Biomarker For Interstitial Lung Disease Research Articles

Cohort study of serological biomarkers for interstitial lung disease in patients with rheumatoid arthritis

Objective Interstitial lung disease (ILD) is an important cause of mortality in patients with rheumatoid arthritis (RA). Early RA-ILD detection is essential to improve prognosis. Here, we investigated eight serological biomarkers that may contribute to RA-ILD detection. Method Fifty-five patients from the Early Rheumatoid Arthritis Program were evaluated for ILD with high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) using the SCAPIS protocol. Blood samples were obtained for biomarker analysis, and patients’ clinical records were reviewed. We defined ILD using five different models based on the measurements used to confirm ILD: Model A = HRCT; B = PFTs; C = A plus B; D = C plus symptoms; and E = D plus inhalations. Results Among 55 patients, two had an ILD diagnosis before the study, but over one-third fulfilled the ILD criteria. Cancer antigen 15-3 (CA15-3) and matrix metalloproteinase-7 (MMP-7) differentiated between RA with and without ILD (all p < 0.05). Surfactant protein D (SP-D) showed similar trends, as did macrophage inflammatory protein-1β (MIP-1β) and chitinase 3-like protein-1 (YKL-40). Based on Pearson’s correlation coefficients, MIP-1β and YKL-40 were significantly correlated with DAS28 (MIP-1β: 0.3; YKL-40: 0.4), ESR (MIP-1β: 0.3; YKL-40: 0.4), and CRP (only MIP-1β: 0.4) (all p < 0.05). CA15-3 was correlated with rheumatoid factor and anti-citrullinated peptide antibodies (Pearson’s correlation 0.3; both p = 0.03). Conclusions CA15-3 was the most significant biomarker for ILD detection in RA patients with stable low disease activity, closely followed by MMP-7. SP-D, MIP-1β, and YKL-40 may also contribute to RA-ILD diagnosis.

Comparative accuracy of CA-153 and KL-6 as diagnostic and prognostic biomarkers for interstitial lung disease

BackgroundsTo discern the potential of KL-6 and CA-153 as diagnostic tools for interstitial lung disease (ILD), understand their relationship with GAP (Gender, Age, and Physiology) stage, and analyze their predictive capacities alongside CT features. This research aims to enhance ILD detection and management in autoimmune patients, emphasizing the diagnostic utility of these biomarkers. MethodsFrom Mar 2017 to Mar 2024, 398 patients from Taichung Veterans General Hospital’s Division of Allergy, Immunology, and Rheumatology with autoimmune diseases were prospectively enrolled. ILD diagnoses were confirmed using High-Resolution Computed Tomography (HRCT) or lung biopsy and characterized by radiologists. GAP scores were calculated for IPF prognosis. 583 serum samples were collected and tested for KL-6, CA-153, CA-199, and CA-125 using specific assays. Statistical analyses compared patients, assessed variables, determined missingness, and predicted ILD, with tools like ROC analysis and logistic regressions. Analyses were performed with IBM SPSS and MedCalc. ResultsILD patients were older, predominantly male, and had more smokers compared to non-ILD. Both KL-6 and CA-153 were higher in ILD and showed a significant, but non-interchangeable correlation. Age, BMI, smoking, and biomarker levels influenced ILD odds, with KL-6 and CA-153 being the strongest predictors. HRCT imaging highlighted these markers’ roles, especially in detecting specific features. Both markers also strongly associated with GAP stages. Stratified analyses emphasized KL-6′s significance in predicting ILD across both AD and non-AD groups. Complete data sensitivity analysis reinforced KL-6 and CA-153 as key ILD predictors. ConclusionsThis research emphasizes CA-153 as a feasible, cost-effective alternative to KL-6 in diagnosing and monitoring ILD. Both CA-153 and KL-6 levels were notably elevated in ILD patients, displaying a strong correlation, especially at CA-153 levels of ≤100 U/ml. They both also have significant associations with CT characteristics and GAP stages. The study reinforces the potential of CA-153, particularly in settings where KL-6 testing might be inaccessible or expensive.

