Defining a natural killer cell-enriched molecular rejection-like state in lung transplant transbronchial biopsies.

In lung transplantation, antibody-mediated rejection (AMR) diagnosed using the International Society for Heart and Lung Transplantation criteria is uncommon compared with other organs, and previous studies failed to find molecular AMR (ABMR) in lung biopsies. However, understanding of ABMR has changed with the recognition that ABMR in kidney transplants is often donor-specific antibody (DSA)-negative and associated with natural killer (NK) cell transcripts. We therefore searched for a similar molecular ABMR-like state in transbronchial biopsies using gene expression microarray results from the INTERLUNG study (#NCT02812290). After optimizing rejection-selective transcript sets in a training set (N = 488), the resulting algorithms separated an NK cell-enriched molecular rejection-like state (NKRL) from T cell-mediated rejection (TCMR)/Mixed in a test set (N = 488). Applying this approach to all 896 transbronchial biopsies distinguished 3 groups: no rejection, TCMR/Mixed, and NKRL. Like TCMR/Mixed, NKRL had increased expression of all-rejection transcripts, but NKRL had increased expression of NK cell transcripts, whereas TCMR/Mixed had increased effector T cell and activated macrophage transcripts. NKRL was usually DSA-negative and not recognized as AMR clinically. TCMR/Mixed was associated with chronic lung allograft dysfunction, reduced one-second forced expiratory volume at the time of biopsy, and short-term graft failure, but NKRL was not. Thus, some lung transplants manifest a molecular state similar to DSA-negative ABMR in kidney and heart transplants, but its clinical significance must be established.

Systemic corticosteroids for outpatient respiratory viral infections in lung transplant recipients.

INTRODUCTION: Respiratory viral infections (RVI) in lung transplant recipients (LTR) have variably been associated with rejection and chronic lung allograft dysfunction. Our center has used systemic corticosteroids to treat outpatient RVI in some cases, but evidence is limited. We reviewed all adult LTR diagnosed with outpatient RVI January 2017 to December 2019. The primary outcome was recovery of lung function (forced expiratory volume in 1 s [FEV1]) at next stable visit between 1 and 12 months postinfection, expressed as a ratio over stable preinfection FEV1 (FEV1 recovery ratio). METHODS: We identified 100 adult LTR with outpatient RVI diagnoses eligible for study, 36% of whom received corticosteroids. We modelled the adjusted association between corticosteroid use and FEV1 recovery ratio using linear regression. RESULTS: Steroid-treated patients had a lower FEV1 presentation ratio (0.92 vs. 1.04, p = .0070) and were more likely to have chronic lung allograft dysfunction at time of infection (25% vs. 5%, p = .0077). Mean FEV1 recovery ratio was 1.02 (SD 0.19) with no association with corticosteroid therapy via multivariable linear regression (p = .5888). CONCLUSIONS: Steroid treatment was not associated with FEV1 recovery. This suggests corticosteroids may not have a role in the management of RVI in this population.

Transcripts associated with chronic lung allograft dysfunction in transbronchial biopsies of lung transplants.

Transplanted lungs suffer worse outcomes than other organ transplants with many developing chronic lung allograft dysfunction (CLAD), diagnosed by physiologic changes. Histology of transbronchial biopsies (TBB) yields little insight, and the molecular basis of CLAD is not defined. We hypothesized that gene expression in TBBs would reveal the nature of CLAD and distinguish CLAD from changes due simply to time posttransplant. Whole-genome mRNA profiling was performed with microarrays in 498 prospectively collected TBBs from the INTERLUNG study, 90 diagnosed as CLAD. Time was associated with increased expression of inflammation genes, for example, CD1E and immunoglobulins. After correcting for time, CLAD manifested not as inflammation but as parenchymal response-to-wounding, with increased expression of genes such as HIF1A, SERPINE2, and IGF1 that are increased in many injury and disease states and cancers, associated with development, angiogenesis, and epithelial response-to-wounding in pathway analysis. Fibrillar collagen genes were increased in CLAD, indicating matrix changes, and normal transcripts were decreased-dedifferentiation. Gene-based classifiers predicted CLAD with AUC 0.70 (no time-correction) and 0.87 (time-corrected). CLAD related gene sets and classifiers were strongly prognostic for graft failure and correlated with CLAD stage. Thus, in TBBs, molecular changes indicate that CLAD primarily reflects severe parenchymal injury-induced changes and dedifferentiation.

