Introduction Idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) can develop insidiously or manifest acutely, either as a fulminant initial presentation or unexpected deterioration of pre-existing ILD. In this study, we sought to characterise the disease course and prognostic determinants of acutely deteriorating IIM-ILD. Methods The Royal Brompton Hospital Immunology database was retrospectively interrogated for results of myositis-specific (MSA) and myositis-associated antibodies (MAA) from Jan 2015-Dec 2022. Patients with at least one acute IIM-ILD episode were identified using the SAS Clinical Data platform accessing Graphnet EPR and critical care systems. IIM were classified according to contemporaneous EULAR/ACR guidance and patients with <1 year follow-up were excluded. Time-to-death modelling was performed by Cox proportional hazards regression for acute and chronic (insidious) IIM-ILD and receiver operating curves generated to assess covariate prediction of mortality. Results 344 patients (median age 61.2, IQR 50.8–69.6; 63.4% female and 63.1% White Caucasian) with acute and chronic IIM-ILD were followed up for a median of 4.5 years (IQR 2.4–8.7 years) and 5.5 years (IQR 3.7–8.4) respectively. MSA including Jo-1 antibody were present in 42.4% and 36.7% while MAA were detected in 78.0% and 80.5% of the acute and chronic subgroups respectively. ILD presentation preceded myositis in 57.8% of cases. Overall, a third (118/344; 34%) of patients were hospitalised for acute IIM-ILD, with a fifth requiring intensive care. 20.4% (68/344) of all patients died during follow-up. MDA5 serology was positive in five patients including two survivors of acute IIM-ILD. Unadjusted hazard ratios (HR) for death were highest for acute ILD deterioration, age >60 and elevated pulmonary arterial pressure. Multivariate regression confirmed that they independently predicted mortality; the highest adjusted HR (6.64, 95% CI:3.7–11.9; P<0.001) was attributed to acute IIM-ILD. The discriminatory index (AUC) for the integrated model was 0.84. Covariate stratification revealed tiered subgrouping with significant survival differences (figure 1). Conclusions In identifying clinical variables that predict a poorer outcome in IIM, acute ILD development but not anti-Jo-1 serology was strongly associated with an increased likelihood of death. Detailed profiling including predictive stratification may allow high-risk patients with IIM-ILD to be triaged for earlier and more intensive intervention.

Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc), although disease behavior is highly heterogenous. While a usual interstitial pneumonia (UIP) pattern is associated with worse survival in other ILDs, its significance in SSc-ILD is unclear. We used the Systematic Objective Fibrotic Imaging analysis Algorithm (SOFIA), a convolution neural network algorithm which provides probabilities of a UIP pattern, to assess its associations with disease severity and progression in patients with SSc-ILD. Patients with SSc-ILD, first seen in our Unit between 1990 and 2019, were included if HRCT images, concomitant lung function tests, and follow-up data were available. Of 736 patients, 214 were excluded because of unavailable/poor quality images or lung function, leaving 522 patients. The SOFIA scores were converted into the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED)-based UIP probability categories: UIP not included in the differential (0–4%); low probability of UIP (5–29%); intermediate probability of UIP (30–69%); high probability of UIP (70–94%); and pathognomonic for UIP (95–100%) (Walsh et al. Am J Respir Crit Care Med. 2022 206(7):883–891). 72.9% of patients were classified as either 'UIP not included in the differential' or 'low probability of UIP', with 25.8% classified as 'intermediate probability of UIP' and 1.3% classified as 'high probability of UIP'. On univariable analysis higher likelihood of UIP probability was associated with worse 5-year survival (1.97 (1.52–2.55), p<0.001 (figure 1). However, on multivariable analyses adjusting for age, gender, ethnicity, and baseline composite physiologic index (CPI), the trend did not reach statistical significance (HR: 1.34 (0.94–1.62), p=0.12), suggesting a link between severity and UIP. The distribution of UIP probabilities was therefore examined according to the CPI quartiles, with higher UIP pattern probability associated with increasing baseline CPI quartiles (intermediate or high probability of UIP pattern: 4.6% in the lowest CPI quartile; 18.3% in the second quartile; 33.6% in the third quartile; 51.5% in the highest CPI quartile; p=0.0001). In conclusion, we observed an association between a higher probability of a SOFIA UIP pattern and severity, suggesting that a UIP pattern may occur in more advanced disease in SSc-ILD. Please refer to page A292 for declarations of interest related to this abstract.

