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Background: Pulmonary rehabilitation (PR) is recommended for the treatment of people with idiopathic pulmonary fibrosis (IPF). Physical activity is an important health behaviour, closely linked to survival in people with IPF. Little is known about the impact of virtual (V) PR on physical activity in people with IPF., Objective: To explore the feasibility of conducting a trial to explore effect of virtual PR on objectively measured physical activity in people with IPF., Methods: All patients with a diagnosis of IPF in a stable phase of the disease were invited to participate in VPR: a 10 week exercise programme delivered twice-weekly for one hour. Data were collected at baseline (BL) and post VPR (10 weeks): Kings Brief Interstitial Lung Disease (K-BILD), Exercise capacity (6-minute walk test (6MWT) or 1-minute sit-to-stand (STS)) and Physical Activity. Physical activity was measured with a triaxial accelerometer for seven days. Screening, recruitment, adherence and safety data were collected., Results: 68 people were screened for this study. N = 16 participants were recruited to the study. There was one dropout. N = 15 completed VPR. All results reported in mean (standard deviation) (SD). Participants attended 18.1(2.0) of the 20 sessions. No adverse events were detected. The mean age of participants was 71.5(11.5) years, range: 47-95 years; 7 M:9 F. Mean (SD) FEV 1 2.3(0.3)L, FVC 2.8(0.7)L. No statistically significant changes were observed in outcome measures apart from exercise capacity. Light physical activity increased from 152(69.4) minutes per day (n = 16) to 161.9(88.7) minutes per day (n = 14), mean change (SD) (CI) p-value: 9.9 (39.8) [-12.3 to 30.9] p = 0.4. Moderate-to-vigorous physical activity increased from 19.1(18.6) minutes per day (n = 16) to 25.7(28.3) minutes per day (n = 14), mean change (SD) (CI) p-value: 6.7 (15.5) [-2.1 to 15.1] p = 0.1. Step count increased from 3838(2847) steps per day (n = 16) to 4537(3748) steps per day (n = 14), mean change (SD) (CI) p-value: 738 (1916) [-419.3 to 1734.6] p = 0.2. K-BILD (n = 15) increased from 55.1(7.4) at BL to 55.7(7.9) post VPR mean change (SD) [95% confidence interval] (CI) p-value: 1.7(6.5) [-1.7 to 5.3], p = 0.3. 6MWT (n = 5) increased from 361.5(127.1) to 452.2(136.1) meters, mean change (SD) (CI) p-value: 63.7 (48.2) [-3.8 to 123.6], p = 0.04 and 1-minute STS increased from 17.6(3.0) (n = 11) to 23.7(6.3) (n = 10), mean change (SD) (CI) p-value 5.8 (4.6) [2.6 to 9.1], p = 0.003., Conclusion: VPR can improve physical activity in people with IPF. A number of important feasibility issues included recruitment, retention, adherence and safety have been reported which are crucial for future research in this area. A fully powered trial is needed to determine the response of people with IPF to PR with regard to physical activity., (© 2024. The Author(s).)

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT , RTEL1 , common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Background: Pulmonary rehabilitation (PR) is recommended in the treatment of people with idiopathic pulmonary fibrosis (IPF). Little is known about the experiences of people with IPF of PR. Due to Covid-19 there has been a rapid shift of PR services to remote/virtual delivery., Objective: To explore people living with IPFs experience of a virtual PR (VPR) programme., Methods: All patients with a diagnosis of IPF in a stable phase of the disease were invited to participate in virtual PR: a 10 week exercise programme delivered twice-weekly for one hour. One-to-one semi- structured interviews were conducted within one week following the programme. All interviews were recorded, transcribed and analysed using Braun and Clarke thematic analysis by two independent assessors., Results: N=13 participants took part in the semi-structured interviews, mean (standard deviation (SD)) age 69.5(10.4) years; 7M:6F. Mean (SD) FEV 1 2.6(0.3)L, FVC 2.9(0.4)L. Four key themes were identified: 1) The impact of VPR on health and outlook, (2) The reality of VPR, (3) Being active after VPR and (4) Living with IPF during the COVID-19 Pandemic. Participants reported high levels of enjoyment and engagement with the programme regardless of the health benefits experienced. Most participants expressed a desire for a longer programme. Participants expressed different levels of maintenance with exercise since finishing the programme, specific motivators and strategies for maintenance included lung transplant, the maintenance of benefits from the programme and social support. COVID-19 and the restrictions imposed had some negative impacts on some participants lives, engaging with PR helped overcome some of these., Conclusion: Despite the progressive nature of IPF, all participants expressed high levels of enjoyment with the programme. Future research should explore strategies for maintenance post PR and the optimum duration of PR for people with IPF., (© 2022. The Author(s).)

