Feasibility of cardiopulmonary exercise testing in idiopathic pulmonary fibrosis

This is the author accepted manuscript. The final version is available from BMJ Publishing Group via the DOI in this recordBritish Thoracic Society Winter Meeting 2018, London, UK, 5-7 December 2018Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of irreversible declining lung function. Reductions in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) are the common clinical endpoints for prognostic monitoring and assessing treatment outcomes. The use of cardiopulmonary exercise testing (CPET) in IPF remains largely unexplored. Objectives To explore the feasibility of CPET as a clinical measure in IPF and identify associations with established clinical variables. Methods Seventeen patients with IPF were approached, and fifteen (88%) were recruited (13 male, 68.1±7.5 years). Incremental exercise testing to exhaustion was undertaken via electronically braked cycle ergometer. Variables included: peak oxygen consumption (VO2peak), peak work rate (WRpeak), nadir SpO2, ventilatory drive (VE/VCO2), alongside standard clinical pulmonary function tests of FVC and DLCO. Pearson’s correlation coefficients established relationships between variables. Results One participant was excluded (high baseline systolic blood pressure). Eight out of fourteen (57%) participants reached volitional exhaustion. Five CPETs were terminated early due to desaturation (SpO2 <88%) and one to an exercise-induced right bundle branch block (recovery within minutes of ceasing exercise). Mean (±SD) pulmonary and exercise results were: FVC, 84.9%±17.0%; DLCO, 56.5%±11.4%; VO2peak, 1.4±0.4 L.min-1, 16.5±5.5 mL.kg-1.min-1; WRpeak, 104±42 W; SpO2, 90±3%; VE/VCO2, 27.1±6.4. Significant correlations were identified between: FVC and SpO2 (r=0.58, p=0.032), DLCO and VE/VCO2 (r=0.81, p<0.001) and WRpeak (r=0.58, p=0.03). Body-mass relative VO2peak held moderate, but not significant relationships with FVC (r=0.44, p=0.11) and DLCO (r=0.53, p=0.51). Conclusions Initial findings from this study have found CPET to be acceptable to patients with IPF and potentially feasible as a testing measure. Preliminary results identified common exercise desaturation, suggesting less conservative SpO2 termination criteria (e.g. 80% cut-off) could be considered. Although exercise parameters held limited relationships with FVC and DLCO, results from VO2peak identifies potential additional and dynamic prognostic information and warrants further investigation.Royal Devon & Exeter Hospita

Cardiopulmonary Exercise Testing as a Longitudinal Clinical Tool in Interstitial Lung Disease Management

This is an abstract from International Conference of the American-Thoracic-Society Location: Dallas, TX Date: MAY 17-22, 2019Royal Devon & Exeter Hospita

A multicentre retrospective cohort comparison of aetiology and survival in patients with chronic hypersensitivity pneumonitis versus idiopathic pulmonary fibrosis

This is the author accepted manuscript. The final version is available from BMJ Publishing Group via the DOI in this recordWinter Meeting of the British Thoracic Society, 5-7 December 2018, London, U

Validity and repeatability of cardiopulmonary exercise testing in interstitial lung disease