Background: High-dose steroids (HDS) are used in specialist settings for the treatment of ARDS with features suggesting steroid responsiveness or as a last resort. Our previous case-matched cohort demonstrated that HDS increase 6mo. mortality (Remmington et. al, 2019). Aims and objectives: Identify if response to HDS predicted favourable outcomes. Methods: A retrospective observational study from a tertiary specialist respiratory ICU identified 79 patients (5 excluded) between 2009-2017 who received HDS for ARDS (AECC/Berlin criteria). Patients were grouped according to the change in lung injury score (LIS) between days 0 and 10 following HDS initiation. A modified LIS (excluding PF ratios for patients on ECMO) was used. Changes in LIS were grouped as follows; full responders (FR) ≥ 2, partial responders (PR) ≥ 1 and < 2, and non-responders (NR) < 1. Results: This study identified 7 (9.5%) FR, 14 (18.9%) PR, and 53 (71.6%) NR. Figure 1 shows the mortality for each group, which was significantly reduced when comparing the combined PR+FR groups to the NR group (p (log rank test) < 0.0001). Figure 1 – mortality over time in patients with different LIS responses Conclusions: A low proportion (28.4%) of ARDS patients given HDS had a FR or PR by day 10 yet these patients had significantly reduced mortality at 24mo. Further research using modified LIS to predict steroid responsiveness may assist clinicians in selecting ARDS patients for rescue therapy.

Abstract Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Introduction Aspergillosis complicating pulmonary sarcoidosis is associated with high mortality.1 The specific prognostic impact of fibrocavitary sarcoid disease, however, remains poorly understood. A better understanding of the factors that determine adverse outcomes in such patients may improve the management of both the underlying sarcoid disease and associated secondary fungal infection. Methods We implemented a clinical informatics pipeline to data-mine the hospital's clinical data warehouse and identify patients for inclusion in this study. Cases of pulmonary sarcoidosis with elevated Aspergillus IgG (>40 mgA/l) presenting between January 2009 and March 2021 were retrospectively identified. Controls (sarcoidosis with normal Aspergillus IgG titer) were case matched by baseline percentage-predicted gas transfer factor (TLco; ±5% variance). CPA cases were identified by using ISHAM criteria for diagnosing CPA, that is Aspergillus IgG >40 mgA/l plus keyword search for cavities or fungal ball in the CT reports based on search terms for aspergilloma, cavity, intra-cavitary, and mycetoma. Computed tomography (CT), baseline lung function, and survival data were analyzed. Results Among 179 cases (high Aspergillus IgG) and 477 controls (normal Aspergillus IgG), no inter-group difference was evident in the median age at presentation [48 (IQR 40-58) vs 50 (IQR 42-59)] or gender (proportion female: 45.5% vs 51.1%). Amongst the cases, 80/179 (45%) had fibrocavitary changes, compared with 14/477 (2.9%) of the controls (P <.001). Radiologically-evident aspergilloma was present in 80% (64/80) of the cases with fibrocavitary sarcoidosis. Evidence of fibrocavitary destruction was associated with higher overall mortality (60% vs 9.1% in the non-fibrocavitary subgroup; <.0001), and poorer median survival (Fig. 1). The median age at death was lower where there was fibrocavitary disease, and even lower with high Aspergillus IgG, and this was statistically significant. These cases also had poorer lung function compared to non-fibrocavitary disease (Fig. 2): mean %-predicted forced vital capacity (FVC) 71.3% vs 91.4% (P <.0001), and in the controls: 69.9% vs 86.0% (P <.01). A similar trend was observed in %-predicted TLco amongst the fibrocavitary cases: 45.8% vs 64.2% non-fibrocavitary (P <.0001) and in the fibrocavitary controls: 39.7% vs 59.0% non-fibrocavitary (P <.0001). Comparing only those with fibrocavitation, neither the percentage-predicted FVC (71.3% vs 69.9% predicted; P = .82) nor the percentage-predicted TLco (45.7% and 39.7% predicted; P = .16) differed between cases and controls. Conclusions Fibrocavitary sarcoidosis is associated with worse lung function and poorer median survival. In this group, elevated Aspergillus IgG highlights a greater incidence of aspergilloma. Implications Fibrotic transformation of pulmonary sarcoidosis heightens symptom burden, predisposes to chronic Aspergillus infection, and is prognostically important particularly when there is supervening fibrocavitary lung destruction. Sensitive stratification of such patients for the long-term outcomes may help identify particular individuals for earlier and more focused therapeutic intervention. Sources

