In-Person Versus Remote 6-Minute Walk and Incremental Shuttle Walk Distances in Advanced Lung Disease.

BACKGROUND: Field-based walk tests conducted remotely may provide an alternative method to a facility-based assessment of exercise capacity for people with advanced lung disease. This prospective study evaluated the level of agreement in the distance walked between a 6-min walk test (6MWT) and an incremental shuttle walk test performed by using standard in-person procedures and test variations and settings. METHODS: Adults with advanced lung disease underwent 4 study visits: (i) one in-person standard 6MWT (30-m corridor) and one in-person treadmill 6MWT, (ii) a remote 6MWT in a home setting (10-m corridor), (iii) 2 in-person standard incremental shuttle walk tests (10-m corridor), and (iv) a remote incremental shuttle walk test in a home setting (10-m corridor). A medical-grade oximeter measured heart rate and oxygen saturation before, during, and for 2 min after the tests. RESULTS: Twenty-eight participants were included (23 men [82%]; 64 (57-67) y old; 19 with interstitial lung disease [68%] and 9 with COPD [32%]; and 26 used supplemental oxygen (93%) [exertional [Formula: see text] of 0.46 ± 0.1]). There was no agreement between the tests. Greater walking distances were achieved with standard testing procedures: in-person 6MWT versus treadmill 6MWT (355 ± 68 vs 296 ± 97; P = .001; n = 28), in-person 6MWT versus remote 6MWT (349 ± 68 vs 293 ± 84; P = .001; n = 24), and in-person incremental shuttle walk test versus remote incremental shuttle walk test (216 ± 62 vs 195 ± 63; P = .03; n = 22). CONCLUSIONS: Differences in the distance walked may have resulted from different track lengths, widths, and walking surfaces. This should be considered in test interpretation if tests are repeated under different conditions.

Clinical implications of frailty assessed in hospitalized patients with acute-exacerbation of interstitial lung disease.

BACKGROUND: Approximately 50% of patients with interstitial lung disease (ILD) experience frailty, which remains unexplored in acute exacerbations of ILD (AE-ILD). A better understanding may help with prognostication and resource planning. We evaluated the association of frailty with clinical characteristics, physical function, hospital outcomes, and post-AE-ILD recovery. METHODS: Retrospective cohort study of AE-ILD patients (01/2015-10/2019) with frailty (proportion ≥0.25) on a 30-item cumulative-deficits index. Frail and non-frail patients were compared for pre- and post-hospitalization clinical characteristics, adjusted for age, sex, and ILD diagnosis. One-year mortality, considering transplantation as a competing risk, was analysed adjusting for age, frailty, and Charlson Comorbidity Index (CCI). RESULTS: 89 AE-ILD patients were admitted (median: 67 years, 63% idiopathic pulmonary fibrosis). 31 were frail, which was associated with older age, greater CCI, lower 6-min walk distance, and decreased independence pre-hospitalization. Frail patients had more major complications (32% vs 10%, p = .01) and required more multidisciplinary support during hospitalization. Frailty was not associated with 1-year mortality (HR: 0.97, 95%CI: [0.45-2.10]) factoring transplantation as a competing risk. CONCLUSIONS: Frailty was associated with reduced exercise capacity, increased comorbidities and hospital complications. Identifying frailty may highlight those requiring additional multidisciplinary support, but further study is needed to explore whether frailty is modifiable with AE-ILD.

Impact of intraoperative therapeutic plasma exchange on bleeding in lung transplantation.