Mismatched perfusion defects on routine ventilation-perfusion scans after lung transplantation.

BACKGROUND: Incidental pulmonary embolism (PE) is a challenging entity with unclear treatment implications. Our program performs routine ventilation-perfusion (VQ) scans at 3-months post-transplant to establish airway and vascular function. We sought to determine the prevalence and prognostic implications of mismatched perfusion defects (MMPD) found on these studies, hypothesizing they would be associated with a benign prognosis. METHODS: We studied VQ scans obtained routinely at 3-months post-transplant from double lung transplant recipients 2005-2016 for studies with MMPD interpreted as high or intermediate probability for PE. We tested the relationship between MMPD and 1-year survival via chi square testing, overall survival via Kaplan Meier analysis with log rank testing and peak forced expiratory volume in 1 second (FEV1) percent predicted via t-testing. RESULTS: Three hundred and seventy-three patients met inclusion criteria, of whom 35 (9%) had VQ scans with MMPDs interpreted by radiologists as high or intermediate probability for PE. Baseline recipient and donor characteristics were similar between groups. Seven patients (20%) in the MMPD group were treated with therapeutic anticoagulation. Patients with MMPD had similar 1-year survival (100% vs. 98%, P = 1.00), overall survival (log rank P = .90) and peak FEV1% predicted (94% [SD 20%] vs. 92% [SD 21%]; P = .58). Anticoagulation did not affect these relationships. CONCLUSION: Mismatched perfusion defects on routine post-transplant VQ scan were not associated with a difference in survival or lung function. A conservative approach to these changes may be a viable option in the absence of other anticoagulation indications.

Hyperammonemia syndrome post-lung transplantation: Case series and systematic review of literature.

BACKGROUND: Hyperammonemia syndrome (HS) is a rare post-transplant complication associated with high morbidity and mortality. Its incidence appears to be higher in lung transplant recipients and its pathophysiology is not well understood. In addition to underlying metabolic abnormalities, it is postulated that HS may be associated with Ureaplasma or Mycoplasma spp. lung infections. Management of this condition is not standardized and may include preemptive antimicrobials, renal replacement, nitrogen scavenging, and bowel decontamination therapies, as well as dietary modifications. METHODS: In this case series, we describe seven HS cases, five of whom had metabolic deficiencies ruled out. In addition, a literature review was performed by searching PubMed following PRISMA-P guidelines. Articles containing the terms "hyperammonemia" and "lung" were reviewed from 1 January 1997 to 31 October 2021. RESULTS: All HS cases described in our center had positive airway samples for Mycoplasmataceae, neurologic abnormalities and high ammonia levels post-transplant. Mortality in our group (57%) was similar to that published in previous cases. The literature review supported that HS is an early complication post-transplant, associated with Ureaplasma spp. and Mycoplasma hominis infections and of worse prognosis in patients presenting cerebral edema and seizures. CONCLUSION: This review highlights the need for rapid testing for Ureaplasma spp. and M. hominis after lung transplant, as well as the necessity for future studies to explore potential therapies that may improve outcomes in these patients.

Association between Mycoplasma and Ureaplasma airway positivity, ammonia levels, and outcomes post-lung transplantation: A prospective surveillance study.

Hyperammonemia syndrome (HS) is a rare complication with high mortality described after lung transplantation. Its pathophysiology is still unclear, but previous studies, including murine models, have linked the identification of Mycoplasmataceae in airway specimens with HS occurrence. This study explores the association between Mycoplasmataceae polymerase chain reaction (PCR) positivity, ammonia levels, HS, and mortality post-lung transplant. Adults who underwent lung transplantation between July 2017 and August 2019 had prospective surveillance testing for Mycoplasma and Ureaplasma using PCR on post-operative bronchoscopy samples. One hundred and fifty-nine patients underwent lung transplantation during the study period. Mean age was 54 (±13) years; baseline diseases were predominantly pulmonary fibrosis (37.7%) and chronic obstructive pulmonary disease (35.8%). Mycoplasma and/or Ureaplasma airway positivity was found in 42 (26.4%) of tested patients, represented mostly by M. salivarium (26/43; 60.4%), U. parvum (7/43; 16.2%), and U. urealyticum (5/43; 11.6%). Median peak ammonia levels were higher in those with Ureaplasma colonization compared to uncolonized patients (p = .04), however, only three patients developed HS. Recipient airway Ureaplasma positivity was independently associated with younger (aOR 0.94, 95% CI 0.88-0.99, p = .04) and female donors (aOR 4.29; 95% CI 1.01-18.2, p = .05).