Interstitial lung disease (ILD) is the most common cause of death in patients with Systemic sclerosis (SSc). Nearly all SSc-ILD patients test positive for antinuclear antibodies, but their autoantigen specificity is known only in a proportion. A large subset of patients with autoantibodies of unknown specificity, have the second highest rate of ILD progression after the Scl70+ group (Nihtyanova et al. doi: 10.1002/art.41153). Identification of patients at higher risk of ILD progression is key to optimal treatment and monitoring. A panel of 64 auto-antibodies was measured in the serum of 288 UK-based SSc patients (243 with ILD), and 50 controls, by Luminex immunoassay. Presence of each auto-antibody was defined as a mean fluorescence intensity >98% of the controls. Associations with the presence of ILD were assessed by Fisher’s exact test, and survival by Cox regression. Novel auto-antibodies to CBLC (6.7% in SSc-no ILD vs 0.8% in SSc-ILD, p=0.03), CD47 (15.6% vs 4.1%, p=0.008), HNRNPA1 (11.1% vs 2.9%, p=0.03), and KDM6B (24.4% vs 4.4%, p=0.002) were associated with absence of ILD. Presence of auto-antibodies to TRIM21 (Ro52), observed in 113 (39.2%) of our SSc cohort, was associated with increased mortality (median survival 12.0 vs 16.3 years), even after multivariable analysis, adjusting for age, gender, smoking history, and baseline lung disease severity (composite physiological index) in all patients (HR:1.48, 95%CI: 1.04-2.10, p=0.029), and in those with ILD (HR:1.56, 95%CI:1.07-2.28, p=0.02). In SSc patients, auto-antibodies, including of novel autoantigen specificity included in this study, can improve disease subgrouping and highlight pathogenetic pathways linked to more progressive ILD.

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

A proportion of patients with fibrotic hypersensitivity pneumonitis (fHP) follow a progressive disease course despite immunosuppressive treatment. We aimed to investigate the impact of routinely measured baseline blood biomarkers on mortality in fHP. Baseline demographics were recorded for consecutive patients with a diagnosis of fHP; discovery cohort (2010–2014) n=125, validation cohort (2015–2019) n=173. Patients were included if they had full blood count measurements performed within 3 months of first lung function test at our unit (baseline). Cox proportional hazards analyses were performed to test for associations with all-cause mortality. Step-wise backwards elimination was used to identify demographic variables independently associated with survival, for inclusion in the multivariable analysis. Univariable analysis in the discovery cohort identified age at baseline, ethnicity, disease severity (composite physiological index (CPI), and recent infection as significantly associated with mortality. Age and CPI remained independently associated following step-wise elimination. On multivariable analyses adjusting for age and CPI, monocyte count (HR:4.5 (95%CI: 2.02–10.06), p<0.001), CRP (HR: 1.06 (1.03–1.10), p=0.001), and median total white cell count (HR: 1.92 (1.20–3.05), p=0.006) and neutrophil count (HR: 1.74 (1.10–2.76), p=0.018) were significantly associated with shorter survival. Total white cell count was closely related to neutrophil count (Spearman's rho =0.92, p<0.001). Platelet, lymphocyte, eosinophil, basophil counts, and the neutrophil-to-lymphocyte ratio were not associated with survival. In the validation cohort, age, gender, smoking history, and CPI were significantly associated with survival on univariable analysis, with age and CPI remaining as independently associated. The associations with CRP (HR: 1.02 (1.00–1.03), p=0.007), median total white cell count (HR:2.00 (1.20–3.34), p=0.008), and neutrophil count (HR:1.95 (1.17–3.24), p=0.01), but not monocyte count, were replicated in the validation cohort on multivariable analysis, adjusting for age and CPI. CRP and median neutrophil count were independently associated with survival when included together in a multivariable analysis along with age and CPI. All associations remained significant when treatment with corticosteroids and recent infection, at the time of the blood test, were also included in the multivariable analysis along with age and CPI. Higher baseline CRP levels, and neutrophil counts, are significantly associated with increased mortality in patients with fHP.

