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Background. Interstitial Lung Disease (ILD) is a frequent manifestation of Sjögren’s Disease (SjD), associated with significant morbidity and mortality. However, data on the prevalence of progressive-ILD in SjD remain scarce, and biomarkers for predicting progression are lacking. Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) is a validated CT-based software that quantifies ILD patterns such as ground-glass opacities, reticulation, honeycombing, and low attenuation areas. CALIPER-derived parameters correlate with pulmonary function tests (PFT) and outcomes in IPF and other autoimmune ILDs, but their role in SjD-ILD is unexplored. Our aim was to assess the prognostic value of CALIPER-derived parameters in SjD-ILD patients   Materials and Methods. SjD patients (2016 ACR/EULAR criteria) with HRCT-confirmed ILD followed from Jan-2018 to Sep-2023 were retrospectively included if >/=1 HRCT was suitable for CALIPER analysis. Clinical, laboratory and PFT data were collected at baseline and follow-up. Progressive-fibrosing ILD (PF-ILD) was defined (ATS criteria) by >/=2 of: worsening symptoms, FVC decline >/=5% or DLCO >/=10%, or radiological progression within 1 year. CALIPER-derived ILD% (sum of ground-glass, reticular, honeycombing) and VRS% (vascular-related structures) were calculated. Visual ILD extent (Warrick score) and pattern were assessed by a thoracic radiologist   Results. Twenty-three patients (F:M=18:5, mean age 66.2±9.5 yrs, mean follow-up 6.1±5 yrs) were enrolled. ILD patterns included NSIP (n=14), UIP (n=6), and NSIP+OP (n=3). Dyspnea and cough occurred in 21 and 19 patients respectively. Median baseline FVC and DLCO were 83% and 64%. Seventeen patients received immunosuppressants; none received antifibrotics. Seven required long-term oxygen (LTO2) and 7 developed PF-ILD. Baseline ILD% and VRS% demonstrated a moderate-strong correlation with FCV% and DLCO%, visual ILD quantification (Warrick score) and between them (table 1). VRS%, Reticulation%, and Honeycombing% were significantly higher in UIP (p=.021, .038, .047 respectively). On univariate regression analysis, VRS% (OR 3.2, 95%CI 1.1-9.1, p=.03) and ILD% (OR 1.13, 95%CI 1.01-1.3, p=.05) were associated with LTO2. According to ROC analysis, VRS% had an AUC of 0.813 (p=.019) with an optimal cut-off of 3.8% yielding a sensitivity of 71.4% and a specificity of 87.5% in predicting LTO2. ILD% had an AUC of 0.777 (p=.038) with a cut-off of 11.6% resulting in a 71.4% sensitivity and a 75% specificity in predicting LTO2. On univariate analysis VRS% (OR 2.8, 95%CI 1-8, p=.05) was associated with a PF-ILD behavior in the next year, with an AUC of 0.85 (p=.023) and an optimal cut-off of 3.8% resulting in a 83.3% sensitivity and 80% specificity.   Conclusions. CALIPER-derived parameters correlate strongly with lung function and predict adverse outcomes in SjD-ILD. Automated HRCT analysis offers promising digital biomarkers for ILD assessment and risk stratification. Integrating these metrics with clinical and functional data could support early identification of progressive-ILD and guide therapy. Further validation in larger cohorts is warranted.

