Catharina C. Moor

Introduction: In the recent PREDMETH trial in patients with pulmonary sarcoidosis, we found that methotrexate (MTX) was non-inferior to prednisone for lung function and health status, with fewer ongoing side effects for MTX after 24 weeks. To gain more granular insights in symptom trajectories, patients completed weekly visual analogue scales (VAS). Aims: To assess change in symptoms and determine time to maximum improvement after start of prednisone and MTX Methods: Patients completed weekly VAS on cough (VASC), dyspnea (VASD), fatigue (VASF) and general wellbeing (VASG) using an online app. Adherence was monitored. We analyzed changes over time and time to maximum improvement using non-linear mixed models (SAEmix). Results: 69 participants in the prednisone group and 67 in the MTX group completed VAS. Mean age was 47 years (SD12); 73.5% was male. Mean adherence for weekly VAS over 24 weeks was 77.8% (SD25.6). All VAS scores significantly improved in patients on MTX, with maximum improvement in VAS scores estimated to be reached between day 135-213 (range 90-275) for different symptoms. VASD, VASC, and VASG did not change over time in the prednisone group, whereas VASF significantly improved with a plateau already after 5 days (figure 1). Conclusions: Symptoms significantly improved over time after start of methotrexate, whereas only fatigue improved in patients on prednisone. Weekly completion of online VAS is feasible and yields detailed insights in symptom trajectories and time to improvement after start of treatment. erj;68/suppl_70/OA3426/F1 F1 F1

Pulmonary fibrosis (PF) is a fibrotic interstitial lung disease that is caused by a heterogeneous group of underlying etiologies [1]. People with PF often experience debilitating symptoms, including dry cough, dyspnea, and fatigue, that negatively influence the quality of life of patients [2, 3] and their families [4]. Understanding perspectives of people with PF is important to address their unmet care needs.

Respiratory medicine is one of the most varied medical specialties, with several subspecialties [1]. Furthermore, respiratory research involves a plethora of preclinical, fundamental and translational science within individual specialities but also spanning across several specialities. For medical professionals, each subspecialty has its own benefits and challenges, and they can be very different from each other: the working life of a thoracic oncologist with a specialist interest in interventional pulmonology is likely to be very different from that of a COPD specialist who primarily works in the community. Similarly, life as a scientist working in cellular/molecular biology may differ in day-to-day tasks when compared with a scientist interested in systems biology or epidemiology.

Introduction: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of rare lung diseases. Symptoms of ILD are nonspecific, and diagnosis requires multiple investigations, including invasive procedures. Therefore, diagnostic delay is common. Previous single-center studies showed that profiling of exhaled volatile organic compounds using noninvasive electronic nose (eNose) sensor technology has potential as a diagnostic tool for ILD. We aimed to validate eNose technology to differentiate various ILDs in an international multicenter cohort. Methods: We included patients with an ILD diagnosis established in a multidisciplinary team (MDT) discussion and pulmonary fibrosis on high-resolution chest computed tomography scans at 5 international ILD expert centers. An eNose (SpiroNose) was used for exhaled breath analysis. We compared eNose breath profiles of different ILD subtypes with all other ILDs combined and across 6 different ILD subtypes. Breath profiles were analyzed with partial least squares discriminant and receiver operating characteristic analyses. Models were trained on data from a selection of centers and externally validated in other centers. Results: Breath profiles of 587 patients were analyzed. Comparing breath profiles of ILD subtypes with all other ILDs resulted in area under the curve (AUC) values ranging from 0.88 to 0.92 in the training set and 0.75 to 0.95 in the validation set. The ILD subtypes could be discriminated with AUCs ranging from 0.95 to 0.98 in the training set and 0.83 to 0.93 in the validation set. Discussion: This international study demonstrates that eNose technology accurately differentiates breath profiles from ­patients with various ILDs. eNose technology holds potential as an easy point-of-care tool for the diagnosis of fILDs.