BACKGROUND: Our program uses a desensitization protocol that includes intraoperative therapeutic plasma exchange (iTPE) for crossmatch-positive lung transplants, which improves access to lung transplant for sensitized candidates while mitigating immunologic risk. Although we have reported excellent outcomes for sensitized patients with the use of this protocol, concern for perioperative bleeding appears to have hindered broader adoption of it at other programs. We conducted a retrospective cohort study to quantify the impact of iTPE on perioperative bleeding in lung transplantation. METHODS: All first-time lung transplant recipients from 2014 to 2019 who received iTPE were compared to those who did not. Multivariable logistic regression was used to determine the association between iTPE and large-volume perioperative transfusion requirements (≥5 packed red blood cell units within 24 hours of transplant start), adjusted for disease type, transplant type, and extracorporeal membrane oxygenation or cardiopulmonary bypass use. The incidence of hemothorax (requiring reoperation within 7 days of lung transplant) and 30-day posttransplant mortality were compared between the 2 groups using chi-square test. RESULTS: One hundred forty-two patients (16%) received iTPE, and 755 patients (84%) did not. The mean number of perioperative pRBC transfusions was 4.2 among patients who received iTPE and 2.9 among patients who did not. iTPE was associated with increased odds of requiring large-volume perioperative transfusion (odds ratio 1.9; 95% confidence interval: 1.2-2.9, p-value = 0.007) but was not associated with an increased incidence of hemothorax (5% in both groups, p = 0.99) or 30-day posttransplant mortality (3.5% among patients who received iTPE vs 2.1% among patients who did not, p = 0.31). CONCLUSIONS: This study demonstrates that the use of iTPE in lung transplantation may increase perioperative bleeding but not to a degree that impacts important posttransplant outcomes.

Oesophageal stasis is a risk factor for chronic lung allograft dysfunction and allograft failure in lung transplant recipients.

Background: Morbidity and mortality in lung transplant recipients are often triggered by recurrent aspiration events, potentiated by oesophageal and gastric disorders. Previous small studies have shown conflicting associations between oesophageal function and the development of chronic lung allograft dysfunction (CLAD). Herein, we sought to investigate the relationship between oesophageal motility disorders and long-term outcomes in a large retrospective cohort of lung transplant recipients. Methods: All lung transplant recipients at the Toronto Lung Transplant Program from 2012 to 2018 with available oesophageal manometry testing within the first 7 months post-transplant were included in this study. Patients were categorised according to the Chicago Classification of oesophageal disorders (v3.0). Associations between oesophageal motility disorders with the development of CLAD and allograft failure (defined as death or re-transplantation) were assessed. Results: Of 487 patients, 57 (12%) had oesophagogastric junction outflow obstruction (OGJOO) and 47 (10%) had a disorder of peristalsis (eight major, 39 minor). In a multivariable analysis, OGJOO was associated with an increased risk of CLAD (HR 1.71, 95% CI 1.15-2.55, p=0.008) and allograft failure (HR 1.69, 95% CI 1.13-2.53, p=0.01). Major disorders of peristalsis were associated with an increased risk of CLAD (HR 1.55, 95% CI 1.01-2.37, p=0.04) and allograft failure (HR 3.33, 95% CI 1.53-7.25, p=0.002). Minor disorders of peristalsis were not significantly associated with CLAD or allograft failure. Conclusion: Lung transplant recipients with oesophageal stasis characterised by OGJOO or major disorders of peristalsis were at an increased risk of adverse long-term outcomes. These findings will help with risk stratification of lung transplant recipients and personalisation of treatment for aspiration prevention.

Incidence of post-transplant cytomegalovirus viremia in patients receiving lungs after ex vivo lung perfusion.