Background: Hypercoagulability and endothelial dysfunction are hallmarks of coronavirus disease 2019 (COVID-19) and appear to predict disease severity. A high incidence of thrombosis despite thromboprophylaxis is reported in patients with moderate to severe COVID-19. Recent randomized clinical trials suggest that therapeutic-intensity heparin confers a survival benefit in moderate-severity COVID-19 compared to standard-intensity heparin, potentially by harnessing heparin-mediated endothelial-stabilizing and anti-inflammatory effects., Objective: We hypothesized that patients with moderate-severity COVID-19 exhibit enhanced hypercoagulability despite standard-intensity thromboprophylaxis with low molecular weight heparin (LMWH) compared to non-COVID-19 hospitalized patients., Methods: Patients with moderate COVID-19 and a control group (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]-negative hospitalized patients) receiving LMWH thromboprophylaxis were recruited. Markers of endothelial damage and plasma thrombin generation parameters were assessed., Results: Tissue plasminogen activator levels were significantly increased in the COVID-19 group (8.3 ± 4.4 vs. 4.9 ± 2.4 ng/ml; P = .02) compared to non-COVID-19-hospitalized patients. Despite thromboprophylaxis, mean endogenous thrombin potential was significantly increased among COVID-19 patients (1929 ± 448 vs. 1528 ± 460.8 nM*min; P = .04) but lag time to thrombin generation was significantly prolonged (8.1 ± 1.8 vs. 6.2 ± 1.8 mins; P = .02). While tissue factor pathway inhibitor (TFPI) levels were similar in both groups, in the presence of an inhibitory anti-TFPI antibody, the difference in lag time between the groups was abrogated., Conclusions: Collectively, these data demonstrate that COVID-19 of moderate severity is associated with increased plasma thrombin generation and endothelial damage, and that hypercoagulability persists despite standard LMWH thromboprophylaxis. These findings may be of clinical interest given recent clinical trial data which suggest escalated heparin dosing in non-severe COVID-19 may be associated with improved clinical outcomes., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Introduction: The use of remote monitoring technology to manage the care of patients with COVID-19 has been implemented to help reduce the burden placed on healthcare systems during the pandemic and protect the well-being of both staff and patients. Remote monitoring allows patients to record their signs and symptoms remotely (eg, while self-isolating at home) rather than requiring hospitalisation. Healthcare staff can, therefore, continually monitor their symptoms and be notified when the patient is showing signs of clinical deterioration. However, given the recency of the COVID-19 outbreak, there is a lack of research regarding the acceptance of remote monitoring interventions to manage COVID-19. This study will aim to evaluate the use of remote monitoring for managing COVID-19 cases from the perspective of both the patient and healthcare staff., Methods and Analysis: Discharged patients from a large urban teaching hospital in Ireland, who have undergone remote monitoring for COVID-19, will be recruited to take part in a cross-sectional study consisting of a quantitative survey and a qualitative interview. A mixed methods design will be used to understand the experiences of remote monitoring from the perspective of the patient. Healthcare staff who have been involved in the provision of remote monitoring of patients with COVID-19 will be recruited to take part in a qualitative interview to understand their experiences with the process. Structural equation modelling will be used to examine the acceptance of the remote monitoring technology. Latent class analysis will be used to identify COVID-19 symptom profiles. Interview data will be examined using thematic analysis., Ethics and Dissemination: Ethical approval has been granted by the ethical review boards at University College Dublin and the National Research Ethics Committee for COVID-19-related Research. Findings will be disseminated via publications in scientific journals, policy briefs, short reports and social media., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Aim To gain an understanding of the impact of COVID-19 on the daily life, healthcare needs, mental wellbeing and outlook of patients with Interstitial Lung Disease (ILD) and their caregivers. Methods ILD patients and caregivers were invited to participate in a quantitative survey. Respondents could self-select to then participate in in-depth structured telephone interviews. Survey data was compared to Department of Health COVID-19 public opinion tracker findings for the comparable time period. Results There were 170 survey respones (111 patients and 59 caregivers) and 14 in-depth interview participants. 32% (n=36) of patients and 42% (n=25) of caregivers expressed extreme worry regarding COVID-19 on a 1-10 scale. 83% (n=92) of patients expressed concern about safe hospital access, 33% (n=37) had received a telephone consultation with their clinician, 43% (n=48) reported test delays, 47% (n=52) were exercising less, 23% (n=26) reported worse sleep and 15% (n=17) reported being financially worse off. Carers reported that sleep was worse for 58% (n=34), 42% (n=25) reported being worse off financially, and 40% (n=24) reported a worse diet. Worry (66%, n=39), stress (51%, n=30), anxiety (49%, n=29) were commonly reported by carers. Discussion ILD patients and caregivers reported higher levels of worry regarding COVID-19 compared to the general public. Alternative pathways for quality ILD patient care and interventions to reduce the burden of care on ILD caregivers are required., Competing Interests: The authors have no conflicts of interest to declare.

