Interstitial lung disease (ILD) affects up to half of individuals with systemic sclerosis (SSc), within which it is a major cause of disease-related morbidity and a leading cause of mortality. Forced vital capacity (FVC) has been endorsed as a primary outcome measure for randomised controlled trials (RCT) assessing the efficacy of novel treatments for SSc-ILD. The FVC is considered a suitable surrogate biomarker, although does not directly capture information on how patients ‘feel’ and ‘function’, which regulators consider essential for marketing authorisation. Only patient-reported outcome (PRO) instruments can provide this insight. This review aims to systematically examine the inclusion, validity and performance of respiratory-specific PRO instruments used in SSc-ILD RCTs, using the COnsensus based Standards for the selection of health Measurement INstruments (COSMIN) framework and regulatory guidance.Our search identified 10 respiratory-specific PRO instruments used in SSc-ILD RCTs. Of these, 4 are single-item instruments and 2 were developed with any ILD patient input. Seventeen studies assessing the measurement properties of respiratory-specific PRO instruments within an SSc-ILD population were identified, with varying methodologies.The findings of this review highlight the lack of consensus for the use of respiratory-specific PRO instrument use in SSc-ILD RCTs. Identified instruments have unproven content validity within this population and limited evidence for other measurement properties, primarily derived from post hoc analyses of RCT data or cross-sectional studies. Future work should prioritise assessing the content validity and measurement properties of existing ILD specific instruments according to COSMIN guidance.

Objectives:Cardiovascular events (CVEs) and malignancy are important non-disease-related causes of mortality in SSc. We evaluated secondary care utilisation and impact of deprivation on comorbidity patterns in SSc in England. Methods:We analysed secondary care service utilisation in SSc using Hospital Episode Statistics for England for 2024. Cases were linked to Index of Multiple Deprivation deciles. Myocardial infarction (MI), lung cancer, breast cancer, melanoma rates and short-term all-cause mortality were explored, alongside comparisons with SLE and RA. Results:In 2024, ≈6000 people with SSc (84.6% female, 70.8% between 51 and 80 years of age, 73.3% White ethnicity) accessed secondary healthcare in England. Older SSc patients were overrepresented in less-deprived postcodes (P < 0.001). MI, lung cancer, breast cancer and melanoma were more common in SSc compared with unmatched estimates in the general population. Lung cancer was more frequent among less-deprived patients (P < 0.001). The all-cause mortality attrition rate was ≈3% in SSc over 3 months (30.8% with lung cancer and >60% with melanoma). Rates of breast cancer were higher in SSc compared with SLE (P = 0.014) and RA (P = 0.012). There was a higher rate of lung cancer in SSc compared with SLE (P < 0.001). Melanoma rates were similar across diseases (≈0.2%). Conclusion:Secondary care utilisation in SSc suggests less deprived SSc patients are older. All-cause mortality is higher in SSc patients receiving cancer care. Cancer occurrence is higher in SSc compared with SLE and RA. Our findings might support healthcare services planning and cancer screening for SSc in England.

Introduction Hospitalisation for respiratory-related events is an important contributor to morbidity and mortality in individuals with fibrotic interstitial lung disease (fILD). Many such hospitalisations are due to acute exacerbations (AE-fILD), but AEs are poorly understood and there are limited evidence-based guidelines for their management. Most research in this area focuses on AEs of idiopathic pulmonary fibrosis (IPF), the commonest fILD and AEs of non-IPF fILD are less well studied. Furthermore, patients with fILD who are hospitalised with a respiratory-related event but do not meet the diagnostic criteria for AE are an important under-studied group. The INterstitial lung Disease EXacerbations (INDEX) study will describe in detail a large real-world population with fILD admitted to hospital for respiratory-related causes, including AE-fILD, as well as identify potential prognostic factors.Methods and analysis This multicentre retrospective cohort study will analyse case notes for patients admitted to hospital between 1 September 2022 and 31 August 2023. Patient demographic data, clinical features on hospital admission, pre and postadmission investigation results, treatment approaches taken and mortality data will be collected. These data will be used to describe the patient population and to identify associations between patient, clinical presentation and treatment factors and outcomes. The primary outcome will be transplant-free survival at 90 days following the commencement of the index admission.Ethics and dissemination The study has been approved by the Health Research Authority (HRA) (IRAS 317419) and has been prospectively registered on clinicaltrials.gov (NCT06685874). The HRA waivered the requirement for Research Ethics Committee approval due to only anonymised routinely collected clinical data being collected.Conclusion This study will enhance our understanding of respiratory-related hospital admissions in fILD, including AE-fILD. The resulting data will describe a real-world patient population, define current standard care and may indicate prognostic and treatment factors to be assessed in future clinical trials.