Background and objective A proportion of patients with fibrotic hypersensitivity pneumonitis (fHP) follow a progressive disease course despite immunosuppressive treatment. Little is known about predictors of mortality in fHP. We aimed to investigate the impact of short-term lung function changes in fHP on mortality. Methods Baseline demographics for 145 consecutive patients with a multi-disciplinary team diagnosis of fHP, as well as baseline and 1-year follow-up of lung function, baseline echocardiographic findings, bronchoalveolar lavage (BAL) cellularity and all-cause mortality were recorded. Changes in forced vital capacity (FVC) >= 5% and >= 10%, and diffusion capacity of the lung for carbon monoxide (DLCO) >= 10% and >= 15% at 1 year were calculated. Cox proportional hazards analysis was performed to test for associations with mortality. Results Baseline lung function severity, age, presence of honeycombing on computed tomography (CT) and echocardiographic pulmonary arterial systolic pressure (PASP) >= 40 mm Hg were associated with early mortality, while BAL lymphocytosis was associated with improved survival. A decline in FVC >= 5% (hazard ratio [HR]: 3.10, 95% CI: 2.00-4.81, p < 0.001), FVC >= 10% (HR: 3.11, 95% CI: 1.94-4.99, p < 0.001), DLCO >= 10% (HR: 2.80, 95% CI: 1.78-4.42, p < 0.001) and DLCO >= 15% (HR: 2.92, 95% CI: 1.18-4.72, p < 0.001) at 1 year was associated with markedly reduced survival on univariable and multivariable analyses after correcting for demographic variables, disease severity, honeycombing on CT and treatment, as well as BAL lymphocytosis and PASP >= 40 mm Hg on echocardiography, in separate models. Conclusion Worsening in FVC and DLCO at 1 year, including a marginal decline in FVC >= 5% and DLCO >= 10%, is predictive of markedly reduced survival in fHP.