Atelectasis in primary graft dysfunction survivors after lung transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is an important contributor to early mortality in lung transplant recipients and is associated with impaired lung function. The radiographic sequelae of PGD on computed tomography (CT) have not been characterized. METHODS: We studied adult double lung transplant recipients from 2010 to 2016 for whom protocol 3-month post-transplant CT scans were available. We assessed CTs for changes including pleural effusions, ground glass opacification, atelectasis, centrilobular nodularity, consolidation, interlobular septal thickening, air trapping and fibrosis, and their relationship to prior post-transplant PGD, future lung function, post-transplant baseline lung allograft dysfunction (BLAD), and chronic lung allograft dysfunction (CLAD). RESULTS: Of 237 patients studied, 50 (21%) developed grade 3 PGD (PGD3) at 48 or 72 h. PGD3 was associated with increased interlobular septal thickening (p = .0389) and atelectasis (p = .0001) at 3 months, but only atelectasis remained associated after correction for multiple testing. Atelectasis severity was associated with lower peak forced expiratory volume in 1 s (FEV1) and increased risk of BLAD (p = .0014) but not with future CLAD onset (p = .7789). CONCLUSIONS: Severe PGD was associated with atelectasis on 3-month post-transplant CT in our cohort. Atelectasis on routine CT may be an intermediary identifiable stage between PGD and future poor lung function.

Molecular phenotyping of rejection-related changes in mucosal biopsies from lung transplants.

Diagnosing lung transplant rejection currently depends on histologic assessment of transbronchial biopsies (TBB) with limited reproducibility and considerable risk of complications. Mucosal biopsies are safer but not histologically interpretable. Microarray-based diagnostic systems for TBBs and other transplants suggest such systems could assess mucosal biopsies as well. We studied 243 mucosal biopsies from the third bronchial bifurcation (3BMBs) collected from seven centers and classified them using unsupervised machine learning algorithms. Using the expression of a set of rejection-associated transcripts annotated in kidneys and validated in hearts and lung transplant TBBs, the algorithms identified and scored major rejection and injury-related phenotypes in 3BMBs without need for labeled training data. No rejection or injury, rejection, late inflammation, and recent injury phenotypes were thus scored in new 3BMBs. The rejection phenotype correlated with IFNG-inducible transcripts, the hallmarks of rejection. Progressive atrophy-related changes reflected by the late inflammation phenotype in 3BMBs suggest widespread time-dependent airway deterioration, which was especially pronounced after two years posttransplant. Thus molecular assessment of 3BMBs can detect rejection in a previously unusable biopsy format with potential utility in patients with severe lung dysfunction where TBB is not possible and provide unique insights into airway deterioration. ClinicalTrials.gov NCT02812290.

Clinical judgment versus lung allocation score in predicting lung transplant waitlist mortality.

Canadian lung transplant centers currently use a subjective and dichotomous "Status" ranking to prioritize waitlisted patients for lung transplantation. The lung allocation score (LAS) is an objective composite score derived from clinical parameters associated with both waitlist and post-transplant survival. We performed a retrospective cohort study to determine whether clinical judgment (Status) or LAS better predicted waitlist mortality. All adult patients listed for lung transplantation between 2007 and 2012 at three Canadian lung transplant programs were included. Status and LAS were compared in their ability to predict waitlist mortality using Cox proportional hazards models and C-statistics. Status and LAS were available for 1122 patients. Status 2 patients had a higher LAS compared to Status 1 patients (mean 40.8 (4.4) vs 34.6 (12.5), P = .0001). Higher LAS was associated with higher risk of waitlist mortality (HR 1.06 per unit LAS, 95% CI 1.05, 1.07, P < .001). LAS predicted waitlist mortality better than Status (C-statistic 0.689 vs 0.674). Patients classified as Status 2 and LAS ≥ 37 had the worst survival awaiting transplant, HR of 8.94 (95% CI 5.97, 13.37). LAS predicted waitlist mortality better than Status; however, the best predictor of waitlist mortality may be a combination of both LAS and clinical judgment.