This is the final version. Available from BMC via the DOI in this record. Availability of data and materials: Data cannot be deposited in open access repositories for ethical reasons. Please contact the corresponding author (CAW) to discuss data access.Background: Cardiopulmonary exercise testing (CPET), and its primary outcome of peak oxygen uptake (VO2peak), are acknowledged as biomarkers in the diagnostic and prognostic management of interstitial lung disease (ILD). However, the validity and repeatability of CPET in those with ILD has yet to be fully characterised, and this study flls this evidence gap. Methods: Twenty-six people with ILD were recruited, and 21 successfully completed three CPETs. Of these, 17 completed two valid CPETs within a 3-month window, and 11 completed two valid CPETs within a 6-month window. Technical standards from the European Respiratory Society established validity, and repeatability was determined using mean change, intraclass correlation coefcient and typical error. Results: Every participant (100%) who successfully exercised to volitional exhaustion produced a maximal, and therefore valid, CPET. Approximately 20% of participants presented with a plateau in VO2, the primary criteria for establishing a maximal efort. The majority of participants otherwise presented with secondary criteria of respiratory exchange ratios in excess of 1.05, and maximal heart rates in excess of their predicted values. Repeatability analyses identifed that the typical error (expressed as percent of coefcient of variation) was 20% over 3-months in those reaching volitional exhaustion. Conclusion: This work has, for the frst time, fully characterised how patients with ILD respond to CPET in terms of primary and secondary verifcation criteria, and generated novel repeatability data that will prove useful in the assessment of disease progression, and future evaluation of therapeutic regimens where VO2peak is used as an outcome measure.Royal Devon and Exeter NHS Foundation Trust HospitalNational Institute for Health Research (NIHR)GW4 BioMed Medical Research Counci

The utility of the oxygen uptake efficiency plateau as a submaximal exercise biomarker in interstitial lung disease

This is the author accepted manuscript. The final version is available from BMJ Publishing Group via the DOI in this recordPaper S14 presented at the British Thoracic Society Winter Meeting, 17 - 19 February 202

Telomere length and risk of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease: a mendelian randomisation study

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease accounting for 1% of UK deaths. In the familial form of pulmonary fibrosis, causal genes have been identified in about 30% of cases, and a majority of these causal genes are associated with telomere maintenance. Prematurely shortened leukocyte telomere length is associated with IPF and chronic obstructive pulmonary disease (COPD), a disease with similar demographics and shared risk factors. Using mendelian randomisation, we investigated evidence supporting a causal role for short telomeres in IPF and COPD. METHODS: Mendelian randomisation inference of telomere length causality was done for IPF (up to 1369 cases) and COPD (13 538 cases) against 435 866 controls of European ancestry in UK Biobank. Polygenic risk scores were calculated and two-sample mendelian randomisation analyses were done using seven genetic variants previously associated with telomere length, with replication analysis in an IPF cohort (2668 cases vs 8591 controls) and COPD cohort (15 256 cases vs 47 936 controls). FINDINGS: In the UK Biobank, a genetically instrumented one-SD shorter telomere length was associated with higher odds of IPF (odds ratio [OR] 4·19, 95% CI 2·33-7·55; p=0·0031) but not COPD (1·07, 0·88-1·30; p=0·51). Similarly, an association was found in the IPF replication cohort (12·3, 5·05-30·1; p=0·0015) and not in the COPD replication cohort (1·04, 0·71-1·53; p=0·83). Meta-analysis of the two-sample mendelian randomisation results provided evidence inferring that shorter telomeres cause IPF (5·81 higher odds of IPF, 95% CI 3·56-9·50; p=2·19 × 10-12). There was no evidence to infer that telomere length caused COPD (OR 1·07, 95% CI 0·90-1·27; p=0·46). INTERPRETATION: Cellular senescence is hypothesised as a major driving force in IPF and COPD; telomere shortening might be a contributory factor in IPF, suggesting divergent mechanisms in COPD. Defining a key role for telomere shortening enables greater focus in telomere-related diagnostics, treatments, and the search for a cure in IPF. Investigation of therapies that improve telomere length is warranted. FUNDING: Medical Research Council.National Institute for Health Research (NIHR

Hypoglycemia Assessed by Continuous Glucose Monitoring Is Associated with Preclinical Atherosclerosis in Individuals with Impaired Glucose Tolerance