Objectives: Cytomegalovirus infection after lung transplant is associated with increased morbidity and mortality. Inflammation, infection, and longer ischemic times are important risk factors for cytomegalovirus infection. Ex vivo lung perfusion has helped to successfully increase the use of high-risk donors over the last decade. However, the impact of ex vivo lung perfusion on post-transplant cytomegalovirus infection is unknown. Methods: We performed a retrospective analysis of all adult lung transplant recipients from 2010 to 2020. The primary end point was comparison of cytomegalovirus viremia between patients who received ex vivo lung perfusion donor lungs and patients who received non-ex vivo lung perfusion donor lungs. Cytomegalovirus viremia was defined as cytomegalovirus viral load greater than 1000 IU/mL within 2 years post-transplant. Secondary end points were the time from lung transplant to cytomegalovirus viremia, peak cytomegalovirus viral load, and survival. Outcomes were also compared between the different donor recipient cytomegalovirus serostatus matching groups. Results: Included were 902 recipients of non-ex vivo lung perfusion lungs and 403 recipients of ex vivo lung perfusion lungs. There was no significant difference in the distribution of the cytomegalovirus serostatus matching groups. A total of 34.6% of patients in the non-ex vivo lung perfusion group developed cytomegalovirus viremia, as did 30.8% in the ex vivo lung perfusion group (P = .17). There was no difference in time to viremia, peak viral loads, or survival when comparing both groups. Likewise, all outcomes were comparable in the non-ex vivo lung perfusion and ex vivo lung perfusion groups within each serostatus matching group. Conclusions: The practice of using more injured donor organs via ex vivo lung perfusion has not affected cytomegalovirus viremia rates and severity in lung transplant recipients in our center.

Outcomes after flow cytometry crossmatch-positive lung transplants managed with perioperative desensitization.

Our program previously reported successful outcomes following virtual crossmatch (VXM)-positive lung transplants managed with perioperative desensitization, but our ability to stratify their immunologic risk was limited without flow cytometry crossmatch (FCXM) data before 2014. The aim of this study was to determine allograft and chronic lung allograft dysfunction (CLAD)-free survival following VXM-positive/FCXM-positive lung transplants, which are performed at a minority of programs due to the high immunologic risk and lack of data on outcomes. All first-time lung transplant recipients between January 2014 and December 2019 were divided into 3 cohorts: VXM-negative (n = 764), VXM-positive/FCXM-negative (n = 64), and VXM-positive/FCXM-positive (n = 74). Allograft and CLAD-free survival were compared using Kaplan-Meier and multivariable Cox proportional hazards models. Five-year allograft survival was 53% in the VXM-negative cohort, 64% in the VXM-positive/FCXM-negative cohort, and 57% in the VXM-positive/FCXM-positive cohort (P = .7171). Five-year CLAD-free survival was 53% in the VXM-negative cohort, 60% in the VXM-positive/FCXM-negative cohort, and 63% in the VXM-positive/FCXM-positive cohort (P = .8509). This study confirms that allograft and CLAD-free survival of patients who undergo VXM-positive/FCXM-positive lung transplants with the use of our protocol does not differ from those of other lung transplant recipients. Our protocol for VXM-positive lung transplants improves access to transplant for sensitized candidates and mitigates even high immunologic risk.

Pulmonary epithelial markers in phenotypes of chronic lung allograft dysfunction.

