Small airway brush gene expression predicts chronic lung allograft dysfunction and mortality.

Background: Chronic lung allograft dysfunction (CLAD) limits survival following lung transplant, but substantial lung damage occurs before diagnosis by traditional methods. We hypothesized that small airway gene expression patterns could identify CLAD risk before spirometric diagnosis and predict subsequent graft failure.

Methods: Candidate genes from 4 rejection-associated transcript sets were assessed for associations with CLAD or graft failure in a derivation cohort of 156 small airway brushes from 45 CLAD cases and 37 time-matched controls with >1-year stable lung function.

CCR5 drives NK cell-associated airway damage in pulmonary ischemia-reperfusion injury.

Primary graft dysfunction (PGD) limits clinical benefit after lung transplantation, a life-prolonging therapy for patients with end-stage disease. PGD is the clinical syndrome resulting from pulmonary ischemia-reperfusion injury (IRI), driven by innate immune inflammation. We recently demonstrated a key role for NK cells in the airways of mouse models and human tissue samples of IRI.

Decreased Lymphocytic Bronchitis Severity in the Era of Azithromycin Prophylaxis.

Unlabelled: Large-airway lymphocytic inflammation (LB), assessed on endobronchial biopsies, has been associated with acute cellular rejection and chronic lung allograft dysfunction (CLAD). Azithromycin (AZI) prophylaxis has been used to prevent airway inflammation and subsequent CLAD, with inconsistent results. We hypothesized that AZI prophylaxis would be associated with reduced LB, changes in bronchoalveolar lavage (BAL) immune cell populations, and improved CLAD-free survival.

Design and implementation of a digital health home spirometry intervention for remote monitoring of lung transplant function.

Background: We developed an automated, chat-based, digital health intervention using Bluetooth-enabled home spirometers to monitor for complications of lung transplantation in a real-world application.

Methods: A chat-based application prompted patients to perform home spirometry, enter their forced expiratory volume in 1 second (FEV), answer symptom queries, and provided patient education. The program alerted patients and providers to substantial FEV decreases and concerning symptoms.

Development of the Lung Transplant Frailty Scale (LT-FS).

Background: Existing measures of frailty developed in community dwelling older adults may misclassify frailty in lung transplant candidates. We aimed to develop a novel frailty scale for lung transplantation with improved performance characteristics.

Methods: We measured the short physical performance battery (SPPB), fried frailty phenotype (FFP), Body Composition, and serum Biomarkers representative of putative frailty mechanisms.

Subphenotypes of frailty in lung transplant candidates.

Heterogeneous frailty pathobiology might explain the inconsistent associations observed between frailty and lung transplant outcomes. A Subphenotype analysis could refine frailty measurement. In a 3-center pilot cohort study, we measured frailty by the Short Physical Performance Battery, body composition, and serum biomarkers reflecting causes of frailty.

NKG2D receptor activation drives primary graft dysfunction severity and poor lung transplantation outcomes.

Clinical outcomes after lung transplantation, a life-saving therapy for patients with end-stage lung diseases, are limited by primary graft dysfunction (PGD). PGD is an early form of acute lung injury with no specific pharmacologic therapies. Here, we present a large multicenter study of plasma and bronchoalveolar lavage (BAL) samples collected on the first posttransplant day, a critical time for investigations of immune pathways related to PGD.

Depressive symptoms in lung transplant recipients: trajectory and association with mortality and allograft dysfunction.

Objective: Most studies observing an association between depressive symptoms following lung transplantation and mortality are limited to depressive symptom measurement at a single time point, unrelated to allograft function. We aimed to test the association of depressive symptoms over multiple assessments with allograft dysfunction and with mortality.

Methods: We assessed depressive symptoms before and serially up to 3 years after lung transplantation in lung transplant recipients.

Lung Allograft Epithelium DNA Methylation Age Is Associated With Graft Chronologic Age and Primary Graft Dysfunction.

Advanced donor age is a risk factor for poor survival following lung transplantation. However, recent work identifying epigenetic determinants of aging has shown that biologic age may not always reflect chronologic age and that stressors can accelerate biologic aging. We hypothesized that lung allografts that experienced primary graft dysfunction (PGD), characterized by poor oxygenation in the first three post-transplant days, would have increased biologic age.

Enabling antibiotic allergy evaluations and reintroduction of first-line antibiotics for patients with cystic fibrosis.

Background: Patients with cystic fibrosis (CF) often have a history of antibiotic adverse drug reactions (ADRs) that pose a barrier to receiving recommended first-line treatment. Targeted antibiotic allergy evaluations are increasingly recognized as an important strategy for optimization of antimicrobial stewardship.

Objective: To improve first-line antibiotic use in patients with CF with antibiotic ADRs by streamlining access to antibiotic allergy evaluations and standardizing documentation of plans for antibiotic reintroduction.

The association of post-operative delirium with patient-reported outcomes and mortality after lung transplantation.

Post-operative delirium after lung transplantation is common. Its associations with health-related quality of life (HRQL), depression, and mortality remains unknown. In 236 lung transplant recipients, HRQL and depressive symptoms were assessed as part of a structured survey battery before and after transplantation.

Construct and Predictive Validity of Sarcopenia in Lung Transplant Candidates.

Sarcopenia is associated with disability and death. The optimal definition and clinical relevance of sarcopenia in lung transplantation remain unknown. To assess the construct and predictive validity of sarcopenia definitions in lung transplant candidates.