Risk Factors and Biomarkers for Interstitial Lung Disease and Pulmonary Arterial Hypertension in Systemic Sclerosis: Experience of Two Tertiary Centers in Turkey

Purpose: To define the clinical and laboratory characteristics of patients with systemic sclerosis (SSc), and to investigate the risk factors affecting the prevalence of interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), which are important causes of morbidity and mortality. Patients and methods: 88 patients with SSc were compared according to the presence of ILD and PAH. ILD was confirmed by chest computed tomography, and PAH was suspected and considered probable PAH when right ventricular systolic pressure was &gt;40 mmHg according to echocardiography. Results: Of the 88 patients, 44.3% had diffuse-type and 55.7% had limited-type SSc. Diffuse type, percentages of positive anti-scleroderma-70 (anti-Scl70) antibody and anti-centromere antibody, white blood cell (WBC), platelet, erythrocyte sedimentation rate (ESR), smoking, and presence of the sclerodactyly and telangiectasia differed significantly in SSc with ILD group. The positive titer of anti-Scl70 antibody (odds ratio (OR)=6.124, p=0.004), platelet count (OR=0.138, p=0.002), ESR (OR=1.042, p=0.035) and presence of telangiectasia (OR=10.571, p=0.001) were associated with ILD in patients with SSc. Also, while diffuse-type (OR=0.223, p=0.010), the presence of sclerodactyly (OR=11.112, p=0.028) and telangiectasia (OR=3.861, p=0.020) were risk factors for the development of ILD in nonspecific interstitial pneumonia pattern, anti-Scl-70 antibody positivity (OR=12.921, p=0.019) and high ESR (OR=1.034, p=0.030) were found to be risk factors for the development of usual interstitial pneumonia pattern. Conclusion: Positive titer of the anti-Scl70 antibody, diffuse type, presence of telangiectasia, and high ESR were independently associated with ILD in SSc patients.

Research progress of serum biomarkers in interstitial lung disease associated with connective tissue disease

Research progress of serum biomarkers in interstitial lung disease associated with connective tissue disease

Krebs von den Lungen-6 (KL-6) and Surfactant-D as Biomarkers of Interstitial Lung Disease: A Literature Review

Interstitial Lung Disease (ILD) is a group of lung diseases characterized by various patterns of lung tissue damage, including inflammation and fibrosis of the lung interstitium, both with known or unknown causes (idiopathic). In establishing the diagnosis of ILD, a comprehensive approach including history-taking, physical examination, and supporting examinations, is needed and managed in a multidisciplinary manner. Biomarkers are diagnostic tools known to be accessible, inexpensive, reproducible, and non-invasive for helping diagnose ILD patients. Growing evidence has supported the idea that many biomarker molecules can detect lung injury in ILD, including Krebs von de lungen-6 (KL-6) and Surfactant D (SP-D). KL-6 and SP-D could be utilized in the detection, disease monitoring, prognostication, and therapeutic responses of ILD patients. This review aimed to discuss several potential Kl-6 and SP-D biomarkers against ILD and discusses their clinical utility.

Panel of serum biomarkers for differential diagnosis of idiopathic interstitial lung disease and interstitial lung disease-secondary to systemic autoimmune rheumatic disease.

Interstitial lung disease (ILD) may complicate the course of systemic autoimmune rheumatic disease (SARD) and diagnostic biomarkers are needed. Krebs von den Lungen-6 (KL-6), ferritin (FER) and interleukin 6 (IL-6) have been involved in the ILD development. Our study aimed to compare KL-6, FER, IL-6 and soluble mesothelin-related peptide (SMRP) concentrations in a cohort of idiopathic and SARD-ILD. 3169 patients were enrolled in the "UK Biomarkers in Interstitial Lung Disease (UK-BILD) Study". We selected patients affected by SARD-ILD and idiopathic ILD (usual interstitial pneumonia-idiopathic pulmonary fibrosis and fibrotic non-specific interstitial pneumonia). Serum marker concentrations were measured through chemiluminescent assays (Fujirebio Europe, Ghent, Belgium). 1013 patients were selected for the study: 520 (51.3%) had idiopathic ILD and 493 (48.7%) SARD-ILD. Idiopathic ILD patients displayed higher KL-6 values than SARD-ILD (p = 0.0002). FER and SMRP, though within normal ranges, were significantly higher in idiopathic ILD (p<0.0001). Logistic regression showed good sensitivity (69.4%) and specificity (80.4%) selecting the variables FER and KL-6 concentrations, age and gender-male correlated with a diagnosis of idiopathic ILD. Our study showed the excellent diagnostic value of KL-6 for detecting ILD, which irrespective of the final diagnosis and extent of disease, is always elevated and is a reliable biomarker of lung fibrosis in various diseases, ranging from idiopathic to autoimmune forms. Our study proposed an ILD differentiation model including clinical background. In this context, combination of serum markers and clinical data, as seen in our cohort, may lead to a further improvement in diagnostic accuracy for ILD.