Hypoglycemia is associated with increased risk of cardiovascular adverse clinical outcomes. There is evidence that impaired glucose tolerance (IGT) is associated with cardiovascular morbidity and mortality. Whether IGT individuals have asymptomatic hypoglycemia under real-life conditions that are related to early atherosclerosis is unknown. To this aim, we measured episodes of hypoglycemia during continuous interstitial glucose monitoring (CGM) and evaluated their relationship with early manifestation of vascular atherosclerosis in glucose tolerant and intolerant individuals. An oral glucose tolerance test (OGTT) was performed in 79 non-diabetic subjects. Each individual underwent continuous glucose monitoring for 72 h. Cardiovascular risk factors and ultrasound measurement of carotid intima-media thickness (IMT) were evaluated. IGT individuals had a worse cardiovascular risk profile, including higher IMT, and spent significantly more time in hypoglycemia than glucose-tolerant individuals. IMT was significantly correlated with systolic (r = 0.22; P = 0.05) and diastolic blood pressure (r = 0.28; P = 0.01), total (r = 0.26; P = 0.02) and LDL cholesterol (r = 0.27; P = 0.01), 2-h glucose (r = 0.39; P<0.0001), insulin sensitivity (r = −0.26; P = 0.03), and minutes spent in hypoglycemia (r = 0.45; P<0.0001). In univariate analyses adjusted for gender, minutes spent in hypoglycemia were significantly correlated with age (r = 0.26; P = 0.01), waist circumference (r = 0.33; P = 0.003), 2-h glucose (r = 0.58; P<0.0001), and 2-h insulin (r = 0.27; P = 0.02). In a stepwise multivariate regression analysis, the variables significantly associated with IMT were minutes spent in hypoglycemia (r2 = 0.252; P<0.0001), and ISI index (r2 = 0.089; P = 0.004), accounting for 34.1% of the variation. Episodes of hypoglycemia may be considered as a new potential cardiovascular risk factor for IGT individuals

Supporting self-management for patients with Interstitial Lung Diseases: Utility and acceptability of digital devices.

This is the final version. Available from Public Library of Science via the DOI in this record. Data Availability Statement: The fully de-identified research data supporting this publication are openly available as S1 Data and at 10.6084/m9. figshare.24569851.INTRODUCTION: Patients diagnosed with Interstitial Lung Diseases (ILD) use devices to self-monitor their health and well-being. Little is known about the range of devices, selection, frequency and terms of use and overall utility. We sought to quantify patients' usage and experiences with home digital devices, and further evaluate their perceived utility and barriers to adaptation. METHODS: A team of expert clinicians and patient partners interested in self-management approaches designed a 48-question cross-sectional electronic survey; specifically targeted at individuals diagnosed with ILD. The survey was critically appraised by the interdisciplinary self-management group at Royal Devon University Hospitals NHS Foundation Trust during a 6-month validation process. The survey was open for participation between September 2021 and December 2022, and responses were collected anonymously. Data were analysed descriptively for quantitative aspects and through thematic analysis for qualitative input. RESULTS: 104 patients accessed the survey and 89/104 (86%) reported a diagnosis of lung fibrosis, including 46/89 (52%) idiopathic pulmonary fibrosis (IPF) with 57/89 (64%) of participants diagnosed >3 years and 59/89 (66%) female. 52/65(80%) were in the UK; 33/65 (51%) reported severe breathlessness medical research council MRC grade 3-4 and 32/65 (49%) disclosed co-morbid arthritis or joint problems. Of these, 18/83 (22%) used a hand- held spirometer, with only 6/17 (35%) advised on how to interpret the readings. Pulse oximetry devices were the most frequently used device by 35/71 (49%) and 20/64 (31%) measured their saturations more than once daily. 29/63 (46%) of respondents reported home-monitoring brought reassurance; of these, for 25/63 (40%) a feeling of control. 10/57 (18%) felt it had a negative effect, citing fluctuating readings as causing stress and 'paranoia'. The most likely help-seeking triggers were worsening breathlessness 53/65 (82%) and low oxygen saturation 43/65 (66%). Nurse specialists were the most frequent source of help 24/63 (38%). Conclusion: Patients can learn appropriate technical skills, yet perceptions of home-monitoring are variable; targeted assessment and tailored support is likely to be beneficial.Health Education Englan