BACKGROUND: Airway epithelial injury is thought to be a key event in the pathogenesis of chronic lung allograft dysfunction (CLAD). We investigated whether markers of epithelial activity and injury in bronchoalveolar lavage fluid (BAL) correlate with CLAD diagnosis and major CLAD phenotypes: bronchiolitis obliterans syndrome (BOS) vs restrictive allograft syndrome (RAS)-related phenotypes (including RAS, mixed phenotype, and all other patients with RAS-like opacities). METHODS: CLAD status and phenotypes were retrospectively determined in a cohort of all consecutive adult, first, bilateral lung transplants performed 2010-2015, with available BAL samples. All patients with RAS-related phenotypes were included and 1:1 matched with BOS patients based on the time from transplant to CLAD-onset. Subjects who were CLAD-free for a minimum of 3 years post-transplant were 1:1 matched to CLAD patients and included as controls. Proteins that maintain the barrier function of the airway epithelial mucosa (club cell secretory protein, surfactant protein-D and epithelial mucins: MUC1, MUC5AC, MUC5B, MUC16), as well as epithelial cell death markers (M30&M65 representing epithelial cell apoptosis and overall death, respectively), were measured in BAL obtained within 6-months post CLAD onset using a double-sandwich ELISA or a multiplex bead assay. Protein levels were compared using Mann-Whitney-U-test. Association between protein levels and graft survival was assessed using Cox proportional hazards models, adjusted for CMV serology mismatch status and CLAD phenotype. RESULTS: Fifty-four CLAD (27 BOS, 11 RAS, 7 mixed, 9 others with RAS-like opacities) patients and 23 CLAD-free controls were included. Median BAL levels were significantly higher in patients with CLAD compared to CLAD-free controls for M30 (124.5 vs 88.7 U/L), MUC1 (6.8 vs 3.2 pg/mL), and MUC16 (121.0 vs 30.1 pg/mL). When comparing CLAD phenotypes, M30 was significantly higher in patients with RAS-related phenotypes than BOS (160.9 vs 114.6 U/L). In multivariable models, higher M30 and MUC5B levels were associated with decreased allograft survival after CLAD onset independent of phenotype (p < 0.05 for all). CONCLUSIONS: Airway epithelial mucins and cell death markers are enhanced in the BAL of patients with CLAD and can assist in differentiating between CLAD phenotypes and post-CLAD outcomes. Abnormal airway mucin expression and epithelial cell death may be involved in the pathogenesis of CLAD, and therefore their detection may aid in future selection of targeted therapies.

Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) increases morbidity and mortality for lung transplant recipients. Club cell secretory protein (CCSP), produced by airway club cells, is reduced in the bronchoalveolar lavage fluid (BALF) of lung recipients with CLAD. We sought to understand the relationship between BALF CCSP and early posttransplant allograft injury and determine if early posttransplant BALF CCSP reductions indicate later CLAD risk. METHODS: We quantified CCSP and total protein in 1606 BALF samples collected over the first posttransplant year from 392 adult lung recipients at 5 centers. Generalized estimating equation models were used to examine the correlation of allograft histology or infection events with protein-normalized BALF CCSP. We performed multivariable Cox regression to determine the association between a time-dependent binary indicator of normalized BALF CCSP level below the median in the first posttransplant year and development of probable CLAD. RESULTS: Normalized BALF CCSP concentrations were 19% to 48% lower among samples corresponding to histological allograft injury as compared with healthy samples. Patients who experienced any occurrence of a normalized BALF CCSP level below the median over the first posttransplant year had a significant increase in probable CLAD risk independent of other factors previously linked to CLAD (adjusted hazard ratio 1.95; p = 0.035). CONCLUSIONS: We discovered a threshold for reduced BALF CCSP to discriminate future CLAD risk; supporting the utility of BALF CCSP as a tool for early posttransplant risk stratification. Additionally, our finding that low CCSP associates with future CLAD underscores a role for club cell injury in CLAD pathobiology.

Experiences and perceptions of receiving and prescribing rehabilitation in adults with cystic fibrosis undergoing lung transplantation.

BACKGROUND: Rehabilitation is prescribed to optimize fitness before lung transplantation (LTx) and facilitate post-transplant recovery. Individuals with cystic fibrosis (CF) may experience unique health issues that impact participation. METHODS: Patient and healthcare provider semi-structured interviews were administered to explore perceptions and experiences of rehabilitation before and after LTx in adults with CF. Interviews were analyzed via inductive thematic analysis. RESULTS: Eleven participants were interviewed between February and October 2021 (five patients, median 28 (IQR 27-29) years, one awaiting re-LTx, four following first or second LTx) and six healthcare providers. Rehabilitation was delivered both in-person and virtually using a remote monitoring App. Six key themes emerged: (i) structured exercise benefits both physical and mental health, (ii) CF-specific physiological impairments were a large barrier, (iii) supportive in-person or virtual relationships facilitated participation, (iv) CF-specific evidence and resources are needed, (v) tele-rehabilitation experiences during the COVID-19 pandemic resulted in preferences for a hybrid model and (vi) virtual platforms and clinical workflows require further optimization. There was good engagement with remote data entry alongside satisfaction with virtual support. CONCLUSIONS: Structured rehabilitation provided multiple benefits and a hybrid model was preferred going forward. Future optimization of tele-rehabilitation processes and increased evidence to support exercise along the continuum of CF care are needed.