Background: The British Thoracic Society (BTS) currently recommends pre-flight clinical assessment of all symptomatic patients with interstitial lung disease (ILD). This may include hypoxic challenge testing (HCT) to determine whether supplemental in-flight oxygen is required, but it is not universally available. Objectives: (1) To validate a previously published pre-flight assessment algorithm in predicting outcomes of HCT in ILD. (2) Compare the sensitivity and specificity of the original algorithm to an amended version published in the BTS clinical statement on air travel. Design: Single centre, cohort study. Methods: A single-centre retrospective cohort analysis of ILD patients attending for HCT between March 2017 and April 2023. Results: A total of 126 patients with a diagnosis of ILD underwent HCT. Median forced vital capacity 75.0% predicted (interquartile range (IQR) 24.8) and transfer factor for carbon monoxide 45.8% predicted (IQR 18.6). Diagnosis of idiopathic pulmonary fibrosis in 50.8% (n = 64). A total of 18 individuals became hypoxic during the test (a fall of PaO2 to <6.6 kPa or oxygen saturations (SpO(2)) < 85% pO(2), 'failed HCT'). The pre-flight algorithm demonstrated moderate sensitivity (69.4%, identifying most 'passed' cases correctly, 43/62) and good specificity (83.3%, most 'failed' cases correctly identified, 10/12). A total of 52 (41.2%) patients would have been referred for HCT, with 11.5% (n = 6) requiring in-flight oxygen ('failed' HCT). The modified BTS algorithm demonstrated a moderate sensitivity of 70.3% (45/64) and good specificity of 83.3% (10/12). In both algorithms, 29 patients would have been advised in-flight oxygen, whilst only 10 of these required supplementary oxygen according to HCT. There were two divergences in algorithmic outcomes, both arising from patients without desaturation on exercise, resulting in two fewer HCT using the BTS algorithm and correctly advising 'no supplemental oxygen' was required. Conclusion: In this validation study, the practical pre-flight algorithm demonstrates good specificity and moderate sensitivity for predicting HCT outcomes. The BTS modified algorithm demonstrates comparable sensitivity and specificity. Additional work is required to further develop practical guidance to reduce both the number of HCT advised and the proportion of patients incorrectly advised to arrange supplemental in-flight oxygen.

Objectives:To describe a novel radiographic phenotype of systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) observed within a regional specialist multidisciplinary (MDT) service. Methods:This was a retrospective case series of patients with SARD-ILD complicated by radiographic pulmonary cystic destruction. Cases were identified through review of MDT records from the North Bristol SARD-ILD service. Cases with MDT reported 'cystic changes' were identified and clinico-radio-pathological features reviewed. Results:Five cases of SSc-associated ILD (SSc-ILD) and two cases of antisynthetase syndrome-associated ILD (ASyS-ILD) with cystic changes were identified among a total of 108 SARD-ILD patients. All seven cases presented with radiological patterns of cellular non-specific interstitial pneumonia (NSIP). The median age at diagnosis with SARD was 33 years and six cases had ILD identified within 6 months of SARD diagnosis. The cohort was ethnically diverse, with one ex-smoker. Microcystic destructive changes appeared and progressed within areas of ground glass despite standard-of-care immunomodulation. Changes are radiographically and histologically distinct from traction bronchiolectasis, honeycombing and smoking-related lung disease. Histological specimens were available for two cases confirming fibrotic NSIP, with one including affected tissue demonstrating intimal thickening of the pulmonary vasculature. Over a median follow-up of 49 months, all cases remain alive and transplant free; five fulfilled criteria for progressive disease and six required ambulatory oxygen. Conclusions:This represents the first western cohort describing microcystic destructive pulmonary changes in SSc-ILD and the first report in ASyS-ILD. Systematic case identification is required to determine demographic associations and prognostic implications.

