Lung Allocation Score Exceptions in Persons with Cystic Fibrosis Undergoing Lung Transplant.

Rationale: Lung transplantation can extend the lives of individuals with advanced cystic fibrosis (CF). Until March 2023, the Lung Allocation Score (LAS) was used in the United States to determine transplant priority. Certain clinical events or attributes ("risk events") that are not included in the LAS (e.g., massive hemoptysis) are relatively common and prognostically important in CF and may prompt an exception request to increase priority for donor lungs. The new Lung Composite Allocation Score (CAS) also allows for exceptions based on the same principles. Objectives: To evaluate the frequency of LAS exceptions in persons with CF (PwCFs) listed for lung transplantation and assess whether LAS exceptions are associated with improved waitlist outcomes for PwCFs compared with similarly "at-risk" individuals without LAS exceptions. Methods: A merged dataset combining data from the CF Foundation Patient Registry and the Organ Procurement and Transplantation Network (2005-2019) was used to identify PwCFs listed for lung transplantation. We compared waitlist outcomes between PwCFs with a LAS exception versus those without an exception despite having a risk event. Risk events were defined as an episode of massive hemoptysis, pneumothorax, at least three moderate/severe pulmonary exacerbations, and/or a decrease in forced expiratory volume in 1 second by ⩾30% predicted (absolute) in the prior 12 months. Analyses were performed using competing risk regression with time to transplantation as the primary outcome and death without a transplant as a competing risk. Results: Of 3,538 listings from 3,309 candidates, 2% of listings (n = 81) had at least one exception. Candidates with an exception and those with a risk event but no exception received lung transplants more slowly than people without an exception or risk event (subdistribution hazard ratio [95% confidence interval]: LAS exception cohort, 0.66 [0.52-0.85]; risk event cohort without exceptions, 0.79 [0.72-0.86]). There was no difference between those with LAS exceptions and those at risk without LAS exceptions: subdistribution hazard ratio, 0.84 (0.66-1.08). Conclusions: LAS exceptions are rare in PwCFs listed for lung transplantation. LAS exceptions resulted in a similar time to transplantation for PwCFs compared with similarly at-risk individuals. As we enter the CAS era, these LAS-based results are pertinent to improve risk stratification among PwCFs being considered for lung transplantation.

Palliative Care Consultation and Family-Centered Outcomes in Patients With Unplanned Intensive Care Unit Admissions.

Context: Hospitalized patients who experience unplanned intensive care unit (ICU) admissions face significant challenges, and their family members have unique palliative care needs. Objectives: To identify predictors of palliative care consultation among hospitalized patients with unplanned ICU admissions and to examine the association between palliative care consultation and family outcomes. Methods: We conducted a prospective cohort study of patients with unplanned ICU admissions at two medical centers in Seattle, WA. This study was approved by the institutional review board at the University of Washington (STUDY00008182). Using multivariable logistic regression, we examined associations between patient characteristics and palliative care consultation. Family members completed surveys assessing psychological distress within 90 days of patient discharge. Adjusted ordinal probit or binary logistic regression models were used to identify associations between palliative care consultation and family symptoms of psychological distress. Results: In our cohort (n = 413 patients and 272 family members), palliative care was consulted for 24% of patients during hospitalization (n = 100), with the majority (93%) of these consultations occurring after ICU admission. Factors associated with palliative care consultation after ICU transfer included enrollment site (OR, 2.29; 95% CI: 1.17-4.50), Sequential Organ Failure Assessment score at ICU admission (OR, 1.12; 95% CI: 1.05-1.19), and reason for hospital admission (kidney dysfunction [OR, 7.02; 95% CI: 1.08-45.69]). There was no significant difference in family symptoms of depression or posttraumatic stress based on palliative care consultation status. Conclusions: For patients experiencing unplanned ICU admission, palliative care consultation often happened after transfer and was associated with illness severity, comorbid illness, and hospital site. Patient death was associated with family symptoms of psychological distress.

Hemoptysis and the Risk for Lung Transplant or Death without Transplant in Individuals with Cystic Fibrosis in the United States.