Evaluation of Frailty Measures and Short-term Outcomes After Lung Transplantation.

BACKGROUND: Frailty, measured as a single construct, is associated variably with poor outcomes before and after lung transplantation. The usefulness of a comprehensive frailty assessment before transplantation is unknown. RESEARCH QUESTION: How are multiple frailty constructs, including phenotypic and cumulative deficit models, muscle mass, exercise tolerance, and social vulnerabilities, measured before transplantation, associated with short-term outcomes after lung transplantation? STUDY DESIGN AND METHODS: We conducted a retrospective cohort study of 515 lung recipients who underwent frailty assessments before transplantation, including the short physical performance battery (SPPB), transplant-specific frailty index (FI), 6-min walk distance (6MWD), thoracic sarcopenia, and social vulnerability indexes. We tested the association between frailty measures before transplantation and outcomes after transplantation using logistic regression to model 1-year survival and zero-inflated negative binomial regression to model hospital-free days (HFDs) in the first 90 days after transplantation. Adjustment covariates included age, sex, native lung disease, transplantation type, lung allocation score, BMI, and primary graft dysfunction. RESULTS: Before transplantation, 51.3% of patients were frail by FI (FI ≥ 0.25) and no patients were frail by SPPB. In multivariate adjusted models that also included FI, SPPB, and 6MWD, greater frailty by FI, but not SPPB, was associated with fewer HFDs (-0.006 per 0.01 unit worsening; 95% CI, -0.01 to -0.002 per 0.01 unit worsening) among discharged patients. Greater SPPB deficits were associated with decreased odds of 1-year survival (OR, 0.51 per 1 unit worsening; 95% CI, 0.28-0.93 per 1 unit worsening). Correlation among frailty measurements overall was poor. No association was found between thoracic sarcopenia, 6MWD, or social vulnerability assessments and short-term outcomes after lung transplantation. INTERPRETATION: Both phenotypic and cumulative deficit models measured before transplantation are associated with short-term outcomes after lung transplantation. Cumulative deficit measures of frailty may be more relevant in the first 90 days after transplantation, whereas phenotypic frailty may have a stronger association with 1-year survival.

Reflux Surgery in Lung Transplantation: A Multicenter Retrospective Study.

BACKGROUND: Aspiration has been associated with graft dysfunction after lung transplantation, leading some to advocate for selective use of fundoplication despite minimal data supporting this practice. METHODS: We performed a multicenter retrospective study at 4 academic lung transplant centers to determine the association of gastroesophageal reflux disease and fundoplication with bronchiolitis obliterans syndrome and survival using Cox multivariable regression. RESULTS: Of 542 patients, 136 (25.1%) underwent fundoplication; 99 (18%) were found to have reflux disease without undergoing fundoplication. Blanking the first year after transplantation, fundoplication was not associated with a benefit regarding freedom from bronchiolitis obliterans syndrome (hazard ratio [HR], 0.93; 95% CI, 0.58-1.49) or death (HR, 0.97; 95% CI, 0.47-1.99) compared with reflux disease without fundoplication. However, a time-dependent adjusted analysis found a slight decrease in mortality (HR, 0.59; 95% CI, 0.28-1.23; P = .157), bronchiolitis obliterans syndrome (HR, 0.68; 95% CI, 0.42-1.11; P = .126), and combined bronchiolitis obliterans syndrome or death (HR, 0.66; 95% CI, 0.42-1.04; P = .073) in the fundoplication group compared with the gastroesophageal reflux disease group. CONCLUSIONS: Although a statistically significant benefit from fundoplication was not determined because of limited sample size, follow-up, and potential for selection bias, a randomized, prospective study is still warranted.

