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RationalePulmonary hypertension from pulmonary arterial hypertension or parenchymal lung disease is associated with an increased risk for primary graft dysfunction after lung transplantation.ObjectiveWe evaluated the clinical determinants of severe primary graft dysfunction in pulmonary hypertension and developed and validated a prognostic model.MethodsWe conducted a retrospective cohort study of patients in the multicenter Lung Transplant Outcomes Group with pulmonary hypertension at transplant listing. Severe primary graft dysfunction was defined as PaO2/FiO2 ≤200 with allograft infiltrates at 48 or 72 hours after transplantation. Donor, recipient, and operative characteristics were evaluated in a multivariable explanatory model. A prognostic model derived using donor and recipient characteristics was then validated in a separate cohort.ResultsIn the explanatory model of 826 patients with pulmonary hypertension, donor tobacco smoke exposure, higher recipient body mass index, female sex, listing mean pulmonary artery pressure, right atrial pressure and creatinine at transplant, cardiopulmonary bypass use, transfusion volume, and reperfusion fraction of inspired oxygen were associated with primary graft dysfunction. Donor obesity was associated with a lower risk for primary graft dysfunction. Using a 20% threshold for elevated risk, the prognostic model had good negative predictive value in both derivation and validation cohorts (89.1% [95% confidence interval, 85.3-92.8] and 83.3% [95% confidence interval, 78.5-88.2], respectively), but low positive predictive value.ConclusionsSeveral recipient, donor, and operative characteristics were associated with severe primary graft dysfunction in patients with pulmonary hypertension, including several risk factors not identified in the overall transplant population. A prognostic model with donor and recipient clinical risk factors alone had low positive predictive value, but high negative predictive value, to rule out high risk for primary graft dysfunction.

RationaleThe frail phenotype has gained popularity as a clinically relevant measure in adults with advanced lung disease and in critical illness survivors. Because respiratory disease and chronic illness can greatly limit physical activity, the measurement of participation in traditional leisure time activities as a frailty component may lead to substantial misclassification of frailty in pulmonary and critical care patients.ObjectivesTo test and validate substituting the Duke Activity Status Index (DASI), a simple 12-item questionnaire, for the Minnesota Leisure Time Physical Activity (MLTA) questionnaire, a detailed questionnaire covering 18 leisure time activities, as the measure of low activity in the Fried frailty phenotype (FFP) instrument.MethodsIn separate multicenter prospective cohort studies of adults with advanced lung disease who were candidates for lung transplant and older survivors of acute respiratory failure, we assessed the FFP using either the MLTA or the DASI. For both the DASI and MLTA, we evaluated content validity by testing floor effects and construct validity through comparisons with conceptually related factors. We tested the predictive validity of substituting the DASI for the MLTA in the FFP assessment using Cox models to estimate associations between the FFP and delisting/death before transplant in those with advanced lung disease and 6-month mortality in older intensive care unit (ICU) survivors.ResultsAmong 618 adults with advanced lung disease and 130 older ICU survivors, the MLTA had a substantially greater floor effect than the DASI (42% vs. 1%, and 49% vs. 12%, respectively). The DASI correlated more strongly with strength and function measures than did the MLTA in both cohorts. In models adjusting for age, sex, comorbidities, and illness severity, substitution of the DASI for the MLTA led to stronger associations of the FFP with delisting/death in lung transplant candidates (FFP-MLTA hazard ratio [HR], 1.42; 95% confidence interval [CI], 0.55-3.65; FFP-DASI HR, 2.99; 95% CI, 1.03-8.65) and with mortality in older ICU survivors (FFP-MLTA HR, 2.68; 95% CI, 0.62-11.6; FFP-DASI HR, 5.71; 95% CI, 1.34-24.3).ConclusionsThe DASI improves the construct and predictive validity of frailty assessment in adults with advanced lung disease or recent critical illness. This simple questionnaire should replace the more complex MLTA in assessing the frailty phenotype in these populations.

Conceptualized first in the field of geriatrics, frailty is a syndrome characterized by a generalized vulnerability to stressors resulting from an accumulation of physiologic deficits across multiple interrelated systems. This accumulation of deficits results in poorer functional status and disability. Frailty is a "state of risk" for subsequent disproportionate declines in health status following new exposure to a physiologic stressor. Two predominant models have emerged to operationalize the measurement of frailty. The phenotype model defines frailty as a distinct clinical syndrome that includes conceptual domains such as strength, activity, wasting, and mobility. The cumulative deficit model defines frailty by enumerating the number of age-related things wrong with a person. The biological pathways driving frailty include chronic systemic inflammation, sarcopenia, and neuroendocrine dysregulation, among others. In adults with chronic lung disease, frailty is independently associated with more frequent exacerbations of lung disease, all-cause hospitalization, declines in functional status, and all-cause mortality. In addition, frail adults who become critically ill are more likely develop chronic critical illness or severe disability and have higher in-hospital and long-term mortality rates. The evaluation of frailty appears to provide important prognostic information above and beyond routinely collected measures in adults with chronic lung disease and the critically ill. The study of frailty in these populations, however, requires multipronged efforts aimed at refining clinical assessments, understanding the mechanisms, and developing therapeutic interventions.

The article focuses on the need to improve body composition measurements for lung transplant candidates beyond using body mass index (BMI). It discusses the limitations of manual measurements and evaluates the reproducibility and validity of automated measurements using TeraRecon software, aiming to enhance candidate selection and prioritize patients accurately.