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome

BackgroundILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. MethodsClinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. ResultsA total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). ConclusionAPCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS.

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome

BackgroundILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. MethodsClinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. ResultsA total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). ConclusionAPCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS.

Correlation of the High-Resolution Computed Tomography Patterns of Intrathoracic Sarcoidosis with Serum Levels of SAA, CA 15.3, SP-D, and Other Biomarkers of Interstitial Lung Disease.

Studies on the serum biomarkers of granulomatous inflammation and pulmonary interstitial disease in intrathoracic sarcoidosis have shown conflicting results. We postulated that differences in the concentrations of serum biomarkers can be explained by the heterogenous patterns of sarcoidosis seen on thoracic HRCT. Serum biomarker levels in 79 consecutive patients, newly diagnosed with intrathoracic sarcoidosis, were compared to our control group of 56 healthy blood donors. An analysis was performed with respect to HRCT characteristics (the presence of lymph node enlargement, perilymphatic or peribronchovascular infiltrates, ground-glass lesions, or fibrosis), CXR, and disease extent. Serum levels of CXCL9, CXCL10, CTO, and CCL18 were statistically significantly increased in all patients compared to controls. Serum levels of CA15.3 were statistically significantly increased in all patients with parenchymal involvement. SAA was increased in patients with ground-glass lesions while SP-D levels were statistically significantly increased in patients with lung fibrosis. Only SP-D and CA15.3 showed a significant correlation to interstitial disease extent. In conclusion, we found that sarcoidosis patients with different HRCT patterns of intrathoracic sarcoidosis have underlying biochemical differences in their serum biomarkers transcending Scadding stages. The stratification of patients based on both radiologic and biochemical characteristics could enable more homogenous patient selection for further prognostic studies.

CCL18 as a Biomarker of Interstitial Lung Disease (ILD) and Progressive Fibrosing ILD in Patients with Idiopathic Inflammatory Myopathies.

To assess CCL18 and OX40L as biomarkers of interstitial lung disease (ILD) and/or progressive fibrosing (PF-) ILD in idiopathic inflammatory myopathies (IIMs). Patients with IIMs seen in our center from July 2020 to March 2021 were consecutively enrolled. ILD was detected by high-resolution CT. CCL18 and OX40L serum levels were measured by validated ELISA assays in 93 patients and 35 controls. At the 2-year follow-up, PF-ILD was evaluated according to the INBUILD criteria. ILD was diagnosed in 50 (53.7%) patients. CCL18 serum levels were higher in IIMs patients vs. controls (232.9 [IQR 134.7-399.07] vs. 48.4 [29.9-147.5], p < 0.0001), with no difference for OX40L. IIMs-ILD patients exhibited higher levels of CCL18 than those without ILD (306.8 [190.8-520.5] vs. 162 [75.4-255.8], p < 0.0001). High CCL18 serum levels were independently associated with IIMs-ILD diagnosis. At follow-up, 22/50 (44%) patients developed a PF-ILD. Patients who developed PF-ILD had higher CCL18 serum levels than non-progressors (511 [307-958.7] vs. 207.1 [149.3-381.7], p < 0.0001). Multivariate logistic regression analysis revealed CCL18 as the only independent predictor of PF-ILD (OR 1.006 [1.002-1.011], p = 0.005). Although in a relatively small sample, our data suggest that CCL18 is a useful biomarker in IIMs-ILD, particularly in the early identification of patients at risk of developing PF-ILD.

IFN-beta and EIF2AK2 are potential biomarkers for interstitial lung disease in anti-MDA5 positive dermatomyositis.