Statin Use May Be Associated With a Lower Risk of Invasive Aspergillosis in Lung Transplant Recipients.

BACKGROUND: Statins are competitive inhibitors of 3-hydroxy-3methylglutaryl coenzyme A reductase (HMG-CoA reductase) that catalyses HMG-CoA conversion to mevalonate, a process involved in synthesizing cholesterol in humans and ergosterol in fungi. The effect of statin use on the risk of development of invasive aspergillosis (IA) in lung transplant recipients (LTRs) is not well documented. METHODS: This retrospective study included LTRs from 2010 to 2017 who were followed for one-year post-transplant. Proven or probable IA was diagnosed as per ISHLT criteria. We performed a multivariable Cox proportional hazards model of the association between IA and statin use (minimum of 2 weeks duration prior to IA), adjusting for other known IA risk factors. RESULTS: We identified 785 LTRs, 44% female, mean age 53 years old, the most common underlying disease being pulmonary fibrosis (23.8%). In total, 451 LTRs (57%) received statins post-transplant, atorvastatin was the most commonly used statin (68%). The mean duration of statins post-transplant was 347 days (interquartile range [IQR]: 305 to 346). And 55 (7%) LTRs developed IA in the first-year post-transplant. Out of these 55 LTRs, 9 (16.3%) had received statin before developing IA. In multivariable analysis, statin use was independently associated with a lower risk of IA (P = .002, SHR 0.30, 95% confidence interval [CI] 95% .14-.64). Statin use was also associated with a lower incidence of post-transplant Aspergillus colonization, 114 (34%) in the no statin group vs 123 (27%) in the statin group (P = .038). CONCLUSIONS: The use of statin for a minimum of two weeks during the first-year post-transplant was associated with a 70% risk reduction of IA in LTRs.

Early Change in Lower Limb Strength and Function in Lung Transplant Patients After Center-Based and Telerehabilitation.

PURPOSE: The aim of this study was to examine the change and relationship among quadriceps torque (QT) and physical function in adult lung transplant (LTx) patients undergoing rehabilitation. METHODS: A prospective study assessed 6-min walk test (6MWT) distance, QT, and Short Physical Performance Battery (SPPB) at the start of pre-habilitation and 10-12 wk post-LTx. Functional outcomes were examined for within-group differences for participants who completed center-based rehabilitation between September 2019 and March 2020 and participants who completed telerehabilitation ("telerehab") between March 2020 and June 2021 during COVID-19. Relationships between QT, SPPB, and 6MWT were examined pre- and post-LTx. RESULTS: A total of 49 LTx recipients were included (30 men, 61 [56-67] yr, 26 center-based rehab, and 23 telerehab). The 6MWT increased (median 75 m: 95% CI, 35 - 117, P < .0001), and the telerehab group showed an LTx decrease in QT (-9.6 Nm: 95% CI, -29 to -2.3, P = .02) and an increased gait speed (0.21 m/sec: 95% CI, 0.11 - 0.47, P < .0001). Pre-LTx QT showed a moderate correlation to pre-LTx SPPB ( r = 0.41, P = .004) and weak correlations to gait speed and 6MWT ( r ranging from 0.21 to 0.35, P < .05). Post-LTx QT showed moderate correlations to post-LTx SPPB ( r = 0.43, P = .002), gait speed ( r = 0.54, P < .001), five-time sit-to-stand ( r =-0.57, P < .0001), and 6MWT ( r = 0.62, P < .0001). CONCLUSIONS: Early post-LTx 6MWT and gait speed increased with no improvement in QT or other SPPB components. Correlations between QT and measures of exercise capacity and lower limb function were stronger post-LTx. Serial measurements may further inform functional trajectories and rehabilitation models.

Strongyloides hyper-infection in a lung transplant recipient: Case report and review of the literature.