Background. Systemic sclerosis (SSc) is a rare immune condition mainly affecting connective tissues with interstitial lung disease (ILD) being a common feature of its clinical milieau. Among others, suffering from autoimmune systemic diseases (ASD) emerged as one of COVID-19 predisposing factors. Objective: the purpose of the present work was to assess the clinical, therapeutic and functional outcomes of a cohort of patients affected by SSc-related ILD (SSc-rILD).   Materials and Methods. We retrospectively analysed data from medical charts of 64 SSc-rILD patients from our Rheumatology Unit of Bari clustered into two groups depending on whether they experienced COVID-19 (35 patients) or not (29 patients). Baseline characteristic intended as the ones acquired at the very last visit before COVID infection or, in the other group, before SARS-CoV2 outbreak, included skin pattern, autoimmune features, ongoing medications, clinical manifestations, respiratory function as assessed through spirometry and radiographic appearance evaluated as TC-scans of the lungs. This information was then newly investigated at the latest available follow-up date as long as COVID-19 outcomes. Standard descriptive statistics were employed to evaluate demographic, clinical and functional characteristics. SPSS IBM was the software of choice in our work.   Results. The mean follow-up period was 46.3 (SD ±10.9) months for the non-COVID and 38.7 (±12.7) months for the COVID cohort. Diffuse cutaneous subset was found to be statistically more frequent in the COVID group (p=0.007) at baseline. The cohort resulted homogeneous when investigated for other demographical characteristics. The main highlight of our work comes from the evaluation of pulmonary functional index variations (Table 1): FVC and FEV1 showed a greater reduction in patients who experienced COVID, respectively -15.7% ±31.4% (vs -0.9%±14.8%, p=0.02) and -15.5% ±30.5% vs -1.7% ±13.9%, p=0.03. A similar trend was observed for DLCOc, -6.1% ±13.5% (vs -0.8% ±17.3%) despite not achieving statistical significance (Tab 1a). Same significance was found in COVID positive limited cutaneous subset subgroup for FVC and FEV1 reduction (p=0.01). In addition, in 2 of the 35 COVID cases (5.7%), the infection resulted in the death of the patients, with SARS-CoV2 being the only reason of death in both groups in the aforementioned follow-up period (Tab. 1b). No clear differences were noticed in ongoing or new onset treatment, while a trend of increasing percentage of digital ulcers, esophagophathy and pulmonary arterial hypertension was found, even if none of the aforementioned reached statistical significance.   Conclusions. Our work highlights the risks related to SARS-CoV2 infection in delicate patients as SSc-rILD ones. Global pulmonary function loss advocates for the necessity of shrewd preventive strategies (as with vaccinations) and careful monitoring of the disease course in those experiencing COVID infection.

BackgroundRheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe condition with an unclear pathogenesis. Here, we investigated the effects of baricitinib on lung fibrosis progression.MethodsA collagen-induced arthritis (CIA) mouse model was established. Lung tissues were analyzed using Western blotting, immunofluorescence staining, immunohistochemical staining, Masson’s trichrome and hematoxylin and eosin staining. Protein expression was assessed in vitro using Western blotting and immunofluorescence staining. The cytokine levels in supernatants were measured using ELISA, and macrophage-derived exosomes were identified using transmission electron microscopy and Western blotting, followed by microRNA sequencing analyses. miR-126a-3p-regulated genes were identified using dual-luciferase reporter assays.ResultsIn vivo, baricitinib reduced iNOS, CD206 and MerTK levels and collagen deposition in the lungs of CIA mice through the JAK/STAT pathway. In vitro, baricitinib downregulated the expression of arginase-1, CD206 and MerTK in macrophages and TGF-β and IL-10 in supernatants. Baricitinib also increased miR-126a-3p expression in macrophage-derived exosomes. miR-126a-3p exerted antifibrotic effects by regulating apoptosis and autophagy via the PI3K/AKT1/mTOR pathway. Silencing JAK1 reduced JAK1 and JAK2 expression.ConclusionBaricitinib targets the JAK/STAT signaling pathway in macrophages, thereby exerting dual anti-inflammatory and anti-fibrotic inhibitory effects on CIA-ILD mice. Meanwhile, it increases miR-126a-3p secretion by suppressing M2 polarization, further contributing to its anti-fibrotic activity in vitro using NIH3T3 cell.