Dermatomyositis (DM) with positive anti-melanoma differentiation-related gene 5 (MDA5) antibody is an autoimmune disease with multiple complications. Interstitial lung diseases (ILD) are significantly associated with DM and are particularly related to MDA5+ DM. This article aimed to explore potential molecular mechanisms and develop new diagnostic biomarkers for MDA5+ DM-ILD. The series matrix files of DM and NSIP were downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) was used to screen the common enriched pathways related to DM and NSIP. Next, the co-expressed differential expressed genes (co-DEGs) between MDA5+, MDA5- and NSIP groups were identified by Venn plots, and then selected for different enrichment analyses and protein-protein interaction (PPI) network construction. The mRNA expression levels of IFN-beta and EIF2AK2 were measured by RT-qPCR. The protein expression levels of IFN-beta were measured by ELISA. Using GSEA, the enriched pathway "herpes simplex virus 1 infection" was both up-regulated in DM and NSIP. Enrichment analysis in MDA5+ DM, MDA5- DM and NSIP reported that the IFN-beta signalling pathway was an important influencing factor in the MDA5+ DM-ILD. We also identified that eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) was an important gene signature in the MDA5+ DM-ILD by PPI analysis. The expression levels of IFN-beta and EIF2AK2 were significantly increased in MDA5+ DM-ILD patients. IFN-beta and EIF2AK2 contributed to the pathogenesis of MDA5+ DM-ILD, which could be used as potential therapeutic targets.

Biomarkers of interstitial lung disease in systemic scleroderma and their significance

Systemic scleroderma (SSD) is a rare immune-inflammatory systemic disease of connective tissue with a typical lesion of skin, blood vessels, musculoskeletal system and internal organs (lungs, heart, digestive tract, kidneys). The SSD pathogenesis is based on activation of a cascade of complex immune interactions that lead to vasculopathy. The presence of many pathophysiological links in the progression of the disease causes a variety of clinical manifestations in various patients with SSD. A full assessment of all stages of SSD development is still being carried out and every newly open element of the interaction of immunological subjects completes the overall picture of the disease. A number of studies show a correlation between level of several biomarkers and both disease prognosis and estimated therapy effectiveness. Recent data confirm importance of the biomarkers for formation of patterns of a particular disease phenotype in a specific patient. Depending on relation of the biomarkers to various biological processes, several of their categories are distinguished: biomarkers expressed in lung tissue, cellular units of immunity, nucleic acids, acute phase indicators, connective tissue growth factors, matrix proteinases and their inhibitors, chemokines and cytokines, as well as biomarkers of endothelial activation. Discovery of a novel set of the indicators can be decisive in determining the management tactics and forecasting the response to therapy of some groups of patients with SSD. By combining the most recent data on significant markers obtained in the framework of extensive studies, we have described the most significant biomarkers of SSD and their link to interstitial lung disease (ILD) that is formed in SSD.

Biomarkers of interstitial lung disease associated with primary Sjögren's syndrome

ObjectivesThe aim of this study was to investigate serum biomarkers linked to primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD).Methods69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs).ResultsAmong consecutively enrolled patients with pSS, the presence of pSS–ILD was 50% based on the presence of radiographically defined interstitial lung abnormalities (ILA) meeting specified criteria for mild/moderate (ILA 2) or severe (ILA 3) disease. Age, immunoglobulin M (IgM), C-reactive protein (CRP), and serum levels of eotaxin/CCL11, Krebs von den Lungen-6 (KL-6), TNFα, and TGFα were significantly higher in the combined pSS–ILD group (ILA 2 + ILA 3) than in the pSS–no-ILD and pSS–indeterminate ILD groups (ILA 0 and ILA 1, respectively) in unadjusted analyses (p < 0.05 for all variables). A binary logistic regression model revealed that disease duration and KL-6 levels were associated with the presence of pSS–ILD (p < 0.05). Complementary least absolute shrinkage and selection operator (LASSO) modeling showed that age, KL-6, and TNF-α effectively differentiated pSS–ILD (ILA 2 + ILA3) from pSS without ILD (ILA 0 + ILA 1), with an area under the curve (AUC) of 0.883 (p value < 0.0001).ConclusionsPatient age, disease duration, and serum levels of both KL-6 and TNFα were the most discriminating factors associated with the presence of ILD in our pSS patients. Higher levels of CRP, IgM, eotaxin, TGFα, and TNFα should also prompt the search for occult as well as clinically evident lung involvement based on statistically significant univariate associations with pSS–ILD.Clinical trial registrationNone.

Usefulness of KL-6 for Predicting Clinical Outcomes in Hospitalized COVID-19 Patients.