OBJECTIVES:Telangiectasia are common in SSc. We explored the relationship between the site and quantity of telangiectasia with disease characteristics in SSc, and the agreement between patient- and physician-reported quantification of telangiectasia. METHODS:A retrospective analysis of a large, cross-sectional international SSc-related vasculopathy study was undertaken, including clinician and patient assessments of telangiectasia counts (0, 1-6, 7-15 or >15) in the face, forearms and hands. Relationships between telangiectasia count at each site, demographics and clinical features including calcinosis, digital ulceration (DU) and pulmonary arterial hypertension (PAH) were examined using proportional odds logistic regression. A binary logistic regression model examined the value of telangiectasia counts on the accuracy of identifying co-existent PAH. Concordance between clinician- and patient-reported telangiectasia counts at each anatomical site was tested. RESULTS:Higher telangiectasia counts over the face and hands were associated with higher prevalence of calcinosis, DU and PAH in univariate analysis (P < 0.001-0.003). In multivariate analysis, the presence of PAH, DU and calcinosis were associated with higher facial telangiectasia (P < 0.05). The logistic regression model for the detection of PAH was enhanced with inclusion of telangiectasia count and site (area under the precision recall curve 0.824-0.875). Strength of agreement between clinician- and patient-reported telangiectasia counts were moderate for face and forearms (kappa 0.648 and 0.605 respectively, P < 0.001) and relatively weaker for hands (kappa 0.584, P < 0.001). CONCLUSION:The number of telangiectasia might be considered a complementary biomarker to the presence of vascular complications of SSc including PAH, DU and calcinosis. The anatomical regions and level of instruction provided for patient-reported count of telangiectasia need further optimization to be considered reliable and feasible. In addition, future work should consider correlations with nailfold capillaroscopic patterns.

BACKGROUND:Pulmonary fibrosis is often accompanied by high levels of unmet supportive care needs that impact psycho-social well-being and overall quality of life for both the person with pulmonary fibrosis and their family. The provision of appropriate services to reduce unmet supportive care needs represents a key health care priority. AIM:To provide the first broad-level overview of the available evidence of the characteristics and impact of interventions developed to address unmet supportive care needs in people with pulmonary fibrosis and/or their caregivers. DESIGN:Scoping review. The protocol was registered with Figshare.com (protocol number 25452100). DATA SOURCES:Systematic electronic searches were performed in Cochrane Central, EMBASE, Medline, PsysINFO and CINAHL from inception to March 2024 to identify all studies describing interventions to address supportive care needs of people with pulmonary fibrosis and/or their carers. RESULTS:A total of 24 studies (1 abstract and 23 full text studies) met inclusion criteria. There was considerable heterogeneity in interventions described and outcome measures used. Multimodal interventions with a focus on symptom control, quality of life, peer support and psychosocial input appear to be crucial to integrated, effective and patient led supportive care. The generalisability of interventions is limited by small sample size, the use of inconsistent and/or non-validated evaluation measures and study attrition. CONCLUSIONS:Further research with greater involvement of key stakeholders is urgently required. Future directions should also assess barriers to supportive care and investigate other avenues such as telehealth or remote delivery to improve access and acceptability.

BACKGROUND:The unpredictable trajectory and heterogeneity of interstitial lung disease (ILDs) make prognostication challenging. Current prognostic indices and outcome measures have several limitations. Quantitative computed tomography (qCT) provides automated numerical assessment of CT imaging and has shown promise when applied to the prognostication and disease monitoring of ILD. This systematic review aims to highlight the current evidence underpinning the prognostic value of qCT in predicting outcomes in ILD. METHODS:A comprehensive search of four databases (Medline, EMCare, Embase and CINAHL (Cumulative Index to Nursing and Allied Health Literature)) was conducted for studies published up to and including 22 November 2024. A modified CHARMS (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies) checklist was used for data extraction. The risk of bias was assessed using a Quality in Prognostic Studies template. RESULTS:The search identified 1134 unique studies, of which 185 studies met inclusion and exclusion criteria. Commonly studied ILD subtypes included idiopathic pulmonary fibrosis (41%, n=75), mixed subtypes (26%, n=48) and systemic sclerosis ILD (16%, n=30). Numerous studies showed significant prognostic signals, even when adjusted for common covariates and/or significant correlation between serial qCT biomarkers and conventional outcome measures. Heterogenous and nonstandardised reporting methods meant that direct comparison or meta-analysis of studies was not possible. Studies were limited by the use of retrospective methodology without prospective validation and significant study attrition. DISCUSSION:qCT has shown efficacy in the prognostication and disease monitoring of a range of ILDs. Hurdles exist to widespread adoption including governance concerns, appropriate algorithm anchoring and standardisation of image acquisition. International collaboration is underway to address these hurdles, paving the way for regulatory approval and ultimately patient benefit.