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Large retrospective clinical studies have demonstrated association between blood leukocytes levels and mortality, but correlation with progression of fibrosis has not been fully explored.ObjectiveDetermine if blood leukocyte levels are associated with progression of fibrosis in IPF using automated CT Lung texture analysis.MethodsWe performed a retrospective analysis of an IPF cohort (n=164) seen in the Oxford ILD Service between 2016–2021. Non-contrast high resolution computed tomography scans were analysed using the CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating) CT algorithm. CALIPER total lung fibrosis (TLF) and pulmonary vessel volume (PVV) scores were calculated at baseline and follow-on CT timepoints.We used Pearson (r) correlation to determine association between blood leukocytes (monocytes, neutrophil and lymphocytes measured <4 months from 1st CT) with baseline CALIPER TLF, CALIPER PVV, and FVC% and TLCO% closest to CT. Leukocyte association with disease progression was explored using a multivariate Cox regression fitting a model around increase in fibrosis >10%/litre of lung.ResultsMean age of cohort 75.1 SD± 7.9 y, 90% male. Median FVC 76.6% (IQR 66.6–91.2), TLCO 56.9% (49.5–67.0). Neutrophil level correlated with TLF (r=0.208, p=0.007) and PVV (r=0.259, p=0.001). There was significant correlation between neutrophils and upper and middle zone fibrosis and PVV, but weaker correlation with FVC% (r=-0.127, p=0.029) and TLCO% (r=-0.104, p=0.079). Neither monocyte or lymphocyte level correlated with TLF, PVV, FVC% or TLCO%.71 cases underwent repeat CT; mean time 28.9 m (±16.7) between CTs. In multivariate analysis adjusted for age, gender and% change in CALIPER lung volume, PVV and leukocyte levels, neutrophil count demonstrated significant association with progression of TLF [HR 2.66, 95%CI, 1.35–5.25, p=0.005]. See table 1.Abstract P27 Table 1Multivariate Cox regression analysis in n=71 cases undergoing follow-on HRCT. HR; Hazard ratio, 95%CI; 95% confidence interval, PVV; Pulmonary vessel volume Model A Outcome: Increase in CALIPER Fibrosis >10%/Litre of lung volume HR 95% CI p Value -Age at CT 0.93 0.84–1.04 0.208 -Male 0.02 0.02–0.46 0.016 -% change inLung Volume (measured by CALIPER) 0.82 0.73–0.92 <0.001 -Total lung fibrosis (%) on 1st CT 1.13 1.03–1.25 0.013 -Total PVV (cm3) 1.04 1.01–1.07 0.037 -Low attenuation areas LAA (%) 1.10 0.97–1.25 0.142 -Monocyte (x103/μl) 2.37 0.09–62.20 0.604 -Neutrophil (x103/μl) 2.66 1.35–5.25 0.005 -Lymphocyte(x103/μl) 0.30 0.07–1.24 0.096 Harrell’s Index of concordance (C Statistic) = 0.93 ConclusionIn our cohort, neutrophil levels showed stronger correlation with CALIPER fibrosis and PVV scores, and radiological progression of fibrosis (within 3 years). Neutrophil levels could indicate patients at greater risk of progression of fibrosis in IPF.

IntroductionFollowing the results of the INBUILD trial, NICE has recommended nintedanib for the management of progressive fibrotic interstitial lung disease (pfILD) in the UK since February 2022.1 The most appropriate way of identifying and prescribing to eligible patients whilst minimising impact on service delivery is unknown.MethodsRetrospective data analysis of patients referred to a tertiary ILD service from November 2021 to June 2022; pfILD patients recommended for nintedanib; and key performance indicators.ResultsThere were 369 new referrals to the ILD service during this time, of whom 9 patients (2.4%) were recommended for nintedanib for the management of pfILD. In addition, 44 patients known to the service were recommended for nintedanib for the management of pfILD; a total of 53 patients (60% female, age 66 ± 12.3 years). 