Non-tuberculous mycobacteria in lung transplant recipients: Prevalence, risk factors, and impact on survival and chronic lung allograft dysfunction.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are environmental organisms that colonize or infect lung transplant recipients. Because of differences in populations studied and geographical diversity of species, risk factors for infection and its impact on patient outcomes post transplant are conflicting in the literature. METHODS: We reviewed the charts of 375 lung transplant recipients at the University of Alberta Hospital (Edmonton, Canada) between 2005 and 2014 to assess NTM epidemiology and risk factors. NTM positivity was determined from a laboratory database. The impact of NTM on patient and graft survival was tested by multivariate Cox regression analysis. RESULTS: Non-tuberculous mycobacteria were cultured from 26 patients before and 17 patients after transplant. The most commonly isolated species were Mycobacterium avium complex (55%) and Mycobacterium abscessus (20%). Five-year mortality was significantly higher in those infected with NTM after transplant (P = .016), but there was no difference in chronic lung allograft dysfunction (CLAD) at 5 years (P = .999). Cystic fibrosis and lower body mass index were associated with pre-transplant but not post-transplant NTM. CONCLUSIONS: Isolation of NTM occurred in 7% of patients before and 4.5% of patients after transplant. In this cohort, NTM isolation was associated with increased risk of death but not CLAD onset at 5 years.

High incidence of clinically significant cytomegalovirus infection in CMV D+/R+ lung transplant recipients receiving 3 months of antiviral prophylaxis.

BACKGROUND: Universal antiviral prophylaxis is the preferred preventive strategy for lung transplant recipients (LTRs) at risk of CMV infection. We compared the risk of CMV infection between CMV D+/R + and D-/R + LTRs after 3 months of prophylaxis. METHODS: This was a retrospective review of CMV R + LTRs transplanted between 2005 and 2013. Patients dying before completing 3 months, or receiving >180 days of prophylaxis were excluded. The primary outcome was proportion of LTRs who developed CMV infection and clinically significant CMV infection defined as CMV infection leading to preemptive therapy or CMV disease. RESULTS: We analyzed 90 D+/R + and 72 D-/R + with a median follow up of 730 days. CMV infection and disease was more common in D+/R + compared to D-/R+ (CMV infection 66% vs 40%; P = 0.001; CMV disease 13% vs 4% P = 0.045). Fifty-nine patients developed at least one episode of clinically significant CMV infection (41/90 [46%] D+/R + and 18/72 [25%] D-/R + P=0.007) with recurrence occurring in 29 LTRs (49% of patients with previous CMV infection), of which 22 (76%) were CMV D+/R+. Thirty percent had side effects related to CMV therapy. CONCLUSION: Three months prophylaxis in D+/R + LTRs was associated with high rates of clinically significant CMV infection and recurrences.

Comprehensive outcomes after lung retransplantation: A single-center review.

INTRODUCTION: Lung retransplantation is an important therapy for a growing population of lung transplant recipients with graft failure, but detailed outcome data are lacking. METHODS: We conducted a retrospective cohort study of adult lung retransplant in the Toronto Lung Transplant Program from 2001 to 2013 (n = 38). We analyzed the postoperative course, graft function, renal function, microbiology, donor-specific antibodies (DSA), quality of life, and survival compared to a control cohort of primary transplant recipients matched for age and era. RESULTS: Indication for retransplant was chronic lung allograft dysfunction in most retransplant recipients (35/38, 92%). The postoperative course was more complex after retransplant than primary (ventilation time, 8 vs 2 days, P < .01; ICU stay 14 vs 4 days, P < 0.01), and peak lung function was lower (FEV1 2.2L vs 3L, P < .01). Quality of life scores were comparable, as were renal function, microbiology, and donor-specific antibody formation. Median survival was 1988 days after primary and 1475 days after retransplant (P = .39). CONCLUSIONS: Lung retransplantation is associated with a more complex postoperative course and lower peak lung function, but the long-term medical profile is similar to primary transplant. Lung retransplantation can be beneficial for carefully selected candidates with allograft failure.

Impact of care coordination on Australia's mental health service delivery system.