Rationale: Hemoptysis is a common and important complication in persons with cystic fibrosis (PwCF). Despite this, there is limited literature on the impact of hemoptysis on contemporary cystic fibrosis (CF) outcomes. Objectives: Evaluate whether hemoptysis increases the risk of lung transplant or death without a transplant in PwCF. Methods: We reviewed a dataset of PwCF ages 12 years or older from the CFFPR (CF Foundation Patient Registry) that included 29,587 individuals. We identified hemoptysis as our predictor of interest and categorized PwCF as either no hemoptysis, any hemoptysis (submassive and/or massive), or massive hemoptysis. We subsequently evaluated whether hemoptysis, as defined above, was associated with death without transplant or receipt of lung transplant via logistic regression. We adjusted for age, sex, body mass index, forced expiratory volume in one second (FEV1), number of exacerbations, supplemental oxygen use, CF-related diabetes, and Pseudomonas aeruginosa colonization status. Subgroup analyses were performed in advanced lung disease, defined as PwCF with an FEV1 <40% predicted. Results: PwCF with any form of hemoptysis were more likely to progress to lung transplant or die without transplant than PwCF who did not have hemoptysis (odds ratio [OR], 1.3 [95% confidence interval (CI), 1.1-1.7]). The effect size of these associations was larger when hemoptysis events were classified as "massive" (massive hemoptysis OR, 2.2 [95% CI, 1.2-3.8]) or in PwCF with advanced lung disease (massive hemoptysis in advanced lung disease OR, 3.2 [95% CI 1.3-8.2]). Conclusions: Hemoptysis is associated with an increased risk of lung transplant and death without a transplant in PwCF, especially among those with massive hemoptysis or advanced lung disease. Our results suggest that hemoptysis functions as a useful predictor of serious outcomes in PwCF and may be important to incorporate into risk prediction models and/or transplant decisions in CF.

ACTH Infusion Impairs Baroreflex Sensitivity-Implications for Cardiovascular Hypoglycemia-Associated Autonomic Failure.

CONTEXT: Hypoglycemia attenuates cardiovascular homeostatic autonomic control. This attenuation, known as the cardiovascular component of hypoglycemia-associated autonomic failure (HAAF), is characterized most notably by decreased baroreflex sensitivity (BRS) that begins during hypoglycemia and persists until at least the next day, despite return to euglycemia. Understanding the mechanisms underlying this reduction in BRS is important because BRS attenuation is associated with increased morbidity and mortality. OBJECTIVE: The objective of this work is to investigate the role of the adrenocorticotropin (ACTH)-adrenal axis in decreasing BRS. We tested the hypothesis that infusion of ACTH 1-24 (cosyntropin), as compared to placebo, would acutely suppress BRS, and that this decrease in BRS would be present the next day. DESIGN: A double-blind, placebo-controlled, random-order, cross-over study was conducted. SETTING: This study took place in a clinical research center. PARTICIPANTS: Participants included healthy men and women. INTERVENTIONS: Interventions included an intravenous infusion of cosyntropin (70 µg/hour for 2.5 hours in the morning and again in the early afternoon) vs normal saline placebo. MAIN OUTCOME MEASURES: Outcome measures included BRS during and 16 hours after cosyntropin vs placebo infusions. RESULTS: Cosyntropin infusion attenuated BRS (mm Hg/ms) as compared to placebo (baseline 17.8 ±â€…1.38 vs 17.0 ±â€…2.07; during 14.4 ±â€…1.43 vs 17.3 ±â€…1.65; and next day 14.8 ±â€…1.42 vs 18.9 ±â€…2.04; P < .05, time by treatment, analysis of variance). BRS was decreased during the final 30 minutes of the morning cosyntropin infusion as compared to baseline (P < .01) and remained suppressed the next day (16 hours after afternoon infusion) (P < .025). Placebo infusion did not significantly change BRS. Corrected QT interval was not affected. CONCLUSIONS: ACTH attenuates BRS, raising the possibility that hypoglycemia-induced increases in ACTH may contribute to the cardiovascular component of HAAF.