Background: Krebs von den Lungen 6 (KL-6) is a novel biomarker for interstitial lung disease, and it reflects acute lung injury. We explored the usefulness of KL-6 to predict clinical outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients. Methods: In a total of 48 hospitalized COVID-19 patients, KL-6 levels were measured using the HISCL KL-6 assay (Sysmex, Kobe, Japan) with the HISCL 5000 automated analyzer (Sysmex). Clinical outcomes (intensive care unit [ICU] admission, ventilator use, extracorporeal membrane oxygenation [ECMO] use, and 30-day mortality) were analyzed according to KL-6 percentiles. Age, initial KL-6 level, Charlson comorbidity index (CCI), and critical disease were compared using the receiver operating characteristic (ROC) curve and Kaplan-Meier methods for clinical outcomes. Results: KL-6 quartiles were associated with ICU admission, ventilator use, and ECMO use (all p < 0.05), except 30-day mortality (p = 0.187). On ROC curve analysis, initial KL-6 level predicted ICU admission, ventilator use, and ECMO use significantly better than age, CCI, and critical disease (all p < 0.05); age, initial KL-6 level, CCI, and critical disease predicted 30-day mortality comparably. On Kaplan–Meier survival analysis, hazard ratios (95% confidence interval) were 4.8 (1.2–19.3) for age, 4.7 (1.1–21.6) for initial KL-6 level, 3.9 (0.9–16.2) for CCI, and 2.1 (0.5–10.3) for critical disease. Conclusions: This study demonstrated that KL-6 could be a useful biomarker to predict clinical outcomes in hospitalized COVID-19 patients. KL-6 may contribute to identifying COVID-19 patients requiring critical care, including ICU admission and ventilator and/or ECMO use.

Early Diagnosis of Interstitial Lung Disease

Interstitial Lung Disease (ILD) includes more than 200 diseases that involve the interstitial lung. The diagnosis of ILD depends on the onset of symptoms, causes, and clinical manifestations. An anamnesis comprehensive and physical examination are essential in diagnosing ILD. In addition, laboratory tests are carried out in certain clinical conditions. The analysis of biomarkers in ILD is helpful for diagnosis, disease monitoring, and prediction of prognosis. Pulmonary function studies support the diagnosis of ILD and as a predictor of prognosis. High-resolution Computed Tomography (HRCT) is the main diagnostic procedure in ILD patients. In certain conditions, a lung biopsy may be considered. Multidisciplinary discussion (MDD) enhances accurate diagnosis. An accurate early diagnosis of ILD is necessary to ensure that patients receive optimal management, reduce the risk of developing pulmonary fibrosis and reduce the risk of death. Early diagnosis of ILD define as early identification of symptoms, laboratory and radiological findings at the early stage of the disease

Plasma IL-36α and IL-36γ as Potential Biomarkers in Interstitial Lung Disease Associated with Rheumatoid Arthritis: a Pilot Study in the Chinese Population.

Interstitial lung disease (ILD) is a frequent extra-articular manifestation of rheumatoid arthritis (RA) and increases mortality in patients with RA. Early identification of ILD, especially the usual interstitial pneumonia (UIP) pattern with a poor prognosis, is important for guiding treatment of RA-ILD and preventing damage resulting from a delay in diagnosis. Interleukin-36 (IL-36) cytokines are involved in connective tissue diseases. However, IL-36 expression in RA-ILD is unknown. In this study, the clinical relevance of plasma IL-36 cytokines was evaluated in 39 patients with RA-ILD and three other groups (30 healthy controls [HCs], 35 RA patients without ILD, and 27 patients with idiopathic pulmonary fibrosis [IPF]) in the Chinese population. Plasma IL-36α and IL-36γ concentrations were elevated in patients with RA-ILD compared with those in HCs and patients with RA. RA-ILD patients with UIP pattern had higher plasma IL-36γ concentrations than those with RA-ILD without UIP, but these were lower than those in patients with IPF. Receiver operating curve analysis suggested that IL-36α and IL-36γ were potential biomarkers for identifying ILD in patients with RA. Additionally, the optimal cutoff value of IL-36γ for distinguishing RA-ILD with the UIP pattern from RA-ILD without UIP was 555.40pg/mL and that for distinguishing RA-ILD from IPF was 655.10pg/mL. No significant difference in plasma IL-36β or IL-36Ra concentrations was found between patients with RA-ILD and the three other groups. We also found that the lungs originating from different types of patients with PF, including RA-ILD and IPF, and those from mice following bleomycin-induced PF were characterized by increased IL-36γ expression. Our findings suggest that using IL-36 cytokines to identify patients with RA for further ILD workups may provide additional diagnostic value to the current clinically available assays. Moreover, IL-36γ may help to identify the presence of the UIP pattern in patients with RA-ILD and to discriminate RA-ILD from IPF.