Interstitial lung disease (ILD) encompasses pulmonary disorders characterised by varying degrees of inflammation and/or fibrosis. The presence and extent of these pulmonary abnormalities on (high-resolution) computed tomography (CT) have consequences for diagnosis and treatment; however, inter-observer assessment varies. Analysis of exhaled volatile organic compounds (VOCs) through gas chromatography-mass spectrometry (GC-MS) offers a noninvasive approach to biomarker discovery and pathophysiology understanding. Our study aims to explore the ability of GC-MS-driven exhaled breath analysis to differentiate ILD patients with predominant fibrotic, inflammatory, or a combination of fibrotic and inflammatory pulmonary abnormalities in a training and an external validation cohort. In a multicentre cross-sectional study, patients diagnosed with ILD were recruited. After central review of chest CT scans by independent radiologists, patients were categorised as fibrotic, inflammatory or mixed phenotype group based on the percentage of chest CT scan abnormalities. Breath samples were collected and analysed via GC-MS. Significantly different VOC fragments between groups were selected and used to differentiate groups in the training cohort with sparse partial least squares discriminant analysis. Analyses were validated with patients from an external cohort. 53 patients were included, 21 patients in the fibrotic, 14 in the inflammatory and 18 in the mixed phenotype group. Area under the curve (AUCs) for discrimination between groups ranged from 0.89–1.00 in training cohorts. An attempt to confirm these findings in our external validation cohort resulted in AUCs of 0.63–0.84. Re-evaluation of the training model led to an AUC of 0.78–0.83. This study shows that GC-MS driven exhaled breath analysis towards differentiation of ILD phenotypes is challenging. Current findings emphasise the importance of predefined validation steps during the process of biomarker discovery.

Introduction: Home monitoring of physical parameters, symptoms, and quality of life by individuals with pulmonary fibrosis (PF) could overcome gaps in clinical care by early detecting disease deterioration, guiding patient management, and improving access to specialized care. However, its global adoption in clinical practice is lacking. The aim of this study is to gain a deeper understanding of healthcare professionals’ (HCPs) perspectives on implementing home monitoring for individuals with PF. Methods: Semi-structured interviews were conducted with HCPs. Transcripts were analysed through an inductive-deductive qualitative thematic analysis using the NASSS framework, which enables a systematic approach to analyse barriers and facilitating factors, that may hamper the implementation of technological innovations. Results: Thirty HCPs from eighteen interstitial lung disease clinics in the Netherlands were interviewed, reflecting varying levels of experience with home monitoring. They were positive towards the implementation of home monitoring for individuals with PF, favouring a tailored hybrid care approach. HCPs preferred incorporating home spirometry and alerts for deterioration. Different barriers were identified to implement home monitoring and hybrid care pathways, including technical challenges, such as reduced reliability of home spirometry in certain patients, and concerns about replacing care for progressive or unstable patients. HCPs emphasized the need for a coordinated hybrid care pathway and they advocated for strong evidence on cost-effectiveness and quality of hybrid care models. Discussion: Home monitoring is considered valuable in the management of PF. Identified preferences, barriers, and facilitators can be used to inform strategies for sustainable implementation of home monitoring in clinical practice.

Background: Interstitial lung disease (ILD) is a frequent manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. Clinical practice guidelines to standardise screening, diagnosis, treatment and follow-up for CTD-ILD are of high importance for optimised patient care. Methods: A European Respiratory Society and European Alliance of Associations for Rheumatology task force committee, composed of pulmonologists, rheumatologists, pathologists, radiologists, methodologists and patient representatives, developed recommendations based on PICO (Patients, Intervention, Comparison, Outcomes) questions with grading of the evidence according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology and complementary narrative questions agreed on by both societies. For both PICO and narrative questions, the Evidence to Decision framework was used to formulate the recommendations. Results: The task force committee concluded with recommendations for 25 PICO and 28 narrative questions, regarding ILD in the context of systemic sclerosis, rheumatoid arthritis (RA), idiopathic inflammatory myopathies, Sjögren disease (SjD), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). In four narrative questions, regarding screening and assessment of risk for ILD progression in MCTD, SjD and SLE and one PICO question regarding pirfenidone in CTD-ILD other than RA-ILD, the task force had insufficient evidence to support recommendations. Screening, diagnostic, monitoring and treatment algorithms were developed based on the recommendations and usual clinical practice. Conclusions: We provide practical guidance by evidence-based recommendations to clinicians for each of the CTDs. In many cases there is low certainty or absence of evidence and we encourage further research to fill these gaps.