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Background and objective: Antifibrotic therapy with nintedanib or pirfenidone slows disease progression and reduces mortality in patients with idiopathic pulmonary fibrosis (IPF). However, patients with advanced IPF, as defined by forced vital capacity (FVC) < 50% and/or diffusion capacity for carbon monoxide (DLCO) < 30% of predicted, have not been included in randomized trials, and the outcomes of such patients who initiate treatment are not well understood. We determined lung function, disease progression and mortality outcomes following initiation of antifibrotic therapy in patients with advanced IPF at the time of treatment initiation compared to those with mild–moderate IPF. Methods: We included 502 patients enrolled in IPF registries from four Nordic countries. Linear mixed models were used to assess change in FVC and DLCO over time. Cox proportional hazards models were used to assess transplant-free survival and progression- and transplant-free survival. Results: Of 502 patients, 66 (13%) had advanced IPF. Annual change in FVC was −125 ml (95% CI −163, −87) among patients with mild–moderate IPF, and +28 ml (95% CI −96, +152) among those with advanced IPF. Advanced IPF at treatment initiation was associated with poorer transplant-free survival (hazard ratio [HR] 2.39 [95% CI 1.66, 3.43]) and progression- and transplant-free survival (HR 1.60 [95% CI 1.15, 2.23]). Conclusion: In a broadly representative IPF population, patients with advanced IPF at the initiation of antifibrotic therapy did not have greater lung function decline over time compared with those with mild–moderate IPF, but had substantially higher mortality. Prospective studies are needed to determine the effect of antifibrotic therapy in patients with advanced IPF.

Importance: Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis. Objective: To assess the effect of antimicrobial therapy on clinical outcomes. Design, Setting, and Participants: Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020). Interventions: Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight

Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation (LuTx) and is associated with elevated proportions of neutrophils in bronchoalveolar lavage (BAL). Induced sputum is a less-invasive sampling method than BAL and assesses markers of inflammation on the surfaces of large central airways. We wanted to examine whether % neutrophil levels in induced sputum were elevated prior to CLAD diagnosis among LuTx recipients, and whether sputum markers of inflammation can be used as a tool for predicting the development of CLAD. Induced sputum samples were collected at 1, 3, 6, 12, and 24 months post-LuTx in 36 patients with a history of COPD or pulmonary fibrosis, and of these, 16 developed CLAD either during or after the sputum surveillance period. At 2 years, median (IQR) % neutrophils in induced sputum were significantly higher among patients with CLAD compared with those without CLAD [73 (52-80) % vs 59 (41-76) %, p = .01]. Interestingly, we found a significant increase in the rate of change in % neutrophils beginning at 90 days preceding the diagnosis of CLAD. This suggests using sputum neutrophil percentage as a surveillance modality for monitoring lung allograft function after LuTx.

Background Loss of bone mineral and skeletal muscle mass is common after lung transplantation (LTx), and physical activity (PA) may prevent further deterioration. We aimed to assess the effects of 20-week high-intensity training (HIT) on body composition, bone health, and PA in LTx recipients, 6–60 months after surgery. Methods In a randomized controlled trial, 51 LTx recipients underwent Dual-energy X-ray absorptiometry (DXA), and PA level and sedentary time were objectively recorded by accelerometers for seven consecutive days. Of these, 39 participants completed the study, including 19 participants in the HIT group and 20 participants in the standard care group. Results Following the intervention, ANCOVA models revealed a nonsignificant between-group difference for change in lean body mass (LBM) and bone mineral density (BMD) of the lumbar spine of 0.4% (95% CI = −3.2, 1.5) (p = .464) and 1.0% (95% CI=−1.3, 3.4) (p = .373), respectively. Trabecular bone score (TBS) of the lumbar spine (L1-L4), however, increased by 2.2 ± 5.0% in the exercise group and decreased by −1.6 ± 5.9% in the control group, giving a between-group difference of 3.8% (95% CI=0.1, 7.5) (p = .043). There were no between-group differences in PA or sedentary time. Conclusion High-intensity training after LTx improved TBS significantly, but not PA, LBM or BMD.

BACKGROUND While expected need for intensive care after lung transplantation (LTx) does not normally affect organ allocation, it would be useful to estimate whether intensive care capacity is limited. The aim of this study was to assess factors available before LTx to identify predictors of prolonged intensive care unit (ICU) length of stay (LOS) after LTx. METHODS All bilateral LTx recipients excluding re-transplantation and multi-organ transplantation at Oslo University Hospital from 2000 to 2013 were included (n = 277). Predictive factors for ICU LOS were identified using pre- and perioperative variables. RESULTS Univariate analyses showed that recipients with pulmonary arterial hypertension, young age, female gender, low body height, low pretransplant actual total lung capacity (aTLC), and recipients who received an oversized donor lung were at risk for long ICU LOS. Patients with emphysema had lower risk of long ICU LOS. In multivariate analyses, a lower aTLC (p