Introduction Aspergillosis complicating pulmonary sarcoidosis is associated with high mortality. The specific prognostic impact of fibrocavitary sarcoid disease, however, remains poorly understood. A better understanding of the factors that determine adverse outcomes in such patients may improve the management of both the underlying sarcoid disease and associated secondary fungal infection. Methods Cases of pulmonary sarcoidosis with elevated Aspergillus IgG (>40 mgA/L) presenting between January 2009 and March 2021 were retrospectively identified. Controls (sarcoidosis with normal Aspergillus IgG titre) were case-matched by baseline%-predicted gas transfer factor (TLco; ±5% variance). Computed tomography (CT), baseline lung function and survival data were analysed. Results Among 180 cases (high Asp IgG) and 229 controls (normal Asp IgG), no inter-group difference was evident in the median age at presentation [48 (IQR 40–58) vs 50 (IQR 42–59)] or gender (proportion female: 45.5% vs 51.1%). Amongst the cases, 81/180 (45%) had fibrocavitary changes, compared with 14/229 (6.1%) of the controls (P<0.001). Radiologically-evident aspergilloma was present in 79% (64/81) of the cases with fibrocavitary sarcoidosis. These cases also had poorer lung function compared to non-fibrocavitary disease: mean%-predicted forced vital capacity/FVC 71.3% vs 91.4% (P<0.0001), and in the controls: 69.9% vs 89.1% (P<0.01). A similar trend was observed in%-predicted TLco amongst the fibrocavitary cases: 45.8% vs 64.2% non-fibrocavitary (P<0.0001) and in the fibrocavitary controls: 39.7% vs 61.8% non-fibrocavitary (P<0.0001). Comparing only those with fibrocavitation, neither the%-predicted FVC (71.3% vs 69.9% predicted; P=0.82) nor%-predicted TLco (45.7% and 39.7% predicted; P=0.17) differed between cases and controls. Evidence of fibrocavitary destruction was associated with higher overall mortality (37% vs 9.1% in the non-fibrocavitary subgroup; <0.0001) and longest median survival (graph). Conclusions Fibrocavitary sarcoidosis is associated with worse lung function and poorer median survival. In this group, elevated Aspergillus IgG highlights a greater incidence of aspergilloma. Implications Fibrotic transformation of pulmonary sarcoidosis heightens symptom burden, predisposes to chronic Aspergillus infection and is prognostically important particularly when there is supervening fibrocavitary lung destruction. Sensitive stratification of such patients for long-term outcome may help identify particular individuals for earlier and more focused therapeutic intervention.

Introduction and Objectives Progressive pleuroparenchymal fibroelastosis (PPFE) is associated with a high symptom burden and frequently co-exists with a separate interstitial lung disease. The prognostic impact of such combinations is unclear and the clinical and computed tomographic (CT) determinants of mortality remain poorly characterised. Methods Patients with a diagnosis of PPFE (2004–19) were retrieved from the Royal Brompton Hospital ILD databases. CTs were evaluated for radiologic features, including: 1) the cranio-caudal extent and the severity of PPFE; 2) the hilar position (ratio of the lung apex to the 'hilar point' distance/lung apex to the diaphragmatic dome distance); 3) upper lobe volume loss, and 4) presence of co-existent ILD. Results 139 patients (75 [54%] female; median age 63.5, IQR 52–71.5) were evaluated, including 51 (36.7%) with idiopathic PPFE, 41 (29.5%) with concomitant idiopathic UIP, 17 (12.2%) with hypersensitivity pneumonitis and 8 (5.8%) with autoimmunity. Histopathological information was available in 50 (36%) patients, including from 39 surgical biopsies. 51 deaths were recorded among 130 patients with longitudinal data, yielding a median survival of 3 years. The mean severity of PPFE was negatively correlated with hilar position (r = -0.38, P<0.0005). Unadjusted hazard ratio (HR) analysis for mortality showed: age (HR 1.03 [95% CI: 1.01–1.05; P <0.01), DLco (HR 0.97 [95% CI: 0.95–0.99; P=0.01), composite physiologic index/CPI (HR 1.04 [95% CI: 1.01–1.07; P<0.005), right and left upper lobe volume loss (HR 0.97 [95% CI: 0.95–0.99]; P <0.01 and HR 0.95 [95% CI: 0.92–0.99; P<0.005, respectively) and the average of the right and left hilar position (HR 1.08 [95% CI: 1.04–1.13; P<0.0005). Although PPFE severity (P<0.001) and co-existent ILD (P<0.0005) were revealed as determinants of the hilar position (R2=0.26), multivariable adjustment confirmed that only CPI (HR, 1.04 [95% CI: 1.00–1.07; P <0.05), increased age (HR, 1.03 [95% CI: 1.01–1.06; P =0.01) and mean hilar position (HR, 1.06 [95% CI, 1.01–1.12; P =0.02) independently predicted mortality. Conclusions Patients with progressive PPFE have a poor outcome, with a median survival that is comparable to IPF. Identifiable and measurable changes in specific clinical, physiologic and radiologic parameters appear to characterise the adverse prognostic profile of these individuals.