Effect of supervised exercise training on exercise capacity, pulmonary function and growth differentiation factor 15 levels in patients with interstitial lung disease: A preliminary study

BACKGROUND: Interstitial lung disease is characterized by exertion dyspnea, exercise limitation and reduced quality of life. The role of exercise training in this diverse patient group is unclear. The growth differentiation factor 15 (GDF15) is a stress-sensitive circulating factor that regulates systemic energy balance and could be a possible biomarker in interstitial lung disease. OBJECTIVE: To evaluate the effect of supervised exercise (endurance and resistance) training (SET) on exercise capacity, pulmonary function parameters and GDF15 levels in patients with interstitial lung disease (PwILD). METHODS: In this non-randomized case-control trial, the experimental group comprised of 10 PwILD (7 women and 3 men) while the control group consisted of of 18 apparently healthy participants s 11 women and 7 men). All subjects completed an 8-week supervised exercise training program, at a rate of twice a week. Dyspnea was evaluated using the Shortness of Breath Respiratory Questionnaire. Exercise capacity was measured using the 6-min walk test while the heart rate (HR) was monitored before and after the exercise training. GDF15 levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: PwILD had significantly shorter 6-min walk distance than the control subjects at both the 1st and the 15th visit. However, both groups improved significantly in this test. The change (pre to post-exercise) in HR value was smaller in PwILD compared to the controls. Moreover, PwILD had higher Shortness of Breath Respiratory Questionnaire score than controls. The mean pre and post GDF15 values in both groups remained statistically unchanged. However the GDF15 values of the PwILD patients were significantly higher compared to the controls with respect to pre and post exercise training respectively. CONCLUSION: Supervised exercise training did not affect GDF15 levels in both patient and control groups but its values in PwILD were significantly higher compared to those of controls (p⩽0.05). The exercise capacity and dyspnea in these patients improved after exercise training program.

P221 Autoantibodies are common in patients with idiopathic interstitial lung disease, suggesting a high prevalence of undiagnosed autoimmune connective tissue disease

Abstract Background/Aims In some patients, interstitial lung disease (ILD) may be the dominant or even sole manifestation of an otherwise unrecognised autoimmune connective tissue disease (CTD). Accurate diagnosis can be challenging given considerable overlap of the clinical, radiological and histological disease features. Distinguishing CTD related ILD (CTD-ILD) from idiopathic ILD, enables appropriate immunosuppressive treatment, informs prognosis and facilitates monitoring for other CTD associated complications. Occasionally a lung biopsy may be necessary to ensure accurate diagnosis. Autoantibodies are a hallmark feature of CTD, are highly disease specific and their presence is strongly suggestive of covert CTD-ILD. We investigated patients with idiopathic ILD for the presence of autoantibodies that may suggest misdiagnosis. Methods The serum from three subgroups of patients recruited to UK Biomarkers of Interstitial Lung Disease (BILD) were analysed: 171 with a diagnosis of idiopathic ILD and non-specific organising pneumonia on HRCT and 27 with a diagnosis of idiopathic ILD and cryptogenic organising pneumonia on HRCT. Autoantibody status was determined by radio-immunoprecipitation. Results Results are summarised in Table 1. Overall CTD-autoantibodies were identified in 15.6% of patients with idiopathic ILD, and were more common in those with NSIP, see table. Autoantibodies identified included those readily detectable e.g. anti-Jo1, in addition to rarer antibodies not included in standard assays e.g. anti-EIF3. Nearly half of all autoantibodies detected were anti-synthetase autoantibodies. Conclusion Covert-CTD is likely to be common amongst patients diagnosed with idiopathic ILD, particularly idiopathic NSIP. More specific guidance on autoantibody testing could improve diagnosis and ensure patients receive appropriate immunosuppressive treatment. Disclosure S. Tansley: None. C. Cotton: None. F.K. McMorrow: None. H. Lu: None. R.P. New: None. L.G. Spencer: None. N.J. McHugh: None. R.G. Cooper: None.