Common variable immunodeficiency (CVID) is characterized not only by recurrent bacterial infections, but also autoimmune and inflammatory complications including interstitial lung disease (ILD), referred to as granulomatous-lymphocytic interstitial lung disease (GLILD). Some patients with GLILD have waxing and waning radiologic findings, but preserved pulmonary function, while others progress to end-stage respiratory failure. We reviewed 32 patients with radiological features of GLILD from our Norwegian cohort of CVID patients, including four patients with possible monogenic defects. Nineteen had deteriorating lung function over time, and 13 had stable lung function, as determined by pulmonary function testing of forced vital capacity (FVC), and diffusion capacity of carbon monoxide (DLCO). The overall co-existence of other non-infectious complications was high in our cohort, but the prevalence of these was similar in the two groups. Laboratory findings such as immunoglobulin levels and T- and B-cell subpopulations were also similar in the progressive and stable GLILD patients. Thoracic computer tomography (CT) scans were systematically evaluated and scored for radiologic features of GLILD in all pulmonary segments. Pathologic features were seen in all pulmonary segments, with traction bronchiectasis as the most prominent finding. Patients with progressive disease had significantly higher overall score of pathologic features compared to patients with stable disease, most notably traction bronchiectasis and interlobular septal thickening. 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/CT (PET/CT) was performed in 17 (11 with progressive and six with stable clinical disease) of the 32 patients and analyzed by quantitative evaluation. Patients with progressive disease had significantly higher mean standardized uptake value (SUVmean), metabolic lung volume (MLV) and total lung glycolysis (TLG) as compared to patients with stable disease. Nine patients had received treatment with rituximab for GLILD. There was significant improvement in pathologic features on CT-scans after treatment while there was a variable effect on FVC and DLCO.ConclusionPatients with progressive GLILD as defined by deteriorating pulmonary function had significantly greater pathology on pulmonary CT and FDG-PET CT scans as compared to patients with stable disease, with traction bronchiectasis and interlobular septal thickening as prominent features.

Background: The Gender-Age-Physiology (GAP) model predicts mortality in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). Whether GAP stage is associated with health-related quality of life (HRQL) in these diseases is unknown. Objective: To determine the relationship between GAP stage and HRQL in IPF and SSc-ILD. Methods: HRQL was assessed using the Kings Brief Interstitial Lung Disease (K-BILD) questionnaire, scored 0-100 with higher scores indicating better HRQL. GAP stage was calculated based on gender, age, FVC and DLCO, with stages 1-3 indicating successively poorer prognosis. ANCOVA was used to compare K-BILD scores across GAP stages, adjusting for diagnosis and diagnosis-by-GAP interaction. Results: Among 58 patients with IPF, 23 (40%) were in GAP stage 1, 28 (48%) in GAP stage 2, and seven (12%) in GAP stage 3. Among 27 patients with SSc-ILD, 22 (81%) and 5 (19%) were in GAP stages 1 and 2, respectively, and none were in GAP stage 3. Mean (95% CI) K-BILD scores are shown in the table. Higher GAP stage was associated with worse K-BILD score independent of ILD diagnosis (p Table: mean (95% CI) K-BILD total scores: Conclusions: A given difference in GAP stage was associated with a greater difference in HRQL among SSc-ILD patients than among IPF patients, suggesting that lung disease severity has an especially large impact on HRQL in SSc-ILD.

IntroductionIdiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) are fibrotic ILDs with divergent disease populations. Little is known about health-related quality of life (HRQL) in SSc-ILD relative to IPF.MethodsWe used the Kings Brief Interstitial Lung Disease Questionnaire (K-BILD) to compare HRQL in a cross-sectional study of 57 patients with IPF and 29 patients with SSc-ILD. Analysis of covariance was used to adjust for age, gender and lung function.ResultsThe unadjusted mean K-BILD score was 63.1 (95% CI 57.1 to 69.1) among patients with SSc-ILD, as compared with 54.7 (51.8–57.5) among those with IPF (p=0.005). However, this difference in HRQL was attenuated after adjustment for age, gender and lung function. In a multivariable model, only forced vital capacity was associated with K-BILD scores. K-BILD scores were correlated with both forced vital capacity and with other relevant HRQL measures, regardless of ILD diagnosis.DiscussionPatients with SSc-ILD may have better ILD-specific quality of life than patients with IPF, but this difference appears to be driven primarily by better lung function. These results underscore the impact of lung function on HRQL in fibrotic ILD and the utility of K-BILD to assess HRQL in SSc-ILD.

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.

Lung transplantation is an accepted and increasingly employed treatment for advanced lung diseases, but the anticipated survival benefit of lung transplantation is poorly understood.To determine whether and for which patients lung transplantation confers a survival benefit in the modern era of U.S. lung allocation.Data on 13,040 adults listed for lung transplantation between May 2005 and September 2011 were obtained from the United Network for Organ Sharing. A structural nested accelerated failure time model was used to model the survival benefit of lung transplantation over time. The effects of patient, donor, and transplant center characteristics on the relative survival benefit of transplantation were examined.Overall, 73.8% of transplant recipients were predicted to achieve a 2-year survival benefit with lung transplantation. The survival benefit of transplantation varied by native disease group (P = 0.062), with 2-year expected benefit in 39.2 and 98.9% of transplants occurring in those with obstructive lung disease and cystic fibrosis, respectively, and by lung allocation score at the time of transplantation (P 0.001), with net 2-year benefit in only 6.8% of transplants occurring for lung allocation score less than 32.5 and in 99.9% of transplants for lung allocation score exceeding 40.A majority of adults undergoing transplantation experience a survival benefit, with the greatest potential benefit in those with higher lung allocation scores or restrictive native lung disease or cystic fibrosis. These results provide novel information to assess the expected benefit of lung transplantation at an individual level and to enhance lung allocation policy.

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.

Introduction: IPF and systemic sclerosis (SSc)-related interstitial lung disease (ILD) are fibrotic ILDs with a poor prognosis. Assessment of health-related quality of life (HRQL) is important to understand disease trajectory and response to therapy in ILD; however, few studies have compared HRQL in these conditions. Objective: To compare HRQL in SSc-ILD and IPF, independent of lung function. Methods: The Kings Brief Interstitial Lung Disease Questionnaire (K-BILD), validated to assess HRQL in IPF and scored 0-100 with higher scores indicating better HRQL, was used to compare HRQL between patients with IPF (n=58) and SSc-ILD (n=29) in a multi-center cross-sectional study. ANCOVA was used to compare mean K-BILD score between the IPF and SSc-ILD groups, with adjustment for age, gender, FVC and DLCO. Values are presented as mean (SD). Results: Demographics and lung function are listed in table 1. K-BILD score was 69.4 (17.9) among patients with IPF and 80.5 (21.2) among those with SSc-ILD (p =0.014), indicating slightly better HRQL in SSc-ILD. After covariate adjustment, however, no statistical difference in K-BILD was observed between patients with IPF (70.5 [19.3]) and SSc-ILD (79.8 [21.2], p = 0.096). Conclusions: K-BILD scores appeared to be similar between patients with IPF and SSc-ILD after adjusting for age, gender and lung function. This new observation underscores the impact of lung function impairment on HRQL in ILD and the need for treatments that positively impact HRQL by preserving lung function.