CASE PRESENTATION: A 63-year-old man with a left single lung transplant for end-stage combined restrictive and obstructive lung disease developed persistent pulmonary infiltrates and recurrent gram-negative bacteremia post-transplant. Bronchoalveolar lavage fluid revealed a nematode on Papanicolau staining compatible with Strongyloides stercoralis larvae on day 50 post-transplant. Although Strongyloides serology performed post-transplant was negative, a retrospective review of the medical record revealed marked peripheral blood eosinophilia on several occasions before transplantation. Despite reduction in immunosuppression and treatment with albendazole and ivermectin, the patient developed another episode of Escherichia coli bacteremia. He died 3 months post-transplant from pulmonary and neurological complications. DIAGNOSIS: Strongyloides hyper-infection. DISCUSSION: Strongyloides hyper-infection syndrome is known to occur in immunocompromised patients, but it has only been reported once in a lung transplant recipient. This case illustrates the importance of screening for parasitic infections before transplantation in patients with marked eosinophilia, especially among immigrants from countries in which Strongyloides is endemic. Hyper-infection syndrome may appear years after infection in the context of immunosuppression or immunodeficiency. This case also highlights the association between Strongyloides hyper-infection and bacteremia with enteric organisms.

PRÉSENTATION DU CAS: Un homme de 63 ans ayant subi une transplantation du poumon gauche à cause d'une pneumopathie en phase terminale à la fois restrictive et obstructive a développé des infiltrats pulmonaires persistants et une bactériémie à Gram négatif récurrente après la transplantation. À la coloration de Papanicolau, le liquide du lavage bronchoalvéolaire a révélé un nématode compatible avec des larves de Strongyloides stercoralis le cinquantième jour après la transplantation. Même si la sérologie du Strongyloides effectuée après la transplantation était négative, une analyse rétrospective de son dossier médical a révélé une éosinophilie sanguine périphérique marquée à plusieurs occasions avant la transplantation. Malgré la diminution de l'immunodépression et un traitement à l'albendazole et à l'ivermectine, le patient a contracté une nouvelle bactériémie à Escherichia coli. Il est décédé de complications pulmonaires et neurologiques trois mois après la transplantation. DIAGNOSTIC: Hyperinfestation à Strongyloides. DISCUSSION: On sait que le syndrome d'hyperinfestation à Strongyloides se déclare chez des patients immunodéprimés, mais il n'a été signalé qu'une fois chez un transplanté du poumon. Ce cas démontre l'importance du dépistage d'infections parasitaires avant la transplantation chez des patients atteints d'éosinophilie marquée, notamment chez des immigrants de pays où le Strongyloides est endémique. Le syndrome d'hyperinfestation peut se manifester des années après l'infection en cas d'immunodépression ou d'immunodéficience. Ce cas fait également ressortir l'association entre l'hyperinfestation à Strongyloides et la bactériémie causée par des organismes entériques.

Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation.

BACKGROUND: Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. METHODS: We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d = 18), a frailty index (FI, d = 66) and a lifestyle/social vulnerability index (LSVI, d = 10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. RESULTS: We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. CONCLUSIONS: In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.

Utility of bile acids in large airway bronchial wash versus bronchoalveolar lavage as biomarkers of microaspiration in lung transplant recipients: a retrospective cohort study.