Chronic lung allograft dysfunction small airways reveal a lymphocytic inflammation gene signature.

Chronic lung allograft dysfunction (CLAD) is the major barrier to long-term survival following lung transplantation, and new mechanistic biomarkers are needed. Lymphocytic bronchitis (LB) precedes CLAD and has a defined molecular signature. We hypothesized that this LB molecular signature would be associated with CLAD in small airway brushings independent of infection.

Primary graft dysfunction attenuates improvements in health-related quality of life after lung transplantation, but not disability or depression.

Disability, depressive symptoms, and impaired health-related quality of life (HRQL) are common among patients with life-threatening respiratory compromise. We sought to determine if primary graft dysfunction (PGD), a syndrome of acute lung injury, attenuates improvements in patient-reported outcomes after transplantation. In a single-center prospective cohort, we assessed disability, depressive symptoms, and HRQL before and at 3- to 6-month intervals after lung transplantation.

Cystic Fibrosis Lung Transplant Recipients Have Suppressed Airway Interferon Responses during Infection.

Lung transplantation can be lifesaving in end-stage cystic fibrosis (CF), but long-term survival is limited by chronic lung allograft dysfunction (CLAD). Persistent upper airway (PsA) colonization can seed the allograft. While PsA infection is associated with CLAD in non-CF recipients, this association is less clear for CF recipients experiencing PsA recolonization.

Improvements in frailty contribute to substantial improvements in quality of life after lung transplantation in patients with cystic fibrosis.

Background: While lung transplantation (LTx) improves health-related quality of life (HRQL) in cystic fibrosis (CF), the determinants of this improvement are unknown. In other populations, frailty-a syndrome of vulnerability to physiologic stressors-is associated with disability and poor HRQL. We hypothesized that improvements in frailty would be associated with improved disability and HRQL in adults with CF undergoing LTx.

Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation.

Cystic fibrosis (CF) lung disease is characterized by an inflammatory response that can lead to terminal respiratory failure. The cystic fibrosis transmembrane conductance regulator (CFTR) is mutated in CF, and we hypothesized that dysfunctional CFTR in platelets, which are key participants in immune responses, is a central determinant of CF inflammation. We found that deletion of CFTR in platelets produced exaggerated acute lung inflammation and platelet activation after intratracheal LPS or Pseudomonas aeruginosa challenge.

Tacrolimus trough monitoring guided by mass spectrometry without accounting for assay differences is associated with acute kidney injury in lung transplant recipients.

Purpose: Tacrolimus is a nephrotoxic immunosuppressant historically monitored via enzyme-based immunoassay (IA). After 2011, the 2 largest laboratory companies in the United States implemented tacrolimus quantification by liquid chromatography-mass spectrometry (LC-MS); this method excludes metabolites, potentially resulting in lower quantified drug concentrations. We sought to determine if tacrolimus therapeutic drug monitoring via LC-MS, as performed using trough targets originally derived from IA values, influences clinical outcomes.

Frailty trajectories in adult lung transplantation: A cohort study.

Background: Frailty is common in adults with advanced lung disease and is associated with death before and after lung transplantation. We aimed to determine whether frailty changes from before to after the lung transplant.

Methods: In a single-center, prospective cohort study among adults undergoing lung transplantation from 2010 to 2017, we assessed frailty by the Short Physical Performance Battery (SPPB; higher scores reflect less frailty) and Fried Frailty Phenotype (FFP; higher scores reflect greater frailty) before and repeatedly up to 36 months after transplant.

Management and clinical outcomes after lung transplantation in patients with pre-transplant Mycobacterium abscessus infection: A single center experience.

Background: Preoperative Mycobacterium abscessus infection is often considered a contraindication to lung transplantation because of its association with poor outcomes after transplant. Detailed strategies for bridging to transplant, post-operative management, and data regarding outcomes are lacking.

Methods: We reviewed outcomes in subjects with M abscessus infection who underwent lung transplantation between 2010 and 2018 at the University of California San Francisco.

Gene signatures common to allograft rejection are associated with lymphocytic bronchitis.

Lymphocytic bronchitis (LB) precedes chronic lung allograft dysfunction. The relationships of LB (classified here as Endobronchial or E-grade rejection) to small airway (A- and B-grade) pathologies are unclear. We hypothesized that gene signatures common to allograft rejection would be present in LB.

Improvement in patient-reported outcomes after lung transplantation is not impacted by the use of extracorporeal membrane oxygenation as a bridge to transplantation.

Objective: Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. The impact of preoperative ECMO on health-related quality of life (HRQL) and depressive symptoms after lung transplantation remains unknown, however.

Methods: In a single-center prospective cohort study, we assessed HRQL and depressive symptoms before and at 3, 6, and 12 months after lung transplantation using the Short Form 12 Physical and Mental Component Scores (SF12-PCS and SF12-MCS), Airway Questionnaire 20-Revised (AQ20R), EuroQol 5D (EQ5D), and Geriatric Depression Scale (GDS).

Cystic Fibrosis Transitions of Care: Lessons Learned and Future Directions for Cystic Fibrosis.

Advances in cystic fibrosis (CF) care transformed the condition from one considered lethal by age 7 into a chronic illness (median lifespan, >40 years). With the growing numbers of adults with CF voicing their preference for care in age appropriate settings, the CF community met the challenge by developing an adult-focused care system modeled on the highly successful pediatric CF centers. Adult CF programs ensure lifelong CF specialty care.