Background: Physical fitness after lung transplantation (LTx) is often severely reduced, despite improvement in lung function. Low physical fitness is associated with increased mortality. We hypothesized that high-intensity training (HIT) would improve peak oxygen uptake (VO2peak) and muscular strength after LTx. Methods: In a randomized controlled trial, 54 LTx-recipients were enrolled 6-60 months after surgery. The HIT group (n=25) followed a 20-week endurance and strength training program three times a week. The control group (n=29) followed the hospital’s general recommendations for physical activity. All patients completed a maximal cardiopulmonary exercise test, arm- and leg press pre- and post-intervention. The primary outcome was change in VO2peak as a measure of cardiorespiratory fitness. Secondary outcomes were change in one-repetition maximum (1RM) in arm- and leg press as measures of muscular strength. ANCOVA was used for per-protocol analyses based on ≥70% attendance of the prescribed sessions. Data are presented as mean±SD. Results: VO2peak at baseline was 71±14 and 68±14% of predicted in the HIT- and control group, respectively. No adverse outcomes related to HIT were reported. Conclusion: HIT improved VO2peak and muscular strength. HIT may represent an effective form of exercise therapy that improves physical fitness and health outcomes after lung transplantation.

Introduction: A thorough risk stratification is necessary to select and allocate patients with cystic fibrosis (CF) for lung transplantation (LTx). Aims: We aimed to estimate survival benefit of LTx in CF in Norway by using validated tools for risk stratification. Methods: All CF patients listed for LTx in Norway from 1990 to 2018 were included. Data was obtained from the national LTx registry and by review of medical records. We evaluated post-LTx survival by Kaplan-Meier statistics. A predicted 5-year survival was calculated in retrospect from baseline characteristics at transplant (Liou score) that stratified patients to risk groups. Survival benefit was inferred by comparing observed post-LTx survival with predicted survival in each risk stratum. Results: In total, 67 CF patients were listed for LTx, of whom 14 died on waitlist and 51 were transplanted. Overall 1-year, 5-year and 10-year survival after LTx was 88%, 66% and 62%, respectively. Median survival from listing was 11,4 years (95% CI: 9.2-13,6) and post-LTx 11,1 years (95% CI: 8.0-14,3), while median survival for those who died on waitlist was 0,65 years (95% CI: 0,0-2,7). Comparison of the observed post-LTx 5-year survival to the predicted using the Liou-risk score indicated greatest survival benefit for the risk group that had a modeled 5-year survival without LTx of 30-50%, while those >70% had no survival benefit. Conclusions: The survival rate of CF patients after LTx in Norway is similar to internationally published data. LTx increases survival significantly compared to the observed survival on the waitlist and patients of intermediary risk seem to have the greatest survival benefit.

Background: Organs from older donors are increasingly used in lung transplantation, and studies have demonstrated that this could be safe in selected recipients. However, which recipient groups that have the largest benefit of older organs are unclear. This multicenter study reviews all bilateral lung transplantations (BLTx) from donors 55 years or older stratified by recipient diagnosis and compares outcomes with transplantations from younger donors. Methods: All BLTx recipients (excluding retransplantation) at 5 Scandiatransplant centers between 2000 and 2013 were included (n = 913). Recipients were stratified to diagnosis groups including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and “other.” Intensive care unit (ICU) length of stay (LOS) and survival were assessed. Results: Overall, there was no difference in survival among patients transplanted from donors 55 years or older compared with younger donors. However, in CF recipients, donor age 55 years or older was associated with inferior survival (P = 0.014), and this remained significant in a multivariate model (hazard ratio, 5.0; 95% confidence interval, 1.8–14.1; P = 0.002). There was no significant effect of donor age on survival in recipients with COPD, ILD, or in the “other” group in multivariate models. Utilization of older donors was associated with increased ICU LOS for recipients with CF and ILD, but not in the COPD or “other” group. Conclusions: The BLTx recipients with CF had inferior survival and longer ICU LOS when receiving organs from donors 55 years or older. Recipients with COPD, ILD, or in the “other” group did not have inferior survival in multivariate models.