P4 Table 1Characteristics of the subjectsCharacteristics Subjects with ILAs on LDCT (n = 39) Age, yr, mean (± SD) 68.8 (± 4.3) Gender, n (%) Female 15 (38.5) Male 24 (61.5) Smoking status, n (%) Current 7 (17.9) Ex 32 (82.1) Respiratory symptoms, n (%) None 19 (48.7) Cough 3 (7.7) Dyspnoea 9 (23.1) Cough & dyspnoea 6 (15.4) N/A 2 (5.1) Physical examination findings, n (%) None 5 (12.8) Crackles 17 (43.6) N/A 17 (43.6) Baseline lung function,%pred, median (range) FEV1,% pred 91 (58 – 130) FVC,% pred 94.8 (65 – 143) TLco,% pred 57.6 (28.4 – 98.8) Kco,% pred 79.5 (36.4 – 94) MDT Diagnosis ILAs, n (%) 8 (20.5) ILD, n (%) IPF 14 (35.9) Smoking-related ILD 6 (15.4) Hypersensitivity pneumonitis 4 (10.3) PPFE 3 (7.7) Sarcoidosis 1 (2.6) Post-COVID ILD 1 (2.6) Vasculitis 1 (2.6) Unclassifiable 1 (2.6) Treatment, n (%) Smoking cessation advice 6 (15.4) Antifibrotic 7 (17.9) Immunomodulatory treatment 2 (5.1) None 23 (59) ResultsILAs of >5% extent on LDCT were identified in 39/1853 (2.1%) subjects screened between August 2018 and April 2021 (table 1). Respiratory symptoms were present in 18/39 (46.1%) and crackles were auscultated in 17 of 22 subjects (77.3%) undergoing physical examination. Past exposure to potential environmental triggers was noted in 21/39 (53.8%). Diagnostic bronchoalveolar lavage was performed in 7/39 (17.9%) and one patient underwent transbronchial lung cryobiopsy. After MDT discussion, ILD was concluded in 31/39 (79.5%) cases, of which 14/31 (45.2%) were diagnosed with IPF. In the IPF subgroup, antifibrotics were initiated in 7/14 (50%) of cases. In those diagnosed with other ILDs, immunomodulatory treatment was initiated in 2/25 (8%) subjects.ConclusionA large proportion of individuals with newly identified ILAs have an abnormal clinical examination and respiratory symptoms, consistent with the widely held suspicion that ILD is underdiagnosed in the community. Lung cancer screening in this demographic provides a unique opportunity to address this unmet health metric. Earlier identification of ILD, specifically IPF, allows institution of antifibrotic therapies proven to modify the natural history of the disease by preserving lung function and extending life. The cost-effectiveness of this approach for ILD screening warrants detailed evaluation.

Background Vitamin D (VitD) has been shown to have anti-fibrotic properties in the bleomycin mouse model of pulmonary fibrosis. This study aimed to establish whether an association exists between VitD deficiency and outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods The VitD status of an anti-fibrotic treated IPF patient cohort at a single UK tertiary centre was retrospectively analysed. Clinical deficiency was defined as VitD<25 nmol/L as per NICE guidelines. Serial lung function was determined in the 12 months (or as close as possible) after the VitD test. Frequency of infections and acute exacerbation events were recorded, and transplant-free survival was calculated from the earliest patient contact. Results Of 300 IPF patients, 92 (30.6%) had documented VitD results (78.3% male, mean age 72±8 years). Sixteen (17.4%) patients were clinically deficient. Baseline FVC and DLco were 70.3%±11.9% and 39.1%±12.9% in the non-deficient and 68.4%±10.7% and 39.8%±8.8% in the deficient groups respectively (p=0.55, p=0.85 respectively). There was no significant difference in the prevalence of VitD deficiency between patients taking Pirfenidone (11/66 (17%)) and Nintedanib (5/26 (19%))(p=0.77). Median transplant-free survival was 1128 days in the non-deficient group and 532 days in the deficient group (p=0.0079)(Figure 1). Following adjustment for age, gender and baseline composite physiologic index (CPI), the Cox proportional hazard ratio for VitD deficiency and transplant-free survival was 2.36 (95% CI 1.128–4.942, p=0.023). There was no difference in mean annual relative change in FVC between deficient (-8.0%±8.9%) and non-deficient patients (-9.1% ±12.9%)(p=0.79). The incidence of infections and acute exacerbations did not significantly differ between groups. Conclusions In this cohort of antifibrotic treated IPF patients, there is an association between VitD deficiency and adverse outcomes. Whether VitD deficiency is associated with a poorer prognosis as a surrogate for a co-morbid state or is relevant to IPF disease pathogenesis remains unclear. Although limited by cohort size, it is curious that reduced survival appears to be independent of lung function decline and further analyses with regard aetiology of mortality is required. Prospective studies of VitD supplementation in antifibrotic treated IPF patients may be indicated to explore a potential therapeutic role.