BACKGROUND: Bronchoalveolar lavage (BAL) is a key tool in respiratory medicine for sampling the distal airways. BAL bile acids are putative biomarkers of pulmonary microaspiration, which is associated with poor outcomes after lung transplantation. Compared to BAL, large airway bronchial wash (LABW) samples the tracheobronchial space where bile acids may be measurable at more clinically relevant levels. We assessed whether LABW bile acids, compared to BAL bile acids, are more strongly associated with poor clinical outcomes in lung transplant recipients. METHODS: Concurrently obtained BAL and LABW at 3 months post-transplant from a retrospective cohort of 61 lung transplant recipients were analyzed for taurocholic acid (TCA), glycocholic acid (GCA), and cholic acid by mass spectrometry and 10 inflammatory proteins by multiplex immunoassay. Associations between bile acids with inflammatory proteins and acute lung allograft dysfunction were assessed using Spearman correlation and logistic regression, respectively. Time to chronic lung allograft dysfunction and death were evaluated using multivariable Cox proportional hazards and Kaplan-Meier methods. RESULTS: Most bile acids and inflammatory proteins were higher in LABW than in BAL. LABW bile acids correlated with inflammatory proteins within and between sample type. LABW TCA and GCA were associated with acute lung allograft dysfunction (OR = 1.368; 95%CI = 1.036-1.806; P = 0.027, OR = 1.064; 95%CI = 1.009-1.122; P = 0.022, respectively). No bile acids were associated with chronic lung allograft dysfunction. Adjusted for risk factors, LABW TCA and GCA predicted death (HR = 1.513; 95%CI = 1.014-2.256; P = 0.042, HR = 1.597; 95%CI = 1.078-2.366; P = 0.020, respectively). Patients with LABW TCA in the highest tertile had worse survival compared to all others. CONCLUSIONS: LABW bile acids are more strongly associated than BAL bile acids with inflammation, acute lung allograft dysfunction, and death in lung transplant recipients. Collection of LABW may be useful in the evaluation of microaspiration in lung transplantation and other respiratory diseases.

Prognostic implications of and clinical risk factors for acute lung injury and organizing pneumonia after lung transplantation: Data from a multicenter prospective cohort study.

We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (>90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention.

Feasibility of Virtual Assessment of Physical Frailty in Solid Organ Transplant Recipients: A Single Center, Observational Study.

Objectives: To describe the feasibility of virtual assessments of physical frailty in solid organ transplant (SOT) recipients using a modified Fried Frailty Index (mFFI) and Short Physical Performance Battery (SPPB), and to describe the prevalence of frailty 12-months post-transplant using virtual assessment. Methods: Virtual assessments were performed using an e-questionnaire and a video-call for functional tests. Feasibility variables included: internet quality, video-call duration, presence of a companion, and adverse events. Results: 34 SOT recipients, median age 62 (46-67), 76% lung recipients, 47% female, were included. The video-call had a median duration of 12 minutes (10-15 min), without adverse events. A companion was present in 23 (68%) video-call assessments. Fifteen SOT recipients (44%) were classified as pre-frail by the mFFI, and none were frail. Three participants (8.8%) were classified as frail using the SPPB. Conclusion: Virtual frailty assessments can be used as an alternative to in-person assessments in SOT recipients.

Plasma CXCL9 and CXCL10 at allograft injury predict chronic lung allograft dysfunction.

Histopathologic lung allograft injuries are putative harbingers for chronic lung allograft dysfunction (CLAD). However, the mechanisms responsible are not well understood. CXCL9 and CXCL10 are potent chemoattractants of mononuclear cells and potential propagators of allograft injury. We hypothesized that these chemokines would be quantifiable in plasma, and would associate with subsequent CLAD development. In this prospective multicenter study, we evaluated 721 plasma samples for CXCL9/CXCL10 levels from 184 participants at the time of transbronchial biopsies during their first-year post-transplantation. We determined the association between plasma chemokines, histopathologic injury, and CLAD risk using Cox proportional hazards models. We also evaluated CXCL9/CXCL10 levels in bronchoalveolar lavage (BAL) fluid and compared plasma to BAL with respect to CLAD risk. Plasma CXCL9/CXCL10 levels were elevated during the injury patterns associated with CLAD, acute rejection, and acute lung injury, with a dose-response relationship between chemokine levels and CLAD risk. Importantly, there were strong interactions between injury and plasma CXCL9/CXCL10, where histopathologic injury associated with CLAD only in the presence of elevated plasma chemokines. We observed similar associations and interactions with BAL CXCL9/CXCL10 levels. Elevated plasma CXCL9/CXCL10 during allograft injury may contribute to CLAD pathogenesis and has potential as a minimally invasive immune monitoring biomarker.