Background:Based on the argument that symptoms define disease, physicians commonly apply the terms “preclinical” or “subclinical” disease to describe patients with disease-related findings but no accompanying symptoms for connective tissue disease associated interstitial lung disease (CTD-ILD). The term subclinical frequently applies to patients with mild ILD changes on high resolution chest tomography (HRCT), normal forced vital capacity (FVC), and without respiratory symptoms. Previous work in systemic sclerosis (SSc)-ILD did show that patients with even minor extent of ILD at baseline often progressed and had increased mortality risk, suggesting that it is not appropriate to define these patients as “subclinical.”Objectives:To identify the prevalence of subclinical ILD across CTD diagnoses, and assess the rate of progression of lung fibrosis compared to CTD without ILD and with clinical ILD.Methods:All CTD patients, including SSc, anti-synthetase syndrome (ASS) and mixed connective tissue disease (MCTD) from the Oslo University Hospital diagnosed before 2015 and assessed for the presence of ILD by HRCT were included. The year 2015 was chosen to secure an observation time of at least five years from ILD diagnosis to study end on 01.01.2021 or time of death. All patients fulfilled the respective CTD classification criteria. Subclinical ILD was defined as an ILD extent 80% predicted and without respiratory symptoms. Clinical ILD was defined as >5% extent of ILD or Results:We identified 525 CTD patients, including 296 with SSc, 135 with MCTD and 94 with ASS who had conducted a baseline HRCT. Of these, 227 (43%) had no ILD, 67 (13%) subclinical and 231 (44%) clinical ILD (Table). Of the 67 subclinical ILD patients, 45 (15%) had SSc, 13 (10%) MCTD and 9 (10%) ASS of thespecific cohorts. Over a median time of 4.5 years between baseline and follow-up HRCT, 95/395 (24%) showed progression of ILD, including 72 (26%) SSc and 23 (19%) MCTD patients. Disease progression frequently occurred in both subclinical ILD (38%) and clinical ILD (51%) patients (Figure). Age, gender, underlying CTD, and baseline lung function were not predictive for the progression of lung fibrosis. Progression was too infrequent to allow for meaningful multivariable regression analyses. After a median observation period of 12 years, 153 (29%) of the patients died. The 1-, 5- and 10-year survival rates in those without ILD, subclinical and clinical ILD were 97%/97%/99%, 88%/91%/82%, and 82%/85%/68% (pTable 1.Clinical characteristics, demographics and outcomeNo ILD (n=227)Subclinical ILD (n=67)Clinical ILD (n=231)Age, y (SD)50 (15.4)51 (14.4)52 (15.3)Male sex, n (%)89 (39)22 (33)111 (48)Deceased, n (%)50 (22)12 (18)91 (39)Observation period, y median (range)13.7 (18.6)13.9 (17.9)11.5 (17.1)FVC% (SD)97 (18.6)99 (17.9)81 (20.9)FVC decline% (SD)-0.70 (11.1)-0.81 (16.5)-1.61 (15.9)DLCO% (SD)73 (19.4)73 (16.9)55 (17.4)Extent of ILD% (SD)0 (0)2.3 (1.5)19.3 (16.8)ILD progression% (SD)0.08 (1.0)3.1 (6.2)3.6 (9.9)ILD progressors, n (%)3 (2)20 (38)72 (51)Figure 1.Time to ILD progression in CTD without ILD, with subclinical and clinical ILDConclusion:Subclinical ILD is frequently present across CTDs and progresses over time in a substantial subgroup of patients, comparable to patients with clinical ILD. Our findings question the terms sub- and preclinical ILD, which may potentially lead to a suboptimal “watchful waiting management strategy”. Monitoring all CTD patients with any ILD is of high importance to identify disease progression early.Disclosure of Interests:Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Lilly and Medscape, Consultant of: Actelion, Boehringer Ingelheim, Bayer, ARXX, and Medscape, Grant/research support from: Boehringer Ingelheim, Helena Andersson: None declared, Silje Reiseter: None declared, Håvard Fretheim Consultant of: Actelion, Bayer., Imon Barua: None declared, Torhild Garen: None declared, Øyvind Midtvedt: None declared, Ragnar Gunnarsson: None declared, Mike Durheim Speakers bureau: Boehringer Ingelheim and Roche, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim, Trond M Aaløkken: None declared, Øyvind Molberg: None declared

The long-term pulmonary outcomes of coronavirus disease 2019 (COVID-19) are unknown. We aimed to describe self-reported dyspnoea, quality of life, pulmonary function, and chest CT findings three months following hospital admission for COVID-19. We hypothesised outcomes to be inferior for patients admitted to intensive care units (ICU), compared with non-ICU patients. Discharged COVID-19-patients from six Norwegian hospitals were consecutively enrolled in a prospective cohort study. The current report describes the first 103 participants, including 15 ICU patients. Modified Medical Research Council dyspnoea scale (mMRC), EuroQol Group's Questionnaire, spirometry, diffusion capacity (DLCO), six-minute walk test, pulse oximetry, and low-dose CT scan were performed three months after discharge. mMRC was >0 in 54% and >1 in 19% of the participants. The median (25th–75th percentile) forced vital capacity and forced expiratory volume in one second were 94% (76, 121) and 92% (84, 106) of predicted, respectively. DLCO was below the lower limit of normal in 24%. Ground-glass opacities (GGO) with >10% distribution in ≥1 of 4 pulmonary zones were present in 25%, while 19% had parenchymal bands on chest CT. ICU survivors had similar dyspnoea scores and pulmonary function as non-ICU patients, but higher prevalence of GGO (adjusted odds ratio [95% confidence interval] 4.2 [1.1, 15.6]) and performance in lower usual activities. Three months after admission for COVID-19, one fourth of the participants had chest CT opacities and reduced diffusion capacity. Admission to ICU was associated with pathological CT findings. This was not reflected in increased dyspnoea or impaired lung function., Three months after discharge, one-fourth of COVID-19 survivors have reduced gas diffusion capacity and persistent parenchymal opacities. ICU treatment is associated with persistent parenchymal opacities, but not with dyspnoea or reduced diffusion capacity.

