Michaela Restivo Anderson

Rationale: Primary graft dysfunction (PGD) after lung transplant is associated with increased mortality. Whether PGD increases mortality via long-term effects on allograft function is poorly understood. Objective: Evaluate the association of PGD with potential lung function and chronic lung allograft dysfunction (CLAD). Methods: We included lung transplant recipients enrolled in an 8-center prospective cohort study from 2007-2018. PGD was defined by ISHLT criteria. Linear mixed effects and logistic regression models evaluated the association between PGD and maximum potential forced expiratory volume in 1 second (FEV1) and whether Global Lung Function Initiative defined (GLI) predicted FEV1 was attained, respectively. Flexible parametric survival models evaluated the association between PGD and CLAD, accounting for confounding and mortality as a competing risk. Measurements and Main Results: Among 2419 recipients, 510 had PGD. Recipients with PGD had lower maximum potential FEV1 (-311 ml, 95% CI -245 to -377 ml) and were less likely to achieve GLI-predicted FEV1 (probability difference -12.5%, 95% CI -17 to -8%). 930 recipients developed CLAD (405 obstructive, 525 restrictive) over median (IQR) 5.9 (3.0-8.0 years). The 5-year cumulative incidence of CLAD did not differ by PGD (cumulative difference: -2.2%, 95% CI - 6.4% to 1.9%). This association was not modified by age, sex, BMI, pretransplant diagnosis, or transplant type. PGD was not associated with a difference in cumulative incidence of obstructive or restrictive CLAD (cumulative difference -1.2% and -0.8%, respectively). Conclusion: PGD is associated with reduced lung function and lower likelihood of achieving GLI-predicted maximum potential lung function but not CLAD.

The Lung Transplant Frailty Scale (LT-FS) is a validated binary measure of frailty in lung transplant candidates. We refined the LT-FS Base and Body Composition measures by developing a three-category classification to improve clinical risk stratification and replacing serum C-reactive protein with albumin as a more clinically practical frailty biomarker. We applied a 4-step measure development method to a multicenter prospective cohort study of lung transplant candidates. Low albumin (<3.5 g/dL) replaced high serum C-reactive protein (≥10 mg/L) as the LT-FS biomarker. Cutpoints balancing discrimination, risk prediction, and calibration defined “frail”, “pre-frail”, and “not frail” categories. We then evaluated these category associations with exercise capacity, patient-reported outcomes, and mortality using multivariate linear and Cox regression. Among 419 participants, the refined LT-FS identified a graded increase in mortality risk across frailty categories. Pre-frailty and frailty by LT-FS Body Composition were associated with 2.9-fold (HR 2.9, 95% CI 1.2–6.9) and 7-fold (HR 6.9, 95% CI 2.6–18.2) higher risks of waitlist delisting or death, respectively. After transplant, pre-frailty and frailty by LT-FS Body Composition were associated with 2-fold (HR 2.1, 95% CI 1.2–3.8) and 3.6-fold (HR 3.6, 95% CI 1.8–7.3) higher mortality risk, respectively. Relationships with exercise capacity and disability were less consistent. A refined Lung Transplant Frailty Scale incorporating serum albumin demonstrates strong associations with waitlist and post-transplant mortality. The addition of a pre-frail category better captures the continuum of frailty and improves clinical risk stratification of lung transplant candidates.

Background: Obesity affects one third of patients with interstitial lung disease (ILD) and increases both fatigue and dyspnea in the general population. Fatigue and dyspnea are commonly reported by patients with ILD and are difficult to treat. We hypothesized that higher body mass index (BMI) would associate with greater fatigue and dyspnea, worse health-related quality of life (HRQoL), and greater changes in symptoms over time in a real-world ILD cohort. Methods: We performed a retrospective analysis of a cohort study of participants in the Pulmonary Fibrosis Foundation Registry with BMI and at least one questionnaire available at enrollment. Symptoms were assessed at enrollment, 6, and 12 months using the Fatigue Severity Scale, UCSD Shortness of Breath, and Short-Form Six-Dimension questionnaires. Linear mixed models with random intercept for participant and interaction between time and BMI evaluated whether BMI correlated with symptoms and changes in symptoms over time. We used random-intercept cross-lagged panel models to evaluate the reciprocal relationship between BMI and symptoms. All models were adjusted for baseline age; sex; ILD diagnosis, diabetes, hypertension, coronary artery disease, and depression diagnoses; use of antifibrotics and corticosteroids; use of supplemental oxygen, and pulmonary function, with forced vital capacity and diffusing capacity of the lung for carbon monoxide as time-varying covariates. Results: 1544 participants were included, 1029 (67%) had 12-month data, with mean (standard deviation) age of 68 (10.3) years, 35% were female, 63% had IPF, percent predicted forced vital capacity of 68% (18.1%), and BMI of 29 (5.8) kg/m2; 87% were using anti-fibrotic therapy at enrollment. Higher BMI was associated with greater fatigue and dyspnea but not with HRQoL. BMI did not moderate changes in fatigue (p-value = 0.29), dyspnea (p-value = 0.98), or HRQoL (p-value = 0.91) over time. BMI and fatigue had bidirectional associations over time wherein lower BMI was associated with greater subsequent symptoms, and greater symptoms were associated with lower subsequent BMI. Conclusion: Higher BMI is associated with greater fatigue and dyspnea on average in patients with ILD, independent of comorbidities and medications. Longitudinally, BMI did not moderate change in these symptoms over time. Further work should investigate whether intentional weight loss can improve fatigue and dyspnea in patients with obesity and ILD.

Purpose Obesity is increasingly encountered among patients requiring extracorporeal membrane oxygenation (ECMO) for severe respiratory or cardiac failure. It alters respiratory and cardiovascular physiology and drug pharmacokinetics and introduces technical and logistical challenges that may complicate patient selection, ECMO initiation, cannulation, anticoagulation, and monitoring. This review summarizes current evidence regarding the epidemiology, physiological implications, outcomes, and management of obesity in patients supported with veno-venous (VV) or veno-arterial (VA) ECMO. Results Available evidence, largely retrospective and based on body mass index classifications, suggests that obesity should not be considered a contraindication to VV-ECMO, with outcomes comparable to or potentially better than those of patients without obesity. However, obesity-related respiratory mechanics may exaggerate the apparent severity of lung injury, emphasizing the need for optimized conventional ARDS management, including appropriate ventilatory strategies and prone positioning, before ECMO initiation. In contrast, outcomes during VA-ECMO are more heterogeneous, particularly in extracorporeal cardiopulmonary resuscitation (ECPR), and may be influenced by patient selection, comorbidities, and timing of support. Obesity also creates important technical challenges requiring individualized cannulation, anticoagulation, and perfusion strategies. Conclusion Obesity alone should not preclude access to ECMO, particularly VV-ECMO. Successful management requires anticipation of obesity-related challenges, appropriate infrastructure, and structured multidisciplinary protocols. Further prospective studies are needed to clarify obesity-specific risks, optimize management strategies, and evaluate long-term outcomes. Graphic abstract

Higher body mass index (BMI) increases risk of respiratory failure and death from SARS-CoV-2 infection. BMI is imprecise and fails to account for adipose t