Background: The ATS/ERS guideline definition of obstructive pattern in lung function tests does not consider measurement of static lung volumes as mandatory. Methods: Patients with pulmonary sarcoidosis (n=1110; 529 males) were enrolled. Static volumes expected in association with an obstructive process was quantified in a control cohort of COPD patients (n=899; 536 males). Ventilatory defects in sarcoidosis patients, were defined according to ATS/ERS and with the reclassification of a sub-group of patients from obstructive to mixed disease, based on TLC values below those expected in the control COPD cohort. Results: A prevalence of 10.4% of mixed disease was identified, which was associated with a higher prevalence of chest radiographic stage IV disease (p The comparison of static lung volumes between sarcoidosis with obstructive pattern (n=329) and COPD patients revealed lower static lung volumes in sarcoidosis patients, (TLC%predicted: 96.6±11.8 vs 121±17.8, p Conclusion: Mixed disease may be underestimated in sarcoidosis using current ATS/ERS guidelines despite its high prognostic value in sarcoidosis.

Introduction Weight loss is a feature of many progressive respiratory conditions. We aimed to establish average weight loss over 12 months in a cohort of patients with Idiopathic Pulmonary Fibrosis (IPF) untreated with steroids or antifibrotic therapy. Our hypothesis is that weight loss is a feature of disease progression in patients with IPF. Methods Patients diagnosed with IPF prior to the availability of antifibrotic therapy were retrospectively identified. Subjects receiving immunosuppressive therapy were excluded. Weight loss was assessed using body mass index (BMI) calculated from height and weight reported on serial PFTs. Longitudinal changes in BMI were assessed using a linear mixed effects model. Continuous variables are presented as means (±SD) and categorical variables as proportions. Differences between subject groups were evaluated with the use of the Mann–Whitney test. Time-to-event curves were calculated using the Kaplan–Meier method and compared with the use of the log-rank test. Results Two hundred and ninety eight patients with baseline BMI data were included. Of those 200 subjects had longitudinal data available with an average follow up time of 17.6 (±13) months. The patients were predominantly male (78%) with a mean age of 68.6 years and moderately severe disease (DLCO 35.7% predicted; FVC 68.9% predicted). Baseline BMI was 27.4 (±4.8). Patients with more severe disease had a lower BMI at the time of diagnosis compared to those with milder disease (GAP Stage 1 vs 3; 28.1(±3.6) vs 25.0(±4.7, P<0.001). On average the cohort experienced an annual decrease in BMI of 0.51 kg/m2 per year. There was no association between baseline BMI and mortality, but longitudinal decline in BMI did confer an increasing mortality risk (RR 1.40 for each 1% change in BMI; 95% CI 1.06–1.98, p<0.019). Those with ≥5% annual decline in BMI were at significant risk of mortality compared to patients not experiencing a decline (RR 2.13, 95% CI 1.46–3.13; p <0.001) (figure 1). Conclusions Patients with more severe disease at baseline have a lower BMI at the time of diagnosis. While baseline BMI does not predict mortality, progressive decline in BMI does.Abstract P10 Figure 1 Patients with IPF who experiencing a 5% or greater decline in BMI over 12 months are at increased risk of mortality. Kaplan Meier curve generated by Cox proportional-hazards model. Log rank P test value reported