OBJECTIVE To examine the prognostic value of select biobehavioral factors in patients with chronic obstructive pulmonary disease (COPD) in a secondary analysis of participants from the INSPIRE-II trial. METHODS Three hundred twenty-six outpatients with COPD underwent assessments of pulmonary function, physical activity, body mass index, inflammation, pulmonary symptoms, depression, and pulmonary quality of life and were followed up for up to 5.4 years for subsequent clinical events. The prognostic value of each biobehavioral factor, considered individually and combined, also was examined in the context of existing Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 risk stratification. RESULTS Sixty-nine individuals experienced a hospitalization or died over a mean follow-up period of 2.4 (interquartile range = 1.6) years. GOLD classification was associated with an increased risk of clinical events (hazard ratio [HR] = 2.72 [95% confidence interval = 1.63-4.54], per stage); 6-minute walk (HR = 0.50 [0.34-0.73] per 500 ft), total steps (HR = 0.82 [0.71-0.94] per 1000 steps), high-sensitivity C-reactive protein (HR = 1.44 [1.01-2.06] per 4.5 mg/l), depression (HR = 1.12 [1.01-1.25] per 4 points), and pulmonary quality of life (HR = 1.73 [1.14-2.63] per 25 points) were each predictive over and above the GOLD assessment. However, only GOLD group and 6-minute walk were predictive of all-cause mortality and COPD hospitalization when all biobehavioral variables were included together in a multivariable model. CONCLUSIONS Biobehavioral factors provide added prognostic information over and above measures of COPD severity in predicting adverse events in patients with COPD.

Background:In systemic sclerosis (SSc) patients with interstitial lung disease (ILD) approximately 30% show progressive ILD. It is unknown whether a progressive ILD period is followed by further lung function decline. In clinical practice, treatment is frequently initiated after observation of lung function decline over 6-12 months and lung function stabilization at follow up is often interpreted as treatment effect.Objectives:Assess the predictive ability of lung function decline over 12 months for further deterioration adjusted for known risk factors for ILD and treatment in two large and well characterized SSc cohorts.Methods:Patients with SSc-ILD by HRCT, fulfilling SSc classification criteria, from the Oslo and Zurich University Hospital were included. The first period with three consecutive annual forced vital capacity (FVC) measurements (i.e. at 0, 12 and 24 months, +/- 3 months) was used. Lung function decline was assessed by absolute changes in FVC% predicted. Moderately progressive ILD was defined as FVC decline of >5-Results:In total, 240 SSc-ILD patients met the inclusion criteria (table). Of these 69 (29%) SSc-ILD patients showed progressive ILD in the first 12 months period; 34 (14%) with moderate (5-10%) and 35 (15%) with significant FVC decline (≥10%). Independent of FVC changes in the first period, 77 (32%) showed progressive ILD in the second period; 44 (18%) moderate and 33 (14%) significant FVC decline. Only 21 (9%) SSc-ILD patients had two progressive periods, and 115 (48%) were stable in the two 12 month’s periods; all independent of treatment. In multivariable logistic regression, progressive ILD in the first period (moderate, significant or combined FVC decline) was not predictive for progression in the following period. Of all applied risk factors, only mRSS was significantly predictive for further FVC decline, also when adjusted for age, gender and treatment (OR 1.03, 95%CI 1.00-1.08, p=0.035).Conclusion:Decline of FVC in one 12 months period did not predict further ILD progression in the following 12 months independent of treatment. These results have important clinical implications. Firstly, a decline of lung function in one period seems not to be the right indicator for initiating treatment. Secondly, stabilization of lung function under treatment initiated after ILD progression cannot necessarily be interpreted as a treatment response on the individual patient level.Table:First periodBoth periodsSSc-ILD (n=240)ILD progression (n=69)ILD progression (n=21)Stable ILD (n=115)Age, years (SD)48 (14.7)49 (13.8)50 (14.3)46 (15.3)Male, n (%)57 (24)18 (26)5 (24)27 (24)Disease duration yrs, mean (SD)10.2 (11.4)9.8 (10.2)8.8 (11.0)10.8 (12.3)Disease duration 68 (28)22 (32)8 (38)29 (25)Diffuse cutaneous SSc, n (%)95 (40)30 (44)11 (52)43 (27)Anti-topoisomerase I Ab, n (%)84 (35)27 (40)9 (43)42 (37)mRSS, mean (SD)10 (9.3)11 (10.2)16 (13.0)8 (8.3)CRPml, mean (SD)3.6 (7.2)3.3 (6.2)4.4 (9.1)3.1 (5.1)GERD, n (%)148 (62)44 (64)15 (74)70 (61)FVC % predicted90 (20.3)90 (21.9)92 (21.7)89 (19.3)DLCO% predicted64 (17.9)64 (16.6)70 (11.3)65 (17.5)Lung fibrosis >20%, n (%)55 (23)16 (23)4 (19)27 (24)Mycophenolate Mofetil, n (%)47 (20)15 (22)5 (24)23 (20)Other immunosuppression, n (%)79 (33)22 (32)9 (43)42 (37)Corticosteroids, n (%)62 (26)18 (26)8 (38)28 (24)Disclosure of Interests:Anna-Maria Hoffmann-Vold Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Håvard Fretheim: None declared, Britta Maurer Grant/research support from: AbbVie, Protagen, Novartis, congress support from Pfizer, Roche, Actelion, and MSD, Speakers bureau: Novartis, Mike Durheim Grant/research support from: BI, Consultant of: BI, Speakers bureau: BI, Øyvind Midtvedt: None declared, Mike O. Becker: None declared, Rucsandra Dobrota: None declared, Øyvind Molberg: None declared, Suzana Jordan: None declared, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

Introduction: Cardiorespiratory fitness (VO2peak) remains low after lung transplantation (LTx) despite improvement in lung function. The extent and reasons for this are unclear. Aim: To evaluate the cardiopulmonary response during a maximal cardiopulmonary exercise test (CPET) in LTx recipients, and to detect exercise limiting factors. Method: Bilateral-LTx recipients (n=47, age 20-67 years, 23 men) underwent a treadmill CPET. Exercise limiting factors were classified as a breathing reserve (BR) Results: Median (range) time since LTx was 29 (6-59) months. The table shows the physiological response during CPET. Five patients had a VO2peak within normal range (VO2peak>80% predicted). Six patients had a small BR, which indicates ventilatory limitations, and 3 had exercise-induced hypoxemia. Thirty-five demonstrated a low VO2peak having none of the limitations above. Seventeen had inefficient ventilation, but did not desaturate. Conclusion: LTx recipients demonstrated low cardiorespiratory fitness. One-fifth had cardiorespiratory limitations, whereas a majority was deconditioned without such limitations. This may suggest a substantial need for exercise training after LTx.

