Pennington, Kelly M.

Background: We examined the association of adult lung transplant candidates’ self-reported affect with transplant-related outcomes, evaluating whether a positive (vs negative) frame of mind might be protective. Method: Consenting waitlisted candidates from 6 centers completed the questionnaires including the Positive and Negative Affect Schedule annually and posttransplant. Univariate logistic regression analysis was performed to determine the association of baseline affect with outcomes of death or delisting. Models were subsequently adjusted for age, marital status, and education. Results: Questionnaires were completed by 169 candidates (77.9% participation). Mean positive affect, negative affect, and positive-to-negative affect ratio (positivity ratio) were similar to expected norms. The scores of the questionnaire did not change significantly over time. Fifteen (8.9%) waitlisted participants died. Candidates who died while waiting had lower positivity ratios compared to those who survived (1.82 vs 2.45; P = .02). A more negative affect was associated with increased death on the waiting list (adjusted odds ratio [OR] 1.10; P = .021). Conversely, a higher positivity ratio was associated with decreased death while waiting (adjusted OR: 0.45; P = .027). Conclusion: Negative affect may represent a novel risk factor for death on the waitlist. Enhancing positive affect may represent a useful target for psychological optimization in lung transplant candidates.

AbstractBackgroundAntifungal prophylaxis strategies for lung transplant recipients vary without consensus or standard of care. Our current study aims to identify antifungal prophylaxis practices in the United States.MethodsFrom November 29, 2018, to February 15, 2019, we emailed surveys to medical directors of adult lung transplant centers. An alternate physician representative was approached if continued non‐response after three survey attempts. Descriptive statistics were used to report findings.ResultsForty‐four of 62 (71.0%) eligible centers responded. All Organ Procurement and Transplantation Networks were represented. Only four (9.1%) centers used pre‐transplant prophylaxis for prevention of tracheobronchitis (3 of 4) and invasive fungal disease (4 of 4). Thirty‐nine of forty (97.5%) centers used post‐transplant prophylaxis: 36 (90.0%) universal and 3 (7.5%) pre‐emptive/selective prophylaxis. Most centers used nebulized amphotericin with a systemic agent (26 of 36, 72.2%). Thirty‐two of thirty‐six (88.9%) centers continued universal prophylaxis beyond the hospital setting. Duration of prophylaxis ranged from the post‐transplant hospitalization to lifelong with most centers (25 of 36, 69.4%) discontinuing prophylaxis 6 months or less post‐transplant.ConclusionMost United States' lung transplant centers utilize a universal prophylaxis with nebulized amphotericin and a systemic triazole for 6 months or less post‐transplant. Very few centers use pre‐transplant antifungal prophylaxis.

AbstractBackgroundLung transplant recipients are prone to invasive fungal infections prompting many transplant centers to use prolonged triazole antifungal prophylaxis. From a practical standpoint, it is unclear if lung transplant recipients are able to continue prolonged or lifelong prophylaxis without premature discontinuation from side effects, drug interactions, development of fungal disease, or medication cost. We examined the number of patients that are able to reach a prophylactic endpoint and understand the reasons for early termination.MethodsWe conducted a retrospective chart review of all lung and heart‐lung transplant patients at Mayo Clinic Rochester from May 1, 2002 to December 31, 2017. Type, duration, and reason for discontinuation of triazole prophylaxis were examined.ResultsDuring the study period, 193 patients underwent lung or heart‐lung transplantation. Itraconazole, voriconazole, and posaconazole were given to 180, 73, and 60 post‐transplant patients, respectively. Providers switched itraconazole to another prophylactic antifungal medication for reasons other than prophylactic completion in 61.8% (126 out of 204) of exposure episodes; this was similar with voriconazole (68.8%, 53 out of 77, P = 0.41). Posaconazole was actively discontinued significantly less often (18.3%, 11 out of 60, P < 0.05). The most common reasons for discontinuing itraconazole were malabsorption (15.5% of exposure episodes) and concern for breakthrough fungal infection (10.2%). In comparison, the most common reason for voriconazole discontinuation was side effect or intolerance (54.5% of VR exposure episodes vs 9.8% of IT exposure episodes, P < 0.05).ConclusionsItraconazole and posaconazole appeared to have fewer side effects prompting discontinuation than voriconazole, but itraconazole was discontinued more often because of malabsorption and clinical suspicion of fungal infections.

Introduction. The diagnostic standard forPneumocystis jiroveciipneumonia (PCP) is direct microscopic identification; however, in recent years, polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL) samples to detectPneumocystisnucleic acids has proven to be more sensitive and specific. Sputum samples have been presumed inferior to bronchoscopic samples secondary to variability and adequacy of sample collection. We observed several cases of positive sputum PCP-PCR results with negative PCP-PCR BAL results. The aim of the current study was to further characterize the clinical setting and outcomes in patients with positive sputum PCP-PCR samples and negative BAL PCP-PCR samples.Methods. We identified all patients who underwentP. jirovecii-PCR testing at Mayo Clinic between 2011 and 2016. Patients with a positive sputum and negative BAL sample collected within a 14-day time frame were identified and underwent further chart review for demographics, immunocompromised state, and clinical outcome.Results. From 2011 to 2016, 4431 respiratory samples from 3021 unique patients were tested for the presence ofP. jiroveciiby PCR. Fifty-five samples (1.2% of all samples collected) belonging to 24 unique patients (0.79% of patients tested) were identified as having a positive and negative sample collected within 14 days. Of these 24 patients, 10 (46%) patients had a positive sputum or tracheal secretion sample with negative BAL or bronchial washings. Out of these 10 patients, 8 were immunocompromised and 9 underwent treatment for PCP with 6 patients improving.Conclusion. Our results suggest that discordantP. jirovecii-PCR testing results from sputum and bronchoscopic specimens are an infrequent occurrence. Patients with positiveP. jirovecii-PCR sputum/tracheal secretion samples and negative bronchoscopic samples appear to be clinically infected and respond to PCP treatment. SputumP. jirovecii-PCR testing may be a viable alternative to invasive testing.

Tumor necrosis factor α antagonists are increasingly used to treat inflammatory and autoimmune disorders and are associated with increased risk of active tuberculosis. Diagnosis of active tuberculosis in patients taking tumor necrosis factor α antagonists can be challenging owing to increased incidence of extrapulmonary manifestations and false-negative results on current available diagnostic tests. We present a case of a young woman on infliximab for ulcerative colitis who presented with disseminated tuberculosis. As part of a research study, we performed flow cytometric immune profiling, which has previously not been reported in patients with active tuberculosis taking tumor necrosis α antagonists. The flow cytometry results were within the positive thresholds for tuberculosis infection. Flow cytometric immune profiling may be a valid diagnostic tool for patients taking tumor necrosis factor α antagonists.