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Background: Peak oxygen uptake (VO 2peak ) remains low after lung transplantation (LTx). We evaluated the effect of high-intensity interval training (HIIT) on VO 2peak , muscular strength, health-related quality of life (HRQOL), pulmonary function, and physical function after LTx., Methods: In this randomized controlled trial, 54 participants were enrolled from 6 to 60 months after LTx. The HIIT group (n = 25) followed a supervised HIIT program, consisting of endurance and strength trainings 3 times a week for 20 weeks. The control group (n = 29) received usual care. The primary outcome was a change in VO 2peak measured by cardiopulmonary exercise testing. The secondary outcomes were changes in 1-repetition maximum (1RM) for arm press and leg press, HRQOL (36-Item Short-Form Health Survey [SF-36]), pulmonary function (forced expiratory volume in 1 sec, diffusing capacity of the lungs for carbon monoxide), and physical function (1RM in handgrip, 15-sec stair run, and 30-sec chair stand)., Results: A total of 46 participants completed the study, including 23 of 25 in the intervention group. For the primary outcome, the intention-to-treat analysis revealed a non-significant between-group difference for change in VO 2peak of 0.7 ml/(kg.min) (95% CI = ‒0.3, 1.8) (p = 0.17). The between-group differences for 1RM arm press and leg press and mental aspect of SF-36 were 4.9 kg (95% CI = ‒0.1, 9.9) (p = 0.05), 11.6 kg (95% CI = 0.1, 23.0) (p < 0.05), and 5.7 kg (95% CI = 0.9, 10.4) (p = 0.02), respectively. There were no between-group differences in pulmonary function or physical function. When excluding participants with an attendance of <70% (n = 16), the between-group difference for VO 2peak was 1.2 ml/(kg.min) (95% CI = 0.1, 2.4) (p = 0.032)., Conclusions: HIIT improved muscular strength and HRQOL but did not improve VO 2peak more than usual care after LTx. However, with acceptable adherence, HIIT appears to have beneficial effects on VO 2peak ., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary fibrosis (PF) is the most common disease indication for lung transplantation. Our recent work implicated an excess of rare genetic variants in the telomere-related genes TERT, RTEL1, and PARN in PF disease risk. The impact of such variants on posttransplant outcomes is uncertain. The objective of this study was to determine if patients with these PF-associated variants have altered rates of posttransplant acute rejection (AR), chronic lung allograft dysfunction (CLAD), and survival., Methods: The study cohort consisted of 262 PF lung transplant recipients previously genetically characterized by whole exome sequencing. Thirty-one patients (11.8%) had variants in TERT, RTEL1, or PARN, whereas 231 (88.2%) did not. Multivariate Cox proportional hazards models adjusted for relevant clinical variables were used to assess the outcomes of death and CLAD. The AR burden was quantified and compared over the first posttransplant year., Results: Patients with PF with disease-associated variants in TERT, RTEL1, or PARN had a significantly higher risk of death (adjusted hazard ratio [HR], 1.82; 95% CI, 1.07-3.08; P = .03) and CLAD (adjusted HR, 2.88; 95% CI, 1.42-5.87; P = .004) than patients without these variants. There was no difference in AR burden or rates of grade 3 primary graft dysfunction between the two groups., Conclusions: Rare variants in the telomere-related genes TERT, RTEL1, or PARN are associated with poor posttransplant outcomes among PF lung transplant recipients. Further research is needed to understand the biological mechanisms by which telomere-related variants increase the risk for death and CLAD., (Published by Elsevier Inc.)