OA12 Autoantibodies are common in patients labelled as “idiopathic” interstitial lung disease suggesting a high prevalence of undiagnosed autoimmune connective tissue disease

Abstract Background/Aims In some patients, interstitial lung disease (ILD) may be the dominant or even sole clinically overt manifestation of an otherwise unrecognised autoimmune connective tissue disease (CTD). Accurate diagnosis can be challenging given considerable overlap of the clinical, radiological and histological disease features. Distinguishing CTD-related ILD (CTD-ILD) from idiopathic ILD can avoid a lung biopsy, enables appropriate immunosuppressive treatment, informs prognosis and facilitates monitoring for other CTD-associated complications. Autoantibodies are a hallmark feature of CTD, are highly disease-specific and their presence is strongly suggestive of covert CTD-ILD. We investigated patients who had been labelled with “idiopathic” ILD by their local hospital teams for the presence of autoantibodies that may suggest misdiagnosis. Methods Serum from two groups of patients recruited to UK Biomarkers of Interstitial Lung Disease (BILD) were analysed: 183 with a local diagnosis of idiopathic non-specific interstitial pneumonia (iNSIP) and 34 with a local diagnosis of idiopathic or Cryptogenic Organising Pneumonia (COP). Autoantibody status was determined by radio-immunoprecipitation. Results Overall, CTD-autoantibodies were identified in 15% of patients with a prior label of “idiopathic” ILD. CTD autoantibodies were more common in those with a prior diagnosis of COP, where more than 1 in 5 patient samples contained a potentially relevant autoantibody, see table. The autoantibodies identified included those readily detectable e.g. anti-Jo1, in addition to rarer antibodies not included in standard assays e.g. anti-EIF2B. Nearly half of all autoantibodies detected were anti-synthetase autoantibodies. Conclusion Covert CTD-ILD is potentially being missed as a diagnosis in patients who have been labelled by local teams as having idiopathic forms of inflammatory ILD (COP or iNSIP). More specific guidance on autoantibody testing and the interpretation of these test results could improve diagnosis and ensure patients receive more appropriate management. Disclosure S.L. Tansley: None. C.V. Cotton: None. F.K. McMorrow: None. H. Lu: None. Z.E. Betteridge: None. R.P. New: None. L.G. Spencer: None. N.J. McHugh: None. R.G. Cooper: None.

The Proteomic Profile of Interstitial Lung Abnormalities.

Rationale: Knowledge on biomarkers of interstitial lung disease is incomplete. Interstitial lung abnormalities (ILAs) are radiologic changes that may present in its early stages. Objectives: To uncover blood proteins associated with ILAs using large-scale proteomics methods. Methods: Data from two prospective cohort studies, the AGES-Reykjavik (Age, Gene/Environment Susceptibility-Reykjavik) study (N = 5,259) for biomarker discovery and the COPDGene (Genetic Epidemiology of COPD) study (N = 4,899) for replication, were used. Blood proteins were measured using DNA aptamers, targeting more than 4,700 protein analytes. The association of proteins with ILAs and ILA progression was assessed with regression modeling, as were associations with genetic risk factors. Adaptive Least Absolute Shrinkage and Selection Operator models were applied to bootstrap data samples to discover sets of proteins predictive of ILAs and their progression. Measurements and Main Results: Of 287 associations, SFTPB (surfactant protein B) (odds ratio [OR], 3.71 [95% confidence interval (CI), 3.20-4.30]; P = 4.28 × 10-67), SCGB3A1 (Secretoglobin family 3A member 1) (OR, 2.43 [95% CI, 2.13-2.77]; P = 8.01 × 10-40), and WFDC2 (WAP four-disulfide core domain protein 2) (OR, 2.42 [95% CI, 2.11-2.78]; P = 4.01 × 10-36) were most significantly associated with ILA in AGES-Reykjavik and were replicated in COPDGene. In AGES-Reykjavik, concentrations of SFTPB were associated with the rs35705950 MUC5B (mucin 5B) promoter polymorphism, and SFTPB and WFDC2 had the strongest associations with ILA progression. Multivariate models of ILAs in AGES-Reykjavik, ILAs in COPDGene, and ILA progression in AGES-Reykjavik had validated areas under the receiver operating characteristic curve of 0.880, 0.826, and 0.824, respectively. Conclusions: Novel, replicated associations of ILA, its progression, and genetic risk factors with numerous blood proteins are demonstrated as well as machine-learning-based models with favorable predictive potential. Several proteins are revealed as potential markers of early fibrotic lung disease.