Care coordination models have developed in response to the recognition that Australia's health and welfare service system can be difficult to access, navigate and is often inefficient in caring for people with severe and persistent mental illness (SPMI) and complex care and support needs. This paper explores how the Australian Government's establishment of the Partners in Recovery (PIR) initiative provides an opportunity for the development of more effective and efficient models of coordinated care for the identified people with SPMI and their families and carers. In conceptualising how the impact of the PIR initiative could be maximised, the paper explores care coordination and what is known about current best practice. The key findings are the importance of having care coordinators who are well prepared for the role, can demonstrate competent practice and achieve better systemic responses focused on the needs of the client, thus addressing the barriers to effective care and treatment across complex service delivery systems.

Metabolic complications in lung transplantation for cystic fibrosis - A case control study.

Background: Metabolic complications post-lung transplant are poorly understood and little is known about how these complications differ between patients with or without cystic fibrosis (pwCF and pwoCF). This study compared post-lung transplant outcomes between pwCF and pwoCF relating to survival and incidence of diabetes, dyslipidaemia, hypertension, and renal impairment. Methods: A retrospective (2004-2017) case-control study involving 90 pwCF and 90 pwoCF (age, sex and year of transplant matched) was conducted. Demographic variables, pre/post-transplant metabolic diseases, blood investigations and medications were extracted. Descriptive statistics were used to describe the cohort. Mann-Whitney U and Chi-squared tests were used to analyse morbidity and mortality data. Regression analyses were used to identity independent variables that impacted clinical outcomes. Kaplan Meier analysis with log-rank testing was used to compare survival. Results: PwCF were younger, had lower BMIs, and were less likely to have pre-transplant extracorporeal membrane oxygenation (ECMO) use. A total of 37 pwCF and 41 pwoCF died (p = 0.65) during the period of observation with no differences in survival. Adjusting for covariates of age, sex and BMI via multiple logistic regression, CF status was associated with a dramatic increased risk of new-onset diabetes post-transplant (adjusted odds ratio 28.7; 95 % CI, 28.76 to 108.7). No other differences in adjusted risk were found. Conclusions: As pwCF had a greater adjusted risk of developing new post-transplant diabetes and experienced metabolic complications at similar rates as pwoCF, the findings highlight the need for rigorous monitoring of pwCF for possible metabolic complications post-transplant.

Safety of Crossing Donor-specific Antibodies in Lung Transplantation.

BACKGROUND: Donor-specific antibodies (DSAs) have been associated with antibody-mediated rejection, chronic lung allograft dysfunction (CLAD), and increased mortality in lung transplant recipients. Our center performs transplants in the presence of DSA, and we sought to evaluate the safety of this practice with respect to graft loss, CLAD onset, and primary graft dysfunction (PGD). METHODS: We reviewed recipients transplanted from 2010 to 2017, classifying them as DSA positive (DSA + ) or negative. We used Kaplan-Meier estimation to test the association between DSA status and time to death or retransplant and time to CLAD onset. We further tested associations with severe PGD and rejection in the first year using logistic regression and Fisher exact testing. RESULTS: Three hundred thirteen patients met inclusion criteria, 30 (10%) of whom were DSA + . DSA + patients were more likely to be female, bridged to transplant, and receive induction therapy. There was no association between DSA status and time to death or retransplant (log rank P = 0.581) nor death-censored time to CLAD onset (log rank P = 0.278), but DSA + patients were at increased risk of severe PGD (odds ratio 2.88; 95% confidence interval, 1.10-7.29; P = 0.031) and more frequent antibody-mediated rejection in the first posttransplant year. CONCLUSIONS: Crossing DSA at time of lung transplant was not associated with an increased risk of death or CLAD in our cohort, but patients developed severe PGD and antibody-mediated rejection more frequently. However, these risks are likely manageable when balanced against the benefits of expanded access for sensitized candidates.

Relative Lung Perfusion on Ventilation-Perfusion Scans After Double Lung Transplant.