Interstitial lung disease (ILD) is the main cause of death in systemic sclerosis (SSc). The progression of SSc associated ILD (SSc-ILD) is highly variable, and markers predictive of severe or progressive ILD are needed to identify patients at risk. Serum levels of 15 biomarkers were measured by Luminex assay and ELISA, as appropriate, in 189 SSc patients. Statistical analysis was performed using STATA12. CCL18 and MMP-7 levels were significantly higher in patients with ILD (median: 61,886 pg/ml and 1,385 pg/ml, respectively) compared to patients without ILD (48,486 pg/ml, p=0.0049 and 1,155 pg/ml, p=0.046, respectively), and periostin levels were significantly lower in patients with ILD than without (84,620 pg/ml compared to 105,096 pg/ml, p=0.027). Serum levels of CCL18 (p=0.038), MMP-7 (p=0.0069), CXCL12 (p=0.016), and MMP-12 (p=0.049) were all significantly higher in patients with extensive, rather than limited, lung involvement according to the Goh et al staging (Goh et al. Am.J. Respir. Crit. Care. Med. 2008 177:1248-1254), while periostin levels were significantly lower in extensive compared to limited lung disease (p=0.025). Higher concentrations of CCL18 (p=0.001) and IL-10 (p=0.018) were associated with mortality. The CCL18 association remained significant following adjustment for disease severity. Neopterin was associated with time to decline in DLCO ≥15% (p=0.042). Our results suggest that CCL18, MMP-7, CXCL12, MMP-12, periostin, and neopterin may be effective biomarkers for predicting severity and/or progression of lung involvement in SSc.

Background Lung cancer is historically described as a late complication of IPF, implying that screening in early IPF would have a low yield. The frequency of finding lung cancer in newly diagnosed IPF is not known. Methods The Lung Cancer multidisciplinary team (LCM) database at the Royal Brompton Hospital was retrospectively examined for the period 2007–18 to identify cases with underlying IPF. Additionally, new ILD referrals seen over the same period were retrospectively filtered for cases with a final/MDT diagnosis of IPF. Results In the period of interest, 3267 cases of suspected lung cancer were referred by various parties to the LCM and a total of 1780 cases of IPF were diagnosed by the RBH ILD Unit. Of the latter, 61 were referred for exclusion of malignancy (mean age 70.7; 84% male; mean predicted FVC 80.1% and TLco 39.7%). Primary lung cancer was histologically confirmed in 30/61 (49.2%) cases and highly suspected in another 16 (26.2%) based on tumour behaviour and/or PET-FDG staging. The rate of cancer diagnosis amongst all IPF patients was therefore 2.6% (46/1780). Coexistent emphysema was present in exactly half (23/46) of this group. Cancer subtyping revealed 24 cases of non-small cell and 7 cases of small cell lung cancer. Patients considered unfit for biopsy had poorer lung function; FVC: 67.6%±21.9% vs. 84.9%±18.3% (P<0.05) and TLco: 32.3±13.1% vs. 42.6±10.5% (P<0.005). Lung cancer and IPF were diagnosed within 12 months of each other in 14/30 (46.7%) of those with confirmed malignancy; in five cases, radiological suspicion of cancer predated IPF diagnosis. The two entities were similarly identified within a 12-month interval in half of cases with a high-probability cancer that could not be biopsied. Overall, 1 in 2 cancers in the cohort was diagnosed at stages III/IV, a frequency lower than that for the general population (70–75%, CRUK 2014–15 data). Conclusions Near-contemporaneous (<12-month interval) presentation of IPF and lung cancer is not rare in ostensibly ‘mild’ IPF especially when there is concomitant emphysema. A number of factors may account for the lower proportion of high-stage cancer in IPF patients including more frequent imaging prompted by symptom change.