recipients were more likely to have death/re-transplantation unrelated to BOS than SLT recipients., Conclusions: The absolute value of baseline lung function appears to be an important confounder in the analyses of BOS, and should be considered in future risk factor analyses.

Background: The objectives of this study were to describe the natural history of bronchiolitis obliterans syndrome (BOS) in a large consecutive series of patients from a national center in accordance with the most recent grading criteria, and to examine the prognosis with respect to onset and severity of BOS., Methods: All patients receiving a cadaveric lung transplant between 1992 and 2004 were included in the study (n = 389). Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and lack of available lung function measurements (n = 4)., Results: The 1-, 3-, 5- and 10-year actuarial survival rates for the entire series were 81%, 67%, 60% and 36%, respectively. The 1-, 3-, 5- and 10-year actuarial freedom from BOS Grade > or = 1 was 81%, 53%, 38% and 15%, respectively. A Cox regression model with BOS grade as a time-dependent covariate was performed in a sub-group of patients surviving at least 3 years (n = 237). Both progression from BOS Grade 1 to 2 and from BOS Grade 2 to 3 were associated with a significant increase in mortality: hazard ratio (HR) = 3.1 (confidence interval [CI] 1.2 to 7.9) and HR = 2.9 (CI 1.6 to 5.3), respectively. The addition of a non-time-dependent covariate to signify early (within 18 months of transplantation) or late (after 18 months) development of BOS was not significant (p = 0.5)., Conclusions: The development and progression of chronic allograft rejection after lung transplantation (BOS Grades 2 and 3) is associated with a 3-fold increase in the risk of death at each stage, irrespective of whether BOS developed early or late.

Objective: Primary graft dysfunction (PGD) causes significant mortality and morbidity after lung transplantation. The objectives of the study were to describe the clinical and histological sequelae of PGD., Methods: Histology of all patients receiving single-lung transplantation 1999-2004 (n=181) was reviewed. PGD was defined as diffuse radiological infiltration of the lung allograft occurring within the first 72h postoperatively., Results: One patient died intra-operatively. PGD was recorded in 63% (n=113) of 180 consecutive transplant recipients. Patients with PGD had a worse 90-day postoperative mortality (14% versus 3%, p=0.03) and 3-year survival (55% versus 77%, p=0.003). Freedom from bronchiolitis obliterans syndrome was similar in both groups. The maximal FEV(1) was significantly lower in patients with PGD, median 54% (quartiles 48-61%) predicted; compared to patients without PGD, median 59% (quartiles 54-69%) predicted (p=0.003). There was a significant linear trend in the decline of maximal FEV(1) with the presence and increasing severity of radiographic infiltrate (p=0.004). During follow-up, patients with PGD were more likely to demonstrate diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (p=0.009 and p=0.01, respectively). Histological findings of diffuse alveolar damage correlated closely with extent of radiological infiltration (p<0.0001)., Conclusions: Transplant recipient survival, lung function, and histological findings of diffuse alveolar damage appear to be closely correlated with the appearance and severity of PGD.

Background: Because bronchiolitis obliterans syndrome (BOS) is defined and graded according to the decline in forced expiratory volume in 1 second (FEV1) relative to a maximal baseline value obtained post-transplantation, the criteria discriminates against recipients with lower maximal baseline values (i.e., constitutes a statistical bias). This study describes the effect of transplant procedure on the development of BOS, adjusting for the absolute value of post-transplant baseline FEV1. Methods: All patients receiving a cadaveric lung transplant from 1992 to 2004 were included in the study (n = 389). Exclusion criteria were patients surviving <3 months (n = 39) and missing spirometry measurements (n = 4). Results: Baseline FEV1 was strongly associated with the freedom from BOS Grade 1, and longer-duration BOS-free survival in univariate and multivariate survival analyses. After adjusting for baseline FEV1, and recipient–donor gender, bilateral lung transplantation (BLT) was associated with an increase in the cause-specific risk of BOS Grade 1 (hazard ratio [HR] 2.0, confidence interval [CI] 1.2 to 3.1, p = 0.004), and an increase in the cause-specific risk of death/re-transplantation or BOS Grade 1 as a combined end-point (HR 2.3, CI 1.5 to 3.4, p < 0.0001) compared with single-lung transplantation (SLT). In the competing risk regression model adjusting for recipient–donor gender and transplant procedure, only baseline FEV1 remained independently associated with the cumulative incidence of BOS Grade 1 (p < 0.05); however, BLT recipients were more likely to have death/re-transplantation unrelated to BOS than SLT recipients. Conclusions: The absolute value of baseline lung function appears to be an important confounder in the analyses of BOS, and should be considered in future risk factor analyses. [Copyright &y& Elsevier]