36 of these patients (67.9%) were discussed in MDT to confirm pfILD diagnosis; the most common diagnosis was progressive fibrotic CTD-ILD (49.1%). Number of cases discussed in ILD MDT remained broadly similar across this time period. Since recommendation, 42 patients have initiated treatment with an average waiting time of 27 days. This is similar to the average waiting time for initiation of nintedanib in IPF, prior to February (29 days). 51 patients (96%) are also prescribed immunosuppression with 28 patients (52.8%) on multiple immunosuppressive agents.ConclusionsPrevious local data indicates 7.5% of new referrals could meet nintedanib treatment criteria2, so our data suggests either a number of eligible patients in whom the clinician decides this treatment is not appropriate, or eligible patients who remain unidentified. CTD-ILD was over-represented compared to previously published data, so there may be other diagnoses we are less good at identifying for this treatment. ILD specialist pharmacist time is unchanged at 1.2 WTE; the addition of 0.5PA consultant time to drug initiation clinics has ensured that decision-to-initiation times remain stable. MDT discussion time has also expanded. Ongoing data collection, including patient outcomes, is planned.ReferencesFlaherty et al. Nintedanib in pfILD. NEJM 2019;381:1718–1727Simpson T, West A. The incidence of pfILD treatable with oral-antifibrotic therapy in a UK specialist centre. ERJ 2020;56:442

IntroductionAwareness of swallowing abnormalities in respiratory conditions such as (COPD) is growing. However, research into swallowing dysfunction in IPF is limited.AimExplore the swallowing safety and performance of the Water Swallow Test (WST) in patients with IPF.MethodsThirty-four IPF patients were recruited from pulmonary fibrosis support groups around the UK or from the Newcastle Interstitial Lung Disease (ILD) clinic between January and October 2021. The WST was conducted via teleconference call or face-to-face in the ILD clinic. Patients took three volumes of water: 5 mL single-sip, 10 mL single-sip and 100 mL consecutive sips. Signs of penetration or aspiration (airway response and/or wet voice after swallow) indicated a WST fail. Three swallowing performance parameters were calculated: swallow volume (mL per swallow), capacity (mL per second) and speed (time per swallow). Swallowing performance parameters were reported by age, gender and% predicted FVC. The cohort was compared with published healthy controls (Hughes and Wiles, 1996). Patients’ HR, RR and SpO2 pre and post WST were obtained.ResultsThirty-three IPF patients (23 M, 10 F) completed the WST, median age 72 (52–92) years. Ten patients (10/33, 30%) were on Long Term Oxygen Therapy (LTOT). IPF patients had poorer swallow performance than the healthy people (figure 1) and six patients (18%, 4 M, 2 F) failed the WST.Post-test SpO2 was higher (p=0.004). Females have lower swallow volume than males (p=0.006, mean rank difference 8.2 mL). However there was no difference for swallow capacity and speed.Abstract P25 Figure 1Performance indicated by swallowing capacity vs. published controls.IPF patients were divided by gender and age ranges from Hughes and Wiles (1996): 56–74 years (group 1), and 75–92 years (group 2). Six patients failed the WST with signs of penetration or aspiration (green asterisks). In addition, using the lower limit of normal swallow capacity (LLN) in control groups as the cut-off, 7 patients (21%, 6 M, 1 F) had reduced swallow capacityConclusionWST is an effective screening investigation in IPF, including frail patients in remote consultation. IPF patients experienced some signs of swallowing dysfunction during WST. Further work is indicated to fully explore swallowing in this vulnerable group.ReferenceHughes TA, Wiles CM. Clinical measurement of swallowing in health and in neurogenic dysphagia. Qjm 1996;89(2):109–16.Please refer to page A213 for declarations of interest related to this abstract.