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.

Background Delirium is relatively common after lung transplantation, although its prevalence and prognostic significance have not been systematically studied. The purpose of the present study was to examine pretransplant predictors of delirium and the short-term impact of delirium on clinical outcomes among lung transplant recipients. Methods Participants underwent pretransplant cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status and the Trail Making Test. After transplant, delirium was assessed using the Confusion Assessment Method until discharge. Results Sixty-three patients were transplanted between March and November 2013, of which 23 (37%) developed delirium. Among transplanted patients, 48 patients completed pretransplant cognitive testing. Better pretransplant cognitive function was associated with lower risk of delirium (odds ratio, 0.69 [95% confidence interval 0.48, 0.99], P = .043); and demographic and clinical features including native disease ( P = .236), the Charlson comorbidity index ( P = .581), and the lung allocation score ( P = .871) were unrelated to risk of delirium, although there was a trend for women to experience delirium less frequently ( P = .071). The presence ( P = .006) and duration ( P = .027) of delirium were both associated with longer hospital stays. Conclusion Delirium occurs in more than one-third of patients after lung transplantation. Delirium was associated with poorer pretransplant cognitive functioning and longer hospital stays, after accounting for other medical and demographic factors.

Introduction: Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation (LTx), associated with elevated proportions of neutrophils (%PMN) in bronchoalveolar lavage (BAL). Induced sputum (IS) is less invasive than BAL to assess markers of inflammation (%PMN) in central airways. Aims: To examine whether IS %PMN levels were elevated early after LTx and further compare the utility of IS (vs BAL) %PMN to predict CLAD development. Methods: IS and BAL samples were collected at 4-8 and 12 weeks post LTx and IS collected annually in 30 patients, of which 10 later developed CLAD. The %PMN were determined by differential cell count and flow cytometry. CLAD was diagnosed in accordance with international guidelines. Results: CLAD occurred after a mean (SD) of 245 (156) days. At this time, %PMN in IS was higher among patients with CLAD, being 69 (17)% vs 49 (21)%, p=0.01. There were no statistical differences in %PMN in BAL or IS at earlier time points between those who later developed CLAD and those who did not. Using logistic regression, we found no relationship between %PMN at either 4-8 or 12 weeks after transplant, and presence of CLAD at 1, 2 or 3 years post LTx. Conclusion: The %PMN significantly discriminated CLAD from non-CLAD patients at time of diagnosis. The %PMN in samples of BAL and IS taken early after LTx did not predict development of CLAD up to 3 years post LTx. IS appears to give comparable information to BAL early after LTx and may be considered as a less invasive alternative to BAL for PMN surveillance post LTx.

Introduction: To extend the number of available organs for lung transplantation (LTx), donors with a smoking history are increasingly accepted. Previous studies show conflicting results as to whether this impairs recipient survival. Aims and objectives: The aim was to assess the effects of using lungs from donors with a smoking history for LTx for recipients with cystic fibrosis (CF). Methods: All recipients of bilateral LTx in Norway and Denmark 1990-2013 were included. Donor information and data about recipient survival and lung function was extracted from existing registries. Results: While there was no negative effect of donor smoking status when including all LTx recipients (n=388), we found a negative association between donor smoking status and post-LTx survival in the CF patients (n=86), in whom one-year survival was 82 % vs 90 % and five year survival was 49 % vs 73 % comparing smoking to non-smoking donors (Log-rank p-value 0.005). The negative effects of using organs from smoking donors remained significant when adjusting for donor and recipient age and sex, organ ischemia time and transplant center location in multivariate cox regression analysis. Conclusion: Using donors with a positive smoking history in double lung transplant recipients with cystic fibrosis is associated with inferior survival and decreased lung function.

Rationale: Older patients are at high risk of death and rehospitalization after hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AE-COPD). Emergency department visits comprise a substantial portion of acute care encounters in this patient population. The risks of mortality and repeat acute care encounters, including both hospital readmission and repeat emergency department visits, after AE-COPD among older adults are not well understood.Objectives: To examine early and long-term rates of death and repeat acute care encounters after hospitalization or emergency department visit for AE-COPD in Medicare fee-for-service beneficiaries and to identify patient characteristics, including medical comorbid conditions, associated with these outcomes.Methods: A retrospective analysis was conducted using a nationally representative 5% sample of Medicare fee-for-service claims data from the U.S. Centers for Medicare and Medicaid Services to identify Medicare beneficiaries 65 years or o...

Endurance exercise (EE) leads to beneficial alterations in skeletal muscle lipid metabolism in overweight and obese individuals; however, the mechanisms of these improvements are poorly understood. The primary goal of the current investigation was to test the hypothesis that long-term EE training (6 mo) leads to alterations in the mRNA abundance of key lipid metabolism enzymes in skeletal muscle of overweight and obese middle-aged women and men. A secondary aim of this study was to investigate the hypothesis that exercise-mediated adaptations in mRNA levels differ between women and men. The mRNA abundance of representative lipogenic and lipolytic genes from major lipid metabolism pathways, as well as representative lipogenic and lipolytic transcription factors, were determined by real-time PCR from skeletal muscle biopsies collected before and approximately 24 h after the final bout of 6 mo of EE. Six months of EE led to increases in muscle lipoprotein lipase, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, carnitine palmitoyltransferase-1 beta, diacylglycerol acyltransferase-1, and acid ceramidase mRNA in women, but not men. In contrast, in men, EE led to reductions in the mRNA content of the lipogenic factors sterol regulatory element binding protein-1c and serine palmitoyl transferase. These data suggest that EE-mediated alterations in the abundance of the lipid metabolism genes studied here are fundamentally different between overweight and obese middle-aged women and men. Future studies should determine whether these adaptations in mRNA levels translate into changes in protein function.