Objectives:Cutaneous manifestations of systemic autoimmune rheumatic disease-interstitial lung disease (SARD-ILD) are clinically useful diagnostic features that can support early diagnosis and management. However, medical education resources often lack diversity in representing skin tones, which lead to inequities in healthcare delivery. Our study aimed to quantify the proportion of skin tones represented in medical literature that depict cutaneous features relevant to SARD-ILD. Methods:A structured search of medical resources was conducted with the support of North Bristol NHS Trust Library and Knowledge Service. We systemically reviewed images of cutaneous signs associated with SSc, DM and vasculitis. Images that did not depict these conditions were excluded. Each image was assigned a Monk Skin Tone (MST) Scale score (1-10). A chi-square goodness-of-fit analysis was used to establish whether the distribution of images was equal. Results:Sixteen e-resources and 26 textbooks were analysed, yielding 790 images: there were 190 depicting SSc, 401 DM and 199 vasculitis. The chi-square indicated a significantly unequal distribution of images across skin tones (P < 0.001), a pattern that persisted across all conditions. Furthermore, there was no significant improvement in skin tone representation from 2009 to 2022 (median skin tone category 1-2). Conclusion:There is persistent underrepresentation of people of global majority in educational resources, despite evidence of higher disease prevalence and severity among individuals with darker skin tones. Increasing the inclusion of diverse skin tones in medical imagery is essential to enhancing diagnostic accuracy, reducing health disparities, and improving clinical outcomes.

INTRODUCTION:Growing evidence suggests that biological sex influences the incidence, presentation, diagnosis and outcomes of many lung diseases. Understanding these differences is the first step towards precision medicine to improve patient care. METHODS:In this cross-sectional study, idiopathic pulmonary fibrosis (IPF) patients enrolled in a national (UK), multicentre registry were categorised by sex and analysed for differences in demographics, pulmonary function tests, high resolution CT radiological pattern, eligibility/uptake of antifibrotics and survival. RESULTS:Of 7177 cases, 77.8% (n=5587) were male, median age 75 years (IQR 69.5-80.5) for both sexes (p=0.83). Males were more likely to have a history of smoking (males 72.9% vs females 60.5%, p<0.001) and lower baseline median forced vital capacity (FVC) % predicted (males 76.4%, IQR 66.2-86.7 vs females 78.8%, IQR 68.6-89.1, p<0.001). Diabetes (males 22.8% vs females 15.1%) and cardiovascular disease (males 58.9% vs females 47.8%) were statistically more common in males (p<0.001), while gastro-oesophageal reflux disease (males 20% vs females 24.6%) and major depressive illness (males 0.8% vs females 2.5%) were more common in females (p<0.001). Significantly, more females experienced symptoms for >24 months prior to first clinic appointment (females 40.1% vs males 36.6%, p=0.03). While more males in the cohort met eligibility criteria for antifibrotics at baseline (pirfenidone FVC 50%-80% males 54.7% vs females 47.6%, nintedanib FVC 50%-80% males 47.0% vs females 41.5%, p<0.001), a larger proportion chose not to commence antifibrotic treatment (males 47.0% vs females 29.6%, p<0.001). Female sex was associated with longer survival; for females, the 75% Kaplan-Meier survival quartile is 7.6 years (95% CI 5.51 to 9.68 years) versus 4.3 years (95% CI 3.82 to 4.78) for males (p<0.001). Male sex (HR 1.76 (95% CI 1.22 to 2.54), p=0.002), higher age (HR 1.042 (95% CI 1.02 to 1.06), p<0.001), lower baseline FVC % predicted (HR 0.98 (95% CI 0.97 to 0.98), p<0.001) and coexistent lung cancer (HR 9.3 (95% CI 2.86 to 30.24), p<0.001) were all independently associated with worse survival. CONCLUSION:This is the first UK study to use national registry data to systematically evaluate IPF disease characteristics stratifying by biological sex and highlights distinct characteristics between groups. Future clinical trials should explicitly explore sex-specific targeted interventions and analyses to optimise future IPF patient care.