BACKGROUND: Pulmonary blood flow can be assessed on ventilation-perfusion (VQ) scan with relative lung perfusion, with a 55% to 45% (or 10%) right-to-left differential considered normal. We hypothesized that wide perfusion differential on routine VQ studies at 3 mo posttransplant would be associated with an increased risk of death or retransplantation, chronic lung allograft (CLAD), and baseline lung allograft dysfunction. METHODS: We conducted a retrospective cohort study on all patients who underwent double-lung transplant in our program between 2005 and 2016, identifying patients with a wide perfusion differential of >10% on a 3-mo VQ scan. We used Kaplan-Meier estimates and proportional hazards models to assess the association between perfusion differential and time to death or retransplant and time to CLAD onset. We used correlation and linear regression to assess the relationship with lung function at time of scan and with baseline lung allograft dysfunction. RESULTS: Of 340 patients who met inclusion criteria, 169 (49%) had a relative perfusion differential of ≥ 10% on a 3-mo VQ scan. Patients with increased perfusion differential had increased risk of death or retransplantation ( P = 0.011) and CLAD onset ( P = 0.012) after adjustment for other radiographic/endoscopic abnormalities. Increased perfusion differential was associated with lower lung function at time of scan. CONCLUSIONS: Wide lung perfusion differential was common after lung transplant in our cohort and associated with increased risk of death, poor lung function, and CLAD onset. The nature of this abnormality and its use as a predictor of future risk warrant further investigation.

Pre-transplant malignancy is associated with increased risk of de novo malignancy post-lung transplantation.

BACKGROUND: At least 20% of lung transplant recipients will be diagnosed with a malignancy within 5 years of transplant. Transplant candidates with a history of pre-transplant malignancy must meet remission criteria before listing to minimize the risk of recurrence, however these patients may have an intrinsic predisposition to developing subsequent cancers which can be amplified by immunosuppression. We assessed whether pre-transplant malignancy was associated with an increased risk of developing malignancy of any type after lung transplant. METHODS: We conducted a single centre retrospective cohort study of patients undergoing lung transplant between January 2006 and December 2017. We used a proportional hazards regression model to test whether preTM was associated with the risk of developing one or more postTM after lung transplant, adjusted for known cancer risk factors. RESULTS: 497 adult patients underwent lung transplantation during the study period and 26 (5.2%) had pre-transplant malignancies. Out of 29 pre-transplant cancer diagnoses, prostate cancer was the most common (17.2%), followed by breast cancer and basal cell carcinoma (13.8% each). 108 (22%) patients developed post-transplant malignancy with a total of 328 cancer diagnoses. The most common post-transplant malignancy was non-melanoma skin cancer (86.3%), followed by solid organ cancers (7.6%). Pre-transplant malignancy was associated with an adjusted HR of 3.24 (95% CI 1.71 to 6.14, p < 0.001) for the development of post-transplant malignancy. Recurrence of the pre-transplant malignancy only occurred in 3 patients post-transplant. CONCLUSIONS: History of pre-transplant malignancy was associated with a more than three times likelihood of development of a post-transplant malignancy compared to recipients without a previous history of cancer, the majority being unrelated to the initial malignancy. These findings highlight the importance of frequent cancer surveillance in lung transplant recipients, especially in those with a history of pre-transplant malignancy.

Corticotropin releasing hormone as an identifier of bronchiolitis obliterans syndrome.

Lung transplantion (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS), an inflammation of the small airways in chronic rejection of a lung allograft. There is great clinical need for a minimally invasive biomarker of BOS. Here, 644 different proteins were analyzed to detect biomarkers that distinguish BOS grade 0 from grades 1-3. The plasma of 46 double lung transplant patients was analyzed for proteins using a high-component, multiplex immunoassay that enables analysis of protein biomarkers. Proximity Extension Assay (PEA) consists of antibody probe pairs which bind to targets. The resulting polymerase chain reaction (PCR) reporter sequence can be quantified by real-time PCR. Samples were collected at baseline and 1-year post transplantation. Enzyme-linked immunosorbent assay (ELISA) was used to validate the findings of the PEA analysis across both time points and microarray datasets from other lung transplantation centers demonstrated the same findings. Significant decreases in the plasma protein levels of CRH, FERC2, IL-20RA, TNFB, and IGSF3 and an increase in MMP-9 and CTSL1 were seen in patients who developed BOS compared to those who did not. In this study, CRH is presented as a novel potential biomarker in the progression of disease because of its decreased levels in patients across all BOS grades. Additionally, biomarkers involving the remodeling of the extracellular matrix (ECM), such as MMP-9 and CTSL1, were increased in BOS patients.

Successful Long-Term Outcome After Transplantation of Lungs Affected by Smoke Inhalation Injury.

We report a case of a 43-year-old woman who underwent double lung transplantation from a donor with severe airway burns following a house fire. The recipient's lung function and quality of life remain excellent 24 months following transplantation. This case is the first to report successful long-term outcomes in transplantation of lungs affected by smoke inhalation.