Summary 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.

The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown.To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group.Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality.Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P=0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P=0.002).Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD.

Neurocognitive impairments are associated with reduced quality of life and may adversely affect medical compliance, but their prevalence after lung transplantation has not been extensively studied.To examine the frequency of neurocognitive impairment after lung transplantation and to examine perioperative factors affecting post-transplant neurocognitive function.We performed serial assessments of neurocognitive function in a consecutive series of 47 subjects who received transplants between March 2013 and November 2013 (45% women; mean age, 53.5 ± 17.2 yr). Neurocognitive function was assessed using a composite measure including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score and Trail Making Test parts A and B obtained before transplant, at hospital discharge, and 3 months after discharge. The presence of neurocognitive impairment was assessed using the Montreal Cognitive Assessment Battery (MoCA), and in-hospital delirium was assessed using the Confusion Assessment Method. Results demonstrated that neurocognitive performance initially worsened among non-cystic fibrosis patients and improved over follow-up (P = 0.002). Time effects were strongest on Trail Making Test part B (P 0.001) and the RBANS (P = 0.054). Participants who exhibited delirium during their hospitalization showed poorer performance during follow-up assessments (P = 0.006). Examination of cognitive impairment rates demonstrated that 21 participants (45%) exhibited neurocognitive impairment (MoCA 26) before lung transplant, whereas 27 (57%) participants exhibited impairment after transplantation, and 19 (57%) participants continued to neurocognitive impairment during a 3-month follow-up.Neurocognitive impairments are prevalent among lung transplant candidates and appear to worsen in some patients after transplant. Delirium during hospitalization is associated with worse neurocognitive function after transplant among patients without cystic fibrosis.

Background: Pulmonary disease has been associated with poor cardiovascular outcomes including heart failure; yet, the relationship between measures of obstructive and restrictive lung disease as defined on pulmonary function testing (PFT) and left ventricular size and function remains unknown. The objective of this study is to determine the correlation between forced expiratory volume/1 sec (FEV1), forced vital capacity (FVC) and FEV1/FVC with left ventricular ejection fraction (LVEF), internal diastolic diameter (LVIDD), and internal systolic dimension (LVISD) as measured by transthoracic echocardiography (TTE). Methods: We selected patients who underwent both TTE and PFT within 7 days from January 2012 to April 2013. We examined for bivariate relationships by using Pearson’s correlation coefficient to determine associations between pre-bronchodilator FEV1, FVC and FEV1/FVC and the following TTE measures: LVEF,LVIDD, and LVISD. Multivariable regression analysis was used to adjust for age and sex. Results: We identified 2238 patients who had TTE and PFT within 7 days. After adjusting for age and sex, FEV1, FVC, and FEV1/FVC were positively correlated with LVEF and LVIDD. Every 100 cc reduction in FVC or 90 cc reduction in FEV1 was associated with a 5% decrease in LVEF (95% CI 0.079- 0.128, 0.068- 0.109). Moreover, a 200 cc reduction in FEV1 or 220 cc reduction in FVC was associated with a 1 cm decrease in LVIDD (95% CI 0.152- 0.247, 0.165- 0.282,). These correlations remained significant when percent predicted instead of absolute FEV1 and FVC were evaluated. Conclusion: Abnormal lung function is associated with reduced LV function without corresponding increases in ventricular size. These findings suggest that the association between pulmonary disease and heart failure may not depend on adverse ventricular remodeling and requires further study.

Chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality and reduced quality of life (QoL). Novel interventions are needed to improve outcomes in COPD patients. The present study assessed the effects of a telephone-based coping skills intervention on psychological and somatic QoL and on the combined medical end point of COPD-related hospitalizations and all-cause mortality.We conducted a dual-site, randomized clinical trial with assessments at baseline and after 16 weeks of treatment. The study population comprised 326 outpatients with COPD aged 38 to 81 years, randomized to coping skills training (CST) or to COPD education (COPD-ED). Patients completed a battery of QoL instruments, pulmonary function tests, and functional measures and were followed up for up to 4.4 years to assess medical outcomes.The CST group exhibited greater improvements in psychological QoL compared with controls (p = .001), including less depression (Cohen d = 0.22 [95% confidence interval, or CI = 0.08-0.36]) and anxiety (d = 0.17 [95% CI = 0.02-0.33]), and better overall mental health (d = 0.17 [95% CI = 0.03-0.32]), emotional role functioning (d = 0.29 [95% CI = 0.10-0.48]), vitality (d = 0.27 [95% CI = 0.11, 0.42]), and social functioning (d = 0.21 [95% CI = 0.03-0.38]). A significant baseline psychological QoL by treatment group interaction revealed that CST with lower QoL at baseline achieved even greater improvements in psychological QoL compared with COPD-ED. CST participants also exhibited greater improvements in somatic QoL (p = .042), including greater improvements in pulmonary QoL (d = 0.13 [95% CI = 0.01-0.24]), less fatigue (d = 0.34 [95% CI = 0.18-0.50]), and less shortness of breath (d = 0.11 [95% CI = -0.01 to 0.23]) and greater improvement in distance walked on the Six-Minute Walk test (d = 0.09 [95% CI = 0.01-0.16]). However, there was no significant difference in risk of time to COPD-related hospitalization or all-cause mortality between CST (34 events) and COPD-ED (32 events; p = 0.430).A telehealth CST intervention produced clinically meaningful improvements in QoL and functional capacity, but no overall improvement in risk of COPD-related hospitalization and all-cause mortality.clinicaltrials.gov Identifier: NCT00736268.