Background: Surgical lung biopsy contributes to establishing a specific diagnosis among many patients with interstitial lung disease (ILD). The risks of death and respiratory failure associated with elective thoracoscopic surgical lung biopsy, and patient characteristics associated with these outcomes, are not well understood., Methods: This is a retrospective cohort study of patients who underwent elective thoracoscopic lung biopsy for ILD between 2008 and 2014, according to The Society of Thoracic Surgeons database. The study determined the incidence of operative mortality and of postoperative respiratory failure. Multivariable models were used to identify risk factors for these adverse outcomes., Results: Among 3,085 patients, 46 (1.5%) died before hospital discharge or within 30 days of thoracoscopic lung biopsy. Postoperative respiratory failure occurred in 90 (2.9%) patients. Significant risk factors for operative mortality among patients with ILD included a diagnosis of pulmonary hypertension, preoperative corticosteroid treatment, and low diffusion capacity., Conclusions: Elective thoracoscopic lung biopsy among patients with ILD is associated with a low risk of operative mortality and postoperative respiratory failure. Attention to the presence of pulmonary hypertension, preoperative corticosteroid treatment, and diffusion capacity may help inform risk stratification for thoracoscopic lung biopsy among patients with ILD., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization., Methods: This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization., Results: A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97)., Conclusion: In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Comorbid chronic obstructive pulmonary disease (COPD) is associated with poor outcomes among patients with cardiovascular disease. The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood., Methods: We analyzed patients from ARISTOTLE, a randomized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism. Using Cox proportional hazards models, we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality, adjusting for treatment allocation, smoking history and other risk factors., Results: COPD was present in 1950 (10.8%) of 18,134 patients with data on pulmonary disease history. After multivariable adjustment, COPD was not associated with risk of stroke or systemic embolism (adjusted HR 0.85 [95% CI 0.60, 1.21], p=0.356). However, COPD was associated with a higher risk of all-cause mortality (adjusted HR 1.60 [95% CI 1.36, 1.88], p<0.001) and both cardiovascular and non-cardiovascular mortality. The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD (HR 0.92 [95% CI 0.52, 1.63] versus 0.78 [95% CI 0.65, 0.95], interaction p=0.617)., Conclusions: COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation, but was not associated with risk of stroke or systemic embolism. The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Mortality is an impractical primary endpoint for clinical trials in patients with idiopathic pulmonary fibrosis who have mild-to-moderate physiological impairment because event rates are low. Change in forced vital capacity (FVC) is widely accepted as a surrogate for mortality and is the most common primary endpoint in clinical trials for this disorder. Use of hospital admission as a predictor for mortality, independent of FVC decline, has not been well defined. We aimed to ascertain the independent and combined association of hospital admission and at least a 10% decrease in FVC with all-cause mortality., Methods: We did a pooled cohort study of 517 patients with idiopathic pulmonary fibrosis from three IPFnet multicentre randomised controlled trials. We compared the incidence of non-elective hospital admission and a 10% or greater reduction in FVC across strata of baseline physiological impairment. We used Cox proportional-hazards models to assess the risk of all-cause mortality associated with these surrogate events, occurring up to a predefined landmark timepoint. The three studies are registered at ClinicalTrials.gov, numbers NCT00650091, NCT00517933, and NCT00957242., Findings: Seven patients died before the landmark timepoint. Of the 510 patients remaining, 38 (7%) were admitted to hospital up to the predefined timepoint and 58 (11%) had a categorical decrease in FVC of at least 10%. Most patients admitted to hospital did not have a 10% or greater decrease in FVC (30 vs eight). Both surrogate events were associated with subsequent time to death from any cause (hazard ratio [HR] for admission 4·05, 95% CI 1·36-12·11 vs HR for 10% or greater decline in FVC 4·68, 1·83-11·99). When causes of hospital admission were considered, only respiratory events were associated with mortality (5·97, 1·81-19·74)., Interpretation: Hospital admission might be an appropriate component of a clinically meaningful composite endpoint that improves the feasibility of clinical trials in idiopathic pulmonary fibrosis. Further studies are needed to refine the most appropriate definition of hospital admission for future trials., Funding: US National Heart, Lung, and Blood Institute (NHLBI), and The Cowlin Family Fund at the Chicago Community Trust., (Copyright © 2015 Elsevier Ltd. All rights reserved.)