IntroductionRemote monitoring of pulse oximetry and spirometry has been proposed as an alternative to hospital based measurements for monitoring patients with interstitial lung disease (ILD). We aimed to understand factors impacting the acceptability of remote monitoring to patients.MethodsSecondary analysis of study NCT04850521: Patients with ILD were asked to record daily spirometry for 91 days. Adherence was defined as the percentage of study days with a spirometry recording. Health related quality of life (HRQoL) was measured using EQ-5D-5L. Patient experience was surveyed at the conclusion. Disease severity was defined by modified ILD-GAP score. Continuous and categorical measures were compared with Spearman’s Correlation and Mann Whitney U Test, accordingly. No correction for multiple testing was performed.Results60 patients were included in analysis, 70% male, age 67.8 years (± 11.2), baseline FVC 3.09L (±1.12). 33/60 (55%) participants had idiopathic pulmonary fibrosis (IPF), 27/60 (45%) had non-IPF ILD. Median modified ILD-GAP score was 3 (IQR 1–4.75). Median adherence to spirometry was 89%.Weak positive correlation was observed between disease severity and adherence (rho= 0.299, p=0.02; figure 1), similarly for age and adherence (rho= 0.276, p=0.03). We observed no significant correlation between baseline HRQoL and adherence (rho = 0.20, p= 0.22), change in HRQoL (rho= 0.007, p=0.97), baseline FVC (rho= -0.105, p=0.45) or baseline TLCO (rho= -0.176, p=0.18). No statistical difference was observed in adherence according to ILD subtype diagnosis (IPF median 92%, non-IPF ILD median 85%, p=0.2).32/60 (53%) patients responded to the experience survey. These patients had higher adherence (0.93 vs 0.81, p=0.02) and lower disease severity (2.5 vs 3 p=0.001) (figure 1). All respondents (32/32) stated home spirometry was easy to perform and 88% (28/32) felt that it was useful. 74% (23/31) of patients wished to continue to monitor their spirometry. Median severity appeared worse in patients who wanted to continue but this did not reach significance (3 vs 1.5, p= 0.16).Abstract P33 Figure 1Severity of disease (modified ILD-GAP score) and adherence to daily spirometry in those who did and did not respond to the experience survey at conclusion of the studyConclusionsRemote monitoring is acceptable to most patients with ILD. Patients with more advanced disease may be more engaged with home spirometry, but their experiences may be under represented.Supported by Innovate UK (ref 66823)Please refer to page A213 for declarations of interest related to this abstract.

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.

BackgroundIdiopathic Pulmonary Fibrosis (IPF) is a progressive scarring lung disease. The antifibrotics pirfenidone and nintedanib are approved for IPF patients with a forced vital capacity% predicted (FVC%) between 50–80%, and either drug may be prescribed in the first instance. Both drugs reduce mortality risk, and disease progression as assessed by FVC% and transfer factor for carbon monoxide% predicted (TLCO%) over 12-months. The effectiveness of antifibrotics beyond 12-months is less established, furthermore there is limited real world data comparing pulmonary function and mortality between both drugs.AimsTo assess the effectiveness of antifibrotics on FVC% and TLCO% over 24-months. To identify if the current clinical rationale of offering either antifibrotic from the outset is appropriate through investigating FVC%, TLCO% and mortality outcomes in IPF patients receiving pirfenidone or nintedanib.MethodsWe carried out a retrospective analysis of IPF patients with an FVC% between 50–80% who commenced antifibrotic treatment between May 2012 and October 2019 at Royal Papworth Hospital (Cambridge, UK). Separate random coefficient regression models were used to assess FVC% and TLCO% at 0, 6, 12, 18 and 24-months. A Cox proportional hazards model was used to assess hazard ratio (HR) and 95% confidence interval (CI) for all-cause mortality in antifibrotic treated patients.Results194 patients were identified from our dataset. FVC% remained stable between 0 and 12-months (p=0.330) but declined between 12 and 24-months (p<0.001). TLCO% decreased between 0 and 12-months (p=0.003) and between 12 and 24-months (p<0.001). Over 24-months, FVC% was similar between pirfenidone and nintedanib (Figure 1) (p=0.495), while TLCO% was greater in pirfenidone treated patients (figure 1), albeit non-significant (p=0.054). No all-cause mortality difference was observed for nintedanib versus pirfenidone (HR = 0.80 [95% CI = 0.46–1.40]; p=0.434).Abstract P147 Figure 1Mean FVC% (Block lines) and TLCO% (Dotted lines) over 24-months in patients treated with pirfenidone (Circle) and nintedanib (Triangle). * Significant difference between nintedanib and pirfenidoneConclusionsData from our centre revealed a greater FVC% decline during the 2nd year of treatment compared to the 1st year of treatment. There appears to be no difference in pulmonary function parameters and all-cause mortality between pirfenidone and nintedanib. This supports the current clinical rationale that if there are no contraindications to either drug, patients should be offered the choice of antifibrotic at the outset.