Background Impaired psychological function is common among lung transplant candidates and may affect clinical outcomes following transplantation. Although numerous studies have examined the relationship between pretransplant depression, quality of life (QoL), and post-transplant outcomes, few have examined the relationship between depression and QoL shortly following transplantation and subsequent clinical outcomes. We therefore examined the association between depression, QoL, and short-term mortality in a consecutive series of lung transplant recipients. Methods Depression (Patient Health Questionnaire-9; Hospital Anxiety and Depression Scale; Centers for Epidemiologic Studies Depression Scale) and QoL (UCSD Shortness of Breath Questionnaire; Pulmonary Quality of Life Scale) were assessed prior to transplantation (median 0.9 months [IQR=1.6]) and again approximately 2 weeks following transplantation (median=0.5 months [IQR=0.5]), in a series of 66 patients transplanted between March 2013 and April 2014. The association between psychiatric diagnoses from participants’ comprehensive pretransplant assessment and mortality also was examined. Cox proportional hazards models were used to examine the association between depression, QoL, and mortality. Results During a median follow-up of 2.8 years (range 0.4-3.3), 21 patients died (32%). Greater depressive symptoms assessed shortly after transplant were associated with subsequent mortality (HR=2.17 [1.01, 4.67], P=.048), and this relationship persisted after controlling for primary graft dysfunction, duration of transplant hospitalization, and gender. In contrast, neither pretransplant depression, history of depression, nor QoL was associated with mortality. Conclusions Greater post-transplant depressive symptoms are independently associated with mortality among lung transplant recipients.

Background Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterised by progressive loss of lung function. Its clinical course is variable but ultimately fatal. There is a need for a multicentre patient registry incorporating longitudinal clinical data and biological samples to improve understanding of the natural history of IPF and contemporary practice patterns. Methods/design The Idiopathic Pulmonary Fibrosis–PRospective Outcomes (IPF-PRO) registry is a national IPF registry in the USA. This registry will enrol approximately 300 patients with newly diagnosed IPF over 2 years at approximately 14 tertiary pulmonary care sites. Participants will be followed for 3–5 years and will receive usual care, as defined by their physician. Clinical data from the year prior to diagnosis will be collected from medical record review on enrolment. Subsequently, data on diagnostic evaluations, pulmonary function tests, physical examinations, laboratory data and clinical events will be collected at routine clinical visits and via a call centre. Participants will complete patient-reported outcome questionnaires at enrolment and then at approximately 6-month intervals. Blood samples for cellular, genetic and transcriptomic analyses will be collected at the same intervals. Results The first results from the IPF-PRO registry will be presented in 2015. Conclusions The IPF-PRO registry will improve understanding of the natural history of IPF, its impact on patients and current practice in the diagnosis and care of patients with IPF. The registry will establish a repository of biological samples from a well-characterised patient population for future research. Clinical trial number NCT01915511.

OBJECTIVE Insulin resistance and β-cell dysfunction both are important contributors to the pathogenesis of type 2 diabetes. Exercise training improves insulin sensitivity, but its effects on β-cell function are less well studied. RESEARCH DESIGN AND METHODS Sedentary, overweight adults were randomized to control or one of three 8-month exercise programs: 1) low amount/moderate intensity, 2) low amount/vigorous intensity, or 3) high amount/vigorous intensity. Of 387 randomized, 260 completed the study and 237 had complete data. Insulin sensitivity (Si), acute insulin response to glucose (AIRg), and the disposition index (DI = Si × AIRg) were modeled from an intravenous glucose tolerance test. RESULTS Compared with control subjects, all three training programs led to increases in DI. However, the moderate-intensity group experienced a significantly larger increase in DI than either of the vigorous-intensity groups and through a different mechanism. The high-amount/vigorous-intensity group improved Si and had a compensatory reduction in AIRg, whereas the moderate-intensity group had a similar improvement in Si but almost no reduction in AIRg. Importantly, the inactive control group experienced a significant increase in fasting glucose. CONCLUSIONS To the extent that the DI accurately reflects β-cell function, we observed that both moderate- and vigorous-intensity exercise training improved β-cell function, albeit through distinct mechanisms. It is not clear which of these mechanisms is preferable for maintenance of metabolic health. While moderate-intensity exercise led to a larger improvement in DI, which may reflect a transition toward a more normal DI, longer-term investigations would be necessary to determine which was more effective at reducing diabetes risk.

Small LDL and HDL particle size are characteristic of a proatherogenic lipoprotein profile. Aerobic exercise increases these particle sizes. Although visceral adipose tissue (VAT) has been strongly linked with dyslipidemia, the importance of intermuscular adipose tissue (IMAT) to dyslipidemia and exercise responses is less well understood. We measured exercise-associated changes in thigh IMAT and VAT and examined their relationships with changes in LDL and HDL particle size. Sedentary, dyslipidemic, overweight subjects ( n = 73) completed 8–9 mo of aerobic training. Linear regression models were used to compare the power of IMAT change and VAT change to predict lipoprotein size changes. In men alone ( n = 40), IMAT change correlated inversely with both HDL size change ( r = −0.42, P = 0.007) and LDL size change ( r = −0.52, P < 0.001). That is, reduction of IMAT was associated with a shift toward larger, less atherogenic lipoprotein particles. No significant correlations were observed in women. After adding VAT change to the model, IMAT change was the only significant predictor of either HDL size change ( P = 0.034 for IMAT vs. 0.162 for VAT) or LDL size change ( P = 0.004 for IMAT vs. 0.189 for VAT) in men. In conclusion, in overweight dyslipidemic men, exercise-associated change in thigh IMAT was inversely correlated with both HDL and LDL size change and was more predictive of these lipoprotein changes than was change in VAT. Reducing IMAT through aerobic exercise may be functionally related to some improvements in atherogenic dyslipidemia in men.