To date, coronavirus disease 2019 (COVID-19) has affected over 100 million people globally. COVID-19 can present with a variety of different symptoms leading to manifestation of disease ranging from mild cases to a life-threatening condition requiring critical care-level support. At present, a rapid prediction of disease severity and critical care requirement in COVID-19 patients, in early stages of disease, remains an unmet challenge. Therefore, we assessed whether parameters from a routine clinical hematology workup, at the time of hospital admission, can be valuable predictors of COVID-19 severity and the requirement for critical care. Hematological data from the day of hospital admission (day of positive COVID-19 test) for patients with severe COVID-19 disease (requiring critical care during illness) and patients with non-severe disease (not requiring critical care) were acquired. The data were amalgamated and cleaned and modeling was performed. Using a decision tree model, we demonstrated that routine clinical hematology parameters are important predictors of COVID-19 severity. This proof-of-concept study shows that a combination of activated partial thromboplastin time, white cell count-to-neutrophil ratio, and platelet count can predict subsequent severity of COVID-19 with high sensitivity and specificity (area under ROC 0.9956) at the time of the patient's hospital admission. These data, pending further validation, indicate that a decision tree model with hematological parameters could potentially form the basis for a rapid risk stratification tool that predicts COVID-19 severity in hospitalized patients., Competing Interests: HA, JC, and ED were employed by company SAS Institute LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Szklanna, Altaie, Comer, Cullivan, Kelliher, Weiss, Curran, Dowling, O'Reilly, Cotter, Marsh, Gaine, Power, Lennon, McCullagh, Ní Áinle, Kevane and Maguire.)

For patients with IPF, length of time in healthcare systems prior to review in an ILD clinic reflects disease severity and may impact upon patient outcome https://bit.ly/2TkO26r., Competing Interests: Conflict of interest: C.J. Brereton reports nonfinancial support from Boehringer Ingelheim outside the submitted work. Conflict of interest: T. Wallis has nothing to disclose. Conflict of interest: M. Casey has nothing to disclose. Conflict of interest: L. Fox reports nonfinancial support from Roche for a study day in Manchester and nonfinancial support from Boehinger Ingelheim to attend ILD INN, outside the submitted work. Conflict of interest: K. Pontoppidan reports personal fees for conference attendance from Bayer outside the submitted work. Conflict of interest: D. Laws has nothing to disclose. Conflict of interest: J. Graves reports personal fees from GSK for an asthma talk to practice nurses and personal fees for a Pfizer-funded smoking cessation webinar, outside the submitted work. Conflict of interest: V. Titmuss has nothing to disclose. Conflict of interest: S. Kearney has nothing to disclose. Conflict of interest: S. Evans has nothing to disclose. Conflict of interest: A. Grove has nothing to disclose. Conflict of interest: S. Hamid has nothing to disclose. Conflict of interest: L. Richeldi reports personal fees from Biogen for consulting activity; grants and personal fees for membership of an advisory board from Roche; personal fees for consulting activity from ImmuneWorks; grants, and personal fees for membership of a steering committee and an advisory board from Boehringer Ingelheim; personal fees for consulting activity from Celgene and Nitto; personal fees for membership of advisory boards from FibroGen and Promedior; and personal fees for consulting activity from Pliant Therapeutics, Asahi Kasei, Toray, BMS, RespiVant and CSL Behring, all outside the submitted work. Conflict of interest: K.M.A. O'Reilly reports grants and personal fees for an advisory board from Boehringer Ingelheim, and personal fees for talks and advisory work from Roche, outside the submitted work. Conflict of interest: S.V. Fletcher reports personal fees and nonfinancial support from Boehringer Ingelheim and Roche/Intermune, outside the submitted work Conflict of interest: M.G. Jones has nothing to disclose., (Copyright ©ERS 2020.)

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects.